Ankylosing spondylitis and the shoulder: commonly involved but infrequently disabling.

OBJECTIVE: To undertake 2 independent studies of shoulder involvement in patients with ankylosing spondylitis (AS) and assess the frequency of shoulder pain, stiffness, and loss of movement and function. To evaluate and correlate shoulder symptoms, function, range of movement, and radiology. METHODS: A cross sectional design was used in both studies. In Study A, a self-administered questionnaire was sent to members of the National Ankylosing Spondylitis Society of the UK and patients attending the Royal National Hospital for Rheumatic Diseases. In Study B, a clinical assessment of 88 patients with AS was undertaken that included a radiological assessment of 26 consecutive patients. RESULTS: In Study A, 15.2% and 13.8% of subjects had severe/very severe shoulder pain or stiffness, respectively. In Study B the corresponding findings were 9.6% and 17.6%. Patient reported disability associated with shoulder involvement was uncommon. Study A revealed that patients with severe/very severe shoulder pain were more likely to have significant hip and knee involvement. Significant shoulder involvement appears to be as common as involvement of the hip joint. In Study B radiological changes were common, being present in 31% of patients, but were often minor. There was a significant correlation between the sum of the stiffness, abduction, and flexion scores for both shoulders and the total radiological score (r = 0.87; p<0.001). CONCLUSION: The results suggest that shoulder symptoms and loss of shoulder mobility are common in patients with AS, and correlate with higher pain scores and influence of AS on their lives as assessed by the Arthritis Impact Measurement Scale, but are rarely disabling. Involvement of the shoulder joint in AS correlates with involvement of other peripheral joints as well as the extent of radiographic change on shoulder radiographs.

Primary ankylosing spondylitis, psoriatic and enteropathic spondyloarthropathy: a controlled analysis.

Within our ankylosing spondylitis (AS) population (n = 1331), 85% (n = 1128) had primary AS (1 degree AS), 9% (n = 121) had psoriatic AS (PsAS) and 6% (n = 82) enteropathic AS (IBDAS). In an attempt to explore further the relationship between 1 degree AS and the secondary spondyloarthritides, we evaluated 121 consecutive patients with PsAS and 82 with IBDAS, as well as 202 controls with primary disease. The patients were matched for sex and age at review PsAS:48.1 (SD 11.3) years vs 1 degree AS:48.4 (SD 11.5), and IBDAS:46.0 (SD 12.7) vs 1 degree AS:45.9 (SD 12.7). The sex distribution for IBDAS (M:F, 1:1), was significantly less (p less than 0.001) than that for PsAS (M:F, 3.5:1) or 1 degree AS (M:F, 2.4:1). Overall, compared to 1 degree AS the PsAS and IBDAS tended to have greater disease severity as defined by e.g., (1) those taking non-steroidal antiinflammatory drugs, 86 vs 72% (p less than 0.01) and 71 vs 60% (p less than 0.05), respectively; (2) decreased spinal mobility (scale 0-8) 5.0 (SD 2.0) vs 4.4 (SD 2.3); p = 0.029 and 4.9 (SD 2.0) vs 3.9 (SD 2.4); p = 0.024, respectively; and (3) PsAS resulted in a higher AIMS pain score; 4.9 (SD 2.5) vs 4.0 (SD 2.4): p = 0.042. By contrast, peripheral joint involvement, number of total hip replacements and capacity for employment were similar in all 3 groups. In conclusion (1) among the AS population the prevalence of 1 degree AS, PsAS and IBDAS is 90, 6 and 4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

New light on uveitis in ankylosing spondylitis.

Inflammatory eye disease is well recognized in ankylosing spondylitis (AS) but the relationship between the uveitis and the spondyloarthropathy is poorly defined. The following conclusions may be drawn from a study of 1331 consecutive patients with AS: the prevalence of uveitis was 40% (535 subjects), almost half of whom had greater than 5 attacks. Family studies of sib pairs, concordant for AS, showed that uveitis occurred randomly with a concordance for uveitis/no uveitis of only 43%. A comparison of patients with (n = 535) and without (n = 796) uveitis showed no important differences. Analysis of potential trigger factors among 72 patients with recurrent disease revealed no seasonal, infective or other correlation. The removal of an intrauterine device from a woman with severe intractable bilateral uveitis was associated with remission of the eye disease. In summary, although genetic background determines susceptibility to uveitis the pattern of the disease suggests the possibility of random environmental triggers unrelated to the course of the underlying rheumatological disorder.

Is there sexual inequality in ankylosing spondylitis? A study of 498 women and 1202 men.

The responses of 1700 members (1202 men) of the National Ankylosing Spondylitis Society to a self-administered questionnaire were analyzed. The male:female ratios for primary ankylosing spondylitis, psoriatic spondylitis and spondylitis associated with inflammatory bowel disease were 2.4:1, 3.5:1 and 1:1, respectively. A positive family history was significantly less prevalent in men than women as were hand, elbow, shoulder and knee symptoms. In a parallel radiographic study, 100 men matched for age of onset and disease duration with 50 women demonstrated similar sacroiliac, cervical and hip disease but worse involvement of the lumbar spine.

Serum keratan sulphate levels rise in rheumatoid arthritis patients, but fall in ankylosing spondylitis patients compared with normal controls.

Serum levels of keratan sulphate (KS) were found to be significantly elevated in patients with destructive and predominantly seronegative rheumatoid arthritis (RA) compared with a control population. Levels in RA did not correlate with clinical or laboratory indices of joint activity or damage. Conversely levels were depressed in ankylosing spondylitis (AS) compared with controls.

Willingness to accept risk in the treatment of rheumatic disease.

STUDY OBJECTIVE: The aim was to assess patients willingness to accept mortal risk in the drug treatment of chronic rheumatic disease. DESIGN: A non-random sample of consecutive patients were interviewed with a standardised survey instrument. SETTING: The study took place in the Royal National Hospital for Rheumatic Diseases, Bath, UK. PATIENTS: 100 consecutive in- and out-patients aged 65 or less were interviewed, 50 with rheumatoid arthritis and 50 with ankylosing spondylitis. Mean age was 48 years with mean disease duration of 14 years. The rheumatoid arthritis group was mainly female (84%), v 26% in the ankylosing spondylitis group. MEASUREMENTS AND MAIN RESULTS: Risk preferences were elicited using the method of standard gamble in the context of a hypothetical new drug. Patients indicated the maximum percentage probability of mortality they regarded as acceptable to achieve four different levels of benefit: total cure (20.7%), relief of pain (16.9%), relief of stiffness (13.1%), return to normal functioning (14.5%). Rheumatoid arthritis patients displayed a higher (p less than 0.05) willingness to accept risk than ankylosing spondylitis patients for all gambles except relief of stiffness. Analysis of variance indicated that willingness to accept risk decreases with the duration of disease and increases with reductions in self assessed health status. CONCLUSIONS: Evaluative methods such as standard gamble can elicit useful risk-benefit preference data from patients to assist those who manage clinical risks.

Selective IgA deficiency and spondyloarthropathy: a distinct disease?

A woman with selective IgA deficiency and severe ankylosing spondylitis (AS), complicated by intractable peripheral arthritis, is described. Three previous cases of selective IgA deficiency and AS have been reported, all of whom had severe AS. It is suggested that selective IgA deficiency is a poor prognostic factor in AS and therefore warrants further investigation to determine the clinical course of such patients.

A prospective nationwide cross-sectional study of NSAID usage in 1331 patients with ankylosing spondylitis.

Drug studies in ankylosing spondylitis (AS) are usually short term, in highly selected patients at academic centers. We present data on 1331 UK patients with AS. Patients were reviewed prospectively in 1985 and 1987. Given the nationwide population base we avoided biases relating to local medical preferences or market forces. Eighty-six percent (n = 1149) were taking medication in 1985 and 78% (n = 1040) in 1987. The most common drug in 1985 was indomethacin (Indo) with 35%, followed by naproxen (N; 21%), piroxicam (P; 9%), diclofenac (D; 7%) and ibuprofen (6%; all others less than 5%). Two years later the figures were Indo 34%, N 19% and D 12%. At followup, survival rates (the number remaining taking each drug) were Indo 75%, N 63%, P 74% and D 67%. The 2 main reasons for stopping a drug were lack of efficacy (Indo 10%, N 25%, P 34%, D 32%) and toxicity (Indo 39%, N 30%, P 30%, D 40%). Sixty percent of patients taking Indo reported good or excellent pain relief, compared with 57% on N, 47% on P and 47% on D. Good or excellent stiffness relief was obtained in 55% of patients on Indo, 38% on N, 44% on P and 40% on D. At any one time over 75% of individuals with AS are receiving drug treatment. The most popular nonsteroidal antiinflammatory drug for AS in 1985 and 1987 was Indo, which scored highest in terms of efficacy, pain relief, stiffness relief and survival. The survival rate over 2 years ranged from 63% (N) to 75% (Indo).

Perception of prescription drug risks: a survey of patients with ankylosing spondylitis.

The ways in which patients perceive the risks of prescription drugs are likely to influence treatment preferences and compliance decisions. But very little is known about the perceived frequency of adverse drug reactions (ADR), their perceived causation and attitudes towards the safety regulation of prescription drugs. A sample of 1,034 patients with ankylosing spondylitis (AS) completed a postal questionnaire on the risks of medicines in general and nonsteroidal antiinflammatory drugs (NSAID) in particular. Serious ADR were perceived to be more frequent with NSAID than prescription drugs generally, and those who had experienced a previous ADR (47%) judged ADR to be more frequent (p less than 0.001). When asked to rate the likelihood that each of 7 reasons were causative of ADR, the most likely reason was perceived to be inadequate information to the patient about the drug, and secondly inadequate patient followup by the prescribing doctor. Responses to a hypothetical AS drug risk scenario indicated high safety expectations for antirheumatic agents; 61% thought that the government should take a drug off the market if there is any evidence of fatal ADR. The results of this survey suggest the need for greater patient information and education on the risks and benefits of medicines to modify perceptions and false expectations.

Postsalmonella reactive phenomena in 2 patients with ankylosing spondylitis: no modification of the underlying disease.

HLA-B27 related disease occurs in 2 main forms, ankylosing spondylitis (AS) or reactive arthropathy/Reiter's syndrome. These entities often "breed true" within families or distinct ethnic groups. Reactive arthropathy/Reiter's syndrome may be complicated by AS, but little is known about the impact on AS of a de novo reactive arthropathy occurring at a later date. We describe 2 patients with AS who developed postsalmonella reactive phenomena several years after the onset of their primary disease. In both patients the intestinal salmonella infection did not modify the course of the AS.

Retrospective analysis of 376 irradiated patients with ankylosing spondylitis and nonirradiated controls.

Controlled, prospective studies of deep X-ray therapy (DXT) in ankylosing spondylitis (AS) are lacking. We studied a self-help group of 1702 consecutive individuals with AS. Of these, most of whom were men, 376 (22%) had undergone DXT. An attempt was made to select a control for each. Because of the difference in ages at onset, 100 treatment recipients were matched with 100 controls (mean ages 44.5 years and 44.7 years, respectively). The mean Ankylosing Spondylitis Assessment Questionnaire disability score (range 0-8) was worse for the DXT group (5.5 vs 4.8 for controls: p less than 0.0001) and most components of the Arthritis Impact Measurement Scales showed a poorer outcome for those irradiated. Thus, 22% of nationwide AS sufferers had irradiation. This group could also have had more severe disease at the outset. At review, somewhat fewer of the irradiated group were taking NSAID. Although irradiation may have favorably affected the course of these patients our data do not support the use of irradiation except in exceptional cases.

Destructive arthritis, rheumatoid factor, and HLA-DR4. Susceptibility versus severity, a case-control study.

In response to the continuing debate as to whether seronegative rheumatoid arthritis (RA) and seropositive RA are part of the same disease spectrum or are distinct disorders, we evaluated 720 patients with definite and classic RA, of whom 53 subjects had definite persistently seronegative destructive disease. For all but 1 seronegative RA patient, a seropositive RA case control was identified and matched for age, disease duration, degree of destruction on hand radiographs, and disease-modifying drug therapy. DR typing was undertaken on these 105 patients, together with scoring of hand radiographs. The frequency of DR4 was 69% in seropositive RA patients and 60% in seronegative RA patients (P = 0.22), versus 36% in 318 healthy controls (P = 0.008 and P = 0.007 versus seropositive and seronegative RA, respectively). Patients were matched and rematched with different controls in a series of subanalyses in order to make comparisons of hand radiograph scores. We found that HLA-DR4 was associated with destructive RA in both seropositive and seronegative RA patients. In general, DR4+ patients had more severe disease by radiologic criteria than did DR4- patients. Thus, HLA-DR4 may be an additive factor to the serologic status and may be more closely related to disease severity than to disease susceptibility.

The outcome of 138 total hip replacements and 12 revisions in ankylosing spondylitis: high success rate after a mean followup of 7.5 years.

The outcome of total hip replacement (THR) in ankylosing spondylitis (AS) is unclear. Concern has often been voiced by both surgeons and physicians regarding potential reankylosis, mechanical failure and poor function. We present an independent review of the patients' perception of outcome in 150 total hip replacements (138 primary + 12 revisions) in 87 subjects with AS. The mean followup was 7.5 years (1-34 years). Twelve were followed for greater than 15 years and 33 for greater than 10 years. Bilateral replacements were performed in 51 of the 87 patients (59%), 33 (65%) of whom had bilateral surgery within a 12-month period. Failures were early and rare. Twelve of 138 (9%) were revised (8 patients, mean of 3.6 years postoperatively) and 3 of the 12 were rerevisions. Twelve total hip replacements followed for 15 years or more resulted in only 2 failures (same patient: reankylosis) while 3 failed out of 33 followed for 10 years or more. Overall, for the 138 total hip replacements in situ (including the revisions), the patients considered outcome to be good or very good in 86%, while 89% had no (63%) or mild (26%) pain. Mobility was good or very good in 44%. On a scale of 1-5 (very poor to very good) patients followed for up to 5 years scored 4.7, as did those followed for greater than 15 years. Sixty-nine percent of the male recipients under age 60 are at work. Reankylosis occurred in only 1 patient (4 hips). In general the first and second hips replaced had an equally good outcome. The long-term outcome of total hip replacement in AS is very good. The few failures occurred early, and patients were as satisfied with the outcome more than 15 years postoperatively as they were within the first 5 years.

Relative role of genetic and environmental factors in disease expression: sib pair analysis in ankylosing spondylitis.

Forty-two sib pairs concordant for ankylosing spondylitis (mean disease duration 20.1 years) were assessed to define the relative role of genetic and environmental factors in determining age and calendar year of disease onset, systemic features, functional outcome and prognosis, and radiologic progression. Twenty-seven pairs were of the same sex (male/male n = 21, female/female n = 6). The correlation coefficient was not significant for age at onset (rs = 0.235), but was much higher for calendar year of onset (rs = 0.702, P less than 0.01). These data were confirmed by two-way analysis of variance: between sibs, the F probability was 0.07 for age at onset (41 degrees of freedom, F ratio 1.6) and was less than 0.001 for calendar year of onset (41 degrees of freedom, F ratio 5.45). Thus, it is suggested that environmental factors play the greater role in the timing of onset. Concordance for the presence or absence of uveitis was only 43%, again suggesting that genetic factors are less significant than the environment. Conversely, genetic factors are more important in influencing prognosis. A disability and pain index revealed that sibs had a closer score than expected by chance alone (P = 0.035); also, the correlation coefficient for blinded radiologic analysis (pelvic and lumbar views) was significant for pairs of sibs (rs = 0.859, P less than 0.01), but was not significant for random pairs of subjects (rs = -0.144). In contrast, within-sib pair and random subject-pair analyses of hip radiographs revealed rs = -0.111 and -0.033, respectively, neither of which was significant.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between pelvic, spinal and hip involvement in ankylosing spondylitis--one disease process or several?

UNLABELLED: One hundred and one consecutive patients with ankylosing spondylitis (males 85%) were reviewed by radiographic evaluation after a mean disease duration of 21.2 years (mean age at onset 22.9 years). Osteitis pubis occurred in seven cases of varied duration and severity of disease. Hip involvement (grade 2-4) occurred in 19%. Their mean age of onset (19.6 years) was younger than for those with normal hips (25.1 years; p = 0.003). Lone sacroiliitis (grade 3 and 4) without ascending spinal disease occurred in 11 patients. The mean age at onset for those with lone sacroiliitis and marked spinal disease was similar (23.3 and 24.9 years respectively; NS). By contrast, disease duration was 13.3 and 28.4 years respectively (p = 0.0007). Five patients (three women) had severe pelvic and cervical spine disease with normal lumbar spine. IN CONCLUSION: 1. Osteitis pubis occurs as an unusual, random event. 2. Hip involvement is an expression of young age at onset. 3. Lone sacroiliitis is uncommon and progression to ascending spinal disease is primarily a function of disease duration. 4. Skip lesions occur rarely and particularly in women. 5. Sacroiliitis and ascending spinal disease are part of the same spectrum.

Ankylosing spondylitis--an analytical review of 1500 patients: the changing pattern of disease.

To avoid biases inherent in the study of referral patients seen at a single unit, we investigated a group of 1500 patients (males 71%), members of the UK National Ankylosing Spondylitis Society (NASS). Patients were divided into 15 cohorts by year of onset (mean size 91). The median delay in diagnosis for these cohorts was greater than 6 years until 1974. Thereafter, there was a marked improvement with the most recent cohort waiting a median of 2 years for diagnosis (e.g., 1969/72 cohorts vs 1979/82 cohorts; mean delay 7.4 years vs 2.3 years, p less than 0.0001). Until 1974 the median delay for women was 9 years compared to 6 years for men (e.g., 1956/62 cohorts 11 and 7 years, p less than 0.0015, falling to 3 and 2.5 years, respectively by 1979/82, p = NS). Major differences were seen when the 14 health regions were taken separately; the median delay ranged from 9 years for the 3 "worst" regions to 4 years for the 3 "best" (p = 0.022). This was reflected in the percentage with delay in diagnosis longer than 2 years (80 and 58%, respectively; chi 2 = 11.31, p less than 0.01). Strikingly, the median age of onset of symptoms steadily increased from 18 years in 1930/40 to 28 years in 1981/82 (e.g., 1956/62 vs 1969/72; mean ages 21.4 vs 23.5 years, p less than 0.004 and 1969/72 vs 1979/82; 23.5 years vs 28.7 years p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic intervention in rheumatoid arthritis: a case-controlled comparison of seronegative and seropositive disease.

The records of 684 patients with rheumatoid arthritis (RA) attending a referral centre were evaluated. All available patients (62 cases) with definite seronegative disease were matched, where possible, for sex, age and year of onset with seropositive controls (54 cases). Seronegative females were just as likely as those who were seropositive to require treatment with disease-modifying antirheumatic drugs, whereas seronegative males were significantly less likely to do so than seropositive controls. There were no major differences in outcome or drug toxicity. Orthopaedic surgery was equally common in the two groups, with a similar spectrum of procedures, but there was a trend towards more frequent upper limb large joint arthroplasty in the seronegative group, and this was particularly evident when elbow prostheses were considered. Seronegative rheumatoid disease (at least in females) may be as severe as seropositive disease in a referral-centre population and should be treated with similar vigour.

The natural history of juvenile-onset ankylosing spondylitis: a 24-year retrospective case-control study.

UNLABELLED: One hundred and thirty-five patients with juvenile-onset ankylosing spondylitis (JAS: less than 16 years at onset, mean 12.8 years) were compared to 135 adult-onset spondylitics (AAS: greater than 21 years at onset, mean 26.1 years), controlled for disease duration (24.5 and 23.5 years, respectively), to assess the outcome of juvenile-onset disease. Review was by postal questionnaire and health-assessment measures. The sex distribution was similar: 73% and 74% males, respectively. All parameters showed comparable outcome with the exception of the numbers in full-time employment (JAS 74%, AAS 56%; p less than 0.01) and total hip replacements (JAS 17%, AAS 4%; p less than 0.01). IN CONCLUSION: (a) the premature hip is particularly at risk in ankylosing spondylitis; (b) there are few differences between the outcome of JAS and AAS; (c) overall, JAS patients do well in adulthood.