Pathogenesis of Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy involving synovial and entheseal structures, associated with psoriasis or similar conditions. The etiopathogenetic mechanisms underlying PsA remain unclarified. The most accredited hypothesis involves a complex interaction among genetic, environmental, and immunological factors. Environmental agents, particularly trauma, mechanical stress, and smoke have been cited as possible factors in triggering the disease in genetically predisposed subjects. Like other forms of spondyloarthropathies, PsA shows several genetic associations with the major histocompatibility complex (MHC) class I alleles located on chromosome 6p21.3, particularly the human leukocyte antigen (HLA)-B27 in axial phenotypes. Recent studies have demonstrated that the most common epigenetic mechanisms that regulate gene expression in PsA are represented by DNA methylation, parent of origin effect or genomic imprinting, expression or activity of epigenetic modifying enzymes, and RNA interference (RNAi) by microRNAs (miRNAs). The mechanisms underlying PsA pathogenesis activate the innate and adaptive immune system and overexpression of TNF associated with amplification of the IL-23/IL-17 axis. In recent years, more PsA susceptibility genes and epigenetic mechanisms have been identified. Advances in the knowledge of innate and adaptive immune mechanisms underlying PsA have contributed to a better understanding of the heterogeneous clinical expression of the disease and, thus, to therapy strategies. The complexity of the pathogenetic aspects involving multiple cytokines, cell lines, and molecules needs to be further investigated to advance personalized therapeutic strategies and to improve outcomes of patients affected by PsA.

Incidence of Malignancies in a Cohort of Psoriatic Arthritis Patients Taking Traditional Disease Modifying Antirheumatic Drug and Tumor Necrosis Factor Inhibitor Therapy: An Observational Study.

OBJECTIVE: Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis. As suggested in 2012 by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), studies devoted to assess cancer in the PsA population are still limited and need to be increased. Therefore, the aim of this study was to determine the incidence of malignancies in patients with PsA who are taking conventional and biologic therapies. METHODS: A cohort of patients with PsA was followed prospectively. At first visit, as well as at each 3-4 month followup visit, according to standardized clinical practice, medical history, and physical and laboratory findings were recorded. Information on the presence of comorbidities, as well as malignancies, was collected. At each visit, data were recorded on radiography and pathology, confirming malignancy diagnosis, when present. RESULTS: A total of 618 patients with PsA were included in the study. In particular, 296 were taking anti-tumor necrosis factor-α (anti-TNF) agents and 322 were taking disease-modifying antirheumatic drugs (DMARD). During the observation period, in the total group, 44 patients (7.1%) had a diagnosis of malignancy. Of them, 14 (4.7%; 95% CI 2.8-7.8; 0.52/100 patient-yrs) received anti-TNF therapy and 30 (9.3%; 95% CI 6.6-13.0; 1.03/100 patient-yrs) received traditional DMARD (p = 0.019). However, after adjusting for major demographic and clinical characteristics, the difference between the 2 treatments was no longer significant (p = 0.480), and the only predictor of malignancy occurrence was age (HR 1.04, 95% CI 1.009-1.073, p = 0.012). CONCLUSION: Data from this study confirm that biological therapies do not lead to any increased risk for cancer development, when adequately administered and with proper followup.

Mud-bath therapy and oral glucosamine sulfate in patients with knee osteoarthritis: a randomized, controlled, crossover study.

OBJECTIVES: To evaluate the efficacy and safety of combined treatment of mud-bath therapy and glucosamine crystalline sulfate (GlcN-S) in patients with knee osteoarthritis (OA). METHODS: This study was a randomised, controlled, crossover investigation. Patients were randomly assigned (1:1) by the investigators to two groups, named group 1 and 2. Group 1 included twenty-three patients receiving oral GlcN-S treatment from the beginning of the study (T0) to the end of the 3rd month of treatment (T3) and a combined treatment of both mud-bath therapy and GlcN-S from T3 to the end of the study at six months (T6). Group 2 included twenty-two patients receiving a combined treatment of both mud-bath therapy and GlcN-S from T0 to T3 and that discontinued mud-bath therapy, receiving GlcN-S treatment alone, from T3 to T6. Primary endpoints of the study consisted of evaluating OA severity and activity at baseline and at follow-up visits. RESULTS: All 45 patients, eligible for the study, completed the period of the crossover. In group 1, no significant difference was shown in the comparison from T0 to T3, while from T3 to T6 most variables were significantly improved. In group 2, instead, the comparison between T0 and T3 showed a significant difference in different parameters. When comparing T3 and T6, despite an improvement of all the variables, no significant difference was shown. CONCLUSIONS: The association of GlcN-S and mud-bath therapy has a positive and safe role in improving pain, function and quality of life in knee OA patients.

Emerging drugs for psoriatic arthritis.

INTRODUCTION: The majority of Psoriatic Arthritis patients experience a good clinical response to anti-Tumor Necrosis Factor (TNF)-α therapies. However, treatment failure with anti-TNF-α can represent a relevant clinical problem. AREAS COVERED: We review the efficacy and safety profile of biological therapies that have been reported from randomized, controlled trials in phase II and phase III available in Pubmed Database for agents targeting IL-12/23p40 antibody (ustekinumab) and IL-17 (secukinumab), inhibitor of phosphodiesterase 4, (apremilast), and of JAK/STAT pathways (tofacitinib) and CTLA4 co-stimulation (abatacept) in Psoriatic Arthritis. EXPERT OPINION: In Psoriatic Arthritis, main emerging drugs are represented by the fully human monoclonal IL-12/23p40 antibody, ustekinumab, the agent targeting IL-17, secukinumab, and the inhibitor of phosphodiesterase 4, apremilast. Results on T cell co-stimulation inhibition by abatacept are insufficient both in psoriasis and in PsA. In vitro investigations on JAK/STAT pathways in PsA suggest that tofacitinib could represent a further valuable therapeutic option. Emerging biological treatments other than anti-TNF agents, ustekinumab, secukinumab and apremilast appear promising for Psoriatic Arthritis and recent studies have showed a good efficacy and an acceptable safety profile; however, further and long-term studies are advocated.

Autoimmunity and autoinflammation as the yin and yang of idiopathic recurrent acute pericarditis.

Autoimmunity and autoinflammation are generally considered as mutually exclusive mechanisms of diseases but may concur to specific syndromes. Idiopathic recurrent acute pericarditis (IRAP) is defined as the recurrence of pericardial symptoms at any point following the prior cessation of acute pericarditis, and the latency is generally 6 weeks. Manifestations of pericarditis such as pericardial friction rub, electrocardiographic changes, and pericardial effusion are less frequent in the subsequent episodes compared to the index attack, and in some cases the only clinical sign is represented by a suggestive chest pain. Several autoimmune diseases may manifest with pericarditis which is often related to viral infections, while postviral pericarditis may in turn display a nonspecific autoimmune background. Similarly, autoinflammatory syndromes such as familial Mediterranean fever and tumor necrosis factor receptor-associated periodic syndrome are characterized by self-limiting pericardial symptoms. Corticosteroids are generally effective, thus supporting the autoimmune nature of IRAP, but dramatic results are obtained with interleukin-1 blocking agents in corticosteroid-dependent cases, pointing to a pathogenic role for the inflammasome. Based on these observations, we submit that IRAP represents a paradigmatic example of the putative coexistence of autoimmunity and autoinflammation: the main aim of this review is to critically discuss the hypothesis as well as the current understanding of this enigmatic clinical condition.