Strong Jennifer, Adhanom Rutha, Kim Caleb S, Saito Yoshine, Meltzer Jasmine C, Hallaert Patrick, Martinez Sophia, Salancy Abigail, Kong Heidi H, Cowen Edward W, Castelo-Soccio Leslie, Murphy Philip M, McDermott David H, Brownell Isaac
Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10 Center Drive, 12N240C, Bethesda, MD, 20892-1908, USA.
Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
Dermatol Ther (Heidelb). 2025 May;15(5):1173-1179. doi: 10.1007/s13555-025-01396-0. Epub 2025 Apr 3.
WHIM syndrome is a rare autosomal dominant inborn error of immunity caused by gain-of-function mutations in the chemokine receptor CXCR4. Patients with WHIM syndrome frequently suffer from an increased risk for bacterial and viral infections, especially warts due to human papillomavirus. Associations between WHIM syndrome and fungal infections have not been previously identified. The objective of this study was to estimate the prevalence of superficial fungal infections in patients with WHIM syndrome.
This retrospective single-institution cohort study assessed patients with genotype-confirmed WHIM syndrome evaluated between March 2007 and March 2024.
Of 45 patients with WHIM syndrome, 18 (40%) were diagnosed with at least one superficial fungal infection. These infections included dermatophytosis (n = 14, 78%), pityriasis versicolor (n = 6, 33%), and pityrosporum folliculitis (n = 1, 6%). No correlation was detected between superficial fungal infection risk and the degree of peripheral neutropenia, lymphopenia, or hypogammaglobulinemia. The median time to resolution of the longest episode of superficial dermatophytosis (skin or hair) was 171.5 (range 53-3650) days, and several patients experienced prolonged courses requiring serial retreatments.
These findings suggest that frequent or prolonged superficial fungal infections may be a useful clinical sign to prompt consideration of a WHIM syndrome diagnosis, especially in patients with numerous cutaneous warts or other history to suggest immunodeficiency.
Participants were enrolled in a natural history trial registered with ClinicalTrials.gov (NCT00128973).
WHIM综合征是一种罕见的常染色体显性遗传性免疫缺陷病，由趋化因子受体CXCR4的功能获得性突变引起。WHIM综合征患者经常面临细菌和病毒感染风险增加的问题，尤其是由人乳头瘤病毒引起的疣。此前尚未发现WHIM综合征与真菌感染之间的关联。本研究的目的是评估WHIM综合征患者浅表真菌感染的患病率。
这项回顾性单机构队列研究评估了2007年3月至2024年3月期间经基因分型确诊的WHIM综合征患者。
在45例WHIM综合征患者中，18例（40%）被诊断患有至少一种浅表真菌感染。这些感染包括皮肤癣菌病（n = 14，78%）、花斑糠疹（n = 6，33%）和马拉色菌毛囊炎（n = 1，6%）。未发现浅表真菌感染风险与外周血中性粒细胞减少、淋巴细胞减少或低丙种球蛋白血症程度之间存在相关性。浅表皮肤癣菌病（皮肤或毛发）最长发作期的中位缓解时间为171.5天（范围53 - 3650天），数名患者病程延长，需要多次重复治疗。
这些发现表明，频繁或长期的浅表真菌感染可能是提示考虑诊断WHIM综合征的有用临床体征，尤其是在有大量皮肤疣或其他提示免疫缺陷病史的患者中。
参与者被纳入一项在ClinicalTrials.gov注册的自然史试验（NCT00128973）。
