Salvatore D'Angelo

European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes

OBJECTIVE To develop criteria for disease activity in systemic sclerosis (SSc) that are valid, reliable, and easy to use. METHODS Investigators from 19 European centres completed a standardised clinical chart for a consecutive number of patients with SSc. Three protocol management members blindly evaluated each chart and assigned a disease activity score on a semiquantitative scale of 0–10. Two of them, in addition, gave a blinded, qualitative evaluation of disease activity (“inactive to moderately active” or “active to very active” disease). Both these evaluations were found to be reliable. A final disease activity score and qualitative evaluation of disease activity were arrived at by consensus for each patient; the former represented the gold standard for subsequent analyses. The correlations between individual items in the chart and this gold standard were then analysed. RESULTS A total of 290 patients with SSc (117 with diffuse SSc (dSSc) and 173 with limited SSc (lSSc)) were enrolled in the study. The items (including Δ-factors—that is, worsening according to the patient report) that were found to correlate with the gold standard on multiple regression were used to construct three separate 10-point indices of disease activity: (a) Δ-cardiopulmonary (4.0), Δ-skin (3.0), Δ-vascular (2.0), and Δ-articular/muscular (1.0) for patients with dSSc; (b) Δ-skin (2.5), erythrocyte sedimentation rate (ESR) >30 mm/1st h (2.5), Δ-cardiopulmonary (1.5), Δ-vascular (1.0), arthritis (1.0), hypocomplementaemia (1.0), and scleredema (0.5) for lSSc; (c) Δ-cardiopulmonary (2.0), Δ-skin (2.0), ESR >30 mm/1st h (1.5), total skin score >20 (1.0), hypocomplementaemia (1.0), scleredema (0.5), digital necrosis (0.5), Δ-vascular (0.5), arthritis (0.5), Tlco <80% (0.5) for all patients with SSc. The three indexes were validated by the jackknife technique. Finally, receiver operating characteristic curves were constructed in order to define the value of the index with the best discriminant capacity for “active to very active” patients. CONCLUSIONS Three feasible, reliable, and valid preliminary indices to define disease activity in SSc were constructed.

European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. III. Assessment of the construct validity of the preliminary activity criteria

Objective: To further assess the construct validity of the three European Scleroderma Study Group (EScSG) preliminary activity indices for systemic sclerosis (SSc): for SSc as a whole, for diffuse SSc (dcSSc), and for limited SSc (lcSSc). Methods: 30/290 SSc clinical charts collected for the EScSG study used to develop activity criteria for SSc were selected and sent to four clinical experts in SSc. The experts ranked the charts from 1 to 30 (1=lowest activity, 30=highest activity). The relationships among the ranks given by each investigator and each of the three scores, and between any two of the ranks were investigated. Results: A consistently significant correlation (rs=0.530–0.712) was found between the ranks given by each of the four investigators and the index for the entire patient group. A similar level of agreement was detected between each couple of the four experts (rs=0.428–0.720). Moreover, the ranks given in patients with an index >3 were significantly higher than those given for patients with an index ⩽3. This cut off point had previously been shown to best discriminate patients with active disease. Conclusions: Of the originally developed activity indexes, the whole series index has been externally validated. The index comprises the first preliminary, but necessary, groundwork to improve the concept of disease activity in SSc, which is still ill defined. It can be used as a preliminary activity index in clinical investigational studies.

Infliximab for the treatment of Neuro-Behçet's disease: A case series and review of the literature

Introduction Behçet’s disease (BD) is a vasculitis in which the hallmark lesions are oral and often genital ulcers. Involvement of parenchymal central nervous system (neuro-Behçet’s) is a serious complication commonly characterized by brainstem and/or basal ganglia lesions. To date, treatment of neuro-Behçet’s remains largely empirical, and may not adequately control the disease (1). Serum tumor necrosis factor (TNF ) levels are increased in active BD (2), suggesting a role for TNF in disease pathogenesis. Clinically, significant improvement of various BD manifestations has been reported with TNF blockade (3). However, evidence for the efficacy of TNF blockers in the treatment of neuro-Behçet’s is scant. We present 8 patients with neuro-Behçet’s who responded favorably to infliximab therapy and review the relevant literature.

European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. IV. Assessment of skin thickening by modified Rodnan skin score

The European Scleroderma Study Group (EScSG) has recently identified three activity 10 point indices devoted to evaluating disease activity in systemic sclerosis (SSc) (table 1),1 which have been externally validated.2nnAn activity index must rely on widely used methods.3 The whole series index includes the total skin score (TSS) evaluated according to the scoring method of Kahaleh et al (KTSS).4 Because, at present, the modified Rodnan TSS (mRTSS)5 is the method most widely used to assess skin induration in SSc, we considered that the …

Identification of the clinical features distinguishing psoriatic arthritis and fibromyalgia.

Objective. To identify the clinical features that can help to distinguish between psoriatic arthritis (PsA) and fibromyalgia (FM). Methods. Our cross-sectional study was carried out in 10 Italian rheumatology centers between January and September 2009, and enrolled all consecutive patients with PsA and FM who agreed to participate. Standard clinical and laboratory data for PsA and FM were collected from all patients. Records were made of somatic symptoms, response to nonsteroidal antiinflammatory drugs (NSAID), self-evaluated pain, general health, disability, and responses to the Fibromyalgia Impact Questionnaire. Data were statistically analyzed by univariate and multivariate analyses, and receiver-operating characteristic curves. The analysis concentrated on the clinical features shared by the 2 conditions. Results. Two hundred sixty-six patients with PsA (mean age 51.7 yrs; disease duration 10.2 yrs) and 120 patients with FM (mean age 50.2 yrs; disease duration 5.6 yrs) were evaluated. Univariate analysis showed that patients with FM had higher mean tender point and enthesitis scores, more somatic symptoms, and responded less to NSAID. Multivariate analysis showed that the presence of ≥ 6 FM-associated symptoms and ≥ 8 tender points was the best predictor of FM. Conclusion. The shared clinical features of PsA and FM that had the greatest discriminating power for FM were the number of FM-associated symptoms and tender point count.

Patient Global Assessment in Psoriatic Arthritis: A Multicenter GRAPPA and OMERACT Study

Objective. During OMERACT 8, delegates selected patient global assessment (PGA) of disease as a domain to be evaluated in randomized controlled trials in psoriatic arthritis (PsA). This study assessed the reliability of the PGA, measured by means of 0–100 mm visual analog scale (VAS), and the additional utility of separate VAS scales for joints (PJA) and skin (PSA). Methods. In total, 319 consecutive patients with PsA (186 men, 133 women, mean age 51 ± 13 yrs) were enrolled. PGA, PJA, and PSA were administered at enrolment (W0) and after 1 week (W1). Detailed clinical data, including ACR joint count, Psoriasis Area and Severity Index (PASI), and Hospital Anxiety and Depression Scale, were recorded. Results. Comparison of W0 and W1 scores showed no significant variations (intraclass correlation coefficients for PGA 0.87, PJA 0.86, PSA 0.78), demonstrating the reliability of the instrument. PGA scores were not influenced by patient anxiety or depression, but were dependent on PJA and PSA (p = 0.00001). PJA was dependent on the number of swollen and tender joints (p < 0.00001). PSA scores were influenced by the extent of skin psoriasis and by hand skin involvement (p = 0.00001). Joint and skin disease were found not to correlate in terms of disease activity as evidenced by the swollen joint count compared to PASI (r = 0.11) and by the PJA compared to PSA (r = 0.38). Conclusion. PGA assessed by means of VAS is a reliable tool related to joint and skin disease activity. Because joint and skin disease often diverge it is suggested that in some circumstances both PJA and PSA are also assessed.

Remission in ankylosing spondylitis treated with anti-TNF-α drugs: a national multicentre study

OBJECTIVEnThe primary objective of this retrospective study was to investigate the possibility of achieving partial remission (PR) in AS patients treated with anti-TNF-α antagonists, such as adalimumab (ADA), etanercept (ETA) and infliximab (INF), in a real clinical practice setting. Predictors of PR were also evaluated.nnnMETHODSnA retrospective study was conducted in patients with AS treated with ADA, ETA and INF from 2000 to 2012. Kaplan-Meier survival curves were plotted to determine the rates of PR during the treatment with anti-TNF-α drugs.nnnRESULTSnA total of 283 patients with AS were treated with ADA (18.7%), ETA (26.8%) and INF (54.4%) as first anti-TNF-α drugs, with a PR rate of 57.6%. The probability of obtaining PR with ADA, ETA or INF was not significantly different among all anti-TNF-α patients. AS patients treated with a second anti-TNF-α drug had a PR rate of 40.5%, but after switching for lack of response, the probability of obtaining PR with a second anti-TNF-α drug was significantly lower from that of the first anti-TNF-α drug (P = 0.0039). The probability of obtaining PR in patients with enthesitis (P = 0.04) or psoriasis (P = 0.0016) or low levels of CRP (P = 0.0225) was significantly lower compared with that of patients without these manifestations at baseline.nnnCONCLUSIONnOur real-life study on PR confirmed the effectiveness of ADA, ETA or INF as first or second anti-TNF-α drugs. The presence at baseline of enthesitis or psoriasis or low CRP values yielded a lower probability of obtaining PR.

Sensitivity of the classification of psoriatic arthritis criteria in early psoriatic arthritis.

Objective. To determine the sensitivity of the CASPAR criteria in patients with early psoriatic arthritis (PsA). Methods. Consecutive patients with a clinical diagnosis of PsA and a disease duration < 12 months were enrolled for study. The proportion of patients meeting the criteria (i.e., the sensitivity) was determined. Results. Forty-four patients with early PsA (23 women, 21 men; mean age 51 yrs, range 16–90) were enrolled. Mean disease duration (± SD) was 15.8 ± 14.3 weeks (range 0.1–50.9 wks). Thirty-four patients satisfied the criteria at the first visit (sensitivity 77.3%). Most patients met the skin and laboratory criterion, i.e., they were rheumatoid factor-negative, while only 2 satisfied the radiologic criterion. Conclusion. Our findings suggest a less satisfactory performance of the CASPAR criteria when applied in early PsA. Lower sensitivity could mainly depend on the small proportion of patients fulfilling the radiologic criterion.

Advances in the management of psoriatic arthritis

Psoriatic arthritis (PsA), which affects musculoskeletal structures, skin and nails, is a heterogeneous chronic inflammatory disease with a wide clinical spectrum and variable course. Patients with PsA are more likely than healthy individuals to have metabolic syndrome or cardiovascular disease. To include these comorbidities, psoriatic disease has been suggested as an umbrella term. The management of PsA has changed tremendously over the past decade owing to early diagnosis and improvement in treatment strategies, including, early referral from dermatologists and primary-care physicians to rheumatologists, early initiation of therapy, treating to the target of remission or low disease activity, and advances in pharmacological therapy. Outcome assessment is also improving, because of validated instruments for clinical disease manifestations. The commercialization of TNF blockers, including adalimumab, etanercept, golimumab and infliximab, is representative of a revolution in the treatment of PsA. A new anti-TNF agent, certolizumab pegol, and a fully human monoclonal antibody against IL-12 and IL-23, ustekinumab, are approved for the treatment of active PsA. The efficacy of ustekinumab suggests that inhibiting the type 17 T helper pathway might be an alternative to blocking TNF. PsA management must now use improved measures to predict patient outcomes and define remission, and develop better-targeted therapies.

Autoantibodies in patients with chronic hepatitis C virus infection: pitfalls for the diagnosis of rheumatic diseases.

Hepatitis C virus infection (HCV) is one of the best mimes in medicine. About 40-70% of patients suffering from this disorder develop at least one extra-hepatic disorder that can have a rheumatic nature (arthralgias, arthritis, vasculitis and sicca syndrome) and must be differentiated from the primitive rheumatic diseases. In addition, HCV infection can also alter the laboratory tests. Several alterations of first line laboratory tests can be usually found in both chronic HCV infection and chronic inflammatory rheumatic disorders. In the present review we analyze the interference of HCV in tests more specifically used in rheumatology: rheumatoid factor and other autoantibodies (ANA, anti-ENA, ANCA, anti-DNA, antiphospholipid, anti-CCP). In patients suffering from HCV infection, the diagnosis of connective tissue diseases (CTD) or rheumatoid arthritis (RA) should be made only when the detected symptoms or laboratory data are not inducible by HCV, otherwise only a diagnosis of possible CTD or possible RA should be considered.