Long-Term Outcome of WHIM Syndrome in 18 Patients: High Risk of Lung Disease and HPV-Related Malignancies

Laura Dotta, Lucia Dora Notarangelo, Daniele Moratto, Rajesh Kumar, Fulvio Porta, Annarosa Soresina, Vassilios Lougaris, Alessandro Plebani, C. I.Edvard Smith, Anna Carin Norlin, Andrea Cecilia Gòmez Raccio, Eva Bubanska, Patrizia Bertolini, Giovanni Amendola, Marcella Visentini, Massimo Fiorilli, Aldo Venuti, Raffaele Badolato

Research output: Contribution to journalArticlepeer-review

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/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.

Original languageEnglish
Pages (from-to)1568-1577
Number of pages10
JournalJournal of Allergy and Clinical Immunology: In Practice
Volume7
Issue number5
DOIs
Publication statusPublished - May 1 2019

Keywords

  • B lymphopenia
  • Congenital neutropenia
  • Human papilloma virus
  • Hypogammaglobulinemia
  • Lung disease
  • Myelokathexis
  • Panleukopenia
  • Tumors
  • Warts
  • WHIM syndrome

ASJC Scopus subject areas

  • Immunology and Allergy

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