Hand-Foot-and-Mouth Disease in Adults

Last Reviewed: September 15, 2023

Clinicians frequently see patients with common communicable illnesses. Adult patients with exposure to children may be particularly vulnerable to acquiring childhood ailments. Therefore, it is important that providers who care for adults also be familiar with common childhood illnesses and understand how they manifest in adults. Hand-foot-and-mouth disease (HFMD) is one such common childhood disease. Although HFMD is usually mild and self-limited in both children and adults, it is possible for the presentation to be much more severe and, in rare cases, lead to meningitis. Generally, HFMD presents with the much milder symptoms that are discussed in this review, which can nonetheless be distressing. Included in this exploration of HFMD is a recent case that has been presented to increase clinicians’ ability to recognize and treat HFMD within adult populations.

What is HFMD?

HFMD is a communicable disease caused by enteroviruses—most commonly coxsackievirus (CV) A16 or enterovirus (EV) 71.¹ It was first described in 1958 during an outbreak in Toronto, Ontario, Canada,^2,3 and most commonly occurs in children. HMFD is transmitted via fecal-oral, oral-oral, and respiratory routes. The virus can be found in the saliva, sputum, nasal mucus, blister fluid, and stool of an infected person. The virus quickly spreads through close personal contact, droplets in the air, contact with feces, or contact with contaminated objects, such as doorknobs and toys. Less commonly, HFMD can be transmitted if someone swallows poorly treated water in a swimming pool that has been contaminated with stool containing the virus.⁴

Epidemiology

HFMD is known worldwide, with reported outbreaks in multiple countries. For example, Australia has reported large outbreaks of EV 71 HFMD since 1986. The most recent outbreak, in which 119 children required hospitalization after presenting with fever, lethargy, myoclonus, and skin rash due to EV 71, lasted from December 2012 until May 2013.⁵

In the United States, HFMD is not a reportable condition. Thus, full statistics for the prevalence and incidence are not available. Large outbreaks are rare in the United States but often occur in Asia.⁵ Statistics are maintained in China, and approximately 1,900,000 cases and four deaths were reported in 2015. The World Health Organization provides reports that are available monthly.⁶

Transmission

The virus has an incubation period of 4 to 6 days, after which fever, malaise, sore throat with vesicles, and then hand vesicles develop. Viremia occurs as the virus replicates at sites, such as the skin, mucous membranes, central nervous system, and other organs.^6,7 Although affected people are most contagious during the first week, they can remain infectious for approximately 4 to 8 weeks after the onset of illness because of residual viral shedding in stool.⁸ Sometimes, people (especially adults) will not have symptoms but can still transmit the virus. HFMD is not transmitted to or from household pets or other animals.⁴ Transmission is usually between family members. Outbreaks tend to be seasonal in temperate climates, occurring more frequently in spring and summer.³

Signs and symptoms

In the United States, the typical case of HFMD is caused by CV A16 and occurs during the warmer months in children younger than 10 years of age.⁹ The median age of infected children is 19 months, and only 24% of children present with typical signs and symptoms of HFMD. The children initially have malaise and possibly fever; these are followed by characteristic mucocutaneous vesicular lesions in the oropharynx and on the hands and feet. Resolution of the symptoms and lesions takes 7 to 10 days. Cases may be more severe and prolonged in children younger than 2 years of age, including infants. In a typical case, bullae are rare¹⁰; however, one-third of patients present with a rash on their feet or buttocks,¹¹ which resolves in about 1 week.

Complications

Fortunately, complications are uncommon. Fingernail and toenail loss can occur but is temporary, and the nails grow back without treatment.^12,13 Rare cases of viral meningitis have been reported that required hospitalization. Even more unusual is encephalitis or paralysis, usually associated with EV 71 infection.¹⁴

Coxsackevirus A6 infection

Recently, severe worldwide outbreaks of HFMD have occurred caused by a strain of coxsackievirus that is less common than EV 71 or CV A16. This newly recognized strain, CV A6, affects both children and adults. The CV A6 strain was first identified in Finland in 2008 during a major outbreak of HFMD. Later outbreaks were detected across Asia and Europe.¹⁶ One outbreak of CV A6 HFMD occurred in Israel during the winter months¹⁶; CV A6 HFMD was diagnosed in five patients between December 2012 and February 2013. The occurrence of this cluster of cases during winter is not typical for HFMD in temperate regions.¹ At Boston Children’s Hospital in the winter of 2012, eight children between 4 months and 3 years of age had HFMD caused by CV A6. The illness was additionally characterized by perioral lesions and lesions on the dorsal surfaces of the hands.¹⁷

Case

Jeff was a 55-year-old married white man working as an attorney in a major city on the eastern coast of the United States. He had been healthy, with all immunizations up-to-date, and had not recently traveled. In late January 2014, Jeff developed fatigue, an elevated temperature, chills, and a sore throat. He noted multiple vesicles in the back of his throat. After 2 days, a pruritic eruption of small vesicles began on the dorsal and palmar surfaces of his hands. The vesicles increased rapidly and also appeared on the sole of one foot, along with a diffuse, raised rash on his lower trunk and upper buttocks. In addition to the vesicles, mild swelling of his hands developed. Over the next few days, the rash and discomfort dramatically increased to the point of causing severe pain; Jeff was unable to sleep and experienced uncontrolled itching. Because of the pain, he was no longer able to button his clothing or hold utensils to feed himself. The fever and symptoms continued during the week after onset. Jeff recorded a temperature of 100.8 degrees after taking ibuprofen. At this point—with the distressing symptoms and continued fever—Jeff sought treatment at an urgent care facility in his community (Figures 1 and 2).

Figure 1. Pruritic eruption of small vesicles on palm.

Other household members were healthy, without any reported recent illnesses. Jeff did like to visit and play with his 2-year-old grandson, who attended day care and had his usual share of viral illnesses.

Figure 2. Diffuse, raised rash on the lower trunk.

Based on Jeff’s presentation and his risk for exposure via his grandchild, the provider diagnosed HFMD but was concerned bout the extent of his discomfort and the severity of the hand rash, stating that it was the “worst case I have ever seen.” The provider attempted to schedule an appointment with an infectious disease specialist for a second opinion and guidance; however, an appointment was not available before 3 weeks. Jeff was sent home with an analgesic (300 mg of acetaminophen with 30 mg of codeine as needed every 6 hours) for pain and an antihistamine (25 mg of hydroxyzine by mouth three times a day) to relieve the itching and help him sleep. Both medications provided some relief. The day following the urgent care appointment, the vesicles continued to grow and enlarged into bullae; some appeared to contain blood or were surrounded by bruising (Figure 3).

Figure 3. Vesicles grow and enlarge into bullae.

After 1 week, the fever had resolved, the rash on his lower back and buttocks had also faded, and the vesicles were in various stages of healing. Jeff was able to move his hands, the swelling decreased, and he could maintain basic self-care. Other vesicles had opened and drained serosanguinous fluid. These vesicles were reported to be the most painful. After a few more days, the vesicles dried and formed crusts.

What is usually a mildly annoying child’s illness caused 3 weeks of despair for this male adult patient. It resulted in 2 weeks of missed work and the need for more than 1 month of care for his hands as the affected areas healed. His healing hands drew attention, particularly while he was in public and especially when he was expected to shake hands with clients at work. After 3 months, remnants of scars remained on Jeff’s hands.

*end of case

Approach to the patient with suspected HFMD

Diagnosis

HFMD is usually diagnosed by history and physical examination. In the presented case, Jeff had frequent contact with his grandchild, who was younger than 4 years of age, so the grandson was the likely source of the illness. The rash usually consists of papules and vesicles, 2 to 6 mm in size, on the gingiva, buccal mucosa, tongue, and pharynx. Lesions may also be found on the skin of the hands, feet, buttocks, and genitalia.¹¹ Of note, the presentation of CV A6 HFMD has some atypical features: lesions on the dorsal surfaces of the hands, areas of eczema, and large purpuric vesicles/bullae.¹⁸ Fever and malaise are often present. CV A6 HFMD has been reported to present with more bothersome symptomatology.

Cases of HFMD caused by CV A6 may occur seasonally and have the appearance of typical cases caused by other strains; however, clustered cases of CV A6 HFMD in Scotland and the United States were noted between October and February, whereas typical HFMD outbreaks take place in the summer and early autumn. Untimely presentations may cause providers to miss the diagnosis. Four children were admitted to a hospital in Edinburgh, United Kingdom, during winter. Initially, these patients were treated with acyclovir for a feared diagnosis of eczema herpeticum; afterward, however, molecular typing identified CV A6.¹⁹

What about the rash on Jeff’s trunk and buttocks? Some literature emphasizes that HFMD should be recognized as hand-foot-and-mouth and buttock disease because lesions appear on the buttocks in one-third of cases. Jeff’s illness occurred in winter.¹¹ As noted, HFMD occurs more commonly in temperate climates during the summer and fall, but outbreaks of CV A6 HFMD can occur in winter. A cluster of cases of CV A6 HFMD was noted in the United States between November 2013 and December 2014.^1,19 CV A6 HFMD also tends to have a more severe course that includes erosive lesions that may be purpuric, and it affects the buttocks.¹⁵ In late disease, desquamation of the hands and feet may have a clinical presentation similar to that of certain fungal infections.¹⁶

A culture specimen can be sent for laboratory analysis, but this is not always readily available and is rarely done. The virus is found and can be cultured from skin  or oral lesions or from stool specimens. The best place to swab for a sample is an oral lesion; however, if there are no vesicles, a rectal swab can be performed.²⁰ The culture result may take longer than 2 weeks, at which point the patient should be recovering.²¹ A culture can be helpful to determine the strain, guide the care of household contacts, and determine whether an outbreak is occurring. Polymerase chain reaction (PCR) and microarray technology can be used to identify the causative virus. Different healthcare settings may have a variety of specific assays.²⁰ An infectious disease consult is rarely necessary but is nevertheless recommended in questionable cases or when the patient is known to be immunosuppressed.

Differential diagnosis

HFMD can be confused with another vesicular eruption, such as herpes simplex or varicella-zoster virus infection.¹⁷ The differential diagnosis in an adult can include a variety of conditions with cutaneous manifestations, including varicella-zoster virus infection, drug reaction, eczema herpeticum, secondary syphilis, and bullous impetigo.^{18, 22, 23} Other viral infections caused by CV strains or versions of the echovirus can present with herpangina but are usually accompanied by a high fever. Aphthous stomatitis may have the appearance of HFMD with oral ulcerations, but the ulcerations are larger than those in HFMD, are not associated with fever, and may be recurrent.^20,21

Eczema herpeticum is a serious skin infection that occurs as a secondary herpesvirus infection within preexisting lesions of atopic dermatitis or another erosive dermatosis. It usually occurs in children and young adults with a history of eczema in which the skin has become compromised and is easily invaded by the herpesvirus. The rash spreads and appears as scattered umbilicated lesions. Eczema herpeticum can become a fulminant disease with systemic symptoms and involvement. Those most at risk are children who have atopic dermatitis or who are immunocompromised. It carries a 10% mortality rate.²⁴

A drug reaction typically presents in the form of pruritic skin lesions. Stevens-Johnson syndrome can be due to a drug reaction. The characteristic features of Stevens-Johnson syndrome include a rapidly developing blistering exanthema and target-like lesions accompanied by mucosal involvement and skin detachment.²⁵ In 2010–2012 in Taiwan, 21 cases of CV A6 HFMD were initially treated as suspected severe drug reactions affecting the skin.²⁵ A drug may be responsible for skin reactions and should always be considered, especially in cases with an atypical clinical presentation, such as that of CV A6 HFMD.²⁵ Drug-induced hypersensitivity syndrome (DIHS) is a multiple-organ drug reaction previously known as drug reaction with eosinophilia and systemic symptoms (DRESS). The former term is now used because eosinophilia is not always present. HFMD is usually limited, milder than DIHS, does not involve organs, other than the skin and mucus membranes and does not lead to full-thickness epidermal necrosis.²⁵

Other childhood illnesses can present with a rash and may be included in the differential diagnosis. A 43-year-old patient in Connecticut developed 2- to 9-mm pink-red papules and papulovesicles on the left forearm, dorsal surfaces of the hands, palms, fingers, and one toe. Small vesicles and erosions were also present on the hard palate and soft palate. The provider ordered a complete blood cell count and PCR of serum for parvovirus B19. The blood cell count was normal, and the result of the test for parvovirus B19 was negative. However, the result of reverse transcriptase (RT)-PCR4 of plasma for enterovirus was positive. A test for viral typing sent to the Centers for Disease Control and Prevention confirmed CV A6 infection.²⁶

Treatment

The treatment of HFMD is supportive and includes consideration of reducing transmission. In Jeff’s case, the primary symptoms were itching and pain from the lesions. He was treated with analgesics and antihistamines for symptom control. He was encouraged to rest, stay away from the workplace with his active lesions and fever, and increase his fluid intake. Cool liquids and the avoidance of acidic and spicy foods are preferred. If lesions in the mouth are severe to the point that they limit intake, intravenous hydration may be necessary.²⁰ To prevent transmission, Jeff should practice frequent handwashing, especially after touching any blisters or using the bathroom and before eating. Although it is assumed that Jeff was exposed to HFMD via his grandchild, he should stay away from children while he is febrile with active lesions. Institutional outbreaks are possible with children, and contact precautions are recommended in healthcare settings. As new cases of CV A6 HFMD appear and affect adults with an atypical presentation, increased vigilance may become necessary to recognize outbreaks.¹⁷

At Jeff’s home, contaminated surfaces and items should be washed and disinfected with dilute chlorine bleach. Jeff should avoid close contact with others while infected—refraining from hugging, kissing, and sharing utensils. Contacts should be observed for the development of symptoms.²⁷ At this time, there is no vaccine for the viruses responsible for HFMD3; however, research is ongoing to develop small-animal models for testing possible vaccines.²⁸

Conclusion

HFMD may often go undiagnosed in adults because the clinicians who treat them are relatively inexperienced in identifying childhood illnesses. This case, diagnosed as HFMD on the basis of the clinical presentation, deviated from what has been commonly seen in the past. Jeff’s lesions were larger and clinically more symptomatic than those commonly seen in children. Fortunately, with some symptomatic support, Jeff’s lesions healed, and he experienced no sequelae. Perhaps he did have HFMD from CV A6. As outbreaks occur, it will be essential for primary care providers to be aware of the adult presentation of HFMD and the newer strain of CV A6.

References

1. Ben-Chetrit E, Wiener-Well Y, Shulman LM, et al. Coxsackievirus A6-related hand foot and mouth disease: skin manifestations in a cluster of adult patients. J Clin Virol. 2014;59:201-203.
2. 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. 1958;79:615-621.
3. Nassef C, Ziemer C, Morrell DS. Hand-foot-and-mouth disease: a new look at a classic viral rash. Curr Opin Pediatr. 2015;27:486-491.
4. Centers for Disease Control and Prevention. Hand, foot, and mouth disease. Causes & transmission. Transmission. http://www.cdc.gov/hand-foot-mouth/about/transmission.html. Updated January 6, 2017. Accessed July 2, 2017.
5. Zander A, Britton PN, Navin T, et al. An outbreak of enterovirus 71 in metropolitan Sydney: enhanced surveillance and lessons learned. Med J Aust. 2014;201:663-666.
6. Centers for Disease Control and Prevention. Hand, foot, and mouth disease (HFMD). http://www.cdc.gov/hand-foot-mouth. Updated January 6, 2017. Accessed July 2, 2017.
7. World Health Organization. Hand, foot, and mouth disease situation update number 478. http://www.wpro.who.int/emerging_diseases/hfmd-biweekly_20151229.pdf?ua=1. December 29, 2015. Accessed July 2, 2017.
8. Romero JR. Hand, foot, and mouth disease and herpangina: an overview. Up to Date. http://www.uptodate.com/contents/hand-foot-and-mouth-disease-and-herpangina-an-overview. Updated June 27, 2017. Accessed July 2, 2017.
9. Buttery V, Kenyon C, Grunewald S, Oberste MS, Nix WA. Atypical presentations of hand, foot, and mouth disease caused by coxsackievirus A6 — Minnesota, 2014. MMWR Morb Mortal Wkly Rep. 2015;64:805.
10. Ventarola D, Bordone L, Silverberg N. Update on hand-foot-and-mouth disease. Clin Dermatol. 2015; 33:340-346.
11. Matsuzawa M, Ishii A, Demitsu T, Sugawara H. Coxsackie A16 virus-associated atypical hand-foot-and-mouth disease. Intern Med. 2014;53:643-644.
12. Abramovici G, Keoprasom N, Winslow CY, Tosti A. Onycholysis and subungual haemorrhages in a patient with hand, foot and mouth disease. Br J Dermatol. 2014;170:748-749.
13. Cuppari C, Manti S, Arrigo T, Salpietro C. Not only fever and palmoplantar vesicular eruption. Infection. 2014;42:947-948.
14. Centers for Disease Control and Prevention. Hand, foot, and mouth disease (HFMD). Complications. http://www.cdc.gov/hand-foot-mouth/about/complications.html. Updated January 6, 2017. Accessed July 2, 2017.
15. Mathes EF, Oza V, Frieden IJ, et al. “Eczema coxsackium” and unusual cutaneous findings in an enterovirus outbreak. Pediatrics. 2013;132:e149-e157. doi:10.1542/peds.2012-3175.
16. Downing C, Ramirez-Fort MK, Doan HQ, et al. Coxsackievirus A6 associated hand, foot and mouth disease in adults: clinical presentation and review of the literature. J Clin Virol. 2014;60:381-386.
17. Flett K, Youngster I, Huang J, et al. Hand, foot, and mouth disease caused by coxsackievirus A6. Emerg Infect Dis. 2012;18:1702-1704.
18. Feder H, Bennett N, Modlin J. Atypical hand, foot, and mouth disease: a vesiculobullous eruption caused by Coxsackie virus A6. Lancet. 2014;14:83-86.
19. Sinclair C, Gaunt E, Simmonds P, et al. Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014. Euro Surveill. 2014;19:20745.
20. Nervi SJ. Hand-foot-and-mouth disease (HFMD) workup. http://emedicine.medscape.com/article/218402-workup. Medscape. Updated June 16, 2017. Accessed July 2, 2017.
21. Johns Hopkins Medicine Health Library. Hand-foot-and-mouth disease. http://www.hopkinsmedicine.org/healthlibrary/conditions/adult/pediatrics/hand-foot-and-mouth_disease_90,p01857. Accessed April 23, 2016.
22. Baughn RE, Musher DM. Secondary syphilitic lesions. Clin Microbiol Rev. 2005;18:205-216.
23. Kazlouskaya V, Wittmann C, Tsikhanouskaya I. Pustular secondary syphilis: report of three cases and review of the literature. Int J Dermatol. 2014;53:e428-e431. doi: 10.1111/ijd.12337.
24. Blanter M, Vickers J, Russo M, Sarai B. Eczema herpeticum: would you know it if you saw it? Pediatr Emerg Care. 2015;31:586-588.
25. Chung W, Shih S, Chang C, et al. Clinicopathologic analysis of coxsackievirus A6 new variant induced widespread mucocutaneous bullous reactions mimicking severe cutaneous adverse reactions. J Infect Dis. 2013;208:1968-1978.
26. Lott JP, Liu K, Landry ML, et al. Atypical hand-foot-and-mouth disease associated with coxsackievirus A6 infection. J Am Acad Dermatol. 2013;69:736-741.
27. World Health Organization. Western Pacific Region. Hand, foot, and mouth disease. http://www.wpro.who.int/mediacentre/factsheets/fs_10072012_HFMD/en/. July 10, 2012. Accessed July 2, 2017.
28. Caine EA, Fuchs J, Das SC, Partidos CD, Osorio JE. Efficacy of a trivalent hand, foot, and mouth disease vaccine against enterovirus 71 and coxsackie viruses A16 and A6 in mice. Viruses. 2015;7:5919-5932.

From the September 01, 2017 Issue of Clinical Advisor