Dermatologic Manifestations of Enteroviral Infections 

  • Author: Susanna Nogués-Siuraneta, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jul 12, 2010
 

Background

The human enterovirus genus is a member of the Picornaviridae family of small, icosahedral, single-stranded, positive-sense RNA viruses. A total of 92 serotypes are currently recognized by the International Committee on Taxonomy of Viruses classification[1] :

  • Human enterovirus type A (17 serotypes): These include coxsackie A virus types 2-10, 12, 14, and 16 and echovirus type 71. New enterovirus serotypes were described in 2005 (types 76, 89, 90, and 91), and it is believed that they are a subgroup of human enterovirus type A.[2]
  • Human enterovirus type B (56 serotypes): These include coxsackie A virus type 9; coxsackie B virus types 1-6; echovirus types 1-7, 9, 11-21, 24-27, and 29-33; and enterovirus type 69. The 13 new serotypes reported in 2007 (enterovirus types 79-88, 97, 100, and 101) are probably members of human enterovirus type B.[2]
  • Human enterovirus type C (16 serotypes) - The most well known are coxsackie A virus types 1, 11, 13, 15, 17-22, and 24. Poliovirus types 1-3 have been included in this group.
  • Human enterovirus type D - Enterovirus types 68 and 70, including several newly identified serotypes, such as enterovirus 73-75[3, 4] and enterovirus types 77-78[5]

Human enteroviruses are distributed worldwide, with 2 major patterns of infections, endemic and epidemic, within a given geographical area.[1]

Enteroviruses usually cause transient, often subclinical, infections. Enteroviruses are also responsible for a wide variety of syndromes, including exanthematic fever, enteritis, encephalitis, aseptic meningitis, myocarditis, and respiratory tract infections. Coxsackieviruses, echoviruses, and enterovirus type 71 are also significant causes of cutaneous disease. A relationship between enterovirus RNA and chronic fatigue syndrome has been described,[6] and these viruses could initiate and perpetuate the immunological response seen in chronic fatigue syndrome.

Coxsackieviruses are separated into 2 groups, A and B. Coxsackie A viruses are the primary etiologic agents of herpangina and hand-foot-and-mouth disease (HFMD). Coxsackie B viruses are associated with epidemic pleurodynia (ie, Bornholm disease), epidemic myalgia, myocarditis, and pericarditis. Bowles et al suggest that coxsackie B virus may be an etiologic agent of juvenile dermatomyositis.[7]

Zahorsky first described the clinical spectrum of herpangina in 1920. Later, coxsackie A virus was isolated from pharyngeal washings and stool samples of patients with herpangina. Subsequently, many reports have confirmed this association. Robinson et al first isolated the coxsackie A virus type 16 serotype in 1957 during a Canadian epidemic of exanthema and stomatitis.[8] Two years later, Alsop et al used the term hand-foot-and-mouth disease to describe a similar eruption in England.[9]

Echoviruses include 34 distinct serotypes, and at least half can cause a rash. The 2 skin diseases specifically associated with echoviruses are Boston exanthem disease (BED), caused by echovirus type 16, and eruptive pseudoangiomatosis, (EP) caused by echovirus types 25 and 32.

Next

Pathophysiology

Enteroviruses are spread from person to person by oral-oral and fecal-oral routes and, because the virus can be isolated from cutaneous and ocular lesions, presumably, may also be transmitted through direct contact with fluid from these cutaneous and ocular lesions.

Another source of infection could be swimming pools because enteroviruses are easily detectable in natural and treated water sources.

It has been suggested that enteroviruses can be transmitted antenatally, either transplacentally or potentially via ascending infection. When maternal enterovirus infection is acquired during late pregnancy, vertical transmission has been shown to be relatively common.[2]

The viral incubation period is usually 2-5 days. The viruses are highly contagious, and they are a common cause of widespread outbreaks. After the ingestion of infectious material, enteroviruses are implanted and replicated in the alimentary tract (nasopharynx and ileum). If local replication is limited, the disease remains asymptomatic. If the virus passes into the regional lymphatic nodes and the reticuloendothelial system organs, minor or nonspecific disease may develop. Virus may also spread by the hematologic route, which results in a more severe and characteristically systemic illness.

Immune activation by the enterovirus leads to the production of immunoglobulin M (IgM) type-specific antibodies, which may be detected in the serum 1 week after infection. They are responsible for neutralization and rapid elimination of the virus from the blood and other sites of implantation. Serum IgM antibodies can be detected for 6 months after the patient's recovery, and convalescent immunoglobulin G can be detected for 1-2 years. Most enteroviral infections confer lifelong immunity to the serotype-specific agent. In addition, antibodies to these related viruses are known to cross-react, and they do so in different patterns, based on the country, serotype, and specific population, making comparisons of disease-based studies amongst these groups difficult.

Previous
Next

Epidemiology

Frequency

United States

Although enteroviruses are responsible for an estimated 50 million infections and 30,000-50,000 hospitalizations each year, note that less than 1% of infections result in significant symptomatic illness and the vast majority of hospitalizations are for aseptic meningitis.[10]

International

The frequency is not known, but some estimates put the number at 1 billion or more annually worldwide. Persons in lower socioeconomic groups are more frequently affected than persons in other groups.

Mortality/Morbidity

Occasionally, cardiac and neurological complications occur. Deaths in neonates infected with enteroviruses have been reported. They are usually the result of fulminant myocarditis.

When viral transmission is antenatal, neonatal enterovirus infection is very severe and has a poor outcome.[2]

Sex

Some authors suggest a slight male predominance, but this has not been confirmed.

Age

Enteroviral infections mainly affect children younger than 10 years, probably because they lack cross-reacting immunity resulting from repeated exposures, but they are not uncommon in adults.

Previous
 
 
Contributor Information and Disclosures
Author

Susanna Nogués-Siuraneta, MD  Resident, Department of Dermatology, Hospital Clinic de Barcelona

Disclosure: Nothing to disclose.

Coauthor(s)

Mercè Alsina-Gibert, MD  Consultant, Department of Dermatology, Hospital Clinic, Spain

Disclosure: Nothing to disclose.

Steven Brett Sloan, MD  Assistant Professor, Department of Dermatology, University of Connecticut School of Medicine; Director of Nail Disease Clinic and Chief of Dermatology, Newington Veterans Affairs Medical Center

Steven Brett Sloan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Connecticut State Medical Society, New England Dermatological Society, and Texas Dermatological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Michelle Pelle, MD  Clinical Assistant Professor, Division of Dermatology, Department of Medicine, University of California at San Diego

Michelle Pelle, MD is a member of the following medical societies: American Academy of Dermatology, California Medical Association, Medical Dermatology Society, and Pennsylvania Medical Society

Disclosure: Nothing to disclose.

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Lester F Libow, MD  Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Texas Medical Association

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References
  1. Trallero G, Avellon A, Otero A, et al. Enteroviruses in Spain over the decade 1998-2007: virological and epidemiological studies. J Clin Virol. Feb 2010;47(2):170-6. [Medline].

  2. Tebruegge M, Curtis N. Enterovirus infections in neonates. Semin Fetal Neonatal Med. Aug 2009;14(4):222-7. [Medline].

  3. Oberste M, Schnurr D, Maher K, al-Busaidy S, Pallansch M. Molecular identification of new picornaviruses and characterization of a proposed enterovirus 73 serotype. J Gen Virol. Feb 2001;82:409-16. [Medline].

  4. Oberste MS, Michele SM, Maher K, et al. Molecular identification and characterization of two proposed new enterovirus serotypes, EV74 and EV75. J Gen Virol. Nov 2004;85:3205-12. [Medline].

  5. Norder H, Bjerregaard L, Magnius L, Lina B, Aymard M, Chomel JJ. Sequencing of 'untypable' enteroviruses reveals two new types, EV-77 and EV-78, within human enterovirus type B and substitutions in the BC loop of the VP1 protein for known types. J Gen Virol. Apr 2003;84:827-36. [Medline].

  6. Chia JK. The role of enterovirus in chronic fatigue syndrome. J Clin Pathol. Nov 2005;58(11):1126-32. [Medline]. [Full Text].

  7. Bowles NE, Dubowitz V, Sewry CA, Archard LC. Dermatomyositis, polymyositis, and Coxsackie-B-virus infection. Lancet. May 2 1987;1(8540):1004-7. [Medline].

  8. Robinson CR, Doane FW, Rhodes AJ. Report of an outbreak of febrile illness with pharyngeal lesions and exanthem: Toronto, summer 1957; isolation of group A Coxsackie virus. Can Med Assoc J. Oct 15 1958;79(8):615-21. [Medline]. [Full Text].

  9. Alsop J, Flewett TH, Foster JR. "Hand-foot-and-mouth disease" in Birmingham in 1959. Br Med J. Dec 10 1960;2(5214):1708-11. [Medline]. [Full Text].

  10. Enterovirus surveillance--United States, 1997-1999. MMWR Morb Mortal Wkly Rep. Oct 13 2000;49(40):913-6. [Medline].

  11. Prose NS, Tope W, Miller SE, Kamino H. Eruptive pseudoangiomatosis: a unique childhood exanthem?. J Am Acad Dermatol. Nov 1993;29(5 Pt 2):857-9. [Medline].

  12. Mirkovic RR, Kono R, Yin-Murphy M, Sohier R, Schmidt NJ, Melnick JL. Enterovirus type 70: the etiologic agent of pandemic acute haemorrhagic conjunctivitis. Bull World Health Organ. 1973;49(4):341-6. [Medline]. [Full Text].

  13. Mirkovic RR, Schmidt NJ, Yin-Murphy M, Melnick JL. Enterovirus etiology of the 1970 Singapore epidemic of acute conjunctivitis. Intervirology. 1974;4(2):119-27. [Medline].

  14. Yaffee HS. Erythema multiforme caused by Coxsackie B5. A possible association with epidemic pustular stomatitis of children. Arch Dermatol. Nov 1960;82:737-9. [Medline].

  15. Jaidane H, Sane F, Gharbi J, Aouni M, Romond MB, Hober D. Coxsackievirus B4 and type 1 diabetes pathogenesis: contribution of animal models. Diabetes Metab Res Rev. Oct 2009;25(7):591-603. [Medline].

  16. Richer MJ, Horwitz MS. Coxsackievirus infection as an environmental factor in the etiology of type 1 diabetes. Autoimmun Rev. Jun 2009;8(7):611-5. [Medline].

  17. Ooi MH, Solomon T, Podin Y, et al. Evaluation of different clinical sample types in diagnosis of human enterovirus 71-associated hand-foot-and-mouth disease. J Clin Microbiol. Jun 2007;45(6):1858-66. [Medline]. [Full Text].

  18. Michos AG, Syriopoulou VP, Hadjichristodoulou C, et al. Aseptic meningitis in children: analysis of 506 cases. PLoS One. Aug 1 2007;2(7):e674. [Medline].

  19. Piqueur et al. Improvement of a real-time RT-PCR asay for the detection of enterovirus RNA. Virology Journal. 2009;6:95.

  20. Haneke E. Electron microscopic demonstration of virus particles in hand, foot and mouth disease. Dermatologica. 1985;171(5):321-6. [Medline].

  21. Parra CA. Hand, foot and mouth disease. Light and electron microscopic observations. Arch Dermatol Forsch. 1972;245(2):147-53. [Medline].

  22. Parra CA. Hand, foot and mouth disease. Light and electron microscopic observations. Arch Dermatol Forsch. 1972;245(2):147-53. [Medline].

  23. Goodfellow IG, Evans DJ, Blom AM, et al. Inhibition of coxsackie B virus infection by soluble forms of its receptors: binding affinities, altered particle formation, and competition with cellular receptors. J Virol. Sep 2005;79(18):12016-24. [Medline]. [Full Text].

  24. Werk D, Schubert S, Lindig V, et al. Developing an effective RNA interference strategy against a plus-strand RNA virus: silencing of coxsackievirus B3 and its cognate coxsackievirus-adenovirus receptor. Biol Chem. Sep 2005;386(9):857-63. [Medline].

  25. Rotbart HA, Webster AD. Treatment of potentially life-threatening enterovirus infections with pleconaril. Clin Infect Dis. Jan 15 2001;32(2):228-35. [Medline].

  26. Waldfahrer F, Iro H. Successful treatment of herpangina with allopurinol mouthwashes. Laryngoscope. Dec 1995;105(12 Pt 1):1405. [Medline].

  27. Lee BE, Davies HD. Aseptic meningitis. Curr Opin Infect Dis. Jun 2007;20(3):272-7. [Medline].

  28. Nathan M, Walsh R, Hardin JT, et al. Enteroviral sepsis and ischemic cardiomyopathy in a neonate: case report and review of literature. ASAIO J. Sep-Oct 2008;54(5):554-5. [Medline].

  29. Ornoy A, Tenenbaum A. Pregnancy outcome following infections by coxsackie, echo, measles, mumps, hepatitis, polio and encephalitis viruses. Reprod Toxicol. May 2006;21(4):446-57. [Medline].

  30. Evans AD, Waddington E. Hand, foot and mouth disease in south Wales, 1964. Br J Dermatol. Jun 1967;79(6):309-17. [Medline].

  31. Haley JC, Hood AF. Hand-foot-and-mouth disease. In: Fitzpatrick's Dermatology in General Medicine. Vol 2. New York, NY: McGraw-Hill; 1999:2403-7.

  32. Pallansch MA. Acute hemorrhagic conjunctivitis. In: Strickland GT, ed. Hunter's Tropical Medicine. Philadelphia, Pa: WB Saunders; 2000:226-7.

  33. Pallansch MA, Roos RP. Enteroviruses: polioviruses, coxsackieviruses, echoviruses, and newer enteroviruses. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE, eds. Fields' Virology. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:723-75.

  34. Pindborg JJ. Atlas of Diseases of the Oral Mucosa. 4th ed. Copenhagen, Denmark: WB Saunders; 1985:36-8.

  35. Raskin CA, Parrot RH. Herpangina. In: Fitzpatrick's Dermatology in General Medicine. Vol 2. New York, NY: McGraw-Hill; 1999:2407-9.

  36. Sterling JG, Kurtz JB. Viral infections. In: Rook/Wilkinson/Ebling Textbook of Dermatology. Vol 2. London, England: Blackwell Science; 1998:995-1096.

Previous
Next
 
Erosions on the base of the tongue.
A red halo surrounds several vesicles on the finger flexures and palms.
Small linear vesicle on the thumb.
Vesicle on the dorsal hand of a young adult.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.