Brief Case | April 3, 2024 | FREE
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Disseminated varicella infection in an immunocompromised patient

A patient with a history of liver transplant presented with a progressive rash.

The patient

A 72-year-old man presented with a rash consisting of small lesions on the hands and trunk that had begun two weeks prior. Over time, these lesions progressed and spread significantly, changing from erythematous, painless, and pruritic to painfully burning with confluent involvement of the face, thorax, and upper extremities. The rash displayed a widespread distribution, crossing the midline, and had a diffuse and vegetative appearance with serous discharge. Some lesions showed signs of superinfection with bacterial pathogens, pus, surrounding erythema, and honey crusting. He had a medical history of hiatal hernia, gastroesophageal reflux disease, dyslipidemia, hearing impairment, acute bronchitis, essential hypertension, and liver transplant in March 2012 due to encephalopathy related to alcohol use, for which he was on tacrolimus.

Image by Getty Images
Image by Getty Images

Initially, the patient presented without fever, systemic symptoms, or evidence of arthropod bites, and there was no history of recent travel or sexual activity. Due to acute prerenal injury, indicated by elevated blood urea nitrogen-to-creatinine ratio, admission was deemed necessary. Initial laboratory tests, including a complete blood count and cardiac enzyme levels, showed normal results. The management plan comprised IV fluid administration and initiation of empirical prophylactic antiviral therapy with acyclovir (10 mg/kg), along with prophylaxis against deep venous thrombosis (DVT) using heparin.

As treatment progressed, gram-positive cocci bacteria (Staphylococcus aureus) were identified in a blood culture. Vancomycin and cefazolin were started, in addition to prophylactic acyclovir. Subsequent blood counts revealed microcytic/normocytic anemia, with a hemoglobin level of 10.5 g/dL (reference range, 13.5 to 17.5 g/dL), hematocrit at 32% (reference range, 41% to 53%), and mean corpuscular volume (MCV) at 80 fL (reference range, 80 to 100 fL). Serum iron levels were 55 μg/dL (reference range, 65 to 175 μg/dL), with total iron-binding capacity at 143 μg/dL (reference range, 250 to 400 μg/dL) and ferritin at 355 ng/mL (reference range, 20 to 250 ng/mL), suggesting anemia of chronic disease/inflammation. The patient also had leukopenia (2,400 cells/mm3; reference range, 4,500 to 11,000 cells/mm3, reactive to viral infection) and thrombocytopenia (90,000 platelets/µL; reference range, 150,000 to 450,000 platelets/µL).

Polymerase chain reaction (PCR) testing for varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) was positive, with a viral load of 23,000 copies/mL. Other relevant CSF values included protein at 80 mg/dL (reference range, 15 to 45 mg/dL), glucose at 50 mg/dL (reference range, 50 to 80 mg/dL), and a cell count of 10 cells/mm3 (reference range <5 cells/mm3). PCR results from a skin lesion swab showed a viral load of 19,000 copies/mL, confirming the diagnosis of disseminated varicella-zoster infection. The patient had not received the recombinant subunit herpes zoster vaccine. Despite extensive medical efforts, including the initiation of appropriate antiviral therapy and supportive care, the patient's condition continued to deteriorate rapidly and he died.

The diagnosis

The diagnosis is disseminated VZV infection. Conventionally, varicella presents with intensely pruritic vesicular lesions and fever, while herpes zoster is characterised by a painful dermatomal rash resulting from VZV reactivation. This patient's presentation did not fit the expected pattern, exhibiting a diffuse and painful rash lacking hallmark vesicles.

Herpes zoster infections occur in more than 1.2 million U.S. patients annually, causing substantial morbidity. The risk is increased in hematopoietic stem-cell and organ transplant recipients compared with the general population. In a large database analysis published in 2014, the incidence of herpes zoster in the total study population was 4.82 per 1,000 person-years, compared with 43 per 1,000 person-years among bone marrow or stem cell transplant recipients. The risk of developing herpes zoster remained increased among stem-cell transplant recipients even with reduced-intensity regimens.

In immunocompetent individuals, herpes zoster diagnosis relies mainly on clinical presentation: unilateral, painful vesicular eruption with a well-defined dermatomal distribution. However, atypical lesions, especially in immunocompromised patients, and zosteriform herpes simplex lesions can complicate diagnosis. Laboratory confirmation, including PCR testing, direct fluorescent antibody (DFA) testing, and viral culture, is crucial when clinical presentation is uncertain. PCR testing is preferred due to its high sensitivity (>95%) and rapid results (<1 day). DFA testing and viral culture are alternative options, with lower sensitivity, and are best done on fresh vesicular lesions. Viral cultures are essential for determining the presence of antiviral drug resistance if needed.

The American Society of Transplantation Infectious Diseases Community of Practice offers guidelines on management of VZV in post-transplant patients. A dual strategy addressing potential bacterial and viral pathogens is needed for effective management of VZV infections in this population. Initiation of empirical antibiotic therapy with vancomycin and cefazolin, with antiviral treatment using acyclovir, addresses potential co-infections while targeting the suspected viral etiology. Patients' immunocompromised condition raises intriguing questions about the "chickenpox-shingles loop" phenomenon. This concept revolves around the interplay among waning vaccine-induced immunity, immunosuppression, and the elevated risk of VZV reactivation.

This case underscores the potential benefits of the recombinant subunit herpes zoster vaccine in preventing primary varicella infection, particularly for individuals who are seronegative. Clinicians should actively educate their patients about the risks of VZV and the available preventive measures, such as vaccination, which can be provided even to immunocompromised patients.


  • Disseminated infection with VZV may manifest atypically, and particular vigilance is warranted for the emergence of diffuse cutaneous eruptions devoid of characteristic vesicles in individuals with compromised immune function.
  • The recombinant subunit herpes zoster vaccine has demonstrated effectiveness in preventing primary varicella, reducing the risk of severe infection and complications.