Research Article
The clinical course of herpes zoster is similar in immunocompetent and immunocompromised pediatric patients
https://doi.org/10.21203/rs.3.rs-1516496/v1
This work is licensed under a CC BY 4.0 License
posted 07 Apr, 2022
You are reading this latest preprint version
Herpes zoster (HZ) is an infectious disease caused by reactivation of latent varicella-zoster virus infection. It manifests with vesicular eruption in an affected dermatome. We aimed to compare clinical manifestation of herpes zoster in 152 immunocompetent and immunocompromised children. Clinical manifestations were similar. Serious complications, although uncommon, affected not only immunocompromised patients but also otherwise healthy children.
herpes zoster
shingles
vesicular rash
VZV
viral infections
Herpes zoster (HZ) is an infectious disease caused by reactivation of latent varicella-zoster virus (VZV) infection. It manifests with vesicular eruption in an affected dermatome. It usually affects adult persons but may also occur in children, especially if they experienced varicella early in life (1). The onset of HZ may be due to declining VZV-specific cell-mediated immunity (2). Therefore, immunodeficiency may be an important factor for developing HZ. Typical rash can be accompanied by fever, pruritus or paraesthesia, pain is uncommon in children. Diagnosis in patients who have history of varicella is usually based on their clinical picture. However, immunocompromised patients with inconclusive clinical presentation may require detecting VZV DNA in vesicular fluid with polymerase chain reaction (PCR) assay (3).
The aim of this study was to analyze clinical course of HZ in children and compare it in both immunocompetent and immunocompromised patients.
Medical charts of all consecutive children hospitalized and/or consulted in the Regional Hospital for Infectious Diseases in Warsaw due to HZ, between June 2013 and August 2018 were retrospectively analyzed. Patients were divided into immunocompromised and immunocompetent groups, based on their immunological status resulting from underlying diseases or immunosuppressive therapy. Age, history of varicella, time interval between varicella and HZ, underlying diseases, immunosuppressive therapy, dermatome involvement, and HZ complications were analyzed in both groups. HZ was diagnosed clinically. HZ duplex was diagnosed when two different non-contiguous dermatomes were involved, and disseminated HZ was diagnosed when there was disseminated cutaneous involvement of more than 2 non-contiguous dermatomes.
Ethical statement
The design of the study conforms to the standards currently applied by the Ethical Committee at the Medical University of Warsaw. Approval number: AKBE/1/2022.
Statistical analysis
Normality of continuous variables was tested using Shapiro-Wilk’s test. The U-Mann Whitney test was used to compare continuous variables and the Fisher’s exact test was used to evaluate categorical variables. A p value of <0.05 was considered significant.
Medical records of 152 children with HZ were analyzed, 56/152 (36.84%) of them were hospitalized, and 96/152 (63.16%) were consulted and discharged home due to good general condition and no indications for intravenous antiviral treatment. Median age was 10 years [interquartile range (IQR): 5.75–12 years]. There were 73/152 (48.03%) boys and 79/152 (51.97%) girls. Median age at varicella onset was 4 years [IQR: 1.5–5 years]. None of the children were vaccinated against VZV. Median time interval between varicella and HZ onset was 5 years [IQR: 2–7 years]. Fever occurred in 15/152 (9.87%) children. In 16/152 (10.5%) one or more complications occurred, including: skin bacterial superinfection (16/17, 94.2 %), sepsis (1/17, 5.9%), meningitis (1/17, 5.9%). Thoracic dermatomes were the most commonly affected (81/152, 53.29%). Most of the children did not have any immunodeficiencies (118/152, 77.6%), and 34/152 (22.4%) of them were immunocompromised (and had been treated with intravenous acyclovir). The baseline characteristics of children diagnosed with herpes zoster including comparison between immunocompromised and healthy children is presented in Table 1.
Our analysis revealed that among causes of immunodeficiency, there were oncologic disorders (22/34, 64.7%) including: 16/34 (47.1%) acute lymphoblastic leukemia, 2/34 (5.8%) acute myeloid leukemia, 2/34 (5.8%) neuroblastoma, 1/34 (2.9%) Ewing’s sarcoma, one child (2.9%) had mandibular tumor; 10/34 (29.4%) were undergoing immunosuppressive treatment due to nephrotic syndrome (n=2), Crohn’s disease (n=3), ulcerative colitis (n=2), juvenile idiopathic arthritis (n=1), Sjögren syndrome (n=1), and idiopathic trombocytopenia (n=1); one (1/34, 2.9%) had aplastic anemia, and one (1/34, 2.9%) had primary immunodeficiency. The clinical picture of the disease was similar in both groups (Table 1). However, immunocompromised children more often had sacral dermatomes affected (5/34, 14.7% vs. 1/118, 0.8%, p=0.0022). Thoracic dermatomes were the most common localization of vesicles in both groups, although in immunocompromised children these dermatomes were less often affected (11/34, 32.4% vs. 70/118, 59.3%, p=0.0065). Moreover, trigeminal nerve was less frequently affected in immunocompromized children (0/34, 0% vs. 15/118, 12.7%, p=0.0239). Interestingly, HZ involving trigeminal nerve was reported only among immunocompetent patients. There was no difference in HZ duplex, HZ disseminated and complications incidence between both groups.
The clinical course of HZ in children was mild, only 10.5% had complications, and none of them were severe, excluding 1 child with both sepsis and viral meningitis. Petursson et al. in their prospective study on HZ in children and adolescents observed that the incidence of reported zoster was 1.6/1000 person years with no seasonal variation, no difference between the sexes were observed, and the disease had a mild course. The most commonly affected dermatomes were thoracic (75%) (4). In our study, the thoracic dermatomes were also the most frequently affected (53.3%). However, their cohort consisted of 121 individuals who did not require hospitalization, and our cohort was bigger (152), and 36.8% of children required hospitalization.
Marra F et al. in their meta-analysis of HZ risk factors analyzed 88 studies, with a total of 3, 768 691 patients included. The authors revealed that malignancy significantly increased the risk of HZ compared with controls (RR=2.17; 95% CI, 1.86–2.53) (5). In our study, 64.7% of immunocompromised children with HZ had underlying oncologic disorders.
Feder et al. investigated the clinical data on healthy children with HZ, and concluded that the interval between varicella and childhood zoster averages 3.8 years if varicella occurs during the first year of life vs. 6.2 years if varicella occured after the age of 1 year (6). In our study the median time interval between varicella and HZ was 5 years (IQR: 2–7 years), and there was not a significant difference between healthy and immunocompromised children. However, we did not investigate whether this time interval was different depending on the patient's age at varicella onset.
Kuchar et al. analyzed clinical manifestations of immunocompetent and immunocompromised children with HZ, and concluded that the clinical picture is comparable (7). However, in their study, they included only hospitalized children, whose condition obviously required hospitalization. In addition, in our cohort every immunocompromised child had been treated with intravenous acyclovir, which may have reduced the risk for developing severe HZ. Moreover, they analyzed medical charts from 72 patients. In our analysis, despite including outpatient children, we had similar results, in a more representative group of 152 children.
The main limitation of our study is that we performed a retrospective analysis. The data were collected from medical records, which were prepared by more than one physician. Moreover, children who did not require hospitalization were lost to further observation, but if their course of HZ would have worsened, one may assume that they would seek medical care in our Hospital.
To conclude, herpes zoster occurs in both immunocompetent and immunocompromised children. Clinical manifestations are similar. Serious complications, although uncommon, affect not only immunocompromised patients but also otherwise healthy children.
Author’s contribution
CB colllected data, analyzed data, wrote the main manuscript
ET performed conceptualizatin, and data curation, edited and reviewed the final version of the manuscript
MPŚ performed conceptualizatin, and data curation, edited and reviewed the final version of the manuscript
Conflict of interest: The authors declare no conflict of interest.
Consent for publication: All authors consent to publishing this work.
Availability of data and material: The data sets used and/or analyzed during the current study can be made available by the corresponding author on reasonable request.
Funding: No funding was received.
All authors have read and approved the final article.
Acknowledgements: Not Applicable
Table 1. Baseline characteristics of children diagnosed with herpes zoster with comparison between immunocompromised and healthy children.
|
Characteristic |
All (n=152) |
Immunocompromised children (n=34) |
Healthy children (n=118) |
p-value |
|
age in years, median [IQR*] |
10 [5.75 - 12] |
10 [8–14] |
9 [4.8–12] |
0.0601 |
|
female sex, n (%) |
79 (51.97) |
16 (47.1) |
63 (53.4) |
0.5624 |
|
age onset of chickenpox in years, median [IQR] |
4 [1.5–5] |
4 [3–6] |
3 [1–5] |
0.1010 |
|
time interval between varicella and herpes zoster in years, median [IQR] |
5 [2–7] |
5 [3–8] |
4.5 [2–7] |
0.4593 |
|
fever (> 38 Celsius degrees), n (%) |
15 (9.9) |
5 (14.7) |
10 (8.5) |
0.3279 |
|
one or more complications, n (%) |
17 (11.2) |
5 (14.7) |
11 (9.3) |
0.3551 |
| • skin bacterial superinfection, n (%) |
16 (10.5) |
5 (14.7) |
11 (9.3) |
0.3551 |
| • sepsis, n (%) |
1 (0.7) |
0 (0) |
1 (0.8) |
1.0000 |
| • meningitis, n (%) |
1 (0.7) |
0 (0) |
1 (0.8) |
1.0000 |
|
Dermatome involvement |
|
|
|
|
|
cervical dermatome involvement, n (%) |
14 (9.2) |
6 (17.6) |
8 (6.8) |
0.0855 |
|
thoracic dermatome involvement, n (%) |
81 (53.3) |
11 (32.4) |
70 (59.3) |
0.0065 |
|
lumbar dermatome involvement, n (%) |
27 (17.8) |
8 (23.5) |
19 (16.1) |
0.3178 |
|
sacral dermatome involvement, n (%) |
6 (4.0) |
5 (14.7) |
1 (0.8) |
0.0022 |
|
trigeminal nerve involvement, n (%) |
15 (10.0) |
0 (0) |
15 (12.7) |
0.0239 |
|
facial nerve involvement, n (%) |
1 (0.7) |
0 (0) |
1 (0.8) |
1.0000 |
|
vestibulocochlear nerve involvement, n (%) |
1 (0.7) |
0 (0) |
1 (0.8) |
1.0000 |
|
herpes zoster duplex, n (%) |
2 (1.3) |
1 (2.9) |
1 (0.8) |
1.0000 |
|
disseminated herpes zoster, n (%) |
6 (4.0) |
3 (8.8) |
3 (2.5) |
0.1259 |
*IQR – interquartile range
No competing interests reported.
posted 07 Apr, 2022
You are reading this latest preprint version