IgG4-related disorder Small intestinal lesion Balloon assist enteroscopy Immunohistochemistry
Immunoglobulin G4 (IgG4)-related disease is a systemic disease characterized by chronic inflammation with abundant IgG4-positive cells and elevated serum IgG4. Previous reports describe infiltration of IgG4-positive cells in multiple organs . In the gastrointestinal (GI) tract, previous reports indicate that inflammation was observed in the esophagus, stomach, and colon [1, 2, 3, 4, 5, 6]. However, there have been few reports regarding small intestinal lesions. We report a case of IgG4-related disease with small and large intestinal lesions.
A 55-year-old man presented to our hospital with 4 months of general fatigue and lower abdominal pain. He had the past history of cholecystectomy and did not take any non-steroidal anti-inflammatory drugs. He was admitted because his abdominal pain was worsening. The findings of abdominal computed tomography (CT) scan indicated that his pancreas was swollen; however, he did not have any ocular, salivary gland, and retroperitoneal lesions. Blood tests revealed high levels of C-reactive protein (4.1 mg/dL), elevated IgG (5,636 mg/dL), and IgG4 (2,480 mg/dl) levels. Nephritis was suspected because urinary tests revealed elevated beta-2 microglobulin and N-acetyl-β-d-glucosaminidase although renal biopsy was not done. Histological findings from cervical lymph node indicated infiltration of IgG4-positive cells while malignant lymphoma and Castleman’s disease were excluded. Esophagogastroduodenoscopy (EGD) and colonoscopic findings revealed multiple erosions and ulcerations in the stomach and colon (Fig. 1a,b). The abdominal CT also indicated increased bowel wall thickness of the proximal small intestine, therefore we performed double balloon enteroscopy (DBE). Small erosions and irregular ulcerations were observed at the jejunum (Fig. 1c,d) while inflammation was not observed in the ileum. These lesions included neither longitudinal nor circular ulcerations. Membranous strictures were not observed. Histological findings from biopsy specimens revealed infiltration of inflammatory cells, including plasma cells (Fig. 2a,b) in the jejunum. The percentage of IgG4-positive cells among IgG-positive plasma cells was approximately 70 % (Fig. 2c,d). IgG4-positive cells were detected not only from specimens containing erosions but also from endoscopically normal mucosa in the ileum (Fig. 2e,f). A total of 40 mg daily of oral prednisolone was given and his symptoms rapidly improved. At 3 months after administration of corticosteroids, the colonoscopy indicated colonic ulceration was improved (Fig. 3). However, IgG4-positive cells remained even after clinical remission was obtained by the use of corticosteroids. Thus, dose of steroid has been gradually decreased to avoid relapsing remission.
On the basis of the elevated serum IgG4 level and histological analysis (ratio of IgG4/IgG > 50 % in the cervical lymph node and GI tracts), this patient was diagnosed as having IgG4-related disorder. The lesions were also observed in pancreas, kidney, and cervical lymph nodes. Recently, IgG4-related disease has been the subject of an increasing number of reports . To our knowledge, however, only 15 cases have been reported regarding GI lesions associated with IgG4-related disease. Gastric lesions were observed in most cases (11/15 cases). Endoscopy or colonoscopy was performed in most cases (14/15); however, DBE has not been performed in the previous reports. Diagnostic procedures for small intestinal lesions were limited in the past, so these lesions could not be detected. Capsule endoscopy may be useful, but it cannot be used to make a pathological diagnosis. Since DBE has been developed, biopsy specimens can be obtained from small intestinal lesions where they cannot be reached by EGD and colonoscopy. Lymphoproliferative disease, tuberculosis, and non-steroidal anti-inflammatory drugs may cause small intestinal lesions. However, histological findings revealed IgG4 positive cells were infiltrated in the small intestine. Thus, we could distinct those diseases from IgG4-related disorder in this case. Our case is the first to detect multiple small intestinal lesions using DBE and confirm the infiltration of IgG4-positive cells using immunohistochemistry.
The authors would like to express thanks to Dr Joseph Onyiah for giving us fruitful comments and editing the English language.
Conflict of interest
Lopes J, Hochwald SN, Lancia N, et al. Autoimmune esophagitis: IgG4-related tumors of the esophagus. J Gastrointest Surg. 2010;14:1031–1034.PubMedCrossRefGoogle Scholar
Lee H, Joo M, Song TJ, et al. IgG4-related sclerosing esophagitis: a case report. Gastrointest Endosc. 2011;73:834–837.PubMedCrossRefGoogle Scholar
Fujita T, Ando T, Sakakibara M, et al. Refractory gastric ulcer with abundant IgG4-positive plasma cell infiltration: a case report. World J Gastroenterol. 2010;16:2183–2186.PubMedCrossRefGoogle Scholar
Chetty R, Serra S, Gauchotte G, et al. Sclerosing nodular lesions of the gastrointestinal tract containing large numbers of IgG4 plasma cells. Pathology. 2011;43:31–35.PubMedCrossRefGoogle Scholar
Shinji A, Sano A, Hamono H, et al. Autoimmune pancreatitis is closely associated with gastric ulcer presenting with abundant IgG4-bearing plasma cell infiltration. Gastrointest Endosc. 2004;4:506–511.CrossRefGoogle Scholar
Ueno K, Watanabe T, Kawata Y, et al. IgG4-related autoimmune pancreatitis involving the colonic mucosa. Eur J Gastroenterol Hepatol. 2008;20:1118–1121.PubMedCrossRefGoogle Scholar