While not every case can make the cut each month and be considered one of my favorites, many still have interesting clinical pearls and lessons worth sharing.

Here’s a collection of some of my favorite additional pearls from May 2026.

I’ve broken this into a few separate posts to keep the length more manageable.

Acute Myeloid Leukemia (AML) with Monocytic Differentiation

Malignant monocytes can infiltrate tissue, which may lead to gingival hyperplasia, skin lesions (like leukemia cutis), lymphadenopathy, and splenomegaly.

Source: CPS - May 21, 2026 VMR with Rabih & Seeme - multiple falls

Iron Overload

An elevated ferritin with an iron saturation > 50% suggests “true” iron overload and not just inflammation.

Source: CPS - May 21, 2026 VMR with Rabih & Seeme - multiple falls

Elevated LDH

An LDH over 1,000 should make you think of hemolysis, metastatic cancer, or bone marrow crowding that can be seen in hematologic malignancies.

Source: CPS - May 21, 2026 VMR with Rabih & Seeme - multiple falls

Synthetic Cannabinoid (K2/Spice) Intoxication

Synthetic cannabinoids are specifically designed to be potent agonists at the cannabinoid receptors CB1 and CB2.

On the other hand, THC from natural cannabis is only a partial agonist.

Patients using these drugs can present with agitation, psychosis, tachycardia, HTN, and mydriasis. Seizures can also happen.

These substances can prolonged the QTc due to the blockage of hERG potassium channels.

They are usually not seen on a standard UDS, so the diagnosis is often clinical.

In patients presenting with agitation and seizures, benzodiazepines are used because antipsychotics are often avoided due to the risk of further QTc prolongation.

Source: CPS - May 22, 2026 VMR with Rabih & Noah - altered mental status

Tachy-Brady Syndrome

Tachy-Brady syndrome is a type of sick sinus syndrome (SSS), and is a dysfunction of the sinoatrial (SA) node.

It is characterized by alternating tachyarrhythmias (most commonly AFib or flutter) and bradycardia (sinus brady, sinus pauses).

Syncope can occur when the SA node is “overdrive suppressed” and does not resume, leading to a “prolonged” pause.

Meds used to control the tachycardia may worsen the bradycardia. The main treatment is a pacemaker which addresses the severe bradycardia and allows for the safe use of medications to control the tachycardia.

Source: CPS - May 25, 2026 Mainstream Mondays VMR with Jas & Zakariyya G - transient loss of consciousness

Warm Autoimmune Hemolytic Anemia (AIHA)

In warm AIHA, IgG antibodies bind to the surface of RBCs, which are then destroyed by macrophages in the spleen and liver via extravascular hemolysis.

Sepsis can be a non-malignant triggers of warm AIHA.

A rapid drop in Hgb with evidence of hemolysis (high LDH, low hapto) and a positive DAT is concerning for warm AIHA.

The presence of many nucleated RBCs (NRBCs) indicates bone marrow stress.

NRBCs might be mistaken for WBCs by automated counters. This may inappropriately lead to concern for a leukemoid reaction.

Cephalosporins like CTX and cefepime are common causes of drug-induced immune hemolytic anemia.

Source: CPS - May 26, 2026 VMR with Ravi & Kirtan - new onset anemia

Sneaky PE Presentations

You should be at least considering PE in patients that present with exertional dyspnea and have a normal physical exam and CXR.

Patients with both dyspnea and orthostasis should make you think of an obstructive process like PE. This is because most causes of orthostasis, such as volume depletion and autonomic dysfunction, do not typically cause SOB.

Source: CPS - May 28, 2026 VMR with Rabih & Sana - cough and dyspnea on exertion for 4 weeks

Secondary Spontaneous PTX (SSP)

Air travel can cause PTX in patients with pre-existing blebs or bullae. This is due to Boyle’s law which explains the expansion of trapped gas at high altitudes.

Low EKG voltage can be a subtle clue that there is some insulation between the heart and the chest wall. This can include PTX, or more classically, fluid, such as a large pericardial or pleural effusion.

Source: CPS - May 29, 2026 VMR with Rabih & Ravi - 49 y/o male w/progressive worsening SOB, chest pain since 1 day

Infective Endocarditis (IE)

IE should be thought of as a systemic disease that has a host of potential complications. These include local cardiac damage, persistent bacteremia, and embolic phenomena such as stroke, septic arthritis, or glomerulonephritis.

Positive ANA, RF, or low complement can be red herrings in patients with chronic infections. They can represent chronic immune stimulation rather than an autoimmune disease. This can lead to diagnostic challenges in patients presenting with a valve vegetation.

Source: CPS - May 30, 2026 Clinical Reasoning Expeditions with Jeffrey & Joshua Oommen - 60 M Found Down

Extramedullary disease (EMD) of Multiple Myeloma

EMD can be the initial presentation of multiple myeloma. It can mimic other malignancies such as lung cancer or lymphoma.

The classic “CRAB” criteria might be absent, especially in cases that present with isolated EMD.

Source: CPS - May 30, 2026 Simplicity in Complexity Clinical Reasoning w/Jeffrey & Kirtan - Dyspnea & Chest Pain

Differentiating Between Causes of Dyspnea

At its core, dyspnea is a neurological sensation. It can be triggered by deficits in oxygenation, ventilation, or perfusion.

Patients with dyspnea that have a normal exam, EKG, and basic labs might have a “hidden” Structural cause, like PE or diaphragmatic issues. They may also have a central or neurogenic cause, such as anxiety, metabolic acidosis, or deconditioning.

A walk test can help differentiate between these. True structural limitations like those seen in PE should lead to overtly reduced exercise capacity.

Source: CPS - May 31, 2026 - Academy VMR w/ Rabih & Team - Dissecting Dyspnea

Causes of Dark Urine

Isolated dark urine without systemic symptoms can be from a local GU problem (painless hematuria), or the presence of a benign molecule such as an exogenous drug (like rifampin) or endogenous bilirubin.

Bilirubin > 10-12 in an otherwise well patient suggests extrahepatic biliary obstruction. Intrinsic liver disease that is severe enough to cause such high bilirubin almost certainly would also cause some sort of profound systemic illness, such as encephalopathy or coagulopathy.

Source: CPS - May 31, 2026 - Academy VMR w/ Rabih & Team - Dark urine with a Dark Dx

While not every case can make the cut each month and be considered one of my favorites, many still have interesting clinical pearls and lessons worth sharing.

Here’s a collection of some of my favorite additional pearls from May 2026.

I’ve broken this into a few separate posts to keep the length more manageable.

Leydig Cell Tumors

Ovarian Leydig cell tumors secrete androgens.

They are a cause of hyperandrogenism and virilization in post-menopausal women

Clinical presentations usually involves hirsutism, androgenic alopecia, a deepening voice, and clitoromegaly. Although onset is often rapid, it can also develop slowly over many years.

Key labs include elevated serum testosterone, often greater than 150 ng/dL, but normal levels of adrenal androgen, such as DHEA-S. This combination of lab findings helps localize the source of the ovaries.

While imaging can identify a solid ovarian mass, Leydig cell tumors are often very small (less than 1 cm) and within normal ovarian stroma, which can lead to a “negative” study.

The definitive diagnosis of a Leydig cell tumor requires the identification of Reinke crystals.

Source: Annals of IM - Postmenopausal Occult Ovarian Disease With Hirsutism – A 6-Year Follow-Up Course

Clopidogrel Non-responders

Clopidogrel is a prodrug requiring hepatic CYP450 enzyme activation (primarily CYP2C19).

Genetic differences can lead to a “nonresponder” or “hyporesponder” state.

In these patients, usual doses of clopidogrel won’t be effective and thus increase the risk of thrombosis after receiving a stent until there has been adequate endothelialization (which can take weeks to months).

Platelet function testing can test for reduced platelet inhibition from clopidogrel.

In such cases, future anti-thrombotic medication should prioritize alternative options like ticagrelor or prasugrel rather than re-challenging with clopidogrel.

Source: Annals of IM - Clopidogrel Nonresponsiveness Mimicking Endocarditis After PFO-Occlusion Combining Aspiration, Retrieval, and Laboratory Assessment for Diagnostic-Therapeutic Work-Up

Bevacizumab-Associated Osteonecrosis

Osteonecrosis (also known as avascular necrosis, or AVN) is ischemic death of bone tissue resulting from poor blood supply. It commonly affects the femoral head.

Though it’s often linked to trauma, corticosteroids, and alcohol, it can also rarely be caused by anti-angiogenic medications such as bevacizumab (Avastin).

Bevacizumab inhibits vascular endothelial growth factor (VEGF) which promotes the formation of blood vessels.

Thus, blocking this pathway impairs perfusion and repair of bone, increasing the risk of osteonecrosis.

Patients will usually present with slow onset of joint pain over time that worsens with weight-bearing.

MRI is best for diagnosing osteonecrosis since it’s highly sensitive for early changes such as “bone marrow edema”, “subchondral signal abnormalities”, and eventually “articular surface collapse”.

Source: Annals of IM - Bevacizumab-Associated Osteonecrosis Of The Femur

Intracardiac Migration of a TIPS Stent

Migration of a transjugular intrahepatic portosystemic shunt (TIPS) stent is rare but can be a potentially fatal complication. It can happen if the stent dislodges and embolizes cranially into the right atrium, right ventricle, or pulmonary artery.

Migration of the stent can cause arrhythmias from direct myocardial irritation, TR, perforation with tamponade, and clot/PE.

Source: Annals of IM - Intracardiac Migration Of A Tips Stent Causing Ventricular Tachycardia

Guillain-Barre Syndrome

The classic presentation of GBS is a rapidly progressive, relatively symmetric ascending weakness that begins in the feet and legs and moves upwards over hours to days.

Flaccid paralysis is the classic finding. It can progress to involve the trunk, upper limbs, cranial nerves, and respiratory muscles, potentially leading to respiratory failure.

Vital capacity (FVC) and negative inspiratory force (NIF) can help you anticipate the need for intubation.

Another sign is areflexia or hyporeflexia.

Paresthesia in the hands and feet is common. Significant sensory loss is not typical.

Autonomic dysfunction, including tachycardia, arrhythmias, labile blood pressure, and urinary retention, can occur in many patients.

The classic CSF finding is “albuminocytologic dissociation”, which means there’s an elevated protein with a normal WBC count. However, this might be absent in the first one to two weeks of illness.

Source: CPS - May 4, 2026 Mainstream Mondays VMR with Youssef & Saketh - B/L lower limb weakness

LGI1 (leucine-rich glioma-inactivated 1) antibody encephalitis

The classic presentation involves cognitive impairment (such as short-term memory deficits) behavioral or psychiatric disturbances, and seizures.

Facial brachial dystonic seizures are essentially pathognomonic for LGI1 encephalitis.

Autoimmune encephalitis can present with a completely normal CSF analysis. A bland CSF does not rule out an inflammatory process.

The onset of hyponatremia in a patient with neuropsychiatric symptoms should raise suspicion for limbic encephalitis, since it’s a common paraneoplastic or autoimmune-related SI/ADH finding.

Source: CPS - May 6, 2026 VMR with Steph & Zaven - 3 months involuntary movements and behavioral changes

CML Presentations and Diagnostic Clues

Around 85% of patients diagnosed with CML are diagnosed in the “indolent chronic phase.” CML is often discovered incidentally. When the patient is symptomatic, they might present with fatigue, weight loss, or LUQ discomfort due to splenomegaly.

The combination of splenomegaly (even when noted incidentally on imaging) and a high WBC should raise suspicion.

The presence of basophilia in a left shift that spans across all myeloid cells are classic findings in CML.

In the setting of significantly elevated WBC from CML, inflammatory markers (CRP/ESR) can be normal. This can be a key negative finding that can help differentiate from a severe reactive or infectious process.

Source: CPS - May 11, 2026 Mainstream Mondays VMR with Maddy & Seeme - worsening depression and suicidal attempt

Aleukemic Variant of Acute Lymphoblastic Leukemia (ALL)

An aleukemic (or leukopenic) variant of ALL can happen when blasts are not seen peripherally and are only in the marrow. This can delay diagnosis, given the classic picture of a high WBC seen on CBC is missing.

The combination of massive splenomegaly and cytopenias (especially plts less than 20,000-30,000) suggests primary marrow failure since hypersplenism alone is unlikely to cause such severe deficits.

An elevated ALP that is seemingly out of proportion to the level of transaminases can be a major clue for malignant infiltration in the liver, especially if there is hepatomegaly.

Source: CPS - May 12, 2026 VMR with Ravi & Kirtan - fever, yellow discoloration of eyes, epistaxis

IgA Nephropathy

“Synpharyngitic” hematuria (gross hematuria seen during a URI, or shortly afterward) is consistent with IgA nephropathy. This distinguishes it from post-streptococcal glomerulonephritis, which usually doesn’t present until one to three weeks after infection.

The combination of hematuria, proteinuria, and casts on a UA is considered “nephritic sediment”. The presence of the sediment helps to localize the pathology to the glomerulus.

Patient diagnosed with IgA nephropathy should also be asked about rash, joint pain, and abdominal pain which may prompt concern for IgA vasculitis.

Source: CPS - May 18, 2026 Mainstream Mondays VMR with Maddy & Magnus - reddish discoloration of urine

While not every case can make the cut each month and be considered one of my favorites, many still have interesting clinical pearls and lessons worth sharing.

Here’s a collection of some of my favorite additional pearls from May 2026.

I’ve broken this into a few separate posts to keep the length more manageable.

Type II (Mixed) Cryoglobulinemic Vasculitis

Cryoglobulinemic vasculitis is a small-vessel vasculitis caused by the deposition of circulating immune complexes (cryoglobulins) that precipitate in the cold.

It’s important to understand the difference between Type 1 and Type 2.

In Type I, the monoclonal immunoglobulin precipitates largely by itself.

In Type II, monoclonal IgM acts as “rheumatoid factor” and precipitates with polyclonal IgG. This is why it’s called a “mixed” cryoglobulinemia.

The sequence is important. First, a clonal B-cell population produces monoclonal IgM. Then the IgM then binds the Fc region of circulating polyclonal IgG. An IgM-IgG immune complex is formed. These complexes precipitate at low temperatures, activate complement, and deposit in small vessels. This leads to cryoglobulinemic vasculitis and often low C4.

Thus, the triad of purpuric rash, AKI, and low C4 should trigger workup for Cryoglobulinemic vasculitis.

Another classic presentation is the “Meltzer’s Triad” which is the combination of palpable purpura, arthralgias, and weakness.

RF is not a specific protein made only in rheumatoid arthritis. It’s an antibody that binds the Fc portion of IgG and is usually itself an IgM. In type 2, a monoclonal IgM often acts as the rheumatoid factor, which can explain a positive RF test in the setting of monoclonal gammopathy.

While it’s historically linked to chronic HCV infection, it’s actually driven by an underlying B-cell clonal process like lymphoma or Waldenstrom macroglobulinemia.

A kidney biopsy showing membranoproliferative glomerulonephritis with intracapillary “cryo plugs” that stain for IgM and C3 is pathognomonic for cryoglobulinemic glomerulonephritis.

Source: NEJM - Case 13-2026 A 76-Year-Old Woman With Fatigue, Rash, And Kidney Failure Case

Overlap syndrome of SLE and idiopathic inflammatory myopathy (IIM)

Unlike mixed connective tissue disease (MCTD), which is defined by the presence of anti-RNP abs and a specific blend of features (myositis, lupus, scleroderma), an overlap syndrome meets the diagnostic criteria of two separate conditions.

From SLE, patients might present with constitutional symptoms (fever, fatigue), rashes (discoid, malar), photosensitivity, arthritis, serositis, cytopenias, and renal disease.

The IIM component may show symmetric proximal muscle weakness (difficulty climbing stairs, raising arms), elevated muscle enzymes (CK, aldolase, AST), and skin findings (heliotrope rash, Gottron's papules) if dermatomyositis is present.

Proximal muscle weakness seen in an SLE patient should prompt a workup for myositis, which includes checking a CK. Such weakness should not be assumed to be from deconditioning or steroid myopathy alone.

A globulin gap, which is defined as total protein - albumin > 4, is a useful clue for an underlying polyclonal gammopathy. This is commonly seen in active autoimmune disease.

Source: NEJM - Case 14-2026 A 50-Year-Old Woman With Vaginal Bleeding And Anemia

Anti-Interferon-Gamma Autoantibody Syndrome

This is an acquired adult-onset immunodeficiency syndrome caused by antibodies against interferon gamma, a cytokine that helps activate macrophages which kill intracellular pathogens.

Without interferon gamma, there’s a defect in cell-mediated immunity, which leaves patients susceptible to disseminated infections from organisms that are usually low virulence in immunocompetent hosts.

Patients are commonly of East or Southeast Asian descent. They are often previously healthy when they present with severe infections caused by non-tuberculous mycobacteria like M. abscessus or M. avium complex. Other common pathogens can include Salmonella, Burkholderia, and endemic fungi.

Since the immunologic defect in this disease affects the control of intracellular pathogens, immunity to most viruses and extracellular bacteria remains intact.

A specific clue for the diagnosis of this disease is an indeterminate TB gold test, which results from a failed positive mitogen control. This happens because the assay measures secreted interferon gamma protein, which in the disease is neutralized by the antibodies. Definitive diagnosis requires a test that detects the anti-interferon gamma antibodies.

Source: NEJM - Immune Interference

HSV-1 Esophagitis

While visceral disease caused by HSV (esophagitis, enteritis, hepatitis) is a well-known complication in immunocompromised patients, it is much rarer in immunocompetent individuals, which can delay diagnosis.

The classic finding for HSV esophagitis is "punched-out" or volcano-like ulcers seen on endoscopy.

Biopsies taken from the ulcer edge often reveal multinucleated giant cells and eosinophilic intranuclear inclusion bodies (Cowdry Type A).

Diagnosis is usually confirmed with IHC or PCR on the tissue biopsy, which is much more reliable than serology.

A positive HSV IgG only indicates prior exposure, and IgM may be negative in cases of reactivation or in atypical presentations.

Management of HSV esophagitis is typically IV acyclovir, often for a 21 day course.

Source: Annals of IM - Acute Severe Enteritis By Hsv-1 Variant In A Young Patient Who Is Immunocompetent

Obstructive Sleep Apnea (OSA) Induced Nocturnal Enuresis

Classic findings in OSA include loud snoring, witnessed apneas, and excessive daytime sleepiness. However, nocturnal enuresis can also be seen but is rarely attributed to the OSA.

Recurrent apneic episodes generate negative intrathoracic pressure, which increases venous return to the RA. This extra atrial stretch triggers the release of atrial natriuretic peptide which itself promotes diuresis and natriuresis. OSA can also affect the normal arousal response to a full bladder.

If you’re concerned that nocturnal enuresis is due to OSA, start with the STOP-BANG questionnaire (Snoring, Tiredness, Observed apnea, high blood Pressure, BMI >35, Age >50, Neck circumference >40cm, male Gender).

Treatment with CPAP often leads to a rapid resolution of nocturnal enuresis.

Source: Annals of IM - Nocturnal Enuresis In An Adult With Obesity

Phenylalanine Hydroxylase (PAH) Deficiency

PAH deficiency is an autosomal recessive inborn error of metabolism caused by mutations in the PAH gene. The deficiency impacts the conversion of phenylalanine to tyrosine, which in turn leads to an accumulation in the blood and brain.

The disease can be variable, all the way from classic phenylketonuria (PKU) to milder forms like hyperphenylalanemia. PKU can cause severe irreversible intellectual disability if untreated at birth. Hyperphenylalanemia on the other hand can present in adulthood with more subtle neurological or psychiatric symptoms, such as anxiety, tremor, or poor concentration.

A lifelong patient-reported history of “protein intolerance” is a red flag for an underlying amino acid disorder, even if symptoms are nonspecific.

Source: Annals of IM - Concurrent Phenylalanine Hydroxylase–Related Disorder And Celiac A Rare Co-Occurrence

Kikuchi-Fujimoto Disease (KFD) and its Association with HLH

KFD, also known as histiocytic necrotizing lymphadenitis, is a rare, largely benign inflammatory condition. It is also usually self-limited.

It most commonly presents in young Asian women with fever and tender cervical lymphadenopathy.

The etiology is unknown but is thought to be a reactive T-cell and histiocyte-mediated immune response to an infectious trigger like EBV or other viruses.

Leukopenia (specifically lymphopenia) is a particularly common finding.

On excisional lymph node biopsy, you will see “pericortical necrosis” with “karyorrhetic debris”, “histiocyte infiltrate”, and the notable absence of neutrophils (which helps distinguish it from bacterial lymphadenitis).

Though often benign, KFD can be a trigger for secondary HLH. If there is evidence of severe systemic inflammation, an HLH workup with ferritin, soluble IL-2 receptor, triglycerides, and fibrinogen is a good next step.

Patients with KFD will need to have long-term rheumatologic follow-up since up to 30% eventually develop SLE.

Diseases like KFD and HLH exist on a clinical spectrum. There is a concept of “partial HLH” where a patient has a clear hyperinflammatory state and meets some but not all of the formal criteria.

Source: Annals of IM - Kikuchi–Fujimoto Disease Presenting With Mesenteric Lymphadenopathy And Partial HLH

Salmonella Osteomyelitis

Salmonella osteomyelitis is a rare manifestation of salmonellosis. It accounts for less than 1% of all osteomyelitis cases.

It often happens due to hematogenous spread from a transient, clinically silent bacteremia after ingesting contaminated food.

While typically associated with immunocompromised patients (especially sickle cell disease, HIV, or malignancy), it can occur in immunocompetent individuals. It may even present without fever or a history of gastroenteritis.

The diagnosis can be tricky since patients will often have negative blood and stool cultures. It’s usually made when the patient develops pain and is found to have destructive bone lesions and/or abscesses on imaging.

Source: Annals of IM - Salmonella Osteomyelitis Of The Rib An Extraintestinal Manifestation

Acquired Angioedema 2/2 Splenic Marginal Zone Lymphoma (SMZL)

Acquired angioedema due to C1 esterase inhibitor deficiency is a rare but serious condition characterized by recurrent episodes of non-pitting swelling of the skin, respiratory tract, and GI tract

Unlike hereditary angioedema, it typically develops later in life and is often a consequence of a lymphoproliferative disorder, most commonly SMZL or another autoimmune condition.

SMZL is indolent and usually presents with massive splenomegaly and cytopenias, but without notable peripheral neuropathy.

In SMZL, the malignant B cell clone is thought to cause increased consumption or inactivation of C1 esterase inhibitor, often via antibodies, which leads to uncontrolled activation of the complement and kallikrein-kinin systems. This in turn results in excessive bradykinin generation, increased vascular permeability, and angioedema.

The classic profile is low C4, low C1-INH (level or function), and a low C1q. The low C1q is the key difference that helps distinguish acquired from inherited disease.

Acute attacks are treated with therapies that target the bradykinin pathway (such as icatibant) or by replacing the deficient protein (via C1-INH concentrate).

Cure can be achieved by treating the underlying lymphoma.

Source: Annals of IM - Case Of Splenic Marginal Zone Lymphoma Presenting As Acquired Angioedema

Hypocalcemia And Hypophosphatemia From Potent Acid Suppression

Acid suppression, particularly with potassium-competitive acid blockers (P-CABs) like vonoprazan, can affect intestinal calcium absorption via reduced ionization. This can then lead to hypocalcemia and a subsequent secondary hyperparathyroidism.

The surge in PTH can lead to significant renal phosphate wasting and hypophosphatemia. A high fractional excretion of phosphate can confirm renal phosphate wasting.

Patients with severe hypophosphatemia may present with unexplained generalized weakness.

Patients with poor oral intake, malabsorption, or an underlying vitamin D deficiency are at higher risk.

Source: Annals of IM - Generalized Weakness Due To Hypocalcemia And Hypophosphatemia From Potent Acid Suppression

This post highlights in-depth breakdowns of my favorite clinical cases from May 2026. I then provide some commentary and build on the lessons from my own experience, where appropriate.

I’ve broken these cases into multiple parts to keep the length of each post more digestable.

May 19, 2026 POCUS VMR with Dr. Jeffrey Kott, Ravi, and Deb - dyspnea on exertion (CPS)

Source

Case Summary

An 81F with AFib on apixaban, mod-severe MR who is 16 days post-hip arthroplasty presented with exertional dyspnea. She was hypoxic and tachycardic in AFib with RVR. BNP was elevated. CTPE confirmed a segmental PE with e/o right heart strain. It also noted diffuse GGOs. A POCUS showed no signs of acute severe RV dysfunction but did show diffuse bilateral B lines. The diagnosis was acute on chronic decompensated heart failure precipitated by A-fib with RVR, which was itself likely triggered by the PE. Given the above, the right heart strain called on the CT was likely related to overload and not hemodynamic compromise from an otherwise stable PE. The patient was managed with diuresis, rate control, and continued anticoagulation.

Hemodynamically Stable Pulmonary Embolism with Acute-on-Chronic Decompensated Heart Failure

This case highlights the importance of differentiating a hemodynamically significant PE from other causes of dyspnea and hypoxia. This can be challenging in patients with underlying cardiopulmonary disease. CTA can identify a thrombus and suggest RV strain by comparing ventricular diameters. However, a functional assessment with echo is essential to guide management.

In acute hemodynamically significant PE, elevated BNP and troponin can reflect myocardial stretch and injury.

POCUS or ECHO is the most critical tool for assessing the physiologic impact of the PE. Signs of acute RV pressure, overload, and failure include RV dilatation based on RV:LV ratio >1, interventricular septal flattening (the “D-sign”), and McConnell’s sign (RV mid-free wall akinesis with apical hyperkinesis), which is highly specific. Other findings can include a depressed RV systolic function (TAPSE <1.6 cm), significant tricuspid regurgitation (TR), and a dilated non-collapsible IVC.

Advanced Doppler findings, like the “6060 sign,” which is defined by pulmonary artery acceleration time < 60 ms and a TR gradient < 60 mmHg, are also highly specific for acute PE. This is because a chronically strained RV can often generate higher pressures than this.

A hemodynamically stable PE without RV dysfunction is treated with AC alone. A hemodynamically significant PE with evidence of RV dysfunction requires consideration of advanced therapies like systemic thrombolysis or catheter-directed thrombectomy.

Pearls

• Though valuable in some cases, a CTA report of “right heart strain” must be correlated with a functional assessment via POCUS or echo.

• The absence of classic echo signs of acute RV failure argues against a hemodynamically significant PE, even if a clot is present on imaging.

• In a patient with multiple potential diagnoses causing dyspnea, a POCUS can rapidly identify the primary derangement. In this case, diffuse B-lines confirmed pulmonary edema was the main driver of hypoxia.

• AFib with RVR can both be a consequence of a PE due to acute artery strain and a cause of decompensated heart failure, especially in patients with preexisting valvular disease and diastolic dysfunction

• Hypercoagulable structures in the right heart are not always caught in transit. True clots are typically mobile and serpiginous, whereas fixed structures are more likely normal variants, such as Chiari network or other pathology.

My Commentary

This case is excellent because it’s a reminder that all clinicians should be trained on POCUS. Though formal echos can often be done quickly in a hospital setting, decisions on patients that are intermediate-risk may be delayed which can be consequential. B-lines are one of the more satisfying things to identify on a POCUS, as this finding can certainly swing your clinical judgment in uncertain cases. This especially comes in handy in patients with multiple comorbidities presenting with dyspnea and you’re unsure whether it is driven by overload from ADHF vs another etiology. Everyone should feel comfortable with a the basic cardiac views, assessing for B-lines, and assessing for lung sliding. POCUS is best when used in addition to your usual focused workup.

May 23, 2026 Clinical Reasoning Expeditions with Jeffrey & Lera - 2 months of fatigue (CPS)

Source

Case Summary

A 56F with breast cancer on tamoxifen presented with several months of fatigue, shifting joint pains (migratory polyarthritis) with significant morning stiffness and subjective fevers. Her workup is notable for a positive COVID-19 test, a low TSH, an ANA 1:640, positive RF. ESR and CRSP were normal. Her physical exam was normal. On further history, the patient was found to be taking biotin supplements, and thus the TSH was favored to be spuriously low. Given she was not having objective fevers during subjective experiences, these experiences were re-characterized as hot flashes. These hot flashes in combination with prominent joint pains led to a diagnosis of tamoxifen-induced adverse effect. The medication was discontinued, and her symptoms completely resolved. The ANA and RF were felt to be red herrings.

Tamoxifen Adverse Effects

Tamoxifen-induced arthralgia is a common MSK side effect of treatment with selective estrogen receptor modulators (SERMs) which are used for hormone-positive breast cancer. The pathophysiology is thought to relate to estrogen deprivation, which is similar to what is seen with aromatase inhibitors.

Common presentations can include vasomotor symptoms such as hot flashes and MSK complaints. The arthralgia seen is often symmetric, affecting both small and large joints, and can be accompanied by significant morning stiffness that can closely mimic an inflammatory condition like RA or lupus. Fatigue is also frequently noted.

Understandably, the diagnosis of one of exclusion is made largely based on history. Key for your chart include the absence of inflammation on labs and a lack of objective synovitis or joint swelling, despite reports of severe pain and stiffness autoantibodies can be coincidentally positive and are common in the age group of women often taking tamoxifen. Positive serology alone does not indicate an underlying connective tissue disease.

Management is primarily symptomatic with analgesics such as NSAIDs. If symptoms are severe and impact quality of life, the definitive intervention is a discussion with the patient’s oncologist about discontinuing or changing therapy. The diagnosis is confirmed after a “de-challenge” where the drug is stopped and symptoms subsequently resolve.

Pearls

• It’s important to consider the difference between discomfort and dysfunction. This patient had significant subjective discomfort, including arthralgias and fatigue, but did not have any objective dysfunction since they had a normal exam, labs, and organ function

• Tamoxifen is a classic mimic of rheumatologic disease, since it can cause arthralgias and prominent morning stiffness.

• Biotin supplementation can interfere with many lab values and can classically cause spurious hyperthyroidism by falsely suppressing TSH and elevating free thyroid hormones

• A positive autoantibody does not equal a diagnosis. Without a compatible clinical syndrome, there are often incidental findings that can lead to a misdiagnosis if not interpreted in the appropriate context.

• Over time and depending on how it is asked, a patient’s description of symptoms can evolve. In this case, “subjective fevers” were later reframed as hot flashes, which was a key clue pointing towards a hormonal or medication-related etiology.

My Commentary

This case is great not only because it includes my favorite lab pearl (biotin producing spurious hyperthyroidism), but also because it includes a number of common pitfalls. The first pitfall taking vocabulary used by patients at face value instead of further questioning to better reinterpret the actual symptoms or sensations that the patient is experiencing. Patients use the terminology that they know, not necessarily the appropriate medical terminology that fits the situation. It’s a good starting point, and it’s valuable to mirror language that the patient uses. However, clinicians should always investigate further what patients mean by the terms that they use. I also loved the lab red herrings - I can’t tell you how many times unexpected abnormal labs that don’t seem to fit a specific clinical picture has led my teams astray. The last major takeaway is to remember that medications have side effects. I have a pet theory that the average complex patient on countless medications is almost certainly having some sort of side effect or nagging symptom that is either a consequence of one of the medications they take or a combination of multiple medications. While we certainly learn about common side effects of commonly prescribed medications, the reality is that it’s simply impossible to know, given it’s unlikely that I’m going to be de-prescribing medications in an inpatient setting unless there’s a clinical reason to do so.

May 27, 2026 VMR with Sharmin & Saketh - fever, diarrhea, RUQ discomfort (CPS)

Source

Case Summary

A 61M with T2DM and HTN presented with five days of fevers, diarrhea, cough, and RUQ discomfort. Shortly after presentation, he clinically deteriorated, developing hypoxemia, confusion, AKI, transaminitis, and rhabdomyolysis. Imaging was notable for a right basilar opacity that progressed to bilateral infiltrates. There was a strong clinical suspicion for Legionnaires disease, however, the urine Legionella antigen test was negative. Given clinical suspicion, a bronchoscopy was performed that showed a positive PCR for Legionella species. It was attributed to a non-serogroup one strain from a recent potting soil exposure. He was treated with azithromycin and improved significantly.

Legionnaires’ Disease

Legionella species are gram-negative intracellular bacteria that can cause an atypical pneumonia known as Legionnaires disease. Transmission occurs via inhalation of aerosolized contaminated water. Sources can include cooling towers, plumbing systems, hot tubs, and, less commonly, soil or compost. The classic presentation is a severe pneumonia that’s accompanied by prominent extrapulmonary manifestations.

Patients often present with high fever, dry cough, and shortness of breath. Diarrhea, nausea, and abdominal pain are very common. Neurological symptoms like headache and confusion are also classic. Relative bradycardia (also known as Faget sign) can also be a clue.

Hyponatremia is also a classic finding. Inflammatory markers such as CRP and ferritin are typically elevated.

Chest imaging usually shows patchy unilobar consolidation that can rapidly progress to bilateral involvement and pleural effusions.

The urine antigen test is rapid and widely used but primarily detects the serogroup 1, which is the most common cause. A negative test does not rule out disease from other serogroups or species. Definitive diagnosis can be made by culture on buffered charcoal yeast extract agar or, more commonly, by PCR on respiratory specimens such as sputum or BAL fluid.

Legionnaires disease is treated with a macrolide (azithromyin), or a respiratory fluoroquinolone such as levofloxacin. In cases where there’s clinical suspicion, they should be started empirically, waiting for confirmatory results.

Pearls

• A negative Legionella urinary antigen does not rule out the diagnosis. It is insensitive for non-serogroup one species like L. longbeachae.

• A detailed exposure history can be invaluable. You should ask beyond water exposure and ask about gardening and exposure to potting soil or compost.

• A sputum gram stain showing many neutrophils but few or no visible organisms is a classic clue for an intracellular pathogen such as Legionella.

• In patients with suspected atypical pneumonia and a negative urine antigen, proceeding to a bronchoscopy for PCR and culture can be a critical diagnostic step.

• Relative bradycardia in a febrile patient should prompt consideration of intracellular pathogens, including Legionella, Salmonella, Chlamydia

My Commentary

What I like about this case is the clinical gumption to feel strongly about a disease despite a negative test. It also brings to mind the importance of covering for atypical infections when there’s concern for a pulmonary source of sepsis. I’ve seen a number of times patients coming in starting cap antibiotics, and when the patient starts to decompensate they are broadened to a regimen such as vancomycin and cefepime, without the inclusion of a medication that will treat atypicals. There are numerous types of atypical infectious processes that can lead to patients deteriorating and having evidence of end-organ dysfunction. Always be mindful of what you are covering for and what the suspected source is! Lastly, I’ve seen conflicting data on whether hyponatremia is actually attributable to Legionnaires specifically, or if it’s just more likely an SIADH related to severe illness and pneumonia. I’d say the most important takeaway is that the absence of hyponatremia shouldn’t dissuade you from thinking about Legionnaires, even though that’s one of the classic associations. Instead, its presence can just be one more data point consistent with the diagnosis.

This post highlights in-depth breakdowns of my favorite clinical cases from May 2026. I then provide some commentary and build on the lessons from my own experience, where appropriate.

I’ve broken these cases into multiple parts to keep the length of each post more digestable.

May 13, 2026 VMR with Sharmin & Kirtan - SOB, headache, fever, confusion (CPS)

Source

Case Summary

A 76F presented with fevers, headache, and confusion. The exam was notable for a facial droop, unilateral weakness, and anisocoria. Brain MRI showed multiple scattered ring-enhancing lesions with central diffusion restriction at the grey-white junction. It also noted microhemorrhages and leptomeningeal enhancement. Together, this was concerning for septic emboli and abscess. Workup was surprisingly negative, including multiple BCx, LP, and TTE/TEE, a clinical diagnosis of disseminated Nocardiosis was made. She was empirically treated with prolonged abx and showed some radiologic improvement. However, she suffered permanent vision loss from ocular involvement and remained functionally impaired after a prolonged four-month hospitalization.

Suspected Disseminated Nocardiosis

Nocardiosis is an opportunistic infection caused by Nocardia species. They are ubiquitous, dwell in soil, are gram positive, weakly acid fast, branching filamentous bacteria. Patients are usually infected via inhalation, which leads to a primary pulmonary process that can mimic TB or malignancy. Imaging might show nodules, consolidation, or cavities. From the lungs, it can disseminate hematogenously to essentially any organ. However, it has a strong predilection for the CNS.

The classic triad includes disease of the lungs, CNS, and skin. CNS involvement is most commonly a single or multiple brain abscess, occurs in up to 40% of disseminated cases. Ocular involvement (endophthalmitis) can also occur.

It primarily affects individuals with impaired cell-mediated immunity (those with solid organ transplant, chronic steroid use, malignancy, or HIV). However, it can occur in patients with underlying lung disease, even if they’re immunocompetent.

Definitive diagnosis depends on isolating the organism via culture. However, Nocardia is notoriously slow-growing and can be missed on routine cultures. It requires prolonged incubation in selective media. Modified acid-fast staining is also a crucial diagnostic step.

Management of disseminated disease requires long-term combination abx therapy often for 6 to 12 months. For severe CNS disease, most courses will start with IV Bactrim plus ceftriaxone or a carbapenem before switching to an oral regimen.

Pearls

• A brain MRI showing multiple ring-enhancing lesions at the gray-white junction is the classic finding of hematogenous spread, most commonly of septic emboli or metastatic disease.

• Nocardia is another “great masquerader” and can be notoriously difficult to isolate. Clinicians must maintain a high degree of suspicion when initial infectious work-ups are negative.

• The presence of both abscesses and hemorrhage on brain imaging points towards some type of angio-invasive infectious etiology.

• Clinical or radiologic response to specific antibiotics can serve as a diagnostic clue when suspected infectious etiologies are susceptible to these drugs.

My Commentary

Cases like this scare me because I found myself many times being confused about a clinical case because “the workup has been completely negative.” I try to remind myself that in certain situations, repeating tests (sometimes multiple times) is required to align on a final diagnosis. Not only that, but sometimes the workup will remain negative, and you need to use your clinical acumen to put your money down and say, “I still think this is what’s going on anyway.” Most clinicians (myself included) don’t receive much training on understanding the sensitivity and specificity of the various labs and imaging tests that we order. Moreover, we certainly don’t learn much about the sensitivity and specificity for the uncommonly ordered tests for various rare diseases that we don’t see often. As such, it’s easy for us to assume that because an initial workup we sent was revealing that this automatically rules out certain diseases. However, this is often not the case.

May 14, 2026 VMR with Kirtan & Sam B - SOB and weight loss (CPS)

Source

Case Summary

A 52M who recently immigrated from India presents with a six-week history of fever, fatigue, SOB, hemoptysis, nosebleeds, hearing loss, and a skin ulcer. Initial imaging showed a suprahilar mass, a cavitary lung lesion, and bilateral nodules. Given the presumed diagnosis of pulmonary tuberculosis, he was treated empirically with RIPE therapy. He was readmitted ten days later in shock with worsening symptoms and new findings of scleral injection and palpable purpura. A broader workup resulted in a positive c-ANCA, and his skin biopsy of his lesions showed small vessel vasculitis. The patient was ultimately diagnosed with granulomatosis with polyangiitis (GPA), which responded to treatment with prednisone and rituximab

Granulomatosis with Polyangiitis (GPA)

GPA is a systemic autoimmune disease with necrotizing granulomatous inflammation and small to medium vessel vasculitis. It is an ANCA-associated vasculitis. Classically, it presents with a triad of upper respiratory tract, lower respiratory tract, and renal disease.

Upper respiratory presentations include sinusitis, nasal crusting, saddle nose deformity, nosebleeds, ear infections, or hearing loss.

Low respiratory symptoms include cough, dyspnea, and hemoptysis.

Renal disease will often show up as a rapidly progressive glomerulonephritis. You will usually see active urinary sediment (hematuria, proteinuria, and RBC casts).

Patients often present with constitutional symptoms (fever, weight loss), skin lesions, (ulcers, palpable purpura) or eye disease (scleritis and uveitis). Neuropathies are also common.

A positive c-ANCA (anti-proteinase 3 or PR3-ANCA) is highly specific (>90%).

CXR or CT chest often reveals nodules (sometimes cavitations), or GGOs (which may suggest alveolar hemorrhage).

The gold standard of diagnosis includes a biopsy of an affected organ such as the kidney, lung, or skin.

Management is focused on inducing remission with high-dose glucocorticoids plus rituximab or cyclophosphamide. This is then followed by maintenance therapy.

Pearls

• GPA notoriously mimics other disseminated infections such as tuberculosis. It can be challenging to differentiate them given overlapping constitutional symptoms and cavitary lung lesions. Failure to improve or clinical worsening on appropriate empiric therapy (like RIPE for suspected TB) is a critical signal to aggressively re-evaluate the initial diagnosis.

• While the classic triad of upper airway, lower airway, and renal disease can suggest GPA, systemic clues like palpable purpura and cranial neuropathy causing hearing loss are hints pointing towards a vasculitic process.

• Though less common, large mass-like lesions can be seen in GPA and reflect intense granulomatous inflammation.

• A positive c-ANCA (PRC-ANCA) this is a specific marker for GPA and should be ordered early if there’s clinical suspicion of some sort of multi-systemic inflammatory process

May 15, 2026 VMR with Zaven and Rabih - Bilateral flank pain with a twist (CPS)

Source

Case Summary

A 20F presents with 8 hours of acute severe epigastric pain, which radiated to the flanks. Initial workup was notable for an elevated lipase, which pointed towards pancreatitis. Despite initial supportive care, she rapidly deteriorated over the subsequent admission. She developed anemia (Hgb 5.7), thrombocytopenia (Plt 28), renal failure requiring CRRT, and evidence of intravascular hemolysis (LDH 2500, hapto undetectable). All together, this was concerning for the development of thrombotic microangiopathy (TMA), with pancreatitis considered to be either a trigger or downstream consequence. ADAMTS13 level was normal, which ruled out TTP. A low C3 level helped align on a diagnosis of atypical hemolytic uremic syndrome (aHUS). She was treated with eculizumab and had dramatic improvement in her clinical status. An endoscopic ultrasound revealed microlithiasis, which solidified a final diagnosis of biliary pancreatitis, which triggered complement-mediated aHUS.

Atypical Hemolytic Uremic Syndrome (aHUS)

aHUS is a rare life-threatening form of TMA. It’s caused by chronic uncontrolled activation of the alternative complement pathway. This activation leads to endothelial damage and systemic microvascular thrombosis. Around 50 to 60% of cases are associated with genetic mutations in complement regulatory proteins, however many are idiopathic. The disease often remains latent until it is unmasked by a complement-activating condition or trigger. Examples include infection, surgery, pregnancy, or, as in this case, severe pancreatitis.

Patients may present with the classic triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and AKI. The ischemic injury with TMA can also affect any other organ, including the pancreas, brain, and heart.

On labs, you’ll see evidence of non-immune intravascular hemolysis, such as anemia, schistocytes, high LDH, indirect bilirubin, undetectable hapto, and a negative Coombs. A normal or near-normal ADAMTS13 activity >10% effectively rules out TTP. Complement studies may show a low C3, but levels are normal in up to 50% of patients.

C5 complement inhibitors, including eculizumab and ravulizumab, are now first-line therapy.

Pearls

• Severe pancreatitis can either be the initial insult or the consequence of TMA.

• A combination of acute anemia, thrombocytopenia, and AKI defines a TMA.

• In cases of TMA, the immediate diagnostic priority is to distinguish TTP from aHUS based on ADAMTS13 activity. TTP requires emergent plasmapheresis, whereas aHUS requires complement inhibition.

• A low C3 level can be a useful clue for complement-mediated aHUS. It’s only found in about half of cases

• Biliary sludge (microlithiasis) it can be a cause of pancreatitis but is often missed on imaging and is only seen on endoscopic ultrasound.

My Commentary

Nearly 10 years ago, when I was an early clerkship student, I helped one of our teams win a Jeopardy-style competition by naming eculizumab and its mechanism. It’s wild that I actually remember that, but I haven’t forgotten eculizumab since! I found this case particularly interesting because the team still wasn’t certain whether pancreatitis was a trigger or downstream consequence of the aHUS. It’s an important reminder for me to not anchor on the initial diagnosis and to ensure I haven’t left any stone unturned when there are abnormal lab values. It’s challenging, given severe pancreatitis alone can lead to clinical deterioration and organ dysfunction - you need to be discerning enough to take each problem by itself and not attribute it just to sepsis or severe inflammation alone. Whenever you have concern for acute anemia and thrombocytopenia, the smear can always be a fun thing to review with your friendly hematology consultant. Whenever I look at a smear with a hematologist or pathologist, I always learn something new!

This post highlights in-depth breakdowns of my favorite clinical cases from May 2026. I then provide some commentary and build on the lessons from my own experience, where appropriate.

I’ve broken these cases into multiple parts to keep the length of each post more digestable.

May 7, 2026 VMR with Rabih & Sarah B - painful urination and hematuria (CPS)

Source

Case Summary

A 28F presented with three days of dysuria along with gross hematuria and right flank pain. Together, these were suggestive of complicated nephrolithiasis. CT revealed bilateral nephrolithiasis and a right ureteral stone. However, labs are also notable for calcium 11.8 mg/dL with a PTH of 145. Together, these were evidence of primary hyperparathyroidism. On further intake, the patient also reported chronic fatigue, constipation, and irregular menses. Additional workup uncovered high prolactin (120 ng/mL). On even further questioning, the patient revealed a family history of endocrine tumors. The patient was ultimately diagnosed with multiple endocrine neoplasia type 1 and (MEN 1). Imaging confirmed a 1.4 cm pituitary macroadenoma. She was started on a dopamine agonist.

Multiple Endocrine Neoplasia Type 1 (MEN1)

MEN1 (also known as Wermer’s syndrome), is it an autosomal dominant disorder caused by mutations in the MEN1 tumor suppressor gene. As you likely recall from your STEP days, it is characterized by the development of tumors in the “three Ps”: parathyroid, pituitary, and pancreas (or duodenum).

The most common manifestation in over 90% of cases is primary hyperparathyroidism. This is also the earliest manifestation. Patients will often present with hypercalcemia or hypercalcemia-related symptoms, including nephrolithiasis, bone pain, constipation, or fatigue. Pituitary adenomas are the next most common, and prolactinomas are the most frequent type. Prolactinomas can cause amenorrhea, galactorrhea, or decreased libido. Pancreatic neuroendocrine tumors (pNETs) include gastrinomas (which cause Zollinger-Ellison syndrome), insulinomas, VIPomas, and non-functioning tumors.

In patients with suspected MEN1, a full endocrine screen should be sent. This includes prolactin, gastrin, IGF-1, insulin, and glucose to screen for the classic “P” tumors.

Once a biochemical diagnosis is made, imaging is needed to help localize tumors. Neck ultrasound or sestamibi scans can evaluate parathyroid glands. Pituitary MRI is the best modality to assess for adenomas. CT or MRI of the abdomen is most commonly used to screen for pNETs.

However, the final diagnosis of MEN1 is confirmed with genetic testing.

Prolactinomas are treated medically with dopamine agonists. Management of hyperparathyroidism in MEN1 is complicated. These cases often involve asymmetric 4-gland parathyroid hyperplasia whereas sporadic cases will have a single adenoma that can simply be removed. All of the parathyroids will often be removed with auto-transplantation. Some patients will need medical therapy with cinacalcet.

All patients with MEN1 will require lifetime imaging surveillance for new tumors.

Pearls

• Vague systemic symptoms like fatigue or constipation, along with an endocrine abnormality such as irregular menses should raise suspicion. The addition of kidney stones should further raise the suspicion, given likely underlying hypercalcemia.

• In patients diagnosed with endocrine tumors at a young age, a detailed family history can be critical given it may change surgical planning for hyperparathyroidism due to four-gland hyperplasia and not a single adenoma that can simply be removed

• Chronic hypercalcemia can mimic IBS, particularly the constipation-predominant type. Before formally diagnosing IBS, you should always check a calcium level.

• Patients with recurrent kidney stones should always have a BMP checked to rule out metabolic causes like hypercalcemia which may lead to further diagnoses

My Commentary

The the very first rotation I ever did during my clerkship year was with an endocrine oncology surgical team. Thus, I have a particular affinity for these unusual endocrine tumors and the nuances of their management. It was an amazing first clinical experience. Although it made me assume that zebras (pheochromocytomas, gastrinomas, insulinomas, MEN1, etc.) are much more common than they are!

This case is particularly interesting because it unfolded in a realistic manner. In my opinion, it highlights how most atypical or rare diseases are ultimately diagnosed. Many case reports will organize information plainly in a streamlined manner, leading us to assume the clinicians went through the diagnostic process in a stepwise manner to arrive at the final diagnosis. However, the reality is that unexpected laboratory and imaging findings will often lead clinicians to pause and go backwards to further clarify history with the patient which then helps them arrive at the diagnosis. Although we were taught in medical school to do a thorough family history and complete a full ROS, in reality, this does not happen. I don’t say this to imply that clinicians (myself included) are lazy, but rather than effective, focused history, exam, and diagnostic workups focus on likely and life-threatening etiologies. When data is introduced that is unexpected or changes the clinical picture, good clinicians will not disregard it but rather will investigate further and not be afraid to move backwards.

I distinctly recall a case of a patient diagnosed with Pasteurella bacteremia when I was a resident. Only after the blood cultures returned positive did I ask the patient if she had any pets or recent bites. She revealed that she did in fact have a new puppy, and showed me a very small, healing red cut on the inside of her index finger. She sheepishly added “he didn’t mean to - he was just playing!” All’s well that ends well.

The case is also a great reminder that some nondescript or common symptoms, such as fatigue, constipation, irregular menses may individually not be particularly notable. However, if such symptoms are persistent, it’s important to think through how they interact and what a common root cause might be. This can be particularly challenging in patients that report many disparate seeming symptoms.

Progressive Internal Carotid Artery Occlusion In IgG4-Related Disease (Annals of IM)

Source

Case Summary

A 56M presented with a number of recurrent ischemic strokes and was found to have progressive upper extremity weakness. These findings were initially attributed to mild carotid plaque. However, his neurological status deteriorated despite antithrombotic therapy. Imaging revealed new scattered infarcts and progression of his right internal carotid artery (ICA) plaque to severe stenosis with occlusion. He had a workup for cryptogenic stroke completed. It was notable for a serum IgG4 level of 2050 mg/dL (very high). Subsequent PET scan showed multifocal hypermetabolism in the Waldeyer ring and cervical lymph nodes. The patient had a tonsillar biopsy that confirmed the diagnosis, showing a dense lymphoplasmacytic infiltrate with IgG4/IgG >40%. He was treated with IVIG and glucocorticoids, then mycophenolate mofetil (MMF). The patient showed partial functional recovery.

IgG4-Related Disease (IgG4-RD)
IgG4-Related Disease is a systemic immune-mediated fibroinflammatory condition with tumefactive lesions that result from the infiltration of IgG4-positive plasma cells into different organs in the body. Classic presentations typically involve the pancreas, salivary or lacrimal glands, and retroperitoneum. However, essentially any organ can be affected by the disease. Patients with neurological involvement will often present as hypophysitis. Synovitis of the intracranial arteries due to large vessel vasculitis is rare in this disease but does happen.

Workup starts with a serum IgG4 concentration. A level >135 mg/dL is consistent with the diagnosis. However, note that this lab is neither 100% sensitive nor specific.

CT or MRI might show organ enlargement or mass-like lesions. If the patient has a concomitant vasculitis, vessel wall imaging might reveal concentric enhancing wall thickening, which will appear different from typical atherosclerosis. A PET can be extremely useful to identify occult sites of inflammation and help guide biopsy.

Histopathology will show lymphoplasmacytic infiltrate, “storiform” fibrosis, and “obliterative phlebitis”. Immunohistochemistry will help confirm the diagnosis by showing >10 IgG4-positive plasma cells per high-power field. Importantly, the IgG4 to IgG cell ratio will exceed 40%.

Glucocorticoids are first-line therapy, which will often lead to rapid responses. Rituximab or MMF are then frequently used for maintenance therapy or in cases where steroids are not working.

Pearls

• IgG4-RD should be considered in the ddx for cryptogenic stroke. Clues can be stroke in patients with multifocal or atypical large vessel vasculopathy who do not have traditional atherosclerotic risk factors.

• Although an elevated serum IgG4 is a major clue, the diagnosis requires a biopsy, since other inflammatory malignant conditions can also raise the IgG4 levels.

• PET scans are especially useful for helping identify biopsy sites. Salivary glands and superficial lymph nodes are easily accessible and often high-yield.

• In patients with vascular stenosis who progress despite typical antiplatelet or AC therapy, you should consider an underlying inflammatory vasculitis.

• Treatment with immunosuppression not only halts progression but can also reverse stenosis.

My Commentary

IgG4-RD is one of those confusing diseases that internal medicine physicians (myself included) love to bring up on their differential. In my experience, working up cryogenic strokes with multifocal scattered infarcts across different vascular territories, it’s almost always been in the setting of occult malignancy like pancreatic cancer. This makes sense simply given the prevalence of the underlying causative diseases (malignancy is much more common than IgG4-RD) . But it’s important to remember that any prothrombotic or inflammatory disease can lead to similar outcomes. When we’ve had a high clinical suspicion for IgG4-related disease in patients I have cared for, I don’t know that the diagnosis was ever truly a slam dunk, even after biopsy. This might be due to the pearl above that IgG4 can be elevated in other inflammatory or malignant conditions.

Atypical Epigastric Pain Reveals Obstructive Urosepsis In A Horseshoe Kidney (Annals of IM)

Source

Case Summary

A 61F with no notable PMH presented in septic shock with severe epigastric abdominal pain and N/V. Despite this, she had no urinary symptoms, and an exam did not show any CVA tenderness. However, UA showed significant pyuria and positive nitrates. CTAP showed a horseshoe kidney with a large obstructing right ureteropelvic junction stone. Despite this, there was only mild to moderate hydronephrosis. The patient recovered after fluid resuscitation, abx, and an emergent PCN for urinary decompression.

Obstructive Urosepsis in a Horseshoe Kidney

Obstructive urosepsis is a life-threatening emergency where UTI is complicated by a blockage and leads to sepsis. The obstruction prevents clearance of infected urine. This leads to pressure building up in the collecting system and facilitates bacterial translocation into the bloodstream. A horseshoe kidney is a congenital disorder where the kidneys are fused at their lower poles, which creates a U-shape. Horseshoe kidneys lead to unusual ureteral courses and change the angle of insertion, which can predispose patients to urinary stasis. This leads to increased risk of nephrolithiasis and obstruction.

Fever, chills, and flank pain are classic signs of sepsis from a urinary source. However, presentations in patients with horseshoe kidneys may be atypical. Such patients may present with abdominal or epigastric pain and lack clear urinary symptoms.

Management requires prompt BSA and urgent urinary decompression to achieve source control. This is most typically achieved with a PCN or ureteral stenting.

Pearls

• In patients with unusual urinary anatomy, infections may present atypically without GU symptoms. The abnormal position and visceral innervation of a horseshoe kidney can refer pain to the mid-abdomen or epigastric region and present more like pancreatitis

• The degree of dilation in hydronephrosis does not always correlate with the severity of an infection; you should not be falsely reassured by a mild to moderate hydronephrosis.

My Commentary

I like this case because it reminds me that patients can still present with sepsis from a urinary source even if they don’t have clear urinary symptoms. In my experience, this most commonly happens in elderly patients, or in those that have unusual anatomy (congenitally, or surgically) or indwelling lines. The latter can be particularly challenging because their urine will often show pyuria due to inflammation from foreign material. More often than not, in my clinical experience, I face the opposite problem: patients with pyuria and positive UCx who do not seem to have any clinical symptoms. I actually feel this might be a more challenging clinical situation because in patients who present with evidence of sepsis or septic shock, you are going to always treat with antibiotics anyway. In clearly ill patients, the real clinical challenge, as this case shows, is to recognize that patients won’t improve without source control and thus, imaging of the abdomen in patients that don’t otherwise have a clear source can be critical to help guide management and potentially save a life.

This post highlights in-depth breakdowns of my favorite clinical cases from May 2026. I then provide some commentary and build on the lessons from my own experience, where appropriate.

I’ve broken these cases into multiple parts to keep the length of each post more digestable.

Case 15-2026 A 64-Year-Old Woman With Fatigue, Memory Changes, And Falls (NEJM)

Source

Case Summary

A 64F with h/o BRCA2 presented with a subacute three-week course of progressive fatigue with cognitive changes, unsteady gait, and repeated falls. An MRI of the brain revealed numerous mildly expansile gadolinium-enhancing white matter lesions. These lesions featured both closed ring and open ring enhancement. An LP subsequently showed lymphocytic pleocytosis. Given uncertain diagnosis, a brain biopsy was performed to rule out malignancy or infection. Pathology showed a macrophage-rich inflammatory process with demyelinization and axonal preservation. Together, these were classic for demyelinating disease. A final diagnosis of Tumefactive Late-Onset Multiple Sclerosis was made. She was treated with high-dose corticosteroids and clinically improved. She was then started on long-term disease-modifying therapy.

Tumefactive Multiple Sclerosis (MS)

Tumefactive MS is a rare variant characterized by large tumor-like demyelinating lesions greater than 2 cm. It can be the initial manifestation of MS. Given it often presents with focal deficits, encephalopathy, and mass effect, the ddx initially is often quite broad and includes primary tumors like gliomas, lymphoma, and abscesses.

MRI is the most crucial non-invasive tool for diagnosis. You’ll see T2/FLAIR hyperintense lesions with an incomplete or “open ring” pattern of enhancement. In comparison, abscesses will show complete uniform rings, and high-grade gliomas will show thick irregular rings. These lesions will also lack central restricted diffusion that is characteristic of a pyogenic abscess.

CSF will often show a mild lymphocytic pleocytosis and elevated protein. The presence of CSF-restricted oligoclonal bans or an elevated free-capital light chain index is supportive of an MS diagnosis.

When biopsies are performed, histology will show an inflammatory infiltrate dominated by foamy :myelin-laden: macrophages. There will be a profound loss of myelin, but relative preservation of axons.

Management consists of high-dose IV corticosteroids for an acute attack, with plasma exchange as a second-line option. Patients have then started on long-term Disease Modifying Therapy (DMT) prevent future relapses and disability.

Pearls

• Tumefactive MS is a great mimicker of CNS malignancy and infection

• The ddx for ring-enhancing brain lesions is broad, and this diagnosis should always be considered.

• The “open-ring” sign on contrast-enhanced MRI is a specific clue for demyelinating disease.

• The absence of restricted diffusion within a ring-enhancing lesion is a critical imaging feature that makes a pyogenic abscess much less likely.

• While MS is typically a disease of young adults, late-onset MS (after age 50) can occur and may present with an aggressive, tumefactive subtype.

My Commentary

In my opinion, a new brain lesion presents one of the more interesting differentials in all of medicine. Given my own clinical blind spots (I only care for MS patients these days if they happen to have it as a co-morbidity), I wasn’t even aware of tumefactive MS and the intricacies of how they appear on imaging. For me, it was a good reminder that not every space-occupying lesion that shows up in the brain is either malignant or infectious.

Glomerulonephritis Caused By Bartonella Quintana Endocarditis (Annals of IM)

Source

Case Summary

A 60M with housing insecurity presented with one week of painful blistering rashes and in one month history of nondescript constitutional symptoms. However, he was notably afebrile. Lab showed that he had a severe AKI along with anemia and thrombocytopenia. He progressed to renal failure and required hemodialysis. A skin biopsy showed leukocytoclastic vasculitis. A renal biopsy revealed a pauci-immune crescentic glomerulonephritis. Workup was otherwise notable for negative BCx, yet a TEE confirmed a mitral valve vegetation. The diagnosis of Bartonella quintana endocarditis was sealed when IgM and IgG serologies were positive. He was treated with a prolonged course of doxycycline and rifampin.

Bartonella quintana Endocarditis

Bartonella endocarditis is a classic cause of culture-negative endocarditis. Bartonella is a slow glowing GNR transmitted by the human body louse. It is historically associated with “trench fever”. It more commonly affects individuals experiencing homelessness, alcoholism, or crowded living conditions.

Clinical presentation is often sub-acute and may lack overt fevers. Patients also frequently present with complications of a chronic infection, such as heart failure from valvular destruction.

The diagnosis relies heavily on serology, given BCx are almost always negative. A high IgG antibody titer (specifically > 1:800), along with a positive IgM is consistent with the disease.

TTE/TEE typically reveal large friable vegetations. These are most commonly on the aortic or mitral valves.

Labs may show anemia, thrombocytopenia, and elevated inflammatory markers (ESR/CRP). Patients with glomerulonephritis will have hematuria, proteinuria, and elevated creatinine, and often low complement levels.

Treatment requires a prolonged course of abx. Typical regimens for native valve endocarditis include doxycycline for at least six weeks. This is often combined with an aminoglycoside such as gentamicin for the initial two weeks. Given its common to see extensive valvular damage and heart failure, valve replacement surgery is often needed.

Pearls

• Bartonella is a leading cause of culture-negative endocarditis.

• Given the presentation of Bartonella endocarditis can be insidious in a febrile, you should be alert for the evidence of immune-mediated complications such as glomerulonephritis or a vasculitic rash.

• Do not rule out endocarditis based on negative BCx alone, especially when the clinical picture is suggestive. Diagnosis of Bartonella endocarditis relies on serology.

• A low C3 with a normal C4 is a clue for an underlying infection-related glomerulonephritis.

My Commentary

This is such a great case given not only because of the the final diagnosis of culture negative endocarditis, but also because of the reminder that endocarditis is a systemic disease process and can lead to various immunological and other manifestations in various organs throughout the body, notably the kidneys in this case. It’s not easy to think about endocarditis and get an echo when BCx are negative, and it takes even more clinical gumption to be concerned enough to get a TEE when a TTE seems normal. In my experience caring for patients with Cx negative endocarditis, I was lucky enough to have the diagnosis sealed with TTE alone.

Polymorphic Ventricular Tachycardia, Sarcoidosis, And The Ultimate Unmasking Of A Pheochromocytoma (Annals of IM)

Case Summary

A 54M with pulmonary sarcoidosis presented with palpitations. He was treated with metoprolol. However, an implantable loop recorder captured polymorphic ventricular tachycardia (PMVT). Given his history of sarcoid, the team initially pursued a diagnosis of cardiac sarcoidosis. However, the patient had a negative cardiac MRI and PET scan. The patient then went on to develop paroxysmal severe HTN with diaphoresis and tremors. This new information prompted his PCP to test for pheochromocytoma. The patient had elevated urine metanephrines and a 3 cm adrenal mass on CT. Surgical resection resolved in a complete resolution of all of his arrhythmias and HTN.

Pheochromocytoma

Pheochromocytomas are rare neuroendocrine tumors of the adrenal medulla. They secrete catecholamines such as epinephrine and norepinephrine. The textbook presentation of pheochromocytoma is a triad of episodic headaches, diaphoresis, and tachycardia. However, the presentation can be highly variable. Most patients experience either sustained or intermittent HTN which can be difficult to control. Catecholamine excess can lead to cardiac manifestations including sinus tachycardia, SVT, ventricular arrhythmias, and stress-induced (Takotsubo) cardiomyopathy.

The initial screen is with plasma-free metanephrines or 24-hour urinary fractionated metanephrines. Both of these tests have high sensitivity.

Once these screens are positive, localization is performed with CT or MRI of the abdomen and pelvis. Functional imaging (MBG, DOTATATE) can be used if localization is difficult.

Management is largely focused on surgical resection. Prior to surgery, patients require preparation with alpha-adrenergic blockade with either phenoxybenzamine or doxazosin. This helps to control blood pressure and prevent intraoperative hypertensive crisis. Beta blockers are only added after adequate alpha blockade to help manage any reflex tachycardia.

Complete surgical removal of the tumor is often curative.

Pearls

• Pheochromocytoma is another “great mimicker”. Catecholamine excess can lead to a number of bizarre symptoms including diverse arrhythmias and paroxysmal HTN.

• Though they are not the most common manifestations, life-threatening ventricular arrhythmias like PMVT are possible

• Initiating beta-blockers before alpha-blocker in a patient with a pheochromocytoma can lead to a hypertensive crisis

My Commentary

This case is a strong reminder of when anchoring on a seemingly straightforward manifestation of an already diagnoses disease can lead clinicians astray. I largely care for oncology patients in the hospital, and the bias of ascribing any symptom/presentation to chemo and/or their primary malignancy is one I fight against every single day. It can be challenging, however, when 99 times out of 100 this assumption is correct. This is why pattern recognition, and trusting your clinical intuition when something seems off, is so important.

TL;DR

Gabapentinoids are useful drugs, but they are not harmless “low-risk” pain meds.

They work best for true neuropathic pain, where alpha-2-delta-1 calcium channel upregulation is part of the biology.

Gabapentin has saturable absorption and diminishing returns at higher doses; pregabalin is more predictable but has higher misuse potential.

Both require renal dose adjustments, can accumulate and cause a neurotoxic syndrome, can cause withdrawal, and increase respiratory depression risk when combined with opioids or other sedatives.

Use them when the pain syndrome fits the drug’s mechanism, dose them appropriately based on renal function and other risks, and don’t escalate indefinitely.

Gabapentinoids are everywhere, but not benign

They feel safer than opioids, less intimidating than a TCA, and easier to prescribe than other alternatives. But gabapentinoids are not benign enough to be used liberally for the “just in case it works” pain.

They have unusual absorption, unpredictable dose-response, renal accumulation, dose-limiting neurotoxicity, withdrawal syndromes, misuse potential, and evidence of respiratory depression when combined with opioids and/or other sedatives. They are also genuinely useful when the pain syndrome is neuropathic, and the drug is dosed with its pharmacology in mind.

Understanding the mechanism explains when it works, when it does not, and why pushing the dose higher often stops making sense.

“Gabapentinoid” is a misnomer.

Despite being structural analogs of GABA, they do not act on GABA receptors at all and instead bind the alpha-2 delta-1 subunit of presynaptic voltage-gated calcium channels. This binding in the CNS reduces calcium influx and dampens release of excitatory neurotransmitters (such as glutamate, substance P, and norepinephrine) into the dorsal horn.

Gabapentin was approved in 1993 for epilepsy, and the neuropathic pain use was a later development. Pregabalin is the S-enantiomer of 3-isobutyl-GABA and was engineered as a successor to gabapentin.

This class of drugs is particularly effective for neuropathic pain because peripheral nerve injuries lead to the upregulation of the alpha-2 delta-1 subunits in the dorsal root ganglia.

Why gabapentin dosing is weird

Its absorption is non-linear, meaning that the bioavailability falls as the dose rises. Thus, giving higher doses leads to diminishing returns.

Gabapentin is absorbed only via an L-amino acid transporter in the proximal small bowel, and this transporter is saturable. At 900 mg a day, bioavailability of gabapentin is about 60%. At 3,600 mg a day, this drops to 33%.

Gabapentin’s half-life is only 5 to 7 hours. Spacing out doses more than 12 hours apart leads to diminishing returns. This is why TID dosing is the norm, and you can’t rely on one single large dose to get through the day.

There is little point in going above doses of 1800 to 2400 mg/day for most indications. Most neuropathic pain patients plateau around 1800 mg/day. The variable bioavailability explains why the dose response is unpredictable between patients.

Starting doses (in those with healthy kidneys) are usually:

• 300mg qhs on day 1

• 300mg BID on day 2

• 300mg TID on day 3

From there, you can increase each dose by 100mg with a general “target” of 1800mg/day divided into TID doses.

Why pregabalin is more predictable

In contrast, pregabalin is rapidly and completely absorbed (it is also taken up in the proximal colon). It also has a flat, predictable bioavailability of over 90% across the entire dose range. It has peak levels at one hour compared to three hours for gabapentin, so it works quicker. It also has roughly six times higher binding affinity for the alpha-2 delta-1 receptor than gabapentin. Altogether, this translates to more reliable dosing, a faster onset of analgesia, and easier titration.

However, the flip side is that this rapid and high bioavailability is what gives pregabalin a higher abuse and dependence potential. This is why pregabalin is a DEA Schedule V controlled substance while gabapentin is not federally scheduled (although several states now schedule it or track it via their PDMP).

Starting doses are usually:

• 50mg TID or 75mg BID

• Titrated up to general goal of 300mg/day within 1 week.

• Alternatively, you can start with 25-50mg qhs in elderly patients.

Like with gabapentin, you shouldn’t chase the max dose. For most use-cases, 300 mg/day captures essentially all of the efficacy.

Both drugs are eliminated unchanged by the kidneys; renal impairment causes accumulation and neurotoxicity

Neither drug is hepatically metabolized, protein bound, or a CYP substrate/inhibitor. While this means there’s no major drug “interactions”, it also means they have to be dose-adjusted for renal impairment.

There is also an increased risk of level accumulation, which can produce a toxidrome of somnolence, confusion, ataxia, and myoclonus.

On the wards, this is a frequently missed cause of unexplained altered mental status in those with an AKI and in the elderly.

Gabapentinoids have a low volume of distribution and are effectively cleared with dialysis. In patients with ESRD, a post-dialysis supplement of 125-350mg is commonly given after each 4 hours HD session.

For gabapentin:

For pregabalin:

Gabapentinoids can cause life-threatening respiratory depression, especially when given concomitantly with opioids or other CNS depressants

An FDA communication in 2019 described serious breathing problems with gabapentin/pregabalin in patients with respiratory risk factors, especially opioid/CNS depressant use, COPD/reduced lung function, and older age. This was based on case reports between 2012 and 2017 in which twelve people died of respiratory depression.

This is why it’s important to start low, avoid stacking with benzos, opioids, or sedating antihistamines, and be cautious in the elderly and those with reduced lung function.

There are numerous dose-limiting toxicities and a serious withdrawal syndrome

Common side effects include sedation, dizziness, ataxia, peripheral edema, and weight gain. The classically associated peripheral edema is diuretic resistant. All together, these side effects can drive falls and fractures in older patients.

Abrupt discontinuation can precipitate withdrawal syndrome, including anxiety, insomnia, diaphoresis, and even seizures in those at risk. It resembles benzo/alcohol withdrawal in high dose / long-term users.

Thus, these medications should be tapered over at least 1 week. Longer tapers are often needed for high-dose, long-term use or patients with seizure risk.

There are several genuine FDA-approved and off-label uses

FDA-approved evidence-supported indications for both gabapentin and pregabalin include post-herpetic neuralgia and partial-onset seizures.

Pregabalin is also approved for use in diabetic peripheral neuropathy (first line), fibromyalgia, and spinal cord injury neuropathic pain.

Gabapentin enacarbil (Horizant) is an extended-release prodrug that is FDA-approved for restless leg syndrome and has some benefits over dopamine agonists since they do not lead to augmentation of symptoms. This long-acting medicine was engineered specifically to bypass gabapentin’s saturable absorption.

Some of the more common off label uses for gabapentin includes refractory chronic cough or hiccups, and uremic/chronic pruritus.

The unifying principle is that these drugs are valuable when pain is genuinely neuropathic and driven by the alpha-2 delta-1 upregulation.

One thing nice about gabapentinoids is that analgesic onset can occur within the first week, unlike many other neuropathic agents (like SNRIs or TCAs) that can take weeks to work.

But gabapentin is often used inappropriately

Routine use of gabapentinoids for perioperative pain is not supported in the literature. They are also largely ineffective for sciatica and nonspecific low back pain. In one trial, pregabalin was no better than placebo and caused more side effects over an 8-week period (NEJM, 2017). Even when symptoms sound “nerve-like,” pregabalin was no better than placebo for acute or chronic sciatica.

It fits mechanistically because radicular (from intermittent nerve compression and not chronic nerve damage) and mechanical back pain are not due to the up-regulated alpha-2 delta-1 driven neuropathic state that these drugs target.

As an aside, gabapentin was at the center of a landmark off-label marketing fraud case, which is one reason physicians believed (and still believe) there was evidence for its use in many other unapproved conditions.

While not every case can make the cut each month and be considered one of my favorites, many still have interesting clinical pearls and lessons worth sharing.

Here’s a collection of some of my favorite additional pearls from April 2026.

Narcolepsy

Narcolepsy type 1 is a chronic central nervous system disorder of hypersomnolence caused by a loss of orexin (hypocretin) producing neurons in the lateral hypothalamus, thought to be due to an autoimmune process.

Cataplexy is the pathognomonic feature - it is the sudden, brief loss of voluntary muscle tone triggered by strong emotions, typically positive ones like laughter or surprise.

The symptoms of narcolepsy are frequently assumed to be psychiatric conditions like depression, ADHD, or laziness, leading to an average diagnostic delay of 8-10 years.

The underlying pathophysiology is a loss of orexin-producing neurons, which disrupts the stability of wakefulness and allows for the inappropriate intrusion of REM sleep phenomena (atonia, dreams) into wakefulness.

Source - NEJM Case 11-2026 A 24-Year-Old Man With Depression, Anhedonia, And Fatigue

Pyogenic Liver Abscess

A pyogenic liver abscess is a pus-filled cavity within the liver caused by bacterial infection.

The most common etiology of pyogenic liver abscess is ascending infection from the biliary tract. Thus, imaging for biliary obstruction (via choledocholithiasis, malignancy, stricture) is crucial.

Patients can present acutely with fever, chills, and RUQ pain. It can also present more insidiously, especially in older adults with non-specific symptoms like malaise, anorexia, and weight loss.

BCx are positive in only about 50% of cases.

Successful management requires source control (abscess drainage and/or biliary decompression via ERCP) and a prolonged course of abx (typically 4-6 weeks).

Source: NEJM - Case 12-2026 An 86-Year-Old Woman With Anorexia, Weight Loss, And Liver Lesions

Dural Venous Sinus Thrombosis

Dural Venous Sinus Thrombosis, also known as Cerebral Venous Sinus Thrombosis, is the occlusion of cerebral venous sinuses or cortical veins by a thrombus.

It is an uncommon cause of stroke that tends to affect younger women. Though clinical presentations vary, headache is the most common symptom. Headaches can be acute and severe ("thunderclap"), subacute, or chronic.

Other presentations include focal neurological deficits, seizures, and signs of increased ICP. A key feature is that a normal neurological exam can be present despite a severe headache, which may delay diagnosis.

Source: CPS - April 1, 2026 VMR with Maddy & Zakariyya G - headache

IDA Causing a Prothrombotic State

Severe iron deficiency anemia is an underrecognized prothrombotic state that can contribute to thrombosis through mechanisms like reactive thrombocytosis and endothelial dysfunction.

Source: CPS - April 1, 2026 VMR with Maddy & Zakariyya G - headache

Creutzfeld-Jakob Disease (CJD)

Brain MRI with DWI is the most critical initial imaging modality for suspected CJD, with cortical ribboning being a highly suggestive finding.

The modern gold-standard CSF test to diagnose CJD is the Real-Time Quaking-Induced Conversion (RT-QuIC) assay, which has high sensitivity and specificity for detecting the pathogenic prion protein. Older, less specific markers include elevated 14-3-3 and Tau proteins.

Definitive diagnosis is via brain biopsy or autopsy showing spongiform degeneration, neuronal loss, and gliosis.

The presence of a normal gait in a patient with significant dementia is a key localizing feature, pointing away from subcortical/limbic diseases (such as Lewy Body Dementia, Vascular Dementia, NPH) and more towards a primary cortical process like Alzheimer's or CJD.

True "reversibility" of a chronic dementia that has evolved over months is exceptionally rare and is primarily a feature of pressure-mediated processes such as NPH and subdural hematomas.

Source: CPS - April 2, 2026 VMR with Rabih & Fahed - forgetfulness & confusion

Immune Thrombocytopenic Purpura (ITP)

Isolated and profound thrombocytopenia (plt <20,000) in an otherwise healthy-appearing patient is highly suggestive of ITP.

Non-palpable purpura suggests a primary platelet disorder, whereas palpable purpura points toward an inflammatory process like vasculitis.

The presence of "wet purpura" (purpura or blood blisters in the mouth) is a red flag for a very low platelet count and a significantly increased risk of severe bleeding.

The peripheral smear is a critical and non-negotiable step in the workup of thrombocytopenia to rule out life-threatening mimics like TTP (schistocytes) and acute leukemia (blasts).

ITP is a diagnosis of exclusion; always consider and rule out secondary causes such as infections (HIV, hepatitis), drugs, and other systemic autoimmune or lymphoproliferative disorders.

Platelet transfusions are generally not indicated in ITP due to rapid destruction by autoantibodies and are reserved for patients with active, life-threatening hemorrhage.

Source: CPS - April 6, 2026 Mainstream Mondays VMR with Maddy & Lera - rash

Streptococcal Toxic Shock Syndrome (STSS)

The syndrome is mediated by streptococcal pyrogenic exotoxins that act as superantigens, triggering a massive, non-specific T-cell activation and subsequent cytokine storm.

This leads to profound capillary leak, diffuse erythroderma (a "sunburn" rash), fever, and multi-organ failure.

Septic cardiomyopathy is a well-described but severe complication of STSS, contributing significantly to refractory shock.

Treatment is a combination of a beta-lactam (Penicillin G) to kill bacteria, and clindamycin to suppress toxin synthesis (via inhibition of ribosomal protein synthesis). IVIG is often used as an adjunct to neutralize circulating toxins. Surgical debridement is crucial for source control in cases of necrotizing soft tissue infection.

Source: CPS - April 7, 2026 VMR with Maddy & Andrew - fever, cough, and widespread body aches

“Unmasking” Sarcoid

The finding of significant interstitial fibrosis in a patient with a long-standing "asthma" diagnosis should prompt consideration of mimickers, including sarcoidosis which can cause airway hyperreactivity.

The withdrawal of a broad immunosuppressant like corticosteroids can unmask an underlying inflammatory disorder, such as sarcoidosis, that was previously being inadvertently treated.

A "silent" lung exam (clear to auscultation) in the presence of interstitial disease on imaging can be a clue for sarcoidosis, in contrast to IPF where bibasilar crackles are nearly universal.

PTH-independent hypercalcemia with an elevated 1,25 vitamin D level is a strong indicator of a granulomatous disease (like sarcoidosis, endemic mycoses, TB) or lymphoma.

Source: CPS - April 8, 2026 VMR with Steph & Zaven - worsening skin lesions

APDS Syndrome - A Primary Immunodeficiency

The combination of recurrent sinopulmonary infections, lymphoproliferation (hepatosplenomegaly, lymphadenopathy), and autoimmunity strongly suggests a CVID-like primary immunodeficiency such as Activated PI3K Delta Syndrome (APDS).

APDS is a syndrome of immune dysregulation, not just deficiency, explaining the concurrent findings of infection susceptibility and hyper-inflammatory states like lymphoproliferation.

Recurrent or severe bacteremia with enteric organisms (E. coli, Salmonella) in an adult should prompt consideration of a primary immunodeficiency.

Source: CPS - April 8, 2026 VMR with Andrew & Kirtan - leukocytosis

Xanthogranulomatous cholecystitis (XGC)

XGC is a rare destructive inflammatory disease of the gallbladder that is a variant of chronic cholecystitis.

It is characterized by a massive inflammatory reaction that often forms a tumor-like mass, making it a well-known mimic of gallbladder carcinoma.

A non-visualized gallbladder replaced by an inflammatory mass containing a large stone is commonly seen on imaging.

The pathophysiology is thought to involve chronic obstruction (typically by a large gallstone), leading to increased intraluminal pressure and rupture of the Rokitansky-Aschoff sinuses. This allows bile to extravasate into the gallbladder wall, inciting a singificant inflammatory response dominated by lipid-laden macrophages (xanthoma cells), lymphocytes, and fibrosis, which can even invade adjacent structures like the liver, making it look like a malignancy.

Source: CPS - April 9, 2026 VMR with Rabih & Siva - chest pain and vomiting

Pancreatitis and Lipase

Lipase, while more specific than amylase, is not perfectly specific for pancreatitis. It can be falsely elevated in DKA/HHS, renal failure, and mesenteric ischemia, creating significant diagnostic pitfalls.

The pathophysiology of severe pancreatitis involves two distinct processes. The first is local autodigestion leading to necrosis and fluid collections, and the second is a systemic vascular leak syndrome causing multi-organ failure like ARDS and shock.

Severe, palpable epigastric tenderness is a classic and crucial clue, suggesting local peritonitis from the inflamed pancreas. It can also help differentiate it from other, less tender causes of epigastric pain like PUD.

Source: CPS - April 11, 2026 Academy with Rabih - pancreatitis

Light Chain Multiple Myeloma

In light chain myeloma, malignant plasma cells exclusively produce and secrete monoclonal free light chains (kappa or lambda) without the corresponding heavy chain.

Light chains are not detected on standard serum protein electrophoresis (SPEP) but are identified by the serum free light chain (SFLC) assay.

The classic presentation of light chain myeloma is captured by the CRAB criteria: hyperCalcemia, Renal insufficiency, Anemia, and Bone lesions.

However, the order of prevalence is more accurately reflected by the BARC mnemonic: Bone lesions, Anemia, Renal failure, hyperCalcemia).

Myeloma causes AKI through several mechanisms, most commonly cast nephropathy, where excessive filtered light chains precipitate in and obstruct the renal tubules.

While myeloma typically causes a normocytic anemia from marrow infiltration, co-existing pathology like severe iron deficiency from chronic blood loss can be present and must be treated as well.

Source: CPS - April 13, 2026 Mainstream Mondays VMR with Youssef & Seeme - fatigue and lightheadedness

Esophageal Rupture / Boerhaave Syndrome

The classic presentation is "Mackler's triad" of vomiting, chest pain, and subcutaneous emphysema, but this is present in less than 20% of cases. Patients more commonly present with non-specific signs of sepsis, shock, chest pain, or dyspnea, often mimicking more common conditions like MI, pulmonary embolism, or PNA.

An extremely low pleural fluid pH (<6.5) and high pleural fluid amylase are pathognomonic for esophageal rupture, reflecting contamination with gastric acid and saliva.

While Boerhaave syndrome classically causes a left-sided hydropneumothorax, it can present with bilateral effusions and may lack overt pneumomediastinum on initial imaging.

Source: CPS - April 14, 2026 VMR with Ravi & Debora - nausea and vomiting

Achenbach Syndrome vs Ischemic Digits

Achenbach syndrome is characterized by the spontaneous development of a hematoma on the volar aspect (underside) of a digit. It is a diagnosis of exclusion, often misdiagnosed as an ischemic or vascular occlusive event. The classic presentation involves a sudden onset of pain or a burning sensation in a finger, followed rapidly by swelling and blue-purple (violaceous) discoloration. It typically affects one finger and is more common in middle-aged women.

The presence of preserved capillary refill and pulses is a critical finding that strongly argues against significant arterial occlusion and points toward a non-vascular emergency like a hematoma.

True critical digital ischemia typically presents with severe pain, pallor or frank cyanosis (not just bruising), and absent or severely delayed capillary refill.

Source: CPS - April 16, 2026 VMR w/Rabih & Krishna - acute onset pain, numbness, discoloration of R index finger

“Incidental” ANA as a Red Herring

A positive ANA, especially at a moderate titer like 1:320, is a common incidental finding in healthy women and must be interpreted in the context of a compatible set of symptoms to be considered significant.

Source: CPS - April 16, 2026 VMR w/Rabih & Krishna - acute onset pain, numbness, discoloration of R index finger

HFpEF and AFib

Patients with HFpEF are particularly dependent on atrial contraction for ventricular filling and are highly susceptible to hemodynamic compromise during AFib.

Source: CPS - April 20, 2026 Mainstream Mondays VMR with Ethan & Magnus - dizziness and low back pain

Pulse Pressure

A wide pulse pressure (ex: 110/45 mmHg) can be a subtle sign of significant underlying cardiovascular disease, such as severe atherosclerosis or aortic insufficiency, which contributes to hemodynamic fragility.

Source: CPS - April 20, 2026 Mainstream Mondays VMR with Ethan & Magnus - dizziness and low back pain

Primary Pancreatic Lymphoma

Primary Pancreatic Lymphoma is a rare extranodal presentation of non-Hodgkin lymphoma. DLBCL is the most common subtype. It accounts for less than 1% of all pancreatic malignancies and can be a critical mimic of the much more common pancreatic adenocarcinoma.

While it can encase major vessels like the SMA or SMV, it often does so without causing significant stenosis or thrombosis, a feature that can help distinguish it from adenocarcinoma.

DLBCL is a "great mimicker" and can present as a localized mass in almost any organ system; it should be considered in the differential for atypical masses, even when initial imaging suggests a more common local primary tumor.

Source: CPS - April 21, 2026 VMR with Ravi & Kirtan - right-sided abdominal pain

Gaucher’s Disease

Gaucher's disease is the most common lysosomal storage disorder, caused by a deficiency of the enzyme glucocerebrosidase (GBA). This leads to the accumulation of its substrate, glucocerebroside, within the lysosomes of macrophages, forming "Gaucher cells." These lipid-laden cells infiltrate various organs, leading to a variable clinical picture that often mimics rheum, heme, and infectious diseases.

Hepatosplenomegaly is a classic finding due to the infiltration of Gaucher cells in the reticuloendothelial system.

Bone pain, lytic lesions, pathologic fractures, and avascular necrosis are common.

Anemia and thrombocytopenia are also common due to bone marrow infiltration and hypersplenism.

Gaucher's disease confers a significantly increased lifetime risk of hematologic malignancies, specifically multiple myeloma and other gammopathies. Patients require lifelong screening with SPEP, UPEP, and SFLC.

The chronic inflammation can manifest as fever, arthritis, and hyperferritinemia, mimicking adult-onset Still's disease.

Source: CPS - April 25, 2026 Simplicity in Complexity - rheumatoid arthritis in the setting of a febrile illness

The Paradox of Weight Loss and Anasarca

The combination of weight loss and anasarca is a clinical paradox that suggests severe protein loss, a profound inflammatory state causing hypoalbuminemia and/or mechanical lymphatic obstruction (retroperitoneal lymphadenopathy).

Source: CPS - April 26, 2026 Academy w/ Rabih & Academy Candidate Javier - Fever & Pancytopenia

Pancytopenia Etiologies

Subacute pancytopenia in an inflammatory setting points to a bone marrow production problem. The presence of extensive extra-marrow disease (hepatosplenomegaly) makes an infiltrative cause far more likely than a primary marrow failure syndrome.

Source: CPS - April 26, 2026 Academy w/ Rabih & Academy Candidate Javier - Fever & Pancytopenia

Interpreting CSF Studies in Bacterial Meningitis

Classic CSF findings in bacterial meningitis include a cloudy appearance, pleocytosis (typically >1,000 cells, with a neutrophilic predominance), elevated protein (>100), and low glucose (<40 or a CSF to serum glucose ratio of <0.4).

CSF glucose must be interpreted in the context of serum glucose; a numerically "normal" CSF glucose can be pathologically low in a patient with hyperglycemia.

Source: CPS - April 27, 2026 Mainstream Mondays VMR with Maddy & Manaswini - AMS

Cryptococcal Meningitis

An elevated opening pressure on lumbar puncture, especially when discordant with a low cell count in the CSF (paucicellular meningitis), is suggestive of cryptococcal meningitis in an immunocompromised host.

While classic for advanced HIV, cryptococcal meningitis must be considered in any patient with impaired T-cell immunity, including those with rheumatologic diseases (like lupus) on immunosuppressants (prednisone, azathioprine).

Aggressive management of intracranial pressure with therapeutic lumbar punctures is as crucial as antifungal therapy for preventing mortality and severe neurological sequelae like vision loss.

Source: CPS - April 27, 2026 VMR with Alec & Austin - headache, nausea and vomiting

Superior Vena Cava (SVC) Syndrome

SVC Syndrome is an oncologic emergency caused by the obstruction of blood flow through the superior vena cava, most commonly due to external compression by a mediastinal mass (most commonly lung cancer and lymphoma) or intravascular thrombosis.

The obstruction leads to venous congestion in the head, neck, and upper extremities.

The classic clinical presentation includes facial plethora (flushing), edema of the face and arms, dyspnea, cough, and distended neck and chest wall veins.

Symptoms can be acutely worsened by maneuvers that increase venous return from the upper body, such as bending forward or raising the arms (Pemberton's sign).

The acute onset of symptoms does not always signify an acute underlying pathology; a slow-growing mass can present acutely once it reaches a critical threshold of compression.

Hodgkin's lymphoma, particularly the “nodular sclerosing” subtype, is a common cause of a large anterior mediastinal mass in young adults.

While classic, the absence of B symptoms (fever, night sweats, weight loss) does not exclude a diagnosis of lymphoma.

Source: CPS - April 29, 2026 VMR with Sharmin & Reza - pain and swelling in the right neck supraclavicular region

VEXAS Syndrome

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a severe, adult-onset autoinflammatory disorder caused by a somatic mutation in the UBA1 gene. The X-linked gene mutation primarily affects hematopoietic stem cells, leading to a clonal myeloid disorder that drives systemic inflammation, almost exclusively in older men.

Thus, VEXAS is fundamentally a hematologic disorder. It exists on a spectrum with (and frequently progresses to) myelodysplastic syndrome (MDS) or other myeloid neoplasms.

Consider VEXAS syndrome in any older male with a refractory, systemic inflammatory illness, especially with the triad of relapsing polychondritis (auricular chondritis), neutrophilic dermatosis (pustules, Sweet syndrome-like lesions), and venous thromboembolism.

Recurrent or extensive superficial thrombophlebitis can be a key clinical sign of an underlying systemic inflammatory disorder.

Optic perineuritis (inflammation of the nerve sheath usually presenting as painful eye movements), is different than optic neuritis and typically points toward a systemic inflammatory or infectious cause (VEXAS, sarcoid, IgG4, syphilis) rather than a primary neurologic disease like MS.

Source: CPS - April 30, 2026 VMR with Rabih & Lourenco - headache and blurry vision

This post highlights in-depth breakdowns of my favorite clinical cases from April 2026. I then provide some commentary and build on the lessons from my own experience, where appropriate.

There will be a separate post highlighting all of my other favorite rapid-fire pearls from other cases that didn’t make the cut.

April 3, 2026 VMR with Rabih & Reza - Lightheadedness

Source

Case Summary

A 59 year-old man with CAD presented with exertional lightheadedness. Initial evaluation was notable for sinus tachycardia and a BUN/creatinine ratio >40. He was briefly discharged after fluid resuscitation but returned hours later with hematochezia and hemorrhagic shock, requiring massive transfusion and vasopressors. An extensive workup including EGD, colo, CTA, and enteroscopy failed to identify a bleeding source, despite evidence of active bleeding in the small bowel on a tagged RBC scan. He underwent an ex lap, which revealed a Dieulafoy’s lesion in the proximal jejunum. The lesion was surgically resected, leading to resolution of the bleeding.

Dieulafoy’s Lesion

A Dieulafoy’s lesion is a rare but important cause of massive GI bleeding. It consists of an abnormally large, tortuous artery in the submucosa that erodes the mucosa without a primary ulcer or vessel wall defect. While most commonly located in the proximal stomach (lesser curvature), these lesions can occur anywhere in the GI tract, including the small bowel, colon, or rectum.

The classic presentation is sudden, massive, painless, and often intermittent GI bleeding. The diagnosis is challenging because the lesion is small and may not be actively bleeding during endoscopy.

Endoscopy is the gold standard for diagnosis, revealing active arterial pumping from a small mucosal defect, a visible vessel protruding from normal-appearing mucosa, or an adherent clot. However, the initial endoscopy is often non-diagnostic.

Management is primarily therapeutic endoscopy (hemoclipping, thermal coagulation, band ligation). If endoscopic therapy fails or is not feasible, angiographic embolization or surgical resection may be required.

Pearls

• A significantly elevated BUN/creatinine ratio (usually defined as >30) can be a crucial early clue to an occult or impending upper/proximal GI bleed, even before overt signs of hemorrhage. In UGIB, Hgb and plasma proteins hit the small bowel and get broken down by proteases and gut flora into amino acids, are absorbed, and are then deaminated in the liver to urea, raising the BUN. A prerenal physiology in significant bleed can also contribute.

• Hematochezia with hemodynamic instability should raise suspicion for a brisk upper or proximal small bowel GI bleed, which carries a higher mortality risk than a typical lower GI source.

• The bleeding pattern of a Dieulafoy’s lesion is often intermittent but massive. This can make endoscopic diagnosis difficult if performed during a non-bleeding interval.

• When standard EGD and colonoscopy are negative in a patient with life-threatening GI hemorrhage, the ddx must include a small bowel source (Dieulafoy’s lesion, AVM) or an aortoenteric fistula.

• Postural lightheadedness or presyncope can be the first manifestation of significant volume loss from an occult GI bleed, preceding obvious hematochezia or melena.

• In cases of severe, unlocalized GI bleeding where endoscopic and radiologic studies are non-diagnostic, an ex lap remains a critical diagnostic and therapeutic intervention.

My Commentary

I don’t think I realized as a resident how challenging it is to do an EGD or colo and actually identify a clear source of a bleed. These lesions in particular can be so frustrating because clearly a patient is bleeding (and seriously so), and yet the source can elude us. The BUN/Cr >30 has actually been something I’ve caught a number of times in patients starting AC for the first time - watch for a drastic and unexplained increase in BUN in the inpatient setting in the days after starting AC and wonder about a slow but serious ooze from an at-risk lesion.

Related Point of Care Medicine Resources:

GI Bleed Admission Template

April 10, 2026 VMR with Rabih & Jas - abrupt, severe epigastric pain

Source

Case Summary

A 62 year-old man with CAD presented with acute, severe epigastric pain and N/V. Initial labs showed mild transaminitis and leukocytosis, but within 24 hours he developed a hepatocellular-pattern liver injury (with AST and ALT >1000), conjugated hyperbilirubinemia, and jaundice. Initial imaging, including a CTA and RUQ ultrasound, was negative for gallstones or biliary ductal dilation. Despite this, high clinical suspicion for biliary obstruction persisted, leading to an MRCP that suggested cholangitis and a subsequent ERCP that confirmed the presence of small common bile duct stones, which were removed. His final diagnosis was acute cholangitis from choledocholithiasis, and he recovered fully after stone removal and cholecystectomy.

Acute Cholangitis from Choledocholithiasis

Acute cholangitis is a bacterial infection of the biliary tree, most commonly occurring secondary to biliary obstruction. The classic presentation is Charcot’s triad: fever, RUQ pain, and jaundice. This can progress to Reynolds’ pentad with the addition of hypotension and AMS. Obstruction is typically caused by a gallstone migrating into the common bile duct (choledocholithiasis).

Key diagnostic findings include:

• Labs: Typically show leukocytosis and a cholestatic pattern of liver injury (elevated bilirubin, alk phos, and GGT). However, sudden obstruction can cause a profound, acute hepatocellular injury pattern with AST and ALT rising into the thousands, often before the alk phos elevates significantly. A normal lipase is crucial to differentiate this from gallstone pancreatitis.

• Imaging: RUQUS is the initial test to look for biliary ductal dilation (typically >6 mm) and stones. However, in early or transient obstruction, or with small stones (microlithiasis) or sludge, the ducts may not be dilated. MRCP is a more sensitive, non-invasive test for visualizing the biliary tree. ERCP is the gold standard for both diagnosis and therapy, allowing for direct visualization, sphincterotomy, and stone removal.

Management is a medical emergency requiring hospitalization, IV fluids, and broad-spectrum IV antibiotics. The definitive treatment is urgent biliary drainage, most commonly via ERCP. Once the acute infection is controlled, a cholecystectomy is typically performed to prevent recurrence.

Pearls

• Sudden, severe biliary obstruction can present with a hepatocellular injury pattern (AST/ALT >1,000), mimicking ischemic or toxic hepatitis, before a classic cholestatic pattern emerges.

• The absence of biliary ductal dilation on initial ultrasound or CT does not rule out acute obstruction or cholangitis, especially early in the course before the ducts have had time to dilate.

• Microlithiasis or biliary sludge can cause significant, functionally complete obstruction and severe cholangitis without a single large, occlusive stone visible on imaging.

• A high index of suspicion for biliary pathology should be maintained in patients with severe epigastric/RUQ pain and rapidly rising liver enzymes, even with initially negative imaging.

• MRCP is the key diagnostic step when non-invasive imaging is unrevealing but clinical suspicion for biliary obstruction remains high.

• ERCP is both diagnostic and therapeutic, serving as the cornerstone of management for acute cholangitis by relieving the underlying obstruction.

My Commentary

In internal medicine world, few presentations are as scary as a septic patient with cholangitis. On the other hand, its hard to think of a more satisfying clinical course than a septic patient with biliary obstruction who gets an ERCP, has their obstruction removed, and you watch as the LFTs rapidly improve over the subsequent days. The bilirubin tends to increase (and fall) more slowly than the improvement in the hepatobiliary enzymes.

I’ve found myself ordering an MRCP in patients who have colic or unexplained LFT abnormalities and are found to have some deal of dilation in their biliary ducts, but no actual stone seen on ultrasound. I’ve diagnosed choledocolithiasis in a few of these cases. It can happen even when a patient has previously had their gallbladder removed! But there is also a higher likelihood of biliary ductal dilation post-cholecystectomy that is unrelated to obsstruction.

Related Point of Care Medicine Resources:

Admission Template for Cholangitis

8 Facts to Help Master the Interpretation of Liver Chemistry Tests

April 11, 2026 Simplicity in Complexity VMR with Jeffrey & Kirtan - dyspnea & vision loss

Source

Case Summary

A 69 year-old woman with diabetes and presumed lupus presented with dyspnea, melena, and painless left vision loss. Initial workup revealed mild pancytopenia, anemia attributed to severe Candida esophagitis, and a retinal detachment related to her diabetes. Her hospital course was complicated by an abrupt decompensation into distributive shock with hypoglycemia and worsening pancytopenia. A CTAP revealed bilateral adrenal hemorrhages with right adrenal vein thrombosis. Despite an extensive negative workup for infection, a hypercoagulable state, and rheumatologic disease, a bone marrow biopsy confirmed Myelodysplastic Syndrome (MDS). The final diagnosis of high-risk MDS with a U2AF1 mutation provided an explanation for her systemic inflammation, paradoxical thrombosis/hemorrhage, and immunodeficiency.

High-Risk Myelodysplastic Syndrome (MDS) with U2AF1 Mutation

MDS is a group of clonal bone marrow disorders characterized by ineffective hematopoiesis, leading to cytopenias and a risk of transformation to AML. While many patients present with symptoms related to low blood counts (fatigue, infection, bleeding), high-risk subtypes can present as severe systemic inflammatory and autoimmune-like syndromes. This is particularly true for MDS associated with mutations linked to clonal hematopoiesis (CHIP), such as in spliceosome genes (U2AF1, SF3B1, SRSF2) or the UBA1 gene (VEXAS).

Key diagnostic findings include:

• Labs: Progressive cytopenias (often pancytopenia). Elevated inflammatory markers (ESR, CRP, Ferritin) that are out of proportion to any identified infection. Standard autoimmune and hypercoagulable workups are often negative.

• Imaging: Can reveal unexpected paraneoplastic phenomena. The bilateral adrenal hemorrhages seen in this case are a classic example of a paradoxical state created by MDS - profound inflammation drives venous thrombosis, while severe thrombocytopenia prevents hemostasis, leading to hemorrhagic infarction.

• Pathology: A bone marrow biopsy reveals dysplasia (abnormal maturation and morphology) in one or more cell lines.

• Genetics: NGS of bone marrow is needed for risk stratification and diagnosis, identifying specific driver mutations like U2AF1.

Management is risk-stratified and largely supportive, including transfusions and infection management. High-risk disease is treated with hypomethylating agents (azacitidine) or (in eligible patients) allogeneic stem cell transplantation.

Pearls

• The triad of unexplained systemic inflammation (high ESR/CRP), progressive cytopenias, and an opportunistic infection (such Candida esophagitis) should raise suspicion for an underlying hematologic malignancy like MDS.

• In complex cases with multiple problems, systematically evaluate each one before attempting to unify them. The patient’s vision loss was a “red herring”- an unrelated diabetic complication - and pursuing it as part of a systemic process would have been misleading.

• Bilateral adrenal hemorrhage is a medical emergency that can be a rare paraneoplastic manifestation of an inflammatory hematologic disorder like MDS, which creates a paradoxical state of thrombosis and hemorrhage (from thombocytopenia).

• Clonal hematopoiesis (MDS, VEXAS syndrome) is an increasingly recognized cause of severe, “seronegative” or atypical autoimmune and vasculitic syndromes, particularly in older adults.

• When faced with persistent, unexplained cytopenias and systemic illness where extensive infectious and rheumatologic workups are negative, a bone marrow biopsy with genetic testing can be a critical diagnostic step.

• The myeloid dysplasia in MDS impairs innate immune function, predisposing patients to opportunistic fungal infections, even without classic risk factors like chemotherapy or high-dose steroids.

My Commentary

I don’t know that I’ve ever diagnosed MDS in the wild, but have certainly admitted patients with MDS for transfusion needs. Unlike its older sibling (AML) it tends to be more of a black box for generalists. But one thing I have done a number of times is identified and worked up new (or never addressed) pancytopenia. The ddx is so broad and spans so many clinical worlds. Plus, it’s fun to look at smears with heme/onc consultants - you always learn a thing or two.

Related Point of Care Medicine Resources:

Admission Template for Pancytopenia

April 23, 2026 VMR with Rabih & Kirtan - SOB, abdominal distension and black tarry stools

Source

Case Summary

A 53 year-old male farmer with a history of chronic heavy alcohol use presented with a two month history of abdominal distension and 15 days of progressive dyspnea and melena. He was found to be in shock with signs of right heart failure, severe anemia (Hgb 4.1), and thrombocytopenia (plt 12,000). His course was complicated by worsening shock after transfusions, AMS, acute liver injury, and ischemic necrosis of his feet, revealing a systemic coagulopathy. Workup demonstrated a “leukoerythroblastic” blood picture, lytic and sclerotic bone lesions, and a bone marrow biopsy confirming metastatic carcinoma. An elevated PSA and subsequent prostate biopsy established the diagnosis of Stage IV prostate adenocarcinoma with bone marrow carcinomatosis, triggering a DIC / Thrombotic Microangiopathy (TMA) syndrome.

Metastatic Prostate Cancer with Bone Marrow Carcinomatosis and Paraneoplastic DIC/TMA

Metastatic prostate cancer is a common malignancy in men that frequently metastasizes to bone, classically causing osteoblastic (sclerotic) lesions and an elevated alk phos. In a subset of patients, the cancer infiltrates the bone marrow itself, a process known as bone marrow carcinomatosis or myelophthisis. This infiltration disrupts normal blood cell development, leading to severe cytopenias and a characteristic “leukoerythroblastic” picture on the peripheral smear, where immature RBCs and WBCs are forced into circulation.

A severe and life-threatening complication is the triggering of a paraneoplastic consumptive coagulopathy, often manifesting as DIC or TMA. Tumor cells interacting with the bone marrow stroma can release prothrombotic factors, leading to widespread microvascular thrombosis, consumption of platelets and coagulation factors, and subsequent multi-organ failure. Clinically, this can present paradoxically with both thrombosis (seen clinically as digital ischemia, pulmonary tumor thrombotic microangiopathy) and bleeding (GI bleeding, low fibrinogen).

Management involves treating the underlying cancer while providing aggressive supportive care for the DIC and organ failure.

Pearls

• The combination of thrombosis (digital necrosis) and severe thrombocytopenia should immediately trigger consideration of a microangiopathic process like DIC or TMA.

• A “leukoerythroblastic” peripheral smear is a red flag for a bone marrow infiltrative process (myelophthisis), with metastatic cancer being a primary consideration in an older adult.

• Pulmonary tumor microthrombi can lead to right heart failure due to severe pulmonary hypertension. This will present as cardiogenic shock with a preserved ejection fraction.

• The triad of cytopenias, bone lesions, and subacute DIC is highly suggestive of a metastatic solid tumor. Prostate, breast, lung, and gastric cancers are common culprits.

• Plt counts below 50,000 are disproportionately low for typical hypersplenism from portal hypertension and warrant an aggressive search for an alternative or superimposed cause.

My Commentary

While I’ve seen DIC most commonly in patients presenting with leukemia, I’ve definitely seen it from time to time in advanced metastatic solid cancers. I don’t know that I’ve ever had a BMBx confirmed carcinomatosis, but have certainly had cases where this was presumed as a patient had DIC/anemias at the end of life. Though it was likely due to prolonged pressors in an ICU setting, the cool black digits that come to mind from residency will forever be top of mind as a sign of ischemia.

It’s also worth distinguishing between different “phenotypes” of DIC. Acute DIC from leukemia tends to cause the hyperfibrinolytic form of DIC which leads to the classic “oozing” around vessels. Chronic DIC on the other hand is often due to metastatic adenocarcinomas and causes a gradual decrease in coagulation factors which the body can usually compensate for.

Related Point of Care Medicine Resources:

DIC Admission Template

April 24, 2026 VMR with Youssef & Mengyu - weakness and hypotension

Source

Case Summary

A 69 year-old man with chronic LE lymphedema and wounds presented with weakness and septic shock, requiring vasopressors. WBC was 24.1, a procalcitonin was >100, and a collapsible IVC was seen on POCUS, confirming a distributive process. Despite initial stabilization on abx, he developed persistent confusion, BiPAP-dependent hypercapnic respiratory failure (pCO2 77), and severe rhabdomyolysis (CK 7,500), while blood cultures grew Streptococcus constellatus, signaling an uncontrolled source of infection. The final diagnosis was made after a wound care consultation revealed a toothpick embedded in his foot, forming an occult abscess. Surgical removal of the foreign body led to the immediate and complete resolution of his multi-organ failure.

Occult Foreign Body Abscess and Sepsis

A retained foreign body, particularly in patients with compromised skin integrity from conditions like lymphedema or peripheral neuropathy, can serve as a nidus for severe infection. Organic materials like wood (toothpicks) are notoriously challenging as they are porous, harbor bacteria, and can incite a significant inflammatory response, often leading to abscess formation. The clinical presentation can be subtle, with minimal localizing signs of infection (pain, erythema, swelling) being masked by underlying conditions, leading instead to a presentation of systemic illness like bacteremia or septic shock.

The isolated organism often provides a clue to the source. Strep constellatus, part of the abscess-forming Strep anginosus group, suggests a purulent collection.

Plain radiographs are not useful for identifying radiolucent organic materials like wood. Ultrasound is the modality of choice for localizing superficial foreign bodies, which typically appear as hyperechoic structures with posterior acoustic shadowing. CT or MRI can identify deeper fluid collections and associated inflammation.

Management is centered on aggressive source control. This involves surgical incision, complete drainage of the abscess, and meticulous removal of the foreign body and any associated necrotic tissue. This must be accompanied by broad-spectrum abx, which can be narrowed based on culture results.

Pearls

• In a patient with sepsis who fails to improve or worsens despite appropriate antibiotics, aggressively search for an undrained abscess or an uncontrolled source, such as a retained foreign body or infected hardware.

• Streptococcus constellatus, a member of the Strep anginosus group, is notorious for its propensity to form abscesses. Its isolation from blood should prompt an aggressive search for a purulent collection.

• Organic foreign bodies like wood are radiolucent and will be missed on X-ray and often on CT. Ultrasound is the preferred initial imaging modality for suspected superficial foreign bodies.

• Profound muscle weakness, severe rhabdomyolysis, and hypercapnic respiratory failure can be atypical but severe manifestations of uncontrolled sepsis, reflecting global tissue hypoperfusion and inflammation.

• A head-to-toe physical examination, including careful inspection of all skin surfaces and wounds, is critical and can reveal a diagnosis missed by advanced imaging.

My Commentary

This might be my favorite case of the year. It underscores the importance of just getting cross-sectional imaging when the patient just doesn’t seem to be getting better. I saw this all the time while rounding with the Onc ID consult teams. At a certain point, you need to go looking for poor source control.

Persistent inpatient fevers is also one of my favorite ddx. Consider the wrong bug (viral, fungal, atypical), wrong drug, wrong process (non-infectious), lack of source control (abscess, endocarditis, indwelling line), or not enough time for fever resolution.

As this case demonstrates, a thorough exam can be just as revealing (if not more so) than the donut of truth. Look under those bandages!

April 28, 2026 VMR with Ravi & Kirtan - transient Loss of Consciousness

Source

Case Summary

A 35 year-old woman presented with syncope, superimposed on a two-month history of progressive heart failure symptoms and exertional chest pain. Findings included severe hypertension (190/130), clinical and lab evidence of heart failure, and an absent left radial pulse. The workup uncovered a widespread, stenosing vasculopathy, including a critical 99% LAD stenosis, subclavian artery stenosis, and bilateral renal artery stenosis (discovered after an AKI following initiation of an ARB). Advanced imaging confirmed aortic wall inflammation, leading to a diagnosis of Takayasu Arteritis. Her condition improved significantly with coronary and renal artery stenting and immunosuppressive therapy with tocilizumab.

Takayasu Arteritis (TA)

TA is a large-vessel vasculitis of unknown etiology that primarily affects the aorta and its branches, typically presenting in women under the age of 50. The clinical course can be biphasic, starting with a systemic inflammatory phase (fever, malaise) followed by a later occlusive or “pulseless” phase driven by vascular stenosis, aneurysm, or dissection. This occlusive phase leads to limb claudication, blood pressure discrepancies between limbs, absent pulses, hypertension (often renovascular), and end-organ ischemia (angina, stroke, syncope).

Key diagnostic findings include:

• Clinical: Blood pressure differentials (>10 mmHg) between arms, bruits over affected arteries (aorta, subclavian, carotid, renal), and diminished or absent peripheral pulses.

• Labs: Nonspecific but may show elevated inflammatory markers like ESR, CRP.

• Imaging: Diagnosis relies on imaging. CT Angiography (CTA) or MR Angiography (MRA) demonstrates vessel wall thickening, stenosis, occlusion, or aneurysms. PET scans are highly sensitive for detecting active vascular inflammation.

Management focuses on suppressing inflammation with corticosteroids and steroid-sparing agents (methotrexate, tocilizumab). Interventions like angioplasty and stenting or surgical bypass are often required to manage stenoses and restore perfusion.

Pearls

• In a young patient with severe or resistant hypertension, a thorough evaluation for secondary causes is mandatory, with renovascular hypertension (from FMD or vasculitis) being a key part of the ddx.

• Worsening renal function after the initiation of an ACE/ARB is a classic clinical sign of hemodynamically significant bilateral renal artery stenosis.

• MI in a young person without traditional atherosclerotic risk factors should prompt a search for alternative etiologies, including coronary vasospasm, anomalous coronary arteries, and vasculitis.

• Takayasu Arteritis is known as the “pulseless disease.” A thorough pulse exam and blood pressure measurement in all four limbs is essential, as discrepancies are a diagnostic hallmark.

• A remote history of ocular inflammation (“red eye” suggesting uveitis or scleritis) can be an early clue to an underlying systemic autoimmune or vasculitic process.

My Commentary

I like this case because it reminds me that this disease process really is so much more interesting than the four or five things we learned for STEP 1 (frankly all of them are). I’ve only taken care of a few patients with the disease, and it was for unrelated things in the hospital.

The one area I’ll call attention to is the poor sensitivity of differential blood pressure readings across limbs. Having a lack of a pulse in one arm/hand is pretty unmistakable, but the blood pressure differences can be so varied and tough to interpret.

While not every case can make the cut each month and be considered one of my favorites, many still have interesting clinical pearls and lessons worth sharing.

Here’s a collection of some of my favorite additional pearls from March 2026.

Non-Islet-Cell Tumor Hypoglycemia (NICTH)

This is a rare paraneoplastic syndrome characterized by severe hypoglycemia caused by a tumor that is not of pancreatic islet cell origin. It is most commonly associated with large mesenchymal tumors (solitary fibrous tumors, leiomyosarcomas) or epithelial tumors (HCC).

The underlying mechanism of the hypoglycemia is the tumor's secretion of a high-molecular-weight form of insulin-like growth factor II ("big IGF-II"). This molecule binds to and activates insulin receptors, leading to increased glucose uptake by peripheral tissues and suppression of hepatic glucose production, mimicking the effects of excess insulin.

You will see low or undetectable insulin, C-peptide, and proinsulin levels. Ketone production is also suppressed due to the insulin-like effect of IGF-II.

Surgical resection of the tumor is curative and results in immediate normalization of the glucose level.

Source: NEJM - Case 9-2026 A 12-Year-Old Girl With Altered Mental Status And Hypoglycemia

Strep Pneumo Meningitis

The classic triad of meningitis (fever, nuchal rigidity, altered mental status) is often absent in elderly or immunocompromised hosts, requiring a high index of suspicion.

In patients with meningitis 2/2 strep pneumo, BCx are often positive and inflammatory markers like procalcitonin are usually elevated.

Empiric treatment for suspected bacterial meningitis must include coverage for drug-resistant strep pneumo (vancomycin plus a third-generation cephalosporin like ceftriaxone), as resistance can lead to clinical failure with monotherapy.

The benefit of adjunctive dexamethasone in bacterial meningitis is greatest when given just before or with the first dose of antibiotics; its utility is diminished in delayed presentations.

Source: March 4, 2026 VMR with Steph & Zaven - altered mental status & fever

Bleeding on DOACs

Bleeding on a renally-cleared anticoagulant (like apixaban) can create a vicious cycle: hemorrhage causes pre-renal AKI, which impairs drug clearance, leading to supratherapeutic anticoagulation and worsening hemorrhage.

Source: March 5, 2026 VMR with Rabih & Mohammed - acute epistaxis

Diagnosing ALS

Progressive, asymmetric weakness with preserved sensation should always raise concern for a motor neuron disease like ALS.

Electrodiagnostics (EMG/NCS) are the cornerstone of diagnosis. NCS should show normal sensory nerve function. EMG confirms widespread lower motor nerve (LMN) damage, revealing evidence of active denervation (fibrillations, positive sharp waves) and chronic reinnervation (large, polyphasic motor unit potentials) in multiple body regions, often demonstrating subclinical involvement.

The Progressive Muscular Atrophy (PMA) subtype of ALS presents with predominantly lower motor neuron signs, making it a key mimic of myopathy or neuropathy and a frequent diagnostic challenge.

In the setting of profound weakness, reflexes will be diminished or absent regardless of etiology; therefore, hyporeflexia loses its specific localizing value for neuropathy versus advanced myopathy.

The "split-hand" sign (preferential atrophy of the thenar/first dorsal interosseous muscles) and its "split-leg" analogue are specific physical signs of ALS.

A low serum creatinine is a powerful indicator of significant muscle atrophy and should not be dismissed as simply "good renal function" in a patient with weakness.

MRI of the brain and spine is crucial to exclude structural mimics like spinal cord compression or myelopathy, but is typically unremarkable in ALS itself.

A muscle biopsy may be performed to exclude myositis; in ALS it shows features of neurogenic atrophy (grouped fiber atrophy), not primary inflammation or necrosis.

Source: March 6, 2026 VMR with Rabih & Rahul - progressive lower extremity weakness

Hypotension vs Shock

Hypotension is a measurement, whereas shock is a clinical syndrome of end-organ hypoperfusion. The primary goal is to determine if hypotension is causing shock by assessing vital organs, primarily the brain (mental status) and kidneys (urine output).

The central venous pressure (CVP) is the most important diagnostic branch point.

Low CVP points to hypovolemic or distributive shock.

Hypovolemic shock is caused by a "hole" in the cardiovascular system leading to intravascular volume loss (via hemorrhage, GI losses, severe dehydration). Management is volume repletion and controlling the source of loss. In hypovolemic shock with no obvious source of bleeding, remember the hidden spaces: the retroperitoneum, thigh, and GI tract.

Distributive shock is a hunt for a "substance" causing vasodilation. Think sepsis, anaphylaxis, drugs, or a critical hormone deficiency like cortisol.

High CVP indicates an "arrest of flow" problem (cardiogenic or obstructive).

"Arrest of Flow" (cardiogenic/obstructive) is uniquely morbid because it reduces organ perfusion from two sides: low arterial inflow and high venous outflow pressure.

The difference between obstructive and cardiogenic shock is myocardial health.

Obstructive shock features a healthy pump facing a mechanical block and may transiently benefit from fluids. Examples include massive pulmonary embolism, cardiac tamponade, tension pneumothorax, dynamic LV outflow tract obstruction. Management involves temporizing with fluids to help the healthy heart push against the obstruction while urgently addressing the mechanical cause via needle decompression, pericardial synthesis, or thrombolysis/thrombectomy.

Cardiogenic shock is primary pump failure where fluids are more likely detrimental. It can be caused by myocardial infarction or end-stage cardiomyopathy. It’s often a slower progressive process. Management involves inotropes, vasopressors, and mechanical circulatory support, as well as addressing the cause of cardiac dysfunction.

Source: Academy w/ Rabih - Hypotension - March 8, 2026

Abdominal Pain in Patients with a VP Shunt

In patients with new VP shunt presenting with fever or altered mental status, shunt-associated meningitis should be a primary consideration even with any typical presentation.

Classic meningeal signs, like nuchal rigidity, are frequently absent in device-related CNS infections. In such cases, fever and confusion might be the only clues.

Abdominal pain can be a red herring in VP Schott infections, representing irritation or infection of the distal catheter tip rather than a primary intra-abdominal process.

Source: March 9, 2026 Mainstream Mondays VMR with Maddy & Zakariyya G - 3 days of weakness and RUQ pain

Signs of a Pulmonary Hypertensive Crisis and RV Failure

The physical exam triad of an elevated JVP, a left parasternal heave, and a loud P2 is highly suggestive of severe pulmonary hypertension and significant RV strain.

A left parasternal heave is a palpable, sustained lifting of the chest wall along the left sternal border (the patient’s left).

A loud P2 (pulmonic component of the second heart sound, S2) is an accentuated sound from the pulmonary valve closing (“slamming shut”) at the end of ventricular systole, and is heard best at the upper left sternal border.

D-shaped left ventricular septum on echocardiography is a classic sign of severe RV pressure overload.

Acute RV failure can trigger a vicious "spiral of death" where hypoxemia and acidosis worsen pulmonary vascular resistance, which further strains the RV, decreases cardiac output, and perpetuates the cycle.

Breaking the RV “death spiral” involves supporting systemic blood pressure which helps perfuse the RV, optimizing preload (often with diuretics), and reducing RV afterload with pulmonary vasodilators such as inhaled nitric oxide or IV prostacyclines. Of course, treating any inciting cause (PE, infection) is also critical.

Intubation is extremely high-risk in patients with acute RV failure, as positive pressure ventilation and sedative agents can precipitate hemodynamic collapse by reducing preload and increasing afterload.

Source: March 11, 2026 VMR with Sharmin & Kirtan - SOB and fever and 1 day of chest pain

Lithium Toxicity

Chronic lithium toxicity is a state of lithium accumulation that occurs in patients on long-term therapy, typically precipitated by a decrease in renal clearance.

Common medications that reduce lithium clearance and precipitate toxicity include NSAIDs, ACE/ARBs, and thiazides.

Unlike acute overdose which presents with prominent GI symptoms, chronic toxicity manifests primarily with neurologic dysfunction.

Common presentations include ataxia, dysarthria (slurred speech), tremor, confusion, and encephalopathy, which can progress to seizures and coma.

An elevated serum lithium level confirms the diagnosis, though the absolute level correlates poorly with the severity of chronic neurologic symptoms.

Lithium can also independently cause a neutrophilic leukocytosis, which can confound the clinical picture when an infection is also present.

Management involves holding Lithium, providing aggressive IV hydration to enhance renal clearance and treating the underlying cause of AKI.

Source: March 13, 2026 VMR with Rabih & Anmolpreet - dysuria, cloudy urine, and urinary incontinence

Drug-Induced Acute Pancreatitis (DIAP)

Lisinopril is a known but rare cause of pancreatitis, with a proposed mechanism involving an idiosyncratic reaction or angioedema of the pancreatic duct.

Drug-induced acute pancreatitis is a diagnosis of exclusion, often suspected when there is a close temporal relationship between starting a medication and the onset of symptoms.

Biliary sludge seen on ultrasound, while not a definitive obstructing stone, can still be a risk factor for pancreatitis and should be considered in the differential diagnosis.

Source: CPS - March 16, 2026 Mainstream Mondays VMR with Youssef & Magnus - acute abdominal pain

Falsely Normal Haptoglobin

Haptoglobin can be falsely normal during active hemolysis if significant systemic inflammation is also present, as haptoglobin is an acute phase reactant.

For example, this may be seen with autoimmune hemolytic anemia in the setting of lupus.

Autoimmune hemolytic anemia (AIHA) can be the first manifestation of SLE, sometimes preceding the full systemic diagnosis by months or years.

Source: CPS - March 17, 2026 VMR with Ravi & Mengyu - fatigue, joint pains, and 1 month of rash

Cardiopathy-Myopathy Syndromes

The combination of significant cardiomyopathy (especially with fibrosis) and skeletal myopathy should strongly raise suspicion for a genetic cause (Danon disease, laminopathies) over an autoimmune process.

Muscle and cardiac MRI patterns are critical for diagnosis; fatty infiltration without edema suggests a chronic dystrophic or metabolic process, not acute inflammation.

A detailed family history is crucial even in elderly patients; a pattern of sudden death in young male relatives is a powerful clue for an X-linked cardiodegenerative disorders.

In X-linked dominant disorders, female carriers often have a later onset and milder phenotype than affected males due to random X-inactivation (lyonization).

Source: CPS - March 20, 2026 VMR with Rabih & CPS Team - lower extremity weakness

Bladder Diverticula and Painless Hematuria

Bladder diverticula are outpouchings of the bladder mucosa through the muscularis propria (bladder wall).

While some are congenital, most are acquired due to chronically elevated intravesical pressure, typically from bladder outlet obstruction (benign prostatic hyperplasia, urethral stricture). This high pressure forces the mucosa to herniate through weaker points in the bladder wall.

Many diverticula are asymptomatic. When symptoms occur, they can include recurrent UTIs (due to urine stasis), incomplete emptying, or gross hematuria.

Bleeding arises from fragile, superficial blood vessels lining the thin diverticular wall, which can rupture spontaneously or from chronic irritation.

The clinical presentation of painless gross hematuria can mimic that of bladder cancer, which must always be ruled out.

Painless gross hematuria, especially with clots, strongly suggests a lower urinary tract source (bladder, prostate) rather than a glomerular origin.

Cystoscopy is the gold standard for diagnosis and management. It allows for direct visualization of the diverticular openings, evaluation of the entire bladder lining to exclude malignancy, evacuation of clots, and potential cauterization of bleeding vessels.

Source: CPS - Mainstream Mondays VMR with Youssef & Sawsan - hematuria

Renal Osteodystrophy and Secondary Hyperparathyroidism

Renal osteodystrophy is a complex bone disease that occurs in patients with CKD.

Its pathogenesis is driven by disturbances in mineral metabolism.

Failing kidneys are unable to excrete phosphate, leading to hyperphosphatemia, and cannot synthesize active vitamin D (calcitriol), which causes hypocalcemia.

These two abnormalities provide a powerful, chronic stimulus for the parathyroid glands to secrete parathyroid hormone (PTH), leading to secondary hyperparathyroidism.

Common presentations range from asymptomatic bone changes to bone pain, muscle weakness, and pathological fractures.

X-rays can reveal a spectrum of findings, including subperiosteal bone resorption, osteopenia, and cystic bone lesions known as osteitis fibrosa cystica or "brown tumors." These are collections of osteoclasts, giant cells, and fibrous tissue that appear as osteolytic lesions and represent a severe manifestation of hyperparathyroidism.

A markedly elevated alkaline phosphatase without significant liver enzyme elevation strongly suggests a bone origin, indicating a state of high bone turnover.

Source: CPS - March 23, 2026 VMR with Alec & Austin - bilateral hip pain for 3 hours

Pulmonary Hydatid Disease

Pulmonary Hydatid Disease is a zoonotic parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus.

Humans are accidental hosts, typically infected by ingesting eggs from the feces of definitive hosts (dogs) that have been in contact with intermediate hosts (sheep). An occupation as a farmer with exposure to both animals can be a critical clue for a zoonotic infection like Echinococcosis.

The combination of a chronic pulmonary process, eosinophilia, and imaging of a complex cystic lesion should strongly raise suspicion for a parasitic etiology.

While the liver is the most common organ affected by hydatid disease, the lungs are the second most common site, and isolated pulmonary disease can occur without hepatic involvement.

Rupture of a pulmonary hydatid cyst into the pleural space is a well-described cause of secondary spontaneous pneumothorax, often presenting as a hydropneumothorax with an air-fluid level.

Recognizing classic radiologic signs on CT, such as the "water lily sign," is virtually pathognomonic for a ruptured hydatid cyst.

Source: CPS - VMR with Ravi & Kirtan - chest pain & SOB for 3 months

Anti-MuSK Myasthenia Gravis

Anti-MuSK Myasthenia Gravis is a rare and often severe autoimmune subtype of MG where antibodies target Muscle-Specific Kinase, a protein essential for organizing acetylcholine receptors at the neuromuscular junction.

This differs from the more common form caused by anti-AChR antibodies. The clinical presentation of MuSK-MG is often distinct, with a predilection for severe bulbar (dysphagia, dysarthria), facial, and respiratory muscle weakness, which can lead to rapid decompensation.

Neck weakness is also common, while significant limb weakness may be less prominent than in AChR-positive MG.

The history of fatigable weakness - symptoms that worsen with activity and progress throughout the day- is the cardinal clue for a neuromuscular junction disorder.

EMG with repetitive nerve stimulation is a critical diagnostic workhorse, providing objective evidence of neuromuscular junction fatigability, especially when serology is negative or ambiguous.

Source: CPS - March 26, 2026 VMR with Rabih & Saketh - progressive weakness

Scurvy and Extensive Bruising

Scurvy is a disease caused by a severe deficiency of vitamin C (ascorbic acid), an essential cofactor for collagen synthesis.

The resulting defective collagen leads to capillary fragility, poor wound healing, and abnormal bone formation.

Classic presentations include cutaneous findings like perifollicular hemorrhages (which may initially be obscured by extensive bruising), "corkscrew" hairs, and ecchymoses, which can become confluent and mimic vasculitis.

Other key features are gingivitis with bleeding gums, poor dentition, and severe myalgias or bone pain from hemarthrosis or subperiosteal hemorrhage.

These findings can be even worse when there’s a coexisting coagulopathy.

Severe pain accompanying cutaneous purpura is atypical for simple bruising and should raise suspicion for bleeding into deeper structures, such as the subperiosteal hemorrhage classic for scurvy.

Management is straightforward with oral vitamin C replacement, leading to a rapid reversal of symptoms. Bleeding often ceases within 24-48 hours, and skin and bone pain improve within weeks.

Source: CPS - March 27, 2026 VMR with Rabih & Reza - rash and bilateral leg pain

Aseptic (Viral) Meningitis Presentations

Enteroviruses (Coxsackievirus, Echovirus) are the most common cause of aseptic (viral) meningitis.

The classic presentation includes fever, headache, photophobia, and nuchal rigidity.

However, enteroviruses can also invade the spinal cord (myelitis), leading to more complex neurological syndromes.

This can manifest as an acute flaccid paralysis similar to poliomyelitis, by affecting the anterior horn cells (lower motor neurons), or as a more complex myelopathy involving other spinal tracts, resulting in a mixed picture of upper and lower motor neuron signs

The hallmark of typical enteroviral meningitis is a lymphocytic pleocytosis with normal glucose and normal or mildly elevated protein in the CSF. However, the CSF can be deceptively normal early in the infection.

Source: CPS - March 31, 2026 VMR with John & Maddy - acute ascending weakness

This post highlights in-depth breakdowns of my favorite clinical cases from March 2026.

There will be a separate post highlighting all of my other favorite rapid-fire pearls from the “honorable mention” cases that didn’t make the cut.

Case 10-2026 A 70-Year-Old Woman With A Racing Heart, Fatigue, And Dyspnea Case (NEJM)

Source

Case Summary

A 70 year-old woman presented with fatigue, dyspnea, and edema one month after a catheter ablation for AFib. Her symptoms were initially attributed to heart failure. However, she developed dysphagia and chest pain. Workup was notable for a pericardial friction rub, polymicrobial bacteremia with oral flora, and new low QRS voltage on ECG. CT chest showed pneumopericardium, moderate bilateral pleural effusions, diffuse pericardial thickening, and circumferential thickening of the esophagus adjacent to the left atrium. She was diagnosed with an esophageal-pericardial fistula, underwent successful emergency surgical repair, and after a prolonged ICU stay, returned to her baseline functional status.

Esophageal-Pericardial Fistula

An esophageal-pericardial fistula is a rare but life-threatening complication that can result from thermal injury to the esophagus, which lies in close proximity to the posterior left atrium. The initial injury evolves into ulceration, full-thickness perforation, and fistulization into the adjacent pericardial space, typically presenting 1-6 weeks after the procedure. An atrioesophageal fistula, which involves a direct connection to the left atrium, is a related and even more lethal variant.

Common presentations are often non-specific and combine both cardiac and gastrointestinal symptoms, including fever, malaise, chest pain, dyspnea, dysphagia, and signs of sepsis.

Key Diagnostic Findings:

• Labs: Leukocytosis and positive BCx, often with oropharyngeal flora (strep viridans), are common.

• EKG: May show signs of pericarditis or new low voltage secondary to pericardial effusion.

Treatment involves prompt initiation of broad-spectrum antibiotics covering oral and gut flora, followed by surgical repair. Surgery includes fistula division, debridement of infected tissues, primary repair of the esophagus and any cardiac defect, and reinforcement with a vascularized tissue flap (intercostal muscle). EGD and TEE are relatively contraindicated due to the risk of iatrogenic air embolism.

Pearls

• Suspect an esophageal fistula in any patient presenting with a combination of cardiac (chest pain, dyspnea) and esophageal (dysphagia, odynophagia) symptoms 1-6 weeks after a catheter ablation procedure.

• Pneumopericardium on chest imaging in a post-ablation patient is a pathognomonic finding for an esophageal fistula and constitutes a surgical emergency.

• The onset of symptoms is usually delayed, reflecting the time required for thermal injury to progress to full-thickness necrosis and perforation.

• Polymicrobial bacteremia with oral flora (strep viridans) in the appropriate clinical context strongly supports a diagnosis of esophageal perforation.

March 10, 2026 VMR with Ravi & Kirtan - difficulty speaking

Source

Case Summary

A 50 year-old man with a hx of alcohol abuse presented with acute-on-chronic tongue swelling causing difficulty speaking. EHR review noted a similar episode two months prior that was attributed to anaphylaxis. His evaluation was notable for severe right hip pain, peripheral neuropathy, and a history of recurrent shingles. Pivotal findings included a profound globulin gap (Total Protein 10, Albumin 2.9), an elevated ESR, pathologic vertebral compression fractures on CT, and a complement profile showing low C4 and C1Q. Further workup revealed a massive monoclonal IgA paraprotein and a bone marrow biopsy showing 80% plasma cells, establishing the diagnosis of IgA kappa multiple myeloma as the cause of a paraneoplastic acquired C1 inhibitor deficiency.

Acquired C1 Inhibitor Deficiency (Acquired Angioedema) secondary to IgA Kappa Multiple Myeloma

Acquired C1 inhibitor deficiency, also known as Acquired Angioedema (AAE), is a rare disorder characterized by recurrent episodes of non-pruritic, non-pitting swelling of the skin and submucosal tissues. Unlike hereditary angioedema, AAE typically presents in adults over 40 and is often associated with an underlying lymphoproliferative disorder, such as multiple myeloma or lymphoma, or an autoimmune condition. The pathophysiology involves the consumption or inactivation of C1 inhibitor protein, often driven by the monoclonal protein or autoantibodies. This leads to dysregulation of the complement and contact systems, resulting in excessive production of bradykinin which is the primary mediator of the angioedema. The swelling does not respond to standard anaphylaxis treatments like epinephrine, antihistamines, or corticosteroids.

Key diagnostic findings include:

• Labs: A classic pattern of low C4, low C1 inhibitor function, and a markedly low C1q level. The low C1q is the key feature distinguishing AAE from most forms of hereditary angioedema.

• Paraprotein evaluation: A serum protein electrophoresis (SPEP) and immunofixation are essential to identify an underlying monoclonal gammopathy, as seen in this case with the large IgA spike.

• Bone Marrow Biopsy: Confirms the underlying hematologic malignancy.

Management involves treating the acute angioedema attacks with specific agents (C1 inhibitor concentrate - icatibant) and, most importantly, directing therapy at the underlying condition (in this case, chemotherapy for multiple myeloma) to control the paraneoplastic syndrome over the long term.

Clinical Pearls

• Late-onset angioedema (first episode >40 years old) should always prompt a workup for an acquired cause, primarily an underlying lymphoproliferative malignancy.

• The laboratory hallmark of acquired angioedema is the combination of low C4 and low C1q levels, which differentiates it from hereditary forms where C1q is typically normal.

• A total protein to albumin gap greater than 4 (a “globulin gap”) is a powerful clue for a monoclonal gammopathy and mandates a workup with SPEP and immunofixation.

• The angioedema in AAE is mediated by bradykinin, not histamine, which is why standard anaphylaxis treatments like epinephrine, antihistamines, and steroids don’t work.

• Multiple myeloma can present with subtle or diverse signs, including pathologic fractures (especially vertebral), recurrent infections (like shingles, suggesting impaired cell-mediated immunity), and peripheral neuropathy.

• A markedly elevated ESR (>100) with a normal or minimally elevated CRP is a classic pattern of “ESR/CRP discordance” that strongly suggests the presence of a paraprotein. This is because immunoglobulins directly accelerate erythrocyte sedimentation via rouleaux formation via a neutralization of the negative charges on RBC surfaces without producing the inflammation that leads to elevated CRP.

March 12, 2026 VMR with Rabih & Krithika - AMS and seizure like activity

Source

Case Summary

A 54 year-old woman with a complex history including Cowden syndrome, multiple malignancies, and a bioprosthetic aortic valve (TAVR) developed acute AMS and seizure-like activity after a prolonged two-week hospitalization for a presumed UTI and influenza. Pivotal findings included significant hypernatremia suggesting a subacute process, and a brain MRI revealing a small acute right occipital infarct. This prompted a TEE which identified a large, 1.4 cm mobile vegetation on the bioprosthetic aortic valve, despite persistently negative blood cultures in the setting of broad-spectrum antibiotic use. She was transferred for valve replacement, and pathology of the explanted valve confirmed the final diagnosis of Fungal Endocarditis.

Fungal Endocarditis

Fungal Endocarditis is rare, and typically occurs in patients with significant risk factors, including the presence of prosthetic valves, prolonged hospitalization with broad-spectrum antibiotic use, central venous catheters, immunosuppression, and IV drug use. The clinical presentation can be insidious, but it is classically associated with large, friable vegetations (>1 cm) which lead to a high rate of major embolic events (stroke, limb ischemia) and valvular destruction.

Key diagnostic findings include:

• Labs: Blood cultures are a cornerstone of diagnosis but have a very low sensitivity for fungi (positive in <50% of cases), making FE a primary consideration in “culture-negative” endocarditis. Fungal biomarkers like (1,3)-beta-D-glucan can be supportive.

• Imaging: Echocardiography, particularly transesophageal echo (TEE), is the most important diagnostic tool for visualizing the characteristic large vegetations.

• Pathology: Definitive diagnosis frequently requires histopathology and culture from surgically resected valvular tissue or an extracted embolus.

Management requires a combined medical and surgical approach. Prolonged courses of systemic antifungal therapy are necessary, but early surgical intervention with valve replacement is the standard of care due to the high risk of catastrophic embolization and frequent failure of medical therapy alone.

Clinical Pearls

• In a patient with a prosthetic heart valve presenting with an embolic event (stroke), infective endocarditis must be considered a primary diagnosis until proven otherwise, often requiring a TEE.

• The triad of large vegetations (>1 cm), major embolic events, and negative blood cultures in a high-risk patient (prolonged hospitalization, broad-spectrum antibiotics, prosthetic valve) is highly suggestive of Fungal Endocarditis.

• Significant hypernatremia greater than 150 in a hospitalized patient implies a prolonged state of reduced water intake, suggesting an altered mental status has been evolving over days, not hours.

• Prior antibiotic exposure is a common cause of culture-negative endocarditis; however, one must also consider intrinsically low-yield organisms like fungi (Candida, Aspergillus) and fastidious bacteria (HACEK, bartonella, coxiella, brucella, etc.)

• A normal or limited transthoracic echocardiogram (TTE) does not rule out endocarditis, especially on a prosthetic valve. A TEE has much higher sensitivity and is required when clinical suspicion remains high.

• While bioprosthetic valves are less thrombogenic than mechanical valves, they remain a significant nidus for infection, making vegetation more likely to be infectious rather than sterile clot.

The NEJM Case “Case 8-2026 A 57-Year-Old Woman With Chest Pain, Dyspnea, And Syncope” from March also actually highlighted a patient with fungal endocarditis!

In this case, there was an aortic root abscess that caused pericardial effusion and tamponade; an aortic root abscess occurs when the infection burrows into the tissue surrounding the aortic valve, which can then erode through the aortic wall to form a pseudoaneurysm or rupture into an adjacent space, such as the pericardium, causing hemopericardium and cardiac tamponade.

March 19, 2026 VMR with Rabih & Eugene - BP 60/40 with rapid, thready pulse

Source

Case Summary

A 29 year-old man presented with acute chest pain and palpitations. BP was 60/40 and EKG showed monomorphic VT initiating an electrical storm that required four synchronized cardioversions and multiple antiarrhythmic drugs. Post-conversion EKG showed a RBBB and a subtle epsilon wave, and an echocardiogram revealing right atrial and ventricular dilatation with dysfunction. A cardiac MRI later confirmed these structural changes, showing aneurysmal outpouchings and fibrofatty replacement of the myocardium. The final diagnosis was Arrhythmogenic Cardiomyopathy (ACM/ARVC), which was managed with an esmolol infusion and subsequent placement of an ICD.

Arrhythmogenic Cardiomyopathy (ACM/ARVC)

Arrhythmogenic Cardiomyopathy, historically known as Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), is a genetic heart muscle disease characterized by the progressive replacement of myocardium with fibrofatty tissue. While it predominantly affects the right ventricle, left ventricular and biventricular involvement is common. This structural change creates a risk of life-threatening ventricular arrhythmias. It typically presents in young adults with palpitations, syncope, or sudden cardiac death, often triggered by physical exertion.

Key diagnostic findings include:

• EKG: T-wave inversions in the right precordial leads (V1-V3), a prolonged S-wave upstroke, and the highly specific but insensitive epsilon wave (a small positive deflection at the end of the QRS complex in V1-V2). The characteristic VT often has a left bundle branch block morphology, originating from the right ventricle.

• Imaging: Echo may show RV dilatation, akinesia, or dyskinesia. Cardiac MRI is the gold standard for non-invasive structural assessment, revealing RV dilatation, regional wall motion abnormalities, and characteristic late gadolinium enhancement indicative of fibrofatty infiltration.

• Genetics: Pathogenic mutations in genes encoding desmosomal proteins are identified in about 60% of cases.

Management aims to prevent sudden cardiac death and control arrhythmias. The cornerstone of therapy is an ICD for patients with sustained VT or other high-risk features. Beta-blockers and other antiarrhythmic drugs are used to reduce arrhythmia burden, and all patients are advised to restrict strenuous and competitive exercise.

Clinical Pearls

• The distinction between VT morphologies is key: monomorphic VT suggests a focal structural origin (scar, fibrofatty tissue), whereas polymorphic VT points toward a diffuse metabolic or ischemic problem (electrolyte imbalance, drug toxicity, acute ischemia).

• The epsilon wave is a small, low-amplitude signal at the end of the QRS complex in V1-V2 that is highly specific for ARVC and represents delayed right ventricular activation.

• Managing an electrical storm requires aggressive suppression of sympathetic drive; after cardioversions and standard antiarrhythmics, IV beta-blockade (esmolol) and deep sedation are critical steps.

• While an echo can provide initial clues (RV dilatation, dysfunction), cardiac MRI is the definitive imaging modality for diagnosing ARVC by visualizing the characteristic fibrofatty myocardial replacement.

March 30, 2026 Mainstream Mondays VMR with Maddy & Saketh - severe right knee pain and swelling

Source

Case Summary

A 78year-old man with a history of OA presented with a three-day history of acute, severe right knee pain, swelling, and warmth. He was afebrile with a normal WBC count, but ESR and CRP were elevated. Knee X-ray showed chondrocalcinosis and an arthrocentesis showed WBC 30,000 with a negative gram stain. The diagnosis of an acute flare of Calcium Pyrophosphate Dihydrate (CPPD) crystal deposition disease (pseudogout) was confirmed by the presence of rhomboid-shaped, weakly positively birefringent crystals in the synovial fluid. He was successfully managed with an intra-articular steroid injection and adjustment of medications known to cause hypomagnesemia (omeprazole) and electrolyte disturbances (chlorthalidone), leading to significant clinical improvement.

Calcium Pyrophosphate Dihydrate (CPPD) Crystal Deposition Disease

CPPD is a crystal-induced arthritis caused by the deposition of calcium pyrophosphate dihydrate crystals in articular and periarticular tissues. It has a varied clinical presentation, ranging from asymptomatic chondrocalcinosis found incidentally on imaging, to acute, severe inflammatory monoarthritis mimicking gout (termed “pseudogout”), to a chronic degenerative polyarthritis resembling osteoarthritis. The knee is the most commonly affected joint. While often idiopathic and associated with advanced age, CPPD can be secondary to metabolic disorders, especially in patients under 60, including hyperparathyroidism, hemochromatosis, and hypomagnesemia.

Key diagnostic findings include:

• Labs: Non-specific elevation of inflammatory markers (ESR, CRP) during acute flares.

• Imaging: Plain radiographs may reveal chondrocalcinosis, the pathognomonic linear calcification of hyaline or fibrocartilage.

• Arthrocentesis: This is the gold standard for diagnosis. Synovial fluid analysis reveals an inflammatory effusion (WBC count typically 2,000-50,000) and the definitive presence of rhomboid-shaped, weakly positively birefringent CPPD crystals under polarized light microscopy. A negative Gram stain and culture are essential to rule out concurrent septic arthritis.

Management of acute flares focuses on rapid inflammation control with NSAIDs, colchicine, or intra-articular glucocorticoid injections. Systemic steroids may be used for severe or polyarticular disease.

Clinical Pearls

• The presence of chondrocalcinosis on an X-ray is highly suggestive of CPPD, but its absence does not rule out the diagnosis, and its presence does not exclude a superimposed septic arthritis.

• The definitive diagnosis of CPPD requires identifying rhomboid-shaped, weakly positively birefringent crystals in synovial fluid via polarized light microscopy.

• A synovial fluid WBC count in a CPPD flare can be markedly elevated, overlapping with the range seen in septic arthritis, reinforcing the critical importance of Gram stain and culture.

• Consider underlying metabolic causes of CPPD (hyperparathyroidism, hypomagnesemia) and contributing medications (PPI, diuretics) in the workup.

• Acute CPPD flares can be precipitated by physiologic stressors such as surgery (especially parathyroidectomy), trauma, or acute medical illness due to shifts in calcium and pyrophosphate levels.

While not every case can make the cut each month and be considered one of my favorites, many still have interesting clinical pearls and lessons worth sharing.

Here’s a collection of some of my favorite additional pearls from February 2026.

Reninoma (Juxtaglomerular Cell Tumor)

A reninoma is a rare, typically benign tumor of the juxtaglomerular cells of the kidney that autonomously secretes excessive amounts of renin. It is a classic cause of secondary hypertension, most often affecting adolescents and young adults.

The overproduction of renin leads to profound activation of the renin-angiotensin-aldosterone system (RAAS), causing severe vasoconstriction (via angiotensin II) and secondary hyperaldosteronism, which results in Na retention and K wasting.

The hallmark is an extremely high plasma renin activity. This typically drives a secondary hyperaldosteronism, although plasma aldosterone levels may be normal or only mildly elevated, as seen in this case. Plasma metanephrines are normal, which helps differentiate it from a pheochromocytoma.

The profound hyperreninemia and downstream effects of angiotensin II can mimic idiopathic intracranial hypertension (IIH), presenting with severe headaches and papilledema.

Resection via partial nephrectomy is curative, resulting in complete resolution of the hypertension and other abnormalities.

Source: NEJM - Case 5 2026 An 18-Year-Old Woman With Headache And Hypertension

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

EGPA is a systemic small-vessel necrotizing vasculitis characterized by asthma, sinusitis, and profound eosinophilia.

It should be suspected in any patient with adult-onset asthma/sinusitis who develops peripheral eosinophilia and systemic symptoms.

The disease often evolves through phases:

1. A prodromal phase with adult-onset asthma and allergic rhinitis

2. An eosinophilic phase with high peripheral eosinophil counts and organ infiltration (most commonly lungs and GI tract)

3. A final vasculitic phase with constitutional symptoms, neuropathy (mononeuritis multiplex), skin purpura, and cardiac or renal disease.

Cardiac involvement is a leading cause of mortality.

Labs may show eosinophilia (typically >1500), elevated IgE, and positive Antineutrophil Cytoplasmic Antibodies (ANCA) in 30-40% of cases. The most common ANCA pattern is perinuclear (p-ANCA) with antibodies against myeloperoxidase (MPO). A cytoplasmic pattern (c-ANCA) with antibodies to proteinase 3 (PR3) is rare (~5%).

Biopsy of an affected organ demonstrates the classic triad of eosinophilic infiltration, necrotizing vasculitis, and extravascular granulomas.

Glucocorticoids are the primary treatment in induction therapy. Biologic therapies that inhibit the interleukin-5 (IL-5) pathway, such as mepolizumab or benralizumab, are highly effective for managing relapsing disease and as steroid-sparing agents.

Source: NEJM - Case 6 2026 A 91-Year-Old Man With Shortness Of Breath, Weight Loss, And Eosinophilia

B12 and Tryptase in Eosinophilia

Elevated IgE + normal B12 + normal tryptase = think EGPA or lymphocytic HES

This triad separates immune-mediated from myeloproliferative HES before FISH/molecular testing.

High IgE - Th2/immune-driven process

High B12 - clonal myeloid expansion (released from eosinophil granules and with myeloid cell turnover)

High Tryptase - mast cell marker; there is often also a systemic mastocytosis when there are oncogenic drivers of myeloid cells present

Source: NEJM - Case 6 2026 A 91-Year-Old Man With Shortness Of Breath, Weight Loss, And Eosinophilia

Periprosthetic joint infection (PJI) with Mycobacterium bovis bacille Calmette-Guérin (BCG)

This is a rare, delayed complication of intravesical BCG immunotherapy for non-muscle-invasive bladder cancer.

The infection results from hematogenous dissemination of the live, attenuated M. bovis strain, which can seed prosthetic material months to years after the initial therapy.

The clinical presentation is typically chronic and indolent, with insidious onset of pain, swelling, and functional decline, often lacking systemic symptoms like fever. It can mimic more common causes of late prosthetic failure, such as aseptic loosening or particle disease.

A key feature is the discrepancy of a positive PJI biomarker (α-defensin) with negative routine bacterial cultures.

M. bovis is intrinsically resistant to pyrazinamide.

Source: NEJM - Case 7 2026 A 91-Year-Old Man With Left Knee Pain

Catheter-Related Blood Stream Infections (CRBSI)

The absence of erythema, tenderness, or purulence at the catheter insertion site does not rule out a CRBSI; systemic symptoms like fever and chills may be the only manifestation.

Staph aureus bacteremia is never a contaminant and mandates a thorough workup for metastatic complications, most importantly infective endocarditis.

Patients on hemodialysis have both structural (the catheter) and functional (uremia-induced) immunocompromise, placing them at very high risk for bloodstream infections.

The duration of therapy ranges from 14 days for uncomplicated cases to 4-6 weeks or longer for complicated infections like endocarditis or osteomyelitis.

Source: CPS - February 2, 2026 Mainstream Mondays VMR with Youssef & Seeme - fever

Chronic Pancreatitis

Chronic pancreatitis can cause a benign biliary stricture, leading to a clinical picture of cholangitis that mimics primary stone disease or malignancy.

An obstructive or cholestatic pattern of liver enzymes (elevated Alk Phos, GGT) without significant hyperbilirubinemia can occur with partial or intermittent biliary obstruction, as seen with strictures or sludge.

Abdominal CT often reveals characteristic findings like pancreatic calcifications, ductal dilation, and pancreatic atrophy. MRCP provides excellent visualization of ductal anatomy, including strictures.

Splenic vein thrombosis is a classic complication of pancreatitis due to inflammation near the pancreatic tail; this can lead to splenomegaly, gastric varices, and rarely, splenic hematoma or infarction.

Murphy's sign has low sensitivity for biliary disease, and its absence should not dissuade the clinician from pursuing a workup for cholangitis or cholecystitis if clinical suspicion is high.

Source: CPS - February 6, 2026 VMR with Youssef & Ann Marie - fever and abdominal pain

Ischemic Optic Neuropathy (Non-Arteritic vs Arteritic)

Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) is the most common form, considered a "stroke" of the optic nerve.

It is caused by transient hypoperfusion of the posterior ciliary arteries, often due to underlying vasculopathic risk factors like HTN, T2DM, HLD, and OSA.

Presentation is typically sudden, unilateral, painless vision loss, classically noted upon waking due to nocturnal hypotension. Key findings include an afferent pupillary defect, optic disc edema.

Arteritic Anterior Ischemic Optic Neuropathy (A-AION) is a true ophthalmologic emergency caused by vasculitis from Giant Cell Arteritis (GCA).

It presents with more profound, sudden, and painless vision loss. It may be accompanied by systemic symptoms of GCA like new-onset headache, jaw claudication, scalp tenderness, or polymyalgia rheumatica.

Key findings include an afferent pupillary defect and a characteristic pale, "chalky-white" swollen optic disc. Inflammatory markers (ESR and CRP are typically elevated).

Source: CPS - February 9, 2026 Mainstream Mondays VMR with Youssef & Manaswini - acute loss of vision

Homocystinuria

Homocystinuria is an inherited metabolic disorder, most commonly caused by a deficiency of the enzyme cystathionine beta-synthase (CBS), which is critical for methionine metabolism.

This defect leads to the toxic accumulation of homocysteine and its precursor, methionine, in the blood and urine.

Patients often present with a multisystem syndrome that can include skeletal abnormalities (Marfanoid habitus, osteoporosis), ocular issues (ectopia lentis, severe myopia), neurological impairment (developmental delay, seizures), and most critically, premature and severe thromboembolic events (stroke, MI, DVT/PE).

The pathophysiology of such vascular complications stems from homocysteine-induced endothelial cell damage, which promotes a severe prothrombotic state through increased platelet aggregation and altered coagulation factors, leading to both arterial and venous thrombosis.

Its a treatable condition; management with high-dose vitamin B6, folate, B12, and dietary changes can significantly lower homocysteine levels and reduce the risk of future life-threatening clots.

Source: CPS - February 11, 2026 VMR with Sharmin & Sarah B. - chest pain & shortness of breath

IgA Vasculitis (Henoch-Schonlein Purpura)

IgA vasculitis is a systemic, small-vessel vasculitis characterized by the deposition of IgA-containing immune complexes. While most common in children, it can affect adults. It is often triggered by an infection, most classically Group A Streptococcus.

The combination of pharyngitis, a palpable purpuric rash, and acute oligoarthritis/arthralgia should prompt consideration of post-infectious syndromes, including IgA vasculitis, acute rheumatic fever, and disseminated gonococcal infection.

Palpable purpura signifies vascular inflammation (vasculitis), not a platelet disorder. A skin biopsy is the key step to confirm the diagnosis and identify the underlying pathology.

The absence of a joint effusion on ultrasound despite a swollen, painful joint points towards periarticular inflammation or tenosynovitis, a common finding in IgA vasculitis and spondyloarthropathies.

When managing IgA vasculitis, you must monitor for organ damage, particularly renal involvement. A urinalysis is mandatory at diagnosis and during follow-up to screen for nephritis.

Source: CPS - February 12, 2026 VMR with Rabih & Julia Z - fever with painful swallowing and ankle swelling

Immune Checkpoint Inhibitor (ICI)-Related Colitis

The clinical presentation of ICI colitis is highly variable, ranging from mild diarrhea to a fulminant, life-threatening colitis with abdominal pain, fever, and hematochezia, which can lead to perforation.

The onset can be delayed, occurring weeks to months after ICI initiation or discontinuation.

ICI-related colitis can be a great mimicker, presenting with localized abdominal pain and imaging findings indistinguishable from sigmoid diverticulitis.

While CT is vital to rule out acute complications like perforation, it is non-specific for the etiology of colitis. Definitive diagnosis of ICI colitis requires colonoscopy with biopsy (which helps to rule out other etiologies like CMV colitis).

Management is guided by severity. Mild cases may resolve with holding the ICI. Moderate-to-severe cases require systemic corticosteroids. Patients with steroid-refractory disease often need second-line immunosuppressive therapy with agents such as infliximab or vedolizumab.

Source: CPS - February 13, 2026 VMR with Rabih & Magnus - acute fever, abdominal pain, nausea and vomiting

Bacterial Pharyngitis

The absence of a cough is one of the strongest clinical predictors of bacterial pharyngitis.

Do not anchor management decisions on a negative rapid Group A Strep antigen test; it has poor sensitivity (~70-80%) and misses other critical pathogens.

Others include Group C & G Streptococcus and Fusobacterium necrophorum (the causative agent of Lemierre's syndrome).

When pharyngitis is accompanied by significant systemic symptoms (profound fatigue, rash, diffuse lymphadenopathy), pivot the workup towards the "two M's": Measles and Mononucleosis syndromes (EBV, CMV, acute HIV).

Source: CPS - Academy Session w/ Rabih - Pharyngitis

ADHF Leading to RUQ Pain

Severe right-sided heart failure can cause profound hepatic congestion, presenting as acute RUQ pain and tenderness that can mimic acute cholecystitis.

On ultrasound, gallbladder wall thickening and pericholecystic fluid in the context of volume overload, but with no gallstones and a negative Murphy's sign, should raise suspicion for congestive hepatopathy over primary gallbladder pathology.

Liver function tests often show a cholestatic or mixed pattern of injury with elevated alkaline phosphatase, bilirubin, and mild transaminitis, known as "congestive hepatopathy."

The absence of pulmonary crackles does not rule out severe heart failure, especially in chronic cases with increased lymphatic drainage or in presentations dominated by right-sided failure.

Source: CPS - February 18, 2026 VMR with Sharmin & Lera - CP, SOB and RUQ pain

Myositis

A normal creatine kinase (CK) does not rule out inflammatory myositis; myositis-specific antibody panels are essential when clinical suspicion is high.

Pain on active but not passive range of motion localizes pathology to periarticular structures (muscles, tendons, bursae), and points away from a true arthritis.

Source: CPS - February 19, 2026 VMR with Rabih & Hans - progressive chest pain

HIV Causing PAH and RV Failure

HIV-associated Pulmonary Arterial Hypertension (PAH) is a serious, non-infectious complication of HIV, classified as Group 1 PH.

The combination of a loud P2 and a parasternal heave on physical exam are clues for severe pHTN and significant RV hypertrophy/strain.

HIV can be a great mimicker of autoimmune disease, causing systemic symptoms, pancytopenia, and false-positive autoantibodies (ANA, anti-RNP) through polyclonal B-cell activation.

Source: CPS - VMR with Rabih & Mengyu - 2 weeks of abdominal pain and dizziness

Rituximab-Induced Serum Sickness

Serum sickness is a Type III hypersensitivity reaction caused by the deposition of circulating immune complexes in tissues, leading to complement activation and inflammation.

A reaction to rituximab can occur because the immune system can form antibodies (human anti-chimeric antibodies, or HACAs) against the murine (mouse-derived) portion of rituximab.

Symptoms typically appear 1-3 weeks after drug exposure. The classic triad is fever, rash (morbilliform or urticarial), and polyarthralgia.

Temporomandibular joint (TMJ) involvement can cause significant pain and trismus.

The most characteristic laboratory abnormality is hypocomplementemia, particularly a low C4 due to consumption by immune complexes. Eosinophilia may be present but is not required.

Diagnosis is primarily clinical, based on a compatible syndrome with a clear temporal link to an offending agent. The mainstay of management is discontinuing the drug.

For moderate to severe symptoms, a course of systemic corticosteroids leads to a rapid and dramatic clinical response, which can be both diagnostic and therapeutic.

Source: CPS - February 24, 2026 VMR with Ravi & Kirtan - progressive diffuse joint and muscle pain

Malakoplakia

Malakoplakia is a rare but important malignancy mimic, presenting as an inflammatory pseudo-tumor in immunocompromised hosts due to defective macrophage function.

It is most strongly associated with immunosuppression (organ transplant, HIV, etc.) and recurrent bacterial infections, most commonly with E. coli.

The underlying pathophysiology involves the incomplete digestion of phagocytosed bacteria by macrophages, leading to the accumulation of mineralized, calcified “concretions” within lysosomes.

Malakoplakia can affect any organ but most commonly involves the genitourinary tract (especially the bladder). It presents as soft, yellowish plaques or tumor-like masses that can be mistaken for malignancy.

The presentation can mimic a disseminated hematologic process with fever, pancytopenia, hepatosplenomegaly, and elevated LDH, alkaline phosphatase, and ferritin.

In an immunosuppressed patient, polymicrobial gram-negative bacteremia should prompt a search for a structural gastrointestinal source (mass, abscess) rather than being attributed solely to systemic immune compromise.

Management typically involves long-term courses of abx with good intracellular penetration (fluoroquinolones, rifampin), a reduction of immunosuppression when feasible, and surgical resection of discrete masses which can actually be curative.

Source: CPS - February 27, 2026 VMR with Rabih & Reza - diarrhea and fever

Diverticulitis Presenting as Urinary Symptoms

Acute diverticulitis is the inflammation and/or infection of a diverticulum, which is an outpouching of the colonic mucosa through the muscular wall, most commonly occurring in the sigmoid colon.

The pathophysiology involves micro or macro-perforation of a diverticulum, often due to erosion by a fecalith.

Common presentations include steady, aching LLQ pain, fever, and a change in bowel habits (constipation or diarrhea).

When the inflamed sigmoid colon is near the bladder, it can cause urinary symptoms such as dysuria, frequency, or urgency, and in severe cases, can lead to a colovesicular fistula.

New-onset dysuria in the setting of left lower quadrant abdominal pain should raise suspicion for sigmoid diverticulitis due to inflammation irritating the adjacent bladder.

The Hinchey classification, based on CT findings, is essential for staging the severity of acute diverticulitis and guiding appropriate management, from outpatient antibiotics to surgical intervention.

Source: CPS - Mainstream Mondays VMR with Maddy & Magnus - constipation

This post highlights in-depth breakdowns of my favorite clinical cases from February 2026.

There will be a separate post highlighting all of my other favorite rapid-fire pearls from the “honorable mention” cases that didn’t make the cut.

February 5, 2026 VMR with Youssef & Ravi - fever, fatigue, generalized weakness, night sweats

Source

Case Summary

A 76 year-old male farmer presented with a 3 month history of progressive fatigue, drenching night sweats, and inflammatory polyarthralgias. His presentation was complicated by an viral illness and the recent development of tender, “violaceous” fingertip lesions and LE edema. Pivotal findings included synovitis of the wrists, dilated nail fold capillaries, mild axillary lymphadenopathy, an elevated CK, a positive ANA and anti-dsDNA, and a nephritic urinary sediment with 2.4 g/day of proteinuria. A renal biopsy confirmed the final diagnosis of Systemic Lupus Erythematosus (SLE) with Class III lupus nephritis.

Systemic Lupus Erythematosus (SLE)

SLE is a chronic, multi-system autoimmune disease characterized by the production of autoantibodies against nuclear antigens, leading to immune complex deposition and widespread inflammation. Its presentation is highly variable, affecting nearly any organ system. Common manifestations include constitutional symptoms (fever, fatigue), arthritis/arthralgias, mucocutaneous lesions (malar rash, photosensitivity, oral ulcers), serositis (pleuritis, pericarditis), cytopenias, and renal disease. While most common in young women, a second peak of incidence occurs in older adults, where it can present more frequently in men.

Key diagnostic findings include:

• Serology: A positive Antinuclear Antibody (ANA) is a sensitive screening test. Highly specific antibodies include anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm). Anti-dsDNA titers often correlate with disease activity, particularly nephritis. Low complement levels (C3/C4) are also common during active disease flares.

• Labs: Urinalysis revealing an active sediment (proteinuria, hematuria, cellular casts) is a critical sign of lupus nephritis. Inflammatory markers (ESR, CRP) are often elevated.

• Pathology: Tissue biopsy is the gold standard for confirming organ involvement. Renal biopsy is crucial for diagnosing and classifying lupus nephritis (Class I-VI), which directly guides the intensity of immunosuppressive therapy.

Management is based on disease severity and organ involvement, ranging from hydroxychloroquine for mild disease to potent immunosuppressants like high-dose glucocorticoids, mycophenolate mofetil (MMF), or cyclophosphamide for organ-threatening manifestations like severe nephritis.

Pearls

• SLE has a bimodal age distribution; late-onset lupus can present in men over 50 and may have a different clinical pattern than classic early-onset disease.

• The presence of an active urinary sediment (proteinuria and hematuria) is a red flag for glomerulonephritis and warrants an aggressive workup, even if serum creatinine is initially normal.

• Anti-dsDNA antibodies are highly specific for SLE and their presence is strongly associated with the risk of developing lupus nephritis.

• Classic serologic markers of a lupus flare, such as hypocomplementemia, may be absent. The diagnosis should be pursued based on the complete clinical and serological picture.

• In a farmer presenting with systemic illness, it is vital to consider and exclude zoonotic infections (such as Brucellosis or Q fever) and endemic mycoses before committing to a dx of an autoimmune disease and initiating immunosuppression.

February 10, 2026 VMR with Ravi & Kirtan - worsening dizziness

Source

Case Summary

A 44 year-old man with T2DM presented with dizziness, tachycardia, and hypotension. His symptoms were initially attributed to volume depletion and improved with fluids. However, labs showed a severe, acute-on-chronic anemia (hemoglobin 6.9 was down from 10.9 one week prior) with clear evidence of hemolysis, including an elevated LDH, undetectable haptoglobin, and elevated retics. With a negative Coombs test and normal peripheral smear, the focus shifted to a non-immune cause, leading to the final diagnosis of sulfonylurea-induced acute hemolytic anemia in the setting of previously undiagnosed G6PD deficiency. The patient improved after stopping the offending medication and receiving a blood transfusion.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

G6PD deficiency is the most common human enzyme defect, an X-linked inherited disorder that makes RBCs susceptible to damage from oxidative stress. Most individuals are asymptomatic until exposed to an oxidative trigger. The classic presentation is acute hemolytic anemia, which can be precipitated by infections, certain foods (classically fava beans), and various medications, including antimalarials (primaquine), sulfonamides, and, as in this case, sulfonylureas.

Key diagnostic findings include:

• Labs: During a hemolytic crisis, labs show signs of intravascular hemolysis: anemia, elevated LDH, low or undetectable haptoglobin, elevated indirect bilirubin, and reticulocytosis as the bone marrow compensates.

• Peripheral Smear: May show bite cells (RBCs with portions removed by splenic macrophages) and Heinz bodies (denatured hemoglobin precipitates within RBCs, visible with a special stain), though these can be transient.

• Specific tests: The definitive diagnosis is a quantitative G6PD enzyme activity assay. A crucial diagnostic caveat is that this test can be falsely normal during or immediately after a hemolytic episode. This is because older, G6PD-deficient cells are preferentially destroyed, leaving a younger population of RBCs and reticulocytes with higher enzyme levels. If initial testing is normal but suspicion remains high, the test should be repeated 2-3 months after the acute episode has resolved.

Management primarily involves avoidance of known oxidative triggers. Acute hemolytic crises are managed supportively by removing the offending agent, ensuring adequate hydration to protect renal function, and providing blood transfusions for severe, symptomatic anemia.

Pearls

• A rapid, dramatic drop in hemoglobin should immediately raise suspicion for two primary processes: acute blood loss or acute hemolysis.

• The triad of high LDH, low haptoglobin, and reticulocytosis is highly specific for hemolysis, even in the absence of significant hyperbilirubinemia.

• A negative direct Coombs test is a critical branch point in the evaluation of hemolytic anemia, effectively shifting the differential away from autoimmune causes and toward non-immune etiologies like enzyme deficiencies, membrane defects, or microangiopathic processes.

• When investigating acute hemolysis, a review of the patient’s medication list, with special attention to recently initiated drugs, is key.

• G6PD enzyme levels can be falsely normal during an acute crisis due to the destruction of the most deficient cells; if clinical suspicion is high, the assay should be repeated 2-3 months later.

• A disproportionately low HbA1c relative to fasting or random glucose levels can be a subtle clue pointing to a state of high red blood cell turnover, such as ongoing hemolysis. Fructosamine can be used instead and is a measure of glycated protein (albumin), and is surrogate for blood sugar levels over the past 2-3 weeks.

February 23, 2026 VMR with Alec & Austin - right flank pain and lower back pain

Source

Case Summary

A 56 year-old man presented with a two months of right flank and back pain that progressed to bilateral lower extremity numbness and significant weakness (L>R), requiring a wheelchair. Exam was notable for 4/5 strength in the LEs, hyperreflexia in the right knee, pointing toward a myelopathy. Though an initial lumbar MRI was unrevealing, a later thoracic MRI identified an enhancing T10 vertebral body lesion with a large posterior epidural mass causing severe cord compression, along with multiple smaller vertebral lesions. Biopsy and subsequent surgical pathology confirmed the diagnosis of clear cell chondrosarcoma of the spine with an IDH1 mutation. The patient underwent urgent surgical decompression and stabilization, followed by radiation therapy.

Multifocal Clear Cell Chondrosarcoma of the Spine

Clear cell chondrosarcoma is a rare, low-grade malignant tumor of cartilage-producing cells that most commonly affects the long bones. Primary spinal involvement is uncommon, and multifocal disease is even rarer. It typically presents with chronic pain. When located in the spine, it can cause progressive radiculopathy or myelopathy due to nerve root or spinal cord compression, leading to symptoms like weakness, sensory deficits, and potential bowel or bladder dysfunction.

Key diagnostic findings include:

• Imaging: MRI with contrast is the modality of choice. It reveals bone destruction with an associated soft-tissue mass. Lesions typically show enhancement and can demonstrate epidural extension causing cord compression, which appears as edema (hyperintensity) within the cord itself on T2-weighted sequences.

• Pathology: Definitive diagnosis requires biopsy. Histology reveals characteristic sheets of tumor cells with clear cytoplasm due to abundant glycogen. Immunohistochemistry is typically positive for S100 and Vimentin.

• Genetics: IDH1 and IDH2 mutations are frequently found in chondrosarcomas and serve as important diagnostic and prognostic markers.

Management for spinal chondrosarcoma with cord compression is a neurosurgical emergency. Treatment involves prompt administration of high-dose steroids, followed by surgical decompression and wide en bloc resection (taking out the entire tumor in one piece) when possible. Radiation therapy is often used adjuvantly. Chemotherapy is generally ineffective.

Pearls

• The combination of progressive bilateral lower extremity weakness and upper motor neuron signs (hyperreflexia, even if subtle or asymmetric) strongly suggests a spinal cord lesion (myelopathy) rather than a simple radiculopathy.

• When a myelopathy is suspected but an MRI of the clinically implicated spinal segment (lumbar spine) is negative, it is crucial to image the entire spinal cord to avoid missing a more proximal lesion.

• “Red flag” symptoms for back pain demanding urgent evaluation include progressive motor or sensory deficits, new-onset weakness causing functional decline, and new sphincter-related symptoms (groin numbness during urination).

• In a middle-aged adult with multiple vertebral lesions, the ddx is led by metastatic carcinoma and multiple myeloma, but primary bone tumors and infections (like Pott’s disease) must also be considered.

• The presence of an enhancing epidural mass causing cord compression on MRI is a neurosurgical emergency requiring immediate high-dose steroids and surgical consultation to prevent permanent neurologic injury.

• For bone tumors, immunohistochemical stains are key. S100 positivity in a cartilaginous tumor is highly suggestive of chondrosarcoma.

• Identifying an IDH1 mutation can confirm a diagnosis of chondrosarcoma and guide therapy, as it often predicts poor response to conventional chemotherapy.

February 25, 2026 VMR with Sharmin & Reza - acute substernal chest pain

Source

Case Summary

A 61 year-old female with HTN presented with two hours of severe, crushing substernal chest pain. Her EKG showed ST elevations in the inferolateral leads, and her initial hs-troponin was 14,000, leading to STEMI activation. Cath revealed no significant atherosclerotic disease but instead identified a spontaneous coronary artery dissection (SCAD) of the proximal LAD with an ejection fraction of 30-35%. Later CTA of the head, neck, abdomen, and pelvis revealed multifocal luminal irregularities of the internal carotid and renal arteries, confirming the underlying diagnosis of Fibromuscular Dysplasia (FMD).

Spontaneous Coronary Artery Dissection (SCAD) & Fibromuscular Dysplasia (FMD)

SCAD results from the separation of coronary artery wall layers by an intramural hematoma, which compresses the true lumen and restricts blood flow. SCAD mostly affects women and often presents as a typical STEMI or NSTEMI, making the initial presentation indistinguishable from a plaque-rupture MI.

Key diagnostic findings include:

• Labs & EKG: Show evidence of myocardial ischemia/infarction (elevated troponins, ST-segment changes).

• Coronary Angiography: This is the definitive diagnostic test. It demonstrates a dissection flap, intramural hematoma, or long, smooth stenosis in the absence of atherosclerotic plaque.

• Systemic Imaging: Once SCAD is diagnosed, it is critical to investigate for an underlying arterial disease. FMD is a non-inflammatory vascular disease causing abnormal cell growth in artery walls and is the most common association. CTA or MRA from the brain to the pelvis is recommended to screen for FMD in other locations, such as the renal and carotid arteries.

Management of SCAD is nuanced. A conservative medical approach is often favored over PCI, as further instrumentation can propagate the dissection. Treatment typically involves beta-blockers, antiplatelet therapy, and BP control. GDMT is initiated for any LV dysfunction.

Pearls

• A STEMI presentation warrants emergent cardiac catheterization, even in patients who lack a classic atherosclerotic risk profile.

• SCAD is a critical diagnosis to consider in any patient presenting with an MI, particularly women and those without significant traditional risk factors.

• A diagnosis of SCAD is not a terminal endpoint; it should immediately prompt the clinical question “Why?” and trigger a workup for underlying systemic arteriopathies like FMD.

• While the EKG pointed to an inferolateral infarct, the culprit lesion was in the LAD, highlighting that EKG localization can be imperfect due to anatomical variations like a “wraparound” LAD.

While not every case can make the cut each month and be considered one of my favorites, many still have interesting clinical pearls and lessons worth sharing.

Here’s a collection of some of my favorite additional pearls from the month of January 2026.

Meningococcemia

Although disseminated meningococcal disease is classically associated with a petechial or purpuric rash, some serotypes, particularly serogroup W, can present atypically with prominent gastrointestinal symptoms, such as severe abdominal pain or diarrhea, which can potentially delay the diagnosis.

Hallmarks of the disease include leukocytosis with prominent left shift, severe thrombocytopenia, and evidence of DIC. Anatomic or functional asplenia, complement deficiencies, and travel to endemic areas increase the risk for invasive disease with encapsulated bacteria like N. meningitidis.

Source: NEJM - Case 1-2026 A 50-Year-Old Woman With Fever And Abdominal Pain

Invasive hypervirulent Klebsiella pneumoniae (hvKP)

hvKP is a distinct clinical entity caused by specific hypermucoviscous strains of Klebsiella. Unlike classic Klebsiella infections, which are often nosocomial and affect immunocompromised hosts, hvKP can affect healthy community-dwelling individuals.

The typical presentation begins with a pyogenic liver abscess, which serves as the primary focus for hematogenous dissemination.

The hallmark of the syndrome is metastatic infections to distant sites. Examples of devastating complications can include endogenous endophthalmitis, which can cause rapid and permanent vision loss, meningitis, brain abscesses and septic pulmonary emboli which present as multiple cavitary lung nodules.

The triad of pyogenic liver abscess, endogenous endophthalmitis, and metastatic septic emboli is pathognomonic for invasive hypervirulent Klebsiella pneumoniae syndrome.

The "string test," where a bacterial colony forms a viscous string >5 mm when lifted with a loop, is a classic bedside indicator of the hypermucoviscous phenotype.

Source: NEJM - Case 2-2026 A 63-Year-Old Man With Pulmonary Nodules, Liver Mass, And Vision Loss

CVID and the Gamma Gap

A low gamma gap (total protein minus albumin, often defined as < 1.2) is clinically useful as a prompt to check serum immunoglobulin levels (IgG, IgA, IgM) and consider an immunodeficiency workup to assess for CVID, especially if the patient has a history of recurrent infections.

The diagnosis of CVID requires evidence of impaired antibody function, demonstrated by a poor or absent antibody response to vaccination, commonly tested with pneumococcal or tetanus vaccines.

While many patients present with recurrent signs of pulmonary infections with encapsulated bacteria, a significant proportion developed non-infectious complications, including autoimmunity such as immune thrombocytopenia or autoimmune hemolytic anemia, benign lymphoproliferation, malignancies such as lymphoma, and granulomatous disease that can mimic sarcoidosis.

Management of CVID includes lifelong immunoglobulin replacement therapy to reduce infection frequency and severity. For those with inflammatory or autoimmune complications, immunosuppressive therapies such as corticosteroids or rituximab are often necessary.

Source: NEJM - Closing The Gap

Acute Polyarticular Calcium Pyrophosphate Deposition (CPPD) Disease (Pseudogout)

CPPD is a crystal-induced inflammatory arthritis. While it often presents as an acute monoarthritis of the knee, it can manifest in several ways, including a chronic symmetric polyarthritis (mimicking rheumatoid arthritis) or progressive degenerative arthropathy (mimicking osteoarthritis).

An acute polyarticular form can present dramatically with migratory pain, high-grade fevers, and marked systemic inflammation, which closely mimics sepsis or new-onset rheumatologic emergency.

The gold standard of diagnosis is a synovial fluid analysis, which reveals inflammatory fluid with a variable white blood cell count and the pathognomonic finding of intracellular weakly positive birefringent rhomboid-shaped crystals under polarized light microscopy.

X-ray may show chondrocalcinosis, which is linear calcifications of hyaline or fibrocartilage, most classically seen in the menisci of the knee. Its absence does not rule out CPPD, and ultrasound is more sensitive.

Given it’s primarily a disease of aging, in patients presenting under age 60, it’s important to screen for secondary metabolic causes such as hyperparathyroidism, hemochromatosis, hypomagnesemia, and hypophosphatemia.

In any patient with an acute hot swollen joint, septic arthritis must be ruled out via arthrocentesis, even if crystals are seen, given the two conditions can co-exist.

Source: CPS - Episode 436 The Clinical Unknown Series New Year New Episode

Alcoholic Ketoacidosis and NAGMA

Ketoacidosis (from alcohol, diabetes, or starvation) can present as a normal anion gap metabolic acidosis (NAGMA) if renal function is preserved.

When renal function is preserved, the kidneys can efficiently excrete the negatively charged keto-anions. To maintain electroneutrality, the renal tubules reabsorb chloride in exchange for the excreted ketones.

This anion exchange effectively "closes" the anion gap by replacing the unmeasured keto-anions with the measured chloride anion, resulting in a hyperchloremic, normal anion gap metabolic acidosis.

Thus, a calculated anion gap should not be used to rule out ketoacidosis; if clinical suspicion is high based on the history, a direct serum beta-hydroxybutyrate level is the definitive test.

Source: CPS - Episode 437 RLR An Abnormal Normal Gap Acidosis

IDA in Limited Cutaneous Systemic Sclerosis

Gastric Antral Vascular Ectasia (GAVE), or “watermelon stomach”, is a significant cause of occult GI bleeding and IDA in patients with autoimmune diseases, particularly systemic sclerosis.

GAVE consists of rows of ectatic blood vessels in the gastric antrum that are prone to chronic bleeding.

The presentation of the disease can be subtle, with visceral involvement (GAVE, esophageal dysmotility) appearing years before or in the absence of prominent skin changes like sclerodactyly.

The acronym CREST describes its classic features: Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasias.

Source: CPS - Episode 439 Spaced Learning Series SOB

Idiopathic Pericarditis and Tamponade

When an extensive evaluation fails to identify a specific cause of pericarditis, it is termed idiopathic, with a viral etiology often presumed. These cases generally respond well to drainage of pericardial fluid if needed, and anti-inflammatory therapy.

The classic teaching in pericarditis is that the pain is relieved by sitting up and leaning forward. This is because the heart moves forward with gravity and takes pressure off of the inflamed posterior pericardium.

The classic finding of pericarditis on EKG is diffuse concave ST elevation with PR depression. However, a large pericardial effusion can cause low-voltage QRS complexes and electrical alternans due to the insulating effect of the fluid.

Cardiac tamponade first impairs diastolic filling of the right ventricle. This leads to the following cascade: reduced preload → reduced stroke volume by Starling's law → reduced cardiac output and shock.

Flat neck veins do not rule out cardiac tamponade, especially in a patient who may also be hypovolemic

Source: CPS - January 1, 2026 - VMR with Rabih & Manaswini - Chest Pain & Dyspnea

Hyponatremia and AMS

Severe metabolic derangements, particularly hyponatremia, can present with focal neurological deficits like vertigo, ataxia, and dysarthria, mimicking an acute stroke.

In a patient with a prior stroke, a systemic stressor like hyponatremia can cause recrudescence, where old deficits transiently reappear without new structural damage.

Oxcarbazepine and carbamazepine are classic culprits of SIADH.

Always rule out hypothyroidism and adrenal insufficiency as part of the workup for euvolemic hyponatremia.

Source: CPS - January 5, 2026 Neurology VMR with Dr. Helen Shi - dizziness

Lymphoma and Richter’s Transformation

Richter's transformation (or Richter's syndrome) is the histopathological transformation of an indolent B-cell lymphoma, most commonly chronic lymphocytic leukemia (CLL) or follicular lymphoma, into a high-grade, aggressive lymphoma, typically diffuse large B-cell lymphoma (DLBCL). This event marks a dramatic shift in the disease's clinical behavior.

A clinical presentation of rapid progression (B symptoms, rapidly growing masses, high LDH) that is discordant with a known diagnosis of an indolent lymphoma should raise immediate suspicion for Richter's transformation.

Excisional biopsy is the gold standard for lymphoma diagnosis because it preserves lymph node “architecture.” Fine-needle aspiration (FNA) can be insufficient or misleading, as it may miss the transformed component of the disease.

Management involves treating the new, aggressive lymphoma with intensive chemoimmunotherapy regimens, such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for DLBCL. The prognosis after Richter's transformation is generally poor.

Remember that a parotid gland mass is not always a primary salivary tumor by default; the gland contains significant lymphoid tissue and can be a site of primary or metastatic lymphoma.

Asking about symptoms when lying down (orthopnea) is a more sensitive method for detecting subtle airway obstruction than asking about dyspnea at rest.

Source: CPS - January 6, 2026 Academy Session with Rabih - Rapid Neck Mass

Acute Necrotizing Eosinophilic Myocarditis (ANEM)

ANEM is a rare and often fatal form of fulminant myocarditis characterized by intense eosinophilic infiltration and widespread myocyte necrosis.

It is most commonly a manifestation of a severe hypersensitivity reaction, such as DRESS syndrome, but can also be idiopathic or associated with other eosinophilic disorders.

Relapse or recurrence of DRESS syndrome can occur weeks after initial presentation, especially with inadequate or prematurely discontinued immunosuppression.

ANEM is a diagnosis of exclusion for cardiogenic shock; it presents as acute heart failure with severe biventricular dysfunction and normal coronary arteries.

The constellation of fever, rash, eosinophilia, and new-onset heart failure should prompt immediate consideration for eosinophilic myocarditis.

Source: CPS - January 7, 2026 VMR with Steph & Zaven - Left-sided chest pain

A New Diagnosis of Cirrhosis

The combination of edema and thrombocytopenia is a powerful clue for chronic liver disease with portal hypertension and splenomegaly.

Marked hypoalbuminemia in the absence of significant proteinuria strongly points toward impaired hepatic synthesis or, less commonly, a protein-losing enteropathy.

While advanced cirrhosis typically causes hypotension, patients with pre-existing hypertension may present with a "normal" or even elevated blood pressure.

Amiodarone can cause a spectrum of liver injury, including steatohepatitis and even non-cirrhotic portal hypertension, and should always be considered a potential culprit in patients with liver dysfunction.

Source: CPS - January 8, 2026 VMR with Rabih & Masah - abdominal pain & B/L LE edema

Renal Medullary Carcinoma (RMC) and Hematuria

RMC is a rare, highly aggressive non-clear cell kidney cancer that almost exclusively affects young individuals with sickle cell trait, and less commonly, sickle cell disease.

It arises from the renal medulla, an environment that is naturally hypoxic, hypertonic, and acidic. These conditions promote sickling of red blood cells even in heterozygotes, leading to chronic microinfarction, inflammation, and ultimately, malignant transformation.

The typical presentation is in adolescents and young adults, often with gross hematuria, flank or abdominal pain, and constitutional symptoms like weight loss.

Due to its aggressive nature, a majority of patients present with metastatic disease at diagnosis, most commonly to the lymph nodes, lungs, and bone.

The absence of significant proteinuria in the setting of hematuria is a key finding that lowers the likelihood of a primary glomerulonephritis and points towards bleeding from a mass, the collecting system, or urothelium.

Source: CPS - January 9, 2026 VMR with Rabih & Zakariyya G - cough and hematuria

HSV Hepatitis

The differential for massive transaminitis (AST/ALT >5,000 U/L) is narrow: 1) ischemic hepatitis, 2) toxin/drug-induced liver injury (especially acetaminophen), 3) acute viral hepatitis (including HSV).

HSV hepatitis should be strongly suspected in cases of massive transaminitis with minimal bilirubin elevation ("anicteric hepatitis") and a paradoxically normal INR early in the course.

Serum HSV PCR is the diagnostic test of choice for disseminated disease; serology (IgG, IgM) is often negative or unhelpful in the acute setting and should not be used to rule out infection.

In a patient with severe acute liver injury and neurologic symptoms like seizures or altered mental status, consider disseminated HSV with both hepatitis and encephalitis.

While seizures cause rhabdomyolysis and elevate AST, an AST in the tens of thousands with a more modest CK points to a primary, severe hepatic injury as the dominant process.

Source: CPS - January 14, 2026 GI/Hep. VMR w/ Dr. Elliot Tapper - elevated liver enzymes & tonic-clonic seizures

Non-Bacterial Thrombotic Endocarditis (NBTE)

In a patient with valvular vegetations, persistently negative blood cultures and a lack of response to broad-spectrum antibiotics should prompt consideration of non-infectious mimics, chiefly NBTE.

NBTE is a classic manifestation of both Antiphospholipid Syndrome (APS) and Systemic Lupus Erythematosus (SLE), where it is called Libman-Sacks endocarditis.

Profoundly elevated inflammatory markers (ESR/CRP) do not exclude an autoimmune cause; they can also be a prominent feature of active APS or SLE, mimicking infection.

While rare, NBTE can occur on prosthetic valves, presenting as a subacute inflammatory syndrome that is clinically indistinguishable from culture-negative infective endocarditis.

CPS - January 14, 2026 VMR with Sharmin & Maryana - fever and progressive fatigue

Cardiac Amyloidosis

The classic finding of cardiac amyloidosis on EKG is low-voltage QRS complexes (especially in limb leads) in striking contrast to myocardial thickening on imaging, a phenomenon known as "electrical-mechanical dissociation."

The hallmark on Cardiac MRI is biventricular myocardial thickening with a "sparkling" or "speckled" appearance. Diastolic dysfunction is severe and occurs early, while LVEF may be preserved until late stages.

Amyloidosis has a strong predilection for the atria, leading to massive bi-atrial enlargement, atrial fibrillation, and even "atrial standstill.”

Severe hypoalbuminemia in the context of amyloidosis can be multifactorial, arising from nephrotic syndrome (renal amyloid), protein-losing enteropathy (GI amyloid), or congestive hepatopathy/enteropathy from severe right-sided heart failure.

Source: CPS - January 15, 2026 VMR with Rabih & Kirtan - progressive breathlessness

Anti-MDA5 Positive Inflammatory Myositis

Anti-MDA5 (anti-melanoma differentiation-associated gene 5) positive inflammatory myositis is a rare and often severe subtype of dermatomyositis, an autoimmune condition causing inflammation of the skin and muscles.

This specific subtype is notorious for causing rapidly progressive and often fatal ILD.

While patients may present with classic dermatomyositis skin findings (Gottron's papules over knuckles, heliotrope rash on eyelids, shawl/V-sign rashes), the muscle involvement can be clinically mild or even absent; a classic pitfall is that CK levels are often normal or only mildly elevated.

Inflammatory markers are often dissociated, with a very high ESR and a disproportionately low or normal CRP; this feature is more common in non-infectious systemic inflammatory diseases.

Source: CPS - January 16, 2025 VMR with Rabih & Lera - Fever, SOB, and SBP of 70-80

Amphetamine-Associated Pulmonary Hypertension (PAH)

Amphetamines and other stimulants are well-established risk factors for the development of PAH.

Amphetamine-associated pulmonary hypertension is a form of Group 1 PAH, characterized by vasoconstriction and proliferative remodeling of the small pulmonary arteries. This leads to increased pulmonary vascular resistance (PVR), progressive RV failure, and eventually death.

The clinical presentation is often insidious, with nonspecific symptoms like exertional dyspnea, fatigue, chest pain, and syncope, which reflect the RV's inability to increase output with demand.

Otherwise young and “healthy” patients with chronic, severe cardiopulmonary disease can remain remarkably well-compensated, presenting with stable vital signs despite being in a state of cardiogenic shock. Sometimes sinus tachycardia is the only clue.

CPS - Source: January 17, 2026 IMG Initiative VMR with Cleveland Clinic IM Residency Program - rectal bleeding

Anti-LGI5 Encephalitis

Anti-LGI5 (Leucine-rich glioma-inactivated 5) encephalitis is a rare autoimmune disorder caused by antibodies targeting the LGI5 neuronal surface protein.

It is a critical "great mimic" of neurodegenerative diseases, often presenting with a unique and complex combination of central and peripheral nervous system symptoms that can evolve over months.

The combination of REM sleep behavior disorder (dream enactment), parkinsonism, and signs of motor neuron disease (fasciculations) is highly suggestive.

The condition is a key autoimmune mimic of neurodegenerative disorders like Lewy Body Dementia, Multiple System Atrophy (MSA), and ALS; its treatable nature makes early suspicion critical.

CPS - January 19, 2026 Neurology VMR with Dr. Helen Shi - 9 months history of dream enactment

Anti-NMDA Receptor Encephalitis

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common form of autoimmune encephalitis, caused by antibodies targeting the GluN1 subunit of the NMDA receptor in the brain.

It is frequently a paraneoplastic syndrome, classically associated with ovarian teratomas in young women, but can occur in all ages and sexes, be associated with other malignancies, or be non-paraneoplastic.

Prominent psychiatric symptoms such as agitation, psychosis, paranoia, and significant behavioral changes often lead to initial misdiagnosis.

The combination of acute psychiatric symptoms, seizures, and autonomic dysfunction preceded by a viral-like prodrome should raise strong suspicion for autoimmune encephalitis.

A lymphocytic pleocytosis in the CSF with a negative infectious workup is a classic red flag for autoimmune or paraneoplastic encephalitis.

Source: CPS - January 20, 2026 VMR with Ravi & Kuchal - AMS

Signs of Chronic HIV

The triad of unintentional weight loss, night sweats, and lymphopenia should always prompt consideration and testing for HIV.

Common non-specific laboratory abnormalities in chronic infection include lymphopenia (a key clue), anemia of chronic disease, thrombocytopenia, polyclonal hypergammaglobulinemia (reflecting B-cell dysregulation), and elevated inflammatory markers like ferritin and CRP.

Mild eosinophilia can also be a feature in 10-30% of untreated patients.

Imaging is often non-specific, but may reveal diffuse lymphadenopathy or splenomegaly.

Source: CPS- January 21, 2026 VMR with Sharmin & Manaswini - weight loss, night sweats, fatigue

Ethylene Glycol Intoxication

Ingestion leads to a severe, life-threatening metabolic acidosis and acute kidney injury.

The parent compound is metabolized by alcohol dehydrogenase to toxic metabolites, primarily glycolic acid and oxalic acid.

Glycolic acid causes the severe anion gap acidosis.

Oxalic acid chelates calcium and precipitates as calcium oxalate crystals, which deposit in the renal tubules, causing acute tubular necrosis and renal failure.

The crystals can be monohydrate (needle or cigar-shaped) or dihydrate (envelope-shaped).

Management involves inhibiting metabolism via and alcohol dehydrogenase inhibitor like fomepizole to prevent the formation of toxic metabolites. Dialysis is effective at removing the parent alcohol and its metabolites.

Source: CPS - January 26, 2026 VMR with Alec & Austin - found collapsed

Signs of GPA

The combination of an acute kidney injury with a nephritic sediment and any upper respiratory symptoms (sinusitis, otitis, nasal deformity) should immediately raise suspicion for GPA.

A saddle nose deformity, even if subtle and of recent onset, is a highly specific physical exam finding for GPA or other destructive processes like relapsing polychondritis.

A long-standing history of a vague autoimmune condition, such as "seronegative polyarthritis," may represent the initial, undiagnosed phase of a systemic vasculitis like GPA.

In the workup of rapidly progressive glomerulonephritis, normal complement levels are a critical finding that significantly narrows the differential diagnosis towards ANCA-associated vasculitis or anti-GBM disease.

Source: CPS - January 28, 2026 VMR with Dr. André Mansoor & Dr. Peter Sullivan - lower extremity swelling

Lab Findings in Rhabdomyolysis

The hallmark is a markedly elevated serum CK, typically defined as >5x the upper limit of normal and often reaching levels in the thousands to hundreds of thousands.

A urinalysis dipstick will be positive for "blood" due to the presence of myoglobin, but microscopic analysis reveals few or no red blood cells.

Transaminases are often elevated, with a characteristic AST to ALT ratio much greater than 2:1, as AST is abundant in muscle tissue.

An elevated Troponin T in the setting of rhabdomyolysis can be a false positive due to assay cross-reactivity with skeletal muscle breakdown; Troponin I is more specific for cardiac injury.

Source: CPS - January 29, 2026 VMR with Rabih & Vini - myalgias x 1 week

This post highlights in-depth breakdowns of my favorite clinical cases from January 2026.

There will be a separate post highlighting all of my other favorite rapid-fire pearls from the “honorable mention” cases that didn’t make the cut.

Case 3-2026 A 58-Year-Old Woman With Diplopia And Fever (NEJM)

Source

Case Summary

A 58-year-old woman presented with fever, diplopia, and an erythematous rash one week after receiving steroids for persistent leg pain following lumbar surgery. Examination was notable for a right-sided abducens nerve (CN 6) palsy (can’t have right eye look to the right). She was also noted to have erythematous macules on her legs and buttocks. Labs were notable for elevated ESR and CRP. An MRI of the head revealed enhancement along multiple right-sided cranial nerves, including cranial nerves 3, 5, 6, and 7. Serologic testing was positive for IgM and IgG antibodies to Borrelia burgdorferi, and PCR testing was also positive for Babesia microti. The patient was diagnosed with Lyme neuroborreliosis with Babesiosis co-infection and was treated with IV ceftriaxone followed by oral doxycycline.

Lyme Neuroborreliosis

Lyme neuroborreliosis is a neurological manifestation of disseminated infection with the spirochete Borrelia burgdorferi which is transmitted by Ixodes ticks. It typically appears weeks to months after the initial tick bite. Classic presentation involves a triad of lymphocytic meningitis, cranial neuropathy (commonly unilateral or bilateral facial nerve palsy), and painful radicular neuritis (which causes shooting pains in a nerve root distribution). Multiple cranial nerves can be affected simultaneously.

The cornerstone of diagnosis is via serology using a two-tier testing algorithm, which includes an EIA followed by a Western blot or two different EIAs. An LP often reveals a lymphocytic pleocytosis with mildly elevated protein and normal glucose. MRI of the brain and spine with contrast can show enhancement of the affected cranial nerves, nerve roots, or meninges, though these findings are not specific to Lyme disease.

Management requires antibiotics with CNS penetration. Standard includes a 14-21 day course of IV ceftriaxone or oral doxycycline. While prognosis is generally favorable, recovery from neurologic deficits can be slow.

Pearls

• Always consider tick-borne co-infections such as babesiosis and anaplasmosis, as they can cause more severe illness and require different antimicrobial therapy.

• Glucocorticoid might impair host immune response, which potentially leads to more severe and disseminated presentations of Lyme and its co-infections.

• A history of a tick bite or erythema migrans rash is not required for diagnosis of Lyme neuroborreliosis, as these are absent in many patients who present with late-stage manifestations (or the patient just won’t remember this happening)

• Intrathecal antibody production in the CSF is the gold standard for confirming CNS infection, but it can take six to eight weeks to become positive after symptom onset. Thus, a negative result doesn’t rule out with the disease.

• Encephalopathy is a real but often subtle manifestation. Patients may present with cognitive slowing, memory complaints, and mood changes that can be mistaken for depression or early dementia.

January 2, 2026 VMR with Rabih & Austin - sudden vision loss 3 days ago (CPS)

Source

Case Summary

A 57 year old male farmer with poorly controlled T2DM and HTN presented with what his family described as a 3-day history of “sudden onset blindness,” which was more accurately a sudden inability to perform his work. His visual acuity was largely preserved, but examination revealed a higher-order visual processing deficit. The exam was notable for optic ataxia (inability to reach for objects under visual guidance), oculomotor apraxia (inability to voluntarily direct his gaze), and simultanagnosia (inability to perceive a visual scene as a whole). An MRI of the revealed an acute infarct in the right parieto-occipital junction and a chronic infarct in the contralateral region, secondary to severe bilateral carotid artery stenosis.

Bálint’s Syndrome

Bálint’s syndrome is a rare neurological disorder of higher-order visual processing caused by damage to the bilateral parieto-occipital lobes. This region constitutes the dorsal visual stream, which is responsible for spatial awareness and visually guided action (the “where” pathway).

The syndrome is defined by a classic clinical triad:

1. Simultanagnosia: The inability to perceive more than one object or the entirety of a visual scene at a time. A patient might identify a single tree but not the forest it is in. This is the most disabling component of the syndrome.

2. Oculomotor Apraxia: The inability to intentionally move the eyes to a target in the peripheral visual field. Patients cannot shift their gaze on command and often compensate by turning their entire head to see something new.

3. Optic Ataxia: A severe deficit in “reaching.” Despite being able to see an object and having intact motor strength, the patient cannot accurately direct their hand to grasp it.

The most common cause is bilateral watershed strokes in the border zones between the middle and posterior cerebral arteries, often due to hypoperfusion (severe carotid stenosis, cardiac arrest) or embolic events.

Pearls

• A complaint of “vision loss” with normal visual acuity should prompt consideration of a higher-order cortical visual processing disorder.

• The triad of simultanagnosia, oculomotor apraxia, and optic ataxia is pathognomonic for Bálint’s syndrome and localizes the lesion to the bilateral parieto-occipital lobes.

• The initial history can be nebulous; observing the patient’s functional deficits, such as trying to reach for an object, is crucial for diagnosis.

• Optic ataxia can be distinguished from cerebellar ataxia: a patient with optic ataxia may be able to touch their own nose (proprioception-guided) but cannot reach accurately for an object in their visual field.

• Bálint’s syndrome is a classic example of a dorsal stream (”where” pathway) deficit, sparing the ventral stream (”what” pathway) and thus preserving object identification.

January 13, 2026 VMR with Ravi & Kirtan - difficulty walking for 1 week (CPS)

Source

Case Summary

An 18 year-old male presented with one week of rapidly progressive, ascending bilateral lower limb weakness, which was preceded by a flu-like illness. Examination was notable for flaccid paralysis with areflexia in the lower limbs, while sensation and upper limb function were preserved. Findings included “albuminocytologic dissociation” on CSF analysis (protein 149 mg/dL, 10 WBCs) and nerve conduction studies showing a mixed demyelinating and axonal polyradiculoneuropathy. An initial diagnosis of Guillain-Barre Syndrome (GBS) was made, but he failed to improve with a course of IVIG. This prompted further investigation, which revealed positive antibodies to Neurofascin-140/186, establishing a diagnosis of an autoimmune nodopathy. Treatment with Rituximab resulted in rapid clinical improvement.

Autoimmune Nodopathy (Anti-Neurofascin Associated)

Autoimmune nodopathies and paranodopathies are a rare subgroup of severe, immune-mediated peripheral neuropathies that can mimic GBS or Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). They are caused by autoantibodies targeting proteins crucial for nerve impulse conduction at the nodes of Ranvier and surrounding paranodal regions, such as Neurofascin, Contactin-1, and CASPR1. The clinical presentation is often a rapidly progressive, severe, and predominantly motor weakness. Key features that may suggest a nodopathy over classic GBS/CIDP include early and severe axonal damage on nerve conduction studies, the presence of ataxia or tremor, and a poor or absent response to standard first-line therapies like IVIG or steroids.

Key diagnostic findings include:

• CSF: Typically shows marked albuminocytologic dissociation (high protein, normal or near-normal cell count), similar to GBS.

• Nerve Conduction Studies: Often reveal features of demyelination such as conduction block and prolonged latencies, but frequently with concurrent and severe signs of axonal damage early in the disease course.

• Serology: Definitive diagnosis relies on identifying specific serum autoantibodies against nodal or paranodal proteins (anti-NF155, anti-NF140/186, anti-Contactin-1).

The pathophysiology often involves IgG4 subclass antibodies, which do not effectively fix complement. This explains their resistance to IVIG and corticosteroids. The treatment of choice is B-cell depleting therapy with Rituximab, which can lead to dramatic clinical recovery.

Pearls:

• The failure of a patient with presumed GBS to respond to IVIG is a critical red flag that should prompt consideration of GBS mimics, particularly autoimmune nodopathies.

• Symmetrical, rapidly progressive bilateral weakness is highly unlikely to be caused by degenerative disc disease, even if an MRI shows incidental disc bulges.

• The classic CSF finding of albuminocytologic dissociation is highly suggestive of an inflammatory polyneuropathy but is not specific to GBS and is also a feature of autoimmune nodopathies.

• The specific autoantibody target in immune-mediated neuropathies dictates treatment; non-complement-fixing IgG4-mediated diseases like many nodopathies require B-cell targeted therapy (Rituximab) rather than IVIG or steroids.

• A post-infectious prodrome is a common trigger for various autoimmune neuropathies and should always heighten suspicion for this category of diseases in a patient with acute weakness.

January 22, 2026 VMR with Rabih & Eyron - chest pain 8/10 and dyspnea (CPS)

Source

Case Summary

An 18 year-old female athlete with a history of a relapsing skin lesion presented with exertional chest pain and fevers. Labs were notable for elevated inflammatory markers (ESR, CRP). She was found to have aortic regurgitation on echocardiogram. Advanced imaging (CTA/MRA) revealed stenosis of the left main coronary artery and diffuse inflammatory wall thickening of the aorta and its branches. The diagnosis of Takayasu’s Arteritis was made, with the skin lesion identified as pyoderma gangrenosum. She was treated with high-dose steroids and tocilizumab, leading to resolution of her skin lesion and stabilization of her vascular disease.

Takayasu’s Arteritis

Takayasu’s Arteritis is a rare, large-vessel granulomatous vasculitis of unknown etiology that primarily affects the aorta and its major branches. It primarily affects women under the age of 50. The clinical presentation is biphasic: an early systemic phase with constitutional symptoms (fever, malaise, weight loss) is followed by a late vascular phase characterized by symptoms of vessel stenosis or occlusion (limb claudication, blood pressure discrepancies, angina, stroke) or aneurysm formation (aortic regurgitation, dissection). Associated skin manifestations like pyoderma gangrenosum or erythema nodosum can occur.

Management involves high-dose corticosteroids to induce remission, followed by a slow taper and the addition of steroid-sparing agents like methotrexate or biologic therapies like tocilizumab or anti-TNF agents. Antiplatelet therapy is often used to prevent thrombotic events, and revascularization may be required for critical stenoses.

Pearls

• The combination of fever and chest pain in a young patient should prompt consideration of rare but serious inflammatory conditions of the mediastinum, pericardium, and aorta (aortitis).

• The finding of new aortic regurgitation in a patient with systemic inflammation is a major red flag for pathology of the aortic root, either from endocarditis or aortitis causing annular dilation.

• Diagnosis of TA is primarily radiologic. CT and MR angiography are essential to visualize vessel wall inflammation and identify the extent of vascular involvement.

• TA can present without the classic findings of asymmetric blood pressures or absent peripheral pulses, especially if the subclavian arteries are spared early in the disease course.

January 27, 2026 Neuro VMR - acute psychiatric disturbance and tremors

Source

Case Summary

A 20 year-old male with no known medical history presented with a two-week history of acute psychiatric changes, including confusion and odd behavior, accompanied by a new, unilateral tremor of his right arm and leg. Exam showed hepatomegaly and a high-amplitude, mixed rest/postural/action tremor. Initial labs revealed thrombocytopenia and mildly elevated transaminases, while an MRI of the brain showed T2 hyperintensities in the basal ganglia. The combination of neurologic and hepatic signs prompted a targeted workup revealing pathognomonic Kayser-Fleischer rings on slit-lamp exam and markedly elevated 24-hour urine copper, confirming the diagnosis of Wilson’s Disease. He was started on chelation therapy with clinical improvement.

Wilson’s Disease

Wilson’s Disease is an autosomal recessive genetic disorder caused by mutations in the ATP7B gene. This leads to impaired copper excretion into bile and reduced incorporation of copper into ceruloplasmin, resulting in toxic copper accumulation, primarily in the liver and brain. It typically presents in adolescence or early adulthood with either hepatic (ranging from chronic hepatitis to fulminant liver failure), neurologic, and/or psychiatric symptoms. Neurologic signs are diverse and can include tremor (classically a high-amplitude “wing-beating” tremor), parkinsonism, dystonia, and dysarthria. Psychiatric symptoms are common and can range from depression and personality changes to frank psychosis. Psychiatric symptoms often preceding motor symptoms.

Key diagnostic findings include:

• Labs: Low serum ceruloplasmin (in most cases), elevated free serum copper, and elevated 24-hour urinary copper excretion. Hepatic dysfunction with elevated transaminases and thrombocytopenia (often due to hypersplenism from portal hypertension) are common.

• Ophthalmology: The pathognomonic Kayser-Fleischer rings (copper deposits in Descemet’s membrane of the cornea) is best visualized on a slit-lamp exam.

• Imaging: Brain MRI may show T2 hyperintensities in the basal ganglia (especially the putamen), thalamus, and midbrain, sometimes creating the “face of the giant panda” sign.

• Pathology: Liver biopsy can confirm diagnosis by showing high hepatic copper content. Genetic testing for ATP7B mutations is also definitive.

Management involves lifelong therapy with copper chelating agents (D-penicillamine, trientine) and/or zinc salts, which block intestinal copper absorption. A paradoxical neurologic worsening can occur upon initiation of chelation therapy. Liver transplantation is an option for fulminant hepatic failure or refractory disease.

Pearls

• The triad of new-onset psychiatric symptoms, a movement disorder, and liver dysfunction in a young adult is highly suggestive of Wilson’s Disease.

• Psychiatric manifestations can be the initial and most prominent feature, often leading to a misdiagnosis of a primary psychiatric disorder. The presence of any subtle neurologic or systemic sign (like hepatomegaly) should prompt a broader workup.

• Wilson’s Disease can present with virtually any movement disorder (tremor, dystonia, parkinsonism, chorea), which can be asymmetric or unilateral, mimicking other conditions.

• A slit-lamp exam is crucial in suspected cases to look for Kayser-Fleischer rings, which are highly specific, though their absence does not rule out the diagnosis, especially in patients with purely hepatic presentations.

• Serum ceruloplasmin is low in most but not all patients with Wilson’s Disease (it is an acute phase reactant and can be falsely normal), making 24-hour urinary copper excretion a more reliable screening test.

• Oral contraceptives can falsely elevate ceruloplasmin levels due to estrogen's effect on hepatic protein synthesis, potentially masking a true deficiency.

• Brain MRI findings, such as T2 hyperintensity in the basal ganglia, are classic but not universally present; a normal MRI does not exclude the diagnosis.

  ---

  Thanks for reading Point of Care Medicine! Subscribe for free to receive new posts and support my work.

Listen along with The Point of Care Podcast

Let’s break down this question in a simple order - what it is, what it looks like on exam, what else causes it, and then why hepatic encephalopathy “owns” the association.

What is Asterixis?

Though asterixis is often referred to as a “flapping tremor”, it’s technically not a tremor. Instead, it’s a lapse in postural control and can be best thought of as negative myoclonus. It reflects an abnormal function in the brain structures responsible for maintaining alertness and posture. There are numerous parts of the brain that need to work in tandem to maintain a posture against gravity, therefore asterixis is considered to be a sign of a “global” cortical disruption.

What Does it Look Like on Exam?

Clinically, you see it when a patient holds their arms outstretched with their wrists extended and fingers straight. There is an occasional and irregular motion. You’ll note that one hand at a time experiences a sudden flexion of the wrist which then immediately snaps back to the previous extended position. This results in a bilateral, asynchronous, and non-rhythmic flapping motion.

What Else Causes It?

So even though it’s usually discussed in the setting of liver failure, asterixis is a general sign of toxic metabolic encephalopathy. Thus, it can be observed in several other medical conditions, including:

• Advanced renal failure due to uremia

• Hypercapnia, as seen in severe COPD, leading to carbon dioxide (CO2) narcosis

• Hypoglycemia

• Electrolyte derangements

  • Hyponatremia can lead to cerebral edema

  • Hypocalcemia Increases neuromuscular excitability

  • Severe hypercalcemia causes lethargy and cognitive slowing

  • Hypomagnesemia can promote tremor, myoclonus, and seizures.

  • Hypo- and hyperkalemia can impair muscle function and contribute to fatigue of sustained contraction.

• Sedatives (benzos), opioids, and anti-convulsant use

• Patients with lesions of the thalamus or basal ganglia (this will usually lead to a contralateral unilateral asterixis)

Why do we typically associate asterixis with hepatic encephalopathy?

First, asterixis is mostly associated with hepatic encephalopathy given it was canonized as the “liver flap” after early descriptions of patients with liver failure. Second, asterixis tends to show up in the sweet spot of hepatic encephalopathy severity, where patients are encephalopathic, yet awake enough to follow the command to hold posture. Patients with mild HE and severe HE will often not display asterixis.

Main Takeaway

So, while the “liver flap” association is real and historically entrenched, the bedside findings itself is a sign of global toxic-metabolic encephalopathy, and it’s most visible when the brain is impaired enough to drop posture, but not so impaired that the patients can’t participate in the exam.

Listen along on the Point of Care Podcast

A Clinical Diagnosis

The main thing to understand is that hepatic encephalopathy (HE) is a clinical diagnosis, not a lab diagnosis. A single venous or arterial ammonia level is neither sensitive nor specific for the diagnosis of HE because ammonia levels do not reliably correspond to a patient’s mental status.

Why Ammonia is Unreliable

Ammonia levels have significant overlap between patients with no encephalopathy and those with mild to moderate encephalopathy, so an ammonia level can be normal in a confused patient and elevated in someone who looks completely fine.

Ammonia levels can also fluctuate considerably throughout the course of a single day, which can make these individual snapshots challenging to interpret and trend.

There is also likely a lag effect, where the development of clinical encephalopathy is delayed by a number of hours relative to the actual blood ammonia level; this is likely due to the time required for ammonia to permeate the blood-brain barrier and actually cause the neurotoxic effect.

It’s also important to remember that ammonia is not the sole cause of hepatic encephalopathy. The condition is driven by a complex interplay of gut-derived toxins, systemic inflammation, renal physiology, and metabolic derangements. Thus, the ammonia level alone doesn’t fully capture the pathophysiology driving the altered mental status.

Why Send an Ammonia Level?

While not useful for treating hepatic encephalopathy and cirrhosis, it has a specific utility in acute liver failure. In that specific setting, an arterial ammonia level of over 200 correlates with a higher risk of cerebral edema and herniation. Thus, save ammonia testing for the one setting where it actually changes your thinking - acute liver failure. Otherwise, you might be led astray.

Listen along on the Point of Care Podcast.

What are the Common Triggers for HE?

Triggers are varied and can be as simple as constipation, dehydration, but can also be from more serious triggers that represent a decompensation of cirrhosis including infections or GI bleeds. Other common causes include overdiuresis, AKI, hypokalemia, alkalosis, and the use of sedatives or opioids.

Let’s work through the mechanism of why each of these may tip the patient into HE.

—

Constipation

Constipation worsens hepatic encephalopathy because it increases intestinal transit time, which increases the time of substrate exposure for gut bacteria to generate ammonia and other neurotoxins, and allows for increased absorption of ammonia across the colon.

—

Infections

Infections trigger HE not because it leads to the production of more ammonia, but because it lowers the brain’s tolerance to the same toxin load. Inflammation increases the blood-brain barrier permeability and microglial activation - together, these allow the same level of ammonia to produce a more significant cognitive impairment.

—

GI Bleed

GI bleeding is a classic precipitant because the gut treats bloods essentially like a high-protein meal. Hemoglobin is digested into amino acids and nitrogenous substrates which can lead to a rapid rise in ammonia and neurotoxins.

—

Dehydration/Diuresis

Overdiuresis or dehydration reduces effective arterial blood volume and renal hypoperfusion, which can decrease ammonia handling and urea excretion. More urea and nitrogen is then available to be converted to ammonia in the gut.

—

Hypokalemia

Hypokalemia leads to higher ammonia levels via stimulation of proximal tubules in the kidneys as part of acid-base adaptation; this activation leads to the generation of more ammonia.

—

Alkalosis

Metabolic alkalosis shifts the ammonia equilibrium towards non-ionized ammonia (NH3). This increases diffusion of ammonia across the gut wall and across the blood-brain barrier, which effectively increases brain exposure.

—

Main Takeaway

At the end of the day, all of these triggers are just different ways of tipping a fragile system past its compensatory limit, either by increasing toxin generation, reducing clearance and buffering, or making the brain more sensitive to the same toxin load. This is why hepatic encephalopathy can look like it comes out of nowhere. The precipitants might be mild, but the physiology isn’t.

#194: Severe Hypertriglyceridemia: 5 Pearls Segment (Core IM)

Listen to the podcast episode.

Source (Core IM)

The risk of acute pancreatitis surges when triglycerides exceed 500 mg per deciliter due to saturation of lipoprotein lipase.

• This enzyme is responsible for breaking down triglyceride-rich lipoproteins such as chylomicrons and VLDL in the bloodstream.

• When the triglyceride level reaches approximately 500 to 600, the clearance of chylomicrons is severely impaired. These large lipid particles can physically obstruct pancreatic capillaries, leading to ischemia, premature activation of pancreatic enzymes, and severe inflammatory response, which results in acute pancreatitis.

• In patients with high triglycerides, the standard LDL-C measurement may underestimate their total burden of atherogenic lipoproteins and thus their overall ASCVD risk.

• An elevated triglyceride over 150 mg per deciliter is an independent risk factor for ASCVD.

Hypertriglyceridemia has many potential secondary causes which should be addressed before initiating treatment.

• Common culprits include poorly controlled diabetes mellitus (insulin resistance impairs LPL function), hypothyroidism, nephrotic syndrome, obesity and excessive alcohol consumption.

• Glucocorticoids, high-dose thiazide diuretics, non-selective beta blockers, oral estrogens, and atypical anti-psychotics (such as olanzapine and quetiapine) are also notorious for raising triglycerides.

• Addressing these secondary factors can sometimes normalize triglyceride levels and avoid the need for dedicated lipid lowering therapy.

The initial inpatient management of severe hypertriglyceridemia centers on NPO status and intravenous fluids.

• Patients with severe hypertriglyceridemia (over 1,000 mg/dL) or associated acute pancreatitis should be made NPO to eliminate all oral intake of fats. This alone can reduce triglyceride levels by as much as 50% within the first 24 hours.

• Aggressive hydration is crucial to treat or prevent pancreatitis.

• An insulin infusion can be valuable (especially if hyperglycemia is present), given insulin enhances LPL activity and suppresses hormone-sensitive lipase and adipose tissue, which reduces the release of free fatty acids into circulation.

• Plasmapheresis is a rescue therapy, not a routine treatment; while it can rapidly lower triglyceride levels by physically removing chylomicrons from the blood, it’s an invasive and resource-intensive procedure.

Fibrates are the most potent oral agent for pancreatic risk and severe hypertriglyceridemia.

• If triglyceride levels are persistently elevated above 500 mg/dL despite lifestyle efforts, fenofibrate is first-line therapy to reduce the risk of pancreatitis.

• Fibrates are PPAR-alpha agonists, which increase the synthesis of LPL and enhance fatty acid oxidation, which leads to a 30 to 50% reduction in triglyceride levels.

• Trials have not demonstrated a clear primary ASCVD benefit with fibrate use when added to statin therapy; however, the role in mitigating pancreatic risk is undisputed.

• Avoid gemfibrozil in combination with statins due to a significantly increased risk of myopathy.

The most critical lifestyle interventions are strict avoidance of alcohol and refined carbohydrates, as both are converted to triglycerides in the liver.

• A low-fat diet, weight loss of 5-10% of body weight, and regular aerobic exercise are also highly effective.

• These changes can often lead to reductions of triglycerides of 50% or more.

439. Atrial Fibrillation: Anti-Arrhythmic Drugs in the Management of Atrial Arrhythmias with Dr. Andrew Epstein (CardioNerds)

Listen to the IM and Hospital Medicine Recaps podcast

Source (CardioNerds)

Class 1C antiarrhythmics, such as flecainide or propafenone, are contraindicated in patients with coronary artery disease or structural heart disease due to increased mortality risk.

• The pro-arrythmia risk is primarily linked to active ischemia, not just the mere presence of atherosclerotic plaque.

• Before initiating a class 1C agent, any patient with risk factors for CAD (for example, a male over 40 or an active smoker) must have a functional stress test to rule out ischemia.

• Periodic (annual) re-evaluation for CAD/ischemia is recommended given ischemia can develop over time.

• These drugs are also negative inotropes and should be avoided in patients with the reduced ejection fraction.

Always co-prescribe an AV nodal blocking agent, like a beta-blocker, with a class 1C antiarrhythmic.

• Class 1c drugs are potent sodium channel blockers that markedly slow intra-atrial conduction.

• While this mechanism suppresses atrial fibrillation, it can also organize into a slower, more organized atrial flutter. Given a typical atrial flutter circuit runs around 300 bpm. A 2:1 AV conduction. Results in a ventricular rate of 150 beats per minute.

• However, if the flutter circuit is slow to 240 bpm by a class 1c agent, it can paradoxically permit a one-to-one AV conduction, leading to a life-threatening ventricular tachycardia-like rate of the mid 200s.

• Co-administration of a beta blocker or a calcium channel blocker is essential to blunt AV nodal conduction and prevent this dangerous complication.

• Propafenone does have some intrinsic beta-blocking activity. However, it’s often insufficient to reliably prevent this one-to-one conduction.

Amiodarone’s extensive toxicity profile reserves it for second-line therapy despite its high efficacy.

• While Amiodarone is likely the most effective antiarrhythmic for maintaining sinus rhythm, its utility is limited by a high rate of organ toxicity.

• It has an extremely long half-life of about 100 days. It also has a large volume of distribution, which means the toxic effects once developed are very slow to resolve.

Toxicities can include:

• pulmonary fibrosis (watch for a new cough and obtain a CT if you have suspicion)

• thyroid dysfunction (both hypo and hyperthyroidism; check a TSH every six months)

• hepatotoxicity (check LFTs every six months)

• corneal micro-deposits (usually benign)

• optic neuropathy (a medical emergency)

Given these considerable risks, agents like dofetilide, sotalol, or catheter ablation are preferred first-line rhythm control strategies in patients with structural heart disease.

Dofetilide and sotalol must be initiated in a hospital setting with continuous telemetry and serial EKG monitoring.

• Both drugs are class III antiarrhythmics that block the delayed rectifier potassium current.

• They can prolong the QT interval and carry a risk of torsades. This risk is highest during initiation and dose titration.

• Thus, the standard protocol requires a three-day hospitalization to allow the drug to reach steady state. During this admission, the patient must be on continuous telemetry, and an EKG must be performed 2-3 hours after each dose to assess the QTC.

• QTC should be manually measured; you shouldn’t rely on the EKG machine’s automated reading. Use of Bazett’s formula is generally preferred.

• If there’s evidence of significant prolongation, the dose must be reduced or the drug should be discontinued.

• Sotalol is contraindicated if CrCl is less than 40, and dofetilide is contraindicated if CrCl is less than 20.

Dofetilide is a preferred antiarrhythmic for maintaining sinus rhythm in patients with severe LV dysfunction and heart failure.

• The DIAMOND-CHF trial demonstrated that dofetilide was not associated with an increase in mortality in patients with recent MI and LV dysfunction.

• It’s a pure class III agent with no negative inotropic or beta-blocking effects, which makes it hemodynamically well-tolerated in this vulnerable population. On the other hand, sotalol has beta-blocking properties that can exacerbate heart failure.

IV ibutalide is a rapid and effective option for pharmacologic cardioversion, particularly when sedation is a high risk.

• Ibutalide is a unique Class III agent used exclusively for the acute termination of AFib and flutter.

• It’s highly effective, with conversion rates often exceeding 60% within one hour. This makes it an alternative to electrical cardioversion in patients with whom sedation and anesthesia pose a significant risk, such as those with tenuous respiratory status.

• The primary risk is torsades. The risk is mitigated by pre-treating the patient with 1 to 2 g of IV mag sulfate. Patients must be monitored on telemetry for at least four hours post infusion.

#507 Swinging the Pendulum on Menopause Care With Dr Rachel Rubin (Curbsiders)

Listen to the IM and Hospital Medicine podcast

Source (Curbsiders)

The primary indication for systemic menopause hormone therapy (MHT) is the treatment of moderate to severe vasomotor symptoms (VMS), but it also effectively prevents osteoporosis.

• The most common and disruptive symptoms of menopause are VMS (such as hot flashes and night sweats).

• Systemic MHT is the most effective treatment available for VMS and can also improve related symptoms like sleep disturbance, mood lability, and joint pain.

• MHT is FDA approved for the prevention of post-menopausal osteoporosis. It works by decreasing osteoclast activity, thereby preserving bone mineral density and significantly reducing the risk of vertebral and hip fractures.

The Women’s Health Initiative (WHI trial), while initially alarming, now informs safer prescribing through age-stratified reanalysis.

• The initial 2002 publication of the WHI trial led to a dramatic decline in MHT use due to reports of increased risk of breast cancer, stroke, and coronary heart disease.

• However, this study’s population had an average age of 63, and many women were more than ten years past their menopause onset.

• Subsequent analyses have revealed a “timing hypothesis”. This hypothesis suggests that women who initiated MHT before age 60 or within 10 years of menopause had a neutral or even reduced risk of CHD and all-cars mortality. The increased risks were primarily seen in older women.

Transdermal estrogen bypasses first-pass metabolism in the liver, which mitigates the risk of venous thromboembolism (VTE)

• Oral estrogen undergoes a first-pass metabolism in the liver, which increases the synthesis of clotting factors such as factor VII and fibrinogen, and decreases natural anticoagulants such as antithrombin 3 and protein S.

• This effect is responsible for the two-fold increase in VTE risk seen with oral MHT.

• However, transdermal estrogen delivered via patches, gels, or sprays is absorbed directly into the systemic circulation, avoiding this hepatic effect.

• Observational studies show that transdermal estradiol at standard doses does not increase the risk of VTE compared to non-users.

• Thus, transdermal estrogen is the preferred route for women with VTE risk factors, such as obesity, a history of VTE, or known thrombophilia.

Progestogen therapy is required to protect the endometrium in the uterus, and micronized progesterone is often preferred.

• Estrogen alone can lead to significant risk of endometrial hyperplasia and adenocarcinoma.

• Progesterone acetate (MPA) is a synthetic progestin which was associated with an increased breast cancer risk in the combined MHT arm.

• Thus, micronized progesterone is preferred. It is typically dosed at 100 mg orally (continuous therapy) at bedtime daily or 200 mg for 12 days per month (cyclical therapy).

Low-dose vaginal estrogen is highly effective for genitourinary syndrome of menopause and carries minimal systemic risk.

• Genitourinary syndrome of menopause encompasses symptoms like vaginal dryness, dyspareunia (painful intercourse), and recurrent UTIs due to vulva, vaginal, and bladder atrophy.

• Low-dose vaginal estrogen is available as creams, tablets, or rings. It directly treats the tissue with negligible systemic absorption. Thus, it doesn’t increase the risk of VTE, stroke, or heart disease.

• Importantly, it also does not require progestogen co-therapy to protect the endometrium.

• The therapy can lead to significant quality of life improvements in patients suffering from genitourinary syndrome of menopause and is a key tool in preventing recurrent UTIs in postmenopausal women by restoring vaginal flora and pH.

MHT is absolutely contraindicated in:

• History of estrogen-sensitive cancer (breast, endometrial)

• h/o DVT/PE

• Active severe liver disease (since the liver metabolizes the hormones)

• An undiagnosed abnormal urine bleeding, which must be evaluated first to rule out endometrial cancer

Migraine with aura was historically considered a contraindication, but transdermal estrogen and the risk of stroke is not clearly elevated.

MHT should be initiated with standard doses and titrated based on clinical symptoms, not serum hormone levels.

• Typical starting regimen for healthy women with uterus and early menopause would be 0.0375 mg or 0.05 mg estradiol patch (changed weekly or twice weekly) combined with a 100 mg oral micronized progesterone nightly. The patient should then be reassessed in two to three months.

• If vasomotor symptoms are not controlled, the estradiol dose can be titrated up.

• Monitoring of serum estradiol or FSH levels is not recommended.

• Unscheduled uterine bleeding is common in the first 3-6 months of continuous combined MHT. If it persists beyond this, the patient should be evaluated with a pelvic ultrasound and potentially an endometrial biopsy.

The duration of MHT should be individualized based on an annual risk-benefit assessment, not an arbitrary stop date.

• There is no mandatory age at which MHT must be stopped.

• In many women, vasomotor symptoms can persist for over a decade.

• The decision should weigh the benefits of controlling ongoing symptoms against their own personal risk for cardiovascular disease or breast cancer.

• For women who choose to stop, it’s best to taper the dose slowly to avoid a sudden recurrence of severe symptoms.

SIBO Part III - Treatment (Run the List)

Source (RTL)

Treatment of SIBO is fundamentally different depending on whether the patient has hydrogen-predominant SIBO or methane-predominant SIBO. This is determined by the breath test results.

For patients with hydrogen-predominant SIBO, the antibiotic rifaximin is the preferred best-study treatment.

The medication is dosed at 550 mg three times a day for 14 days. It is generally well tolerated; however, the most significant barrier to use is high cost. Effective alternatives include amox-clav, metronidazole, ciprofloxacin, and trimethoprim-sulfamethoxazole.

Methane predominant SIBO it’s caused by methane-producing organisms, which are more resilient and often require a dual antibiotic approach for effective eradication.

Recommended regimen combines rifaximin (standard dose, as above) with neomycin, taken at 500 mg twice daily for 14 days. Neomycin is an aminoglycoside antibiotic with a more concerning side effect profile, including the potential for permanent hearing damage, kidney injury, and nerve damage. In patients with preexisting hearing, kidney, or nerve issues, or those who wish to avoid the risks, treating with rifaximin alone is a reasonable first step, even if it might be less efficacious.

Dietary modification is the primary non-antibiotic strategy.

The goal is to limit foods that fuel problematic bacteria in the small intestine. This is most reliably achieved by following a low FODMAP diet that restricts fermentable carbohydrates that bacteria thrive on. While effective, this diet can be very challenging to follow as it often eliminates otherwise healthy foods like broccoli and cauliflower. To help patients navigate the complexity, a referral to a dietician or nutritionist is highly recommended.

Despite their popularity, probiotics are generally not recommended for treating SIBO.

To address discomfort of gas and bloating, over-the-counter options like peppermint oil and some methadone can be helpful for managing symptoms while the underlying bacterial overgrowth is being addressed.