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Q1: What is the diagnosis?

Varicella zoster virus (VZV) or chickenpox pneumonitis.

Q2: How might the diagnosis be confirmed?

Diagnosis can be made in most circumstances clinically. Confirmation and identification of the virus can be made in a number of ways using laboratory tests:

  • Polymerase chain reaction—With high sensitivity (97%–100%) and specificity for viral DNA with rapid diagnosis time, this is a useful test, as it can be applied to most clinical specimens and is likely to replace older tests.1

  • Serology—Anti-VZV IgM can be used to detect active disease, while the presence of anti-VZV IgG is a marker of previous infection/inoculation.

  • Electron microscopy—This is very sensitive but expensive and unable to differentiate between VZV and other herpes viruses—for example, herpes simplex virus (HSV).

  • Viral culture—This is the gold standard for establishing the diagnosis, though VZV is more difficult to culture than HSV.

  • Tzanck smear—An inexpensive “bedside” test from vesicular fluid with a sensitivity reported at 80%–100%.2 Under light microscopy, the pathognomonic triad includes multinucleated giant cell formation, ground glass appearance of the nuclear chromatin, and nuclear contours that appear moulded together.

  • Direct immunofluorescence—This utilises fluorescein-tagged antibody; more accurate than the Tzanck smear and able to differentiate between VZV and HSV.

Q3: What is the differential diagnosis of findings on the chest radiograph (see p 679)?

Miliary mottling is seen in a number of different disease processes; it describes a diffuse pattern of lung infiltration seen as numerous small opacities. Causes include: VZV pneumonitis, acute respiratory distress syndrome, miliary tuberculosis, fungal infection (invasive aspergillosis), extrinsic allergic alveolitis, fibrosing alveolitis, pneumoconiosis, and sarcoidosis.

Progress

The patient subsequently required admission to the intensive care unit where continuous positive airways pressure ventilation was used to maintain oxygenation. Over a course of 12 days he responded well to intravenous acyclovir and flucloxacillin. One month after discharge the patient was symptom-free, and a repeat chest radiograph demonstrated near complete resolution of infiltrates.

Discussion

VZV is a double stranded DNA virus of the alphaherpes virus family. Primary infection results in chickenpox and reactivation of the virus in later life causes shingles, or in severely immunocompromised patients, disseminated zoster.

VZV pneumonitis complicates between 2% and 10% of cases of adult chickenpox.3 The severity of VZV pneumonitis is highest in immunosuppressed persons, pregnant women, and in individuals who smoke.4

Microscopy of lung parenchyma in VZV pneumonitis shows focal necrosis, consolidation, a mononuclear infiltrate, and intranuclear inclusion bodies. VZV can be identified from vesicular fluid, respiratory secretions, or blood (as above).

Radiographic findings are diffuse, fluffy, reticular, or nodular infiltrates that can be rapidly progressive; this can give rise to the miliary pattern seen in the case presented. Pleural effusions can also occur. Radiographic abnormalities are often non-specific and more prominent during the peak of the rash and resolve rapidly with clinical improvement. Long term respiratory sequelae are infrequent in survivors, although small, diffusely scattered calcifications may persist on chest radiographs.

Treatment of VZV pneumonitis includes respiratory isolation until skin lesions heal, intensive respiratory support, administration of antiviral agents, particularly acyclovir and related compounds, antibiotics, and active and passive immunisation. Intravenous acyclovir is the drug of choice and needs to be started within 72 hours of symptom onset. Empiric antibacterial therapy is indicated in immunocompromised patients with VZV pneumonitis; respiratory failure may develop secondary to superimposed bacterial infection, with Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae commonly implicated.5

In conclusion, immunocompetent adults who contract VZV are at risk of developing life threatening complications including pneumonitis, and thus clinicians must have a high index of suspicion when attending these patients. Patients with respiratory failure will require admission for supportive measures and treatment.

Final diagnosis

Varicella zoster virus pneumonitis.

References

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