A cutaneous alarm: severe ecthyma gangrenosum heralding immunodeficiency-centromeric instability syndrome

Abstract Purpose Immunodeficiency, Centromeric Instability, and Facial Anomalies (ICF) syndrome is a rare autosomal recessive disorder associated with a defect in the DNA methylation process. ICF syndrome type 1 (ICF1) is the most prevalent subtype resulting from mutations in the DNMT3B gene. While ecthyma gangrenosum (EG) is a known complication of acquired immunodeficiencies, it is a rare initial manifestation of primary immunodeficiency. This case highlights EG as the initial clue that led to ICF1 diagnosis. Methods We report the case of a 3-year-old male with a history of recurrent infections who presented with persistent high-grade fever, neutropenia, and rapidly progressive necrotic skin lesions. Blood cultures, skin biopsy and immunological workup were conducted to determine the etiology. Molecular genetic testing was initiated given the suspicion of underlying immunodeficiency. Results Immunological tests revealed hypogammaglobulinemia and severe neutropenia. The patient received broad-spectrum antibiotics, intra-venous immunoglobulins, Granulocyte Colony-Stimulating Factor, and underwent surgical debridement, with gradual clinical improvement. The child was found to have Pseudomonas aeruginosa bacteremia complicated by a biopsy-confirmed Ecthyma gangrenosum. Genetic testing identified a homozygous mutation in the DNMT3B gene, confirming the diagnosis of ICF syndrome type 1. Conclusion This case illustrates EG as a rare but significant presentation of ICF1, emphasizing the need to evaluate for underlying primary immunodeficiencies in children with chronic or unusual infectious histories. Early recognition, early aggressive broad-spectrum antimicrobial therapy, immunological support, genetic molecular diagnosis and multidisciplinary approach are essential to guide management and improve outcomes.