Ibuprofen-Induced Pancytopenia and Erythema Multiforme in an Elderly Female Patient

Erythema multiforme (EM) is a delayed, cell-mediated cutaneous disease with varying clinical manifestations. It is most commonly associated with infections but can also be associated with medications, vaccines, and autoimmune diseases. Non-steroidal anti-inflammatory Drugs (NSAIDs) are commonly used analgesics that have rare associations with EM and pancytopenia. These adverse reactions to NSAIDs can obscure definitive diagnosis due to their rarity. We present a case where an elderly female patient taking 600mg of ibuprofen up to four times a day for shoulder bursitis developed EM and pancytopenia. In this case, a 75-year-old female with a medical history of atrial fibrillation, essential hypertension, non-insulin-dependent type 2 diabetes mellitus, and ischemic stroke with residual right-sided visual impairment presented to our Emergency Department in 2023 with neck swelling, skin rash, and ulceration of the oral cavity. She reported a generalized, targetoid body rash that occurred 15 days after she started taking ibuprofen regularly for left shoulder bursitis. No other medications were started before, after, or during this time period. CBC on admission was remarkable for a white blood cell count of 1.5x10⁹/L, hemoglobin of 6.5 g/dL, and platelet count <10x10⁹/L, consistent with pancytopenia. Ibuprofen was discontinued, and the patient was treated supportively with analgesia and packed red blood cell transfusions. Testing for HIV, antinuclear antibodies (ANA) panel, Hepatitis panel, and copper and zinc levels were negative. A biopsy of a targetoid lesion on the skin showed changes consistent with EM. Esophagogastroduodenoscopy revealed no actively bleeding lesions or ulcers in the stomach mucosa. The patient's blood counts eventually recovered with supportive treatment, and symptomatology improved. The patient was discharged six days after admission. Healthcare professionals should be aware of rare hematologic and immunologic side effects of NSAIDs, which may often be overlooked and misdiagnosed. More studies are needed to build on our wealth of knowledge regarding the etiology and management of EM, Steven Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).