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 CXCR4 antagonist show promising results. OBJECTIVE: We sought to characterize the largest cohort of WHIM patients 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, while the disease diagnosis was delayed until 12.5±10.4 years of age. WHIM patients 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, while Human Papilloma Virus (HPV)-related malignancies manifested in 16% of patients. All the patients had severe neutropenia (195±102 cells/mmc at onset), while lymphopenia and hypogammaglobulinemia were detected in 88% and 58% of patients, respectively. Approximately 50% of patients received antibiotic prophylaxis, while G-CSF and immunoglobulin treatments were used in 72% and 55% of patients, respectively. CONCLUSION: The WHIM syndrome onsets early in life and should be suspected in patients with chronic neutropenia. WHIM patients need careful monitoring and timely intervention for complications, mainly lung disease and HPV-related malignancies. We suggest that immunoglobulin replacement therapy should be promptly considered to control the frequency of bacterial infections and prevent chronic lung damage.

Long term outcome of WHIM syndrome in 18 patients: high risk of lung disease and HPV-related malignancies / Dotta, L; Notarangelo, Ld; Moratto, D; Kumar, R; Porta, F; Soresina, A; Lougaris, V; Plebani, A; Smith, Cie; Norlin, Ac; Gòmez Raccio, Ac; Bubanska, E; Bertolini, P; Amendola, G; Visentini, M; Fiorilli, M; Venuti, A; Badolato, R.. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE. - ISSN 2213-2198. - (2019). [10.1016/j.jaip.2019.01.045]

Long term outcome of WHIM syndrome in 18 patients: high risk of lung disease and HPV-related malignancies.

Visentini M;Fiorilli M;
2019

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 CXCR4 antagonist show promising results. OBJECTIVE: We sought to characterize the largest cohort of WHIM patients 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, while the disease diagnosis was delayed until 12.5±10.4 years of age. WHIM patients 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, while Human Papilloma Virus (HPV)-related malignancies manifested in 16% of patients. All the patients had severe neutropenia (195±102 cells/mmc at onset), while lymphopenia and hypogammaglobulinemia were detected in 88% and 58% of patients, respectively. Approximately 50% of patients received antibiotic prophylaxis, while G-CSF and immunoglobulin treatments were used in 72% and 55% of patients, respectively. CONCLUSION: The WHIM syndrome onsets early in life and should be suspected in patients with chronic neutropenia. WHIM patients need careful monitoring and timely intervention for complications, mainly lung disease and HPV-related malignancies. We suggest that immunoglobulin replacement therapy should be promptly considered to control the frequency of bacterial infections and prevent chronic lung damage.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/1245706
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