Severe skin complications of varicella in previously healthy children in Iran: emerging concern (2025)

Background

Varicella, commonly known as chickenpox, is typically considered a mild childhood illness but can lead to severe complications necessitating hospitalization. In Iran, the varicella-zoster vaccine is not currently included in the routine immunization schedule. This case series study aimed to characterize severe skin complications of varicella in children admitted to an Iranian referral hospital.

Materials and methods

This case series study reviewed 17 pediatric cases hospitalized for severe skin complications of varicella and demographics data, clinical presentation, and the outcomes were collected.

Results

Between December 2023 and March 2024, a total of 98 cases diagnosed with varicella were screened in our hospital, of which 17 cases (17.3%) presented with severe skin complications. Among 17 cases analyzed, 82.3% were males (n = 14) with a mean age of 6.9 ± 3.9 years. Severe skin complications of varicella manifested across diverse anatomical sites, with the chest and neck emerging as the most frequently affected areas. Cellulitis was a consistent finding across all cases, while abscess formation was noted in six instances. Particularly noteworthy was a case of necrotizing fasciitis localized to the thigh and leg region, underscoring the potential severity of varicella-related complications. Furthermore, we documented an instance of preseptal cellulitis linked to varicella zoster virus infection. Treatment involved local wound care, broad-spectrum antibiotics, and surgical intervention in six cases. Bacterial cultures identified Group A β-hemolytic Streptococcus in 35.3% of cases.

Conclusion

Our study highlights the spectrum of severe varicella-related skin complications and underscores the importance of prompt recognition and management to prevent morbidity and optimize outcomes. Further research and analysis of varicella epidemiology in Iran are essential to evaluate the benefits and feasibility of integrating the varicella-zoster vaccine into the national immunization program.

Varicella, commonly known as chickenpox, is typically considered a common childhood illness, usually benign and self-limiting. However, in some cases, it can lead to severe complications requiring hospitalization [1,2,3]. In regions without widespread vaccination, varicella predominantly affects children under 13, particularly those in preschool. This viral illness is globally endemic, with outbreaks occurring every few years in populations large enough to sustain year-round transmission [4].

Among children, varicella lesions are most commonly observed on the trunk, with the abdominal wall being the area most frequently affected. Although rare, involvement of the neck can lead to severe complications due to the potential spread to the mediastinum [5, 6]. Frequently reported varicella-associated complications included bacterial infections, skin, and soft tissue infections, followed by neurological and respiratory complications [7,8,9,10,11]. Varicella skin complications encompass a range of conditions such as cellulitis, abscesses, necrotizing fasciitis, impetigo, and gangrene, with prevalence rates in the pediatric population varying widely [12]. Necrotizing fasciitis is an uncommon but serious complication of varicella-zoster infection [13]. Diagnosis of necrotizing fasciitis can be challenging as it closely mimics cellulitis [14, 15], potentially leading to delayed treatment and increased risk of mortality and morbidity.

Since the varicella-zoster vaccine is not currently integrated into Iran’s routine immunization schedule [16], understanding the epidemiology and impact of varicella outbreaks is crucial for informing vaccination strategies and public health interventions. This study aimed to provide a detailed description of severe skin complications of varicella in previously healthy children admitted to an Iranian referral hospital.

This study presents findings from an analysis of 17 cases involving varicella skin complications that required hospitalization at Children’s Medical Center, a prominent referral hospital in Iran.

Cases were diagnosed based on clinical criteria, encompassing history, physical examination findings, and supportive laboratory or imaging tests. Laboratory investigations, including complete blood count (CBC) and inflammatory markers, were performed to aid in diagnosis and assess for signs of systemic infection and inflammation. In cases of diagnostic uncertainty or suspected complications, imaging modalities such as ultrasound or MRI were utilized to evaluate tissue involvement and rule out other conditions.

For cases requiring incision and drainage due to varicella complications, the procedure involved administering local anesthesia, making a precise incision over the abscess, draining pus, irrigating the cavity, and applying a sterile dressing. Post-procedure, patients received pain medication and wound care instructions, with a follow-up appointment scheduled for monitoring.

Details collected included admission time, gender, age, underlying health conditions, the reason for admission, type of varicella-related complications, duration of hospital stay, smear microscopy and culture results, and details of antibiotic treatment and surgery.

Between December 2023 and March 2024, a total of 98 cases diagnosed with varicella were screened in our hospital, of which 17 cases (17.3%) presented with severe skin complications. Among17 cases, 14 were males (82.3%). The detailed information of the cases is provided in Table1. The mean age of the cases was 6.9 ± 3.9 years. The mean time from rash to cellulitis onset was 4.6 ± 2.5 days. Additionally, the mean duration of hospital stay following varicella skin complications onset was 15.0 ± 7.5 days.

The median white blood cell count (WBC) was 11,800 cells/mm³ (IQR: 8,865 − 16,550 cells/mm³), while the median neutrophils were 8,910 cells/mm³ (IQR: 5,030 − 12,863 cells/mm³). Lymphocyte count had a median of 2,160 cells/mm³ (IQR: 1,253–3,009 cells/mm³), and platelet count had a median of 219 × 10³/mm³ (IQR: 159–387 × 10³/mm³). The median erythrocyte sedimentation rate (ESR) was 41mm/h (IQR: 29–66mm/h). Additionally, the median C-reactive protein (CRP) level was 86mg/L (IQR: 53–192.5mg/L).

The bacterial culture results revealed that out of the total cases examined, the majority (n = 10, 59%) showed a positive culture. Group A β-hemolytic Streptococcus was identified in 6 cases (35.3%), while Streptococcus sinovium and Stenotrophomonas maltophilia were each found in 1 case.

Severe skin complications of varicella occurred at various locations (Figs.1 and 2), with the chest and neck being the most commonly affected sites. Cellulitis was observed in all cases, with abscesses found in six cases. Notably, one case in our study developed necrotizing fasciitis localized to the thigh and leg area, highlighting the potential severity of varicella-related complications. Additionally, we reported a case of preseptal cellulitis associated with Varicella zoster virus infection.

Complications of varicella-related skin infections were managed through a combination of local wound care and the administration of appropriate broad-spectrum antibiotics. In six cases, surgical intervention was necessary to effectively address the complications.

In Case 3, a 6.2-year-old female underwent incision and drainage procedures to address varicella complications affecting the hypogastrium and pubis area. She was admitted to the hospital for 21 days. Upon admission, her WBC was notably elevated at 23,700, with a predominance of neutrophils at 18,723 with ESR of 41mm/hour and a CRP level of 200mg/L. Cultures and smears revealed the presence of Group A β-hemolytic Streptococcus, indicating a bacterial infection. Post-surgery, she received ampicillin-sulbactam, clindamycin, and vancomycin to prevent secondary infections.

In Case 7, an 8.4-year-old male underwent incision and drainage procedures to address an abscess resulting from complications of varicella affecting the abdominal wall. The decision for surgical intervention was prompted by the severity of the abscess, leading to a 10-day hospital stay. Upon admission, there waselevated white blood cell count (16200), with a predominance of neutrophils (8910) and lymphocytes (4536), indicated significant inflammation. Following surgery, he received a combination of antibiotics, including ampicillin-sulbactam, rifampin, and amikacin, to prevent potential secondary infections.

In Case 14, a 6.2-year-old male underwent incision surgery for varicella complications affecting his scrotum. This surgical intervention was necessitated by the severity of the condition, leading to a hospital stay of 9 days. Although culture and smear tests did not reveal any bacterial or fungal infections, the negative results could have been impacted by antibiotic administration before sample collection, potentially inhibiting microbial growth. The decision for incision surgery was made to address the critical nature of the scrotal involvement. Post-surgery, he received a combination of antibiotics, including ampicillin-sulbactam, meropenem, and vancomycin, aiming to prevent potential secondary infections.

Case 17, a 7.7-year-old male, developed varicella complications resulting in extensive tissue damage in the thigh and leg area. Due to the severity of the condition and the presence of necrotic tissue, he underwent several debridement procedures to remove the non-viable tissue and promote wound healing. Following debridement, he required skin grafting to replace the lost tissue and facilitate the closure of the wound. Multiple grafting sessions were performed to cover the affected area adequately. Throughout the treatment process, he received comprehensive wound care, including infection control measures and supportive therapy to optimize healing outcomes. Close monitoring and post-operative care were provided to prevent complications and ensure the success of the grafting procedures. This case underscores the challenging nature of managing varicella complications, particularly when extensive tissue loss occurs, necessitating aggressive surgical interventions like debridement and grafting to promote recovery and restore function.

In Case 10, a 5-month-old male presented with varicella complications characterized by bilateral preseptal cellulitis. Despite his young age, the severity of the infection necessitated hospitalization for 10 days. Upon admission, his WBC was elevated at 10,600, with a high neutrophil count of 7102 and a normal lymphocyte count of 2120. CRP level was elevated at 125mg/L, indicating an acute-phase response. Culture and smear tests were negative. However, due to the severity of the cellulitis and the risk of secondary infections, this case received treatment with a combination of antibiotics. Meropenem, vancomycin, and ampicillin-sulbactam were administered to cover a broad spectrum of potential pathogens and prevent the development of bacterial superinfection.

In Case 11, a 5.3-year-old male presented with varicella complications involving the neck and hemithorax. His symptoms prompted hospitalization for 12 days due to the severity of the condition. Upon admission, his WBC was elevated at 14,300, with a predominance of neutrophils at 9295. The ESR was 60mm/hour, and the CRP level was elevated at 90mg/L. Culture and smear tests were negative. Despite this, he received treatment with a combination of antibiotics, including ceftazidime and clindamycin. These antibiotics were chosen empirically to cover a broad spectrum of potential bacterial pathogens and prevent the development of secondary infections.

In case 12, a 1-year-old male presented with Varicella infection manifesting as lesions in the inguinal region. He had no history of underlying health conditions. Upon admission, he had a white blood cell count of 8110 cells/mm³, with a predominance of neutrophils (4217 cells/mm³). The ESR was 27mm/h, and the CRP level was 64mg/L. He received antibiotic treatment consisting of ampicillin-sulbactam, vancomycin, and clindamycin. The duration of the hospital stay was 5 days.

Our findings did not identify any association between the use of ibuprofen and an elevated risk of invasive group A streptococcal disease in cases with varicella zoster virus infection.

Our study highlights the increasing concern about the severity of varicella-related complications, particularly with a rise in hospitalization rates between December 2023 and March 2024. This increase, compared to last year’s hospitalization rates at our hospital, suggests a concerning trend of more severe cases or complications associated with the disease.

Despite the evident impact of varicella, particularly in terms of severe complications, the epidemiological and economic data on the burden of the disease in the Middle East remain limited [7]. Over the past decade, several countries around the world have included varicella vaccination in their national immunization programs [7, 17,18,19,20,21]. However, Iran has not yet integrated the varicella-zoster vaccine into its routine immunization schedule [7, 22].

A previous decision-tree model evaluating the cost-effectiveness of introducing a varicella vaccination program for 12-month-old children in Iran indicated that the vaccine might not be cost-effective under the current assumptions about the disease burden. Nevertheless, this assessment is hampered by the lack of local epidemiological data on varicella, which limits the ability to accurately determine the cost-effectiveness and potential benefits of including the varicella-zoster vaccine in Iran’s national immunization program [22].

Varicella, typically considered a mild illness, can result in hospitalizations due to various complications affecting both children and adults, with rates typically below 1% [23]. Symptoms usually start with a rash progressing from papules to itchy blisters, often accompanied by fever, fatigue, headaches, and loss of appetite. While the illness typically resolves within 4 to 7 days, severe complications can arise, including pneumonia, bacterial skin infections, neurological issues, dehydration, and in rare cases, systemic complications or death [23, 24].

Our case series study exhibited a spectrum of severe skin complications like cellulitis, abscesses, and necrotizing fasciitis. Despite being previously healthy, all cases in our study developed severe varicella complications, emphasizing the susceptibility of children to these conditions [8, 25,26,27]. This highlights the importance of vaccination and preventive measures in mitigating the risk of varicella-related complications, even in seemingly healthy individuals. In the United States, 70% of varicella-related hospitalizations were among healthy individuals with no contraindications for vaccination [28]. Similarly, in Turkey, 80% of hospitalized children with varicella during the study period had no underlying diseases [11].

In our study, the mean duration of hospital stays following the onset of varicella skin complications was 15.0 ± 7.5 days. This duration is notably longer than the median hospital stays reported in Turkey (5–8 days) [8] and the mean duration in the UAE (7.5 days) [7]. The prolonged duration of hospital stays observed in our study compared to previous reports highlights the substantial burden imposed by varicella-related complications. Understanding the factors contributing to these prolonged hospitalizations is crucial for optimizing patient care and resource allocation.

Bacterial superinfection, particularly by group A β-hemolytic Streptococcus, emerged as a significant concern in our study, necessitating prompt diagnosis and appropriate antibiotic treatment. Varicella is a substantial risk factor for the development of invasive group A streptococcal disease [4].

In our study, one case developed varicella complications resulting in necrotizing fasciitis localized to the thigh and leg area. The bacterial culture identified group A β-hemolytic Streptococcus as the causative organism. During 16 years in Portugal, among hospitalized patients with varicella as a primary diagnosis, necrotizing fasciitis occurred in 0.5% of cases, while cellulitis occurred in 6.3% of cases [29]. In our study, the majority of cases examined (10 out of the total) showed a positive bacterial culture result. Specifically, group A β-hemolytic Streptococcus was identified in 6 cases (35.3%), while S. sinovium and S. maltophilia were each found in 1 case. This suggests a diverse range of bacterial pathogens contributing to cellulitis in varicella-infected patients. Comparatively, findings from a study conducted in a tertiary children’s hospital in London revealed group A β-hemolytic Streptococcus was identified as the causative organism in 90% of cases [30]. This emphasizes the significance of bacterial superinfection in varicella-related cellulitis and underscores the importance of prompt diagnosis and appropriate antibiotic treatment.

While previous studies have suggested a potential link between ibuprofen use and an increased risk of invasive group A streptococcal disease in varicella cases [4, 31], our findings did not support this association.

This study has several limitations. It primarily addressed the acute management and immediate outcomes of severe varicella complications, without assessing long-term sequelae or post-recovery quality of life. Additionally, the analysis did not systematically explore specific risk factors, such as the use of nonsteroidal anti-inflammatory drugs (NSAIDs), immunocompromised states, or underlying conditions that predispose individuals to bacterial superinfections, limiting the ability to draw definitive conclusions. Although bacterial culture results were included, prior antibiotic use and limitations in culture techniques may have influenced pathogen identification, potentially underestimating the range of pathogens involved. Furthermore, while the study underscored the burden of varicella-related complications, it did not incorporate a cost-effectiveness analysis of introducing varicella vaccination, which could have offered more actionable insights for public health decision-making.

It is strongly recommended to conduct cost-effectiveness analyses to evaluate the economic feasibility of incorporating the varicella vaccine into the national immunization program. These analyses should assess both the direct and indirect costs of the disease, such as healthcare expenses related to hospitalizations, treatments, and long-term complications, and compare them with the costs of vaccination. This would offer essential evidence to policymakers regarding the financial advantages of vaccination. Additionally, examining the long-term effects of severe varicella complications is also highly recommended.

In this study, we reported one case with preseptal cellulitis associated with varicella-zoster virus infection. This occurrence is rare and typically arises as a secondary complication due to bacterial superinfection [24].

In conclusion, our study provides valuable insights into severe skin complications of varicella in children, including their clinical characteristics, management, and outcomes. Further research is needed to deepen our understanding of the epidemiology, pathogenesis, and optimal management strategies for these complications. Timely recognition and management of these complications are essential to mitigate their potentially life-threatening consequences, especially in the context of varicella infection.

Authors and Affiliations

1. Department of Infectious Diseases, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

   Hamed Tabasizadeh,Mahmoud Khodabandeh,Hamid Eshaghi,Mohammad Reza Abdolsalehi,Maedeh Gooran,Hani Rostami Rad&Setareh Mamishi

2. Pediatric Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran

   Shima Mahmoudi,Reihaneh Hosseinpour Sadeghi&Setareh Mamishi

Contributions

HT and SM1 contributed equally to this work. SM1 specifically contributed to drafting the manuscript. HT, MK, HE, MRA, MG, HRR, RHS, SM1, and SM2 participated in case findings, data acquisition, and data interpretation, and each reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Setareh Mamishi.

Ethics approval and consent to participate

This research was conducted in accordance with the principles of the Declaration of Helsinki. This study received ethical approval from Tehran University of Medical Sciences (IR.TUMS.CHMC.REC.1403.129). Written informed consent was obtained from the individuals involved, as well as from the legal guardians, for the inclusion of any potentially identifiable images or data. Participants/patient/parent/legal guardian/relative of the patient gave written informed consent for their personal or clinical details along with any identifying images to be published in this study.

Consent for publication

We confirm that all participants, or their parents/legal guardians in the case of minors, provided written informed consent for the publication of their personal or clinical details.

Competing interests

The authors declare no competing interests.

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