Jacob Lui, BS1, Jaime de La Fuente, MD2, Magnus Halland, MD2; 1Mayo Clinic College of Medicine, Rochester, MN; 2Mayo Clinic Health System, Rochester, MN
Introduction: Although a known of cause diarrhea, the pyrimidine synthesis inhibitor leflunomide is a rare cause of overt pancolitis that presents a formidable diagnostic challenge.
Methods: A 46-year-old female with a medical history of psoriatic arthritis was admitted with a two-week history of progressive right upper-quadrant pain, frequent non-bloody diarrhea, tenesmus, and non-bloody emesis. Her immunosuppressant therapy included certolizumab for the past five years and leflunomide for the past 17 months. She denied use of other medications. Initial laboratory evaluation was significant for a mild leukocytosis, lipase of 476 U/L (normal: 12-61 U/L) and C-reactive protein of 50.8 mg/L (normal ≤8.0 mg/L). A stool pathogen panel including Clostridioides difficile was negative. RUQ ultrasound revealed cholelithiasis without cholecystitis. Computed-tomography imaging with contrast revealed no evidence of pancreatitis and mild wall thickening with mucosal hyperenhancement, consistent with ileocolitis (Figure A). A subsequent colonoscopy was notable for circumferential, contiguous inflammation throughout the colon but a normal terminal ileum. Sigmoidal inflammation was mild with a decreased vascular pattern, erythema, and mild friability (Figure B). Biopsy of the descending colon (Figure C) demonstrated surface erosion, crypt abscess (arrowhead) and destruction, and increased lamina propria inflammation without the chronic inflammation classically seen in inflammatory bowel disease. Cytomegalovirus immunostaining was negative. Symptoms persisted despite a three-day course of high-dose intravenous steroids. The decision was made to stop leflunomide, the disease-modifying anti-rheumatologic drug, due to select case reports documenting rare leflunomide-induced colitis. Symptoms improved within two weeks of drug cessation, with a reduction of stool frequency to two formed bowel movements daily, resolution of abdominal pain, and improvement of erythema on repeat flexible sigmoidoscopy. Discussion: This case demonstrates the value of a comprehensive medication history and the diagnostic challenge of leflunomide-induced colitis. Patients with rheumatologic diseases are often on medications with adverse gastrointestinal effects, including biologics, steroids, NSAIDs and other immunomodulators. The lack of randomized studies, vague radiologic, endoscopic and histologic findings, as well as the variable onset after medication initiation makes leflunomide-induced colitis a challenging and rare diagnosis.
Figure A. Abdominal CT with contrast revealing ileocolitis, mild wall thickening, and mucosal hyperenhancement of the entire colon, consistent with colitis.
Figure B. Colonoscopy of sigmoid colon revealing mild inflammation with erythema, decreased vascular pattern, and mild friability.
Figure C. Descending colon; biopsies show surface erosion, crypt abscesses and crypt destruction. There is also increased laminar propria inflammation (100x).
Disclosures: Jacob Lui indicated no relevant financial relationships. Jaime de La Fuente indicated no relevant financial relationships. Magnus Halland indicated no relevant financial relationships.