Patients with WHIM syndrome have increased susceptibility to cutaneous fungal infections

Authors

• JC Meltzer
• J Strong
• S Martinez
• A Salancy
• DH McDermott
• PM Murphy
• L Castelo-Soccio
• I Brownell

Abstract

WHIM syndrome (WHIMS) is a rare primary immunodeficiency caused by autosomal dominant activating mutations in the CXCR4 gene. WHIM refers to warts, hypogammaglobulinemia, infections, and myelokathexis, the primary phenotypes of the syndrome. Myelokathexis is a retention of granulocytes in the bone marrow that results in chronic peripheral neutropenia and lymphocytopenia. Recurrent infections starting in childhood are associated with WHIMS including bacterial infections of the middle ear, skin, soft tissues, lungs, sinuses, joints, teeth, and gums. HPV infections of the skin and mucosa are also common in patients with WHIMS. However, unlike other conditions with low neutrophil counts or neutrophil dysfunction, patients with WHIMS rarely get invasive fungal infections. We conducted a retrospective study of 47 patients with WHIMS evaluated at the NIH Clinical Center between 2005 and 2023. We identified 14 patients (30%) who were diagnosed with a cutaneous fungal infection (dermatophyte, Malassezia, or Pityrosporum) at least once. The cutaneous fungal infections ranged from mild, short-term infections to chronic, recalcitrant infections. The fungal infections remained restricted to the skin as no patients developed invasive infections. Our study has identified a novel association between cutaneous fungal infections and WHIMS. These findings suggest that hyperactive CXCR4 signaling alters cutaneous immunity, conferring susceptibility to superficial fungal infections. Due to their high frequency, fungal infections should be considered as a cause for skin eruptions in patients with WHIMS. Increasing awareness of the elevated risk for cutaneous fungal infections in patients with WHIMS will facilitate earlier diagnosis and treatment with antifungal agents.

Scientific Focus Area: Microbiology and Infectious Diseases

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