Effects of a motor imagery-based exercise protocol on chronic pain and emotional distress in patients with fibromyalgia syndrome: A pilot study.

BACKGROUND: Fibromyalgia (FM) is a chronic condition characterized by widespread muscular or musculoskeletal pain of at least 3 months' duration, occurring above and below the waist, on both sides of the body. OBJECTIVE: The aim of this study was to evaluate the effectiveness of a rehabilitation program based on motor imagery versus a conventional exercise program in FM in terms of pain, functional and psychological outcomes. METHODS: Twenty-nine female subjects were randomly assigned to a group receiving motor imagery-based rehabilitation (MIG) or to a control group (CG) performing conventional rehabilitation. Outcome assessments were performed before (T0) and after 10 sessions of treatment (T1) and at a 12-week follow-up (T2). Pain, function and psychological measurements were conducted by means of different questionnaires. RESULTS: Both treatments improved all outcomes at post-treatment (T1) and follow-up (T2). The MIG showed a significant improvement in anxiety disorder associated with FM with respect to the CG, as well as improvements in coping strategies. CONCLUSIONS: Rehabilitation treatment based on motor imagery showed a stronger effect on anxiety and coping behavior than traditional physiotherapy in patients with FM. Integrated psychological support would be desirable in this setting. Further research is needed to explore the aspects investigated in more depth.

May Bacterial Infections Trigger Bullous Pemphigoid? Case Report and Review of Literature.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease, mainly observed in the elderly. Infections have been suggested as possible disease triggers. However, infections may even heavily influence the disease clinical course and mortality. A 75-year-old woman was admitted to hospital for severe erythematosus blistering disease, accompanied by hyper-eosinophilia and hyper-IgE. The culture of bullous fluid was positive for Enterococcus faecalis, the blood culture was positive for Staphylococcus aureus, and the urine culture was positive for Proteus mirabilis and Escherichia coli. Moreover, circulating anti-BP180 IgG was present and the histopathological/ultrastructural examination of a lesional skin biopsy was compatible with BP. High eosinophil levels (up to 3170/µL) were found throughout the clinical course, while values below 1000/µL were associated with clinical improvement. The total IgE was 1273 IU/mL, and specific anti-G/V-penicillin/ampicillin IgE antibodies were positive. The patient had a complete clinical recovery in two months with methyl-prednisolone (40 then 20 mg/day) and low-dose azathioprine (50 mg/day) as a steroid-sparing agent. The steroid treatment was tapered until interruption during a one-year period and intravenous immunoglobulins have been administered for three years in order for azathioprine to also be interrupted. The patient stopped any treatment five years ago and, in this period, has always been in good health. In this case, the contemporaneous onset of different bacterial infections and BP is suggestive of bacterial infections acting as BP trigger(s), with allergic and autoimmune pathways contributing to the disease pathogenesis.

Different Electrophysiological Responses to Pain-Related Visual Stimuli Between Fibromyalgia and Chronic low Back Pain Women: A Pilot Case-Control Study.

BACKGROUND: Fibromyalgia is a chronic pain syndrome which occurs in the absence of an organic damage, whom causes is still unclear. Aims of this pilot study were to investigate the neural correlates of fibromyalgia in response to pain-related visual stimuli and explore the psychological differences among fibromyalgia, chronic low back pain (CLBP) and healthy conditions. METHODS: After a clinical assessment, electrophysiological responses to pain-related visual stimuli were recorded using a 256-Hydrocel Geodesic-Sensor-Net. Event-related potentials (ERPs), standardised low-resolution electromagnetic tomography (sLORETA), and psychological (Symptom Checklist-90-Revised) data were analysed for a total sample of 23 women (5 healthy volunteers, 12 fibromyalgia patients, 6 CLBP patients). RESULTS: The main finding was that fibromyalgia women reported a different brain response to pain-related visual stimuli on the frontal montage compared to women with CLBP (p = .028). Moreover, fibromyalgia women showed an increased activity mainly on the hippocampus (p = .003) and the posterior cingulate cortex (p ≤ .001) in response to algic stimuli compared to not algic ones. Lastly, these women presented higher scores on the somatization (p = .002), obsession-compulsion (p = .045), depression (p = .043) and positive symptom distress (p = .023) dimensions compared to the healthy women. CONCLUSIONS: These preliminary results suggest that although the painful symptoms are similar, the central elaboration of pain could be different between women with fibromyalgia and those with CLBP. Moreover, these findings provide preliminary evidences about the great alert and the central sensitivity to pain-related information regarding fibromyalgia patients.

Impact of Mediterranean Diet on Disease Activity and Gut Microbiota Composition of Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is an autoimmune disorder in which gut and oral microbiota play a crucial role. Diet is a modifiable factor that can influence both microbiota composition and arthritis outcome; previous studies have suggested associations between dietary habits and RA, with contrasting results. We investigate the protective effect of the Mediterranean diet (MD) on disease activity and the gut microbiota profile in RA patients. Sixty consecutive RA patients were enrolled upon filling a validated 14-item questionnaire for the assessment of adherence to the Mediterranean diet (Prevention with Mediterranean Diet-PREDIMED). Then, 16S analysis was employed to explore the gut microbiota within the two cohorts of patients. Patients with high adherence to MD (20) had a significantly lower C-reactive protein (p < 0.037) and disease activity (p < 0.034) than the 40 patients with low/moderate adherence to MD. An inverse association between MD and disease activity was confirmed by multivariate analysis after adjustments for all the different demographic, clinical and serologic variables. A healthier gut microbiota composition was observed in the high adherence group, with a significant decrease in Lactobacillaceae and an almost complete absence of Prevotella copri with respect to the low/moderate adherence group. In conclusion, our findings support the protective role of MD on disease activity and microbiota composition in RA patients, and suggest the feasibility of shifting the habitual diet to modulate the gut microbiota and promote the benefits associated with MD.

Prevalence of Hepatitis B Virus Markers in Patients with Autoimmune Inflammatory Rheumatic Diseases in Italy.

Chronic hepatitis B virus (HBV) infection may be reactivated by immunosuppressive drugs in patients with autoimmune inflammatory rheumatic diseases. This study evaluates HBV serum markers' prevalence in rheumatic outpatients belonging to Spondyloarthritis, Chronic Arthritis and Connective Tissue Disease diagnostic groups in Italy. The study enrolled 302 subjects, sex ratio (M/F) 0.6, mean age ± standard deviation 57 ± 15 years, 167 (55%) of whom were candidates for immunosuppressive therapy. The Spondyloarthritis group included 146 subjects, Chronic Arthritis 75 and Connective Tissue Disease 83 (two patients had two rheumatic diseases; thus, the sum is 304 instead of 302). Ten subjects (3%) reported previous anti-HBV vaccination and tested positive for anti-HBs alone with a titer still protective (>10 IU/mL). Among the remaining 292 subjects, the prevalence of positivity for HBsAg, isolated anti-HBc, anti-HBc/anti-HBs, and any HBV marker was 2%, 4%, 18%, and 24%, respectively. A total of 26/302 (9%) patients with γ-globulin levels ≤0.7 g/dL were more frequently (p = 0.03455) prescribed immunosuppressive therapy, suggesting a more severe rheumatic disease. A not negligible percentage of rheumatic patients in Italy are at potential risk of HBV reactivation related to immunosuppressive therapy. Before starting treatment, subjects should be tested for HBV markers. Those resulting positive should receive treatment or prophylaxis with Nucleos (t) ides analogue (NUCs) at high barrier of resistance, or pre-emptive therapy, according to the pattern of positive markers. HB vaccination is recommended for those who were never exposed to the virus.

Psychological Distress in Patients with Autoimmune Arthritis during the COVID-19 Induced Lockdown in Italy.

Lockdowns imposed by governments worldwide as a way to limit the spread of severe atypical respiratory syndrome-coronavirus-2 (SARS-CoV2) have had heavy psychological and economic consequences. Arthritis patients are a vulnerable population at an increased risk of peritraumatic stress. This could be due to several reasons, including the fear of shortage of medicine and difficulty receiving periodical medical checks. In the present case-control study, psychological distress in patients with autoimmune arthritis during the coronavirus disease 2019 (COVID-19) pandemic were investigated. An electronic survey was conducted to gather information on the perceived change in the emotional state, general health (GH), fatigue, joint pain, and disease activity during the lockdown, in 100 patients with autoimmune arthritis and 100 controls. Mental health status was measured using the Depression, Anxiety and Stress Scale (DASS-21). The COVID-19 Peritraumatic Distress Index (CPDI) was used to assess the frequency of peritraumatic stress disorders related to COVID-19. Patients reported a significant worsening of perceived GH (36% vs. 7%; p < 0.001), a significantly higher mean CPDI score (p < 0.001) than controls. Using multivariate analysis, arthritis patients had significantly higher CPDI scores (+3.67 points; p = 0.019), independent of depression, anxiety, and stress symptoms, comorbidities, and sociodemographic and lifestyle characteristics. Logistic regression analysis showed that the risk of reporting worsened GH was 9-fold higher in patients than controls (p < 0.001). Patients with autoimmune arthritis are at higher risk of psychological distress related to COVID-19 pandemic; thus targeted intervention should be designed to strengthen coping capacity in this vulnerable population.

Analysis of Gut Microbiota in Rheumatoid Arthritis Patients: Disease-Related Dysbiosis and Modifications Induced by Etanercept.

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota.

Anti-polysaccharide and anti-diphtheria protective antibodies after 13-valent pneumococcal conjugate vaccination in rheumatoid arthritis patients under immunosuppressive therapy.

Immunogenicity of 13-valent pneumococcal polysaccharide (PnPS) conjugate vaccine (PCV13) was evaluated in 38 rheumatoid arthritis patients under immunosuppressive treatment and 20 healthy controls (HC). Antibodies to all PnPS and diphtheria-toxin analogue conjugate protein were measured pre- (T0), 1 (T1), 6 (T2), 12 (T3) months post-immunization. Patients and HC had similar response to individual PnPS. Mean antibody levels to all PnPS but one doubled at T1 compared with T0, with T3 persistence for only 8-7/13 PnPS. Baseline antibody levels was inversely associated with the rate of responders at T1 (T1/T0≥2) to 11/13 PnPS. Few subjects reached protective IgG levels against some serotypes frequently isolated in Italian patients with invasive pneumococcal disease. Antibody response was not influenced by therapy, except the one to PS7F, which was reduced by tumor necrosis factor-α-inhibitors. Vaccination increased also anti-diphtheria IgG. Despite this study substantially confirmed the PCV13 immunogenicity in immunocompromised patients, it also revealed some limitations.

TCD4pos lymphocytosis in rheumatoid and psoriatic arthritis patients following TNFα blocking agents.

BACKGROUND: Lymphocyte expansion and true lymphocytosis are commonly observed in the everyday clinical practice. The meaning of such phenomenon is often poorly understood so that discrimination between benign and malignant lymphocytosis remains difficult to establish. This is mainly true when lymphocytosis rises in patients affected by immune-mediated chronic inflammatory diseases under immunosuppressive treatment, conditions potentially associated with lymphomagenesis. In this brief report the development of mild T CD4pos lymphocytosis in a group of patients with chronic arthritis under anti-TNF-α treatment is described. METHODS: Two hundred eight rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients have been evaluated longitudinally for at least 1-year before and 2-years after anti-TNF-α therapy introduction for the possible appearance of a lymphocyte expansion. In patients who developed lymphocyte expansion, T, B and NK cells were analysed. RESULTS: Twenty-five out of 208 (12%) subjects developed a mild T CD4pos lymphocytosis, during anti-TNF-α therapy, which reverted after its interruption. Higher lymphocyte count, more frequent use of steroids and shorter disease duration, before biological therapy start, have emerged as risk factors for lymphocytosis development. CONCLUSIONS: This is the first longitudinal cohort study evaluating the onset of lymphocytosis in RA and PsA patients under anti-TNF-α treatment and its possible clinical relevance. A mild T CD4pos lymphocytosis has been observed in 12% of RA and PsA patients probably related to anti-TNF-α treatment as previously reported by anecdotal cases. Patients with higher baseline lymphocyte count, use of steroids and shorter disease duration before the introduction of biologic therapy, seem to be prone to develop this laboratory reversible abnormality.

MMPI-2 profiles and illness perception in fibromyalgia syndrome: The role of therapeutic exercise as adapted physical activity.

BACKGROUND: Control of pain management is an important up-stream process in fibromyalgia (FM) mechanisms. OBJECTIVE: To investigate whether adapted physical activity (APA) could change the illness perception in relation to the FM personality profile. METHODS: Thirty-seven women with FM allocated randomly: 19 treatment group (TG) and 18 control group (CG). Interventions: exercises program included ten sessions, two times for week for one hour each and observation for CG. Scales: Illness Perception Questionnaire-revisited (IPQ-r) for the mental representation of the disease, Minnesota Multiphasic Personality Inventory profiles (MMPI-2) for personality tool and Fibromyalgia Impact Questionnaire (FIQ) for function, impact and symptoms. Outcome assessments were performed before rehabilitation treatment (T0) than at the end (T1), and a follow-up 12 weeks after treatment (T2). RESULTS: APA was efficacy to improve FIQ values in TG at T1 and T2 test days (P = 0.014). Changes in IPQ-R values in T2 were not significant. All patients presented a baseline T-score≥65 in at least one of the basic and content MMPI-2 scales (Hy, D, Hs and Hea and Anx). CONCLUSION: APA was efficacy in FM, but further research to differentiate between illness experience rather than focus ona strict personality profile are necessary.

Psoriatic arthritis and CARD15 gene polymorphisms: no evidence for association in the Italian population.

Psoriatic arthritis (PsA) has been defined as an inflammatory arthritis associated with psoriasis that may affect as many as 30% of psoriasis patients. Epidemiological study reported strong familial clustering of PsA although the precise etiology of PsA is poorly understood. Recently, a genomewide linkage scan in PsA revealed a LOD score of 2.17 on chromosome 16q and provided strong evidence for a paternal imprinting effect. That region surrounds a psoriasis susceptibility locus including the CARD15 gene which has convincingly been shown to confer susceptibility to Crohn's disease. The existence of a common susceptibility gene for psoriasis/PsA and Crohn disease was recently demonstrated by evidence of association of CARD15 polymorphisms with PsA. To confirm these results in an independent population, we analyzed a data set of 193 Italian PsA patients and 150 controls for CARD15 polymorphisms (R702W, G908R and leu1007finsC) previously demonstrated associated with PsA. Here we report no evidence for association in the examined population for CARD15 polymorphisms, suggesting that the positive association previously reported in a genetically isolated population was the result of a linkage disequilibrium due to a founder effect.