Influence of biologic therapy on return to work in people with work disability due to ankylosing spondylitis.

OBJECTIVE: To answer the question 'does TNF blockade therapy enable people with severe AS to return to work or work more productively?'. METHODS: All patients with AS currently receiving anti-TNF therapy at two UK Hospitals were asked to complete a questionnaire. This asked about occupational history, type of work, degree of job-related physical activity, working hours and sickness absence from work both currently (on anti-TNF treatment) and pre-treatment. RESULTS: Sixty-five patients (72.3% male), aged 29-64 (mean 46.1) yrs, whose duration of anti-TNF treatment ranged from 3 to 56 (mean 19.1) months were studied. Twenty-four (36.9%) patients were receiving infliximab, 21 (32.3%) etanercept and 20 (30.8%) adalimumab. Pre-treatment, 46 (70.8%) were in employment (1 was a student); 38 (58.5%) were working full-time and 8 (12.3%) part-time; 19 (29.2%) were not working. On treatment, 50 (76.9%) patients were working, 44 (67.7%) full-time and 6 (9.2%) part-time. Two individuals who worked part-time pre-treatment had returned to work full-time. Thus, on treatment, 4 of the 19 patients who were previously unable to work returned to employment, and 2 others increased their work from part-time to full-time. Patients rated the effect of AS on work capacity as 7.05/10 pre-treatment and 2.92/10 post-treatment. Those who were working lost, on average, 15 days from work due to sick leave in the 12 months pre-treatment and 0.91 days in the first 12 months on treatment. CONCLUSIONS: Treatment of active AS with TNF blockade appears to be associated with improved capacity for work.

Extraintestinal manifestations of ulcerative colitis following restorative proctocolectomy.

BACKGROUND: Rheumatological and other extraintestinal manifestations (EIM) are common in inflammatory bowel disease (IBD) but also seem to occur in patients after restorative proctocolectomy and formation of an ileo-anal pouch. The prevalence and significance of these symptoms have not been established in this clinical context. OBJECTIVE: To evaluate prospectively the prevalence and associations of EIM of IBD in ulcerative colitis (UC) patients following restorative proctocolectomy (RP) and to compare the findings to those in a control group of familial adenomatous polyposis (FAP) patients who had undergone similar surgery. METHODS: One hundred and twenty-three (97 UC and 26 FAP) consecutive patients with ileal pouches undergoing long-term follow-up underwent an assessment of rheumatological symptoms and signs, similarly of other EIM; each underwent pouch endoscopy and biopsy. RESULTS: Symptoms in the joints were reported in 30 (31%) of UC patients compared to two (8%) FAP patients (P = 0.02). Twenty-four (80%) of the affected patients had a polyarticular arthralgia affecting primarily the knees, and small joints of the hands. Clinical findings and radiological investigations were almost exclusively normal. Most patients had mild symptoms, with only 12 of the 30 reporting interference with daily life. The presence of symptoms in the joints was not associated with a positive family history for IBD or other EIM, the presence of non-rheumatological EIM or the presence of pouchitis. Histological scores of pouch inflammation did not differ between those with and without symptoms of the joints. CONCLUSIONS: A mild polyarticular arthralgia, similar to that associated with active IBD, is common following RP and may commence after surgery. It is not associated with the presence of pouch inflammation.

Perioperative use of methotrexate--a survey of clinical practice in the UK.

We have surveyed the use of methotrexate in the perioperative period in patients with rheumatoid arthritis (RA) undergoing surgery. A total of 200 consultant rheumatologists and 200 consultant orthopaedic surgeons in the UK were sent a postal questionnaire. Thirty-five per cent of rheumatologists and 46% of orthopaedic surgeons were concerned that the drug may increase the risk of post-operative complications, although significantly less 'always' stopped the drug around the time of surgery. There was great variation in the timing of stopping the drug with most stopping treatment within 2 weeks before surgery and restarting within 2 weeks after surgery. The majority of clinicians surveyed (70%) felt that national guidelines for the perioperative use of methotrexate would be helpful.

Antigen-presenting cells but not lymphocytes in the joint may indicate the cause of reactive arthritis.

T cells and antigen-presenting cells (APC) accumulate in the joint in reactive arthritis and there are reports that the T cells are a population selected for responsiveness to the causative agent. In this work, the latter view is questioned by detailed studies of the antigen specificities of the lymphocytes within the joint (SFMC) and peripheral blood (PBMC) of patients with reactive arthritis triggered by infection with Chlamydia trachomatis. Using a hanging-drop microculture system. SFMC displayed enhanced responses not only to antigens from the triggering organism, but also to other antigens, including PPD and tetanus toxoid, to which the patients were likely to have had prior exposure. No evidence was obtained for a dominant cross-reactive T-cell response to epitopes common to these antigen preparations, confirming the polyclonal nature of the infiltrate. In contrast to the broad specificity of the T-cell infiltrate, two experimental approaches indicated that APC within the joint carried chlamydial antigen. The failure of antigen-bearing APC to interact with T cells at this site may underlie the inability to clear microbial antigen from the joint.

Reiter's syndrome and reactive arthritis: a current view.

This paper reviews advances in the understanding of the pathogenesis of reactive arthritis that have occurred over the last decade. Inflammatory aseptic joint disease has been linked with prior infection initiated by many different species of microorganisms. The presence of intra-articular bacterial antigens has now been firmly established with the demonstration of bacteria, bacterial fragments, DNA, RNA, and bacterial lipopolysaccharide in joints of patients with reactive arthritis. Chlamydia trachomatis, Salmonella enteritidis, and Shigella flexneri have all been detected in the joint by immunological techniques, although there is still some doubt as to the form in which they reach the joint and whether or not they persist. A number of phlogistic bacterial components could be acting as arthritogens. Negative joint culture results from patients with reactive arthritis make it unlikely that bacteria in the joint are viable, although chlamydial DNA has been shown in the joints of patients with sexually acquired reactive arthritis using the polymerase chain reaction. The use of antimicrobial therapy in the treatment of reactive arthritis is under review; data suggests that long-term antibiotic treatment warrants further study. The role of HLA-B27 in disease pathogenesis is discussed as are possible mechanisms of interplay between germ and gene. HLA-B27 might confer disease susceptibility by affecting immune mechanisms other than classical antigen presentation. The immunopathogenesis of joint inflammation in reactive arthritis is explored with reference to studies of humoral and cellular immune responses. Serological evidence to support the concept of molecular mimicry is far from conclusive; the results of relevant studies are summarized. Lymphocyte proliferation experiments suggest that antigen presenting cells play an important role. Finally, our views on reactive arthritis in the 1990s, and areas of new and potentially fruitful future research are presented.

Infectious agents in reactive arthritis.

It is now clear that the deposition and persistence of bacterial antigens in the joint are significant features of reactive arthritis. It is possible that in some instances this represents persistence of live bacteria, and several studies point to the potential value of antimicrobial therapy. Searches for bacterial DNA and RNA have yielded conflicting data, however, so further developments in this area will be of great importance. It is likely that bacterial antigens interact in some way with class I major histocompatibility complex (MHC) antigens in the pathogenesis of reactive arthritis. However, with the increasing understanding of the structure and function of HLA molecules, some evidence of a classic antigen-class I MHC-CD8 T-lymphocyte interaction is now emerging. Thus far, the mechanisms that link HLA-B27 and bacterial antigens with reactive arthritis remain unclear.

HLA-B27 subtypes in the spondarthropathies.

The spondarthropathy (Sp)-associated HLA-B27 antigen includes at least seven subtypes, B*2701-07, of which 01, 02, 05 and 07 occur in Caucasians. This study examined the B27 subtype distribution in British patients with Sp. The 133 HLA-B27+ subjects comprised 94 European Caucasian Sp (58 ankylosing spondylitis (AS), 22 reactive arthritis (ReA; 11 sexually acquired (SARA), 11 enteric (EReA)), eight undifferentiated Sp (USp), and six pauciarticular juvenile-onset chronic arthritis (pJCA)) patients, and 34 healthy Caucasian controls, together with four Asian Indian and one Chinese. 35S-labelled B27 was immunoprecipitated with anti-B27 MoAbs, and subtyped according to isoelectric point (pI) following isoelectric focussing. The use of B27 MoAb permitted subtype assignment without full class I HLA typing. The vast majority (95%) were B*2705 (Caucasian controls 31/34; AS 55/58; ReA 21/22; USp 8/8, and pJCA 6/6; Indian control 1/1 and AS 2/3; Chinese pJCA 1/1), and the remainder B*2702. No B*2701 or 07 subjects were identified. AS occurs in both B*2702 and 05 subjects, and we extend this observation to small numbers of ReA and of Indian AS subjects. This implicates molecular features shared between B27 subtypes, rather than subtype-determining regions of the antigen, in Sp pathogenesis.

Detection of Chlamydia trachomatis DNA in joints of reactive arthritis patients by polymerase chain reaction.

In 1986, Chlamydia trachomatis elementary bodies were found by direct immunofluorescence (DIF) in synovial-fluid cell deposits and synovial-membrane biopsy samples from five of eight patients with sexually acquired reactive arthritis (SARA) but in none of eight controls with other types of arthritis. Cells from the original slides (stored at 4 degrees C) have now been examined by a polymerase chain reaction (PCR) that amplifies DNA for the major outer membrane protein of C trachomatis. Chlamydial DNA was found in samples from four DIF-positive patients, one DIF-negative patient, and one DIF-negative control. Overall, there was 80% concordance for DIF and PCR results. This study supports our previous finding of chlamydiae in joints in reactive arthritis.

Septic bone, joint and muscle lesions associated with human immunodeficiency virus infection.

Ten episodes of musculoskeletal sepsis have been seen in nine patients with HIV infection. Seven patients had AIDS, circulating CD4-positive lymphocyte counts being less than 0.1 x 10(9)/l in six. Septic arthritis recurred in seven patients, osteomyelitis in three and pyomyositis and bursitis each occurred in one patient. Staphylococcus aureus was isolated from four patients, atypical micro-organisms being found in three. Presentation of musculoskeletal infection in this patient group may be atypical but rapid diagnosis is important as early antimicrobial therapy is often successful.

Intra-articular chlamydial antigen and inflammatory arthritis.

Joint material from 133 patients with well-characterized inflammatory arthritis, including individuals likely to have suffered reactive arthritis, was studied. The majority of patients were also examined for the presence of genital tract infection with Chlamydia trachomatis. Fluorescein-conjugated monoclonal antibodies demonstrated the presence of C. trachomatis antigen in synovial fluid cell deposits or synovial sections from inflamed knee joints of seven patients with reactive arthritis. The significance of these findings is discussed, as is the low rate of detection of chlamydial antigen in either the genital tract or the joint from patients in this study. We emphasize the need for further work aimed at identifying the relevant immunogenic chlamydial antigens responsible for the initiation of reactive arthritis.

Echocardiographic diastolic abnormalities of the left ventricle in inflammatory joint disease.

Echocardiographic early diastolic abnormalities have been shown recently in 50% of men with ankylosing spondylitis. Similar techniques were used to investigate subjects with rheumatoid arthritis and psoriatic arthritis with or without spondylitis. These subjects had no clinical, radiographic, or electrocardiographic evidence of cardiac or respiratory disease. Echocardiographic abnormalities seen resembled those of ankylosing spondylitis in that the interval between minimum left ventricular dimension and mitral valve opening was prolonged in 12 of 22 subjects with rheumatoid arthritis and in seven of 11 subjects with psoriatic arthritis. Isovolumic relaxation time was significantly prolonged in four subjects with rheumatoid arthritis and one with psoriatic arthritis. Unlike ankylosing spondylitis, however, there was consistent reduction in peak rate of left ventricular dimension increase in subjects with rheumatoid arthritis and psoriatic arthritis. In addition, the dimension increase during atrial systole was greater than normal in nine subjects with rheumatoid arthritis and two with psoriatic arthritis. The most likely cause of these abnormalities is increased connective tissue deposition in the myocardium.