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The incidence of primary varicella zoster virus infection (VZV) in young adults and pregnant women has risen in recent years and is accompanied by a greater risk of serious complications.1 VZV disease in the elderly usually presents as shingles, as a result of secondary reactivation of latent infection, and can be treated successfully with early antiviral therapy. We report a case of fatal primary infection in an elderly man.J Clin Pathol 2001;54:494–496
A 66 year old Bangladeshi man with fibrosing alveolitis and non-insulin dependent diabetes mellitus was admitted to hospital with increasing shortness of breath for one week. He was a smoker and had been well controlled on 25 mg of prednisolone daily for the previous two months.
On admission he was febrile (38.5°C), tachypnoeic (50 breaths/minute), and hypotensive (blood pressure, 85/60 mm Hg), with severe mucosal candidiasis. An extensive maculopapular rash, present for three days, was noted and thought to be consistent with amoxicillin treatment, which had been started before admission. Coarse crepitations were heard throughout the chest, oxygen saturation was 80% on air, and blood gases showed type I respiratory failure (pH 7.3; partial CO2 pressure, 4.8 kPa; partial O2 pressure, 8.39 kPa; HCO3 19.4 mmol/litre). Haemoglobin was 180 g/litre, white blood cell count was 8.5 × 109/litre, serum creatinine was 180 mmol/litre, and blood glucose was 22.2 mmol/litre. Chest x ray showed right mid zone confluent consolidation (fig 1). Bronchopneumonia was diagnosed; intravenous cefuroxime, clarithromycin, and fluconazole were commenced. After consultation with the virologists the patient also received aciclovir (10 mg/kg) intravenously.
He required intubation, ventilation, and inotropic support within 14 hours of admission. He remained persistently hypoxic despite 100% oxygen, positive end expiratory pressure, inverse ratio ventilation, and nebulised prostacyclin. Oxygenation improved dramatically with prone ventilation. Renal replacement treatment was started on day 3.
On day 4 the rash was noted to be vesicular. Skin scrapings and respiratory secretions were then examined for herpes simplex virus (HSV) and VZV by immunofluorescence (Dako, Ely, UK) and were positive for VZV. Subsequent enquiry did not reveal a chickenpox contact. VZV serology (Dade Behring, Deerfield, Illinois, USA) was positive for VZV IgM and negative for VZV IgG antibodies and a diagnosis of chickenpox was made. He received a single dose of normal immunoglobulin (Sandoglobulin; Novartis, Camberley, Surrey, UK; 200 mg/kg) and the aciclovir was continued for 14 days. Respiratory function gradually deteriorated despite 16 hours of prone ventilation each day and he died 23 days after admission.
VZV pneumonitis after primary infection is a severe disease with high mortality, especially in non-immune pregnant women, neonates, and the immunosuppressed. Smoking and previous treatment with steroids have been identified as independent risk factors.2 In the UK, primary disease in the elderly is a very unusual occurrence because there is almost universal seroconversion by early adulthood. In the tropics, seroconversion occurs at a later age, with seronegativity as high as 42% being found in rural Bangladeshi adults.3 It is interesting that although this patient had been resident in the UK for over 20 years he remained susceptible.
Intensive therapy unit (ITU) management of respiratory failure with ventilatory support is essential in varicella pneumonitis. Retrospective analysis of patients treated with aciclovir has shown some benefit of treatment,4, 5 especially when instigated early,6 but there has been no large randomised trial to date.7 High doses (10 mg/kg) are essential to obtain serum titres that are inhibitory to VZV (0.08–1.2 mg/litre).8 The use of steroids in varicella pneumonia is controversial, with one small trial showing a reduction in ITU and hospital stay, but no effect on overall mortality.9 Normal immunoglobulin (100–300 mg/kg) has also been given, with variable results.2 Prophylaxis using varicella zoster immunoglobulin (VZIG) has been successful in preventing or attenuating disease in non-immune contacts of primary cases after exposure. A live attenuated vaccine (Oka strain) has been licensed in some countries, but is available on a named patient basis only in the UK.10
This is the fourth fatal case of adult varicella pneumonitis we have seen in six years, and the second in an elderly Bangladeshi man taking steroids for lung disease. Although a characteristic chickenpox rash can precede the onset of pneumonitis by three to five days,11 our experience in these patients is that it may not be present or may be atypical. Diagnosis is often delayed and initial treatment may sometimes be inappropriate. Varicella is a preventable disease and consideration should now be given to the identification and vaccination of seronegative individuals at risk of severe infection.