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Case Report: Diagnosing Zika Virus Through a Diffuse and Morphologically Diverse Rash in a Traveler

By Nathan Cleaver, DO, David Cleaver, DO, and Leslie Marshall, DO

A previously healthy, non-pregnant 22-year-old Hispanic female presented with a five-day history of a pruritic eruption on her dorsal right hand, upper arms, and back. She had returned to the United States four days prior after a two-week trip to Santa Anna, El Salvador. Her symptoms began one week after her arrival in El Salvador with neck swelling and general malaise. One day before returning home (day seven of illness), she developed tenderness and swelling surrounding a mosquito bite on her right ankle followed by a rash on her arms, back, and thighs. Accompanying symptoms included arthralgias in her hands, a low-grade fever, headache, and paresthesias. She reported being bitten several times by mosquitos while in El Salvador.

Physical examination revealed tender right anterior cervical lymphadenopathy. Punctate erythematous follicular-based papules were scattered on the arms, back, and thighs (Figure 1). An erythematous papule with surrounding induration was present on the lateral right ankle (Figure 2). In addition, there was an annular, erythematous plaque with a fine scale on the dorsal right hand (Figure 3).

Figure 1: Punctate erythematous follicular-based papules scattered on the arms, back, and thighs.

Figure 2: An erythematous papule with surrounding induration was present on the lateral right ankle.

Figure 3: Annular, erythematous plaque with a fine scale on the dorsal right hand.

Figure 4: Punch biopsy of the lower leg revealed superficial and deep perivascular lymphocytic infiltrate with dense infiltrate of eosinophils extending down to the dermal subcutaneous fat junction consistent with arthropod assault.

Punch biopsy for histological analysis from the lateral ankle revealed superficial and deep perivascular lymphocytic infiltrate with dense infiltrate of eosinophils extending down to the dermal subcutaneous fat junction consistent with arthropod assault (Figure 4).

Positive Zika IgM Antibody ELISA performed by The Centers for Disease Control and Prevention (CDC) indicated ZIKV infection and was confirmed by neutralizing antibody testing. The initial real-time reverse transcription-polymerase chain reaction (rRT-PCR) was negative.

At the two-week follow-up appointment, her cutaneous findings had improved with topical steroid therapy. The patient was advised to use barrier methods for contraception for the next eight weeks following diagnosis.

Discussion

ZIKV is a single-stranded positive RNA arbovirus belonging to the family Flaviviridae, genus Flavivirus. It is related to West Nile virus, dengue virus, and yellow fever. ZIKV was first isolated in 1947 from a rhesus monkey in Uganda’s Zika Forrest.¹ It is a mosquito-borne virus transmitted by various species belonging the Aedes genus. Aedes aegypti and Aedes albopictus are the most common transmitting species and are of particular concern due to their increasing geographic distribution.²

For decades following the identification of the virus in 1947, only few sporadic cases of ZIKV were reported in Asia and Africa. In 2013, an epidemic struck French Polynesia with an estimated 28,000 cases.³ Experts speculate that ZIKV was introduced to Brazil during the 2014 World Cup when participants arrived from the affected Pacific countries.⁴ The Brazilian epidemic that followed in 2015 was the largest epidemic in history. Currently, there are more than 40 countries and territories with active ZIKV transmission, including 29 locally acquired cases in the United States.⁵

The World Health Organization declared the increased incidence of infants born with microcephaly a public health emergency on February 1, 2016. A definitive correlation has since been established between ZIKV and microcephaly in infants born to infected mothers. The virus has been isolated from the amniotic fluid of two women who gave birth to infants with microcephaly, and the virus has been identified in the brain tissue of five fetuses with microcephaly.⁶ Guillain-Barré syndrome has also been positively associated with ZIKV infection.⁵

ZIKV infection may be subclinical in up to 80 percent of those infected.⁷ It is typically a mild, self-limited dengue-like illness with myalgia, headache, fever, arthralgias and conjunctivitis. Typical cutaneous signs include pruritic, blanchable macules and papules beginning on the face then spreading to the trunk and extremities three to 12 days after infection.⁵ This is in contrast to the cutaneous manifestations discussed in the above case.

A similar clinical picture may be seen with other mosquito-borne viral illness such as dengue and chikungunya virus. However, these generally result in more severe illness than ZIKV. Severe muscle pain and bleeding complications secondary to thrombocytopenia are characteristic of dengue infection. Chikungunya virus presents with high fever and severe, diffuse joint pain.⁸

Other modes of transmission reported include blood transfusion and sexual transmission. To date, cases of transmission via transfusion have been limited to Brazil. Sexual transmission from males to females, males to males, and most recently, from a symptomatically infected female to a male sex partner have been reported.⁵ ZIKV RNA has been detected in semen up to 93 days and in cervical mucous up to 11 days after symptom onset.⁹ Infected males and non-pregnant females should use barrier methods or abstain from sex for at least six months and eight weeks respectively after the onset of illness.¹⁰ Importantly, patients with ZIKV infection should be advised to protect themselves from additional bites in attempt to hinder the viral transmission cycle.⁵

Epidemiological shifts and increased prevalence of ZIKV have caused international concern, and it is imperative that healthcare providers promptly recognize the initial signs and symptoms of infection, especially in any patient of reproductive age.

Dermatologists should maintain a high level of suspicion for ZIKV infection and a comprehensive travel and sexual history should be elicited from patients who present with signs and symptoms suggestive of a recent viral infection, even in the presence of atypical cutaneous manifestations.

The authors have no conflicts of interest or financial disclosures.

Nathan Cleaver, DO is a dermatologist at Cleaver Dermatology in Kirksville, MO,

David Cleaver, DO is a dermatologist at Cleaver Dermatology in Kirksville, MO, and

Leslie Marshall, DO is a dermatologist at the Northeast Regional Medical Center in Kirksville, MO.

1. Dick GW, Kitchen SF, Haddow AJ. Zika virus: Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952;46:509-20.

2. Smith DR, Wikan N. Zika Virus; history of a newly emerging arbovirus. Lancet Infect Dis 2016; 16: e119–26.

3. Cao-Lormeau VM, Roche C, Teissier A, Robin E, Berry AL, Mallet HP, et al.Zika virus, French Polynesia, South Pacific, 2013 [Letter]. Emerg Infect Dis. 2014;20:1085-6.

4. Musso D. Zika virus transmission from French Polynesia to Brazil. Emerg Infect Dis.2015;21(10):1887.

5. Centers for Disease Control and Prevention website. Zika Virus. Available at: http://www.cdc.gov/zika.

6. Anderson KB, Thomas SJ, Endy TP. The emergence of zika virus. Ann Intern Med. 2016;165:175-183.

7. Brasil P, Pereira JP Jr, Raja Gabaglia C, Damasceno L, Wakimoto M, Ribeiro Nogueira RM, et al. Zika virus infection in pregnant women in Rio de Janeiro - Preliminary Report. N Engl J Med. 2016.

8. Zika virus infection and Zika fever: Frequently asked questions. Available at: http://www.paho.org/hq/index.php?option=com_content&view=article&id=9183%3A2015-preguntas-frecuentes-virus-fiebre-zika&catid=3986%3Azika-virus-infection&Itemid=41463&lang=en.

9 Mansuy J, Pasquier C, Daudin M, et al. Zika virus in semen of a patient returning from a non-epidemic area. Lancet Infect Dis. 2016;16:894–5.

10. Brooks JT, Friedman A, Kachur RE, LaFlam M, Peters PJ, Jamieson DJ. Update: Interim Guidance for Prevention of Sexual Transmission of Zika Virus — United States, July 2016. MMWR Morb Mortal Wkly Rep. 2016;65:745–747. DOI: http://dx.doi.org/10.15585/mmwr.mm6529e2.