Digestive and Liver Disease 38 (2006) 276–278
Brief Clinical Observation
Non-steroidal anti-inflammatory drug (NSAID)-induced colonic strictures and perforation: A case report M.M. Aloysius a , P.V. Kaye b , D.N. Lobo a,∗ a
Section of Surgery, Division of Gastrointestinal Surgery, University Hospital, Queen’s Medical Centre, E Floor West Block, Nottingham NG7 2UH, UK b Department of Pathology, University Hospital, Queen’s Medical Centre, Nottingham, UK Received 18 July 2005; accepted 2 September 2005 Available online 3 October 2006
Abstract Although non-steroidal anti-inflammatory drug-induced colopathy is well described, colonic perforations complicating non-steroidal antiinflammatory drug intake are rare. We report a patient with rheumatoid arthritis who was on long-term diclofenac and presented with early colonic stricture formation and a caecal perforation, which to the best of our knowledge, has only been reported once before. It is important to suspect this diagnosis in patients on non-steroidal anti-inflammatory drug therapy who present with an acute abdomen. © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Colon; Colopathy; Complication; Diclofenac; Histology; Non-steroidal anti-inflammatory drugs; Perforation; Stricture
1. Introduction Patients on non-steroidal anti-inflammatory drugs (NSAIDs) often present as surgical emergencies with duodenal and gastric perforations. Although NSAID-induced colopathy is well described [1–3], colonic perforations complicating NSAID intake are rare. We report a patient who was on long-term diclofenac and corticosteroid therapy for rheumatoid arthritis, and presented with early colonic stricture formation and a caecal perforation. This, to the best of our knowledge, has been reported only once before .
2. Case report A 65-year-old female patient who had bilateral knee replacements for severe rheumatoid arthritis 3 years previously, developed septic arthritis of the right knee joint. She underwent surgical wash out of the joint and was ∗
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referred from the orthopaedic unit with symptoms of an acute abdomen 5 days later. Her symptoms included sudden onset lower abdominal pain, diarrhoea and vomiting. She also had myelodysplasia, osteoporosis and hypertension. Her usual oral medications were diclofenac sodium 50 mg tds, hydrocortisone 50 mg tds, ranitidine 150 mg bd, folic acid 5 mg od (all for 3 years) and methotrexate 7.5 mg once a week for a year. She had features of intra-abdominal sepsis at the time of referral and required inotropic support in the Intensive Care Unit. Computed tomography revealed a pneumoperitoneum and multiple fluid loculations between small bowel loops. At laparotomy there were 1.5 L purulent fluid and widespread fibrinous exudates from a small caecal perforation. There was no obvious diverticular disease or any other pathology of note on exploration. A right hemicolectomy was performed and the patient made an uneventful recovery. Gross pathology of the resected specimen showed multiple early strictures in the caecum near the ileocaecal valve associated with mucosal ulcerations (Fig. 1). Microscopy revealed circumferential submucosal fibrosis (Fig. 2) and ulcerations (Fig. 3), characteristic of NSAID-induced colopathy.
1590-8658/$30 © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2005.09.003
M.M. Aloysius et al. / Digestive and Liver Disease 38 (2006) 276–278
Fig. 1. Gross specimen of caecum and ascending colon showing focal areas of narrowing due to early stricture formation (arrow) with underlying ulceration.
Fig. 2. Haematoxylin and eosin stain (×20) of the whole mount demonstrating the ulcer with underlying submucosal fibrosis (arrow) with normal surrounding mucosa (arrowhead).
Fig. 3. Haematoxylin and eosin stain (×20) demonstrating deep ulceration (arrow) through the muscle close to the site of perforation with overlying peritonitis.
The most widely recognised complications of NSAID therapy are consequences of gastroduodenal inflammation and ulceration: pain, bleeding and perforation. NSAIDinduced small bowel strictures were not described until 1987  and this unusual pattern of stricturing was characterised by Lang et al.  in a large retrospective series of small bowel resections. They hypothesised an evolution of pathological changes in which tall, thin mucosal diaphragms evolve into broad based humps, progressing to flat strictures due to fibrous obliteration of the submucosa. A similar process may occur in NSAID-induced colonic strictures. The first case of a colonic stricture caused by NSAID use was described by Sheers and Williams in 1989 . Since then several sporadic cases have been reported and most of them have a similar pattern of occurrence in terms of the location, implicated NSAID, microscopic and macroscopic appearances [2,6–10]. All strictures were broad based diaphragmatic strictures with a pinhole lumen at the site [2,6–10]. Histology confirmed submucosal fibrosis. All the colonic strictures occurred in the ascending and proximal transverse colon. Diclofenac, notably its slow release preparation, was the drug implicated in most cases. The first reported case of colonic ulceration associated with oxyphenbutazone and indomethacin therapy was in 1966  and diclofenac-induced ileo-caecal ulceration was described by Hudson et al. in 1993 . A possible mechanism underlying NSAID-induced colonic ulceration is increased intestinal permeability in the face of reduced mucosal prostaglandin E (cyclo-oxygenase inhibition) making the colonic mucosa vulnerable to toxic small bowel contents . Prevention of enteropathy (strictures and perforation) in those taking NSAIDs may be possible by the addition of misoprostol, although the pathological basis of these strictures needs to be investigated further. It is still unclear if colonic strictures are a sequel to ulceration or occur de novo. NSAID-induced colonic strictures, when diagnosed in an elective clinical situation, can be treated by colonoscopic balloon dilatation, but they tend to recur . Recently, Penner and Williams  used prednisolone monotherapy for 20 weeks successfully in a patient, with complete resolution of multiple colonic strictures. This can be considered a useful adjunct to stopping the offending drug . However, in the present case, concurrent hydrocortisone therapy did not appear to protect the patient from this complication. Matolo et al.  were first to describe the role of immunosuppressive drugs, including steroids in causing colonic perforation in a series of eight patients. Four patients were on high-dose steroids and all of them were on cytotoxic agents. Five patients had caecal and ileal perforations (three being distal). This was accompanied by infarction and necrosis of the caecum and terminal ileum. Absence of features of ischaemia in our case may preclude steroid or cytotoxic therapy as a cause for the perforation.
M.M. Aloysius et al. / Digestive and Liver Disease 38 (2006) 276–278
Review of the literature suggests that NSAID-induced strictures causing colonic obstruction and perforation is a rarity and the first case was reported by Robinson et al. in 1995 . We believe that this is the second case to be reported with this presentation and it is important to suspect this diagnosis in patients on NSAID therapy who present with an acute abdomen. However, in our case, the stricture was not tight enough to cause obstruction and the perforation of the caecum was a result of ulceration due to NSAID colopathy rather than from the effects of closed-loop obstruction.
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