COLCHICINE TOXICITY IN A PATIENT WITH CHRONIC URTICARIA MASQUERADING WITH FEATURES OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Introduction Up to 25% of patients with chronic urticaria encounter symptoms refractory to antihistamines. Colchicine is considered a well-tolerated alternative. However, colchicine has a narrow therapeutic window with potential for severe toxicity. Case Description A 19-year old female with chronic urticaria was admitted to the hospital for acute hepatitis presenting with abdominal pain and emesis. Tryptase, C3/C4/C1q, and anti-nuclear-antibody were previously normal. She had failed antihistamines, omalizumab, and dapsone (for methemoglobinemia). Active medications included colchicine 0.6mg Q8h and erythromycin ethylsuccinate 300mg Q6h, added two weeks prior for gastroparesis. Infectious testing was negative. She developed fever >38.5C, cytopenias (hemoglobin 8.9g/dl, platelets 9 × 10 9 /L, ANC 300), hyperferritinemia (18,160ng/ml), and hypertriglyceridemia (286mg/dl) concerning for hemophagocytic lymphohistiocytosis (HLH). Evaluation revealed normal NK cell number (171cells/µl, 10.7% lymphocytes), function, and perforin/granzyme-B expression; mildly-elevated soluble interleukin-2 receptor (2196units/ml; normal 45-1105units/ml); and hypocellular bone marrow without hemophagocytosis. She was diagnosed with colchicine toxicity (serum level 6.3ng/ml; therapeutic range 3-4ng/ml) secondary to macrolide exposure, which was complicated by reversible posterior leukoencephalopathy syndrome. After two weeks of supportive care, she was discharged in stable condition. Discussion Colchicine undergoes first-pass metabolism and biliary excretion that is impeded by CYP3A4 and P-glycoprotein inhibitors (such as macrolides). Concurrent use of these medications increases serum colchicine concentrations and can incite multi-organ failure, associated with up to 10% mortality. Bone marrow suppression is a hallmark of toxicity. Systemic inflammation, which in this patient provoked concern for HLH, may occur. Clinicians must know the potentially-fatal drug interactions that may limit colchicine use.