Department of Pediatrics, Institute of Molecular Medicine "Angelo Nocivelli," Asst Spedali Civili of Brescia, Brescia, Italy.
Pediatric Hematology Oncology Unit, Asst Spedali Civili of Brescia, Brescia, Italy.
J Allergy Clin Immunol Pract. 2019 May-Jun;7(5):1568-1577. doi: 10.1016/j.jaip.2019.01.045. Epub 2019 Feb 2.
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 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.
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.
在疣、低丙种球蛋白血症、感染和骨髓嗜中性粒细胞减少症（WHIM）综合征中，可变的表型表达可能会延迟诊断。全肠炎、恶性肿瘤和慢性肺部疾病都会影响发病率和死亡率风险。常用的治疗方法包括免疫球蛋白、粒细胞集落刺激因子（G-CSF）和抗生素；最近针对 CXCR4 趋化因子受体 4（CXCR4）拮抗剂的试验显示出了有前景的结果。
我们旨在描述最大的 WHIM 患者队列，并评估他们的诊断和治疗管理。
从一个包含 18 名 CXCR4 突变患者的国际队列中收集数据。
临床特征在 2.2±2.6 岁时表现出来，而疾病诊断被延迟到 12.5±10.4 岁。患有 WHIM 的患者通常表现为严重的细菌感染（78%）。61%的患者出现肺炎复发，27%的患者并发支气管扩张。61%的患者在 11 岁时出现皮肤疣，而 16%的患者出现与人类乳头瘤病毒（HPV）相关的恶性肿瘤。所有患者均有严重的中性粒细胞减少症（发病时 195±102 个细胞/mm3），88%和 58%的患者分别出现淋巴细胞减少和低丙种球蛋白血症。约 50%的患者接受了抗生素预防，72%和 55%的患者分别接受了 G-CSF 和免疫球蛋白治疗。
WHIM 综合征在生命早期发病，应怀疑患有慢性中性粒细胞减少症的患者。WHIM 患者需要仔细监测和及时干预并发症，主要是肺部疾病和 HPV 相关的恶性肿瘤。我们建议应迅速考虑免疫球蛋白治疗，以控制细菌感染的频率并预防慢性肺部损害。
