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Le Infezioni in Medicina, n. 3, 274-276, 2017 274 CASE REPORT

Acute localized due to Coxsackievirus A4

Francesco Drago, Giulia Ciccarese, Lodovica Gariazzo, Margherita Cioni, Aurora Parodi DISSAL Department of Dermatology, IRCCS A.O.U. San Martino-IST, Genoa, Italy

SUMMARY

Enteroviruses are the leading cause of in plasma and faeces. Diagnosis of an acute localized children, especially during summer and autumn. En- exanthem due to Coxsachievirus A4 was performed. terovirus may occur in epidemics or small Skin lesions improved in seven days and completely outbreaks. A 30-year-old woman presented with a cleared in two weeks without any systemic or topical three-day history of an erythematous maculopapular treatment. Physicians should be aware of the possibil- skin with petechiae localized exclusively under ity that may determine localized skin the nipple of the right breast. The skin eruption was eruptions in addition to hand-foot-mouth disease and associated with an erythematous-petechial enanthem. atypical exanthems. Viral infections should be consid- The patient complained of low-grade fever, headache, ered in the differential diagnosis of localized dermati- asthenia, sore throat and arthromyalgias. IgM (1:128) tis especially when the skin eruption is associated with and IgG (1:640) antibodies against Coxsackievirus A4 enanthems and with systemic symptoms. were detected by the virus neutralization test. Reverse transcriptase real time polymerase chain reaction Keywords: coxsackieviruses; viral , skin erup- (PCR) assay detected RNA in the patient’s tion.

n INTRODUCTION gias. The patient denied drugs intake nor previ- ous topical treatments. nteroviruses are the leading cause of exan- Physical examination of the entire skin surface Ethems in children, especially during summer revealed and erythematous maculo-papular skin and fall. Enteroviruses infections may occur in ep- rash with petechiae localized exclusively under idemics or small outbreaks [1]. There is a marked the nipple of the right breast, involving the infra- variation in the clinical expression of a viral infec- mammary fold (Figure 1 A, B). Examination of the tion: the same virus may cause a different pattern oral mucosa revealed an enanthem with an ery- of exanthem during the same epidemic and even thematous-petechial pattern. Bilateral, tender, en- in the same patient [2, 3]. larged, cervical lymph nodes were palpable and there was no hepatosplenomegaly. The ausculta- tion of and lungs did not detect pathological n CASE REPORT sounds. Laboratory investigations, including anti-strep- A 30- year-old girl presented us with a 3 days his- tolysin-O titer and total IgE antibodies levels, tory of skin eruption, low-grade fever (37,4° C), resulted within normal ranges. IgM and IgG an- headache, asthenia, sore throat and arthromyal- tibodies against Epstein-Barr virus (EBV), cyto- megalovirus, echovirus, adenovirus, parvovirus B19, rubella and toxoplasma were negative. IgM (1:128) and IgG (1:640) antibodies against Cox- Corresponding author sackievirus A4 were detected by the virus neutral- Giulia Ciccarese ization test. Moreover, the reverse transcriptase E-mail: [email protected] real time polymerase chain reaction (PCR) assay Exanthem due to Coxsachievirus A4 275

Figure 1 - A) Erythematous maculo-papular lesion with petechiae on the breast; B) Erythemato-vescicular lesions on the soft palate with sparse petechiae; C) Resolution of the lesion fifteen days after the first visit. targenting the 5’ untranslated genome region ieviruses A9 and B5) or vesicular (mainly A4, A9 showed Enterovirus RNA in the patient’s plasma and A12) pattern [1, 2, 5, 6]. The maculopapular and feces during the acute eruption. Human her- eruption can progress, especially in case of A4 pesviruses -6 and -7 plasma viremia performed infection, becoming vesicular and the vesicular by calibrated quantitative real time PCR, as previ- lesions, often yellowish and opaque, may occur ously described, was negative [4]. Skin lesions im- in crops, mimicking bug bites [2]. Usually, the proved in seven days and completely cleared in skin lesions symmetrically involve the trunks and two weeks without systemic or topical treatment very rarely cause a localized eruption. Indeed, it (Figure 1 C). A serum sample taken two month is well known that varicella zoster, but also other after resolution of the skin eruption showed a viruses, has tendency to photodistribution or tro- decreased titer of Coxsackievirus A4 IgG (1:160) pism for inflamed skin [7, 8]. However, even in whereas Coxsackievirus A4 IgM antibodies were such circumstances the skin eruption spreads to negative. Allergy tests (skin prick and patch test) other areas. In literature, it has been described a performed after healing were negative, ruling out handful of viral exanthems that remain localized the possibility of an allergic dermatitis. Conse- to a single cutaneous area for the entire course of quently, a diagnosis of acute localized exanthem the infection. Yoshida et al. reported five children due to Coxsachievirus A4 was performed. who exhibited an exclusively papular facial rash that was diagnosed as Gianotti-Crosti syndrome dute to EBV [9]. Recently, we described the case n DISCUSSION of a patient with a maculopapular symmetric skin eruption localized on the buttocks due to Echovi- Enteroviruses inhabit the human alimentary tract rus 9 infection [10]. and leave the host through throat secretions and To our knowledge, the patient presented herein feces; infection of the new host is acquired through is the first case of localized viral exanthem due oral cavity. Acquiring an Enterovirus infection to Coxsackievirus A4. Possibly, these localized may determine maculopapular and/or vesicular eruptions are underestimated because confused skin rash or hand-foot-mouth disease, often asso- with other diseases. Indeed, in case of localized ciated with oral lesions and systemic symptoms. skin eruptions, the differential diagnoses include Fever, upper-respiratory symptoms and, rarely, insect bites, drug hypersensitivity or contact der- and neurologic involvement matitis [1,10]. can occur, simultaneously or preceding the skin Finally, physicians should be aware of the possi- lesions [1,5,6]. Our patient is the first described bility for Enteroviruses to cause localized skin case of localized skin eruption related to Coxsack- eruptions in addition to the hand-foot-mouth dis- ievirus A4. Coxsackieviruses may cause diffuse ease and to the atypical exanthems. Viral infections exanthems with maculopapular (mainly Coxsack- should be considered in the differential diagnosis 276 F. Drago, et al.

of localized dermatitis especially when the skin [5] Rodà D., Pérez-Martínez E., Cabrerizo M., et al. eruption is associated with enanthems and with Clinical characteristics and molecular epidemiology of systemic symptoms [1,2]. Indeed, to make a correct Enterovirus infection in infants <3 months in a refer- etiological diagnosis is crucial for both the patient ral paediatric hospital of Barcelona. Eur. J. Pediatr. 174, and for community concerning issues, such as time 1549-1553, 2015. [6] Ooi M.H., Wong S.C., Lewthwaite P., Cardosa M.J., off school and risk in pregnancy and immunocom- Solomon T. Clinical features, diagnosis, and manage- promised individuals [1,2,11,12]. ment of enterovirus 71. Lancet Neurol. 9, 1097-1105, 2010. Conflict of interest [7] Castrow F.F., Wolf J.E. Photolocalized varicella. None Arch. Dermatol. 107, 628, 1973. [8] Belhorn T.H., Lucky A.W. Atypical varicella exan- Financial support thems associated with skin injury. Ped. Dermatol. 11, None 129-132, 1994. [9] Yoshida M., Tsuda N., Morihata T., Sugino H., Iizu- ka T. Five patients with localized facial eruptions asso- n REFERENCES ciated with Gianotti-Crosti syndrome caused by prima- ry Epstein-Barr virus infection. J. Pediatr. 145, 843-844, [1] Drago F., Ciccarese G., Gasparini G., et al. Contem- 2004. porary infectious exanthems: an update. Future Micro- [10] Drago F., Ciccarese G., Broccolo F., Toniolo A., Javor biol. 12, 171-193, 2017. S., Parodi A. Localized exanthem due to echovirus 9. J. [2] Drago F., Paolino S., Rebora A., et al. The challenge Med. Virol. 87, 1447-1448, 2015. of diagnosing atypical exanthems: a clinico-laboratory [11] Drago F., Broccolo F., Javor S., Drago F., Rebora A., study. J. Am. Acad. Dermatol. 67, 6, 1282-1288, 2012. Parodi A. Evidence of human herpesvirus-6 and -7 re- [3] Drago F., Rebora A. Viral reactivation and skin erup- activation in miscarrying women with . tions. Dermatology. 207, 1-2, 2003. J. Am. Acad. Dermatol. 71, 198-199, 2014. [4] Broccolo F., Drago F., Cassina G., et al. Selective re- [12] Drago F., Ciccarese G., Parodi A. Atypical exan- activation of human herpesvirus 6 in patients with au- thems related to human herpesvirus-6 reactivations in toimmune connective tissue diseases. J. Med. Virol. 85, transplant recipients. Transpl. Infect. Dis. 18, 639-640, 1925-1934, 2013. 2016.