Severe Pemphigus Vulgaris Successfully Treated With Intravenous Immunoglobulin

A novel preparation of intravenous immunoglobulin (IVIG) was successful in a patient with severe and recurrent pemphigus vulgaris (PV) after an original IVIG treatment led to burdensome side effects, according to a case study published in Dermatology and Therapy.¹

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PV is one of the most severe and common autoimmune bullous dermatoses (AIBDs), which comprise a varied collection of autoimmune diseases that present with erosions and bullae on the skin and mucous membranes. The disease causes autoantibodies to fight against desmosomal adhesion proteins, which results in the loss of epidermal integrity and “clinically apparent” blistering.¹

The disease is often fatal due to infections, malnutrition, or sepsis, according to the study authors. Corticosteroids, alone or used in conjunction with rituximab, are the standard treatment, but some patients do not respond successfully or experience serious side effects.¹

IVIG has been considered in cases of severe/refractory PV or in patients for which standard therapy is intolerable. Preparations contain several disease-fighting mechanisms, including inhibiting complement-mediated tissue destruction and functionally blocking Fc receptors on phagocytes, leading to less cellular destruction.¹

Ahmed et al. conducted a study of 21 patients with PV who were treated with IVIG as monotherapy that were analyzed at a 20-year follow-up point. The participants experienced no disease and had to receive no additional drugs.²

In a significant testament to its effectiveness as a treatment for severe PV, IVIG led to sustained clinical, serological, and immunopathological remission, according to the Ahmed et al..²

There are a variety of different IVIG preparations with almost equivalent efficacy; however, side effect profiles can be slightly different, and there is a lack of literature on the subject. In this case study, the investigators Wiedenmayer et al. treated a patient with well-controlled PV under long-term IVIG therapy who changed IVIG preparations due to experiencing side effects.¹

The patient, a 73-year-old female, first developed painful lesions in January 2012. A prescription of high-dose immunosuppressive therapy was initiated, and her symptoms began to rapidly improve to the point where her therapy could be reduced. However, 4 years later the patient experienced a relapse and a dramatic worsening of her condition.¹

Due to the severity of her relapse and the delayed response to immunosuppressive therapy, she initiated IVIG in July 2016. This led to a sustained treatment response, though after an interruption in treatment from October to December 2020, another relapse occurred in January 2021.¹

Once again, high-dose immunosuppressive therapy was initiated, and further-on IVIG therapy was reinstated, leading to a long-lasting stabilization of skin lesions. With this IVIG preparation, though, the patient experienced headaches and severe nausea following administration.¹

Therefore, in September 2023 she was switched to a new IVIG preparation; the patient continued to report headaches following infusions, but an improvement in their nausea was observed by the investigators.¹

IVIG has been used in a variety of disease states, with indications including primary immune thrombocytopenia and Kawasaki disease. The overall tolerability of IVIG is considered very strong, and severe side effects are rare, as reported by Guo et al. in their analysis of the adverse effects of IVIG therapy, though they note that “many factors affect the rate of immunoglobulin-related adverse effects.³

Wiedenmayer et al. caution that “the incidence of adverse reactions associated with IVIG varies widely between studies, and side effects are only rarely discussed in the literature.” They note some strategies for managing the side effects associated with IVIG therapy, including a reduction in the infusion rate or premedication with corticosteroids or antihistamines.¹

The investigators also discussed the tendency for IVIG side effects to be patient-specific, determining that “further evidence from real-life experience with this new IVIG preparation is needed to fully evaluate the effectiveness and tolerability and to make favorable long-term management decisions.”¹

References

1. Wiedenmayer N, Vollmer A S, Winkler J K, et al. Successful treatment of severe pemphigus vulgaris with reduced side effects using a novel IVIG preparation. Dermatol Ther. 2024. doi:10.1007/s13555-024-01191-3

2. Ahmed A R, Kalesinskas M, Kaveri S. Restoring immune tolerance in pemphigus vulgaris. PNAS. 2024;121(5):e2317762121. doi:10.1073/pnas.2317762121

3. Guo Y, Tian X, Wang X, et al. Adverse effects of immunoglobulin therapy. Front Immunol. 2018;7(9). doi:10.3389/fimmu.2018.01299