Treatment of ankylosing spondylitis and extra-articular manifestations in everyday rheumatology practice

The SpAs are a group of overlapping, chronic, inflammatory rheumatic diseases including AS, a chronic inflammatory disease primarily affecting the SI joints. In addition to inflammatory back pain, AS patients are also more likely to experience extra-articular manifestations belonging to the SpA concept which can affect the eyes, the gastrointestinal tract and the skin and other related inflammatory conditions. This review focuses on current progress in treatment options in SpA with special emphasis on extra-articular features. TNF inhibition has demonstrated effectiveness in the treatment of AS symptoms and all currently available anti-TNF agents appear to have similar efficacy. However, the efficacy of anti-TNF agents varies in the treatment of extra-articular manifestations and comorbidities. Analyses of trials of anti-TNF agents in patients with AS have revealed significant reductions in the incidence of flares of uveitis and IBD with infliximab and adalimumab (uveitis only) treatment but not with etanercept. All three anti-TNF agents (infliximab, adalimumab, etanercept) have demonstrated efficacy in psoriasis (not associated with AS). When evaluating as to which agent to use in the treatment of AS, an important consideration is the overall well-being of the patient. This should include any additional inflammatory burden that manifests in other parts of the body, which may currently be subclinical. Based on current evidence, among TNF inhibitors, the monoclonal antibodies (infliximab and adalimumab) are more appropriate than etanercept if extra-articular manifestations or comorbid conditions are present or suspected. To date, infliximab appears to be the best studied agent with a wide spectrum of proven efficacy

Registry Evaluation of Digital Ulcers in Systemic Sclerosis

Digital ulcers are a very frequent complication of systemic sclerosis affecting about half of the SSc patients, and about 75% of the affected patients have their first DU episode within 5 years from their first non-Raynaud symptom. The lack of adequate classification criteria as well as the lack of knowledge of the development of DU have contributed to the opening of specific registries to better understand the natural history of these lesions. For these reason, specific disease registries play a fundamental role in this field of research. Thanks to the systematic collection of data and their subsequent analysis and comparison between different cohorts, it is possible to improve understanding of the underlying trigger mechanisms of DU development and to determine temporal trends. In the future, the development of recommendations for the management of DU remains of pivotal importance to prevent DU development and obtain rapid healing as well as reduction of pain and disability

Rheumatologic rehabilitation: the great expectation for rheumatic patients

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Pathophysiology of Hemophilic Arthropathy

Spontaneous joint bleeding and repeated hemarthroses lead to hemophilic arthropathy—a debilitating disease with a significant negative impact on mobility and quality of life. Iron, cytokines, and angiogenic growth factors play a pivotal role in the onset of the inflammatory process that involves the synovial tissue, articular cartilage, and subchondral bone, with early damages and molecular changes determining the perpetuation of a chronic inflammatory condition. Synovitis is one of the earliest complications of hemarthrosis, and is characterized by synovial hypertrophy, migration of inflammatory cells, and a high degree of neo-angiogenesis with subsequent bleeding. The pathogenic mechanisms and molecular pathways by which blood in the joint cavity causes articular cartilage and subchondral bone destruction have yet to be fully elucidated. Both cytokines and matrix metalloproteinases and hydroxyl radicals may induce chondrocyte apoptosis. Members of the tumor necrosis factor receptor superfamily (such as the molecular triad: osteoprotegerin—OPG; receptor activator of nuclear factor κB—RANK; RANK ligand—RANKL) seem instead to play a major role in the inflammatory process. These pathogenic processes interact with each other and ultimately lead to a fibrotic joint and the disabling condition characteristic of hemophilic arthropathy

The crowded crossroad to angiogenesis in systemic sclerosis: where is the key to the problem?

In systemic sclerosis (SSc), peripheral vasculopathy is characterized by a progressive and irreversible loss of capillaries following endothelial cell injury, due to defects in both vascular repair and expected increase in new vessel growth (angiogenesis). The discovery of key molecular targets may help to develop the most effective therapeutic strategy for the SSc-related vasculopathy. A pathway worth targeting in SSc may include vascular endothelial growth factor, 165b isoform, an endogenous angiogenesis inhibitor abnormally expressed and released by different cell types, including activated endothelial cells and platelets

Cyclophosphamide in systemic sclerosis: still in search of a 'real life' scenario

In systemic sclerosis (SSc), there is no proven treatment to prevent disease progression. In a recent meta-analysis of three randomised controlled trials (RCTs) and six open prospective studies on cyclophosphamide (CYC), no significant changes in lung function were observed. However, CYC is associated with an improvement of Mahler's dyspnea index, short form-36 (physical and mental domains), and health-related quality of life, contributing to the amelioration of patients' functional status. Further RCTs on early SSc are needed to assess the real efficacy of CYC in inducing remission and increasing survival

Future targets in the management of systemic sclerosis

CTDs—such as SSc and SLE and related rheumatic diseases such as RA—have complex, underlying pathogeneses that include fibrosis, vascular dysfunction, activation of the immune system and inflammation. Although some current therapies for SSc offer benefits to patients, there is a clear need to investigate potential therapeutic targets. However, the breadth and diversity of cellular pathways and mediators implicated in these diseases, coupled with inherent redundancies in these systems, has made pre-clinical investigation difficult. Despite this, recent advances have been made in elucidating the immunological aspects of CTD, including the roles of B cells, T cells, matrix-remodelling cells and autoantibodies, enabling novel therapeutic approaches including immunoablation to be investigated. The mechanisms underlying the fibrosis that characterizes SSc are also becoming clearer; and as the putative events that trigger excessive collagen deposition are identified, so too are potential junctures at which these aberrant processes may be deactivated. Progress is also being made in understanding the vasculopathy in SSc, and the potential benefits of antioxidants and endothelin receptor antagonists. There have been some significant advances in the treatments available to SSc patients; however, this spectrum of diseases remains challenging, and continues in some cases to be associated with high morbidity, increased mortality and poor prognosi

Vasculogenesis and angiogenesis: vascular damage in systemic sclerosis

La sclerosi sistemica (SSc) è una malattia multisistemica del connettivo caratterizzata dalla presenza di alterazioni microvascolari con deficit angiogenetico (1). Suddividendo la patogenesi della SSc in momenti successivi è possibile considerare il microcircolo come la struttura colpita dalla malattia che in più fasi coinvolge l’organismo del paziente affetto da SSc (2). La cellula endoteliale (CE) viene inizialmente attivata tramite una noxa ignota alla produzione di molecole di adesione, chemiochine, citochine e fattori di crescita. In tal modo viene facilitato il passaggio (homing) linfocitario nei tessuti. Inizialmente si ha un danno a carico della CE seguito da un ispessimento dell’intima e da un progressivo restringimento del lume fino alla completa ostruzione del vaso..