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Case 5 cuvelier - drug induced perforation of the small intestine.pages
DRUG INDUCED ULCERATION AND PERFORATION OF THE SMALL
Claude Cuvelier, MD, PhD
Academic Department of Pathology,
This case is the strangest drug induced ulcer with perforation of the small intestinal wall that I
have ever seen! The patient had taken his drug (Motilium) just like the nurse had told him to
do, but as he was confused he did not remove the package and swallowed it with the known
results of clinical perforating terminal ileal tumour and the histology of ileal perforation as
The majority of changes amongst drug induced pathology consist of ulcerations, stricture
formation, inflammatory processes and ischaemia which are really non-specific signs. Clues
indicating drug-induced aetiology may be apoptotic epithelial cells, increased intra-epithelial
lymphocytes and the presence of eosinophils.
The drug-induced pathology has been claimed to be responsible for a large proportion of the
pathological conditions affecting the small intestine (present in up to 70% of chronic non-
steroidal anti-inflammatory drugs -NSAID- users!). The morphological features as seen in
drug induced small intestinal the various conditions which may lead to a diagnosis and to
consider mechanisms in important for the pathogenesis of the small intestinal damage.
The presence of focal active inflammation can indicate acute infectious ileitis, resolving
infectious enteritis and early chronic inflammatory bowel disease - especially when
eosinophilic cryptitis and crypt abscesses occur but it can also be related to the use of drugs
like NSAID and is then called NSAID enteropathy. Although the gastric and duodenal
ulcerations are known since many years, the small intestinal drug-induced alterations are less
recognized and this because the ileum is less frequently reached at endoscopy. The exact
pathogenesis of NSAID enteropathy is not fully understood but increased mucosal
permeability, loss of tight junction function, intracellular organelle damage are implicated and
factors that contribute further to the mucosal lesions are vascular. They include a decrease in
blood flow, impaired neutrophil function, defects in mucosal defence and inhibition of
prostaglandins. Access of luminal content and bacteria to the mucosa will induce an
inflammatory infiltration and ulceration, responsible for the clinical symptoms of protein loss
and unexplained anaemia. In ileal biopsies the lesions are mostly mild and present as
superficial erosions, increased apoptotic figures as well as eosinophilic infiltrates causing
cryptitis and crypt abscesses. Non-specific ileal ulcers may be induced by NSAID.
One condition which is very rare is distinctive and is claimed to be typical of NSAID
enteropathy, namely diaphragm disease. This typically presents with single (rarely) or many
diaphragms that are web-like mucosal septa causing luminal narrowing and obstruction. They
are in general perpendicular fibrotic bands covered by a reactive mucosa that can be ulcerated
Drugs which can cause intestinal damage include potassium chloride, administered orally in
the treatment of hypokalemia. It may cause ulcers and strictures throughout the
gastrointestinal tract by irritation of localized high salt concentrations or localized ischaemia.
Kayexalate, sodium polystyrene sulphonate in sorbitol, that is administered orally, via a
nasogastric tube or by enema in patients with hyperkalemia can induce ulceration, necrosis,
perforation. It is well distinguishable in slides as polygonal basophilic crystals, staining
Selective Internal Radiation Therapy (SIRT), radioembolization of primary or metastatic liver
tumours by injection of biocompatible microspheres carrying radioisotopes into hepatic artery
or its branches can induce gastroduodenal injury due to misplacement of radioactive
microspheres in the gastrointestinal tract.
Cuvelier C, Demetter P, Mielants H, Veys EM, De Vos M.
The interpretation of ileal biopsies: morphological features in normal and diseased mucosa.
Histopathology 2001, 38: 1-12
Evans SM, Whittle BJR.
Role of bacteria and inducible nitric oxide synthase activity in the systemic inflammatory microvascular response provoked by indomethacin in the rat. Eur J Pharmacol 2003, 461: 63-71
Hotz-Behofsits CM, Walley MJ, Simpson R, Bjarnason IT.
COX-1, COX-2 and the topical effect in NSAID-induced enteropathy. Inflammopharmacol 2003, 11: 363-370
Lee F D.
Drug-related pathological lesions of the intestinal tract. Histopathology 1994, 25: 303-308
Leite AZA, Sipahi AM, Damião et al.
Protective effect of metronidazole on uncoupling mitochondrial oxidative phosphorylation induced by NSAID: a new mechanism. Gut 2001, 48: 163-167
Misdraji J. Drug-induced pathology of the upper gastrointestinal tract. Diagnostic Histopathol, 2008, 14: 411-418
Parfitt JR, Driman DK. Pathological effects of drugs on the gastrointestinal tract: a review. Hum Pathol 2007, 38: 527-536
Price AB. Pathology of drug-associated gastrointestinal disease.Br J Clin Pharmacol 2003, 56: 477-482
Schneider A R, Benz C, Riemannn J F.
Adverse effects of nonsteroidal anti-inflammatory drugs on the small and large bowel. Endoscopy 1999, 31: 761-767
Smale S, Tibble J, Sigthorsson G, Bjarnason I.
Epidemiology and differential diagnosis of NSAID-induced injury to the mucosa of the small intestine. Best Pract Res Clin Gastroenterol 2001, 15: 723-38
Tanaka A, Hase S, Miyazawa T, Takeuchi K.
Up-regulation of cyclooxygenase-2 by inhibition of cyclooxygenase-1: a key to nonsteroidal anti-inflammatory drug-induced intestinal damage. J Pharmacol Exp Ther 2002, 300: 751-764
Should we farm native geckos? A discussion document by Rod Rowlands If you always do what you've always done, you'll always get what you've always got. In New Zealand, although it is possible to obtain a permit to keep and breed some native reptile species in captivity, such permits have always forbidden the sale of captive bred animals. Most local herpetoculturists seem to have
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