Israel Medical Association Journal

Biomarkers are important for guiding the clinical and therapeutic management of all phases of rheumatoid arthritis because they can help to predict disease development in subjects at risk, improve diagnosis by closing the serological gap, provide prognostic information that is useful for making therapeutic choices and assessing treatment responses and outcomes, and allow disease activity and progression to be monitored. Various biomarkers can be used to identify subjects susceptible to the disease and those with pre-clinical rheumatoid arthritis before the onset of symptoms such as rheumatoid factor and anti-citrullinated protein antibodies. They can be correlated with a risk of developing rheumatoid arthritis and can predict more bone erosions and severe disease progression. Biomarkers such as the erythrocyte sedimentation rate and C-reactive protein levels provide information about disease activity, while predictive biomarkers allow clinicians to assess the probability of a treatment response before starting a particular therapy particularly in the era of biological drugs. This move from traditional approaches to patient stratification and targeted treatment should greatly improve patient care and reduce medical costs.

Background: Abatacept acts as a co-stimulation modulator preventing activation of T cells. Although it is approved for the treatment of rheumatoid arthritis (RA), its effects on adaptive immune response have not been fully elucidated. 

Objectives: To observe, in a cohort study, based on a clinical practice setting, the variation of peripheral blood T cells, immunoglobulin levels, and autoantibodies in the serum of RA patients during abatacept therapy. 

Methods: Our study comprised 48 RA patients treated with abatacept. All clinical data were collected at baseline and after 3 months of treatment. Clinical and laboratory tests included erythrocyte sedimentation rate, C-reactive protein, 28-joint disease activity score, RF, anti-citrullinated protein antibody, total immunoglobulins, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and lymphocyte sub-population. 

Results: Total immunoglobulin serum levels significantly decreased after 3 months of treatment and correlated positively with disease activity both at baseline and after 3 months of abatacept treatment. A reduction of serum IgM, IgG, IgA and RF was also demonstrated. The absolute number and percentage of cytotoxic (CD8+) T cells significantly decreased after 3 months of abatacept treatment, in particular the percentage of cytotoxic (CD8+) T cells significantly decreased only in patients responding to the treatment.

Conclusions: Our results highlight a different role of abatacept in the modulation of the adaptive immune response in RA by the reduction of polyclonal B-cell activation and cytotoxic T cells. 

 

Background: Arthritis and arthralgia are painful symptoms experienced by many elderly patients during hospitalization. Crystal-induced arthritis (CIA) is one of the most common causes of arthritis worldwide and represents the most common cause of acute arthritis in the elderly.  

Objective: To determine the incidence of both acute new onset or acute exacerbation of CIA among elderly patients hospitalized due to an acute medical illness.

Method: This study comprised 85 patients. Patients aged 70 years and older who complained of any articular pain were included in the study. Exclusion criteria were signs of septic arthritis, chronic use of steroids or non-steroidal anti-inflammatory drugs, or admission to the hospital due to an acute attack of CIA. 

Results: Synovial aspiration was performed in 76 patients (89%). Joint aspiration yielded a diagnosis in 67 of them (79%). The predominant type of crystal was calcium pyrophosphate dehydrate (68%) followed by monosodium urate (20%). The main causes of hospitalization were acute infectious disease (57%) followed by neurologic and cardiac diseases, 14% and 9% respectively, and orthopedic problems (6%). Among patients with acute infectious disease, the main causes were pulmonary (57%) and gastrointestinal (22%) infections. In 9 patients (12%) who underwent synovial aspiration, visible crystals were identified without a definite diagnosis.

Conclusion: Our study showed that hospitalization could be a risk factor for the development of CIA, and the time to diagnose CIA is during hospitalization for other acute illnesses.

 

Background: The effects of balneotherapy on rheumatoid arthritis (RA) are still controversial partly due to poor methodology used in randomized controlled trials, as reported in the international medical literature. 

Objectives: To determine whether spa therapy plus pharmacological treatment offers any benefit in the management of RA as compared to pharmacological treatment alone.

Methods: We conducted a prospective, controlled, unblinded randomly assigned study of patients with RA according to American College of Rheumatology criteria. Following the 2007 recommendations of AFRETH, the method designed for this study was “immediate treatment versus delayed treatment.” All patients were followed at the Centro Hospitalar do Porto and each physician observed the same patients throughout the study. Patients continued with their usual medications and maintained their daily life activities at home, at leisure and/or in the workplace. The spa therapy group received spa treatments for 21 days at S. Jorge Spa-Santa Maria da Feira. The main outcome measure was the HAQ-DI; the moderated regression analysis, together with the Johnson-Neyman technique, was used for statistical analysis.

Results: HAQ-DI at the end of treatment (21 days) and at the 3 month follow-up was improved in the spa group (odds ratio 0.37, confidence interval 0.09–0.64, P = 0.01 at 21 days, and 0.44, 0.15–0.72, P = 0.004 at 3 months).

Conclusions:

Background: Tumor necrosis factor-alpha (TNFα) inhibitors are indicated for patients with psoriatic arthritis (PsA) in whom conventional disease-modifying anti-rheumatic drugs (DMARDs) are insufficient to achieve disease remission. 

Objectives: To determine the value of acute-phase reactant levels at diagnosis of psoriatic arthritis in predicting the need for biologic treatment with TNFα inhibitors.

Methods: We conducted a longitudinal observational study of an inception cohort of 71 consecutive patients diagnosed with psoriatic arthritis. C-reactive protein (CRP) was assayed for all patients at their first visit.

Results: All patients were treated with one or more DMARDs, mainly methotrexate (81.6%). Thirty-seven patients (52.11%) had an inadequate response and received at least one TNF inhibitor. CRP level at diagnosis was positively correlated with need for a TNF inhibitor (P = 0.009, HR 1.8, 95%CI 1.27–1.85). Patients with CRP > 0.9 mg/dl at diagnosis started biologic treatment significantly earlier than patients with a lower level (P = 0.003, HR 2.62, 95%CI 0.393–2.5).

Conclusions: In patients with psoriatic arthritis, CRP ≥ 0.9 mg/dl at diagnosis significantly predicts an earlier need for a TNF inhibitor to achieve disease control.

 

Lung involvement is a well-recognized extra-articular manifestation of ankylosing spondylitis (AS). Anecdotal reports suggest that the use of anti-TNF drugs may be related to lung disease and pulmonary fibrosis. To examine the association between anti-TNF drugs and the development of lung disease in patients with AS or  psoriatic arthritis (PsA) we conducted a systematic review. Of the 670 papers identified by means of key word and hand search, only one full-text paper was considered potentially relevant but had to be discarded as it did not meet the eligibility criteria. Although no conclusion was reached, this is the first systematic review to examine this problem which is becoming increasingly important as these drugs are widely prescribed in patients with spondyloarthritis.

Chikungunya fever (CHIK-F) has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular tourist sites.  We present three Israeli travelers who developed fever, maculopapular rash and long-standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic. We also present an epidemiological review of the chikungunya epidemic over the past decades. Rare systemic manifestations of this disorder, like catastrophic antiphospholipid syndrome (CAPS) and adult onset still’s syndrome, are discussed. The present era of international travel poses a novel diagnostic and epidemiologic challenge and we must increase our awareness to the possibility of an exotic tropical infectious disease.

Psoriatic arthritis (PsA) is a chronic inflammatory condition associated with skin psoriasis and manifests a wide clinical phenotype, with proposed differences between sexes. Current treatments are based on traditional disease-modifying anti-rheumatic drugs (DMARD), and biologic agents and studies have reported different clinical response patterns depending on sex factors. We aimed to identify sex differences in drug retention rate in patients with PsA and performed a systematic research on MEDLINE, EMBASE and Cochrane databases (1979 to June 2015) for studies regarding effectiveness (measured as drug retention rate) in PsA in both traditional DMARDs and biologics. Demographic data as well as retention rates between sexes were extracted. From a total 709 retrieved references, we included 9 articles for the final analysis. Only one study reported data regarding DMARDs, while eight studies reported retention rate for anti-tumor necrosis factor (TNF) biologics, mainly infliximab, adalimumab and etanercept. No differences were reported in retention rates between sexes for methotrexate, while women manifested lower retention rates compared to men with regard to anti-TNF. We highlight the need to include sex differences in the management flow chart of patients with PsA.

Background: Balneotherapy is one of the most commonly used non-pharmacological approaches for osteoarthritis (OA). Recent data indicate that some biomarkers could be useful to predict OA progression and to assess therapeutic response.

Objectives: To evaluate the effects of mud-bath therapy on serum biomarkers in patients with knee OA. 

Methods: The study group comprised 103 patients with primary symptomatic bilateral knee OA who were randomly assigned to receive a cycle of mud-bath therapy over a period of 2 weeks or to continue their standard therapy alone. Clinical and biochemical parameters were assessed at baseline and after 2 weeks. Clinical assessments included global pain score on a Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Index (WOMAC) subscores for knee OA. Cartilage oligomeric matrix protein (COMP), C-terminal cross-linked telopeptide type II collagen (CTX-II), myeloperoxidase (MPO) and high sensitivity C-reactive protein (hsCRP) serum levels were assessed by ELISA.

Results: At the end of mud-bath therapy we observed a statistically significant improvement in VAS and WOMAC subscores. Serum levels of COMP, MPO and hsCRP did not show any significant modification in both groups, while a significant increase (P < 0.001) in CTX-II serum levels was observed in the mud-bath group after the treatment.

Conclusions: A cycle of mud-bath therapy added to usual treatment had a beneficial effect on pain and function in patients with knee OA. The evaluation of serum biomarkers showed only a significant increase of CTX-II, perhaps due to an increase of cartilage turnover induced by thermal stress.

The term non-radiographic axial spondyloarthritis (nrAxSpA) was coined for patients who have a clinical picture of ankylosing spondylitis (AS) but do not exhibit radiographic sacroiliitis. The ASAS classification criteria for nrAxSpA, ensuring the recruitment of homogenous study cohorts, were accepted in 2009, although the respective diagnostic criteria for daily clinical practice have not yet been developed. The clinical diagnosis should be based on the composite of clinical symptoms and signs of the disease, HLA B27 status, and magnetic resonance imaging (MRI) of sacroiliac joints. Notably, a negative MRI or HLA B27 does not exclude the diagnosis in patients with a high clinical suspicion for nrAxSpA. The prevalence of nrAxSpA is similar to that of AS, but the former has a higher female preponderance. The rate of progression of nrAxSpA to the radiographic stage of disease (AS) ranges from 10% to 20% over 2 years. Current treatment strategies for nrAxSpA are the same as for AS and include non-steroidal anti-inflammatory drugs and inhibitors of tumor necrosis factor-alpha. While this review summarizes the current achievements in the field of nrAxSpA, further understanding of the epidemiology and natural history of the disease and, particularly, mechanisms of inflammation and subsequent new bone formation is essential for the development of new treatment strategies for nrAxSpA patients.