Prevalence and progression of pneumonia in immunocompetent adults with varicella

Varicella, a highly contagious disease often experienced in childhood, is associated with fever and a characteristic vesicular rash that occurs mainly on the trunk, head, and face [1]. The resulting skin vesicles are filled with infectious virus particles that eventually aerosolize, thereby transmitting the varicella-zoster virus to healthy individuals via the nose and mouth [1]. Adults are more prone to severe infections than are healthy children [2‐4]. Varicella vaccination provides effective protection and significantly reduces the associated disease burden [5‐8]. Since the introduction of treatment with two doses of varicella attenuated live vaccine (VarV), the incidence of varicella has declined [9‐11], and to date, VarV has been adopted in routine vaccination programs for children in 36 countries and regions, including the United States, Australia, and Germany [5, 12]. However, given concerns regarding cost-effectiveness, this varicella vaccine has not been implemented in China, and notably, during the period from 2005 to 2019, the annual average incidence of varicella in China increased by more than 60% [13, 14]. This trend is a cause for concern, as although varicella is generally a mild and self-limiting disease, it can give rise to severe complications.

By definition, pneumonia is an infection of the lungs or pulmonary parenchyma [15], which is the most frequent serious complication of varicella in adults [16, 17], in whom pneumonia has been reported to occur in < 5 to 50% of all cases of varicella infection [18‐22]. Whereas most studies on adult varicella pneumonia have tended to focus on immunocompromised patients and pregnant women [16, 23‐25], this complication can also occur in immunocompetent adults [26]. Accordingly, in this study, we sought to establish the rates of consecutive varicella pneumonia in immunocompetent adult patients and document the resulting disease prognoses.

Compared with children, adults with varicella infections tend to have a higher frequency of complications, particularly respiratory and neurological conditions, of which pneumonia is the most commonly reported [27]. Given that radiography and CT scans are generally considered unnecessary in the event of unremarkable findings based on physical examinations of the lungs, the true incidence of varicella pneumonia is difficult to assess. In this study, the enrolled patients tended to be young without any underlying chronic disease. They were medically evaluated and could be included in retrospective case series analyses. Among the 186 patients for whom records were assessed, the reported incidence of pneumonia was 70.9%, and all underwent chest CT scans, which could readily detect asymptomatic pneumonia. Respiratory symptoms (such as cough and chest pain) were not considered indicators of pneumonia in this study.

Varicella pneumonia is characterized by a wide range of clinical manifestations, ranging from asymptomatic through mild illness to death, with a mortality rate of between 11 and 20% [28‐30]. Histological features of pneumonia associated with chickenpox include an interstitial mononuclear inflammatory infiltrate associated with intra-alveolar proteinaceous exudate, hyaline membrane formation, and type II cell hyperplasia (diffuse alveolar damage) [29]. Chest radiography has revealed that varicella pneumonia causes the development of multiple 5 to 10-mm ill-defined nodules that may be confluent and appear and disappear from different areas of the lungs [28, 29, 31, 32]. Comparatively, high-resolution CT facilitates a more precise detection of varicella-zoster pneumonia. Previously reported high-resolution CT findings of varicella pneumonia in immunocompetent individuals have revealed a range of manifestations, including small nodules, nodules with surrounding ground-glass attenuation, patchy ground-glass attenuation, and consolidation [33]. Pleural effusions may also occur during the acute phases of the disease but are unusual and were observed in only one patient assessed in the present study. Previous studies have reported that small consolidations generally resolve within a month after the disappearance of the rash. In a few patients, however, the lesions tend to persist indefinitely as randomly scattered, 2- to 3-mm calcifications in otherwise normal lungs [28, 29, 31, 32]. In the present study, among the 37 patients assessed over a mean follow-up period of 156.7 days, 24 reported the complete resolution of pneumonia, whereas the remaining 13 patients were characterized by persistent calcifications. Antiviral treatment might, nevertheless, contribute to the regression of persistent nodules.

Healthy adults and immunocompromised patients who develop varicella should receive treatment. The antiviral agents licensed for varicella treatment include acyclovir, valaciclovir, and famciclovir; the latter two are preferred owing to their higher bioavailability [34, 35]. Treatment is generally administered daily for 7–10 days and should be tailored based on individual clinical assessments [36]. If feasible, antiviral therapy is recommended within 24 h of the initial appearance cutaneous lesions. However, it should still be initiated if patients are later observed to be presenting with the continual appearance of new lesions. In the present study, 175 (94.1%) of the enrolled patients received antiviral treatment. Seventy patients who reported pneumonia were contacted after discharge; all of them reported being well, and the small, round consolidations in these patients resolved within 3 months.

Early antiviral treatment could improve prognosis and reduce mortality for immunocompetent adult patients. According to previous studies, pregnant women with varicella pneumonia have been established to be at a greater risk of a severe clinical course and death [37, 38]. Although acyclovir is not licensed for use during pregnancy, a prospective follow-up of 1,207 women receiving acyclovir failed to detect any significant increase in birth defects compared with those expected in the general population [39]. Regardless, early treatment of varicella at any stage of pregnancy is considered essential and potentially lifesaving.

Despite these important findings, the current study does have certain limitations. First, this was a single-center retrospective study. Second, we only examined a subgroup of patients with skin manifestations, whereas varicella can occur in the absence of a skin rash. Third, we may have missed patients with varicella who had been given other primary diagnoses. Fourth, we were unable to obtain follow-up data for approximately half of the patients, which may have biased the study findings.

Based on the findings of this study, it appears that the true incidence of varicella pneumonia is higher than that reported previously; however, in the case of immunocompetent hosts, the prognosis is generally good. Adults without significant hypoxia or respiratory distress secondary to pneumonia and without significant comorbid disease or other varicella-associated complications can probably be treated safely as outpatients with oral acyclovir, valaciclovir, or famciclovir administration and subsequent close follow-up.