Scleroderma, meaning "hard skin," refers to a heterogeneous group of disorders in which patients often experience skin thickening and fibrosis. In the systemic form of the disease, systemic sclerosis (SSc), internal organ involvement and vasculopathy are prominent features, with gastrointestinal (GI) involvement especially common and affecting the esophagus in approximately 90% of patients. Symptoms and clinical disorders that reflect GI involvement in the cardinal pathogenic features of scleroderma (ie, vasculopathy, immune-mediated inflammation, and neuropathy) emanate from every segment of the GI tract: dysphagia and gastroesophageal reflux disease from the esophagus; gastroparesis and gastric antral vascular ectasia from the stomach; telangiectasia, pseudo-obstruction, and small intestinal bacterial overgrowth from the small intestine; constipation and colonic dilatation; and fecal incontinence due to thinning of the anal sphincters. Impaired motility is a cardinal feature reflective of atrophy of smooth muscle and scattered areas of fibrosis throughout the GI tract and results in impaired transit, stasis, and luminal dilation leading to complications such as small intestinal bacterial overgrowth, megacolon, and pneumatosis cystoides intestinalis. Symptoms often correlate poorly with the underlying GI pathology and functional impairment in SSc, and associations between GI manifestations, SSc disease features, and autoantibody titers are variable. High-quality SSc-specific evidence regarding the impact of various therapies on GI manifestations remains limited, and management recommendations for most GI manifestations are largely derived from experience in non-SSc patients. In caring for the patient with SSc with GI problems, a gastroenterologist should be aware of the particularities of clinical presentation and natural history of GI disease in this patient population, maintain diagnostic vigilance, and tailor their therapeutic approach mindful of the SSc disease process.

Hirschsprung's disease (HSCR) is a congenital disorder of the distal intestine characterized by aganglionosis of the enteric nervous system. While defective migration of neural crest-derived precursors is a well-established hallmark, how the intestinal microenvironment contributes to impaired neuronal support remains poorly understood. Here, we combined histochemical analyses of human HSCR colon with functional assays to investigate the role of muscularis macrophages (MMs) and a miR-93-5p-AHNAK pathway in regulating enteric neurons. Using immunohistochemistry and immunofluorescence on ganglionic and aganglionic segments, we mapped the density, spatial distribution, and phenotype of MMs, and quantified the expression of miR-93-5p and its predicted target AHNAK. In vitro, polarized M2-like macrophages were cocultured with enteric neuronal cell lines to assess neuronal migration, proliferation, and apoptosis. Gain-of-function and loss-of-function approaches for miR-93-5p, together with a dual-luciferase reporter assay, were used to validate AHNAK as a direct target. M2-like MMs (CD163+/CD206+) were abundant around myenteric ganglia in ganglionic colon but reduced in aganglionic segments, where AHNAK expression was increased. M2 macrophages enhanced neuronal migration and proliferation and protected against apoptosis, whereas disruption of the miR-93-5p-AHNAK axis impaired these neuro-supportive effects. Together, our data identify a muscularis macrophage-miR-93-5p-AHNAK axis that supports enteric neurons and demonstrates that loss of M2-like MMs and dysregulated miR-93-5p-AHNAK signaling compromise neuronal homeostasis in HSCR. These findings add a histochemical microenvironment perspective to HSCR pathogenesis and support a candidate neuroimmune pathway for restoring immune-neuronal balance, pending in vivo and clinical validation.

Toxic megacolon is a life-threatening condition characterized by acute colonic dilation and systemic toxicity, most commonly associated with inflammatory or infectious colitis. However, ischemic colitis represents an important and underrecognized etiology in elderly patients with significant vascular comorbidities. We report the case of a 71-year-old male with a history of long-standing hypertension, type 2 diabetes mellitus, and chronic kidney disease, receiving losartan, nifedipine, and insulin therapy, who presented with five days of progressive diffuse abdominal pain, severe distension, obstipation, and systemic deterioration. On admission, he was febrile, tachycardic, metabolically acidotic, and demonstrated leukocytosis, elevated inflammatory markers, hyperlactatemia, and renal dysfunction. Initial management included aggressive intravenous fluid resuscitation, broad-spectrum antibiotics, electrolyte correction, and bowel rest. Computed tomography without intravenous contrast revealed severe diffuse colonic dilation with a maximal cecal diameter of 14 cm, without mechanical obstruction or perforation. Given the extreme dilation, systemic toxicity, and early organ dysfunction, urgent surgical intervention was performed within hours of admission. Exploratory laparotomy demonstrated diffuse colonic dilation with mural thinning and serosal inflammatory changes, and total colectomy with end ileostomy was undertaken. Histopathological examination confirmed extensive ischemic colitis with mucosal and submucosal necrosis, without evidence of inflammatory bowel disease or pseudomembranous colitis. The patient required short-term vasopressor support postoperatively but recovered without major complications and was discharged on postoperative day 12. This case emphasizes that toxic megacolon may occur in elderly patients without prior colonic disease and highlights extreme cecal dilation as a critical indicator for early surgical management to improve survival.