Increased intestinal permeability in ankylosing spondylitis--primary lesion or drug effect?

Abstract

We have found increased small intestinal permeability to 51Cr-ethylenediaminetetra acetate in patients with ankylosing spondylitis compared with controls. There is no significant difference between patients with ankylosing spondylitis and patients with rheumatoid arthritis taking non-steroidal anti-inflammatory drugs (NSAID). The increased intestinal permeability in ankylosing spondylitis is independent ofdisease activity. These findings suggest that the increased permeability is caused by NSAID treatment and is probably not a primary lesion of small bowel mucosa. PATIENTSSeventeen patients with ankylosing spondylitis taking NSAIDs who were attending our rheumatology outpatient clinic were studied. They were compared with two control groups, the first comprising 16 healthy volunteers and the second 19 patients with rheumatoid arthritis being treated with NSAIDs. In our clinical practice we had insufficient patients with ankylosing spondylitis who were not taking NSAIDs to form a separate control group. In these groups, coeliac disease, inflammatory bowel disease, alcohol abuse, and, in the volunteers, NSAID therapy were excluded on the basis ofhistory and clinical examination. The ankylosing spondylitis patients were all men aged 29-63 years, healthy volunteers (eight men and eight women) were aged 24-63 years, and the rheumatoid group (10 men and nine women) were aged 37-82 years. All tests were performed on an outpatient basis and informed consent was obtained before each procedure. METHODSAfter an overnight fast, patients and controls received 150 ml of solution containing 2 g mannitol, 5 g lactulose, 1 g L-rhamnose, 20 g sucrose, 20 g lactose, and 4 MBq of 51Cr-EDTA. The patients' urine was collected for 24 hours after taking the test solution. The collection period was divided into 0-6 hours and 6-24 hours. One ml of thiomersol (10% w/v) was added to the containers as preservative. The addition ofsugars (sucrose and lactose) to the test solution rendered the final solution hyperosmolar at 1200 mOsmol/l.Estimation of urinary recovery of 51Cr-EDTA used the methods described by Bjarnason.56 Urinary L-rhamnose, mannitol, and lactulose were estimated by modification of two gas liquid chromatography methods.910Statistical tests were performed using the Wilcoxon rank sum test, Mann-Whitney U test, and Pearson's correlation test. ResultsWe found that intestinal permeability to 5 Cr-EDTA in the 0-6 hours collection was median 0.35% (range 0.09-0 70) in controls, 0-61% (range 0. 15-1-29) in ankylosing spondylitis and 0 54% (range 0. 12-1.27) in rheumatoid arthritis. In the 6-24 hours collection values were: median 1.23% (range 0@43-21) control; 1.31% (0 3-2.28) ankylosing spondylitis, and 2.12 (0-12-11-40) rheumatoid arthritis. The sugar permeability results were: lactulose 0.25% (0.05-1 1), rhamnose 8-6% (4 9-24 9), and lactulose/ rhamnose (L/R) ratio 0.02 (0.01-0.05) in controls; lactulose 0-26% (0.04-0 59), rhamnose 8-8% (1-2-11-6), and L/R ratio 0.03 (0-01-0-27) in ankylosing spondylitis; and lactulose 0...

Intestinal permeability in the ileal pouch.

“…One patient had arthritis, pyoderma, and erythema nodosum (19.5% 51Cr-EDTA) and the other patient had arthritis (8.5% 51Cr-EDTA). Although anecdotal, it supports the concept that reduced barrier function to luminal content may be important in the pathogenesis of extraintestinal manifestations of inflammatory bowel disease.41 42 A small unblinded control study assessing the effect of transdermal nicotine on preclosure ileal pouch permeability was performed in eight patients. Although these data should be regarded as preliminary a pronounced reduction in permeability was seen in the patients treated with nicotine.…”

Ileitis in Ulcerative Colitis: Is It a Backwash?

“…Increased pouch mucosa permeability may lead to a reduction in barrier function and has been hypothesized in the pathogenesis of both pouchitis and extraintestinal manifestations of inflammatory bowel disease. [21][22][23] The current treatment of pouchitis has mainly been empirical and directed at presumed bacterial or inflammatory mechanisms. The mainstays of therapy include antibiotics or anti-inflammatory agents.…”

The G.U.T. of gut

“…The increased intestinal permeability and inflammatory changes seen in the patients with ankylosing spondylitis are identical to those seen in NSAIDenteropathy and indeed most of these patients were on or had received NSAIDs (147)(148)(149). However, their 1st-degree relatives and the relatives of patients with Crohn disease (that had not received NSAIDs) have identical prevalence of increased intestinal permeability (10%-30%) (149)(150)(151) and half have evidence of intestinal inflammation (increased 3-fold) (152,153).…”