Best of Clinical Cases from December 2025! Check out the most recent Substack post published this AM! A deep-dive of my favorite lessons and pearls from the best clinical cases. Zero fluff, high-yield. Will continue to post pearls from these posts every day. Link below!

Daily Pearl(s): Up to 40% of patients with Sjogren’s Syndrome are seronegative for anti-SSA/SSB antibodies Yet, combined anti-SSA and/or anti-SSB testing has a sensitivity of 83.7% and a specificity of 91.5% for diagnosing Sjogren’s syndrome.

Daily Pearl(s): Syphilitic hepatitis usually presents with a cholestatic pattern and an elevated alk phos. A negative CSF VDRL does not rule out neurosyphilis. Instead, the diagnosis relies on clinical findings, a pleocytosis on CSF, and positive serum serologies.

Daily Pearl(s): The clinical presentation of subacute painless ("silent") thyroiditis is a transient phase of thyrotoxicosis due to hormone leakage, which can cause neuro symptoms including psychosis, delirium, and rarely, seizures (”thyrotoxic encephalopathy”).

Daily Pearl: Refractory or recurrent giardia is a red flag for a humoral immunodeficiency (such as CVID, IgA deficiency) Patients with CVID have an increased lifetime risk of cancer, especially B-cell lymphoma and gastric cancer due to immune dysregulation and impaired tumor surveillance

Daily Pearl: Sarcoidosis can present primarily with bone pain from lytic lesions, even in the absence of classic pulmonary findings.

Daily Pearl: Type B lactic acidosis should be considered in patients receiving high doses of beta 2 agonists (albuterol) which can cause a dramatic non-hypoxic rise in lactate. Source: CPS - November 26, 2025 VMR with Sharmin & Rahul - SOB, cough, malaise

Daily Pearl: In patients with pneumonia, failure to improve after 48-72 hours of appropriate empiric antibiotics warrants investigation for a resistant organism, a complication like an abscess or empyema, or an endobronchial obstruction requiring source control.

Daily Pearl: While the liver is the most common site of hydatid disease (70%), the spleen is involved in about 2-3% of cases. Eosinophilia is present in about 25-50% of cases. Management is based on cyst size, stage, and presence of symptoms.

Daily Pearl: Unlike the often-chronic presentation of pulmonary TB, TB pleuritis can present acutely or subacutely over days to weeks, mimicking bacterial pneumonia.

Daily Pearl: Myeloid sarcoma, also known as granulocytic sarcoma or chloroma, is a rare extramedullary tumor composed of immature myeloid blast cells. It’s a localized manifestation of acute myeloid leukemia occurring outside of the bone marrow.

Daily Pearl: Management of thyroid storm is multi-pronged and should be initiated promptly. 1. Block new hormone synthesis with a thionimide, like methimazole or PTU.

Daily Pearl: Colesteatoma is a cystic lesion in the middle ear or mastoid composed of keratinizing squamous epithelium. It is a “benign” process histologically, but is locally destructive and can lead to complications like deafness, vertigo, facial nerve palsies, and intracranial infections.

Daily Pearl: Platypnea-Orthodeoxia Syndrome (POS) should be suspected in any patient with hypoxemia that worsens in the upright position and improves when lying down, the clinical opposite of orthopnea.

Daily Pearl: Acute urinary retention is a critical red flag for central neurological processes, specifically in myelopathy or cauda equina syndrome. This is especially true when there is associated bilateral limb weakness. Source: CPS - November 14, 2025 VMR with Reza & Rabih

Daily Pearl: Bacillary Angiomatosis is a vascular proliferative disease caused by gram-negative bacilli, primarily Bartonella henselae or Bartonella quintana. It almost exclusively affects immunocompromised individuals, most classically patients with advanced HIV and a CD4 count below 100.

Daily Pearl: Systemic lupus erythematosus (SLE) has a highly variable presentation ranging from mild mucocutaneous and joint disease to life-threatening organ failure. Lupus nephritis is a major cause of morbidity and mortality.

Daily Pearl: Myocardial infarction in young adults (typically defined as <45 years old) is often missed due to atypical presentations and a low index of suspicion.

Daily Pearl: Anemia requiring transfusion signifies hematologic failure, making non-specific causes like anemia of chronic disease less likely and mandating an urgent workup for a primary bone marrow process or significant blood loss.

Daily Pearl: An asymptomatic patient with a critically low glucose level should trigger consideration of pseudohypoglycemia. Finger sticks should be avoided on arms that have an AV fistula for dialysis.

Daily Pearl: The phenomenon of pseudo-bradycardia in atrial fibrillation is the presence of a lower peripheral pulse rate than the apical or EKG rate. It is a subtle sign of poor perfusion and impending hemodynamic compromise.

Daily Pearl: The development of proteinuria in an active sediment can be the first localizing sign of a systemic vasculitis like microscopic polyangiitis (MPA). MPA can lead to rapidly progressive glomerulonephritis.

Daily Pearl: A hyperdynamic “flow murmur” can indicate high output heart failure. This state means that despite an increase in cardiac output, the patient is experiencing tissue hypoperfusion.

Daily Pearl: The yield of blood cultures in uncomplicated cellulitis is low, typically less than 5%, and thus they are not routinely recommended.

Daily Pearl: Atrial fibrillation is rarely the sole cause of complete loss of cardiac output. The loss of the atrial kick can contribute to a 15% to 25% reduction in cardiac output, which can cause hypotension in a vulnerable patient but is unlikely to be the cause of a PEA arrest.

Daily Pearl: Sarcoidosis affects the lungs and intrathoracic lymph nodes in over 90% of cases. However, any organ can be affected. Hepatic involvement is common in 50-65% of patients but is often asymptomatic.

Daily Pearl: Subacute “AMS” tied to personality changes should prompt head imaging, namely for a local process like a primary CNS malignancy or metastatic disease in the frontal lobes. Source: CPS - Episode 431: The Clinical Unknown Series with Anmolpreet Kaur

Daily Pearl: Severe hypomagnesemia can independently cause both hypokalemia (by affecting the ROMK channel in the kidneys) and hypocalcemia (by inducing PTH resistance). Long-term PPI use can lead to profound hypomagnesemia. Source: CPS - Episode 431: The Clinical Unknown Series

Daily Pearl: An extremely high platelet count in the setting of infection should raise suspicion for “pus under pressure” - a walled-off, encapsulated infection like an abscess that the body is struggling to contain.

Daily Pearl: Behcet’s disease is a chronic, relapsing, multi-system inflammatory disorder of unknown etiology, characterized by a vasculitis that can affect both arteries and veins of all sizes. The classic triad is recurrent oral ulcers, genital ulcers, and uveitis.

Best of Clinical Cases from October 2025! IM and Hospital Medicine Recap Check out the most recent Substack post published this AM! My favorite lessons and pearls from the best clinical cases from @CPSolvers @Dx_Atypia @runthelistpod @NEJM Zero fluff, high-yield. Link below!

Daily Pearl: In aspiration PNA, elderly patients may present with atypical signs of infection, such as functional decline, confusion, or tachypnea, in the absence of fever due to immunosenescence.

Daily Pearl: Lithium is a major cause of thyroid dysfunction (hypothyroidism, goiter, and thyroiditis). The effects can persist after cessation.

Daily Pearl: Refractory or recurrent giardia is a red flag for a humoral immunodeficiency (such as CVID, IgA deficiency). Patients with CVID have an increased lifetime risk of cancer, especially B-cell lymphoma and gastric cancer.

Daily Pearl(s): The triad of trismus ("lockjaw") , dysphagia, and reflex spasms in a patient with a potential wound is tetanus until proven otherwise.

Daily Pearl: Postpartum heart failure is not always peripartum cardiomyopathy. Also consider thyrotoxicosis, as pregnancy can trigger or unmask Graves disease.

Daily Pearl: Disseminated histoplasmosis is a key (albeit rare) cause of bilateral adrenal destruction and Addison disease, particularly in endemic areas like the Mississippi River Valley.

Daily Pearl: The combination of hypertension and thrombocytosis in a patient with new ascites is a major red flag against a diagnosis of cirrhosis. A low SAAG (<1.1 g/dL) reliably indicates a non-portal hypertensive cause of ascites.

Daily Pearl: Cocaine can cause profound ischemia due to severe vasoconstriction, leading to rare catastrophes like acute necrotizing esophagitis.

Daily Pearl: Late-onset asthma (especially after age 40) that is severe or steroid-dependent should always prompt a search for mimics like EGPA. "Migratory pulmonary infiltrates" are a classic sign of eosinophilic lung diseases, including EGPA and Chronic Eosinophilic Pneumonia.

Daily Pearl: New-onset nephrotic syndrome in an older adult, especially with signs of multi-organ dysfunction (cardiac, hepatic), should immediately raise suspicion for AL amyloidosis.

Daily Pearl: Mild elevations in ALT and AST without elevations in bilirubin, alk phos, or GGT should reflex to a CK to assess for extra-hepatic source of elevation such as muscle damage especially in patients where NAFLD, alcohol use, and DILI is less likely.

Daily Pearl: Syphilitic osteomyelitis is a rare but classic presentation where the infection has a known tropism for the skull. Source: CPS, Episode 429 – RLR – Forehead Bump

Daily Pearl: A creatinine level >10 mg/dL should always be considered post-renal obstruction until proven otherwise. The absence of hydronephrosis on imaging does not rule out obstruction, especially from chronic, infiltrative processes like TB or retroperitoneal fibrosis that encase the ureter.

Daily Pearl: Bell’s palsy presents over hours to a few days with weakness of all muscles of facial expression on one side, including the forehead. However, a rare stroke location can produce a similar clinical deficit.

Daily Pearl: In aortic stenosis (AS), exertional syncope occurs due to profound cerebral hypoperfusion when vasodilation in exercising muscles is not matched by a sufficient increase in cardiac output across the fixed obstruction (the stenosed valve).

Daily Pearl: Chilaiditi’s syndrome is a rare condition where a segment of the colon (typically the hepatic flexure or transverse colon) becomes trapped between the liver and the right hemidiaphragm.

Daily Pearl: Organophosphate poisoning presents with muscarinic effects (diarrhea, urination, miosis, bronchospasm, bronchorrhea, emesis, lacrimation, salivation - “DUMBELS”) and nicotinic effects (muscle fasciculations, cramping, weakness, paralysis, tachycardia, hypertension).

Daily Pearl: Severe, unexplained thrombocytopenia or other cytopenias can be the presenting manifestation of disseminated TB due to bone marrow infiltration. Source: CPS, October 14, 2025 VMR with Ravi & Deb - worsening SOB for 15 days

Daily Pearl: Flash pulmonary edema is a disease of afterload mismatch, making vasodilation (afterload reduction via nicardipine, nitroglycerin, etc.) the cornerstone of therapy.