Current Rheumatology Reviews - Volume 8, Issue 3, 2012

The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPL), hypercoagulability leading to vascular thrombosis, and pregnancy morbidity. Since its recognition, a great number of cardiac manifestations have been reported in association with these antibodies, but heart valve abnormalities are the most common cardiac manifestations of the syndrome. They include valve thickness >3 mm, localized thickening involving the leaflet's proximal or middle portion, and/or irregular nodules on the atrial face of the edge of the mitral valve, and/or the vascular face of the aortic valve. A consensus committee recommended anticoagulation in symptomatic valvular disease. Asymptomatic patients should be prophylactically treated with aspirin.

This article explores the strategies of systemic lupus erythematosus (SLE) Pharmacotherapy. SLE is a multisystem autoimmune disease, which affects different tissues and organs in the body, causing damage and dysfunction. Some patients with lupus have a very mild disease that can be treated with simple medications, whereas others have serious, lifethreatening complications. Treatments vary according to the variability in the clinical presentation of disease, and should be highly individualized. Optimal care of the patient with SLE includes education and support services in addition to the pharmacologic and non-pharmacologic treatments. Drug therapy for SLE is often designed to suppress the immune response and inflammation. Minor manifestations can be treated with, less toxic agents, such as non-steroidal antiinflammatory drugs, topical intra-lesion corticosteroids, and anti-malarial drugs. Aggressive therapy with high-dose corticosteroids is necessary in patients with worsening lupus nephritis. Central Nervous System (CNS) lupus has responded in various degrees to dexamethasone and methylprednisolone. Immunosuppressive have become the gold standard for the treatment of major organ involvement in SLE. The treatment of moderate to severe disease comprises initially a period of intensive immunosuppressive therapy aimed at halting immunological injury followed by less aggressive maintenance therapy to consolidate remission and reduce the risk of flares. Recently, specific drugs are used as adjuvants to the previous therapy including intravenous immunoglobulins (IVIg), plasmapharesis, and dehydroepiandrosterone (DHEA). However, most drugs are associated with certain levels of toxicity therefore it is important to understand the toxicity profiles of these drugs and their implications on management in order to offer sound medical care.

Individuals with Rheumatoid Arthritis (RA) have increased mortality when compared with the general population. Much of this increased mortality can be attributed to cardiovascular causes. The exact cause for this increased risk has not been fully determined, although some potential mechanisms have been postulated. This overview aims to outline and discuss some of the potential factors which relate to this increased cardiovascular disease risk in the RA population. Inflammation is one such potential factor as inflammation has been shown to play a central role in all phases of atherosclerosis. Therefore, assessment of inflammatory markers may help identify those at high risk of future cardiovascular events. This paper aims to provide a deeper understanding of the links between inflammation and atherosclerosis and cardiovascular disease. Physical activity is associated with improvements in cardiovascular health in many populations. A link between inflammatory marker levels and physical activity has been determined and the literature specifically assessing this link is analysed in this overview. Although the literature is scarce regarding the RA population, two studies which investigate the relationship in this population are presented and discussed.

Osteoarthritis (OA) refers to a group of mechanically-induced joint disorders to which both genetic and acquired factors contribute. Whilst, the pathogenesis of the disease is unclear, there are, currently, no treatments that prevent the development or the progression of osteoarthritis. An improved mechanistic and pathologic understanding of OA will likely reveal new therapeutic targets to slow or halt disease progression. The ability to slow progression of OA in older adults will have enormous public health implications given the aging of our population and the increase in other OA risk factors such as obesity. This review is seeking to gain insight into recent concepts in osteoarthritis aetio-pathogenesis dealing with the joint as an organ and OA as a disease of the whole joint. The focus is on highlighting the use of biomarkers for early diagnosis of joint degeneration and whether imaging can be used as a biomarker for early diagnosis as well as disease progression of joint affection. The article will also review recent opportunities and challenges in the management of osteoarthritis and the possibility of a unique window of opportunity to limit the disease chronic consequences.

Osteopenia and osteoporosis occur at a higher frequency in adults with Systemic Lupus Erythematosus (SLE) compared to healthy controls. Similar findings have been demonstrated in children as well as in adults with juvenile-onset SLE, though the data are limited. The etiology of poor bone health in these patients is multi-factorial. Causes include direct effects of the disease itself, with its associated chronic inflammation and low vitamin D levels, as well as indirect effects such as fatigue resulting in decreased physical activity and poor nutrition. Disease therapy, including medications such as corticosteroids or non-medical therapy such as sunscreen and sun avoidance, also impacts bone health. Being cognizant of the long-term effects of SLE itself as well as its treatments on bone health is especially critical in the pediatric population, as adolescence is the time of peak bone mass accrual. If this window is missed, patients are at an increased lifetime risk of complications from osteopenia and osteoporosis. In this review article, we will evaluate the published data regarding bone health in patients who develop SLE in childhood and adolescence as well as risk factors associated with increased risk of osteopenia and osteoporosis. We will also review the current available imaging techniques and recommendations for monitoring and maintenance of bone health.

Interleukin-6 (IL-6), originally identified as a B cell differentiation factor, is a typical cytokine featuring redundancy and pleiotropic activity. IL-6 provides a warning signal and participates in host defense against acute environmental stress such as infections and injuries by inducing immune responses, hematopoiesis and acute-phase reactions. However, its abnormal persistent production plays an important pathological role in the development of various immune-mediated diseases through its pleiotropic activity, in particular induction of an imbalance of CD4 positive effector subsets (Th17 >> regulatory T cells), and autoantibody production. IL-6 blockade was thus expected to constitute a novel strategy for the treatment of diseases and to this purpose tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, was developed. World-wide clinical trials have proved the efficacy and tolerable safety of TCZ for patients with moderate-tosevere rheumatoid arthritis and it is now used as an innovative biologic for rheumatoid arthritis in more than 90 countries. Moreover, findings of recent pathological analyses of other immune-mediated diseases as well as favorable results of pilot or case studies with off-label use of TCZ strongly imply that IL-6 blockade strategy will be broadly applicable for the treatment of various systemic autoimmune diseases including systemic lupus erythematosus, systemic sclerosis, polymyositis and large-vessel vasculitis, as well as of chronic inflammatory diseases such as polymyalgia rheumatica and Bechet's disease.

Many pivotal studies and post-marketing experiences have confirmed the safety and efficacy of biologics in treating psoriasis. However, only limited data are available in Asia-Pacific region. Open label studies of efalizumab and alefacept have been conducted in Taiwan. A phase II/III randomized controlled study and an open label study of adalimumab have been conducted in Japan and Taiwan. As for infliximab, randomized, double-blind, placebo-controlled multicenter trials of psoriasis have been conducted in Japan and China. For etanercept, retrospective studies have been reported in South Korea and Taiwan in addition to two clinical studies (PRESTA and PRISTINE) which both involved Taiwanese and Korean patients. Three phase 3 randomized placebo-controlled studies for ustekinumab have been conducted, PEARL (in Korea and Taiwan), Jpn-02 (in Japan) and LOTUS (in China). The safety profiles of the above biologics used among Asia-Pacific population were generally consistent with the results published in the pivotal studies except for high incidence of newly onset arthritis and anti-drug antibodies in the efalizumab studies. Besides, a higher incidence of anti-drug antibodies was also found after infliximab use. The therapeutic efficacy of the biologics showed a mixed result in Asia- Pacific region. This review article offers a detail summary on the already published data in Asia-Pacific region, of the six biologics indicated for treating psoriasis, namely alefacept, efalizumab, adalimumab, infliximab, etanercept, and ustekinumab. Currently, secukinumab is already under phase III studies (ERASURE and SCULPTURE) in Japan, Taiwan, and Vietnam. In addition, we have also provided a summary of the current status of individual government reimbursement of the biologics in Asia-Pacific region.