Efficacy of spa-therapy, mud-pack therapy, balneotherapy and mud-bath therapy in the management of knee osteoarthritis. A systematic review

Background: Osteoarthritis (OA) is the most common musculoskeletal disease in the world. OA is the result of an inflammatory and degenerative process affecting the entire joint. Osteoarthritis, especially involving the knee, has a relevant socio-economic impact in terms of drugs, hospital admissions, work absences and temporary or permanent invalidity. Therapy of knee osteoarthritis is based on pharmacological and non-pharmacological measures. Methods: We conducted a systematic review of the studies published between 2002 and 2017 on spa-therapy, mud-pack therapy, balneotherapy and mud-bath therapy in the treatment of knee osteoarthritis in order to investigate the evidence of the efficacy of such treatment on pain, functional limitation, drug use and quality of life. Overall, 35 studies were examined among which 12 were selected and included in the review if trial comparative. Each report was reviewed to identify the criteria used for study enrolment and for assignment to experimental vs control groups, sample size, type and characteristics of treatment, features of mineral water, control intervention, assessment point, endpoints, outcome measures, tests used for statistical analysis of the results. We have been able to illustrate the main results obtained in the individual studies and to elaborate these results in order to allow as much a unitary presentation as possible, and hence an overall judgment. Results: Because the studies we reviewed differed markedly from one another in terms of the methods used, we were unable to conduct a quantitative analysis (meta-analysis) of pooled data from the 12 studies. For the purposes of the present review, we re-evaluated the results of the different studies using the same statistical method, the Student’s t test, which is used to compare the means of two frequency distributions. Among all the studies, the most relevant indexes used to measure effectiveness of spa therapy were improved including VAS, Lequesne’s and WOMAC Score. Conclusions: The mud-pack therapy, balneotherapy, mud-bath therapy and spa therapy has proved to be effective in the treatment and in the secondary prevention of knee osteoarthritis, by reducing pain, non-steroidal antiinflammatory drug consumption, functional limitation and improving quality of life of affected patients. Is a noninvasive, complication-free, and cost-effective alternative modality for the conservative treatment of knee osteoarthritis

Early Origins of Psoriatic Arthritis

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Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the antidsDNA status. Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM). Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was signifiantly more frequent in anti-dsDNA + (30.2%), compared with antidsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.; = 0.001). Serositis resulted signifiantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.; < 0.0001). Th reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with antidsDNA − (21.8%, = 0.005). We did not identify significant differences in the mean ECLAM values before and after modifiation of anti-dsDNA status ( = 0.7). Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity

Neuropsychiatric manifestations associated with anti-endothelial cell antibodies in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem involvement due to immune dysregulation. Neuropsychiatric systemic lupus erythematosus (NPSLE) includes neurological syndromes involving the central, peripheral and autonomic nervous system, as well as psychiatric syndromes observed in patients with SLE in which other causes have been excluded. The pathogenesis of NPSLE has been attributed to many different mechanisms. In particular, autoantibody-mediated vasculopathy seems to play a major role in the pathogenesis of the clinical features. Several autoantibody specificities have been reported in the serum and cerebrospinal fluid of NPSLE patients. Recently, we demonstrated an association between serum antiendothelial antibodies (AECA) and psychosis or depression in SLE patients, strengthening the notion of a possible role of this class of autoantibodies in the pathogenesis of the disease. The study of these autoantibodies could be a useful diagnostic and prognostic tool in patients with NPSLE

Cognitive dysfunction improves in systemic lupus erythematosus: Results of a 10 years prospective study

Objective Cognitive impairment (CI) has been described in 3–80% of Systemic lupus erythematosus (SLE) patients but only short-term studies evaluated its over-time changes, suggesting that CI is usually a stable finding. We aimed at evaluating the changes of SLE-related CI in a 10-years prospective single center cohort study. Methods We evaluated 43 patients (M/F 5/38; mean age = 45.7±10.1 years; mean disease duration = 230.8±74.3 months) at baseline (T0) and after 10 years (T1). A test battery designed to detect fronto-subcortical dysfunction across five domains (memory, attention, abstract reasoning, executive and visuospatial function) was administered. A global cognitive dysfunction score (GCD) was obtained and associated with clinical and laboratory features. Results Prevalence of CI was 20.9% at T0 and 13.9% at T1 (P = NS). This impairment was prevalently mild at T0 (55.5%) and mild or moderate at T1 (36.3% for both degrees). After 10 years, CI improved in 50% of patients, while 10% worsened. Impaired memory (P = 0.02), executive functions (P = 0.02) and abstract reasoning (P = 0.03) were associated with dyslipidemia at T0. Worsening of visuospatial functions was significantly associated with dyslipidemia and Lupus Anticoagulant (P = 0.04 for both parameters). Finally, GCD significantly correlated with chronic damage measured by SLICC/damage index at T0 (r = 0.3; P = 0.04) and T1 (r = 0.3; P = 0.03). Conclusions For the first time, we assessed CI changes over 10-years in SLE. CI improved in the majority of the patients. Furthermore, we observed an improvement of the overall cognitive functions. These results could suggest that an appropriate management of the disease during the follow-up could be able to control SLE-related CI

Autophagy and rheumatoid arthritis: Current knowledges and future perspectives

Autophagy is a degradation mechanism by which cells recycle cytoplasmic components to generate energy. By influencing lymphocyte development, survival, and proliferation, autophagy regulates the immune responses against self and non-self antigens. Deregulation of autophagic pathway has recently been implicated in the pathogenesis of several autoimmune diseases, including rheumatoid arthritis (RA). Indeed, autophagy seems to be involved in the generation of citrullinated peptides, and also in apoptosis resistance in RA. In this review, we summarize the current knowledge on the role of autophagy in RA and discuss the possibility of a clinical application of autophagy modulation in this disease

Anti-carbamylated protein antibodies as a new biomarker of erosive joint damage in systemic lupus erythematosus

Background: The application of more sensitive imaging techniques, such as ultrasonography (US), changed the concept of non-erosive arthritis in systemic lupus erythematosus (SLE), underlining the need for biomarkers to identify patients developing the erosive phenotype. Anti-citrullinated peptide antibodies (ACPA), associated with erosions in inflammatory arthritis, have been identified in about 50% of patients with SLE with erosive arthritis. More recently, anti-carbamylated proteins antibodies (anti-CarP) have been associated with erosive damage in rheumatoid arthritis. We aimed to assess the association between anti-CarP and erosive damage in a large SLE cohort with joint involvement. Methods: We evaluated 152 patients (male/female patients 11/141; median age 46years, IQR 16; median disease duration 108months, IQR 168). All patients underwent blood draw to detect rheumatoid factor (RF) and ACPA (commercial enzyme-linked immunosorbent assay (ELISA) kit), and anti-CarP ("home-made" ELISA, cutoff 340aU/mL). The bone surfaces of the metacarpophalangeal and proximal interphalangeal joints were assessed by US: the presence of erosions was registered as a dichotomous value (0/1), obtaining a total score (0-20). Results: The prevalence of anti-CarP was 28.3%, similar to RF (27.6%) and significantly higher than ACPA (11.2%, p=0.003). Erosive arthritis was identified in 25.6% of patients: this phenotype was significantly associated with anti-CarP (p=0.004). Significant correlation between anti-CarP titer and US erosive score was observed (r=0.2, p=0.01). Conclusions: Significant association was identified between anti-CarP and erosive damage in SLE-related arthritis, in terms of frequency and severity, suggesting that these antibodies can represent a biomarker of severity in patients with SLE with joint involvement

IL-18 Serum Level in Adult Onset Still's Disease: A Marker of Disease Activity

Introduction. Immunological factors seem to play a pivotal role in Adult Onset Still's Disease (AOSD). Among all, IL-18 cytokine is overexpressed and drives the inflammatory process. Objective. We aimed to investigate the levels of IL-18 in sera of Italian patients with AOSD and to assess its possible role as a marker of disease activity. Methods. IL-18 serum levels were determined by ELISA in 26 Italian patients with AOSD. Disease activity was assessed using Pouchot's criteria. As controls, 21 patients with Rheumatoid Arthritis (RA), 21 patients with Sjogren's Syndrome (SS), 20 patients with Systemic Lupus Erythematosus (SLE), and 21 healthy subjects (normal human sera, NHS) were evaluated. Results. IL-18 serum levels were significantly higher in patients with active AOSD than in non-active (P = 0.001) and control groups (RA P = 0.0070, SS P = 0.0029, SLE P = 0.0032, NHS P = 0.0004). A significant correlation between IL-18 serum levels and disease activity (P < 0.0001), and laboratory parameters as ferritin (P = 0.0127) and C-reactive protein (P = 0.0032) was demonstrated. Conclusions. Higher levels of IL-18 are detected in active AODS patients and correlate with disease activity and inflammatory laboratory features. ROC-AUC analysis of the serum concentration of IL-18 suggests that it can be considered a diagnostic marker of AOSD. This paper supports the targeting of this cytokine as a possible therapeutic option in AOSD

Myocardial Ischaemia, Coronary Atherosclerosis and Pulmonary Pressure Elevation in Antiphospholipid Syndrome Patients

Thrombotic events in antiphospholipid syndrome (APS) involve venous and arterial circulation with the possible involvement of coronary or pulmonary microcirculation.To evaluate the influence of antiphospholipid antibodies (aPL) and on myocardial ischaemia assessed by single-photon emission computerized tomography (SPECT), coronary atherosclerosis assessed by multidetector computerized tomography (MDCT) and pulmonary pressure assessed by transthoracic echocardiography (TTE) in patients with primary antiphospholipid syndrome (PAPS).TTE, SPECT (Tc 99m sestamibi) and MDCT-based coronary calcium scoring were performed in 26 consecutive PAPS patients (20 females, 6 males, aged 20-61, mean 39.7) without any signs of other autoimmunological disease and without clinical symptoms of heart disease.Out of 26 patients, TEE showed normal left and right ventricle function in 25 (96.2%) and elevated (≥ 30 mm Hg) right ventricle systolic pressure in 7 (26.9%) patients. SPECT revealed myocardial perfusion defects in 15 (57.7%) patients: exercise-induced in 6 (23.1%) and persistent in 11 (42.3%). MDCT revealed coronary calcifications in 4 (15.4%) patients. The number of plaques ranged from 1 to 11 (median 2), volume 3-201.7 mm³ (median 7), calcium scores 1.3-202.6 (median 5.7). In the group with perfusion defects or coronary calcifications (n = 15), all the patients showed elevated aCL IgG.In most of the relatively young APS patients, without any symptoms of ischemic heart disease, SPECT showed myocardial perfusion defects, and coronary calcifications in 1/6 of them. Right ventricle systolic pressure was elevated in 1/4 of APS patients. These pathologies, well known as cardiovascular risk markers, were associated with elevated levels of the IgG class of both anti-cardiolipin and antiB2 GPI antibodies. Thus, in a high percentage of APS patients, clinically silent myocardial ischaemia, pulmonary pressure elevation and coronary atherosclerosis are present and related to the presence of antiphospholipid antibodies