Long-Term Outcome of WHIM Syndrome in 18 Patients: High Risk of Lung Disease and HPV-Related Malignancies.
Abnormalities, Multiple
Adolescent
Adult
Age of Onset
Anti-Bacterial Agents
/ therapeutic use
Antineoplastic Agents
/ therapeutic use
Anus Neoplasms
/ etiology
Bronchiectasis
/ physiopathology
Child
Child, Preschool
Chronic Disease
Codon, Nonsense
Cohort Studies
Cryosurgery
Delayed Diagnosis
Disease Progression
Female
Frameshift Mutation
Granulocyte Colony-Stimulating Factor
/ therapeutic use
Heart Defects, Congenital
Humans
Imiquimod
/ therapeutic use
Infant
Infant, Newborn
Keratolytic Agents
/ therapeutic use
Limb Deformities, Congenital
Lung Diseases
/ physiopathology
Lymphopenia
/ physiopathology
Male
Middle Aged
Papillomavirus Infections
/ complications
Pneumonia
/ physiopathology
Primary Immunodeficiency Diseases
/ genetics
Receptors, CXCR4
/ genetics
Retinoids
/ therapeutic use
Salicylic Acid
/ therapeutic use
Uterine Cervical Neoplasms
/ etiology
Warts
/ genetics
Young Adult
B lymphopenia
Congenital neutropenia
Human papilloma virus
Hypogammaglobulinemia
Lung disease
Myelokathexis
Panleukopenia
Tumors
WHIM syndrome
Warts
Journal
The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220
Informations de publication
Date de publication:
Historique:
received:
26
08
2018
revised:
07
01
2019
accepted:
08
01
2019
pubmed:
5
2
2019
medline:
18
8
2020
entrez:
5
2
2019
Statut:
ppublish
Résumé
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. We sought to characterize the largest cohort of patients with WHIM and evaluate their diagnostic and therapeutic management. Data were collected from an international cohort of 18 patients with CXCR4 mutations. 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 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.
Sections du résumé
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
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.
Identifiants
pubmed: 30716504
pii: S2213-2198(19)30117-5
doi: 10.1016/j.jaip.2019.01.045
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Antineoplastic Agents
0
CXCR4 protein, human
0
Codon, Nonsense
0
Keratolytic Agents
0
Receptors, CXCR4
0
Retinoids
0
Granulocyte Colony-Stimulating Factor
143011-72-7
Salicylic Acid
O414PZ4LPZ
Imiquimod
P1QW714R7M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1568-1577Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.