TY - JOUR
T1 - Long-Term Outcome of WHIM Syndrome in 18 Patients
T2 - High Risk of Lung Disease and HPV-Related Malignancies
AU - Dotta, Laura
AU - Notarangelo, Lucia Dora
AU - Moratto, Daniele
AU - Kumar, Rajesh
AU - Porta, Fulvio
AU - Soresina, Annarosa
AU - Lougaris, Vassilios
AU - Plebani, Alessandro
AU - Smith, C. I.Edvard
AU - Norlin, Anna Carin
AU - Gòmez Raccio, Andrea Cecilia
AU - Bubanska, Eva
AU - Bertolini, Patrizia
AU - Amendola, Giovanni
AU - Visentini, Marcella
AU - Fiorilli, Massimo
AU - Venuti, Aldo
AU - Badolato, Raffaele
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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/mm 3 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.
AB - 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/mm 3 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.
KW - B lymphopenia
KW - Congenital neutropenia
KW - Human papilloma virus
KW - Hypogammaglobulinemia
KW - Lung disease
KW - Myelokathexis
KW - Panleukopenia
KW - Tumors
KW - Warts
KW - WHIM syndrome
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U2 - 10.1016/j.jaip.2019.01.045
DO - 10.1016/j.jaip.2019.01.045
M3 - Article
C2 - 30716504
AN - SCOPUS:85065068244
VL - 7
SP - 1568
EP - 1577
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
SN - 2213-2198
IS - 5
ER -