Disease activity in and quality of life of patients with psoriatic arthritis mutilans: the Nordic PAM Study.

OBJECTIVE: To describe the social status and health-related quality of life of patients with psoriatic arthritis mutilans (PAM) in the Nordic countries. METHOD: Patients with at least one mutilated joint confirmed by radiology were studied. Disease activity involving joints and skin, physician-assessed disease activity, and patient's education and work status were recorded. Data from the 36-item Short Form Health Survey, Health Assessment Questionnaire and Dermatology Life Quality Index questionnaire were gathered and correlated with disease duration, pain, and general well-being (visual analogue scale). The controls were 58 Swedish patients with long-standing psoriatic arthritis sine PAM. RESULTS: Sixty-seven patients were included. Patients with PAM had a protracted disease history (33 ± 14 years) and disease onset at a relatively early age (30 ± 12 years). Overall inflammatory activity at inclusion was mild to moderate. The mean number of mutilated joints was 8.2 and gross deformity was found in 16% of patients. Forty per cent were treated with biological and 32% with conventional synthetic disease-modifying anti-rheumatic drugs. Forty-two per cent had retired early or were on sick leave. Impaired functional capacity with little or no ability to perform self-care or everyday tasks was reported by 21% of the patients. Patients between 45 and 60 years of age reported the most impaired quality of life in comparison to the control group. CONCLUSION: PAM seriously affects social functioning. Whether early recognition of PAM and new forms of therapy can improve disease outcome and quality of life remains to be studied.

Concomitant fibromyalgia in rheumatoid arthritis is associated with the more frequent use of biological therapy: a cross-sectional study.

OBJECTIVES: To compare the 28-joint Disease Activity Score (DAS28) and its components in patients with rheumatoid arthritis (RA) with and without concomitant fibromyalgia (FM), and to investigate the use of biological treatment in the two groups. METHOD: Questionnaires developed to diagnose FM were handed out among RA patients during their planned visits. Values for DAS28 were obtained from the DANBIO registry. Demographic data and data on patients' medical treatment, disease duration, serological and radiological status were retrieved from patients' files. The χ2 test and an unpaired t-test were applied to investigate group differences in the use of biological therapy, baseline characteristics, patient-reported outcomes, and DAS28 between groups when appropriate. RESULTS: Questionnaires were completed by 162 out of 264 (61%) patients. Twenty-five patients (15.4%) with concomitant FM were identified. No group differences were found regarding disease duration, age, gender, and serological status. Of the RA patients with concomitant FM, 64% were treated with biological therapy vs. 32% of RA patients without concomitant FM (p = 0.002). The mean DAS28 in the FM group was 4.4 compared to 2.9 in the non-FM group (p < 0.001). Elevated DAS28 in the FM group resulted from a high tender joint count (p = 0.003) and a high visual analogue scale (VAS)-global score (p < 0.001). Erosions were more frequent in the non-FM group (p = 0.04). CONCLUSIONS: Concomitant FM in patients with RA is associated with a higher DAS28 due to subjective parameters and with the more frequent use of biological treatments. This raises the question of whether the more frequent use of biologics in these patients is justified by inflammation, or is instead due to persistent pain and other centrally mediated symptoms.

Cardiac Abnormalities in Adult Patients With Polymyositis or Dermatomyositis as Assessed by Noninvasive Modalities.

OBJECTIVE: Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies. The study objective was in a controlled setting to describe cardiac abnormalities by noninvasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction. METHODS: In a cross-sectional study, 76 patients with PM/DM and 48 matched healthy controls (HCs) were assessed by serum levels of cardiac troponin I, electrocardiography, Holter monitoring, echocardiography with tissue Doppler imaging, and quantitative cardiac (99m) Tc-pyrophosphate ((99m) Tc-PYP) scintigraphy. RESULTS: Compared to HCs, patients with PM/DM more frequently had left ventricular diastolic dysfunction (LVDD) (12% versus 0%; P = 0.02) and longer QRS and QT intervals (P = 0.007 and P < 0.0001, respectively). In multivariate analysis, factors associated with LVDD were age (P = 0.001), disease duration (P = 0.004), presence of myositis-specific or -associated autoantibodies (P = 0.05), and high cardiac (99m) Tc-PYP uptake (P = 0.006). In multivariate analysis of the pooled data for patients and HCs, a diagnosis of PM/DM (P < 0.0001) was associated with LVDD. CONCLUSION: Patients with PM or DM had an increased prevalence of cardiac abnormalities compared to HCs. LVDD was a common occurrence in PM/DM patients and correlated to disease duration. In addition, the association of LVDD with myositis-specific or -associated autoantibodies and high cardiac (99m) Tc-PYP uptake supports the notion of underlying autoimmunity and myocardial inflammation in patients with PM/DM.

Psoriatic arthritis mutilans (PAM) in the Nordic countries: demographics and disease status. The Nordic PAM study.

OBJECTIVE: To determine the prevalence and clinical characteristics of psoriatic arthritis mutilans (PAM) in the Nordic countries. METHOD: Patients with putative PAM aged ≥ 18 years were recruited. Fifty-nine patients were included after clinical examination. RESULTS: The prevalence of PAM in the adult Nordic population was estimated to be 3.69 per million inhabitants [95% confidence interval (CI) 2.75-4.63]. The female to male ratio was close to 1:1. The mean age of skin disease onset was 25 years and the mean age of onset of joint disease was 30 years. The onset of skin disease was 2 years earlier among female patients. At inclusion, the mean duration of arthritis was 27 ± 11 years for male patients and 33 ± 11 years for female patients. PAM was most frequently seen in the distal interphalangeal (DIP) joints of the toes, followed by the IP joint of the thumb and the DIP joint of the little finger on the left hand. Female and male patients had similar numbers of painful and swollen joints. Enthesitis was found in 19 patients (32%), while 38 patients (64%) had a history of dactylitis. Twenty-three of these 38 patients (61%) had a history of dactylitis in the same finger/toe as they had PAM. At the time of inclusion, 45% of the patients were found to have clear or almost clear skin. CONCLUSIONS: PAM in the Nordic countries has a low prevalence, with only three to five cases per million inhabitants. The majority of the patients present with mild skin disease.

Ankylosing spondylitis in Danish and Norwegian twins: occurrence and the relative importance of genetic vs. environmental effectors in disease causation.

OBJECTIVE: To estimate the influence of genetic effects in the aetiology and pathogenesis of ankylosing spondylitis (AS). METHODS: The study comprised one Norwegian and two Danish nationwide twin surveys. In 1994 and 2002, respectively, 37,388 and 46,331 Danish twin individuals were asked by questionnaire if they had AS. Similarly, in 1998, 12,718 Norwegian twins were asked if they had AS using a questionnaire phrased according to the Danish survey. Twins reporting AS were categorized according to the modified New York criteria. RESULTS: A total of 113 twin individuals reported AS, of whom 81 (72.3%) participated in validation of the diagnosis. After validation, 39 probands were diagnosed with AS. Subsequent invitation of co-twins resulted in 27 complete pairs. The point prevalence and the annual incidence of AS was 0.1% and 3/100,000 person-years (pyr) among the Danish twins. The positive predictive value of self-reported AS was 49.3%. Probandwise concordance rates on AS were (2/5) 40% in monozygotic (MZ) and (1/23) 4% in dizygotic (DZ) twins [difference 35% (95% CI 2.9-72.8), p = 0.26]. Heredity analysis including previously published and the present HLA-B27-positive twin pairs indicated that additive genetic effects account for 94% (95% CI 0.56-0.99) of the variance in the causation of AS. CONCLUSION: Self-reported AS needs careful validation. The occurrence of AS in a Danish twin population was 0.1% and accords well with previous studies on singletons in hospital settings. The present study adds to previous evidence of a major genetic effect in the pathogenesis of AS.

On the heritability of psoriatic arthritis. Disease concordance among monozygotic and dizygotic twins.

OBJECTIVE: A nationwide unselected twin population to estimate the relative importance of genetic and environmental effectors in the aetiopathogenesis of psoriatic arthritis (PsA). METHODS: The study comprised three Danish nationwide twin cohorts. In 1994 and 2002 a total of 37 388 and 46 418 Danish twin individuals respectively were asked by questionnaire if they had PsA. Twins reporting PsA were invited to participate in a clinical examination. Patients were classified according to the Moll and Wright and the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria. Heritability was estimated by probandwise concordance rates and variance component analysis. RESULTS: 228 twin individuals reported PsA. Following diagnostic validation in 164 (70%), 50 probands were diagnosed with PsA according to the Moll and Wright criteria. Five of their co-twins were either dead, had emigrated, or did not participate in the twin study and nine did not respond, resulting in 36 complete pairs. A total of one of 10 monozygotic pairs and one of 26 dizygotic pairs were concordant for PsA, yielding a 6.2% difference in proportions (95% CI: -11%, 37%). Five of 10 monozygotic pairs and four of 26 dizygotic pairs were concordant for psoriatic skin disease implying a 35% difference (95% CI: 2%, 60%, p<0.05). CONCLUSIONS: This first twin study on PsA confirms that genes are important in the causation of psoriatic skin disease. Despite the limited statistical power, the almost identical concordance rates for PsA in monozygotic and dizygotic twins stresses the importance of the continued search for non-genetic effectors in PsA.

The occurrence of psoriatic arthritis in Denmark.

OBJECTIVE: To apply and compare different classification criteria on a representative nationwide sample of psoriatic arthritis (PsA) twins and to estimate the prevalence and incidence of PsA. METHODS: The study comprised three Danish nationwide twin cohorts. In 1994 37 388 Danish twin individuals and in 2002 46 418 twin individuals received a questionnaire, including questions on rheumatic diseases. Twins reporting PsA and their co-twins were classified according to the Moll and Wright and CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria based on interview, clinical examination and scrutiny of medical records. RESULTS: 228 twin individuals reported PsA and 164 (72%) participated in clinical validation. By using the Moll and Wright and CASPAR criteria, 54 and 50 cases were diagnosed with PsA respectively. The positive predictive value of self-reported PsA was 31%. According to the Moll and Wright and CASPAR criteria the prevalence was 0.15% (95% CI: 0.13%, 0.22%) and 0.14% (95% CI: 0.11%, 0.19%) respectively. The annual incidence rate based on new self-reported cases in 2002 was 6/100 000 person-years (95% CI: 3/100 000 person-years, 11/100 000 person-years). CONCLUSIONS: The positive predictive value of self-reported PsA was 31%. The prevalence and incidence figures of PsA were equivalent to the previously reported occurrence in population- and hospital-based studies.

Adaptation of the Bath measures on disease activity and function in ankylosing spondylitis into Danish.

OBJECTIVE: Adaptation of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Global Score (BASG), and the Bath Ankylosing Spondylitis Functional Index (BASFI) for defining disease status in ankylosing spondylitis (AS) and related diseases for use in Denmark. METHODS: The BASDAI, BASFI, and BASG were translated into Danish and subsequently field-tested among 17 AS patients for relevance, face, and content validity. Reliability and validity were assessed by administering the new measures and a comparator instrument to 113 AS patients on two occasions. RESULTS: Test-retest reliability was high (>0.90) and the random measurement error was within+/-2.0 for the BASG and within approximately+/-1.5 for BASDAI and BASFI, which is acceptable for most clinical settings. The measures have good internal consistency and are able to discriminate between functional impairment and disease activity according to the Nottingham Health Profile (NHP) and the Stanford Health Assessment Questionnaire (HAQ). CONCLUSION: Danish versions of the BASG, BASDAI, and BASFI are feasible for application in clinical trials and epidemiological studies on AS in Denmark.

Limited effect of sulphasalazine treatment in reactive arthritis. A randomised double blind placebo controlled trial.

OBJECTIVE: To assess the efficacy and safety of sulphasalazine in reactive arthritis. METHODS: Double blind placebo controlled trial of six months duration comparing sulphasalazine 2-3 g per day (n = 37) with matching placebo (n = 42) in adults with active reactive arthritis (age 19-57 years, median 34). Treatment response was evaluated once a month by changes in erythrocyte sedimentation rate (ESR), pain, peripheral arthritis, tender iliosacral joints, entesopathy, extra-articular manifestations, and working ability. RESULTS: 15 patients in the sulphasalazine group and eight in the placebo group withdrew from the study prematurely. Adverse events, primarily gastrointestinal, were the main reason for withdrawal in the actively treated group. Intention-to-treat analyses showed significant improvements over time in both groups in ESR, pain, and number of swollen joints (P < 0.01). Number of days on sick leave decreased significantly in the sulphasalazine group only (P < 0.01). No significant differences between the two groups were present after six months. Among the patients completing the trial according to protocol, persistent complete remission had occurred within two months in five (23%) of the actively treated, but in no placebo treated patients (P = 0.013). CONCLUSIONS: Sulphasalazine seemed to improve only the very short term outcome of reactive arthritis. The possible beneficial effect of the drug should also be weighed against the risk of adverse events. Although these were mainly mild, almost 25% of the patients in the actively treated group gave up treatment for this reason.

The humoral immune response to Chlamydia trachomatis in patients with acute reactive arthritis.

Sera from 25 patients with clinical signs of reactive arthritis were analysed for antibodies against Chlamydia trachomatis by immunoblotting. Purified elementary bodies, purified Chlamydia outer membrane complexes, and purified recombinant subcomponents were used as antigens. Antibodies against C. trachomatis cysteine rich outer membrane protein 2 (Omp2) and lipopolysaccharide (LPS) were detected in 10 patients. Thus 40% of the patients presented antibodies specific for C. trachomatis. There was no correlation between acute reactive arthritis and antibodies to heat-shock proteins GroEL, GroES and DnaK.

Intravenous methylprednisolone pulse therapy in ankylosing spondylitis.

The aim of this double-blind study was to compare the effect of high-dose (1000 mg) and low-dose (375 mg) methylprednisolone pulse therapy administered intravenously once daily for three consecutive days, in active ankylosing spondylitis. Seventeen patients with active ankylosing spondylitis were randomly allocated to high-dose (8 patients) or low-dose (9 patients) regimen. Although there was no placebo group in this study, it is our impression that in patients with active ankylosing spondylitis, both high-dose (1000 mg) and low-dose (375 mg) methylprednisolone pulse therapy given on three consecutive days, is effective as regards pain relief and improvement in spinal mobility. There were no statistically significant differences between the two groups, though there was a trend towards the high dose yielding a greater and longer lasting improvement. No serious adverse reactions were observed.

A randomised double-blind multicentre trial comparing tenoxicam and ketoprofen in osteoarthritis.

A double-blind multicentre study was conducted to compare the efficacy and safety of tenoxicam and ketoprofen in the treatment of osteoarthritis (OA). The study comprised 307 patients and the treatment period was 12 weeks. One-hundred and fifty-five patients received 20 mg tenoxicam once-daily and 152 patients received 100 mg ketoprofen b.i.d. Seventy-seven patients were prematurely withdrawn; 32 patients in the tenoxicam group and 45 in the ketoprofen group (p less than 0.05). There were only small insignificant differences in the efficacy parameters with the exception that significantly more patients in the tenoxicam group took paracetamol tablets during treatment. Adverse events developed in 29.0% of the patients on tenoxicam and in 47.3% of the patients on ketoprofen, this difference was statistically significant (p less than 0.05). The adverse events were predominantly from the gastrointestinal tract and the central nervous system. No serious side-effects occurred and the laboratory parameters showed no clinically relevant changes. The investigator's overall impression of treatment showed no significant difference between groups. Excellent or good results were judged in 55.2% of the patients on tenoxicam and in 62.1% on ketoprofen (p greater than 0.05). Tenoxicam appears to have a reasonable balance between efficacy and side-effects in the treatment of OA.

Intravenous methylprednisolone pulse therapy in ankylosing spondylitis.

For several years the medical treatment of active ankylosing spondylitis (AS) has been NSAID because gold, penicillamine, antimalarials and steroids have been without efficacy. In 1981, Mintz et al reported that methylprednisolone pulse therapy (MPPT) had an excellent effect in patients with AS. Seven patients with active AS and insufficient efficacy of NSAID for three months were treated with one gram methylprednisolone daily given intravenously for three successive days. Mobility and pain were recorded before, during, and after treatment. Significant pain relief and improvement of mobility of the spine for at least six weeks were clearly demonstrated (p less than 0.05). Finger to floor distance and chin manubrium distance improved significantly for at least six months (p less than 0.05). We conclude that intravenous MPPT is a useful treatment in patients with active AS when NSAID is insufficient.

Steroids reduce complement activation in rheumatoid arthritis.

Patients with seropositive, classical rheumatoid arthritis (RA) with severe active disease have raised plasma concentrations of the complement C3 split product C3d. These values display little diurnal or circadian variation in the individual patient. During a 3-month period the variation was within 10 mU/l in 45 patients (ref. range 20-52 mU/l, RA patients up to 120 mU/l.) Six RA patients were treated with steroids on clinical indication, and the plasma C3d, Ritchie index and pain score before and during the treatment (30 mg prednisolone per day) were measured. The variables showed a steady decrease during the next 14 days. Plasma C3d fell 2/3 of the total fall within the first 48 hours, while the serum total haemolytic complement activity, complement C3 and C4 did not change significantly. This shows that the anti-inflammatory effect of steroids is accompanied by a reduction of complement activation.

Controlled release indomethacin (Indotard). Clinical trial in patients with rheumatoid arthritis.

In a double-blind, crossover multicentre trial the effect on morning stiffness and occurrence of side effects of a controlled-release indomethacin preparation, Indotard, was compared with a conventional preparation, Indocid. 30 Patients between 38 and 74 years of age--six from each centre--underwent the investigation: A 4-day escalating period and 2 X 7 days' treatment. In the average figures, no difference in effect or side effects could be seen between Indotard 50 mg given twice and Indocid 25 mg given four times daily. There was, however, a marked preference among the younger (less than 62 years) for the controlled-release formulation and a preference among the older for the conventional preparation.