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

Zachary C. Junga, MD, Nisha A. Shah, MD, and John D. Betteridge, MDGastroenterology Service, Walter Reed National Military Medical Center, Bethesda, MD

• Pancreatitis and drug fever are well-known idiopathic side effects of the immunomodulatory drugs

• Erythema nodosum (EN) and episcleritis arewell-known extra intestinal manifestations of Inflammatory Bowel Disease (IBD)

• 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 and started on 6-MP in addition to prior adalimumab

• Later presented to clinic with six days of epigastric pain, vomiting, fevers, and scleral injection and three days of multiple red, tender, non-pruritic nodules on her anterior tibia bilaterally all while her bowel frequency had improved from 12 to 4 stools per day

• Pertinent Work Up:• elevated lipase, CRP, and neutrophil predominant

leukocytosis• Dermatology concluded lesions consistent with EN• Ophthalmology concluded scleral injection was

consistent with episcleritis

• Negative work up• Liver enzymes normal• Imaging negative for biliary disease.• No history of alcohol consumption• Blood, urine, and stool cultures negative• Stool negative for c. difficile

• Diagnosed with pancreatitis and 6-MP stopped

• Within 24 hours, patient tolerating normal diet, leukocytosis resolved and lower extremity lesions improved

• No change in the character or frequency of the patient's bowel movements throughout hospitalization

• 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

• Differential to include:• IBD flare• Inflammatory panniculitis secondary to pancreatitis

• Argument for 6-MP toxicity• Improvement in baseline Crohn's symptoms with

medical therapy• Timing of new symptoms related to initiation of 6-MP• Rapid improvement in symptoms after

discontinuation of 6-MP

The views expressed in this poster are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, the Department of Defense, or the United States Government

REFERENCES1. Haber CJ, et al. Nature and course of pancreatitis caused by 6-mercaptopurine in the treatment of inflammatory bowel disease. Gastroenterology 1986; 91:982-5.2. Korelitz BI, et al. Allergic reactions to 6-mercaptopurine during treatment of inflammatory bowel disease. Journal of Clinical Gastroenterology 1999; 28(4):341-4.3. Bermejo F, et al. Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis. Aliment Pharmacol Ther 2008;28:623-628.4. Pitchumoni CS, Rubin A, Das K. Pancreatitis in inflammatory bowel diseases. J Clin Gastroenterol 2010;44:246-253.5. Lamers CB, et al. Azathioprine: an update on clinical efficacy and safety in inflammatory bowel disease. Scand J Gastroenterol 1999;34 Suppl 230:111-5.6. de Fonclare AL, et al. Erythema nodosum-like eruption as a manifestation of azathioprine hypersensitivity in patients with inflammatory bowel disease. Arch Dermatol 2007; 143:744-8.

Key Learning Points

• Rapid clinical recognition of thiopurine toxicity & discontinuation of the medication

• No prior reported cases of thiopurine toxicity consisting of above mentioned symptomatology

CASE VIGNETTE DISCUSSIONINTRODUCTION