Physical activity and body composition in patients with ankylosing spondylitis.

OBJECTIVE: Patients with ankylosing spondylitis (AS) are at risk for accelerated muscle loss and reduced physical activity. Accurate data are needed on body composition and physical activity in this patient group. The purpose of this study was to investigate body composition and objectively assessed physical activity in patients with AS. METHODS: Twenty-five AS patients (15 men, mean ± SD age 48 ± 11 years) were compared with 25 healthy adults matched for age, sex, and body mass index. Body composition was measured using a 3-compartment model based on air-displacement plethysmography to assess body volume and deuterium dilution to assess total body water. The fat-free mass index (FFMI; fat-free mass divided by height squared) and the percent fat mass (%FM) were calculated. Daily physical activity was assessed for 7 days using a triaxial accelerometer and physical fitness with an incremental test until exertion on a bicycle ergometer. Blood samples were taken to determine C-reactive protein (CRP) level and tumor necrosis factor α. RESULTS: Accelerometer output (kilocounts/day) showed the same physical activity level for patients and controls (mean ± SD 319 ± 105 versus 326 ± 66). There was no difference in the FFMI or %FM between the patients and controls. Physical activity was positively related to the FFMI (partial R = 0.38, P = 0.01) and inversely related to CRP level (R = -0.39, P < 0.01), independent of group. CRP level was inversely related to the FFMI, but the effect was less strong than with physical activity (partial R = -0.31, P = 0.03). CONCLUSION: Daily physical activity may help preserve fat-free mass in patients with AS.

[Eosinophilic fasciitis; the importance of early detection for optimal outcomes]. / Eosinofiele fasciitis, het belang van een tijdige herkenning voor de genezing.

Eosinophilic fasciitis (EF) is a disease with unknown aetiology, although an immunologic pathogenesis is suspected. The characteristic features of this inflammatory disease include scleroderma-like skin indurations, predominantly on the extremities, and peripheral blood eosinophilia. Internal organs are generally not affected. Initiation of systemic glucocorticoid therapy at an early stage results in a good response and remission of symptoms. This is illustrated in 3 cases of EF to demonstrate the importance of early detection in this disease.

Poncet's disease: reactive arthritis accompanying tuberculosis. Two case reports and a review of the literature.

OBJECTIVE: Reactive arthritis (ReA) in tuberculosis (TB) is known as Poncet's disease. It is a rare aseptic form of arthritis observed in patients with active TB. We present two such patients and review the literature on Poncet's disease. METHODS: Two patients who were identified with Poncet's disease at the Department of Rheumatology of Erasmus MC, Rotterdam University Hospital, during the last 5 yrs are reported. In addition, a review of the literature on Poncet's disease is given: the PubMed/MEDLINE database was studied up to December 2005 using the term 'Poncet's disease' and the terms 'arthritis', 'reactive' and 'tuberculosis'. RESULTS: After careful work-up, the polyarthritis and erythema nodosum in both presented patients with active TB could be diagnosed as Poncet's disease. Resolution of the arthritis with anti-TB drugs occurred in just a few days. Reviewing the literature, 50 case reports were found. In most reports 'Poncet's disease' was described as an aseptic polyarthritis, presumably ReA arthritis developing in the presence of active TB elsewhere. However, no uniform characterization of the term 'Poncet's disease' could be abstracted from these reports. CONCLUSION: Both presented patients and the review of the literature demonstrate that active TB may be complicated by ReA known as Poncet's disease. Early recognition of this rare complication of TB is of major importance to avoid delayed initiation of appropriate treatment.

Diagnostic value of blind synovial biopsy in clinical practice.

OBJECTIVE: To assess the diagnostic value of blindly performed synovial biopsies in carefully selected patients with unclassified arthritis. METHODS: Synovial tissue was obtained blindly under local anaesthesia. The Arthroforce III take-apart 3.5 mm needle and 1.5 mm grasping forceps were used for this purpose. RESULTS: Four patients with unclassified arthritis could be diagnosed properly based upon examination of synovial tissue of the knee obtained by an easy-to-perform blind biopsy. The arthritis of the four patients was diagnosed as being part of Erdheim-Chester disease, sarcoidosis, multicentric reticulohistiocytosis and arthritis caused by foreign-body material, respectively. CONCLUSIONS: Analysis of synovial tissue obtained during a blind biopsy procedure has diagnostic potential in carefully selected patients with unclassified arthritis. The common denominator in all the cases presented was a differential diagnosis consisting of a rheumatological disease with characteristic histological features.

Tumour necrosis factor alpha blockade in treatment resistant pigmented villonodular synovitis.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is considered to be a neoplastic-like disorder of the synovium histologically characterised by villonodular hyperplasia, resulting in dense fibrosis and haemosiderin deposition. The pathogenesis of the disease is still unknown. CASE REPORT: A patient presented with severe treatment resistant PVNS of the right knee joint. Several conventional treatment regimens, including open surgical synovectomy and intra-articular injections of yttrium-90 ((90)Y) failed to control the disease. After finding marked tumour necrosis factor alpha (TNF alpha) expression in arthroscopic synovial tissue samples, treatment with an anti-TNF alpha monoclonal antibody (infliximab) at a dose of 5 mg/kg was started. Additional courses with the same dose given 2, 6, 14, and 20 weeks later, and bimonthly thereafter up to 54 weeks, controlled the signs and symptoms. Immunohistological analysis at follow up identified a marked reduction in macrophage numbers and TNF alpha expression in the synovium. DISCUSSION: This is probably the first case which describes treatment with TNF alpha blockade of PVNS in a patient who is refractory to conventional treatment. It provides the rationale for larger controlled studies to elucidate further the efficacy of TNFalpha blockade treatment in refractory PVNS.

Adalimumab, a fully human anti-TNF-alpha monoclonal antibody, treatment does not influence experimental UV response in the skin of rheumatoid arthritis patients.

TNF-alpha is known to play an important role in UV-induced immunomodulation and photodamage. It plays a role in UVB-mediated induction of apoptosis and is a strong inducer of the c-Jun N-terminal kinase (JNK) pathway, which eventually leads to the loss of dermal collagen and elastin content. Recently chimeric anti-TNF-alpha has been introduced as a therapy for rheumatoid arthritis. The aim of the present study was to investigate the effect of anti-TNF-alpha treatment on UV-induced DNA damage, apoptosis, and induction of matrix metallo proteinases. Twelve patients with rheumatoid arthritis were included and irradiated with 2 MED broadband UVB before and after administration of 0.5 mg/kg anti-TNF-alpha monoclonal antibody. Twenty-four hours after irradiation biopsies were taken. Frozen and paraffin sections were stained for p53, c-Jun, phosphorylated c-Jun, sunburn cells and MMP-1. No significant changes were observed in the expression of p53 and sunburn cells and MMP-1 content after treatment with anti-TNF-alpha, whereas a slight but significant decrease in c-Jun and phosphorylated c-Jun expression was noted (P = 0.0250 and P = 0.0431, respectively). Our results showed no influence of anti-TNF-alpha on UV response at therapeutic doses in patients with rheumatoid arthritis.

Chronic comorbidity in patients with early rheumatoid arthritis: a descriptive study.

OBJECTIVE: To study the presence of chronic coexisting diseases in patients with rheumatoid arthritis (RA) and its effect on RA treatment, disease course, and outcome during the first years of the disease. METHODS: From January 1985 to December 1990, 186 patients with recent onset RA were enrolled in a prospective longitudinal study. Between January 1991 and November 1992 patients were interviewed on the basis of a comorbidity questionnaire. For analysis the diseases were coded according to the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) medical diagnoses. Disease activity during the period of followup was measured by the Disease Activity Score. Outcome in terms of physical disability (Health Assessment Questionnaire) and radiological damage (Sharp's modified version) over 3 and 6 year periods was determined. RESULTS: In the group of 186 patients, with mean disease duration of 4.3 years at January 1991, 50 patients (27%) reported at least one chronic coexisting disease. The most frequently reported coexisting diseases were of cardiovascular (29%), respiratory (18%), or dermatological (11%) origin. For the major part (66%) chronic coexisting diseases were already present before onset of RA. No statistically significant differences in use of disease modifying antirheumatic drugs or corticosteroids were observed between RA patients with and without chronic coexisting diseases. No statistically significant differences were found in disease activity or in outcome in terms of physical disability and radiological damage over 3 and 6 year periods between the 2 groups with RA. CONCLUSION: The results showed that about 27% of patients with RA in this inception cohort had at least one chronic coexisting disease. Treatment, disease course, and outcome did not differ between patients with and without chronic coexisting diseases during the first years of the disease.

Change in bone mineral density in patients with rheumatoid arthritis during the first decade of the disease.

OBJECTIVE: Rheumatoid arthritis (RA) has been reported to be associated with bone loss during the first years of the disease. The magnitude of this problem after the initial years has not yet been evaluated. In the present study, the change in bone mineral density (BMD) in patients with recent-onset RA as well as the effects of inflammation, mobility, and the use of prednisone on this change were studied in the first decade of the disease. METHODS: BMD was measured twice in 76 RA patients with mean disease durations of 2.35 years at the first BMD measurement and 8.90 years at the second BMD measurement. BMD was measured in both hips using dual x-ray absorptiometry. Results were expressed as mean +/- SEM Z scores (using age- and sex-matched reference values) and as mean +/- SEM percent change in BMD (in gm/cm2) per year. The effects of inflammation, mobility, and the use of prednisone on change in BMD were evaluated using multiple linear regression analyses. RESULTS: At the first BMD measurement, RA patients had lower BMD compared with the reference values (Z score -0.42+/-0.11, 95% confidence interval [95% CI] -0.64, -0.20). Between the 2 measurements, we observed a small decrease in BMD of -0.28+/-0.11%/year (95% CI -0.07 to -0.49). However, the rate of bone loss was smaller than expected. The Z score increased by 0.13+/-0.05 between the 2 BMD measurements (95% CI 0.02, 0.23). Only the use of prednisone was significantly associated with increased bone loss. In a separate analysis that included only postmenopausal women, increased physical activity and longer time since menopause were both associated with decreased bone loss. In this subgroup of patients, the use of prednisone was significantly associated with increased bone loss as well. A high erythrocyte sedimentation rate was associated with increased bone loss, but this did not reach statistical significance. CONCLUSION: After the initial years of the disease, bone loss in RA patients is lower than expected compared with age- and sex-matched reference values. Postmenopausal RA patients with low levels of physical activity are at increased risk of losing bone. Use of prednisone was the only variable consistently associated with reduction in BMD in RA patients.

No increased mortality in patients with rheumatoid arthritis: up to 10 years of follow up from disease onset.

OBJECTIVE: To investigate mortality, functional capacity, and prognostic factors for mortality in an inception cohort of patients with recently diagnosed RA followed up for up to 10 years. METHODS: The observed mortality of this inception cohort with recently diagnosed RA, was analysed in relation to the expected mortality, calculated with the aid of life tables of the general population of the Netherlands (matched for age and sex). Functional capacity was measured by the Health Assessment Questionnaire. Prognostic factors for mortality were analysed multivariately by the Cox proportional hazards model. RESULTS: Between January 1985 and April 1997, 622 patients entered the study, and were included in the analysis of mortality. The death rate in the first 10 years of the disease was not significantly different from that of the general population. Fifty five patients from the study group died (16% up to 10 years of follow up). The most commonly reported causes of death were of cardiovascular and respiratory origin. The other causes of death could be classified into cancer, sepsis, amyloidosis, leukaemia, renal insufficiency of unknown cause, perforation of the oesophagus, probably related to the treatment with non-steroidal anti-inflammatory drugs, and pancytopenia during aurothioglucose treatment. Functional capacity improved significantly during the first six years compared with the value at start. Statistically significant predictors for death were age at the start and male sex. CONCLUSIONS: In contrast with earlier studies performed, no excess mortality in the first 10 years of an inception cohort of patients with RA was seen. In addition, the functional capacity was relatively constant during the first six years after an initial improvement from baseline. Age at start and male sex were the only statistically significant predictors for death.

The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis.

OBJECTIVE: To study the predictive value of anticyclic citrullinated peptide antibody (anti-CCP) in patients with recent-onset rheumatoid arthritis (RA). METHODS: Outcome in terms of physical disability (Health Assessment Questionnaire) and radiologic damage (modified Sharp method) over 3-year and 6-year periods was determined in an inception cohort of 273 RA patients who had had disease symptoms for <1 year at study entry. Anti-CCP titers were determined at baseline and considered positive as recently described. Their prognostic value was studied by means of multiple regression analysis, in which anti-CCP positivity, sex, age at study entry, IgM rheumatoid factor (IgM-RF) status, Disease Activity Score (DAS), HLA-DR4 status, and (in a separate group of patients) shared epitope status were used as independent variables, and radiologic damage and functional disability as dependent variables. RESULTS: Patients with anti-CCP had developed significantly more severe radiologic damage after 6 years of followup. In multiple regression analysis, radiologic damage after 6 years followup was significantly predicted by IgM-RF status, radiologic score at entry, and anti-CCP status. Functional disability was significantly predicted by sex, age at entry, IgM-RF status, and DAS. CONCLUSION: Our data show that in almost 70% of RA patients, anti-CCP antibody is present at the early stages of disease. Anti-CCP-positive patients developed significantly more severe radiologic damage than patients who were anti-CCP negative, although in multiple regression analysis the additional predictive value was rather moderate.

Management of refractory rheumatoid arthritis.

Based on the results of a MEDLINE search (1992-1997), the term 'refractory rheumatoid arthritis' (refractory RA) is ill-defined, in terms of both patient characterization and description of previous treatments. Current strategies of management of refractory RA include increasing disease-modifying anti-rheumatic drug dosage above standard dosage regimens, using combination therapy, and adding or increasing the dosage of corticosteroids. Options for further strategies include target-oriented biological agents (e.g. anti-tumour necrosis factor), gene therapy, stem-cell treatment and oral tolerance induction.

Management of therapy-resistant rheumatoid arthritis.

During the last two decades, newly introduced therapeutic strategies have resulted in satisfactory modification of the disease course in the majority of the patients with rheumatoid arthritis (RA). Nevertheless, a definite number of RA patients remain therapy-resistant, and for this group more aggressive treatment may be required for preventing permanent disability and progressive joint damage necessitating surgical procedures. Therefore, management of therapy-resistant RA is one of the major challenges in modern rheumatology. RA patients who have not responded to conventional disease-modifying antirheumatic drug (DMARD) therapy are defined as refractory RA patients. However, a uniform description or definition for 'refractory' RA does not appear to be available. In this article we will deal with, and discuss, the term 'refractory RA' based on a MEDLINE database search using this term, currently available therapeutic options, data on therapy-resistant RA patients from an inception cohort of RA patients attending the Nijmegen University Hospital, management of extra-articular manifestations and future management strategies.

The immunohistochemical effects of a single challenge with an intermediate dose of ultraviolet B on normal human skin.

Ultraviolet B (UVB) irradiation has extensively been advocated for use in the investigation of cutaneous inflammation in vivo. Mostly doses above the threshold of skin damage have been used. Therefore it is not clear whether the changes observed are specific effects of UVB or to a certain extent represent wound healing. In this study the dose-dependent effects of UVB on normal human skin were assessed using histology and immunohistochemistry. The dose of 1 MED was chosen as a dose unducing tissue changes with adequate morphology: no toxicity but evident immunohistochemical changes. The sequential effects of this 1 MED of UVB were studied for up to 14 days after irradiation, using immunohistochemistry with a panel of monoclonal antibodies. Substantial effects were observed, mainly on proliferation and differentiation; the markers for inflammation did not reveal major changes. This model might be a promising approach to evaluate the effect of drugs on epidermal proliferation and differentiation in vivo.