Czech Mary, Cuellar-Rodriguez Jennifer, Patel Bhavisha A, Groarke Emma M, Cowen Edward W, Turturice Benjamin, Beck David B, Wilson Lorena, Goodspeed Wendy, Darden Ivana, Young Neal S, Hickstein Dennis, Ombrello Amanda, Hoffman Patrycjia, Arikan Evsen Apaydin, Sinaii Ninet, Hathaway Londa, Castelo-Soccio Leslie, Fike Alice, Kastner Daniel B, Grayson Peter C, Ferrada Marcela A
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
National Heart, Blood, and Lung Institute, National Institutes of Health, Bethesda, Maryland, USA.
Open Forum Infect Dis. 2024 Jul 23;11(7):ofae405. doi: 10.1093/ofid/ofae405. eCollection 2024 Jul.
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a genetic disorder characterized by bone marrow failure and systemic inflammation, putting patients at risk for infections. This study comprehensively examines the prevalence of opportunistic infections in patients with VEXAS, evaluating their impact on clinical outcomes and potential preventive measures.
Patients with confirmed VEXAS were included. Survival analysis and logistic regression were used to identify associations between opportunistic infections and mortality. Infection rates (IRs) for pneumonia (PJP) and alphaherpesviruses were calculated over a prospective 8-month observation period in relationship to prophylaxis.
Of 94 patients with VEXAS, 6% developed PJP; 15% had alphaherpesvirus reactivation, with varicella zoster virus (VZV) being the most common herpesvirus; and 10% contracted a nontuberculous mycobacterial (NTM) infection. Risk of death was significantly increased per month following a diagnosis of PJP (hazard ratio [HR], 72.41 [95% confidence interval {CI}, 13.67-533.70]) or NTM (HR, 29.09 [95% CI, 9.51-88.79]). Increased odds for death were also observed in patients with a history of herpes simplex virus (HSV) reactivation (odds ratio [OR], 12.10 [95% CI, 1.29-114.80]) but not in patients with VZV (OR, 0.89 [95% CI, .30-2.59]). Prophylaxis for PJP (IR, 0.001 vs 0 per person-day, < .01) and VZV (IR, 0.006 vs 0 per person-day, = .04) markedly decreased infection rates with a number needed to treat of 4 and 7, respectively.
Opportunistic infections are common in patients with VEXAS. Patients who develop PJP, HSV, or NTM are at increased risk for death. Prophylaxis against PJP and VZV is highly effective.
VEXAS（空泡、E1酶、X连锁、自身炎症性、体细胞）综合征是一种遗传性疾病，其特征为骨髓衰竭和全身炎症，使患者面临感染风险。本研究全面调查了VEXAS患者中机会性感染的患病率，评估其对临床结局的影响以及潜在的预防措施。
纳入确诊为VEXAS的患者。采用生存分析和逻辑回归来确定机会性感染与死亡率之间的关联。在为期8个月的前瞻性观察期内，计算肺炎（肺孢子菌肺炎）和α疱疹病毒的感染率，并与预防措施相关联。
94例VEXAS患者中，6%发生了肺孢子菌肺炎；15%出现α疱疹病毒再激活，其中水痘带状疱疹病毒（VZV）是最常见的疱疹病毒；10%感染了非结核分枝杆菌（NTM）。诊断为肺孢子菌肺炎（风险比[HR]，72.41[95%置信区间{CI}，13.67 - 533.70]）或NTM（HR，29.09[95%CI，9.51 - 88.79]）后，每月死亡风险显著增加。有单纯疱疹病毒（HSV）再激活病史的患者死亡几率也增加（优势比[OR]，12.10[95%CI，1.29 - 114.80]），但VZV患者未增加（OR，0.89[95%CI，0.30 - 2.59]）。肺孢子菌肺炎预防（感染率，0.001对每人每天0，<0.01）和VZV预防（感染率，0.006对每人每天0，=0.04）显著降低了感染率，治疗所需人数分别为4和7。
机会性感染在VEXAS患者中很常见。发生肺孢子菌肺炎、HSV或NTM的患者死亡风险增加。预防肺孢子菌肺炎和VZV非常有效。
