Intravenous immunoglobulin (IVIG) in the vanguard therapy of Systemic Sclerosis
Introduction
Systemic sclerosis (SSc) is a rare autoimmune disease that is characterized by a progressive skin fibrosis, an obliteration of the microvasculature and an exaggerated extracellular matrix deposition [1]. Those phatophysiolofgical alterations result in a multi systemic dysfunction and the symptoms depend on the affliction of each organ. People with a diagnosis of SSc have a risk of mortality three- to five-times greater than the general population and the involvement of major organs (cardiac, interstitial lung disease, pulmonary hypertension and scleroderma renal crisis) affects the morbidity and increases the mortality [2].
SSc is classified into different clinical subsets, depending on skin involvement. The limited cutaneous SSc (lcSSc) is a subset characterized by skin sclerosis of the hands and feet distal to the elbows and knees, respectively, as well as the face [2]. This subset is usually associated with anticentromere and anti-Th/To antibodies [2]. On the other hand, the diffuse cutaneous SSc (dcSSc) is associated with the presence of anti-topoisomerase I and anti-RNA polymerase III antibodies, without a restricted skin involvement [2]. This last form has a high frequency of internal involvement and a rapidly progressive course of the disease, which affects the prognosis [2].
The therapy for SSc ranges between corticosteroids to hematopoietic stem cells transplantation, depending on the tissue affected [1]. Until today, none of the therapies have been described as a successful anti-fibrotic therapy [1] with a limited efficacy [3]. There are different reasons that can justified this unsuccessful response beyond SSc therapy: the underlying pathogenic mechanism of the disease is still undefined; most of the interventional therapies are based on case series; in the cohort studies, the patients that were recruited were in different phases of the disease [3].
Section snippets
IVIG therapy and its biological role
Intravenous immunoglobulin (IVIG) has been used for a long time in various autoimmune diseases [4,5]. Its first use in SSc was described in 2000, in three patients that presented with a rapidly progressive manifestation of the disease, by Levy and colleagues [6]. IVIG is a human specific immunoglobulin G, that is derived from 6000 to 20,000 healthy blood donors. Beyond its multiple non-specific mechanisms of action, it has been used in different autoimmune diseases as hematologic diseases
Conclusion
SSc is a rare currently disease, that have two different subsets differentiated by skin affliction. SSc lacks a successful therapy. The rational use of IVIG in SSc has a pathological background and recent studies show IVIG as an efficacious and safe therapy in SSc. Its success is so far described on muscle, skin and joint involvement as well in corticosteroid tapering. The lung disease is still a challenge, but more studies are required. If the patients are judicious recruited (early stages),
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Intravenous immunoglobulins reduce skin thickness in systemic sclerosis: evidence from Systematic Literature Review and from real life experience
2021, Autoimmunity ReviewsCitation Excerpt :Nevertheless, IVIG can be a useful choice in patients refractory to first-line therapies and in those where disease modifying treatments were not tolerated. In SSc, the use of IVIG has been suggested by several studies [12,13] with a peculiar efficacy in refractory cases, and in cutaneous, gastrointestinal [14–18] and joint involvement [19–23]. The reported efficacy may be explained by the fact that the significant involvement of inflammatory cytokines (IL-6, IL-13), B cells and of TGFβ in SSc pathogenesis [1], may constitute a substrate for IVIG activity [6,24].
Recognition and Management of Cutaneous Connective Tissue Diseases
2021, Medical Clinics of North AmericaCitation Excerpt :Rituximab can also help cutaneous sclerosis in some patients. IVIG and tocilizumab have also demonstrated benefit for cutaneous sclerosis in SSc.64–66 Additionally, it is crucial for patients with cutaneous sclerosis to participate in occupational and physical therapy to improve and maintain mobility, particularly hand mobility.67,68
Connective Tissue Disease–Associated Interstitial Lung Disease: Evaluation and Management
2019, Clinics in Chest MedicineCitation Excerpt :Intravenous immunoglobulin (IVIG) may be useful in PM/DM-ILD specifically, MDA-5–associated ILD.131,132 Its use in SSc-ILD is of unclear benefit.133 In spite of its high cost, IVIG is increasingly being used as adjunctive therapy for refractory CTD-ILD.134
Intravenous immunoglobulins improve skin fibrosis in experimental models of systemic sclerosis
2023, Scientific Reports