Case Report: Immunoglobulin G4-Related Disease Mistaken for Crohn’s Disease

Background: Immunoglobulin G4-related disease (IgG4-RD) is a rare fibrous and chronic immune-mediated inflammatory disorder that can affect most organ systems and is characterized by a histopathological lymphoplasmacytic infiltrate rich in IgG4+ plasma cells. IgG4-RD is difficult to diagnose and requires a combined analysis of radiologic, histopathological, and laboratory findings to distinguish it from other conditions, including inflammatory bowel disease (IBD). Methods: We describe a 37-year-old man previously diagnosed with Crohn’s disease (CD) of the colon in 2020 and suspected granulomatosis with polyangiitis (GPA) with limited involvement of his sinuses, who presented 3 years later for an opinion regarding his management. Review of his CD history included endoscopic and histologic reports describing CD of the colon and a CT abdomen and pelvis at the time of his diagnosis which did not show additional small bowel involvement. After his diagnosis he was treated with infliximab, adalimumab, ustekinumab, and later risankizumab, but despite drug escalation, had partial clinical response with endoscopic findings of persisting pancolitis. Upon presentation to our center, his dominant symptom was severe abdominal pain. Stool calprotectin was >2000 ug/g, and point-of-care intestinal ultrasound (in clinic) revealed active inflammation in the rectum and sigmoid colon characterized by increased bowel wall thickness, hyperemia, mesenteric fat stranding and lymphadenopathy. Given medically resistant disease and his history of granulomatosis with polyangiitis, an alternative diagnosis to CD was suspected. The patient’s prior colonoscopic biopsies were subsequently reviewed by two expert IBD pathologists at our center and were interpreted as patchy active colitis with ulceration, erosion, mild crypt architectural distortion, and a poorly formed granuloma. However, CD-type granulomas were not identified, and there was no evidence of vasculitis. Some areas of crypt epithelial attenuation were present, and a patchy prominence of lamina propria eosinophils was seen. Simultaneously, the patient had additional immunologic evaluation which revealed a serum IgG4 level 1951.5 mg/dL, elevated beta 2 globulin, low gamma protein fraction, a low albumin/globulin ratio. Pan-CT identified extensive lymphadenopathy throughout the patient‘s neck, chest, and abdomen. The patient was referred to hematology and a subsequent bone marrow biopsy was performed to rule out myeloma prior to possible lymph node excision. Marrow assessment was normal, and the patient proceeded with left axillary lymph node excision which revealed follicular hyperplasia and increased IgG4+ plasma cells. Subsequently, immunohistochemical staining for IgG4 was performed on the patient’s colon biopsies, which revealed a high percentage of the IgG cells in the lamina propria with > 50% positivity for IgG4. This confirmed the patient’s IgG4 mediated colitis, and he has now started rituximab therapy. Conclusions: We demonstrate a case of IgG4-RD misclassified as CD and GPA and emphasize the importance of consideration of this rare disorder in appropriate patients. Clinical follow-up and response to rituximab will be described at the time of this case presentation.