Case Reports

Atypical Disseminated Herpes Zoster: Management Guidelines in Immunocompromised Patients

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Reactivation of the varicella-zoster virus (VZV) causes dermatomal herpes zoster (HZ) and more rarely severe disseminated HZ including diffuse rash, encephalitis, hepatitis, and pneumonitis. An atypical form of VZV infection, disseminated HZ has been described primarily in immunocompromised hosts. We report 2 cases of atypical disseminated HZ in immunocompromised patients presenting with diffuse, nondermatomal, vesicular eruptions. We also provide a review of the literature and summarize the current guidelines for the treatment and prophylaxis of HZ in patients with human immunodeficiency virus (HIV) infection, solid organ transplantation (SOT), and hematopoietic stem cell transplantation (HSCT). Given the atypical presentation of VZV infection among some immunocompromised patients, this case series emphasizes the need for clinical suspicion for disseminated HZ to facilitate timely diagnosis and initiation of antiviral therapy. Clinician awareness of methods for prevention and treatment of VZV infection in immunocompromised individuals also is critical to minimize the risk for disease and associated morbidity in these patients.

Practice Points

  • Clinician awareness of management guidelines for the prevention and treatment of varicella-zoster virus infection in immunocompromised individuals is critical to minimize the risk for disease and associated morbidity.
  • Antiviral prophylaxis is recommended for 6 months following solid organ transplantation or 1 year following hematopoietic stem cell transplantation, and prompt treatment is warranted in cases of reasonable clinical suspicion for herpes zoster.



Well-known for its typical presentation, classic herpes zoster (HZ) presents as a dermatomal eruption of painful erythematous papules that evolve into grouped vesicles or bullae.1,2 Thereafter, the lesions can become pustular or hemorrhagic.1 Although the diagnosis most often is made clinically, confirmatory techniques for diagnosis include viral culture, direct fluorescent antibody testing, or polymerase chain reaction (PCR) assay.1,3

The main risk factor for HZ is advanced age, most commonly affecting elderly patients.4 It is hypothesized that a physiological decline in varicella-zoster virus (VZV)–specific cell-mediated immunity among elderly individuals helps trigger reactivation of the virus within the dorsal root ganglion.1,5 Similarly affected are immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection, due to suppression of T cells immune to VZV,1,5 as well as immunosuppressed transplant recipients who have diminished VZV-specific cellular responses and VZV IgG antibody avidity.6

Secondary complications of VZV infection (eg, postherpetic neuralgia, bacterial superinfection progressing to cellulitis) lead to increased morbidity.7,8 Disseminated cutaneous HZ is another grave complication of VZV infection and almost exclusively occurs with immunosuppression.1,8 It manifests as an eruption of at least 20 widespread vesiculobullous lesions outside the primary and adjacent dermatomes.6 Immunocompromised patients also are at increased risk for visceral involvement of VZV infection, which may affect vital organs such as the brain, liver, or lungs.7,8 Given the atypical presentation of VZV infection among some immunocompromised individuals, these patients are at increased risk for diagnostic delay and morbidity in the absence of high clinical suspicion for disseminated HZ.

Case Reports

Patient 1
A 52-year-old man developed a painless nonpruritic rash on the left leg of 4 days’ duration. It initially appeared as an erythematous maculopapular rash on the medial aspect of the left knee without any prodromal symptoms. Over the next 4 days, erythematous vesicles developed that progressed to pustules, and the rash spread both proximally and distally along the left leg. Shortly following hospital admission, he developed a fever (temperature, 38.4°C). His medical history included alcoholic liver cirrhosis and AIDS, with a CD4 count of 174 cells/µL (reference range, 500–1500 cells/µL). He had been taking antiretroviral therapy (abacavir-lamivudine and dolutegravir) and prophylaxis against opportunistic infections (dapsone and itraconazole).

Physical examination was remarkable for an extensive rash consisting of multiple 1-cm clusters of approximately 40 pustules each scattered in a nondermatomal distribution along the left leg (Figure 1). Many of the vesicles were confluent with an erythematous base and were in different stages of evolution with some crusted and others emanating a thin liquid exudate. The lesions were nontender and without notable induration. The leg was warm and edematous.

Figure 1. Herpes zoster with grouped vesicles on the left thigh following acute reactivation of varicella-zoster virus.

Clinically, the differential diagnosis included disseminated HZ with bacterial superinfection, Vibrio vulnificus infection, and herpes simplex virus (HSV) infection. The patient was treated with intravenous vancomycin, levofloxacin, and acyclovir, and no new lesions developed throughout the course of treatment. On this regimen, his fever resolved after 1 day, the active lesions began to crust, and the edema and erythema diminished. Results of bacterial cultures and plasma PCR and IgM for HSV types 1 and 2 were negative. Viral culture results were negative, but a PCR assay for VZV was positive, reflective of acute reactivation of VZV.

Patient 2
A 63-year-old man developed a pruritic burning rash involving the face, trunk, arms, and legs of 6 days’ duration. His medical history included a heart transplant 6 months prior to presentation, type 2 diabetes mellitus, and chronic kidney disease. He was taking antirejection therapy with mycophenolate mofetil (MMF), prednisone, and tacrolimus.

Physical examination was remarkable for an extensive rash consisting of clusters of 1- to 2-mm vesicles scattered in a nondermatomal pattern. Isolated vesicles involved the forehead, nose, and left ear, and diffuse vesicles with a relatively symmetric distribution were scattered across the back, chest, and proximal and distal arms and legs (Figure 2). Many of the vesicles had an associated overlying crust with hemorrhage. Some of the vesicles coalesced with central necrotic plaques.

Figure 2. Herpes zoster with diffuse vesicles on the chest (A) and back (B), as well as a hemorrhagic, necrotic, vesiculobullous lesion with surrounding vesicles on the left leg (C), following acute reactivation of varicella-zoster virus.

Given a clinical suspicion for disseminated HZ, therapy with oral valacyclovir was initiated. Two punch biopsies were consistent with herpesvirus cytopathic changes. Multiple sections demonstrated ulceration as well as acantholysis and necrosis of keratinocytes with multinucleation and margination of chromatin. There was an intense lichenoid and perivascular lymphocytic infiltrate in the dermis. Immunohistochemistry staining was positive for VZV and negative for HSV, indicating acute reactivation of VZV (Figure 3). Upon completion of an antiviral regimen, the patient returned to clinic with healed crusted lesions.

Figure 3. Biopsy showed multinucleated giant cells and margination of chromatin, consistent with herpes group infection (A)(H&E original magnification ×20) as well as diffuse positive varicella-zoster virus on immunohistochemistry (B)(original magnification ×20).


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