High-Dose Intravenous Immunoglobulin in Skin Autoimmune Disease

Abstract

The immunomodulatory potential and low incidence of severe side effects of high-dose intravenous immunoglobulin (IVIg) treatment led to its successful application in a variety of dermatological autoimmune diseases over the last two decades. IVIg is usually administered at a dose of 2 g per kg body weight distributed over 2–5 days every 4 weeks. They are most commonly used as a second- or third-line treatment in dermatological autoimmune disease (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, dermatomyositis, systemic vasculitis, and systemic lupus erythematosus). However, first-line treatment may be warranted in special circumstances like concomitant malignancy, a foudroyant clinical course, and contraindications against alternative treatments. Furthermore, IVIg can be considered first line in scleromyxedema. Production of IVIg for medical use is strictly regulated to ensure a low risk of pathogen transmission and comparable quality of individual batches. More common side effects include nausea, headache, fatigue, and febrile infusion reactions. Serious side effects are rare and include thrombosis and embolism, pulmonary edema, renal failure, aseptic meningitis, and severe anaphylactic reactions. Regarding the mechanism of action, one can discriminate between functions of the Fcγ region and the F(ab)2 region and their effects on a cellular level. These functions are not mutually exclusive, and more than one pathway may contribute to the beneficial effects. Here, we present a historical background, details on manufacturing, hypotheses on the mechanisms of action, information on the clinical application in the abovementioned conditions, and a brief outlook on future directions of IVIg treatment in dermatology.

COVID-19: Immunology and treatment options

“…Intravenous immunoglobulins (IVIG) are used in systemic autoimmune/inflammatory conditions to control systemic inflammation through several mechanisms, including the capture of activated complement factors, blockade of Fcγ receptors, inhibition of B and T lymphocyte differentiation and activation, neutralisation of cytokines and antibodies, etc. [195]. As mentioned above, immune complexes containing viable virus may mediate infection, activate Fcγ receptors, and/ or be deposited in tissues and organs, lastly resulting in pro-inflammatory responses [196].…”

Treatment of scleromyxedema with lenalidomide, bortezomib and dexamethasone: A case report and review of the literature

“…IVIG is hypothesized to have antifibrotic properties through modulation of cytokine production and it may have a role in blocking an unknown circulating factor. 18,20 Frequent relapses after stopping treatment are common and long-term IVIG treatment with maintenance infusions is necessary to control the disease. However, as evident in our case, there may be delay in initiation of treatment with IVIG due to lengthy insurance approval process, high cost and, time-consuming administration.…”

Phenotyping of Adaptive Immune Responses in Inflammatory Diseases

“…Furthermore, autoantibody arrays can be used to identify additional autoantibody reactivity beyond known autoantibodies, for example in pemphigus (62, 63). However, the mere detection of autoantibodies in any given population is usually not informative because autoantibodies can be detected at high frequency also in healthy blood donors (64,65) and, are even present in IVIG preparations (66) used to treat autoimmune diseases (67). Thus, in depth characterization of their functions and of the corresponding B and T cells is mandatory.…”