Unmasking of Crohn’s Disease With Interleukin-17 Inhibitor Therapy
Background:
Interleukin-17 (IL-17) inhibitors such as ixekizumab are among the most potent therapies for psoriasis and spondyloarthropathies. Despite only infrequent reports of inflammatory bowel disease (IBD) in clinical trials, biologics may contribute to de novo IBD or exacerbations of pre-existing disease. Here we report a case of a patient with psoriasis and psoriatic arthritis treated with ixekizumab who presented with chronic diarrhea complicated by pulmonary embolism and hemorrhagic shock. Ultimately, the patient was diagnosed with new onset Crohn’s disease.
Methods:
A 64-year-old male with a history of psoriasis and psoriatic arthritis presented with five months of large volume watery diarrhea, dyspnea, and multiple falls. He reported a 40-pound weight loss during this time. He denied recent travel, sick contacts, or history of IBD. Notably, the patient was initiated on ixekizumab a month prior to symptom onset. Initial evaluation revealed tachycardia (HR 122 bpm) and elevated inflammatory markers including a C-reactive protein (CRP) of 64 mg/L and fecal calprotectin of 9867 ug/g. Infectious workup was negative. CT scan of the abdomen and pelvis showed bowel wall thickening suggestive of colitis in the transverse, descending, and sigmoid colon with involvement of the splenic flexure. Prior to the patient’s colonoscopy, he developed chest pain and persistent tachycardia. Workup was significant for left popliteal vein DVT and bilateral pulmonary thromboemboli for which enoxaparin was initiated. His case was further complicated by hemorrhagic shock in the setting of large volume hematochezia with a hemoglobin of 5.8 g/dL (baseline 11).
Results:
After stabilization, colonoscopy revealed ulceration in the transverse, descending, and sigmoid colon. There was also a visible vessel below a clot in the descending colon that required two hemostatic clips and was thought to be the culprit of the bleeding event. Biopsies were consistent with Paneth cell metaplasia and a small granuloma, characteristic of Crohn’s disease. Ixekizumab was discontinued and he was transitioned to budesonide, infliximab, and azathioprine for Crohn’s disease with significant clinical improvement.
Conclusions:
Anti-IL-17 inhibitors such as ixekizumab are becoming increasingly prevalent for the treatment of psoriatic diseases. This case demonstrates ixekizumab induced Crohn’s disease within one month of starting treatment, a rare occurrence, and is the first to report venous thromboembolic events and GI hemorrhage. Although their precise action in the gut mucosa remains unclear, our case raises concern that IL-17 inhibition may improve one inflammatory condition while worsening the other. We suggest that before starting anti-IL-17 agents, patients be screened with a thorough personal and family history for IBD and counseled on this association.
