What is the most common cause of agranulocytosis?

Correct Answer: D. Drug toxicity

Agranulocytosis is defined as an absolute neutrophil count <500/μL, and drug toxicity is the single most common cause accounting for 70–80% of cases in clinical practice. The mechanism is typically dose-dependent myelosuppression (predictable) or idiosyncratic (unpredictable, immune-mediated). Common Indian culprits include antithyroid drugs (propylthiouracil, carbimazole), NSAIDs (phenylbutazone—still used in rural India), sulfonamides, chloramphenicol, and antituberculous agents (rifampicin, isoniazid in susceptible individuals). The classic presentation is acute onset fever, sore throat, and oral ulceration within days to weeks of drug initiation. Bone marrow examination shows hypocellularity with selective absence of myeloid precursors. Recovery typically occurs within 1–3 weeks of drug withdrawal, though some cases progress to aplastic anemia. This is why drug history is the first and most critical clinical question in any patient presenting with agranulocytosis.

Why the other options are wrong

A. Autoimmune — While autoimmune mechanisms can cause agranulocytosis (e.g., systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis), autoimmune causes account for only 5–10% of cases. This is a distant second to drug toxicity. NBE may trap students who recall autoimmune causes but forget the epidemiological hierarchy. B. Marrow infiltration — Marrow infiltration by leukemia, lymphoma, or metastatic malignancy causes agranulocytosis but is much rarer than drug toxicity. It typically presents with pancytopenia (not isolated neutropenia) and is usually accompanied by other cytopenias. This is a classic distractor for students who confuse frequency with severity. C. Radiation exposure — Radiation-induced agranulocytosis is rare in civilian practice and occurs only after significant occupational or accidental exposure. It is not a common outpatient cause. In India, drug-induced cases vastly outnumber radiation-related cases, making this a low-yield distractor.

High-Yield Facts

Mnemonics

DRUGS causing Agranulocytosis (common in India) Propylthiouracil/Phenylbutazone, NSAIDs, Sulfonamides, Antituberculous (INH, RIF), Chloramphenicol, Thionamides (carbimazole). Use this when a patient with fever and sore throat has recent drug exposure. Memory Hook: 'DRUGS first, then rare causes' When you see agranulocytosis, think Drugs (70–80%), then Radiation, Utogenic (autoimmune), Growth (marrow infiltration). This reinforces the epidemiological hierarchy.

NBE Trap

NBE pairs agranulocytosis with autoimmune and marrow infiltration to lure students who recall these causes but forget that drug toxicity is far more common in everyday clinical practice. The trap is confusing "possible cause" with "most common cause."

Clinical Pearl

In Indian outpatient practice, a patient presenting with acute fever, sore throat, and oral ulcers after starting antithyroid drugs or NSAIDs should trigger immediate CBC and drug withdrawal—this is the classic presentation of drug-induced agranulocytosis. Early recognition prevents progression to sepsis and aplastic anemia.

_Reference: Robbins Ch. 12 (Hematologic Disorders); Harrison Ch. 109 (Disorders of Granulocytes); KD Tripathi Ch. 14 (Hematologic Toxicity of Drugs)_