Elsevier

Clinical Immunology

Volume 199, February 2019, Pages 25-28
Clinical Immunology

Intravenous immunoglobulin (IVIG) in the vanguard therapy of Systemic Sclerosis

https://doi.org/10.1016/j.clim.2018.12.006Get rights and content

Abstract

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, which lead to a multisystemic dysfunction. Various pathogenetic mechanisms were described. The lack of a successful therapy make SSc a disease with a poor prognosis. The intravenous immunoglobulin (IVIG) has been used for a long time in different autoimmune diseases, and firstly used in SSc patients in 2000. IVIG has multiple non-specific mechanisms of action and, beyond an impressive improvement in muscle symptoms, a French nationwide cohort demonstrated that IVIG ameliorates the skin disease and systemic inflammation, and helps the daily dose corticosteroid's tapering at the end of the treatment. The benefits on gastrointestinal symptoms of IVIG was reported by a recent English article, in which the patients consistently reported a decrease in the gastro-esophageal reflux disease symptoms and their frequencies. The impact on the lung involvement still remains unclear. One of the advantages of IVIG is its safe profile. Few adverse effects were reported and most of them are mild, and can be managed and usually they do not relapse. Harmful effects were described, but they can be avoid with cautious and judicious use of this therapy.

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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