Pain in systemic connective tissue diseases

Pain is frequent in patients with connective tissue diseases (CTDs), particularly those affected by systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) in which it is virtually ubiquitous and can have different causes. The SLE classi fi cation criteria include pain associated with musculoskeletal involve- ment, which are frequently the initial symptom of SLE and can include arthralgia, arthritis and/or myalgia. Chronic widespread pain, the cornerstone of fi bromyalgia (FM), is also frequently associated with CTDs. Chronic pain has a considerable impact on mental health, and the professional and family lives of patients. It can be due to many disorders, but there are few reports concerning its prevalence during the course of other diseases. It is essential to identify the origin of pain in CTDs in order to avoid dangerous over-treatment in patients with co-existing widespread pain. Effective pain management is a primary goal of patient care, although it has not been investigated in detail in patients with SSc

Biomarkers in fibromyalgia: a review

Camillo Giacomelli,* Francesca Sernissi,* Alessandra Rossi, Stefano Bombardieri, Laura BazzichiRheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy *These authors contributed equally to the manuscript Abstract: Fibromyalgia is a common syndrome diagnosed by clinical criteria. The main symptom of fibromyalgia is pain, but patients frequently also complain about other nonspecific symptoms, such as headache, sleep disturbance, mood disorder, and cognitive impairment. In the light of the multifactorial origin of the disease and of the lack of objective diagnostic findings, several attempts have been made to find a reliable biomarker. For this reason, over the years, a number of patients and various biological samples have been studied, using many different approaches and techniques. Despite this, none of these studies has been able to find the proper biomarker. The aim of this review is to provide a critical overview of the current environment characterizing the search for fibromyalgia biomarkers. Keywords: genetics, proteomics, oxidative stress, fibromyalgi

Gender differences on psychological factors in fibromyalgia: a systematic review on male’s experience

Objectives: Fibromyalgia (FM) is highly prevalent in female gender. Scarce attention has been given to the exploration and description of this syndrome, from a psychological point of view, when occurring in males. The aim of the present study is to develop further knowledge, and to summarise the literature regarding subjective psychological experience, characteristics of symptoms presentation (both onset and development), and treatment options for FM in male patients, in order to highlight differences with FM in females. Methods: All studies published between January 1993 and February 2020 using PubMed and PsycInfo were included, provided that they met the following criteria: 1) written in English; 2) original articles on studies with a longitudinal design; 3) prospective or retrospective, observational (analytical or descriptive), experimental or quasi-experimental, controlled or noncontrolled studies. Reviews and nonoriginal articles (i.e, editorials, Letters to the Editor, and book chapters) were not included. We utilised the following keywords: (male), (female), (fibromyalgia), combined with Boolean operators 'AND' and 'NOT'. Results: We found an initial number of 55 papers. Duplicated records were excluded (n=13), as well as papers not focusing on male patients or not fulfilling inclusion criteria (n=25), narrowing the research to 17 papers. Conclusions: FM male patients consider their masculine identity as inefficiently re-negotiated after symptoms' onset. FM males tend to endure pain for longer periods of time than females before seeking for treatment; bodily symptoms are prevalent with a compromised exploration of feelings about FM. Unfortunately, there is still paucity of evidence on clinical characterisation and treatment options when FM occurs in males. Moreover, no studies addressed the issue of the psychopharmacological/non-pharmacological management of males with FM and comorbid psychiatric syndromes

Salivary psoriasin (S100A7) correlates with diffusion capacity of carbon monoxide in a large cohort of systemic sclerosis patients

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive fibrosis of the skin and the internal organs. In a previous work we suggested a correlation between levels of salivary psoriasin (S100A7) and pulmonary involvement in SSc patients. The goals of this study are to determine the distribution characteristics of psoriasin in whole saliva (WS) of SSc and healthy donor populations and define its predictive value on diffusion capacity of carbon monoxide (DLCO), along with others clinical parameters. Methods: Salivary level of psoriasin was determined by ELISA kit in 134 SSc patients, 63 Raynaud syndrome patients, 40 patients affected by other connective diseases (non-case) and 74 healthy control subjects. Results: A significant increase of salivary psoriasin was observed in SSc patients when compared with other healthy and pathological controls. Moreover, we confirmed the efficacy of salivary psoriasin to correlate with DLCO in a large cohort of SSc patients. Conclusions: Overall our results suggest a rapid, non invasive and low costing method which can help clinicians in the evaluation of SSc pulmonary involvement

A(2B )adenosine receptor activity is reduced in neutrophils from patients with systemic sclerosis

We conducted the present study to investigate protein expression and functioning of A(2A )and A(2B )adenosine receptors (ARs) in neutrophils of patients affected by systemic sclerosis (SSc). The presence of A(2A )and A(2B )ARs was assessed by immunoblotting using specific antibodies. Equilibrium A(2A )and A(2B )ARs binding parameters were evaluated by radioligand binding assay. Functional studies were conducted to investigate coupling of the A(2B )AR to the adenylyl cyclase pathway. This is the first report of the use of Western blot analysis to confirm the presence of A(2A )and A(2B )ARs in human neutrophils. No significant changes in A(2A )AR binding parameters or expression levels were detected between SSc patients and healthy control individuals. A significant decrease (65%) in the maximum density of A(2B )AR binding sites occurred in SSc neutrophils, whereas no changes in the affinity constant values were found. Moreover, a decrease in A(2B )AR mediated adenylyl cyclase activity was observed in patients with SSc. Our findings demonstrate the occurrence of selective alterations in A(2B )AR density and signalling in SSc

Alteration of serotonin transporter density and activity in fibromyalgia

The aim of the study was to evaluate the kinetic parameters of a specific serotonin transporter (SERT) and serotonin uptake in a mentally healthy subset of patients with fibromyalgia. Platelets were obtained from 40 patients and 38 healthy controls. SERT expression and functionality were evaluated through the measurement of [(3)H]paroxetine binding and the [(3)H]serotonin uptake itself. The values of maximal membrane binding capacity (B(max)) were statistically lower in the patients than in the healthy volunteers, whereas the dissociation constant (K(d)) did not show any statistically significant variations. Moreover, a decrease in the maximal uptake rate of SERT (V(max)) was demonstrated in the platelets of patients, whereas the Michaelis constant (K(m)) did not show any statistically significant variations. Symptom severity score (tiredness, tender points index and Fibromyalgia Impact Questionnaire) were negatively correlated with B(max )and with V(max), and positively correlated with K(m). A change in SERT seems to occur in fibromyalgic patients, and it seems to be related to the severity of fibromyalgic symptoms

A multidisciplinary approach to study a couple of monozygotic twins discordant for the chronic fatigue syndrome: a focus on potential salivary biomarkers

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a severe, systemic illness characterized by persistent, debilitating and medically unexplained fatigue. The etiology and pathophysiology of CFS remains obscure, and diagnosis is formulated through the patient’s history and exclusion of other medical causes. Thereby, the availability of biomarkers for CFS could be useful for clinical research. In the present study, we used a proteomic approach to evaluate the global changes in the salivary profile in a couple of monozygotic twins who were discordant for CFS. The aim was to evaluate differences of salivary protein expression in the CFS patient in respect to his healthy twin. METHODS: Saliva samples were submitted to two-dimensional electrophoresis (2DE). The gels were stained with Sypro, and a comparison between CFS subject and the healthy one was performed by the software Progenesis Same Spot including the Analysis of variance (ANOVA test). The proteins spot found with a ≥2-fold spot quantity change and p<0.05 were identified by Nano-liquid chromatography electrospray ionization tandem mass spectrometry. To validate the expression changes found with 2DE of 5 proteins (14-3-3 protein zeta/delta, cyclophilin A, Cystatin-C, Protein S100-A7, and zinc-alpha-2-glycoprotein), we used the western blot analysis. Moreover, proteins differentially expressed were functionally analyzed using the Ingenuity Pathways Analysis software with the aim to determine the predominant canonical pathways and the interaction network involved. RESULTS: The analysis of the protein profiles allowed us to find 13 proteins with a different expression in CFS in respect to control. Nine spots were up-regulated in CFS and 4 down-regulated. These proteins belong to different functional classes, such as inflammatory response, immune system and metabolism. In particular, as shown by the pathway analysis, the network built with our proteins highlights the involvement of inflammatory response in CFS pathogenesis. CONCLUSIONS: This study shows the presence of differentially expressed proteins in the saliva of the couple of monozygotic twins discordant for CFS, probably related to the disease. Consequently, we believe the proteomic approach could be useful both to define a panel of potential diagnostic biomarkers and to shed new light on the comprehension of the pathogenetic pathways of CFS

Antipolymer antibody in Italian fibromyalgic patients

The objectives of the present study were to evaluate the presence of antipolymer antibody (APA) seropositivity in 285 Italian patients affected by primary fibromyalgia (FM) and to verify whether APA levels correlate with disease severity and with cytokine levels