fA' IN'
Collagenous Colitis in a Patient with Systemic Sclerosis: A Rare Entity Fuat Ekiz, MD; Sahin Qoban, MD; Berna Savas, MD; Deniz Goren, MD; Arzu Ensari, MD; and Necati Ormeci, MD
Collagenous colitis has been associated with autoimmune diseases. Co-occurence of systemic sclerosis and collagenous colitis is particularly rare. Herein, we described a 65-year-old woman with systemic sclerosis whose diarrhea and abdominal cramping were due to collagenous colitis. We have reviewed the clinical and histopathological features of collagenous colitis with regard to its concomitance with systemic sclerosis. Key words: collogenous colitis * systemic sclerosis U autoimmunity © 2007. From the Departments of Gastroenterology (Ekiz and G6ren, research fellows; Ensari and Ormeci, professors) and Pathology (Savas, specialist) Ankara University Medical School, Ankara, Turkey and Department of Gastroenterology, Kirikkale Yuksek lhtisas Hospital, Kirikkale, Turkey (Coban, specialist). Send correspondence and reprint requests for J NotI Med Assoc. 2007;99:681-682 to: Dr. Sahin Qoban, 39. Cd. Pembe K6sk Apt. 1/4, Qukurambar Mah. Balgat, Ankara, Turkey, 06520; phone: +90 312 286 68 03; fax: +90 312 310 6371; e-mail:
[email protected]
INTRODUCTION C ollagenous colitis is an inflammatory disease of unknown etiology characterized by chronic diarrhea and a thickened band of subepithelial collagen. Since it was first described in 1976 by C.G. Lindstrom,' a lot of studies have demonstrated the possible association of collagenous colitis with autoimmune diseases2-4 such as Sjogren's syndrome,45 rheumatoid arthritis,56 systemic lupus erythematosus5 and psoriatic arthritis.7 However, systemic sclerosis8' 0 associated with collagenous colitis has rarely been reported before. Here, we describe a patient who had collagenous colitis with systemic sclerosis.
CASE REPORT A 65-year-old woman who had been followed with a diagnosis of systemic sclerosis since 2001 was admitted to our clinic with a complaint of diarrhea and weight loss. She developed abdominal cramps and watery diarrhea 20-30 times a day for two months. There was no blood or mucus in the stool. She had lost 4 kg since then. On admission to our department, physical examinations were as follows: body temperature was 37.60C, blood JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
pressure 120/80 mmHg and pulse rate 68/min. Other remarkable findings on physical examination were a diminished skin turgor-tonus and slight abdominal tenderness on palpation. The skin overlying her hands and fingers was thickened. Laboratory investigation showed an erythrocyte sedimentation rate (ESR) of 52 mm/h and C-reactive protein (CRP) of 116 mg/dL. Antinuclear antibody was positive. Stool microscopy and cultures were normal. Esophageal manometry revealed decreased contraction amplitudes consistent with esophageal involvement of scleroderma. Endoscopical examinations of the stomach, duodenum and colon were normal. Blinded biopsies from the colon demonstrated a thickened collagenous subepithelial band distributed throughout the colon in a patchy fashion. The collagen band measured 50 gm in thickness (Figure 1). Lamina propria contained a mononuclear inflammatory infiltrate consisting of plasma cells and lymphocytes (Figure 2). A focal increase in intraepithelial lymphocytes was also observed in the surface epithelium. All the above findings were considered as diagnostic for collagenous colitis. A combination of loperamide and sulfasalazine commenced along with Dpenicillamine, which she had already been taking, dramatically Feduced the frequency of stool movements after two weeks. Laboratory parameters of inflammation returned to normal after one month of treatment. Her complaints disappeared at the end of four months, and loperamide and sulphasalazine were stopped. She is still on D-penicillamine treatment.
DISCUSSION Systemic sclerosis is a chronic multisystemic disorder of unknown etiology characterized clinically by thickening of the skin caused by accumulation of connective tissue and by structural and functional abnormalities in visceral organs, including the gastrointestinal tract, lungs, heart and kidneys.3 Preliminary criteria for the classification of systemic sclerosis were developed by the American College of Rheumatology.3 Our patient had sclerodermatous involvement proximal to the digits, sclerodactyly and bibasilar pulmonary fibrosis. According to these criteria, our patient was diagnosed as systemic sclerosis. VOL. 99, NO. 6, JUNE 2007 681
COLLAGENOUS COLITIS AND SYSTEMIC SCLEROSIS
Figure 1. Subepithelial a thick layer of collagen band (H&E x200)
_ AI.1111.. Etiopathogenesis of collagenous colitis is still unknown. It has female predominance (9:1 ratio) and high prevalence in the late sixth or early seventh decade. The main clinical feature of collagenous colitis is chronic watery diarrhea, with abdominal pain and/or flatulence, but with normal endoscopical and radiological appearances. Affected patients are generally well and without any nutritional impairment. Watery diarrhea, up to 20 bowel movements per day, is a consistent feature, whereas abdominal pain, flatulence, abdominal distension, nausea and vomiting are variable.4 Collagenous colitis has been considered a consequence of a microscopic colitis when fibroblasts' response to an infection or inflammatory responsive is pronounced. Histologically, the surface epithelial injury seen in the colon in collagenous colitis is reminiscent of the lesion seen in the small intestine in celiac disease.8 Collagenous colitis is characterized by a thickened subepithelial collagen layer, the upper limit of which is normally 6-10 ,um.4 In our patient, the thickness of this layer was 50 gm. The disease is also histologically characterized by a chronic inflammatory cell infiltration of the lamina propria of variable intensity and damage to the surface epithelium, accompanied by increased intraepithelial lymphocytes. A number of autoimmune diseases were reported to be associated with collagenous colitis, mostly thyroid diseases and rheumatologic diseases. Two cases of scleroderma (one in a juvenile patient) and one case with CREST syndrome associated with collagenous colitis were reported previously.8'10 Gastrointestinal involvement of systemic sclerosis should be considered in differential diagnosis of collagenous colitis in patients with systemic sclerosis. In the colonic involvement of systemic sclerosis, submucosal collagen deposition is found, whereas subepithelial deposition is the characteristic feature of collagenous colitis. Colonic involvement results in chronic constipation and obstipation in patients with systemic sclerosis. If patients with systemic sclerosis have diarrhea, one common cause is small-intestinal bacterial overgrowth. Bacterial overgrowth is the most common cause of malabsorption
682 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
Figure 2. High magnification of subepithelial collagen band (H&E x400)
. in systemic sclerosis, as well. Malabsorption is a common feature in systemic sclerosis secondary to small intestinal involvement; however, collagenous colitis does not involve the small intestine and cause malabsorption." Herein, we described a rare case with collagenous colitis and systemic sclerosis. The association of systemic sclerosis and collagenous colitis can actually be more frequent than we currently know, as the diagnosis of collagenous colitis requires specific consideration and colonoscopy with blinded biopsies. Both diseases possibly share similar autoimmune mechanisms, which further increases the likelihood of this association. Therefore, collagenous colitis should also be kept in mind in the differential diagnosis of chronic diarrhea seen in patients with systemic sclerosis and colonoscopy with blinded biopsies should be performed in the work-up of these patients.
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1. Lindstrom CG. Collagenous colitis with watery diarrhea. A new entity? Pathol Eur. 1976;1 1:87-89. 2. Wang KK, Perrault J, Carpenter HA, et al. Collagenous colitis: a clinicopathologic correlation. Mayo Clin Proc. 1987;62:665-671. 3. Charles C, Clements P, Furst DE. Systemic sclerosis: hypothesis-driven treatment strategies. Lancet. 2006;367(9523):1683-91. 4. Pimentel RR, Achkar E, Bedford R. Collagenous colitis. A treatable disease with an elusive diagnosis. Dig Dis Sci. 1995;40:1400-1404. 5. Bohr J, Tysk C, Eriksson S, et al. Collogenous colitis: a retrospective study of clinical presentation and treatment in 163 patients. Gut. 1996;39:846-851. 6. Wengrower D, Pollak A, Okon E, et al. Collagenous colitis and rheumatoid arthritis with response to sulfasalazine. J Clin Gostroenterol. 1987;9:456-460. 7. Taccari E, Spada A, Giuliani A, et al. Co-occurrence of Psoriatic arthritis with collagenous colitis: clinicopathologic findings of a case. Clin Rheumatol. 2002;21:335-38. 8. Widgren S, Jlidi R, Cox JN. Collagenous colitis, histologic, morphometric, immunohistochemical and ultrastructural studies. Report of 21 cases. Virchows Arch Pathol Anat. 1988;413:287-296. 9. Esselinckx W, Bernard R, Colin JF, et al. Juvenile scleroderma and collagenous colitis. The first case. J Rheumotol. 1991;16:834-836. 10. Kenesi-Laurent MA, Chapelon-Abric C- Fattah ZA, et al. The first case of CREST syndrome associated with collagenous colitis. J Rheumotol. 199 1 1 8:1756-1 757. 11. Jaovisidha K, Csuka ME, Almagro UA, et al. Severe gastrointestinal involvement in systemic sclerosis: report of five cases and review of the literature. Semin Arthritis Rheum. 2004;34:689-702. 1
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