AZA has been used as maintenance therapy in SSc-ILD after initial therapy with CyP.25 In a randomized, open-label trial of oral AZA (2.5 mg/Kg/day) versus oral CyP in early diffuse cutaneous SSc, AZA showed no efficacy on skin thickness and pulmonary function,33 whereas a retrospective study reported effectiveness of AZA in stabilizing lung function and improvement of mRSS.34 Adverse effects of AZA include bone marrow suppression, hepatotoxicity and gastrointestinal upset. Mycophenolate Mofetil. methotrexate, mycophenolate mofetil, tocilizumab, (-)-DHMEQ transplantation Introduction Systemic sclerosis (SSc) is usually a chronic connective tissue disease (CTD), which affects skin, blood vessels, lungs, heart, kidneys, gastrointestinal (GI) tract and musculoskeletal system. It is characterized by three cardinal features: early microvascular obliterative changes, activation of the immune system and widespread fibrosis of skin and internal organs. Involvement of internal organs results (-)-DHMEQ in significant morbidity and mortality. Microvascular changes are exemplified by Raynaud’s phenomenon (RP) and microvascular injury seen as nailfold capillaroscopy abnormalities, whereas immune activation is usually exemplified by SSc-related autoantibodies (auto-Abs).1C3 Systemic sclerosis affects all races and may be diagnosed at any age although most cases develop in individuals aged 20C60?years. As data continue to gather from around the world, it is shown that while the incidence of SSc exhibit remarkable variation across different geographic regions (ranging 2C23 cases per million), it appears to rise over the past three decades. Prevalence is also documented to span between 46C655 cases per million among different centers.4,5 Female predominance is evident among cases with limited SSc, while diffuse SSc appear to affect males and females at more comparable rates.2C6 SSc is considered to be a chronic, gradually deteriorating disease across several months to years. Some cases can stabilize for prolonged (-)-DHMEQ periods of time while others, primarily with diffuse disease, show a fulminate clinical course with detrimental consequences within few months. Mortality as well morbidity among patients with scleroderma is usually increased. Ten-year cumulative survival rate was found 66% during the 1990s.7 Major morbidity is related to the type and extent of internal organ involvement, such as (-)-DHMEQ pulmonary fibrosis and/or pulmonary hypertension that often lead to severe dyspnoea and oxygen dependence.6 GI tract involvement includes both the upper (common) and the lower part (less common); it may also be quite severe leading to malnutrition and death. 8 Infections also play significant role for the increased morbidity and mortality of patients with SSc. Propensity to infections is derived from both poor functional status and immunosuppressive treatment. Hand dysfunction due to tight skin, joint contractures and ulceration of the fingertips represent a common disabling factor among patients with SSc, which Rabbit Polyclonal to SCNN1D also leads to significant morbidity due to pain, frequent injuries, gangrene secondary to ischemia and self-amputations.6 In overall diffuse skin disease, male gender, older age at onset, cardiopulmonary involvement, renal crisis and the absence of (-)-DHMEQ Raynaud’s phenomenon as the initiating clinical symptom represent bad prognostic factors.9,10 Vascular abnormalities and immune abnormalities appear early in the disease course and are likely to drive the pathogenetic cascade of the disease. SSc-related auto-Abs, such as anti-topoisomerase I (anti-Topo; formerly anti-Scl70), anti-centromere (ACA), and anti-RNA polymerase III auto-Abs, appear before, and sometimes years before clinical fibrosis.2 Longitudinal skin biopsies from patients with SSc reveal inflammatory infiltrates early before histological fibrosis, but as the disease progresses inflammatory infiltrates greatly diminish and fibrosis dominates the histological picture.11 Pro-fibrotic cytokines, such as transforming growth factor (TGF), are considered pivotal for the disease pathogenesis. Evidence from animal models and in vitro studies indicates that T cells through cell contact, and cytokines activate fibroblast to produce collagen.3,12 Increased levels of T cell cytokines, including the pro-fibrotic IL-4 and IL-13 (Th2 cells), are seen in peripheral blood from SSc patients.13,14 Although aberrations in the expression of individual cytokines may be shared among.