Intravenous immunoglobulins (IVIG) in systemic sclerosis: a challenging yet promising future

Abstract

The etiology and pathogenesis of systemic sclerosis are still largely unknown, but a variety of humoral and cellular autoimmune phenomena have been documented. In addition, the rarity of the disease, the broad spectrum of clinical manifestations, and the relevant risk of severe complications as well as the highly variable disease course render its management a major challenge. Some immunomodulatory agents have been used, but no single agent has given a convincing proof of effectiveness, and treatment has remained largely symptomatic through recent years. Novel therapies are currently being tested and may have the potential of modifying the disease process and overall clinical outcome. Efficacy of intravenous immunoglobulins (IVIG) in different regimens (1-2 g/kg of body weight, administered over 2-5 consecutive days) has been described in a limited number of trials and small case series, showing benefits in skin, articular, and lung interstitial disease symptoms. However, studies on IVIG in systemic sclerosis still remain few, and further randomized controlled trials should be undertaken to assess their clinical effectiveness or define the optimal dosage and times of administration.

Treatment of rapidly progressive systemic sclerosis: current and futures perspectives

“…Usually a reduction of mRSS is detectable after 6 to 8 months of therapy although stabilization may be evident a few months earlier. For patients considered refractory to MMF (ie progression of skin disease after 6 months), the addition of a second agent such as MTX [104–106] or D-Penicillamine [81,159] or the use of IVIG therapy should be considered [114,160]. …”

Immunotherapy of systemic sclerosis

“…53 IVIg has been increasingly used during the last decades for an growing number of systemic immunemediated and heterogeneous inflammatory diseases The mechanism of high-dose IVIg remains unclear, but probably works in multiple fronts, such as blocking the binding of serum immunoglobulins, B cell surface immunoglobulins, and T cell antigen receptors to their respective antigens. 54 IVIg reduced skin fibrosis and inhibited IL-4 and TGF-b production in tight skin (TSK) mice. 55 In two small open-label studies in patients with SSc, IVIg reduced histological skin fibrosis and joint pain and improved hand function.…”

Treatment of recalcitrant generalized morphea with mycophenolate mofetil and intravenous immunoglobulin

“…Several novel treatment options, such as imatinib (Alcántara-Reifs et al, 2015), infliximab (Diab et al, 2010), and everolimus (Frumholtz, Roux, Bagot, Rybojad, & Bouaziz, 2016), have been reported to be effective in refractory cases. MMF and IVIG are well-tolerated, promising alternative treatment modalities reported to be effective for skin sclerosis in the systemic scleroderma setting, with a remarkable restoration of movement capability and reduction in mRSS reported in recent clinical trials and case reports (Yanaba, 2016;Cantarini et al, 2015). Moreover, reliable data from case reports supporting the use of MMF in refractory GM are available (Martini et al, 2009).…”