Free perforation of the small intestine in collagenous sprue

A 67-year-old man with celiac disease developed recurrent diarrhea,profound weakness and weight loss, with evidence of marked protein depletion.His clinical course was refractory to a strict gluten-free diet and steroid therapy.Postmortem studies led to definition of unrecognized collagenous sprue that caused ulceration and small intestinal perforation.Although PCR showed identical monoclonal T-cell populations in antemortem duodenal biopsies and postmortem jejunum,careful pathological evaluation demonstrated no frank lymphoma.Rarely,overt or even cryptic T-cell lymphoma may complicate collagenous sprue,however, small intestinal ulcers and perforation may also develop independently.The dramatic findings here may reflect an underlying or early molecular event in the eventual clinical appearance of overt T-cell lymphoma.

Update on collagenous sprue

Collagenous sprue has traditionally been defined as a small intestinal mucosal disorder characterized by persistent diarrhea, severe malabsorption with multiple nutrient def iciencies and progressive weight loss. Pathologically, a severe to variably severe "flattened" mucosal biopsy lesion with distinctive sub-epithelial deposits in the lamina propria region is detected. Histochemical stains and ultrastructural studies have conf irmed that these deposits contain collagens. Often, an initial diagnosis of celiac disease is considered but no continued response to treatment with a gluten-free diet occurs. Recent reports indicate an intimate relationship between collagenous sprue and celiac disease, sometimes with concomitant T-cell enteropathy. In addition, permanent disappearance of these deposits after resection of a localized colon cancer suggested that this disorder could actually represent a paraneoplastic morphologic marker of an occult malignancy. Studies showing either gastric or colonic involvement (or both) with this unusual collagenous inflammatory mucosal process may also reflect a far more extensive and heterogeneous process than previously appreciated.

Complications of collagenous colitis

Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue （or collagenous enteritis） may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn＇s disease, may evolve from coUagenous colitis. Submucosal ＂dissection＂, colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease.

Spontaneous free perforation of the small intestine in adults

Spontaneous free perforation of the small intestine is uncommon, especially if there is no prior history of visceral trauma. However, free, even recurrent, perforation may complicate a defined and established clinical disorder, such as Crohn’s disease. In addition, free perforation may be the initial clinical presentation of an occult intestinal disorder, such as a lymphoma complicating celiac disease, causing diffuse peritonitis and an acute abdomen. Initial diagnosis of the precise cause may be difficult, but now has been aided by computerized tomographic imaging. The site of perforation may be helpful in defining a cause (e.g., ileal perforation in Crohn’s disease, jejunal perforation in celiac disease, complicated by lymphoma or collagenous sprue). Urgent surgical intervention, however, is usually required for precise diagnosis and treatment. During evaluation, an expanding list of other possible causes should be considered, even after surgery, as subsequent management may be affected. Free perforation may not only complicate an established intestinal disorder, but also a new acute process (e.g., caused by different infectious agents) or a longstanding and unrecognized disorder (e.g., congenital, metabolic and vascular causes). Moreover, new endoscopic therapeutic and medical therapies, including use of emerging novel biological agents, have been complicated by intestinal perforation. Recent studies also support the hypothesis that perforation of the small intestine may be genetically-based with different mutations causing altered connective tissue structure, synthesis and repair.