Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement

Abstract

Inborn errors of immunity associated with atopy (IEIs-A) are a group of inherited monogenic disorders that occur with immune dysregulation and frequent skin involvement. Several pathways are involved in the pathogenesis of these conditions, including immune system defects, alterations of skin barrier and metabolism perturbations. Current technological improvements and the higher accessibility to genetic testing, recently allowed the identification of novel molecular pathways involved in IEIs-A, also informing on potential tailored therapeutic strategies. Compared to other systemic therapy for skin diseases, biologics have the less toxic and the best tolerated profile in the setting of immune dysregulation. Here, we review IEIs-A with skin involvement focusing on the tailored therapeutic approach according to their pathogenetic mechanism.

Targeted treatments for immune dysregulation in inborn errors of immunity

“…Majeed syndrome [48] IEIs with significant cutaneous atopy Wiskott Aldrich syndrome [61] ARPC1B deficiency DOCK8 deficiency [62][63][64][65][66][67][68][69][70] CARD11 deficiency [62][63][64][65][66][67][68][69][70] Netherton syndrome [62][63][64][65][66][67][68][69][70] RAG1/RAG2 immunodeficiency [62][63][64][65][66][67][68][69][70] STAT3 LOF [62][63][64][65][66][67][68][69][70] ZNF341 deficiency [62][63][64]...…”

“…Dupilumab is a monoclonal antibody that binds to IL-4Rα and inhibits signaling of both IL-4 and IL-13, thereby blocking signaling and achieving regulation of immune function. It decreases the expression of more than 800 genes affected in atopic dermatitis with potent inhibition in the Th2-associated chemokines and does not have a significant decrease in Th1-associated genes (Figure 1) [60,61]. Dupliumab is FDA approved for multiple atopic conditions including atopic dermatitis, eosinophilic esophagitis, asthma, and sinusitis with nasal polyposis.…”