Francesca Nacci

Prevalence of Fibromyalgia: A Survey in Five European Countries

OBJECTIVE A survey was performed in 5 European countries (France, Germany, Italy, Portugal, and Spain) to estimate the prevalence of fibromyalgia (FM) in the general population. METHODS In each country, the London Fibromyalgia Epidemiological Study Screening Questionnaire (LFESSQ) was administered by telephone to a representative sample of the community over 15 years of age. A positive screen was defined as the following: (1) meeting the 4-pain criteria alone (LFESSQ-4), or (2) meeting both the 4-pain and the 2-fatigue criteria (LFESSQ-6). The questionnaire was also submitted to all outpatients referred to the 8 participating rheumatology clinics for 1 month. These patients were examined by a rheumatologist to confirm or exclude the FM diagnosis according to the 1990 American College of Rheumatology classification criteria. The prevalence of FM in the general population was estimated by applying the positive-predictive values to eligible community subjects (ie, positive screens). RESULTS Among rheumatology outpatients, 46% screened positive for chronic widespread pain (LFESSQ-4), 32% for pain and fatigue (LFESSQ-6), and 14% were confirmed FM cases. In the whole general population, 13 and 6.7% screened positive for LFESSQ-4 and LFESSQ-6, respectively. 3The estimated overall prevalence of FM was 4.7% (95% CI: 4.0 to 5.3) and 2.9% (95% CI: 2.4 to 3.4), respectively, in the general population. The prevalence of FM was age- and sex-related and varied among countries. CONCLUSION FM appears to be a common condition in these 5 European countries, even if data derived from the most specific criteria set (LFESSQ-6) are considered.

Digital ulcers in scleroderma: staging, characteristics and sub-setting through observation of 1614 digital lesions

OBJECTIVE To evaluate in SSc, the frequency of digital lesions and the morphology, characteristics, natural course and time to healing of 1614 digital ulcers (DUs). METHODS One hundred SSc patients were followed up for 4 years. In the first step, the digital lesions were observed and classified at the time of presentation [digital pitting scar (DPS); DU; calcinosis; gangrene]. In the second step, DUs were divided into subsets according to their origin and main features. In the third step, the time to healing was recorded for each DU and the influence of DU main characteristics on time to healing was also evaluated. RESULTS In the first step, 1614 digital lesions were observed: DPS, 712 (44.1%) lesions; DU, 785 (48.6%); calcinosis, 110 (6.8%); and gangrene, 7 (0.8%). In the second step, DUs were subsetted as follows: DU developed on DPS (8.8%), pure DU; DU developed on calcinosis (60%); DU derived from gangrene. In the third step, the mean time to healing was 25.6 (15.6) days in DPS, 76.2 (64) days in pure DU, 93.6 (59.2) days in calcinosis ulcers and 281.1 (263.3) in gangrene. CONCLUSIONS In SSc, digital lesions are represented by DPS, DU, calcinosis and gangrene, and provide an evidence-based DU subsetting according to their origin and main characteristics. Subsetting may be helpful for a precise DU evaluation and staging, and in randomized controlled trials for a precise identification of those DUs that are to be included in therapeutic studies.

Lung CT Densitometry in Systemic Sclerosis: Correlation With Lung Function, Exercise Testing, and Quality of Life

BACKGROUND To ascertain if analysis of lung density histograms in thin-section CT was more reproducible than visual assessment of lung changes in systemic sclerosis (SSc), and if such density histogram parameters as mean lung attenuation (MLA), skewness, and kurtosis could more closely reflect pulmonary function as well as exercise and quality of life impairment. METHODS The intraoperator and interoperator reproducibility of visual and densitometric lung CT analysis in 48 SSc patients examined with CT were evaluated by means of weighted kappa statistics. Univariate and multivariate regression analyses were applied to evaluate the relationship of visual and densitometric CT measurements with functional parameters including functional residual capacity (FRC), FVC, FEV(1), diffusion capacity of the lung for carbon monoxide (Dlco), 6-min walking testing (6MWT), and health-related quality of life questionnaire (QLQ) parameters. RESULTS The intraoperator and interoperator reproducibility of MLA (intraobserver weighted kappa = 0.97; interobserver weighted kappa = 0.96), skewness (intraobserver weighted kappa = 0.89; interobserver weighted kappa = 0.88), and kurtosis (intraobserver weighted kappa = 0.89; interobserver weighted kappa = 0.88) were higher than those of visual assessment (intraobserver weighted kappa = 0.71; interobserver weighted kappa = 0.69). In univariate analysis, only densitometric measurements were correlated with some exercise and QLQ parameters. In multivariate analysis, MLA (square regression coefficient corrected [R(2)c] = 0.70), skewness (R(2)c = 0.78), and kurtosis (R(2)c = 0.77) were predicted by FRC, FVC, Dlco, 6MWT, and QLQ parameters, while visual assessment was associated only with FRC and FVC (R(2)c = 0.40). CONCLUSIONS In SSc, densitometric analysis is more reproducible than visual assessment of lung changes in thin-section CT and more closely correlated to pulmonary function testing, 6MWT, and QLQ. Density histogram parameters may be useful for cross-sectional and longitudinal studies of lung involvement in SSc.

Intravenous immunoglobulins improve the function and ameliorate joint involvement in systemic sclerosis: a pilot study

Background: In systemic sclerosis (SSc), joint involvement may reduce the functional capacity of the hands. Intravenous immunoglobulins have previously been shown to benefit patients with SSc. Aim: To verify the efficacy of intravenous immunoglobulins on joint involvement and function in SSc. Patients and methods: 7 women with SSc, 5 with limited and 2 with diffuse SSc, with a severe and refractory joint involvement were enrolled in the study. Methotrexate and cyclophosphamide pulse therapy did not ameliorate joint symptoms. Hence, intravenous immunoglobulins therapy was prescribed at a dosage of 2 g/kg body weight during 4 days/month for six consecutive courses. The presence of joint tenderness and swelling, and articular deformities (due to primary joint involvement and not due to skin and subcutaneous changes) were evaluated. Before and after 6 months of treatment, patients were subjected to (1) Ritchie Index (RI) evaluation of joint involvement; (2) Dreiser Algo-Functional Index (IAFD) evaluation of hand joint function; (3) pain visual analogue scale (VAS) to measure joint pain; (4) Health Assessment Questionnaire (HAQ) to evaluate the limitations in everyday living and physical disability; and (5) modified Rodnan Skin Score for skin involvement. Results: After 6 months of intravenous immunoglobulins therapy, joint pain and tenderness, measured with the VAS, decreased significantly (p<0.03), and hand function (IAFD) improved significantly (p<0.02), together with the quality of life (HAQ; p<0.03). All patients significantly improved, except for one. The skin score after 6 months of intravenous immunoglobulins therapy was significantly reduced (p<0.003). Conclusion: This pilot study suggests that intravenous immunoglobulins may reduce joint pain and tenderness, with a significant recovery of joint function in patients with SSc with severe and refractory joint involvement. The cost of intravenous immunoglobulins might limit their use only to patients who failed disease-modifying antirheumatic drugs.

The autonomic nervous system in systemic sclerosis. A review

The autonomic nervous system is an underestimated target of systemic sclerosis alterations. In this review we analyzed the major manifestations of its involvement, reconsidering the main theories of its pathogenesis.

High frequency ultrasound can detect improvement of lesions in juvenile localized scleroderma.

Abstract Background. Juvenile Localized Scleroderma (JLS) causes functional disabilities and cosmetic deformities. Evaluation and follow-up of lesions are mandatory to understand the disease evolution. The objective of this study is to evaluate the usefulness of skin ultrasonography (US) in monitoring the response to treatment in JLS. Methods. Ten patients (age: 101,7 ± 66,2 months; 7 M, 3 F) affected by juvenile onset LS underwent sequential US exams (at baseline and after 6 months). Skin thickness was measured by using high-frequency US (18 MHz). All patients were evaluated both clinically (modified Rodnan Skin Score, mRSS) and by US (dermal thickness) at baseline and at 6 months. At baseline, 6/10 patients received 3 pulses of corticosteroids (solumedrol 30 mg/kg/day for 3 consecutive days, then oral steroids (1mg/kg), and methotrexate s.c. (15 mg/mq/week). After 6 months, 1/6 was switched to mycophenolate mofetil (25 mg/kg/day) due to inefficacy of MTX; 4/10 did not receive any further therapy. Results. US showed a thicker dermis and a thinned hypodermis in the lesional skin areas in respect to the healthy ones (p < 0.05). After treatment, in seven patients a clinical improvement (decrease of mRSS) was found. In six of these patients, US showed a decrease of dermal thickness showing a correlation with clinical data. Three patients who did not receive drugs showed unmodified images and clinical findings. Conclusion. US can help the assessment of skin and hypodermis in JLS and can detect an improvement of the lesions.

Tuberculosis and other infections in the anti-tumour necrosis factor-alpha (anti-TNF-α) era

We review the global experience of infections in patients treated with tumour necrosis factor (TNF)-α inhibitors, which shows that the overall incidence of severe infections is at least doubled. In particular, this is true regarding tuberculosis. Screening and prophylactic measures have substantially reduced but not eliminated the risk. Recent improvements in immunologic testing for non-Bacillus Calmette-Guerin (BCG)-related antigens allow more sensitive identification of latent tuberculosis and wider use of such methods holds promise as pre-treatment screening instruments.

Neuropeptides activate TRPV1 in rheumatoid arthritis fibroblast-like synoviocytes and foster IL-6 and IL-8 production

Neurogenic inflammation is caused by neuropeptides which are released by peripheral neurons and induce inflammatory signals. Two of the main neuropeptides involved are substance P (SP) and calcitonin gene related peptide (CGRP),1 both acting through several molecular mechanisms including activation of transient receptor potential vanilloid (TRPV) cation channels, particularly TRPV1 (also called vanilloid receptor type 1 or capsaicin (CAP) receptor).2 ,3 SP and CGRP have been found increased in synovial fluid from rheumatoid arthritis (RA) patients4 ,5 and may induce the production of interleukin (IL)-6 and IL-8 in RA synoviocytes,6 suggesting that neuropeptides may have a role in joint inflammation during RA. Interestingly, TRPV cation channels are expressed in various non-neuronal cell types and, recently, they have been found expressed in human synoviocytes.7 No previous study has investigated the possible link among SP, CGRP and TRPV channels in the inflammation process driven by RA synoviocytes. The aim of our work was to investigate whether SP, CGRP and CAP, a potent activator (agonist) of TRPV1, can increase IL-6 and IL-8 production by RA and healthy fibroblast-like synoviocytes, and whether neuropeptides may modulate TRPV1 expression in RA and healthy cells. Synoviocytes were obtained from knee-biopsy of three patients with active RA diagnosed according to the American College of Rheumatology 1987 revised criteria undergoing surgical joint replacement. Patients had not received any disease-modifying antirheumatic drug treatment. Healthy synoviocytes were collected from knee-biopsy of three subjects who underwent surgical intervention after accidental trauma. Synoviocytes (passage 2–4) were cultured at confluence, serum-starved for 24 h and incubated for …

Thin-section and low-dose volumetric computed tomographic densitometry of the lung in systemic sclerosis.

Objective: To correlate lung density measurements with the results of visual assessment of thin-section computed tomography (CT) and of pulmonary function tests (PFT) in Systemic Sclerosis (SSc). Methods: Thirty-nine SSc patients underwent sequential thin-section CT and spiral low-dose whole-lung acquisitions. The thin-section CT scans were evaluated with a dedicated visual scale. Mean lung density, skewness, and kurtosis were calculated from the lung density histogram. In addition from the spiral low-dose acquisition, the lung volume was computed. The visual score, the densitometric parameters, and the lung volume were correlated with the PFT. Results: Mean lung density, skewness, and kurtosis computed from thin-section (R = 0,66; R = −0,74; R = −0,75) and low-dose volumetric (R = 0,72; R = −0,71; R = −0,71) CT and the lung volume (R = −0.54) correlated with the visual score. Densitometric values and lung volume consistently better correlated with PFT than the visual score. Conclusions: In SSc the histogram results are more closely correlated to PFT than the visual score. The low-dose spiral CT seems ideal for longitudinal studies.

Systemic Sclerosis Sera Impair Angiogenic Performance of Dermal Microvascular Endothelial Cells: Therapeutic Implications of Cyclophosphamide

In systemic sclerosis (SSc), dermal capillaries are progressively lost with consequent chronic tissue hypoxia insufficiently compensated by angiogenesis. Clinical studies reported that intravenous cyclophosphamide (CYC) may improve SSc-related peripheral microvascular damage. Recently, we showed that CYC treatment may normalize SSc sera-induced abnormalities in endothelial cell-matrix interactions. Our objective was to evaluate in vitro the effects of sera from treatment-naïve or CYC-treated SSc patients on dermal blood microvascular endothelial cell (dMVEC) angiogenesis, migration, proliferation and apoptosis. dMVECs were challenged with sera from 21 SSc patients, treatment-naïve (n = 8) or under CYC treatment (n = 13), and 8 healthy controls. Capillary morphogenesis on Geltrex matrix was significantly reduced upon challenge with sera from naïve SSc patients compared with healthy controls. When dMVECs were challenged with sera from CYC-treated SSc patients, their angiogenic capacity was comparable to that of cells treated with healthy sera. Wound healing capacity and chemotaxis in Boyden chamber were both significantly decreased in the presence either of naïve or CYC-treated SSc sera compared with healthy sera. WST-1 assay revealed that cell proliferation was significantly decreased in dMVECs challenged with sera from naïve SSc patients compared with healthy sera. Conversely, dMVEC proliferation was not impaired in the presence of sera from CYC-treated SSc patients. Accordingly, the percentage of TUNEL-positive apoptotic dMVECs was significantly higher in the presence of sera from naïve SSc patients than healthy controls, while CYC-treated SSc sera did not induce dMVEC apoptosis. Levels of the angiostatic mediators endostatin, pentraxin 3, angiostatin and matrix metalloproteinase-12 were all significantly elevated in sera from naïve SSc patients compared with sera from both healthy controls and CYC-treated SSc patients. In SSc, CYC treatment might boost angiogenesis and consequently improve peripheral microangiopathy through the normalization of the endothelial cell-matrix interactions, reduction of endothelial cell apoptosis and rebalance of dysregulated angiostatic factors.