IgG4-Related Disease with Esophageal Involvement

31 Jan, 2020 ,

This is the case of a 56-year-old man who presented with dysphagia and weight loss. An esophagoduodenoscopy revealed a severe esophageal stricture in the distal esophagus. After surgical resection, the final pathologic analysis revealed that the tumor was comprised of benign-appearing fibroinflammatory cells with an increase and predominance of IgG4-positive plasma cells. He did not, however, have any other symptoms indicative of systemic autoimmune disease or connective tissue disorders. The patient was diagnosed with IgG4-related disease, definitive, with esophageal involvement. 

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Three years ago, A 56-year-old Asian man presented to our clinic with debilitating dysphagia involving solids for several months. The patient had a heavy smoking history (3 packs/day, 30 years), but no alcohol drinking history. He had uncontrolled diabetes mellitus over 10 years, and underwent coronary artery bypass graft surgery 8 years previously.

The patient had previously visited a local clinic with heartburn and dysphagia, where he underwent esophagogastroduodenoscopy (EGD) without a biopsy. EGD revealed esophageal stricture and mucosal abrasion. When initially referred to our clinic, provisional diagnosis included gastroesophageal reflux disease, thus, proton pump inhibitor therapy began at first visit. We planned further evaluations like computed tomography (CT), barium swallow, esophageal manometry, and endoscopic biopsy, but he constantly refused admission or further evaluations and was lost to follow-up for 18 months because of his poor economic status.

As time went by, his dysphagia became aggravated and was associated with weight loss. He revisited the clinic with a body weight loss of 7 kg (47 kg at visit; usual weight 54 kg) and dysphagia involving both solids and liquids; he could barely swallow a liquid diet and had difficulty even in swallowing pills.

Physical examination revealed no superficial lymph nodes. A blood test showed that complete blood cell counts, creatinine, and liver function tests were normal. EGD showed severe esophageal stricture at 32 cm from incisors and mucosal erosions with exudate.

 Biopsies were performed at erosions (only 2 pieces of tissue). Biopsy results showed necroinflammatory exudate. Barium swallow showed stricture in the mid-to-distal esophagus and delayed contrast passage. CT scan demonstrated an esophageal lesion, length about 70 mm, in the lower esophagus with marked luminal narrowing and wall thickening, without enlarged lymph nodes. An abdominopelvic CT scan of the pancreas was performed and showed normal.

Previous proton pump inhibitor therapy was not effective and the lesion was long. Findings of body weight loss of 7 kg and wall thickening of the esophagus might suggest malignancy, but no lymph node enlargement was revealed on CT scan. There was a previous CT scan a year previously, because of coronary artery bypass graft history. In the previous scan, there was no esophageal wall thickening or enlarged lymph nodes. To evaluate esophageal motility disorders, esophageal manometry was planned but the stricture was too narrow for a catheter to pass.

As the disease showed benign features (benign biopsy, no lymph node enlargement), we suggested esophageal dilatation rather than surgical resection. But the patient wanted immediate resolution of symptoms and refused the step-wise procedure. Thus, the surgical measure Ivor-Lewis esophagectomy was performed. His postoperative course was uneventful, and he was discharged on postoperative day 10. The oral intake of soft diet was tolerable at the time of discharge.

Upon gross examination, the resected specimens showed marked wall thickening and stricture with mucosal erosion in the lower esophagus. Histologically, scattered lymphoid follicles and prominent muscular hypertrophy were observed in the submucosal layer. Dense lymphocyte and plasma cell infiltration was observed in the submucosal layer and the proper muscle layer. Immunohistochemistry revealed IgG4+ plasma cells at a level of >50/HPF and a ratio of >90′ IgG4+/IgG+ plasma cells. Postoperative serum level of IgG was 1,450 mg/dL (normal range: 700–1,600) and IgG4 was 171.0 mg/dL. Based on the comprehensive diagnostic criteria for IgG4-RD , He was diagnosed with an IgG4-RD, definitive, with esophageal involvement.

Following achievement of remission by surgical method, the patient received maintenance prednisolone therapy (30 mg/day), which was slowly tapered. His dysphagia improved greatly and he returned to his usual weight (54 kg). After prednisolone therapy, follow-up serum IgG4 level dropped to 48.9 mg/dL and prednisolone therapy was tapered. Serum IgG4 level sustained a similar level (52.1 mg/dL after 6 months; 49.0 mg/dL after 11 months).