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On February 1&#44; 2016&#44; the World Health Organization declared ZIKV infection a Public Health Emergency of International Concern&#46; One week later&#44; the Centers for Disease Control and Prevention upgraded its response to the outbreak to Level 1 activation&#44; the agency&#39;s highest level&#46; We present the case of a patient diagnosed with ZIKV infection in our center&#46; Our aim is to increase awareness of this emerging arbovirus among dermatologists&#46; Given the mainly cutaneous symptoms of the infection and the intensity of travel and migratory flows from Latin America&#44; it seems highly likely that we will be diagnosing ZIKV in the coming months&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 25-year-old woman from the Dominican Republic with no personal history of interest who had been living in Spain for 8 years was referred to the dermatology emergency department for assessment of a pruriginous exanthem that had started 48<span class="elsevierStyleHsp" style=""></span>hours previously and was extending down her body&#46; She also had intense asthenia&#44; sensation of poor temperature regulation&#44; mild joint and muscle pain&#44; headache&#44; and ocular pruritus&#46; Physical examination revealed bilateral malar erythema and edema&#44; together with marked conjunctival injection &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figures 1 and 2</a>&#41; and subtle generalized micropapular exanthema with follicular accentuation &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>&#41;&#46; The blood workup revealed only slightly altered cytolysis in the liver&#46; The fact that she had spent a month in her home country and arrived in Spain 12<span class="elsevierStyleHsp" style=""></span>hours before the onset of symptoms led us to suspect ZIKV infection&#46; Therefore&#44; we ordered serology tests and nucleic acid testing in serum and urine using reverse transcriptase polymerase chain reaction &#40;RT-PCR&#41; to detect ZIKV&#46; We also requested a workup for dengue virus and chikungunya virus and the usual protocol for exanthematous viruses&#46; The result of the pregnancy test was negative&#46; Histopathology of the skin revealed a mild superficial perivascular lymphocytic infiltrate&#46; The symptoms resolved completely 6 days after onset&#46; RT-PCR in urine and serum was positive for ZIKV in samples collected at 48<span class="elsevierStyleHsp" style=""></span>hours from onset&#46; The results of serology testing were negative&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">ZIKV is a single-stranded RNA virus belonging to the genus <span class="elsevierStyleItalic">Flavivirus</span> of the Flaviviridae family&#46; It is transmitted mainly by bites from mosquitos of the <span class="elsevierStyleItalic">Aedes</span> genus&#44; in most cases <span class="elsevierStyleItalic">A aegypti</span> &#40;although it is also carried by other species&#44; including <span class="elsevierStyleItalic">A albopictus</span>&#41;&#46; As with other arboviruses&#44; vector-independent routes of transmission have been identified &#40;eg&#44; vertical and transfusional&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> Remarkably&#44; in contrast with other arboviruses&#44; sexual transmission has also been documented&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> It remains to be determined whether there is a risk of transmission via other fluids where viral RNA has been detected&#44; such as saliva or breastmilk&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">It is estimated that only 1 in 5 infected persons develops clinical manifestations&#44; which are generally mild and self-limiting&#46; After an incubation period lasting between 3 and 12 days&#44; the typical manifestations are pruriginous maculopapular rash that extends down the body&#44; mild fever&#44; mild pain affecting mainly the small joints of the hands and feet&#44; and nonpurulent conjunctivitis&#46; The manifestations last 2 to 7 days&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> Although the clinical picture coincides with that of other viruses transmitted by the same vector&#44; such as dengue or chikungunya&#44; certain characteristics can orient us toward the causative agent&#44; namely&#44; predominance of rash with little involvement of the patient&#39;s general status in ZIKV infection&#44; persistent joint pain in chikungunya infection&#44; and the classic picture of rash respecting specific areas of skin&#44; thrombocytopenia&#44; and bleeding complications in dengue&#46; The absence of pathognomonic findings&#44; however&#44; necessitates a microbiologic diagnosis based on the detection of viral RNA using RT-PCR assay in serum during the first 5 days with symptoms or in urine for up to 10-15 days&#46; This study can be extended to cerebrospinal fluid in patients with neurological symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> RT-PCR assay is followed by serology testing&#46; This approach is of particular interest in pregnant women&#44; although it is limited because of cross-reactivity with other flaviviruses&#46; Available evidence indicates that ZIKV infection can confer prolonged immunity&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Up to mid-March 2016&#44; the Spanish National Microbiology Center had confirmed 43 cases of ZIKV infection in Spain&#44; all of which were imported&#46; However&#44; the presence of <span class="elsevierStyleItalic">A&#160;albopictus</span> &#40;commonly known as the tiger mosquito&#41;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> along the Mediterranean coast and in the Basque Country and Aragon enables autochthonous transmission of ZIKV in Spain&#44; mainly during summer and winter&#44; which is when vector activity is most intense and more people travel from epidemic areas&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Journal Information
Vol. 107. Issue 8.
Pages 687-689 (October 2016)
Vol. 107. Issue 8.
Pages 687-689 (October 2016)
Case and Research Letters
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Zika Virus Infection: An Emerging Disease the Dermatologist Must Know About
Infección por virus del Zika: una enfermedad emergente que el dermatólogo debe conocer
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S. Burillo-Martíneza,
Corresponding author
sburillo@hotmail.com

Corresponding author.
, M. Fernández-Ruizb, A. Pérez-Rivillac, C. Zarco-Olivoa
a Servicio de Dermatología, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain
b Unidad de Enfermedades Infecciosas, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain
c Servicio de Microbiología, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain
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Dear Editor:

In contrast to infection by other arboviruses such as dengue virus, which can cause potentially severe disease in humans, infection by Zika virus (ZIKV) is generally benign and self-limiting, with mainly asymptomatic episodes. Recent epidemiological shifts in the geographic distribution of ZIKV, however, have raised health care alarms around the world because of the possible association between ZIKV infection and congenital malformations, particularly microcephaly, and neurologic disorders, including Guillain-Barré syndrome. Although the discovery of the virus in the Zika forest in Uganda dates back to 1947, fewer than 20 cases of ZIKV infection had been reported in humans up to 2007. Preceded by the outbreaks on the island of Yap in Micronesia in 2007 and in French Polynesia in 2013, the epidemic that started in May 2015 in Latin America continues to expand uncontrolled. On February 1, 2016, the World Health Organization declared ZIKV infection a Public Health Emergency of International Concern. One week later, the Centers for Disease Control and Prevention upgraded its response to the outbreak to Level 1 activation, the agency's highest level. We present the case of a patient diagnosed with ZIKV infection in our center. Our aim is to increase awareness of this emerging arbovirus among dermatologists. Given the mainly cutaneous symptoms of the infection and the intensity of travel and migratory flows from Latin America, it seems highly likely that we will be diagnosing ZIKV in the coming months.

A 25-year-old woman from the Dominican Republic with no personal history of interest who had been living in Spain for 8 years was referred to the dermatology emergency department for assessment of a pruriginous exanthem that had started 48hours previously and was extending down her body. She also had intense asthenia, sensation of poor temperature regulation, mild joint and muscle pain, headache, and ocular pruritus. Physical examination revealed bilateral malar erythema and edema, together with marked conjunctival injection (Figures 1 and 2) and subtle generalized micropapular exanthema with follicular accentuation (Figure 3). The blood workup revealed only slightly altered cytolysis in the liver. The fact that she had spent a month in her home country and arrived in Spain 12hours before the onset of symptoms led us to suspect ZIKV infection. Therefore, we ordered serology tests and nucleic acid testing in serum and urine using reverse transcriptase polymerase chain reaction (RT-PCR) to detect ZIKV. We also requested a workup for dengue virus and chikungunya virus and the usual protocol for exanthematous viruses. The result of the pregnancy test was negative. Histopathology of the skin revealed a mild superficial perivascular lymphocytic infiltrate. The symptoms resolved completely 6 days after onset. RT-PCR in urine and serum was positive for ZIKV in samples collected at 48hours from onset. The results of serology testing were negative.

Figure 1.

Bilateral malar erythema and edema and conjunctival injection.

(0.12MB).
Figure 2.

Detailed image of marked conjunctival injection.

(0.12MB).
Figure 3.

Subtle rash comprising micropapules on a background of generalized erythema.

(0.08MB).

ZIKV is a single-stranded RNA virus belonging to the genus Flavivirus of the Flaviviridae family. It is transmitted mainly by bites from mosquitos of the Aedes genus, in most cases A aegypti (although it is also carried by other species, including A albopictus). As with other arboviruses, vector-independent routes of transmission have been identified (eg, vertical and transfusional).1 Remarkably, in contrast with other arboviruses, sexual transmission has also been documented.2 It remains to be determined whether there is a risk of transmission via other fluids where viral RNA has been detected, such as saliva or breastmilk.3,4

It is estimated that only 1 in 5 infected persons develops clinical manifestations, which are generally mild and self-limiting. After an incubation period lasting between 3 and 12 days, the typical manifestations are pruriginous maculopapular rash that extends down the body, mild fever, mild pain affecting mainly the small joints of the hands and feet, and nonpurulent conjunctivitis. The manifestations last 2 to 7 days.5 Although the clinical picture coincides with that of other viruses transmitted by the same vector, such as dengue or chikungunya, certain characteristics can orient us toward the causative agent, namely, predominance of rash with little involvement of the patient's general status in ZIKV infection, persistent joint pain in chikungunya infection, and the classic picture of rash respecting specific areas of skin, thrombocytopenia, and bleeding complications in dengue. The absence of pathognomonic findings, however, necessitates a microbiologic diagnosis based on the detection of viral RNA using RT-PCR assay in serum during the first 5 days with symptoms or in urine for up to 10-15 days. This study can be extended to cerebrospinal fluid in patients with neurological symptoms.6 RT-PCR assay is followed by serology testing. This approach is of particular interest in pregnant women, although it is limited because of cross-reactivity with other flaviviruses. Available evidence indicates that ZIKV infection can confer prolonged immunity.

Up to mid-March 2016, the Spanish National Microbiology Center had confirmed 43 cases of ZIKV infection in Spain, all of which were imported. However, the presence of A albopictus (commonly known as the tiger mosquito)7 along the Mediterranean coast and in the Basque Country and Aragon enables autochthonous transmission of ZIKV in Spain, mainly during summer and winter, which is when vector activity is most intense and more people travel from epidemic areas.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Acknowledgments

We are grateful to the patient for giving her written permission to publish the images shown in the manuscript.

References
[1]
J.F. Chan, G.K. Choi, C.C. Yip, V.C. Cheng, K.Y. Yuen.
Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease.
J Infect, 72 (2016), pp. 507-524
[2]
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Potential sexual transmission of Zika virus.
Emerg Infect Dis, 21 (2015), pp. 359-361
[3]
M. Besnard, S. Lastere, A. Teissier, V. Cao-Lormeau, D. Musso.
Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014.
Euro Surveill, 19 (2014),
pii: 20751
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D. Musso, C. Roche, T.X. Nhan, E. Robin, A. Teissier, V.M. Cao-Lormeau.
Detection of Zika virus in saliva.
J Clin Virol, 68 (2015), pp. 53-55
[5]
J. Heukelbach, C.H. Alencar, A.A. Kelvin, W.K. de Oliveira, L. Pamplona de Góes Cavalcanti.
Zika virus outbreak in Brazil.
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[6]
A.C. Gourinat, O. O’Connor, E. Calvez, C. Goarant, M. Dupont-Rouzeyrol.
Detection of Zika virus in urine.
Emerg Infect Dis, 21 (2015), pp. 84-86
[7]
J. Lucientes-Curdi, R. Molina-Moreno, C. Amela-Heras, F. Simon-Soria, S. Santos-Sanz, A. Sánchez-Gómez, et al.
Dispersion of Aedes albopictus in the Spanish Mediterranean Area.
Eur J Public Health, 24 (2014), pp. 637-640

Please cite this article as: Burillo-Martínez S, Fernández-Ruiz M, Pérez-Rivilla A, Zarco-Olivo C. Infección por virus del Zika: una enfermedad emergente que el dermatólogo debe conocer. Actas Dermosifiliogr. 2016;107:687–689.

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