1. Long-Term Outcome of WHIM Syndrome in 18 Patients: High Risk of Lung Disease and HPV-Related Malignancies
- Author
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Vassilios Lougaris, Patrizia Bertolini, E. Bubanska, Raffaele Badolato, Aldo Venuti, Laura Dotta, Anna Carin Norlin, Marcella Visentini, Andrea C. Gómez Raccio, Massimo Fiorilli, Rajesh Kumar, Daniele Moratto, C. I. Edvard Smith, Annarosa Soresina, Fulvio Porta, Giovanni Amendola, Alessandro Plebani, and Lucia Dora Notarangelo
- Subjects
Lung Diseases ,Male ,Delayed Diagnosis ,Uterine Cervical Neoplasms ,Congenital neutropenia ,Cryosurgery ,Cohort Studies ,Hypogammaglobulinemia ,0302 clinical medicine ,Granulocyte Colony-Stimulating Factor ,Immunology and Allergy ,030212 general & internal medicine ,Age of Onset ,Antibiotic prophylaxis ,Child ,Frameshift Mutation ,Imiquimod ,Middle Aged ,Myelokathexis ,Anus Neoplasms ,Panleukopenia ,Anti-Bacterial Agents ,Bronchiectasis ,Codon, Nonsense ,Child, Preschool ,Cohort ,Disease Progression ,Female ,Warts ,Salicylic Acid ,WHIM syndrome ,Adult ,Heart Defects, Congenital ,Whim syndrome, congenital neutropenia, Panleukopenia, B lymphopenia, Human Papilloma Virus, Warts, Lung disease, Tumors, Hypogammaglobulinemia, Myelokathexis ,Receptors, CXCR4 ,medicine.medical_specialty ,Adolescent ,Primary Immunodeficiency Diseases ,Limb Deformities, Congenital ,B lymphopenia ,Human papilloma virus ,Lung disease ,Tumors ,Antineoplastic Agents ,Retinoids ,Young Adult ,03 medical and health sciences ,Keratolytic Agents ,Lymphopenia ,Internal medicine ,medicine ,Humans ,Abnormalities, Multiple ,Congenital Neutropenia ,business.industry ,Papillomavirus Infections ,Infant, Newborn ,Infant ,Pneumonia ,medicine.disease ,030228 respiratory system ,Chronic Disease ,business - Abstract
Background In the warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, variable phenotypic expression may delay diagnosis. Panleukopenia, malignancy, and chronic lung disease all affect morbidity and mortality risks. Routinely used treatments include immunoglobulins, granulocyte-colony stimulating factor (G-CSF), and antibiotics; recent trials with a target C-X-C chemokine receptor type 4 (CXCR4) antagonist show promising results. Objective We sought to characterize the largest cohort of patients with WHIM and evaluate their diagnostic and therapeutic management. Methods Data were collected from an international cohort of 18 patients with CXCR4 mutations. Results The clinical features manifested at 2.2 ± 2.6 years of age, whereas the disease diagnosis was delayed until 12.5 ± 10.4 years of age. Patients with WHIM commonly presented with a severe bacterial infection (78%). Pneumonia recurrence was observed in 61% of patients and was complicated with bronchiectasis in 27%. Skin warts were observed in 61% of patients at a mean age of 11 years, whereas human papilloma virus (HPV)-related malignancies manifested in 16% of patients. All the patients had severe neutropenia (195 ± 102 cells/mm3 at onset), whereas lymphopenia and hypogammaglobulinemia were detected in 88% and 58% of patients, respectively. Approximately 50% of patients received antibiotic prophylaxis, whereas G-CSF and immunoglobulin treatments were used in 72% and 55% of patients, respectively. Conclusions The WHIM syndrome onsets early in life and should be suspected in patients with chronic neutropenia. Patients with WHIM need careful monitoring and timely intervention for complications, mainly lung disease and HPV-related malignancies. We suggest that immunoglobulin therapy should be promptly considered to control the frequency of bacterial infections and prevent chronic lung damage.
- Published
- 2019