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 Table of Contents  
BRIEF REPORT
Year : 2018  |  Volume : 4  |  Issue : 2  |  Page : 73-75

Oral acyclovir for severe hand, foot and mouth disease


Consultant Dermatologist, Dr. Damle Skin and Laser Clinic, Pune, Maharashtra, India

Date of Web Publication31-Dec-2018

Correspondence Address:
Dr. Dhananjay K Damle
Dr. Damle Skin and Laser Clinic, 1st Floor, Pathare Complex, Bhaji Mandai, Near Vijay Sales, Chandan Nagar, Pune-14, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_35_18

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  Abstract 

Hand, foot and mouth disease (HFMD), an acute viral illness caused by coxsackieviruses or enteroviruses, is predominantly encountered in children under 10 years of age. Although it is usually self-resolving, there are a few rare cases which have an extremely aggressive clinical presentation and need to be treated on a priority. Many affected children present with florid or unusual lesions; are highly febrile, with high irritability or listlessness; and also refuse to eat. Such cases could be considered as severe ones. With no specific effective antiviral available to tackle HFMD cases, acyclovir may be used in severe cases for its antiviral effect. We describe three such cases of HFMD in children, treated with oral acyclovir, with gratifying results.

Keywords: Acyclovir, hand, foot and mouth disease, severe


How to cite this article:
Damle DK. Oral acyclovir for severe hand, foot and mouth disease. Indian J Drugs Dermatol 2018;4:73-5

How to cite this URL:
Damle DK. Oral acyclovir for severe hand, foot and mouth disease. Indian J Drugs Dermatol [serial online] 2018 [cited 2019 Sep 18];4:73-5. Available from: http://www.ijdd.in/text.asp?2018/4/2/73/249194


  Introduction Top


Hand, foot and mouth disease (HFMD), an acute viral illness caused by coxsackieviruses or enteroviruses, is predominantly encountered in children under 10 years of age.[1] Since its first report from New Zealand in 1957, there have been several reports of HFMD outbreaks from different parts of the world.[2],[3],[4] Since 2004, several outbreaks of varying intensities have been reported from numerous parts of India.[5] The typical clinical presentation includes crops of round-to-oval papulovesicular eruptions over the distal extremities and oral mucosa with preceding or accompanying fever and constitutional symptoms.[6] Although usually self-resolving, the clinical presentation in a few of the affected children could be severe. In 2011, the WHO laid down the criteria to assess the severity of HFMD cases with emphasis on neurological and cardiorespiratory complications.[7] These subsets of severe cases are those that are caused by human enterovirus 71 (HEV71) and reported from Southeast Asian countries and China. However, there are currently no standardized criteria in place to assess the severity of clinical presentation of cases which are not affected by HEV71 strains, which is more often the situation in the Indian subcontinent. Many affected children present with florid or unusual lesions; are highly febrile, with high irritability or listlessness; and also refuse to eat. Such cases could be considered as severe ones. We describe three such cases of HFMD in children, treated with oral acyclovir, with gratifying results.


  Case Reports Top


Case 1

A 1-year-old male child was brought by parents with complaints of multiple oral erosions over the palate. Palmoplantar surface showed oval-to-elongate-shaped vesicles along with involvement of thighs and buttocks. Within a period of 12 h, the vesicles rapidly progressed to involve almost the entire body and extremities [Figure 1]a and [Figure 1]b. The child was admitted under the care of a pediatrician, and symptomatic and supportive therapy in the form of IV fluids and antipyretics was initiated. The child had no history of any cutaneous rashes. As the clinical presentation was typical of HFMD case, oral acyclovir suspension was started in a dose of 10 mg/kg/dose 4 times a day. This was continued for a total period of 7 days. Within 48 h of beginning the acyclovir therapy, there was a remarkable improvement in the clinical condition of the patient with crusting of vesicles and improvement of constitutional symptoms [Figure 1]c and [Figure 1]d.
Figure 1: (a) Papulovesicular eruptions on an erythematous base with few accompanying erosions present over the right arm. (b) Papulovesicular eruptions on an erythematous base with few accompanying erosions present over the right leg. (c) Crusted vesicles present over the right arm after starting acyclovir. (d) Healing crusted scales present over both the lower limbs

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Case 2

A 15-month-old female child was brought by parents with a history of fever, sore throat, and listlessness for 2 days. This was followed by appearance of vesicles over the palms, elbows, and buttocks. The child subsequently developed bullae over both the soles, painful in nature, making the child irritable [Figure 2]a and [Figure 2]b. The child also refused to feed due to ongoing symptoms which made the parents extremely anxious. Oral acyclovir was given in a dose of 10 mg/kg/dose 4 times a day. By the 3rd day, there was a significant improvement in the clinical status of the child. The child started to feed within 48 h of starting acyclovir. The bullae and vesicles almost dried up within 72 h [Figure 2]c. However, acyclovir was continued for a total duration of 7 days.
Figure 2: (a) Single bulla presents over the plantar aspect of the right foot. (b) Single bulla presents on the sole of the left foot. (c) Dried bullae present on the soles of both feet within 72 h of initiation of acyclovir

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Case 3

A 2-year-old male child presented with extensive distribution of vesicles over the buttocks and lower limbs progressing to erosions and ulcerations. The child had typical oval-shaped vesicles on an erythematous base over the palms and soles. Oral examination revealed discrete erosions over the palate. The clinical condition of the patient deteriorated rapidly, worsened by the decreased food intake and accompanying high-grade fever. He was admitted under the care of a pediatrician for supportive treatment. In view of classical clinical features suggestive of HFMD, the child was started on oral acyclovir in a dose of 10 mg/kg/dose 4 times a day. This was continued for 7 days with a good response.


  Discussion Top


HFMD is a relatively mild childhood viral disease caused by coxsackievirus A16 (CVA16) or HEV71 but may occasionally be caused by CVA 4–7, A9, A10, B1–3, and B5. This condition is known to occur as periodic outbreaks, with predilection for summer and early fall in temperate climates, but throughout the year in the tropics.[6] Although maximum number of cases occur in children under the age of 10 years, adult cases have also been reported in literature.[8] Usually, HFMD has self-resolving course, although there are a few exceptional cases which have an extremely aggressive clinical presentation and need to be treated on a priority. Mathes et al. identified four morphologies that characterize the severe end of the spectrum of HFMD and distinguish it from classic HFMD: (1) widespread vesiculobullous and erosive lesions extending beyond the palms and soles, (2) an eczema herpeticum-like eruption termed “eczema coxsackium,” (3) an eruption similar to Gianotti–Crosti, and (4) a petechial or purpuric eruption.[9]

Currently, there is no specific effective antiviral available to tackle HFMD cases. Acyclovir, the most widely used antiviral drug, exerts its therapeutic effect by undergoing phosphorylation to be activated into acyclovir triphosphate.[10],[11]

This action is done first by thymidine kinase (present in viruses such as herpes simplex, herpes zoster, and Epstein–Barr virus) and consequently by cellular enzymes. The triphosphylated form of acyclovir inhibits viral DNA, resulting in irreversible inhibition of further viral DNA synthesis. Enteroviruses, however, lack thymidine kinase, and in vitro studies have failed to show any inhibitory effect of acyclovir on them.[12],[13] Thus, acyclovir is believed to work in HFMD by modulating the patient's own interferon for its antiviral effect.[14]

Shelley et al.[12] demonstrated the valuable therapeutic effect of acyclovir in 12 children and one adult with HFMD in 1996. These patients were treated with oral acyclovir (200–300 mg five times daily for 5 days) within 1–2 days of onset of the rash. Symptomatic relief, defervescence, and significant involution of lesions were seen within 24 h of starting acyclovir.

Other situations where it may be reasonable to consider treatment with oral acyclovir include in infants who generally have a more severe course and in severely symptomatic patients. Rarely, myocarditis, meningitis, encephalitis, paralysis, or pulmonary edema can occur.[15],[16] These serious complications and even death are much more likely to be associated with epidemics of HEV71 rather than CVA16 and may warrant oral acyclovir. Infection with coxsackie A16 has been associated, however, with fatal rhabdomyolysis and renal failure,[17] and with spontaneous abortion in the first trimester of pregnancy.[18]


  Conclusion Top


In a resource-poor setting with no laboratory support to confirm the diagnosis, it would be worthwhile to consider acyclovir in the management of clinically diagnosed severe HFMD cases. However, multicenter, randomized, controlled studies for severe cases of HFMD are required for validating the role of acyclovir.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Chatproedprai S, Theanboonlers A, Korkong S, Thongmee C, Wananukul S, Poovorawan Y, et al. Clinical and molecular characterization of hand-foot-and-mouth disease in Thailand, 2008-2009. Jpn J Infect Dis 2010;63:229-33.  Back to cited text no. 1
    
2.
Hagiwara A, Tagaya I, Yoneyama T. Epidemic of hand, foot and mouth disease associated with enterovirus 71 infection. Intervirology 1978;9:60-3.  Back to cited text no. 2
    
3.
Schmidt NJ, Lennette EH, Ho HH. An apparently new enterovirus isolated from patients with disease of the central nervous system. J Infect Dis 1974;129:304-9.  Back to cited text no. 3
    
4.
Zhu Z, Zhu S, Guo X, Wang J, Wang D, Yan D, et al. Retrospective seroepidemiology indicated that human enterovirus 71 and coxsackievirus A16 circulated wildly in central and Southern China before large-scale outbreaks from 2008. Virol J 2010;7:300.  Back to cited text no. 4
    
5.
Sasidharan CK, Sugathan P, Agarwal R, Khare S, Lal S, Jayaram Paniker CK, et al. Hand-foot-and-mouth disease in Calicut. Indian J Pediatr 2005;72:17-21.  Back to cited text no. 5
    
6.
Belazarian L, Lorenzo ME, Pearson AL, Sweeney SM, Wiss K. Exanthematous viral diseases. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: McGraw-Hill; 2012. p. 2360-2.  Back to cited text no. 6
    
7.
World Health Organization. A Guide to Clinical Management and Public Health Response for Hand, Foot and Mouth Disease (HFMD). Public Health; 2011.  Back to cited text no. 7
    
8.
Shin JU, Oh SH, Lee JH. A case of hand-foot-mouth disease in an immunocompetent adult. Ann Dermatol 2010;22:216-8.  Back to cited text no. 8
    
9.
Mathes AE, Oza V, Ilona J, Cordoro KM, Yagi S, Howard R, et al. “Eczema Coxsackium” and unusual cutaneous findings in an enterovirus outbreak. Pediatrics 2013;132:e149-e157.  Back to cited text no. 9
    
10.
Evans TY, Tyring SK. Advances in antiviral therapy in dermatology. Dermatol Clin 1998;16:409-19.  Back to cited text no. 10
    
11.
Wagstaff AJ, Faulds D, Goa KL, Cordoro KM, Yagi S, Howard R, et al. Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994;47:153-205.  Back to cited text no. 11
    
12.
Shelley WB, Hashim M, Shelley ED. Acyclovir in the treatment of hand-foot-and-mouth disease. Cutis 1996;57:232-4.  Back to cited text no. 12
    
13.
Rawlinson WD. Antiviral agents for influenza, hepatitis C and herpesvirus, enterovirus and rhinovirus infections. Med J Aust 2001;175:112-6.  Back to cited text no. 13
    
14.
Faulkner CF, Godbolt AM, DeAmbrosis B, Triscott J. Hand, foot and mouth disease in an immunocompromised adult treated with aciclovir. Australas J Dermatol 2003;44:203-6.  Back to cited text no. 14
    
15.
Chang LY, Lin TY, Huang YC, Tsao KC, Shih SR, Kuo ML, et al. Comparison of enterovirus 71 and coxsackie-virus A16 clinical illnesses during the Taiwan enterovirus epidemic, 1998. Pediatr Infect Dis J 1999;18:1092-6.  Back to cited text no. 15
    
16.
Gilbert GL, Dickson KE, Waters MJ, Kennett ML, Land SA, Sneddon M, et al. Outbreak of enterovirus 71 infection in victoria, Australia, with a high incidence of neurologic involvement. Pediatr Infect Dis J 1988;7:484-8.  Back to cited text no. 16
    
17.
Cooper DJ, Shaw DR, LaBrooy JT, Blumbergs P, Gilbert J, Simmons A, et al. Fatal rhabdomyolysis and renal failure associated with hand, foot and mouth disease. Med J Aust 1989;151:232-4.  Back to cited text no. 17
    
18.
Ogilvie MM, Tearne CF. Spontaneous abortion after hand-foot-and-mouth disease caused by coxsackie virus A16. Br Med J 1980;281:1527-8.  Back to cited text no. 18
    


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