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Varicella zoster-induced viral sepsis

Pathogen:DNA viruses →herpesviruses →Varicella zoster
Geographical range:Worldwide
Incidence:Rare cause of sepsis

Case history

A 22-year old female with a history of severe back ache, trunk rash, high fever, exposure to chickenpox in her family, highly increased liver enzyme tests and worsening coagulation with high prothrombin time (PT), and activated partial thromboplastin time (APTT), was admitted to the intensive care unit. The woman had a high fever and was severely tachycardic and tachypneoic, with a pulse rate of 140 and respiratory rate of 30. The clinician immediately started non-invasive ventilation. A complete blood count and an urgent chest X-ray were ordered.

Varicella zoster pathophysiology and diagnostics

Varicella zoster virus is a member of the Herpesviridae family of viruses, which are large DNA viruses. The virus belongs to the Alphaherpesvirinae sub-family and is also known as human herpesvirus type 3 (HHV-3). Varicella zoster may cause chickenpox in children and young adults and herpes zoster in adults.

The primary varicella zoster infection results in chickenpox (varicella). The infection may result in complications including encephalitis, pneumonia or bronchitis. Even when clinical symptoms of chickenpox have been resolved, the virus may remain latent in the infected person's nervous system and, in some cases, may reactivate later in life in the form of herpes zoster disease.

Varicella zoster virus is usually acquired by inhaling contaminated, airborne respiratory droplets from an infected person. The highly contagious nature of this virus underlies the outbreaks which spread quickly through schools. High viral concentrations are found in the characteristic vesicles of chickenpox and viral transmission may also occur through direct contact.

After initial inhalation, the virus infects the mucosae of the upper respiratory tract. Varicella zoster proliferation occurs approx. 3 days after the initial infection, in the lymph nodes of the upper respiratory tract, followed by primary viremia approx. 5 days after onset of the infection. A second round of viral replication occurs in the body's internal organs, most notably in the liver and spleen. This is followed by a secondary viremia approx. 15 days after infection. This is characterised by diffuse viral invasion of capillary endothelial cells and the epidermis. The infection of cells in the Malpighian layer produces both intercellular and intracellular oedema, resulting in the characteristic vesicular lesions.

Varicella zoster infections are generally considered to be mild and ubiquitous infections, predominantly affecting the paediatric population. However, in adults and specific groups of patients, such as those who are immunosuppressed, varicella infections can be life threatening (1). Varicella infection in immunocompromised adults can be severely complicated and potentially fatal. Several studies have shown that the rate of multi-organ involvement in varicella infection in immunocompromised patients to be around 30-50%. In the absence of treatment, 15% of cases can be lethal (2).

A person, who has been infected with varicella zoster virus, will develop antibodies to the virus. The virus can be detected in lesions by direct fluorescent antibodies and fluorescent microscopy or polymerase chain reaction (PCR).

Laboratory results

Case interpretation

The XN complete blood count revealed moderate thrombocytopenia and a normal RBC and WBC count. The WDF channel showed normal absolute and relative differentiation of all leucocytes except for a slightly increase in the absolute monocyte count. However, the abnormal cell distribution in the upper area of the lymphocytes in the WDF scattergram triggered the ‘Atypical Lympho?’ flag. The WDF scattergram showed a highly increased reactive lymphocytes count (Re-LYMP# = 0.76 x 109/L), and these activated lymphocytes with increased fluorescence intensity made up 27% of all lymphocytes and more than 8% of all leukocytes (Re-LYMP% = 8.6%). Furthermore, the monocytes showed an increase in fluorescence intensity, which can be a sign of reactivity. The presence of atypical, reactive lymphocytes and monocytes, visible in the WDF scattergram, and an increased Re-LYMP value, are often observed during early stages of viral infection. The results suggest that the severe infection triggers high activation of a cell-mediated response, which is a typical profile for the early stage of particular viral infections. In case of bacterial infection, activation of neutrophils (NEUT-RI) and a negative Delta-He value would typically be present. Moreover, a high level of reactive cellular lymphocyte response (as in this case) would not be present.

The PLT count from the PLT-F channel was low (PLT = 94 x 109/L) and the slightly increased immature platelet fraction (IPF = 7.8 %) and normal immature platelet count (IPF# = 7.3 x 109/L), which could be interpreted as the cause of thrombocytopenia, are due to the increased consumption of thrombocytes in the peripheral blood, likely due to a mildly commencing disseminated intravascular coagulation phenomena commonly observed in severe infection and sepsis.

The overall results likely exclude bacterial infection and non-infectious inflammation as possible sources of the patient’s severe condition. The suspected fulminant varicella zoster viral infection was confirmed by a positive virus-specific polymerase chain reaction test indicating ongoing viraemia. A peripheral blood smear examination showed the atypical reactive lymphocytes. The final diagnosis, on successful discharge from the intensive care unit 21 days after admission, was varicella zoster infection with varicella hepatitis, pneumonia and coagulopathy.


  1. Arvin A (2005): Ageing, Immunity and Varicella zoster viruses. N Eng J Med; 352:2266-2267.
  2. Whitley RJ (2006): Varicella zoster virus infections. In: Harrisons Principles of Internal Medicine. 16th ed. New York: McGraw Hill, p. 1042-1045

Advanced clinical parameters

Reference ranges

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