Background. The purpose of study was to evaluate the diagnostic yield of capsule endoscopy for NSAID-induced enteropathy and clinical, laboratory, and endoscopic characteristics of disease in patients with rheumatoid arthritis. Methods. 37 rheumatoid arthritis patients (30 women; mean age 55) treated with NSAIDs (>1 month), presented with anaemia and/or positive faecal occult blood testing, entered the study and underwent capsule endoscopy (EndoCapsule; Olympus), laboratory tests, and filled in questionnaires. Results. The prevalence of NSAID-induced enteropathy diagnosed by capsule endoscopy was 68% (25/37), classified as mild (red spots or erosions) in 18 (49%), moderate (10-20 erosions) in 4 (11%), and severe enteropathy (>20 erosions or ulcers) in 3 (8%) patients. We did not find statistically significant relationship between the enteropathy and gender, age, haemoglobin, leukocytes, albumin and CRP, or dyspepsia. The difference between subgroups of NSAIDs according to the COX specificity was not statistically significant. Conclusions. Capsule endoscopy is a highly accurate noninvasive method for evaluation of NSAID-induced enteropathy. It was revealed in a substantial section of the patients with rheumatoid arthritis and occult gastrointestinal bleeding, mostly classified as mild damage. No simple clinical or laboratory markers of the presence or severity of NSAID-induced enteropathy were recognised. This trial is registered with DRKS00004940.

2nd Department of Internal Medicine Gastroenterology Charles University Prague Faculty of Medicine in Hradec Králové and University Hospital Sokolská 581 500 05 Hradec Králové Czech Republic

See more in PubMed

Singh G, Ramey DR. NSAID induced gastrointestinal complications: the ARAMIS perspective—1997. Arthritis, rheumatism, and aging medical information system. Journal of Rheumatology, Supplement. 1998;25(51):8–16. PubMed

Lai LH, Chan FKL. Nonsteroid anti-inflammatory drug-induced gastroduodenal injury. Current Opinion in Gastroenterology. 2009;25(6):544–548. PubMed

Douthwaite AH, Lintott GAM. Gastroscopic observation of effect of aspirin and certain other substances on stomach. The Lancet. 1938;232(6013):1222–1225.

Sturges HF, Krone CL. Ulceration and stricture of the jejunum in a patient on long-term indomethacin therapy. The American Journal of Gastroenterology. 1973;59(2):162–169. PubMed

Davies NM, Saleh JY, Skjodt NM. Detection and prevention of NSAID-induced enteropathy. Journal of Pharmacy & Pharmaceutical Sciences. 2000;3(1):137–155. PubMed

Hotz-Behofsits CM, Walley MJM, Simpson R, Bjarnason IT. COX-1, COX-2 and the topical effect in NSAID-induced enteropathy. Inflammopharmacology. 2003;11(4–6):363–370. PubMed

Sigthorsson G, Simpson RJ, Walley M, et al. COX-1 and 2, intestinal integrity, and pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in mice. Gastroenterology. 2002;122(7):1913–1923. PubMed

Zardawi IM, Prematilake S. NSAID-associated protein losing enteropathy with fatal outcome. Pathology. 2012;44(5):489–492. PubMed

Bjarnason I, Takeuchi K. Intestinal permeability in the pathogenesis of NSAID-induced enteropathy. Journal of Gastroenterology. 2009;44(supplement 19):23–29. PubMed

Sakuma T, Gocho S, Ogasawara F, et al. A case of small bowel ulcer caused by NSAIDs and detected after capsule endoscope retention. Tokai Journal of Experimental and Clinical Medicine. 2012;37(1):14–18. PubMed

Risty GM, Najarian MM, Shapiro SB. Multiple indomethacin-induced jejunal ulcerations with perforation: a case report with histology. The American Surgeon. 2007;73(4):344–346. PubMed

Lang J, Price AB, Levi AJ, Burke M, Gumpel JM, Bjarnason I. Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs. Journal of Clinical Pathology. 1988;41(5):516–526. PubMed PMC

Scholz FJ, Heiss FW, Roberts PL. Diaphragmlike strictures of the small bowel associated with use of nonsteroidal antiinflammatory drugs. The American Journal of Roentgenology. 1994;162(1):49–50. PubMed

Tachecí I, Kopácová M, Rejchrt S, Bures J. Non-steroidal anti-inflammatory drug induced injury to the small intestine. Acta Medica. 2010;53(1):3–11. PubMed

Allison MC, Howatson AG, Torrance CJ, Lee FD, Russell RI. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. The New England Journal of Medicine. 1992;327(11):749–754. PubMed

Morris AJ, MacKenzie JF. Small-bowel enteroscopy and NSAID ulceration. The Lancet. 1991;337(8756):p. 1550. PubMed

Graham DY, Opekun AR, Willingham FF, Qureshi WA. Visible small-intestinal mucosal injury in chronic NSAID users. Clinical Gastroenterology and Hepatology. 2005;3(1):55–59. PubMed

Goldstein JL, Eisen GM, Lewis B, Gralnek IM, Zlotnick S, Fort JG. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clinical Gastroenterology and Hepatology. 2005;3(2):133–141. PubMed

Maiden L, Thjodleifsson B, Seigal A, et al. Long-term effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a cross-sectional capsule enteroscopy study. Clinical Gastroenterology and Hepatology. 2007;5(9):1040–1045. PubMed

Hawkey CJ, Ell C, Simon B, et al. Less small-bowel injury with lumiracoxib compared with naproxen plus omeprazole. Clinical Gastroenterology and Hepatology. 2008;6(5):536–544. PubMed

Watanabe T, Tanigawa T, Nadatani Y, et al. Risk factors for severe nonsteroidal anti-inflammatory drug-induced small intestinal damage. Digestive and Liver Diseases. 2013;45(5):390–395. PubMed

Tachecí I, Drastich P, Suchánek Š, et al. Kapslová endoskopie—standard endoskopického vyšetření tenkého střeva. Česká a Slovenská Gastroenterologie a Hepatologie. 2007;61:269–275.

Ladas SD, Triantafyllou K, Spada C, et al. European society of gastrointestinal endoscopy (ESGE): recommendations (2009) on clinical use of video capsule endoscopy to investigate small-bowel, esophageal and colonic diseases. Endoscopy. 2010;42(3):220–227. PubMed

Li F, Gurudu SR, de Petris G, et al. Retention of the capsule endoscope: a single-center experience of 1000 capsule endoscopy procedures. Gastrointestinal Endoscopy. 2008;68(1):174–180. PubMed

Sigthorsson G, Tibble J, Hayllar J, et al. Intestinal permeability and inflammation in patients on NSAIDs. Gut. 1998;43(4):506–511. PubMed PMC

Kessler WF, Shires GT, III, Fahey TJ., III Surgical complications of nonsteroidal antiinflammatory drug-induced small bowel ulceration. Journal of the American College of Surgeons. 1997;185(3):250–254. PubMed

Bjarnason I, Zanelli G, Prouse P, et al. Blood and protein loss via small-intestinal inflammation induced by non-steroidal anti-inflammatory drugs. The Lancet. 1987;2(8561):711–714. PubMed

Goldstein JL, Eisen GM, Lewis B, et al. Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Alimentary Pharmacology and Therapeutics. 2007;25(10):1211–1222. PubMed

Matsumoto T, Kudo T, Esaki M, et al. Prevalence of non-steroidal anti-inflammatory drug-induced enteropathy determined by double-balloon endoscopy: a Japanese multicenter study. Scandinavian Journal of Gastroenterology. 2008;43(4):490–496. PubMed

Smale S, Tibble J, Sigthorsson G, Bjarnason I. Epidemiology and differential diagnosis of NSAID-induced injury to the mucosa of the small intestine. Best Practice and Research: Clinical Gastroenterology. 2001;15(5):723–738. PubMed

Abrahamian GA, Polhamus CD, Muskat P, Karulf RE. Diaphragm-like strictures of the ileum associated with NSAID use: a rare complication. Southern Medical Journal. 1998;91(4):395–397. PubMed

Yousfi MM, de Petris G, Leighton JA, et al. Diaphragm disease after use of nonsteroidal anti-inflammatory agents: first report of diagnosis with capsule endoscopy. Journal of Clinical Gastroenterology. 2004;38(8):686–691. PubMed

Hawkey CJ. Gastrointestinal toxicity of non-steroidal anti-inflammatory drugs. In: Vane JR, Motting MR, editors. Therapeutic Roles of Selective COX-2 Inhibitors. London, UK: Wiliam Harvey Press; 1991.

Rejchrt S, Koupil I, Kopáčová M, et al. Prevalence and sociodemographic determinants of uninvestigated dyspepsia in the Czech Republic. European Journal of Gastroenterology and Hepatology. 2008;20(9):898–905. PubMed

Dequeker J, Hawkey C, Kahan A, et al. Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the safety and efficacy large-scale evaluation of COX-inhibiting therapies (SELECT) trial in osteoarthritis. The British Journal of Rheumatology. 1998;37(9):946–951. PubMed

Hawkey C, Kahan A, Steinbruck K, et al. Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. International MELISSA study group. Meloxicam large-scale international study safety assessment. The British Journal of Rheumatology. 1998;37(9):937–945. PubMed

Maiden L, Thjodleifsson B, Seigal A, et al. Long-term effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a cross-sectional capsule enteroscopy study. Clinical Gastroenterology and Hepatology. 2007;5(9):1040–1045. PubMed

Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthritis