New Onset Crohn’s Disease with Ixekizumab Initiation

A male in his mid-60s with a 7-year history of psoriasis and psoriatic arthritis presented to the emergency department with five months of large-volume watery diarrhea, dyspnea, and multiple falls. He described having eight to ten large-volume, watery bowel movements daily. During the five months, he reported a substantial weight loss of 40 pounds. He denied recent travel, sick contacts, or a history of IBD. Notably, the patient had initiated ixekizumab therapy approximately one month before symptom onset.

He has a history of hypothyroidism, hypertension, and insomnia. His home medications included levothyroxine 75 mcg/day, losartan 100 mg/day, metoprolol 100 mg twice/day, and amitriptyline 10 mg/night.

Previous treatments for psoriasis and psoriatic arthritis include methotrexate 15 mg/weekly which was stopped due to intolerance and etanercept 50 mg/weekly. However, because the patient had a flare despite etanercept treatment, he was switched to ixekizumab 80 mg/weekly after induction. After only one month of ixekizumab, the patient developed a large volume of watery diarrhea.

On initial evaluation, the patient was tachycardic to 122 beats per minute. Laboratory tests revealed elevated inflammatory markers, with a C-reactive protein (CRP) of 64 mg/L and fecal calprotectin of 9867 μg/g. The infectious workup was negative. Computed tomography (CT) of the abdomen and pelvis demonstrated bowel wall thickening suggestive of colitis in the descending, transverse, and sigmoid colon with involvement of the splenic flexure (Figure 1A). However, before the patient’s colonoscopy, he developed chest pain in addition to persistent tachycardia. The workup unveiled a left popliteal vein DVT and bilateral pulmonary thromboemboli for which he was started on enoxaparin 90 mg/twice daily. Interestingly, the patient’s diarrhea improved with dicyclomine 10 mg/four times daily as needed and loperamide 2 mg/three times daily as needed, allowing for the deferral of colonoscopy to an outpatient setting, and the patient was discharged.

Unfortunately, two weeks later, the patient returned to the ED with pleuritic chest pain, dyspnea, and diarrhea. He discontinued enoxaparin therapy as he didn’t understand the necessity for its continuation. On evaluation, he was tachycardic to 140 beats per minute with a temperature of 100.8°F. Further investigation revealed a notable increase in CRP to 197 mg/L. The infectious workup was again negative. A CT pulmonary angiogram illustrated worsened pulmonary embolus thrombus burden, including a new thrombus occluding the entire right lower lobe pulmonary arteries and a new embolus in the left lower lobe, for which the patient was heparinized. A repeat CT scan of the abdomen and pelvis was significant for colitis, consistent with findings from the previous scan. Due to his persistent diarrhea, a flexible sigmoidoscopy was performed, showing patchy ulceration, granulation tissue, and reactive epithelial changes in the colon. Biopsies were not significant for histopathologic changes.

The patient’s clinical course was further complicated by hemorrhagic shock, precipitated by hematochezia with a hemoglobin drop from 11 to 5.8 g/dL. After stabilization in the intensive care unit, an inferior vena cava filter was placed and the patient underwent colonoscopy revealing ulceration in the transverse, descending, and sigmoid colon (Figures 1B-1D). Additionally, a visible vessel below a clot in the descending colon necessitated hemostatic intervention with two hemostatic clips (Figures 1B & 1C). Biopsies were consistent with Paneth cell metaplasia and a small granuloma, concerning for Crohn’s disease (Figures 2A & 2B). In light of these findings, ixekizumab therapy was discontinued.

Based on the patient’s colonoscopy findings, ixekizumab was felt to be suspicious for this adverse event. The patient was started on budesonide 9 mg at hospital discharge. At his gastroenterology clinic appointment one month later, he reported continued bowel movements every two hours. He was initiated on infliximab and azathioprine. After induction, he was continued on 500 mg every 8 weeks and azathioprine 50 mg/daily. One month later, he was symptom-free and had a CRP of 5 mg/L. The patient has remained asymptomatic since ixekizumab was discontinued. The adverse event was reported to the Food and Drug Administration.