Postdoctoral Researcher Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center Dallas, Texas, United States
Introduction
Ustekinumab is a monoclonal antibody commonly used in the management of Crohn’s disease (CD). ANCA-associated vasculitis (AAV), a type of vasculitis characterized by the presence of anti-neutrophil cytoplasmic antibodies, can arise from various etiologies, including drug-induced mechanisms. However, reports of ustekinumab-associated AAV are rare, with only one other documented case. We present a case of possible ustekinumab-induced AAV in a patient receiving treatment for CD, contributing to the growing understanding of biologic-induced vascular inflammation.
Case Report A 65-year-old male with a history of penetrating ileocolonic and perianal CD and chronic eczematous dermatitis presented with a two-week history of fatigue, night sweats, and high-grade fevers. Following multiple treatment failures, the patient started ustekinumab therapy in 2017. This led to clinical remission and endoscopic improvement for four years prior to presentation, with only mild inflammation on the latest colonoscopy.
Upon presentation, the patient was febrile (39.3°C) with otherwise normal vital signs. Initial laboratory investigations revealed elevated serum creatinine (1.40 mg/dL), AST (88 U/L), ALT (152 U/L), alkaline phosphatase (251 U/L), and WBC count (17.52 thousand/uL). An extensive infectious workup, including a CT scan and a nuclear medicine white blood cell scan, was unrevealing. Rheumatology consultation found low suspicion for an autoimmune etiology following a positive antinuclear antibody (ANA) test (1:640) and a negative smooth muscle antibody test. A liver biopsy suggested possible drug-induced injury. A bone marrow biopsy and flow cytometry did not reveal evidence of malignancy. After these evaluations, no clear etiology was found, and the patient was ultimately discharged on antipyretics.
Following persistent fevers after discharge, an outpatient ANCA panel returned positive for P-ANCA with an MPO > 8. A subsequent kidney biopsy confirmed MPO-ANCA-associated glomerulonephritis, revealing focal necrotizing glomerulonephritis with 17% crescents. The patient was started on rituximab and prednisone, and ustekinumab, thought by rheumatology consultants to be an inciting factor, was discontinued. Prednisone was tapered off, and rituximab was continued for 2 years before the patient experienced a flare of his CD. This led to the discontinuation of rituximab and initiation of upadacitinib for CD, chronic eczematous dermatitis, and vasculitis.
Discussion
This case highlights the rare occurrence of potentially ustekinumab-induced AAV in patients treated for CD, underscoring the need for a high index of suspicion for uncommon adverse events. Understanding these potential risks can pave the way for future pathophysiological insights and improved clinical awareness.
