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WHIM Syndrome: Long-Term Evolution of an Adult Patient

Year: 2025
Type: article
Study design: Case Report
Abstract: Introduction WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis) is an inborn error of immunity, caused by a heterozygous gain-of-function mutation in the CXCR4 gene. Therapeutic options aim to overcome the main causes of mortality (infections and HPV-associated neoplasms). These are granulocyte colony-stimulating factors (G-CSF), antibiotic prophylaxis, IgG replacement therapy (IgGRT), bone marrow transplantation (BMT), and, lately, CXCR4-specific nanobodies and CXCR4 antagonists. Presentation of the Case A 30-year-old female patient presented during her childhood leukopenia, chronic neutropenia, recurrent infections, bronchiectasis, splenomegaly, and two bone marrow biopsies with myeloid hyperplasia. At age 14, she started IgGRT due to hypogammaglobulinemia. At age 20, warts were found on hands, knees, abdomen, and face. Direct sequencing of the CXCR4 gene reported a heterozygous p.Arg334STOP mutation. The patient evolved favorably maintaining treatment with G-CSF, antibiotic prophylaxis, and IgGRT and HPV vaccination. Three years ago, she abandoned treatment, presenting pneumonia, upper airway, and skin and soft tissue infections. Laboratories showed hypogammaglobulinemia, 296 neutrophils, and 846 lymphocytes. Clinically, there was no progression of skin warts, with stable splenomegaly and normal respiratory functional test. It was indicated to restart treatment. Discussion Treatments in WHIM syndrome aim to correct neutropenia and hypogammaglobulinemia, avoiding associated infections, including those due to HPV that could progress to neoplasia. The most commonly used are G-CSF, IgGRT, and antibiotic prophylaxis. The few reports of BMT show humoral immunity reconstitution and increase of peripheral white blood cells, low mortality, but limited experience in adult patients. CXCR4-specific nanobodies have limited clinical validation. CXCR4 antagonists decrease the frequency of infections and extension of warts; however, these are short-term studies involving small populations. Although our patient presented infections associated with treatment discontinuation, no significant organ involvement nor progression of wart lesions were observed. Under this scenario, therapeutic decisions, such as BMT or CXCR4 antagonists, are questionable given an adult, clinically stable patient.
DOI: 10.70962/lasid2025abstract.87
Authors: Maria Gabriela Vasquez Ortuño, Ana Laura Lopez, Diego S. Fernandez Romero
Language: English
Subfield: Immunology
Open Access status: diamond
OpenAlex ID: W7116707394
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