Francesca Ometto

Adult-onset Still’s disease with myocarditis successfully treated with the interleukin-1 receptor antagonist anakinra

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 30 octobre 2010

Elderly onset of primary Sjögren’s syndrome: Clinical manifestations, serological features and oral/ocular diagnostic tests. Comparison with adult and young onset of the disease in a cohort of 336 Italian patients

OBJECTIVES To study and compare the clinical and serological features of patients with elderly versus adult and younger onset of primary Sjögrens syndrome (pSS). METHODS We analyzed retrospectively 336 consecutive pSS patients followed at our unit. They were subdivided into three groups according to the age at disease onset: elderly (>65 years), adult (>40 and ≤65 years), and young (≤40 years). Clinical and immunological features of the disease, labial salivary glands biopsy, ocular and oral tests were collected at time of diagnosis and then compared among the three groups. RESULTS In 21 (6%) patients, disease onset occurred after the age of 65 years. At the time of diagnosis, 15 (71.4%) of these patients reported symptoms of dry mouth and 16 (76.1%) of dry eye. The most common extraglandular manifestation were arthralgias in 14 (66.7%), Raynauds phenomenon in five (23.8%) and purpura in three (14.2%) cases. Ocular diagnostic tests (Schirmers I and Rose-Bengal staining) were positive respectively in 17 (80%) and nine (44.4%) patients. In eight (38%) cases, unstimulated whole salivary flow showed normal values, while 12 patients (57.1%) showed positivity for salivary sialography. A focus score greater or equal to 1 per 4mm(2) was demonstrated in 11 (53.3%) of the 21 cases. CONCLUSION Elderly onset of pSS was associated with similar incidence of the diagnostic tests positivity (parotid sialography, ocular tests, minor salivary gland biopsy) in comparison with adult and younger onset. Moreover, no statistical differences were found among the three groups concerning sex, disease duration, as well as ocular and oral symptoms.

Refractory pemphigus foliaceus and Behçet's disease successfully treated with tocilizumab.

Pemphigus foliaceus (PF) and Behçet’s disease (BD) are immune-mediated conditions which are usually treated with corticosteroids, immunosuppressants, and, when refractory, with biologic agents. In both diseases, interleukin (IL)-6 serum levels are increased driving the immune-mediated inflammatory process. Tocilizumab is a humanized monoclonal antibody, targeting IL6-receptor, used in the treatment of rheumatoid arthritis. Besides the current indication, it has been recently administered to patients with refractory immune inflammatory diseases as an off-label treatment. Here, we report the case of a woman affected with PF and BD, who did not respond to corticosteroids, immunosuppressants, and biologic agents including adalimumab, anakinra, and infliximab. A complete, long-lasting, clinical, and serological remission was achieved only with tocilizumab. To the best of our knowledge, the association between PF and BD has never been reported. Moreover, only two cases of BD and no cases of PF treated with tocilizumab have been described to date. A literature review on the use of biologic agents on patients with PF and BD was also carried out.

Methods used to assess remission and low disease activity in rheumatoid arthritis

The aim of the treatment in rheumatoid arthritis (RA) is to prevent articular damage and functional loss by decreasing the activity of the disease. The overall goal is the full suppression of the activity of the disease, also called clinical remission. The most reliable indices to assess RA activity were defined by the American College of Rheumatology (ACR), the European League Against Rheumatism (EULAR) and the International League Against Rheumatism (ILAR) and are habitually used for the evaluation of remission. The Food and Drug Administration (FDA) established three increasingly restrictive categories of disease remission: complete clinical response, major clinical response, and remission. Then, OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) advanced the concept of low disease activity state (LDAS) or minimal disease activity (MDA). Thus, those reported by FDA are the only criteria for remission which consider radiographic arrest of the disease. This review aims to describe the criteria for RA remission and to discuss their advantages and limitations.

Hypovitaminosis D and orthostatic hypotension: a systematic review and meta-analysis.

Objectives: Orthostatic hypotension is a common condition among older adults and is associated with a range of deleterious outcomes. Recently, interest has developed in hypovitaminosis D (defined as low 25 hydroxiyvitamin D levels) as a potential risk factor for orthostatic hypotension. We conducted a systematic review and meta-analysis examining the association of orthostatic hypotension between study participants with and without hypovitaminosis D, including the adjustment of potential confounders (age, sex, BMI, renal function, comorbidities, seasonality, use of antihypertensive medications, and supplementation with cholecalciferol). Methods: A systematic literature search of major electronic databases from inception until 09/2015 was made for articles providing data on orthostatic hypotension and hypovitaminosis D. A random effects meta-analysis of cross-sectional studies investigating orthostatic hypotension prevalence comparing participants with vs. those without hypovitaminosis D was undertaken, calculating the odds ratios (ORs) and 95% confidence intervals (CIs). Results: Of 317 initial hits, five cross-sectional studies were meta-analysed including 3646 participants (1270 with hypovitaminosis D and 2376 without). The participants with hypovitaminosis D had a higher prevalence of orthostatic hypotension (OR = 1.88; 95% CI: 1.25–2.84; I2 = 68%) that was not affected by adjusting for a median of five potential confounders (OR = 2.03; 95% CI: 1.13–3.68; I2 = 73%). People with orthostatic hypotension had significantly reduced serum vitamin D concentrations (standardized mean difference = −0.42; 95% CI: −0.72 to −0.12). One longitudinal study confirmed the association between hypovitaminosis D and orthostatic hypotension. Conclusion: Our meta-analysis highlights that hypovitaminosis D is associated with orthostatic hypotension, independent of potential confounders. Further longitudinal studies and clinical trials are required to confirm these findings.

Calprotectin in rheumatic diseases.

Calprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-α inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker. Impact statement Calprotectin is an acute-phase protein produced by monocytes and neutrophils in the circulation and inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to detect minimal residual inflammation and is a candidate biomarker in inflammatory diseases. High serum levels are associated with some severe manifestations of rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin levels in other fluids, such as saliva and synovial fluid, might be helpful in the diagnosis of rheumatic diseases. Of interest is also the potential role of calprotectin as a target of treatment.

Inefficacy or Paradoxical Effect? Uveitis in Ankylosing Spondylitis Treated with Etanercept

Ankylosing spondylitis (AS) is presented with axial and peripheral articular involvement. Uveitis is a severe and rather specific manifestation of AS. Biologics targeting tumor necrosis factor (TNF) α are effective on both articular and ocular manifestations of disease. The occurrence of uveitis in patients that never had eye involvement or the relapse of uveitis is described during anti-TNFα treatment. The frequency of these events is slightly higher during therapy with etanercept. The available TNFα blockers show different pharmacokinetics and pharmacodynamics yielding different biological effects. There is an ongoing debate whether uveitis during anti-TNFα has to be considered as paradoxical effect or an inadequate response to therapy. Here, we present a case report and review what the evidences for the two hypotheses are.

Takayasu arteritis and NYHA III/IV idiopathic cardiomiopathy: Tocilizumab proves effective and safe

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 1 janvier 2014

AB0217 Construct validation of the italian version of the 5-item compliance questionnaire for rheumatology (I-CQR5)

Background The 5-item Compliance Questionnaire for Rheumatology (CQR5) allows the identification of patients likely to be high adherers (HA) to anti-rheumatic treatment (i.e. taking ≥80% of their medications correctly), or “low” adherers (LA).1 Objectives The objective was to validate the construct of an Italian version of CQR5 in rheumatoid arthritis (RA). Methods Cross-cultural adaptation comprised: forward translation, synthesis of the translations, back-translation, expert committee assessment and field-testing. Validation was conducted administering the adapted version (I-CQR5) to RA patients (disease duration >1 year, treated with ≥1 self-administered disease-modifying anti-rheumatic drug, capable of completing the questionnaire unaided) on one occasion. Questionnaires were anonymous but contained self-reported data. Construct validity and reliability were assessed with Rasch analysis (Partial Credit model Parametrisation, PCM). Martin-Loef Likelihood ratio test assessed invariance for gender, age, education, social status and disease duration. Results The adaptation process was closed by the expert committee assessment. I-CQR5 is reported in Figure 1. Among 604 patients, 274 were included in the validation process, 6 questionnaires were incomplete. Median age was 57 years (48–67), females were 201 (77%), disease duration was 13.5 years (8.8–19.3), most patients lived with partner/family (159,75%) and had a middle/secondary school education (184,69%). HA were 93 (67%) and LA 179 (35%). Factor analysis revealed ordered thresholds in most items, 2 factors were sufficient to explain variability (Chi-square=0.46,p=0.5) (Tab.1). Item-fit statistics showed overall agreement of items with parametrisation (Infit statistics=0.6–1.4; excluding item no.5). Chi-square showed agreement with PCM parametrisation by item (excluding the item no.1). Martin-Loef likelihood ratio test confirmed unidimensionality (Chi-square 65.8, df=53,p=0.11) and Separation Reliability Index confirmed internal consistency (Patient Separation Index 0.91) (Tab.1). I-CQR5 was invariant to age (Chi-square=40.6, df=28,p=0.059), education level (Chi-square=49.9, df=42,p=0.187), social status (Chi-square=10.5, df=15,p=0.79), disease duration (Chi-square=13.6, df=36,p=0.220); Martin-Loef test was significant for gender (Chi-square=25.4, df=14,p=0.031).Abstract AB0217 – Table 2 Conclusions I-CQR5 was well understood by patients and construct validity, unidimensionality and internal consistency were confirmed by factor analysis and PCM. Reference [1] Hughes L, et al. A 5 item version of the Compliance Questionnaire for Rheumatology (CQR5) successfully identifies low adherence to DMARDs. BMC Musculoskelet Disord2013;14:286. Disclosure of Interest None declaredAbstract AB0217 – Table 1 Factor analysis Item-fit statistics Loadings Chi-square df p Outfit mean square Infit mean square Outfit t Infit t All† HA Item no. 1 0.721 0.460 224.213 183 0.020 1.219 1.111 1.96 1.05 Item no. 2 0.629 0.522 205.899 183 0.118 1.119 1.132 1.17 1.29 Item no. 3 0.750 0.522 142.900 183 0.987 0.777 0.740 −2.18 −2.65 Item no. 4 0.660 0.675 95.060 183 1.000 0.517 0.523 −4.90 −5.34 Item no. 5 0.534 0.807 131.885 183 0.998 0.7171 0.682 −3.05 −3.45 Factor 1 Factor 2 Sum of square loadings 2.210 1.869 Proportion Variance 0.442 0.374 Cumulative Variance 0.442 0.816

Grade and location of power Doppler are predictive of damage progression in rheumatoid arthritis patients in clinical remission by anti-tumour necrosis factor α

Objectives To investigate power Doppler (PD) signal, grade and location and their association with radiographic progression in RA patients in remission. Methods A prospective observational study was conducted in 125 consecutive RA patients in stable 28-joint DAS (DAS28) remission (⩾6 months) achieved on anti-TNF-α. At baseline, patients in stable remission underwent radiographic and US examination of the wrists and MCP, PIP and MTP joints. Semi-quantitative PD scoring (0-3) was recorded. We scored PD according to two locations: capsular or within synovial tissue without bone contact (location 1) and with bone contact or penetrating bone cortex (location 2). Radiographic progression was evaluated at the 1 year follow-up and defined as a change in van der Heijde-modified total Sharp score >0. Risk ratios (RRs) of radiographic progression according to presence, grade and location of PD were calculated. Results Four patients were excluded because of missing data. At baseline, 59/121 (48.7%) patients had a PD signal in one or more joints. PD location 2 was found in 74.6% patients (44/59). At the 1 year follow-up, 17/121 patients experienced radiographic progression: all had PD signal in one or more joints at baseline (RR 2.47, P < 0.0001). Radiographic progression was associated with the following baseline US features: PD grade 2 (RR 4.58, P < 0.01), PD grade 3 (RR 3.49, P < 0.05), total PD score ⩾2 (sum of all PD scores) (RR 3.19, P < 0.0001) and PD location 2 (RR 3.49, P < 0.0001). Conclusion Higher PD grades and PD in contact with/or penetrating bone are associated with radiographic progression in patients in DAS28 remission.