A Novel Itgb2 Variant in a Patient With Severe Recurrent Pyoderma Gangrenosum-Like Lesions and Underlying Leukocyte Adhesion Deficiency Type I: Case Report and Literature Review Publisher Pubmed



Norouzibarough L¹ ; Olyaei NA^{2, 3} ; Carapito R^{2, 3, 4} ; Molitor A^{2, 3} ; Biglari S⁵ ; Poostiyan N⁶ ; Shahrooei M^{7, 8} ; Vahidnezhad H^{9, 10, 11, 12} ; Tabatabaiefar MA⁵ ; Bahram S^{2, 3, 4} ; Sherkat R¹
Source: Archives of Dermatological Research Published:2025

Abstract

Leukocyte adhesion deficiency (LAD) is a group of inborn errors of immunity caused by mutations of integrin subunit b2 gene (ITGB2). Pyoderma gangrenosum (PG) is an uncommon neutrophilic dermatosis characterized by recurrent, sterile, and enlarging necrotic ulcers which may manifest as a single or multiple new lesions simultaneously. Here we report a 43-year-old woman from a consanguine marriage who was diagnosed with LAD-I in childhood, recurrent severe PG-like lesion, and atypical manifestations including celiac disease and low CD19 B-cell subsets. A targeted genetic panel revealed a novel homozygous missense variant c.988T>C (Tyr330His) in ITGB2 gene. While the treatment with prednisolone, cyclosporine, and antibiotics led to partial improvement, the patient unfortunately discontinued the therapy and later died from septicemia. Early hematopoietic cell transplantation (HCT) shortly after birth can be highly effective in managing patients with LAD and preventing life-threatening infections. However, evidence suggests that HCT does not prevent autoinflammatory and autoimmune disorders such as PG. Therefore, it is important to monitor LAD patients for the potential development of PG, even after HCT. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.