Leflunomide-induced colitis with clinical, endoscopic & microscopic findings: a case report

Background: Leflunomide is used to treat inflammatory arthritis. The evaluation of diarrhea includes a broad differential, dependent on chronicity and presentation. Drug-induced colitis includes multiple culprits ranging from common medications to immunomodulators and chemotherapeutics. Leflunomide's long halflife causes colitis weeks to years after its initiation. It is rarely reported in the literature with both endoscopy and histology. We present an elderly woman with rheumatoid arthritis (RA), who was hospitalized for diarrhea secondary to leflunomide colitis with endoscopic and microscopic findings. With the pathology, we have evidence for a possible etiology for leflunomide colitis relating to the drug's immunomodulating mechanism. Our hope is to aid in the recognition of leflunomide colitis to reduce hospitalization length and to improve outcomes. Case Description: A 79-year-old Caucasian woman with a medical history of RA, chronic obstructive pulmonary disease (COPD) and gout, presented to the hospital on April 4th, th , 2022, with 7 days of watery diarrhea with greater than six bowel movements daily. Two months ago, she started taking leflunomide 10 mg once daily. Vitals were stable. Computed tomography (CT) abdomen/pelvis demonstrated wall thickening from the splenic flexure to the rectum. Labs included C reactive protein at 40.7 mg/L, erythrocyte sedimentation rate at 58%, and a positive fecal lactoferrin. She was started on ceftriaxone and metronidazole. Leflunomide was stopped. Stool cultures and C. difficile toxin were negative. Colonoscopy showed areas of erythematous mucosa and vascular effacement. Biopsies demonstrated lymphocytes in the lamina propria and a thickened epithelial layer. Follow-up at 2 weeks revealed resolution of symptoms and the patient was prescribed hydroxychloroquine for RA by her rheumatologist. Conclusions: Drug-induced colitis has been described in few case reports. This patient had other etiologies of diarrhea ruled out and cessation of leflunomide led to improvement. Leflunomide colitis clearly represented with clinical, endoscopic, and histologic findings in one case gives an opportunity to better characterize this condition and distinguish it from microscopic colitis and other drug-induced colitis. As leflunomide's active metabolite affects pyrimidine synthesis, which is an important process completed by T lymphocytes, the biopsy results including lymphocytic infiltrates point towards a possible mechanism by which colitis stems from leflunomide.