This study has identified a group of patients with inflammatory chronic, or relapsing acute arthritis who even in the absence of gastrointestinal symptoms have histological evidence of ileocolitis. At colonoscopy simultaneous biopsies of the terminal ileum and colon were taken from 108 patients with reactive arthritis (n = 55) or ankylosing spondylitis (n = 53), 47 patients with other rheumatic diseases and 19 control patients suffering from colonic polyps, adenocarcinoma, or chronic constipation. All control patients and all but one patient with rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus, lumbar back ache, and psoriatic arthritis did not have histological evidence of acute or chronic inflammatory bowel disease. In contrast, in 30 of 35 (56.6%) patients with ankylosing spondylitis, and in 37 of 55 (67%) patients with reactive arthritis, regardless of HLA B27 phenotype, there was histological evidence of inflammatory bowel disease with features either of acute enterocolitis, or early Crohn's disease. Only 18 of 67 (27%) of the patients with histological gut inflammation, however, had intestinal symptoms.

https://gut.bmj.com/content/gutjnl/28/4/394.full.pdf

Histopathology of intestinal inflammation related to reactive arthritis.

Objectives: To study the incidence and clinical picture of Shigella associated reactive arthritis (ReA) and the arthritogenicity of various Shigella species in the population. 

Methods: A questionnaire on enteric and extraintestinal, especially musculoskeletal, symptoms was sent to 278 consecutive patients with Shigella positive stool culture and to 597 controls. Analysis of self reported musculoskeletal symptoms was supplemented with clinical examination of those subjects with recent symptoms. 

Results: Of the patients, 14/211 (7%) had ReA, and a further 4/211 (2%) other reactive musculoskeletal symptoms (tendonitis, enthesopathy, or bursitis). Of the 14 patients with ReA, all adults, 10 had S sonnei, three S flexneri, and one S dysenteriae infection. HLA-B27 was positive in 36% of the patients with ReA. One control subject had ReA. In the patients with Shigella infection, the odds ratio for developing ReA was 16.2 (95% confidence interval 2.1 to 123.9), p = 0.001. 

Conclusions: ReA occurred in 7% of patients after Shigella infection, with an annual incidence of 1.3/1 000 000 in Finland. Besides S flexneri, S sonnei and S dysenteriae can also trigger ReA.

https://ard.bmj.com/content/annrheumdis/64/4/594.full.pdf

Reactive arthritis attributable to Shigella infection: a clinical and epidemiological nationwide study

Objectives: To estimate the incidence of postinfectious joint complaints after Campylobacter jejuni/coli enteritis compared with enteritis caused by enterotoxigenic E coli (ETEC). To compare gastrointestinal symptoms, antibiotic treatment, and antibody levels among patients with and without joint symptoms. 

Method: Questionnaires were sent to 210 consecutive patients with Campylobacter infection and an equal number of patients with E coli (ETEC). Blood samples for anti-Campylobacter antibodies were collected after two weeks, three months, six months, and two years. 

Results: Twenty seven of 173 (16%) patients with Campylobacter and 10/177 (6%) with E coli (ETEC) reported joint symptoms (p=0.004). In the Campylobacter group duration of diarrhoea was a median of 13 days for patients with arthralgia and seven days for those without joint pain (p=0.0058). Patients with E coli had diarrhoea of longer duration than patients infected with Campylobacter (14 days v seven days; p=0.0005). E coli patients had fewer gastrointestinal symptoms than Campylobacter patients (p=0.0001). Fifty nine per cent of Campylobacter patients with joint pain had received antibiotic treatment because of enteritis compared with 26% with enteritis only (p=0.03). Campylobacter species and serotypes were equally distributed in both groups and there was no difference in anti-Campylobacter antibody levels between the groups. 

Conclusion: There was a significantly increased risk of developing joint symptoms after contracting Campylobacter infection compared with E coli. Campylobacter patients with joint pain had more severe gastrointestinal symptoms and longer duration of diarrhoea. Antibiotic treatment does not seem to prevent reactive joint symptoms. Levels of anti-Campylobacter antibodies were the same in both groups.

https://ard.bmj.com/content/annrheumdis/61/5/448.full.pdf

Comparison of rheumatological and gastrointestinal symptoms after infection with Campylobacter jejuni/coli and enterotoxigenic Escherichia coli.

We attempted to induce experimental arthritis in rats by systematically testing the effect of Yersinia infections in five strains of rats, using the intragastric, intraperitoneal, and intravenous routes of inoculation. We observed that Lewis rats which were given 10(4) to 10(5) Yersinia enterocolitica WA organisms via the intravenous route consistently developed arthritis. The arthritis was most severe at 3 weeks and subsided at 6 weeks. No arthritis was observed when this bacterial strain was administered to Buffalo, Fisher, DA, and LDA rats. No replicable bacteria were detected in the joints. This aseptic characteristic parallels that seen in the human condition and establishes this as an animal model of Yersinia-induced arthritis. The probable reason for arthritis development in only the Lewis rats became apparent when we analyzed the numbers of live bacteria in the spleens and livers of these infected animals. The arthritis-susceptible Lewis rats harbored 10-fold more bacteria than the arthritis-resistant rat strains, and this systemic infection also persisted for a significantly longer period. Speculations as to why human subjects who develop Yersinia-induced arthritis are genetically predisposed have been centered principally around the role of the HLA-B27 histocompatibility antigens. The present study reveals a heretofore unrecognized critical factor: the susceptibility of the hosts to the virulence of the infectious organisms. In addition, the present animal model will provide the necessary tool for the investigation of this and other important host and bacterial factors.

Development of an experimental animal model for reactive arthritis induced by Yersinia enterocolitica infection.

Non-steroidal anti-inflammatory drug induced small intestinal inflammation may have an adverse effect on the joints of patients with rheumatoid arthritis. We therefore assessed small intestinal and joint inflammation in patients with rheumatoid arthritis before and after three to nine months' treatment with sulphasalazine (n = 40) and other second line drugs (n = 20), while keeping the dosage of non-steroidal anti-inflammatory drug at the same level. Sulphasalazine significantly decreased the mean (SD) faecal excretion of 111indium labelled leucocytes from 2.39 (2.22)% to 1.33 (1.13)% (normal less than 1%, p less than 0.01) and improved the joint inflammation as assessed by a variety of parameters. There was no significant correlation between the effects of sulphasalazine treatment on the intestine and the joints. Treatment with other second line drugs had no significant effect on the faecal excretion of 111indium (1.58 (1.04)% and 1.86 (1.51)%, respectively) but improved joint inflammation significantly. The lack of correlation between the intestinal and joint inflammation and their response to treatment suggests that the two are not causally related.

https://gut.bmj.com/content/gutjnl/31/7/777.full.pdf

H R Noer

Papers

An 'Experimental' Epidemic of Reiter's Sydrome