A Novel Presentation of 6-Mercaptopurine Toxicity in a Patient With IBD

Abstract

Pancreatitis and drug fever are well-known idiopathic side effects of the immunomodulatory drugs. Erythema nodosum (EN) and episcleritis are well-known extra intestinal manifestations of Inflammatory Bowel Disease (IBD). We present a unique case of 6-MP induced pancreatitis, drug fever, episcleritis, and erythema nodosum in a patient with IBD. A 30-year-old female with Ulcerative Colitis status post proctocolectomy with an IPAA re-presented with inflammatory arthritis and diarrhea. Endoscopy showed proximal ileitis consistent with Crohn's. She was started on combination immunosuppression with adalimumab and 6-MP. She later presented to clinic with six days of epigastric pain, vomiting, fevers, and scleral injection. Three days prior she had developed multiple red, tender, non-pruritic nodules on her anterior tibia bilaterally. Her bowel frequency had improved from 12 to 4 stools per day. She was febrile with an elevated lipase, CRP, and a neutrophil predominant leukocytosis. She was diagnosed with pancreatitis and admitted. Liver enzymes were not elevated and imaging was negative for biliary disease. There was no history of alcohol consumption. Blood, urine, and stool cultures were negative and her stool was negative for c. difficile. Dermatology concluded the lesions were consistent with EN and ophthalmology concluded the scleral injection was consistent with episcleritis. The 6-MP was stopped and the patient improved rapidly. By hospital day 2, she was tolerating a normal diet and her leukocytosis had resolved. The lower extremity rash also rapidly improved. Throughout the patient's hospitalization, there was no change in the character or frequency of the patient's bowel movements. While pancreatitis and EN are documented side effects of 6-MP, the combination along with episcleritis and presence of fever make for a novel presentation of 6-MP toxicity in a patient with IBD. Although IBD flare was on the differential as well as inflammatory panniculitis secondary to pancreatitis, the improvement in baseline Crohn's symptoms with medical therapy, the timing of new symptoms related to initiation of 6-MP, as well as rapid improvement in symptoms after discontinuation of 6-MP are all indicative of a drug-related etiology. While this is a very unique case, its importance lies with appropriate management of thiopurine toxicity which includes quick clinical recognition and discontinuation of the medication which can be challenging in such complicated patients.Figure 1Figure 2