Giacomo Cafaro MD, Elena Bartoloni MD, Alessia Alunno MD PhD, Onelia Bistoni BSc, Sabrina Cipriani PhD, Fabiana Topini PhD and Roberto Gerli MD
Platelets have the ability to influence the immune system and the inflammatory process and may be strongly involved in the whole pathogenic process of chronic inflammatory joint diseases, such as rheumatoid arthritis. They may play a significant role even before the clinical onset of the disease, contributing to the loss of tolerance of the immune system and the induction of autoimmunity. Subsequently, they can interact with the most important cellular players involved in autoimmunity and inflammation, namely innate immunity cells and T cells and eventually contribute to the building of inflammation in the synovium, thus inducing the activation, migration, and proliferation of fibroblasts that eventually lead to joint damage. Due to their peculiar features, studying the behavior of platelets is a challenging task; however, platelets may prove to be valuable therapeutic targets in the future.
Mohammad Adawi MD MHA, Sabbah Firas MD and Arnon Blum MD
Inflammation is the basic mechanism leading to many pathological processes, including degenerative diseases, atherosclerosis, and cancer. We found an interesting link connecting rheumatoid arthritis and atherosclerosis that may explain the high cardiovascular event rate among patients with rheumatoid arthritis, but also may lead to a new way of thinking and a better understanding of atherosclerosis. Rheumatoid arthritis could serve as a model of accelerated atherosclerosis. Understanding the basic mechanisms of rheumatoid arthritis may solve some of the complexity of atherosclerosis.
Laura Andreoli MD PhD, Antía García-Fernández MD, Maria Chiara Gerardi MD and Angela Tincani MD
Rheumatic diseases commonly affect women of childbearing age, when women may be contemplating pregnancy or they discover an unplanned pregnancy. Therefore, specific issues about pregnancy planning and management are commonly encountered in patients during these times. Knowledge of the effect of pregnancy on disease activity is important for counseling. This review summarizes recent data on the course of different rheumatic diseases during pregnancy and the postpartum period. Rheumatoid arthritis and systemic lupus erythematosus are the most commonly investigated diseases. Data are increasing about spondyloarthritis. Sparse data are available for other rheumatic diseases. Despite the differences in these diseases and the various courses these disease take during pregnancy, a common feature is that active maternal disease in the months prior to conception increases the risk of flares during pregnancy, which in turn can lead to adverse pregnancy outcomes. Therefore, maternal and fetal health can be optimized if conception is planned when disease is inactive so that a treatment regimen can be maintained throughout pregnancy.
Paola Di Benedetto PhD, Piero Ruscitti MD, Vasiliki Liakouli MD PhD, Paola Cipriani MD PhD and Roberto Giacomelli MD PhD
Microvascular damage, clinically expressed by Raynaud’s phenomenon, is generally the first symptom of the disease and the injured vascular cells, both endothelial and perivascular, may transdifferentiate to myofibroblasts, thus leading to collagen deposition in the tissue and consequent fibrosis. Systemic sclerosis (SSc, scleroderma) is complex disease characterized by autoimmunity, vasculopathy, and fibrosis. It has been shown that microvascular damage may be the first symptom of SSc. Injured endothelial cells and pericytes may transdifferentiate into myofibroblasts, the cells responsible for fibrosis and collagen deposition in the tissue. Based on these factors, the process of myofibroblast generation may link two pivotal events of SSc: microvascular damage and fibrosis. Understanding the development, differentiation, and function of myofibroblasts is therefore crucial to individuate early pathogenetic events and develop new therapeutic target for SSc, a condition in which no disease-modifying agents are available. The aim of this review was to discuss the possible origins of myofibroblasts in SSc, highlighting the process of endothelial mesenchymal transition and pericytes to myofibroblast transition and to show how these events may contribute to pathogenesis of the disease.
Lisa Gamalero MD, Gabriele Simonini MD, Giovanna Ferrara MD, Silvio Polizzi MD, Teresa Giani MD and Rolando Cimaz MD
Uveitis is an inflammatory disorder of the uveal tract of the eye that can affect both adults and children. Non-infectious uveitis can be an expression of a systemic autoimmune condition, or it can be idiopathic. It is a serious disease, associated with possible severe complications leading to visual impairment and blindness. For this reason, a prompt diagnosis and assessment of an appropriate treatment, with the collaboration of specialists such as ophthalmologists and rheumatologists, are extremely important. Many treatment options may be associated to side effects; therefore, clinicians should follow a stepladder approach starting with the least aggressive treatments to induce remission of inflammation. In this review, we reported the current evidence-based treatments for non-infectious uveitis in pediatric and adult patients with particular attention to the biologic response modifier treatment options. Important multicenter studies have demonstrated the efficacy of adalimumab, both in adults (VISUAL I, VISUAL II, VISUAL III) and in children (SYCAMORE, ADJUVITE), while for other agents data are still scarce.
Jakub Moll MD, Natasa Isailovic MsC, Maria De Santis MD PhD and Carlo Selmi MD PhD
Serum rheumatoid factors are autoantibodies of different isotypes directed against the Fc fraction of immunoglobulin G (IgG) and represent paradigmatic autoantibodies that have been largely used in clinical practice for decades. Traditionally IgG has been associated with rheumatoid arthritis and more recently included also in the classification criteria for Sjӧgren’s syndrome. Researchers have established that rheumatoid factors are positive in a variety of infectious, autoimmune, and neoplastic disorders, thus requiring a comprehensive evaluation of seropositive patients. Of note, hepatitis B and C viruses represent a crossroad that includes the high rheumatoid factor seroprevalence and chronic inflammatory disease, as well as progression to non-Hodgkin's lymphomas. Chronic antigen stimulation is the likely common ground of these processes and rheumatoid factors may represent mere bystanders or drivers of pathology. Mixed cryoglobulinemia and lymphoproliferative disease are prime examples of the deleterious effects of rheumatoid factor-B cell activity, possibly associated with hepatitis B and C. More importantly, they show a clear association in a physiological host response to infection, chronic inflammation, and the slide toward autoimmunity and malignancy. The association between hepatitis B and C infections and the appearance of serum rheumatoid factors is further supported by prevalence data, which support a coexistence of these markers in a significant proportion of cases, with viral infections being frequent causes of rheumatoid factors in patients without a rheumatic condition. We provide a comprehensive overview of the known connections between hepatitis B and C infections and rheumatoid factors.
Carlo Perricone MD PhD, Daphna Katz, Cinzia Ciccacci PhD, Fulvia Ceccarelli MD PhD, Guido Valesini MD, Yehuda Shoenfeld MD FRCP MaACR, Paola Borgiani PhD and Fabrizio Conti MD PhD
Recurrent pericarditis is a state of repetitive inflammation of the pericardium with intervals of remission. The etiology of recurrent pericarditis is still largely unknown, yet most causes are presumed to be immune mediated. Genetic factors, including human leukocyte antigen (HLA) haplotypes, can be involved in dysregulation of the immune system and as a predisposition to several autoimmune conditions, including recurrent pericarditis. Several diseases are frequently associated with such manifestations. They include systemic lupus erythematosus, familial Mediterranean fever, and tumor necrosis factor receptor-associated periodic syndrome. However, idiopathic recurrent pericarditis remains the most frequently observed clinical condition and the conundrum of this disease still needs to be solved.