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The nerve of Zika!

DII small banner By Warren R. Heymann, MD
April 17, 2017

Zika virus–associated skin exanthem. Peripheral edema of bilateral hands (A) and feet (B). Generalized lymphadenopathy was also present.
Credit: JAAD

Zika virus infections have dominated the headlines, most notably because of its association with microcephaly. According to the valuable CDC website (www.cdc.gov/zika) there have been 5,234 cases in the United States, including 1716 pregnant women (as of March 28th, 2017). An increasing number of cases are anticipated with the rise in global temperatures (1).

While the overwhelming number of cases has been travel-related, Hafeez et al reported the first non-travel-associated case of Zika infection in the United States. They presented a 23-year-old woman with a few follicular macules and papules on the trunk and extremities with scattered tender pink papules on the palms, and a few palatal petechiae.  A biopsy demonstrated a superficial perivascular mononuclear infiltrate with some neutrophils. This was accompanied by fever, myalagias, and joint pain. There was no lymphadenopathy or conjunctivitis. Fortunately, she delivered a normal child at full-term (2).
The Zika virus is an RNA arbovirus within the Flaviviridae family, related to Dengue, West Nile, yellow fever, and Japanese encephalitis viruses. It is predominantly transmitted by the mosquito vectors Aedes aegypti and Aedes albopictus, although transmission may occur via blood transfusion, sexual contact, or from mother to fetus. Only 20% of infections are symptomatic. The incubation period is from 3 to 12 days, with symptomatic adults commonly displaying fever, rash, myalgia, arthralgia, headache and non-purulent conjunctivitis. Most reports of the rash have been non-descript; morbilliform, scarlatiniform, and minimally petechial, the rash spreads in a cepahalo-caudad manner, with a tendency to spare the palms and soles. It may be pruritic, and it usually heals with desquamation (3). In a study of 60 confirmed cases of Zika infection in Guadeloupe, most patients (19 adults and 12 children; 31 of 60 [52%]) complained of dysesthesia, which was possibly associated with the following autonomic symptoms: dry mouth (21 of 57 cases [37%]), lack of tolerance to heat (15 of 60 [25%]), sweating disorder (11 of 59 [19%]), dry eyes (8 of 57 [14%]), and bladder incontinence (6 of 60 [10%]). Pruritus was noted in >80% of cases. The authors propose that the association of pruritus with dysesthesia and autonomic symptoms is due to a small-fiber neuropathy resulting from the Zika virus, for which neurological tropism has now been clearly demonstrated (4).
It is the neurologic complications of Zika virus that are so devastating. Aside from microcephaly and other birth defects, Guillain-Barré syndrome, meningoencephalitis, myelitis, and various ophthalmologic abnormalities (including optic nerve hypoplasia and chorioretinal atrophy) may occur. Neuropathologically, the Zika virus appears to infect neural stem cells.

The diagnosis is best confirmed by molecular detection of the Zika virus by RT-PCR. IgM antibody for the Zika virus by ELISA is suggestive, but not specific, because of significant cross-reactivity among the flaviviruses (5).

As in other viral diseases, treatment is supportive. Those in endemic areas should use insect repellent (such as DEET), wear long-sleeve shirts and long pants, and use window screens and air conditioning when indoors, if possible. Sexually active couples should avoid unprotected sexual intercourse for 2 months if the woman has traveled to an endemic area or 6 months if the male partner was in such a region. Candidate vaccines are currently being researched.

For dermatologists, if a patient was in an endemic region, the presence of dysesthesia with an exanthema may be an important diagnostic clue suggesting a Zika infection. It is then essential to report such cases to the local health department, and in the event the patient is pregnant, referral to a high-risk obstetric team.

Much remains to be learned about this bizarre virus. Why are these complications first occurring now, 70 years after the virus was first isolated? Why are there geographic differences in complication rates? Why are there reports of microcephaly in only one twin, when both fetuses were exposed to the virus? Can the presumed small fiber neuropathy be predictive of other neural complications? Zika has gotten the world’s attention. Hopefully, it will be eradicated, and become a historical footnote in viral history, before too long.

1. Kaffenberger BH, et al. The effect of climate change on skin disease in North America 2017; 76: 140-7.
2. Hafeez F, et al. Cutaneous eruption in a US woman with locally acquired Zika virus infection. N Engl J Med 2017; 376: 400-1.
3. Farahnik B, et al. Cutaneous manifestations of the Zika virus. J Am Acad Dermatol 2016; 74: 1286-7.
4. Cordel N, et al. Main characteristics of Zika virus exanthema in Guadeloupe. JAMA Dermatol 2017; 153: 326-8.
5. Duca L, et al. Zika virus disease and associated neurologic complications. Curr Infect Dis Rep 2017;19: 4

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