Abstract
Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome is a rare immunodeficiency caused by gain-of-function mutations in the chemokine receptor CXCR4. While human papillomavirus (HPV) skin infection (warts) is the dermatological hallmark of the disease, individuals with WHIM have high rates of other skin manifestations that may aid early diagnosis and management. This study was a retrospective review of medical records from a United States National Institutes of Health natural history cohort of patients with WHIM syndrome seen between 2005 and 2024, including a cross-sectional analysis of cutaneous manifestations and CXCR4 variants. The cohort compromised 45 patients with genetically confirmed WHIM syndrome, 16 men and 29 women, with a mean age of 33.3 years (range, 0-69 years) and mean age at diagnosis of 20.4 years (range, 0-59 years). The cohort exhibited a range of skin manifestations which included cutaneous infections with HPV in 34 (76%) patients, bacteria in 32 (71%) patients, other viruses in 27 (60%) patients, and fungi in 25 (56%) patients. Inflammatory conditions included six (13%) patients with seborrheic dermatitis, five (11%) with contact dermatitis, four (9%) with psoriasis, three (7%) with nummular eczema, and 13 (29%) with other eczematous dermatitis. Despite the young median age, seven (16%) patients had skin cancer. All seven patients had CXCR4 truncation mutations, while those with a missense mutation (E343K) generally had fewer skin manifestations. Our study found that WHIM syndrome is associated with diverse infectious, inflammatory, and neoplastic skin conditions beyond HPV skin infection.