An Atypical Presentation of Varicella-Zoster Virus with Progression to Meningitis
A 50-year-old man presented to clinic with a ten-day history of a painful, swollen red plaque on his right lateral eyebrow. The rash had worsened despite a 5-day course of oral doxycycline 100 mg twice daily for presumed cellulitis.
History. The patient had a history of childhood varicella. On physical examination, the patient had an edematous red plaque on the right superior eyebrow with overlying small coalescing erosions, as well as extensive soft tissue swelling and erythema of the right preauricular cheek with right submandibular lymphadenopathy (Figure 1). Findings included the maxillary and mandibular (V2/V3) dermatomes but excluded ocular involvement (V1).
Figure 1. Edematous erythematous plaque on the right superior eyelid with overlying erosions.
Diagnostic testing. Bacterial culture and varicella-zoster virus (VZV) polymerase chain reaction (PCR) skin swabs were performed. PCR studies returned positive for VZV.
Differential diagnosis. The initial differential diagnosis included cellulitis, acute febrile neutrophilic dermatosis, herpes simplex virus (HSV), varicella zoster, Kimura disease, and cat scratch disease.
Methicillin resistant Staphylococcus aureus (MRSA) abscess was lower on the differential given the lack of fluctuance or pustulation and the lack of response to doxycycline. Zoster ophthalmicus was also ruled out given lack of V1 involvement and therefore low risk of ocular complications. The remaining differentials were ruled out by the results of the PCR studies.
Treatment and management. Upon receipt of positive PCR results, the patient was initiated on oral valacyclovir 1 g three times daily. However, one day after returning home he developed a severe, bitemporal headache with fever and intermittent photophobia and phonophobia. He was then admitted inpatient with concern for VZV meningitis. Ophthalmologist evaluation showed no ocular surface involvement. A lumbar puncture showed pleocytosis, and cerebrospinal fluid PCR was VZV positive. The patient was treated for VZV meningitis with intravenous acyclovir 10 mg/kg every 8 hours for 14 days.
Patient outcome and follow-up. After 14 days of inpatient treatment, he was discharged in stable condition. He suffered no permanent neurologic sequelae from his infection. Ophthalmologist evaluation 1 week later also showed no evidence of ocular involvement.
Discussion. VZV is a common, self-limited herpes virus infection that typically first presents in childhood as chickenpox, with a prevalence of 90% before 15 years of age.1 Although most children in the United States are vaccinated against chickenpox, there are still approximately 150,000 cases each year.2 Once the primary infection of varicella resolves, VZV establishes latency in sensory ganglia. Reactivation of latent VZV occurs in about one-third of infected individuals, usually with advancing age or immunosuppression, and is known as herpes zoster or shingles.3 During both primary varicella infection and herpes zoster, VZV interacts with and infects adjacent lymphoid tissues as well as immune cells. Subsequent trafficking of peripheral immune cells to the skin produces clinical manifestations of vesicular cutaneous lesions.4
Herpes zoster characteristically presents with fever and a painful, vesicular dermatomal rash, typically in thoracic dermatomes, although any dermatome can be affected.5 Diagnosis is often clinical, based on the characteristic rash, and can be confirmed with PCR testing. Viral culture and Tzanck smear are less commonly used but are alternative tests. Atypical presentations of VZV can complicate the differential and delay diagnosis. In our case, the patient presented with a non-vesicular, non-dermatomal plaque with swelling, which is not characteristic of zoster. Other atypical presentations include zoster sin herpete, which presents with zoster-like neuropathic pain and rising titers of VZV-specific antibody in the serum and cerebrospinal fluid but in the absence of a dermatomal rash.6 Patients with HIV may present with atypical lesions that follow no dermatomal pattern and appear as multiple hyperkeratotic papules.7,8 Disseminated ecthymatous VZV lesions, which appear as central black eschars surrounded by vesicles, have also been described.7,9
Complications of herpes zoster include scarring, postherpetic neuralgia, VZV pneumonitis, and hepatitis.10 Central nervous system manifestations are rare with an incidence of one to three neurologic complications per 10,000 cases.11 Furthermore, complications typically occur in immunocompromised populations or those over 60 years of age.10 Our patient was a 50-year-old previously healthy man, and thus progression to VZV meningitis was very unusual. Previous literature examining complications associated with zoster found that the risk of progression from shingles to meningitis was 0.5-4.0% and most commonly presented with a craniocervical rash.12,13 Overall, there have been few case reports describing zoster meningitis in young, immunocompetent patients.13-16 In a study of 144 immunocompetent patients with viral meningitis, VZV was identified as the least common causative agent (8%), compared with enteroviruses (26%) and HSV-2 (17%).17
Despite the low incidence of VZV meningitis, central nervous system involvement of VZV produces high morbidity, with cognitive impairment and sensorimotor deficits reported in approximately 45% of patients.18 Therefore, timely recognition and treatment is essential. While Infectious Diseases Society of America guidelines for VZV meningitis treatment are not currently available, it is common practice to administer a 10- to 14-day course of intravenous acyclovir 5-10 mg/kg every 8 hours due to its efficacy in treating other VZV manifestations, including VZV encephalitis, and its low potential for drug-related adverse events.19-21
Conclusion. VZV is a common virus that typically first presents in childhood. Reactivation of latent VZV occurs in one-third of individuals and is typically diagnosed via a characteristic dermatomal rash. Atypical presentations of zoster can complicate the diagnosis and delay treatment. While this case report is limited in generalizability, it demonstrates that clinicians should stay alert for unique presentations of VZV and consider the patient’s neurological sequelae.
- Fairley CK, Miller E. Varicella-zoster virus epidemiology-a changing scene? J Infect Dis. 1996;174(3):S314-319. doi:10.1093/infdis/174.supplement_3.s314.
- Chickenpox vaccine saves lives and prevents serious illness infographic. Centers for Disease Control and Prevention. Updated October 20, 2022. Accessed October 11, 2023. https://www.cdc.gov/chickenpox/vaccine-infographic.html
- Laemmle L, Goldstein RS, Kinchington PR. Modeling varicella zoster virus persistence and reactivation – closer to resolving a perplexing persistent state. Front Microbiol. 2019;10:1634. doi:10.3389/fmicb.2019.01634.
- Moffat J, Ku CC, Zerboni L, Sommer M, Arvin A. Human herpesviruses: biology, therapy, and immunoprophylaxis. https://www.ncbi.nlm.nih.gov/books/NBK47382/
- Arvin AM. Varicella-zoster virus. Clin Microbiol Rev. 1996;9(3):361-381. doi:10.1128/CMR.9.3.361.
- Zhou J, Li J, Ma L, Cao S. Zoster sine herpete: a review. Korean J Pain. 2020;33(3):208-215. doi:10.3344/kjp.2020.33.3.208.
- Gnann, JW. Varicella‐zoster virus: atypical presentations and unusual complications. J Infect Dis. 2002;186(s1):S91-S98. doi:10.1086/342963.
- LeBoit PE, Límová M, Yen TS, Palefsky JM, White CR, Berger TG. Chronic verrucous varicella-zoster virus infection in patients with the acquired immunodeficiency syndrome (AIDS). Histologic and molecular biologic findings. Am J Dermatopathol. 1992;14(1):1-7. doi:10.1097/00000372-199202000-00001.
- Gilson IH, Barnett JH, Conant MA, Laskin OL, Williams J, Jones PG. Disseminated ecthymatous herpes varicella-zoster virus infection in patients with acquired immunodeficiency syndrome. JAAD. 1989;20(4):637-642. doi:10.1016/S0190-9622(89)70076-1.
- Weinberg JM. Herpes zoster: epidemiology, natural history, and common complications. JAAD. 2007;57(6):S130-S135. doi:10.1016/j.jaad.2007.08.046.
- Guess HA, Broughton DD, Melton LJ, Kurland LT. Population-based studies of varicella complications. Pediatrics. 1986;78(4 Pt 2):723-727.
- Galil K. The sequelae of herpes zoster. Arch Intern Med. 1997;157(11):1209. doi:10.1001/archinte.1997.00440320105010.
- Bateman R, Naples R. Herpes zoster meningitis in a young, immunocompetent adult. J Emerg Med. 2021;60(5):e99-e101. doi:10.1016/j.jemermed.2020.12.029.
- Iyer S, Mittal MK, Hodinka RL. Herpes zoster and meningitis resulting from reactivation of varicella vaccine virus in an immunocompetent child. Ann Emerg Med. 2009;53(6):792-795. doi:10.1016/j.annemergmed.2008.10.023.
- Kangath RV, Lindeman TE, Brust K. Herpes zoster as a cause of viral meningitis in immunocompetent patients. BMJ Case Rep. 2013;2013:bcr2012007575-bcr2012007575. doi:10.1136/bcr-2012-007575.
- Kushawaha A, Mobarakai N, Tolia J. A 46-year-old female presenting with worsening headache, nuchal rigidity and a skin rash in varicella zoster virus meningitis: a case report. Cases J. 2009;2:6299. doi:10.4076/1757-1626-2-6299.
- Kupila L, Vuorinen T, Vainionpaa R, Hukkanen V, Marttila RJ, Kotilainen P. Etiology of aseptic meningitis and encephalitis in an adult population. Neurology. 2006;66(1):75-80. doi:10.1212/01.wnl.0000191407.81333.00.
- Alvarez JC, Alvarez J, Ticono J, et al. Varicella-zoster virus meningitis and encephalitis: an understated cause of central nervous system infections. Cureus. 2020;12(11):e11583. doi:10.7759/cureus.11583.
- Becerra JCL, Sieber R, Martinetti G, Costa ST, Meylan P, Bernasconi E. Infection of the central nervous system caused by varicella zoster virus reactivation: a retrospective case series study. Int J Infect Dis. 2013;17(7):e529-e534. doi:10.1016/j.ijid.2013.01.031.
- Brown M, Scarborough M, Brink N, Manji H, Miller R. Varicella zoster virus-associated neurological disease in HIV-infected patients. Int J STD AIDS. 2001;12(2):79-83. doi:10.1258/0956462011916820.
- Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008;47(3):303-327. doi:10.1086/589747.
1Medical Student, Department of Dermatology, University of Virginia School of Medicine, Charlottesville, VA
2Resident, Department of Dermatology, University of Virginia School of Medicine, Charlottesville, VA
3Assistant Professor, Department of Dermatology, University of Virginia School of Medicine, Charlottesville, VA
Dong V, Martin S, Flowers RH. An atypical presentation of varicella-zoster virus with progression to meningitis. Consultant. 2023;63(11):e4. doi:10.25270/con.2023.10.000005
Received January 30, 2023. Accepted June 14, 2023. Published online October 25, 2023.
The authors report no relevant financial relationships.
Vivian Dong, BS, 852 West Main Street, Charlottesville, VA 22903 (firstname.lastname@example.org)