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Intravenous immunoglobulins, cyclosporine, and best supportive care in epidermal necrolysis: Diverse effects on systemic inflammation

Allergy, 2022

Schmidt V., Lalevée S., Traidl S., Ameri M., Ziadlou R., Ingen‐Housz‐Oro S., Barau C., de Prost N., Nägeli M., Mitamura Y., Meier‐Schiesser B., Navarini A., French L., Contassot E., Brüggen M.

Disease areaApplication areaSample typeProducts
Immunological & Inflammatory Diseases
Pathophysiology
Serum
Olink Target 96

Olink Target 96

Abstract

Background

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially life‐threatening cutaneous adverse reactions. There is still no consensus on adjuvant treatments, and little is known about their effects on systemic inflammation in SJS/TEN. Our aim was to characterize the systemic and cutaneous immune profiles of SJS/TEN patients and to investigate whether/how intravenous immunoglobulins (IVIG), cyclosporine A (CSA), and best supportive care only (BSCO) affected the systemic immune signature and clinical outcome (6 week‐mortality, complications, hospitalization stay).

Methods

We included 16 patients with SJS/TEN, treated with high‐dose IVIG (n = 8), CSA (n = 4) or BSCO (n = 4). Serial serum samples were obtained prior‐, 5–7 days, and 21 days after treatment onset. Serum levels of inflammation−/immune response‐associated proteins were measured by high‐throughput proteomics assay (OLINK) and cytotoxic molecules by ELISA. RNA extracted from skin biopsies collected prior treatment was analyzed by Nanostring.

Results

Serum inflammatory profiles in SJS/TEN patients were notably characterized by massive upregulation of type 1 immune response and proinflammatory markers. Surprisingly, there was limited overlap between cutaneous and serum immune profiles. Serial serological measurements of immune response markers showed very diverse dynamics between the different treatment groups. IVIG‐treated patients showed completely different dynamics and most significant proteomic changes in an early phase (Day 5–7). In all treatment groups, type 1−/inflammatory response markers were dampened at day 21. Clinically, there were no outcome differences.

Conclusion

Our study demonstrates that BSCO, CSA, and IVIG have very diverse biological effects on the systemic inflammatory response in SJS/TEN, which may not correlate with clinical outcome differences.

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