Scleroderma Presenting As Chronic Intestinal Pseudo-Obstruction

A CASE TO REMEMBER

Scleroderma Presenting as Chronic Intestinal Pseudo-Obstruction

by Matthew M. Baichi, Razi M. Arifuddin, Parvez S. Mantry

Scleroderma is a systemic disease characterized by deposition of collagen and other matrix elements in the skin as well as multiple internal organs. Clinically significant gastrointestinal involvement occurs in approximately 50% of all patients with the disease. The esophagus is the most common site of involvement followed by ano-rectum, small bowel, colon, and stomach. Following is a case of diffuse gastrointestinal scleroderma presenting as chronic intestinal pseudo-obstruction.

INTRODUCTION CASE REPORT cleroderma is a systemic disease characterized by The patient is a 52-year-old female with a 30-year his- the deposition of excessive collagen and other tory of GERD, 10-year history of chronic constipation, Smatrix elements in the skin as well as multiple and questionable four-year history of Crohn’s disease. internal organs. Scleroderma can be classified into dif- The patient was in her usual state of health until three fuse cutaneous disease and limited cutaneous disease months prior to current admission. At that time, she (1). Limited cutaneous disease is characterized by skin was hospitalized for nausea and vomiting. Work up involvement limited to the hands, face, feet, and fore- revealed non-mechanical small bowel obstruction that arms; it includes the CREST variant (calcinosis, Ray- resolved with conservative management. She was re- n a u d ’s, esophageal dysmotility, sclerodactyly, and hospitalized six times for similar complaints. Each telangiectasia). Diffuse cutaneous disease is character- admission revealed non-mechanical small bowel ized by more diffuse skin involvement as well as early obstruction. Her last admission, however, revealed an and diffuse visceral involvement including diffuse gas- ileal stricture, which was subsequently removed. The trointestinal disease. Clinically significant gastroin- patient now presents to our hospital with complaints of testinal involvement occurs in approximately 50% of nausea, vomiting of bilious emesis, bloating, abdomi- all patients with scleroderma (2). The esophagus is the nal distention, increased belching, and decreased most common site of involvement followed in order by appetite. She denies dysphagia, abdominal pain, ano-rectum, small bowel, colon and stomach. Several melena, hematochezia, or diarrhea. She denies a his- recent reviews of the gastrointestinal manifestations of tory of hepatitis, pancreatitis, or gallbladder disease. scleroderma have been written (3–5). Described here Since her first hospitalization three months ago she is a case of diffuse gastrointestinal scleroderma pre- has lost 25 pounds. Social history is remarkable for senting as chronic intestinal pseudo-obstruction. 2 packages of cigarettes per day for ten years. Family history reveals no gastrointestinal disease. Review of Matthew M. Baichi, M.D., Razi M Arifuddin, M.D. and systems is remarkable for chronic numbness and cold- Parvez S Mantry, M.D., Department of Medicine, ness in fingers with discoloration when cold. Digestive Disease Division, University of Rochester, The patient is a moderately cachectic white Rochester, NY. female. Vital signs are normal except for mild tachy-

PRACTICAL GASTROENTEROLOGY • AUGUST 2004 53 Scleroderma Presenting as Chronic Intestinal Pseudo-Obstruction A CASE TO REMEMBER

cardia. Abdominal exam reveals normal bowel sounds, esophageal dysmotility (longstanding GERD) and Ray- marked distention, tympanic percussion, soft and non- n a u d ’s phenomenon. Recent ileal biopsy shows patchy tender palpation, no guarding or rebound, no hernia. atrophy and fibrosis of the muscularis with preferential Rectal exam reveals external hemorrhoids with brown involvement of the circular layer. These findings are stool positive for occult blood. Rheumatologic exam consistent with scleroderma. Histologically, the most reveals mildly thickened and cool fingers, no inflamed significant changes occur in the muscularis layer of joints, normal skin. Neurologic exam reveals normal bowel. Atrophy and fragmentation of smooth muscle muscle tone and strength. Blood count is remarkable occurs. Initially the atrophy is patchy and later becomes for white count 14.6 with normal differential. Chem- more extensive with associated fibrosis (10,11). These istry profile is remarkable for potassium 2.5. Liver changes are more pronounced in the circular smooth profile, amylase, and lipase are normal. ESR 17, ANA muscle layer (12), and atrophy usually exceeds fibrosis 1:40, speckled. Anticentromere Ab and Anti Scl 70 Ab (13). Subsequent small bowel imaging and esophageal are negative. Obstruction series shows multiple dilated manometry confirmed the diagnosis. small bowel loops with relative collapse of large bowel, air fluid levels within small bowel, and no intra-peritoneal free air. Pathology of terminal ileal DISCUSSION resection (from previous hospitalization) reveals The following discussion will focus on the abnormal patchy marked atrophy and fibrosis of muscularis pro- motility, clinical presentation, and diagnosis of sclero- pria with preferential involvement of circular layer, derma in each segment of the alimentary tract. vacuolar degeneration of muscle fibers is present, no The esophagus is the most commonly affected inflammatory changes of Crohn’s are seen. Esophageal organ in the gastrointestinal tract. Normal esophageal manometry reveals lower esophageal sphincter resting manometry shows high amplitude, ordered peristaltic pressure in lower range of normal with esophageal waves and a high resting pressure of the lower body aperistalsis. Small bowel radiographs reveal esophageal sphincter (LES). On swallowing, the LES moderate mega-duodenum with “hide-bound” config- relaxes to baseline, and the LES relaxation preceeds uration of mucosal folds throughout small intestine, no the arrival of the peristaltic wave. Manometry studies structure. Upper endoscopy reveals erosive esophagitis in early scleroderma show increased speed of the peri- and moderate hiatel hernia. Colonoscopy reveals staltic wave, incoordination of the arrival of the peri- neoileo-colonic anastamosis that is friable and ulcer- staltic wave with LES relaxation, and failure to the ated. Biopsy of anastamosis shows granulation tissue LES to relax to gastric baseline. Later findings include and lamina propria compatible with anastamotic site. decreased amplitude of peristalsis and low LES resting pressure progressing to aperistalsis in the smooth muscle portion of the esophagus with absent LES resting DIAGNOSIS pressure (14,15). Gastroesophageal reflux disease Our patient presents with chronic intestinal pseudo- (GERD) is the most significant clinical condition. obstruction (6–9). This is a rare condition characterized GERD occurs as a result of both the decreased LES by recurrent episodes of intestinal obstruction in the resting pressure, which allows an increased number of absence of any mechanical defect. Symptoms include reflux events, and the poor peristalsis, which delays nausea, vomiting, abdominal distention, bloating, acid clearance (16,17). The complications of long- abdominal pain, and constipation. The differential diag- standing GERD include candida esophagitis, erosive nosis can be divided into myopathic vs neuropathic dis- esophagitis, stricture, Barret’s esophagus, and aspira- orders. Myopathic conditions include infiltrative tion. Diagnostic evaluation should therefore include processes such as scleroderma and amyloidosis, famil- upper endoscopy to rule out complications. ial conditions such as visceral myopathies, and neuro- The small intestine is also commonly involved. In logic conditions such as myotonic and other dystro- the normal small bowel, a cyclic pattern of contractile phies. In this case, the history is significant for (continued on page 56)

54 PRACTICAL GASTROENTEROLOGY • AUGUST 2004 Scleroderma Presenting as Chronic Intestinal Pseudo-Obstruction A CASE TO REMEMBER

(continued from page 54) activity occurs at regular intervals. This is called the 3 . Rose S, Young MA, Reynolds JC. Gastrointestinal disorders and systemic disease, part 1. Gastroenterol Clin North Am, migrating myoelectric complex (MMC). The MMC 1 9 9 8 ; 2 7 : 5 6 3 - 5 9 4 . acts as “intestinal housekeeper” by clearing remnants 4 . Lock G, Holstege A, Lang B, et al. Gastrointestinal manifestations of progressive systemic sclerosis. Am J Gastroenterol, of digestion and preventing bacterial overgrowth (18). 1 9 9 7 ; 9 2 : 7 6 3 - 6 7 1 . Patients with scleroderma often lack this MMC. Clini- 5 . Sjogren RW. Gastrointestinal motility disorders in scleroderma. cally, chronic intestinal pseudoobstruction and malab- Arthritis Rheum, 1994; 37:1265-1282. 6 . Faulk DL, Anuras S, Christensen J. Chronic intestinal pseudo- sorbtion are seen. Malabsorbtion is the result of bacte- obstruction. Gastroenterol, 1 9 7 8 ; 7 4 : 9 2 2 - 9 3 1 . rial overgrowth (19). The H breath test is a noninva- 7 . Schuffler MD, Rohrmann CA, Chaffee RG, et al. Chronic intesti- 2 nal pseudoobstruction: a report of 27 cases and review of the lit- sive and reliable diagnostic procedure. A nonab- erature. Medicine, 1 9 8 1 ; 6 0 : 1 7 3 - 1 9 6 . sorbable carbohydrate such as lactulose is ingested and 8 . Schuffler MD. Chronic intestinal pseudo-obstruction syndromes. Med Clin North Am, 1 9 8 1 ; 6 5 : 1 3 3 1 - 1 3 5 8 . a premature rise in exhaled H2 suggests the presence of 9 . Colemont LJ, Camilleri M. Chronic intestinal pseudo-obstruction: intestinal bacteria. The diagnosis of chronic intestinal diagnosis and treatment. Mayo Clin Proc, 1 9 8 9 ; 6 4 : 6 0 - 7 0 . 1 0 . Rosson RS, Yesner R. Peroral duodenal biopsy in progressive sys- pseudoobstruction from scleroderma can be made with temic sclerosis. N Engl J Med, 1 9 6 5 ; 2 7 2 : 3 9 1 - 3 9 4 . small bowel barium imaging or biopsy (20,21). A 1 1 . Greenberger NJ, Dobbins WO, Buppert RD. Intestinal atony in “hide-bound” configuration of the small bowel is a progressive systemic sclerosis (scleroderma). Am J Med, 1 9 6 8 ; 4 5 : 3 0 1 - 3 0 8 . characteristic mucosal fold pattern in which there is a 1 2 . Stafford-Brady FJ, Kahn HJ, Ross TM, et al. Advanced sclero- relative decrease in the distance separating the valvu- derma bowel: complications and management. J Rheumatol, 1 9 8 8 ; 1 5 : 8 6 9 - 8 7 4 . lae connivents. This creates an accordion like appear- 1 3 . D’Angelo WA, Fries JF, Masi AT, at al. Pathologic observations ance. This finding is uniquely associated with sclero- in systemic sclerosis (scleroderma). Am J Med, 1 9 6 9 ; 4 6 : 4 2 8 - 4 4 0 . 1 4 . Blom-Bulow B, Sundstrom G, Jonson B, et al. Early changes in derma. Less common intestinal presentations include oesophageal function in progressive systemic sclerosis: a compar- pneumatosis cystoides intestinalis, small intestine ison of manometry and radiology. Clin Physiol, 1 9 8 4 ; 4 : 1 4 7 - 1 5 8 . 1 5 . Hamel-Roy J, Devroede G, Arhan P, et al. Comparative telangiectasia, and small bowel diverticula. Prokinetic esophageal and anorectal motility in scleroderma. G a s t r o e n t e r o l , drugs such as metachlopramide, erythromycin, and 1 9 8 5 ; 8 8 : 1 - 7 . octreotide are the treatments of choice. 1 6 . Zamost BJ, Hirschberg J, Ippoliti AF, et al. Esophagitis in scleroderma: prevalence and risk factors. Gastroenterol, 1 9 8 7 ; 9 2 : 4 2 1 - In the colon, the ano-rectum is commonly aff e c t e d . 4 2 8 . Manometry reveals an absent or diminished rectoanal 1 7 . Murphy JR, McNally P, Peller P et al. Prolonged clearance is the primary abnormal reflux parameter in patients with progressive inhibitory reflex (22). Also, colonic transit is prolonged systemic sclerosis and esophagitis. Dig Dis Sci, 1 9 9 2 ; 3 7 : 8 3 3 - 8 4 1 . (23) and the normal postprandial increase in rectosig- 1 8 . Code CE, Schlegel JF. The gastrointestinal interdigestive housekeeper: motor correlates of the interdigestive myoelectric complex moid motility is lost (24). Clinically, fecal incontinence of the dog. Proceedings of the Fourth International Symposium on and constipation are the most common presentations. Gastrointestinal Motility, Edited by EE Daniel, K Bowes, JAL Less common presentations include diarrhea, rectal pro- Gilbert, B Schofield, TK Schnitka, G Scott. Vancouver, Mitchell Press, 1974. lapse, spontaneous perforation, and colonic infarction. 1 9 . Vantrappen G, Janssens J, Hellemans J, et al. The interdigestive Radiographic evaluation of colonic involvement motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest, 1 9 7 7 ; 5 9 : 1 1 5 8 - 6 6 . includes barium enema, which may show characteristic 2 0 . Rohrmann CA, Ricci MT, Krishnamurthy S, et al. Radiologic and “wide mouth,” or “fish mouth” diverticula, which are histologic differentiation of neuromuscular disorders of the gastrointestinal tract: visceral myopathies, visceral neuropathies, and broad based true diverticula caused by the uneven dis- progressive systemic sclerosis. Am J Roentgenol, 1 9 8 4 ; 1 4 3 : 9 3 3 - tribution of atrophic muscularis (20). Tr e a t m e n t 9 4 1 . includes conservative measures such as increased fluid 2 1 . Schuffler MD, Beegle RG. Progressive systemic sclerosis of the gastrointestinal tract and hereditary hollow visceral myopathy: and fiber intake. Prokinetic agents can be used for Two distinguishable disorders of intestinal smooth muscle. G a s - colonic inertia. ■ t r o e n t e r o l , 1 9 7 9 ; 7 7 : 6 6 4 - 6 7 1 . 2 2 . Leighton JA, Valdovinos MA, Pemberton JH, et al. Anorectal dys- function and rectal prolapse in progressive systemic sclerosis. D i s References Colon Rectum, 1 9 9 3 ; 3 6 : 1 8 2 - 1 8 5 . 1. LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic 2 3 . B a silisco G, Barbera R, Vanoli M, et al. Delayed colonic transit sclerosis): classification, subsets and pathogenesis (editorial). J in constipated patients with progressive systemic sclerosis (PSS). Rheumatol, 1 9 8 8 ; 1 5 : 2 0 2 - 2 0 5 . Gastroenterol, 1992;102:A421. 2 . Cohen S, Laufer I, Snape WJ, et al. The gastrointestinal manifes- 24. Battle WM, Snape WJ, Wright S, et al. Abnormal colonic motil- tations of scleroderma: Pathogenesis and management. G a s t r o e n - ity in progressive systemic sclerosis. Ann Intern Med, terol, 1 9 8 0 ; 7 9 : 1 5 5 - 1 6 6 . 1981;94:749-752.

56 PRACTICAL GASTROENTEROLOGY • AUGUST 2004