Collagenous Colitis in Systemic Sclerosis
Collagenous colitis (CC) is an inflammatory bowel condition of unknown etiology. Systemic sclerosis (SSc) has been associated with CC in a few cases, but it is not clear whether CC could be considered an unusual manifestation of SSc or an independent condition. Here we present a case of SSc-associated CC and compare routine histology and immunofluorescence studies for allograft inflammatory factor 1 and caveolin 1 expression with other cases of CC and healthy controls. All CC biopsies showed characteristic sublaminal collagen accumulation and a decrease of caveolin 1 expression, this latter finding consistent with and common in any fibrotic reaction. In contrast, the expression of allograft inflammatory factor 1 was increased only in the SSc-CC specimen, suggesting a distinct pathogenesis. A literature review revealed 6 previously reported cases of SSc-CC with common clinical features. These observations suggest that CC should be suspected as a rare gastrointestinal complication of SSc and that clinicians should be aware of the possibility in SSc patients developing watery diarrhea.
Collagenous colitis (CC) is an inflammatory condition of the large bowel of unknown etiology, mainly affecting middle-aged and elderly women. It is characterized, clinically, by chronic watery and nonbloody diarrhea, abdominal pain, and mild weight loss. Colonic mucosa shows characteristic histopathologic findings, namely, a thickened subepithelial collagen layer of 10 μm or greater, intraepithelial lymphocytes, inflammatory infiltrate in the lamina propria, and epithelial flattening and detachment. Together with lymphocytic colitis (LC), CC is considered 1 of the 2 subtypes of microscopic colitis, well-described condition of chronic watery diarrhea. Both conditions have similar clinical and macroscopic features with distinct microscopic findings, the LC being characterized by a markedly increased number of intraepithelial lymphocytes without a thickened subepithelial collagen band.
Microscopic colitis is often associated with autoimmune diseases, and comorbidity with several rheumatic diseases has been reported. Systemic sclerosis (SSc) has been associated with CC in a number of cases and with LC in 1 case, this latter reporting an interchange between CC and LC. Such cases indicate a possible association or alternatively an unusual manifestation of SSc in the gut. Mechanisms have been proposed to explain the collagen deposition occurring in CC, some of which also have been described in SSc. In addition to increased extracellular matrix deposition, the histopathology of SSc is characterized, at least in the lung and skin, by specific histopathologic findings such as increased expression of allograft inflammatory factor 1 (AIF-1) in the infiltrate and the decreased expression of caveolin 1 (CAV-1) in tissue fibroblasts. We present a case of SSc-associated CC, compare the immunohistochemistry, and AIF-1 and CAV-1 immunofluorescence (IF) expression in colon biopsy specimens of the SSc-CC case with paraffin-embedded sections obtained from 3 patients with CC and 3 healthy controls (HCs). We also review previously 6 well-described cases of SSc-CC from the English literature.
Abstract and Introduction
Abstract
Collagenous colitis (CC) is an inflammatory bowel condition of unknown etiology. Systemic sclerosis (SSc) has been associated with CC in a few cases, but it is not clear whether CC could be considered an unusual manifestation of SSc or an independent condition. Here we present a case of SSc-associated CC and compare routine histology and immunofluorescence studies for allograft inflammatory factor 1 and caveolin 1 expression with other cases of CC and healthy controls. All CC biopsies showed characteristic sublaminal collagen accumulation and a decrease of caveolin 1 expression, this latter finding consistent with and common in any fibrotic reaction. In contrast, the expression of allograft inflammatory factor 1 was increased only in the SSc-CC specimen, suggesting a distinct pathogenesis. A literature review revealed 6 previously reported cases of SSc-CC with common clinical features. These observations suggest that CC should be suspected as a rare gastrointestinal complication of SSc and that clinicians should be aware of the possibility in SSc patients developing watery diarrhea.
Introduction
Collagenous colitis (CC) is an inflammatory condition of the large bowel of unknown etiology, mainly affecting middle-aged and elderly women. It is characterized, clinically, by chronic watery and nonbloody diarrhea, abdominal pain, and mild weight loss. Colonic mucosa shows characteristic histopathologic findings, namely, a thickened subepithelial collagen layer of 10 μm or greater, intraepithelial lymphocytes, inflammatory infiltrate in the lamina propria, and epithelial flattening and detachment. Together with lymphocytic colitis (LC), CC is considered 1 of the 2 subtypes of microscopic colitis, well-described condition of chronic watery diarrhea. Both conditions have similar clinical and macroscopic features with distinct microscopic findings, the LC being characterized by a markedly increased number of intraepithelial lymphocytes without a thickened subepithelial collagen band.
Microscopic colitis is often associated with autoimmune diseases, and comorbidity with several rheumatic diseases has been reported. Systemic sclerosis (SSc) has been associated with CC in a number of cases and with LC in 1 case, this latter reporting an interchange between CC and LC. Such cases indicate a possible association or alternatively an unusual manifestation of SSc in the gut. Mechanisms have been proposed to explain the collagen deposition occurring in CC, some of which also have been described in SSc. In addition to increased extracellular matrix deposition, the histopathology of SSc is characterized, at least in the lung and skin, by specific histopathologic findings such as increased expression of allograft inflammatory factor 1 (AIF-1) in the infiltrate and the decreased expression of caveolin 1 (CAV-1) in tissue fibroblasts. We present a case of SSc-associated CC, compare the immunohistochemistry, and AIF-1 and CAV-1 immunofluorescence (IF) expression in colon biopsy specimens of the SSc-CC case with paraffin-embedded sections obtained from 3 patients with CC and 3 healthy controls (HCs). We also review previously 6 well-described cases of SSc-CC from the English literature.