Introduction
This article reports reported a case of chronic watery nonbloody diarrhea of rare etiology.
Case data
Male, 50 years old, Presented with chronic watery, non-bloody diarrhea for 4 months (up to 10 times daily) with weight loss. Past history: thymoma was first diagnosed 7 years ago, and histological examination after resection showed positive margins. There was no macroscopic residual disease or vascular invasion.
The patient did not receive any adjuvant therapy and developed a recurrent Masaoka-Koga stage IVa thymoma with pleural, pericardial and pulmonary infiltrates that required further resection, Chemotherapy (3 cycles of cisplatin, doxorubicin, and cyclophosphamide) and radiotherapy (54 Gy dose in 30 doses) were administered. There was no evidence of mediastinal lymph node involvement and distant hematogenous metastasis. Histopathology showed the presence of multiple nodules with a mixture of WHO types B1 and B2, but predominantly type B1 thymoma. PatientStarted after thymoma recurrencediarrhea , without any features suggestive of other autoimmune diseases associated with thymoma, including myasthenia gravis.
Physical examination and preliminary laboratory tests were unremarkable. Fecal cultures were negative for bacterial, viral, and parasitic infections. Abdominal CT, colonoscopy, and colon biopsy results are shown in Figure 1, and immunofluorescence staining results are shown in Figure 2.
Fig.1 >
Figure 2
What should be the diagnosis?
Analysis Diagnostics
Diagnosis: Thymoma-associated autoimmune enteropathy.
Abdominal CT showed thickening and fat accumulation in the small bowel and colon (Figure 1a). Correspondingly, colonoscopy revealed mild patchy erythematous colitis in the rectum and sigmoid colon (Fig. 1b). Histologically, colonic biopsy showed active colitis with marked regenerative changes. Goblet cells were markedly absent and there was significant apoptosis, which is typical of autoimmune enteropathy (Figure 1c).
The patient serum was cultured with frozen sections of normal small intestinal mucosa, and immunofluorescence showed strong staining of human IgA and IgG, and the distribution of goblet cells (Fig. 2). Therefore, a diagnosis of thymoma-associated autoimmune enteropathy was made.
Expanding Knowledge: Thymoma-Associated Autoimmune Bowel Disease
In up to 30% of patients, thymoma is associated with a concomitant autoimmune disease, possibly due to defective immune regulation. The differential diagnosis of thymoma-associated autoimmune diseases that cause diarrhea includes autoimmune enteropathy and Good syndrome (thymoma-associated hypogammaglobulinemia).
Thymoma-associated autoimmune enteropathy is very rare, and only 5 cases. Recommended diagnostic criteria include chronic diarrhea lasting more than 6 weeks, malabsorption, and abnormal small bowel histology (blunted villi, deep crypt lymphocytosis, minimal intraepithelial lymphocytosis, and increased crypt apoptotic bodies). A range of changes were observed in the colon, including increased mononuclear inflammatory infiltrates, active inflammation (including neutrophilic cryptitis and microabscesses), intraepithelial lymphocytosis, and increased crypt epithelial apoptosis. Chronic changes include crypt structural deformation and Paneth cell metaplasia. The presence of anti-enterocyte or anti-goblet antibodies is supportive, but the sensitivity and specificity of these markers is unclear.
Steroids are first-line treatments for autoimmune bowel disease, but up to 90 % of cases may require furtherimmunosuppression (azathioprine, cyclosporine, tacrolimus, or infliximab) . for thymomaIn people with autoimmune bowel disease, removal of the thymoma may also improve symptoms.
References: Gu B, Liu C, McKenzie et al. Gastrointestinal: Autoimmune enteropathy associated with thymoma[J]. J Gastroenterol Hepatol. 2021 Oct 10. doi: 10.1111/jgh.15692.