Digestive Diseases and Sciences, Vol. 35, No. 2 (February 1990), pp. 257-260

CASE REPORT

Collagenous Colitis in Setting of Nonsteroidal Antiinflammatory Drugs and Antibiotics F R A N C I S M. G I A R D I E L L O , MD, F. C H R I S T I A N H A N S E N III, MD, A U D R E Y J. L A Z E N B Y , MD, D A V I D B. H E L L M A N , MD, F R A N C I S D. M I L L I G A N , MD, T H E O D O R E M. B A Y L E S S , MD, and J O H N H. Y A R D L E Y , MD KEY WORDS: collagenous colitis; nonsteroidal antiinflammatory drugs.

Collagenous colitis is a newly recognized diarrheal disorder of unknown etiology (1). Over 80% of patients are middle-aged w o m e n with no other known predisposing factors (2). We report unusual presentations of collagenous colitis in two men in whom there was closely linked use of nonsteroidal antiinflammatory drugs and antibiotics. CASE R E P O R T S Patient 1. A 60-year-old white man was hospitalized with six weeks of five watery bowel movements per day and two weeks of fever. The patient took enalapril and metolazone for hypertension, and allopurinol and indomethacin for gout. Nine months before, his bowel habits changed from one formed stool per day to two soft bowel movements per day. Ten weeks before, while traveling in Bulgaria, the patient developed sinusitis and received an unknown antibiotic for two days. Two weeks later he had acute epigastric pain attributed to pancreatitis. While recovering, he developed acute painful swelling of the right wrist and received indomethacin 50 mg twice a day. He soon developed five watery bowel movements a day. Stool cultures for enteric pathogens, examination for ova and parasites, and barium studies were negative. The patient failed to improve after two days of metronidazole and was admitted with fever and leukocytosis. During hospitalization, sigmoidoscopy revealed pseudomembranes (Figure IA) confirmed histopathologManuscript received December 19, 1988; revised manuscript received May 30, 1989; accepted November 2, 1989. From the Department of Medicine, Divisions of Gastroenterology and Rheumatology, and The Department of Pathology, The Johns Hopkins University School of Medicine. Supported in part by a research grant from the National Foundation for Ileitis and Colitis. Dr. Lazenby is the recipient of a fellowship from the National Foundation of Ileitis and Colitis. Address for reprint requests: Dr. Francis M. Giardiello, The Meyerhoff Digestive Disease InflammatoryBowel Disease Center, 600 North Wolfe Street, Baltimore, Maryland 21205.

ically (Figure 1B). Cultures for C. difficile and assays for C. difficile toxins A and B were negative. Arthrocentesis of the right wrist demonstrated no crystals, few leukocytes, and no Yersinia on culture. Cholestyramine for four days gave no improvement, but the patient promptly defervesced on oral vancomycin. However, the diarrhea continued, and colonoscopy one week later revealed resolution of pseudomembranes (Figure 1C), and biopsies showed collagenous colitis (Figure ID). The histopathologic features of collagenous colitis were seen in multiple biopsies throughout the colorectum (ascending colon through rectum), and included a thickened subepithelial collagen layer (maximum of 50-70 Ixm), increased lamina propria mononuclear cells, and prominent intraepithelial lymphocytes. Review of the initial biopsy showed mildly increased subepithelial collagen, not initially appreciated. Masson trichrome stains on both sets of biopsies highlighted the subepithelial collagen thickening. Sulfasalazine 1 g four times a day and prednisone 40 mg per os every day were prescribed and colchicine was substituted for indomethacin. The patient was discharged without wrist symptoms, passing one semisolid stool a day and has remained well for three months. A repeat colonic biopsy has not been obtained. Patient 2. A 77-year-old white male presented with a three-month history of four watery bowel movements per day. A trial of ibuprofen for arthralgias four years before resulted in diarrhea that resolved when the medication was discontinued. A barium enema and colonscopy revealed one adenomatous sigmoid colon polyp. Otherwise the mucosa appeared normal. Two months before the illness, the patient received indomethacin 100 rag/day for arthritic complaints. Three days before onset of diarrhea the patient underwent dental work and took penicillin for seven days followed by seven days of erythromycin. Investigation, at the time of diarrhea, revealed a hematocrit of 33.3%, and an elevated Westergren erythrocyte sedimentation rate of 31 mm/hr (normal 0-10 mm/hr). Stools were negative for ova and parasites, bacterial pathogens, and C. difficile. Colonoscopy was macroscopically normal, and biopsies of ascending

Digestive Diseases and Sciences, Vol. 35, No. 2 (February 1990) 0163-2116/90/021)04)25756.00/0 9 1990Plenum Publishing Corporation

257

GIARDIELLO ET AL

Fig 1. Patient 1, after long-term indomethacin and short-term antibiotics. (A) At initial colonoscopy, the descending colon has numerous pseudomembranes adherent to the intraluminal surface (arrowhead). (B) The initial biopsy of the sigmoid colon demonstrates a surface erosion with overlying pseudomembrane (arrow), prominent lamina propria mononuclear cells, and mildly increased subepithelial collagen. (C) Repeat colonoscopy seven days later, after vancomycin, shows resolution of pseudomembranes but residual gross inflammation with a reticular pattern apparent beneath the surface epithelium. (D) Colonic biopsy of the transverse colon from repeat endoscopy reveals no pseudomembranes and a thickened subepithelial collagen layer (between arrowheads), consistent with collagenous colitis. Both photomicrographs, hematoxylin and eosin, bar = 50 ~m.

through sigmoid colon revealed typical collagenous colitis. The histological features included increased lamina propria mononuclear cells, a thick subepithelial collagen band, prominent intraepithelial lymphocytes, and no crypt abcesses. The patient was treated with prednisone 25 mg orally per day with prompt cessation of diarrhea. The prednisone was gradually discontinued over a one-year period. He remained asymptomatic on no medication for one year, and his biopsies returned to normal. However, his diarrhea flared again and then abated with a second course of prednisone. At present he is asymptomatic on 5 mg/day of prednisone; colonic biopsies still reveal collagenous colitis.

258

DISCUSSION Collagenous colitis is a newly recognized syndrome of chronic watery diarrhea and mild abdominal pain, o c c u r r i n g primarily in middle-aged women. On colorectal biopsy, these cases have a combination of mucosal inflammatory changes and subepithelial collagen thickening (2). The recent recognition of this disorder may be due to the more widespread use o f colonoscopic biopsies. H o w e v e r , a new type of colonic insult, such as a recently Digestive Diseases and Sciences, Vol. 35, No. 2 (February 1990)

COLLAGENOUS COLITIS AND DRUG USE available drug, could be involved. We report two cases in which collagenous colitis developed following prolonged use of nonsteroidal antiinflammatory agents and short-term use of antibiotics. Prior to the development of diarrhea both patients used nonsteroidal medications. Patient 1 took indomethacin intermittently for years and continuously for six weeks before admission. Patient 2 had a short course of ibuprofen, clearly associated with diarrhea, as well as a two-month course of indomethacin prior to the diagnosis of collagenous colitis. The presentation of collagenous colitis closely tied to recent nonsteroidal antiinflammatory drug use has not been, to our knowledge, previously reported. However, review of our collagenous colitis registry revealed seven of 33 patients had used these agents. While it is possible that the association with nonsteroidal antiinflammatory drug administration was fortuitous and that collagenous colitis was present ~efore drug use, the circumstantial evidence seems to warrant further investigation. Nonsteroidal medications have been implicated in various forms of colitis (3, 4), but the exact relationship is unclear. Case reports exist of these drugs activating quiescent inflammatory bowel disease (ulcerative colitis) (5), and provoking de novo inflammatory colitis (6). Studies using indiumtagged cells show that these drugs can cause blood and protein loss and leukocyte accumulation in the small bowel (7). Furthermore, these medications inhibit colonic mucosal prostaglandin synthesis (8), perhaps resulting in a local imbalance of inflammatory mediators. Therefore, there are several potential mechanisms through which nonsteroidal antiinflammatory agents might interact with collagenous colitis. Both patients in our report were taking antiinflammatory agents for treatment of joint disease. Arthritis and arthralgias have a documented association with collagenous colitis (9-15). In several cases the arthritis has developed after the diarrhea and is presumably a reactive arthritis secondary to colitis, analogous to arthritis in patients with idiopathic inflammatory bowel disease (16). Other patients have a long history of primary arthritis (osteoarthritis, gout) before diarrhea occurs. Whether the arthritis is primary or secondary, these patients often are taking nonsteroidal antiinflammatory drugs. Thus, the use of nonsteroidal antiinflammatory agents by patients with collagenous colitis and arthritis may be either exacerbating or inciting the diarrhea. Digestive Diseases and Sciences, Vol. 35, No. 2 (February 1990)

The exact role of antibiotics in these two cases is unclear. Both patients had diarrhea before taking antibiotics and antibiotics were used for only a short time just prior to the current presentation. Stool cultures for enteric pathogens and assays for C. difficile toxin were negative in both cases. However, patient 1 partially responded to oral vancomycin therapy with resolution of pseudomembranes and fever but not diarrhea. While antibiotics (or the combination of antibiotics and nonsteroidals) may have merely exacerbated the underlying collagenous colitis, it is also possible that the patient developed a superimposed antibiotic-associated colitis. Review of our other collagenous colitis cases revealed no other patient that used antibiotics in close association with onset of symptoms. Lymphocytic (microscopic) colitis (17) is closely related to collagenous colitis. In both disorders patients present with chronic watery diarrhea. In addition, both have similar colonic histopathology. However, collagenous colitis has a distinctive subepithelial collagen band, and there are clinical differences between the two disorders. In collagenous colitis the subepithelial thickening is patchy and may be absent from the rectum (18, 19). Thus multiple biopsies proximal to the rectum are necessary to distinguish between lymphocytic and collagenous colitis. Resolution of the subepithelial collagen in patients treated with antiinflammatory medications and those without treatment has been reported. There appears to be no association between collagenous or lymphocytic colitis and idiopathic inflammatory bowel disease (17). In conclusion, we suggest that diarrhea in the setting of nonsteroidal antiinflammatory agents may be due to underlying colitis including collagenous colitis. Discontinuation of nonsteroidal antiinflammatory agents should be considered. Furthermore, cases of unresolving antibiotic-associated diarrhea may deserve investigation for collagenous colitis. The possible relationship between collagenous colitis and drug treatment warrants a careful drug history in these patients and may provide a clue to the pathogenesis and treatment of this disorder. SUMMARY

Collagenous colitis is a clinicopathologic syndrome characterized by chronic watery diarrhea and a mucosal inflammatory process with increased subepithelial collagen band on colonic biopsy. This disorder occurs primarily in females, and the etiol-

259

GIARDIELLO ET AL ogy is u n k n o w n . W e r e p o r t the a t y p i c a l p r e s e n t a tion o f c o l l a g e n o u s colitis in t w o older-aged m e n f o l l o w i n g p r o l o n g e d u s e o f n o n s t e r o i d a l antiinflamm a t o r y a g e n t s a n d s h o r t - t e r m u s e of a n t i b i o t i c s . Although one patient had colonic p s e u d o m e m b r a n e s , n e i t h e r p a t i e n t h a d m i c r o b i o l o g i c a l evid e n c e o f C . d i f f i c i l e t o x i n or i n f e c t i o n . A v a r i e t y o f m e d i c a t i o n s w e r e initially g i v e n to t h e s e p a t i e n t s w i t h o u t r e s o l u t i o n o f diarrhea. O n l y after the diagn o s i s of c o l l a g e n o u s colitis w a s m a d e a n d a n t i i n f l a m m a t o r y drugs d i r e c t e d at the colitis g i v e n did the d i a r r h e a a b a t e . T h e s e cases illustrate a n u n u s u a l p r e s e n t a t i o n o f c o l l a g e n o u s colitis with p o s s i b l e i m p l i c a t i o n s for p a t h o g e n e s i s . ACKNOWLEDGMENTS The authors thank Dr. William J. Ravich for referring patients, Dr. Thomas Hendrix for advice and support, Mr. Raymond Lund for photography, and Ms. Linda M. Welch for secretarial assistance.

REFERENCES 1. Lindstrom CG: "Collagenous colitis" with watery diarrhea. A new entity? Pathol Eur 11:87-89, 1976 2. Giardiello FM, Bayless TM, Jessurun J, Hamilton SR, Yardley JH: Collagenous colitis: physiological and histopathological studies in seven patients. Ann Intern Med 106:46-49, 1987 3. Rampton DS: Non-steroidal and anti-inflammatory drugs and the lower gastrointestinal tract. Scand J Gastroenterol 22:1-4, 1987 4. Rigas B: Eicosanoids and the gastrointestinal tract: Promising but no verdict yet. Am J Gastroenterol 81:218-221, 1986 5. Kaufman HJ, Taubin HL: Nonsteroidal antiinflammatory drugs activate quiescent inflammatory bowel disease. Ann Intern Med 107:513-516, 1987 6. Hall RI, Petty AH, Cobden I, Lendrum R: Enteritis and colitis associated with mefenamic acid. Br Med J 287:16261627, 1983 (letter)

260

7. Bjarnason I, Prouse P, Smith T, Gumpel MJ, Zanelli G, Smethurst P, Levi S, Levi AJ: Blood and protein loss via small-intestinal inflammation induced by non-steroidal antiinflammatory drugs. Lancet 2:711-714, 1987 8. Whittle B: Temporal relationship between cyclooxygenase inhibition, as measured by prostaglandin biosynthesis and the gastrointestinal damage induced by indomethacin in the rat. Gastroenterology 80:94-98, 1981 9. Maroy B, Moullot P: Colite collagene: Association a une arthropathie inflammatoire chronique. Press-Med 13:1516, 1984 (letter) 10. Erlendsson J, Fenger C, Meinicke J: Arthritis and collagenous colitis: Report of a case with concomitant chronic polyarthritis and collagenous colitis. Scand J Rheumatol 12:93-95, 1983 11. Maroy B: Une autre cause de rhumatism enteropathique: La colite collagene. Rev Med Interne 6:331, 1985 12. Archimandritis A, Tzivras M, Delladetsima A, Tryphonos M: Collagenous colitis in Greece. Gut 28:230, 1987 13. Fauso O, Foerster A, Hovig T: Collagenous colitis: A clinical, histological and ultrastructural study. Scand J Gastroenterol 107:8-23, 1985 14. Teglbjaerg PS, Thaysen EH, Jensen HH: Development of collagenous colitis in sequential biopsy specimens. Gastroenterology 87:703-709, 1984 15. Farah DA, Mills PR, Lee FD, McLay A, Rusell RI: Collagenous colitis: Possible response to sulfasalazine and local steroid therapy. Gastroenterology 88:798-807, 1985 16. Roubenoff R, Ratain J, Giardiello FM, Hochberg MC, Bias W, Lazenby AJ, Yardley JH: Collagenous colitis, enteropathic arthritis, and autoimmune diseases: Results of a patient survey. J Rheumatol 16:1229-1232, 1989 17. Lazenby AJ, Yardley JH, Giardiello FM, Jessurun J, Bayless TM: Lymphocytic ("microscopic") colitis: A comparative histopathologic study with particular reference to collagenous colitis. Hum Pathol 20:18-28, 1989 18. Jessurnn J, Yardley JH, Giardiello FM, Hamilton SR, Bayless TM: Chronic colitis with thickening of the subepithelial collagen layer (collagenous colitis). Histopathologic findings in 15 patients. Hum Pathol 18:839-848, 1987 19. Rams H, Rogers AI, Ghandur-Mnaynmeh L: Clinical review: Collagenous colitis. Ann Intern Med 106:108-113, 1987.

Digestive Diseases and Sciences, Vol. 35, No. 2 (February 1990)

Collagenous colitis in setting of nonsteroidal antiinflammatory drugs and antibiotics.

Collagenous colitis is a clinicopathologic syndrome characterized by chronic watery diarrhea and a mucosal inflammatory process with increased subepit...
1016KB Sizes 0 Downloads 0 Views