Age and immunodeficiency are the most important predictors of severity, with adults and infants having more severe disease. Cellular rather than humoral immunodeficiency is associated with more severe disease. Nonetheless, most cases of severe disease (and 90% of the deaths) occur in previously healthy people.

Average age is falling, now under 5 (presumably increased day care) cf underdeveloped countries, where average age is older eg teens. Peak incidence March to May.

There are 3 genotypes but they are virtually identical, and only 1 circulates in Europe; it remains theoretically possible, therefore, to get chickenpox twice!  But more likely is that one or more episodes were due to another virus eg enterovirus.

Starts as small spots, spreading over the trunk within 24 hr. There is usually no prodrome in children, can be 1-2 days in adults. Within 24-48 hours the classic vesicles, followed by pustules, develop. Burst to leave a scab which falls off after 4-5 days. There may be several crops of these blisters which follow the same pattern. The classical distribution is on the trunk but lesions can be widespread and can affect the mouth, the eyes and the urethra.

Onset of the rash is often associated with fever and other systemic symptoms. The disease can however be subclinical (or at least unrecognized) in some cases. Secondary cases in a household on the other hand tend to be more severe, probably due to increased viral load.

In the immunocompromised, there may be a prodrome ie symptoms at the time of initial viraemia, around day 7 of the incubation period. The classic prodrome is of abdominal symptoms and/or hyponatraemia, and can precede the classic vesicular rash by several days (up to 3 weeks). Abdominal manifestations include severe pain, diarrhoea, or vomiting which are explained by hepatitis, gastritis, oesophagitis, pancreatitis, and paralytic ileus owing to viral spreading from the posterior nerve roots that supply abdominal organs. The mechanism of hyponatraemia is presumed to be SIADH.

See Congenital varicella for infection in pregnancy and neonatal period.

Diagnosis

Usually clinical. If in doubt, PCR and culture can be done on skin scrapings (particularly from the base of lesions, but potentially also from the crust) or from other sites eg CSF.

IgM can be positive from as early as 1-2 days after appearance of the rash. But serology is not 100% sensitive. Antibodies persist lifelong and are useful for indicating previous exposure and hence immunity; they may however be passed on passively through transfusion. Not very good for confirming response to vaccination, as levels are 10 times lower than after disease.

Complications of varicella occur in the immunocompetent, as well as the immunocompromised :

• Bacterial superinfection of the rash, potentially cellulitis, even necrotizing fasciitis. Streptococcal infections are more common after chickenpox, and not just in the skin.
• Pneumonitis
• Meningoencephalitis – usually after onset of rash but may present before.  High mortality.
• Hepatitis
• Glomerulonephritis
• Haemorrhagic disease (purpura fulminans) – with shock, DIC
• Post varicella cerebellar ataxia – sudden onset but 2-3 weeks later (immune)

See also Congenital varicella.

Spread

Incubation period is 10-21 days, typically 14 days.  Longer in some situations (eg post ZIG).   Infectivity (by aerosol spread) begins up to 48 hours before onset of the rash and persists until all lesions have dried (crusted), usually 1-2 weeks but may be longer in the immunocompromised. In theory transmission from a moist spot can occur but infection is generally by respiratory route.

Infectious or isolation period is until all lesions crusted, or else 5 days after the last spot appears. UK HPA guidance is available on exclusion periods from school or nursery on health grounds. Infectivity can persist in the immunocompromised for up to several weeks. Note also that after VZIG administration, incubation period is prolonged.

Treatment

Chickenpox can be treated with aciclovir or the like. Oral aciclovir in the healthy child reduces fever by 1 day and symptoms by 15-30%; not clear if complications are reduced. NEJM 1991;325(22):1539-44. Not standard practice, however! Adolescents and adults should be offered it.

Oral aciclovir only works if given in first 24 hours; IV most effective if given within 72 hours of onset of the rash.

A variety of topical products are available eg calamine.  Antihistamines.

Various studies have found an association between severe soft tissue infection and use of ibuprofen (in children, anyway – rate ratio 4.9 [Br J Clin Pharmacol. 2008 Feb;65(2):203-9. doi: 10.1111/j.1365-2125.2007.02997.x]).  Likely to be confounding, but in absence of prospective studies, NICE recommends avoiding non-steroidal anti-inflammatories in varicella [https://cks.nice.org.uk/chickenpox#!scenario].

Prevention

See Vaccines for details on live attenuated vaccine.

Post-exposure prophylaxis (PEP) is required for at risk groups who have had significant exposure. This includes:

• pregnant women,
• immunodeficient (except those receiving regular normal immunoglobulin),
• susceptible neonates exposed up to 7 days after birth (which includes mum developing chickenpox up to 7 days before or after birth), or any neonate (susceptible or otherwise) that require intensive or prolonged special care).

Specific Varicella Zoster Immunoglobulin (VZIG) is effective at reducing the likelihood of disease, and where disease occurs it tends to be less severe. It is given intramuscularly.  Should be given within 10 days of exposure. Protection lasts 3 weeks, after which a further dose should be considered if re-exposure occurs and antibody has not persisted. Can prolong period of infectivity though.  See Greenbook for more details.

Aciclovir can also be used for PEP.

Varivax vaccine is also licensed for this indication, but of course contraindicated in the type of patient who might need it: 18% of healthy contacts developed varicella compared with 78% who did not get vaccine. Of the vaccine recipients who nonetheless developed varicella, the majority only had mild disease (with less than 50 skin lesions).  Evidence only really supports PEP within three days following exposure.