Clinicopathologic analysis of atypical hand, foot, and mouth disease in adult patients

doi:10.1016/j.jaad.2016.10.022

Journal of the American Academy of Dermatology

Volume 76, Issue 4, April 2017, Pages 722-729

https://doi.org/10.1016/j.jaad.2016.10.022 Get rights and content

Background

Hand, foot, and mouth disease is a contagious viral infection usually affecting children. A resurgence of cases in adults, mainly caused by coxsackievirus A6 and with an atypical and more severe presentation, has taken place.

Objective

The goal was to examine the clinical, histologic, and immunohistochemical features of this disease in adults.

Methods

This is a retrospective study on documented cases of adult hand, foot, and mouth disease from France's Dermatology Department of Strasbourg University Hospital and Bel-Air Hospital in Thionville.

Results

Six patients with severe and atypical presentation were included, 4 caused by coxsackievirus A6. The histologic features were: spongiosis, neutrophilic exocytosis, massive keratinocyte necrosis, shadow cells in the upper epidermis, vacuolization of basal cells, necrotic cells in follicles and sweat glands, dense superficial dermal infiltrate of CD3⁺ lymphocytes, and strong granulysin expression.

Limitations

This is a retrospective case series.

Conclusion

In adult patients presenting with atypical hand, foot, and mouth disease caused by coxsackievirus A6, biopsy specimens show distinctive changes in the epidermis but also in adnexal structures. The inflammatory infiltrate is made of T cells with a cytotoxic profile, with numerous granulysin-positive cells, as observed in severe drug-induced eruption with necrosis of keratinocytes.

Section snippets

Methods

We performed a retrospective study of HFMD in adults occurring between July 2011 and July 2015 in 2 French dermatology departments. The patients were selected by consultation of hospitalization files, photographs, or biopsy specimens.

The criteria for inclusion were: age 18 years or older and HFMD proven by serology, positive polymerase chain reaction for enterovirus RNA, or a suggestive clinical picture with performance of a skin biopsy. The clinical criteria required in the absence of

Results

Nine cases were identified, of which 3 were excluded owing to the absence of virologic confirmation or biopsy specimen.

The main clinical data are presented in Table I. All patients had painful or pruritic erythematous lesions (sometimes grayish) and palmoplantar papulovesicles that spread to the back of the hands or feet (Fig 1, A and B). One had bullous lesions (Fig 1, B). In 5 patients the skin was diffusely affected: face (Fig 1, C), scalp, buttocks, thighs, genitalia, back, and upper limbs.

Discussion

HFMD is generally linked to coxsackievirus A16 or enterovirus 71. Its typical form usually results in moderate fever, vesicular enanthem of the oral mucosa, followed by a palmoplantar papulovesicular eruption, after an incubation period of 3 to 5 days. Recovery is spontaneous in 7 to 10 days.

Coxsackievirus A6 is generally responsible for herpangina. Since 2008, coxsackievirus A6–associated HFMD have become more frequent, with outbreaks in many countries, frequently affecting adults.12, 13, 14,

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Cited by (33)

Emerging infectious diseases of the skin: a review of clinical and histologic findings
2023, Human Pathology
Detecting Lesional Granulysin Levels for Rapid Diagnosis of Cytotoxic T lymphocyte–Mediated Bullous Skin Disorders
2021, Journal of Allergy and Clinical Immunology: In Practice
Citation Excerpt :
In addition, pathological examination using immunohistochemistry has revealed strong positive staining for CD8 and CD56, with granulysin in epidermal blisters.9 Another retrospective study has assessed the expression of granulysin by immunohistochemical evaluation in 6 adult-onset hand, foot, and mouth disease cases caused by the coxsackievirus A6 without obvious blistering, and demonstrated apparent granulysin mainly in the infiltrate around vessels of the papillary dermis, rather than within the epidermis.39 Interestingly, we identified 1 case of GvHD presenting bullous formation mimicking SJS/TEN, with an elevated granulysin level (228.7 ng/mL) in the blister fluid.
Bullous skin disorders are induced by different pathomechanisms and several are emergent, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Rapid diagnostic methods for SJS/TEN or cytotoxic T-lymphocyte (CTL)-mediated bullous disorders are crucial for early treatment. Granulysin, primarily expressed by CTLs, is a specific cytotoxic protein responsible for SJS/TEN and similar skin reactions.
To assess granulysin levels in blister fluids to differentiate SJS/TEN and similar CTL-mediated bullous reactions from other autoimmune bullous disorders.
Using ELISA, we measured granulysin in blister fluids from patients with bullous skin disorders, including SJS/TEN, erythema multiforme major, bullous fixed-drug eruption, bullous lupus erythematosus, paraneoplastic pemphigus, pemphigus vulgaris, bullous pemphigoid, purpura fulminans–related bullae, and hand-foot syndrome/hand-foot-skin reactions. We compared serum and blister granulysin levels in patients with SJS/TEN presenting varying severity, monitoring serial granulysin levels from acute to late stages.
Overall, 144 patients presenting with bullous skin disorders were enrolled. Blister granulysin levels (mean ± SD) in CTL-mediated disorders, including TEN (n = 28; 3938.7 ± 3475.7), SJS-TEN overlapping (n = 22; 1440.4 ± 1179.6), SJS (n = 14; 542.0 ± 503.2), erythema multiforme major (n = 7; 766.3 ± 1073.7), generalized bullous fixed-drug eruption (n = 10; 720.4 ± 858.3), and localized bullous fixed-drug eruption (n = 16; 69.0 ± 56.4), were significantly higher than in non–CTL-mediated bullous disorders (P < .0001), including bullous lupus erythematosus (n = 3; 22.7 ± 20.1), paraneoplastic pemphigus (n = 3; 20.3 ± 8.6), pemphigus vulgaris (n = 3; 4.4 ± 2.8), bullous pemphigoid (n = 18; 4.0 ± 2.7), purpura fulminans (n = 4; 5.9 ± 5.5), and hand-foot syndrome/hand-foot-skin reactions (n = 6; 4.6 ± 3.5). Blister granulysin levels correlated with clinical severity of SJS/TEN (P < .0001).
Determination of blister granulysin levels is a noninvasive and useful tool for rapid differential diagnosis of SJS/TEN and other similar CTL-mediated bullous skin disorders for treatment selection.
Cutaneous manifestations of enterovirus infections: An expanding clinical spectrum
2020, Annales de Dermatologie et de Venereologie
Atypical hand, foot and mouth disease in adults: A note on 6 cases
2020, Annales de Dermatologie et de Venereologie
Le syndrome main-pied-bouche (SMPB) est une dermatose virale connue chez l’enfant où sa présentation clinique est souvent caractéristique. Sa survenue chez l’adulte est plus rare, de présentation polymorphe et peut représenter un vrai défi diagnostique pour le clinicien.
Il s’agit d’une série de cas rétrospective de 2013 à 2018 de SMPB chez l’adulte, tous confirmés par amplification en chaîne par polymérase (PCR) positive à entérovirus. Nous avons étudié les caractéristiques cliniques, épidémiologiques, et virologiques de chaque patient.
Nous rapportons les cas de quatre hommes et deux femmes d’âge moyen 42,5 ans. Cinq patients avaient des lésions purpuriques étendues, quatre patients avaient des lésions bulleuses, trois patients avaient une atteinte cutanée pure sans atteinte des muqueuses et quatre patients avaient des lésions étendues sur le tronc. Deux patients ont présenté soit des lésions en cocarde et pustuleuses des extrémités, soit une plaque eczématiforme étendue avec une atteinte du cuir chevelu. Enfin, un purpura en nappe plantaire a été observé chez un patient.
Ces différents cas de SMPB chez l’adulte posent la question du diagnostic différentiel avec d’autres éruptions aiguës cutanéomuqueuses. La connaissance de ces présentations diverses chez l’adulte est essentielle afin de pouvoir établir le diagnostic et appliquer les conseils de prévention.
Hand, foot and mouth disease (HFMD) is form of viral dermatosis well known among the pediatric population, in whom it has a typical presentation. However, it is less common in adults, with a more heterogeneous presentation, potentially making diagnosis extremely challenging for the clinician.
This was a retrospective case series from 2013 to 2018 of HFMD in adults, with all cases being confirmed by cutaneous polymerase chain reaction (PCR). We studied the clinical, epidemiological and viral characteristics of each patient.
This series of 6 cases comprised 4 men and 2 women, with a mean age of 42.5 years. Five patients presented extended purpuric lesions, four had bullous lesions, and three showed cutaneous signs without any mucosal lesions. Extended lesions on the trunk were found in four patients. One patient presented rosette-shaped pustular lesions on the limbs, one had eczema-like lesions on the scalp, and one presented extended purpuric lesions on the soles.
These different cases of adult HFMD raise questions about differential diagnosis in relation to other acute cutaneous and mucous diseases. It is essential to be aware of these different types of presentation of the disease in order to determine the diagnosis and discuss preventive measures.
Management guidelines for pregnant health care workers exposed to infectious dermatoses
2020, International Journal of Women's Dermatology
Citation Excerpt :
Other features include widespread vesiculobullous and erosive lesions extending beyond the palms and soles, an eczema herpeticum-like eruption termed “eczema coxsackium,” and an eruption similar to Gianotti-Crosti in children (Mathes et al., 2013). There can also be occasional sparing of the oral mucosa (Second et al., 2017). Outbreaks of HFMD in adults that have been reported in the literature have typically occurred in adults after exposure to children with HFMD (Centers for Disease Control and Prevention [CDC] Morbidity and Mortality Weekly Report, 2012) or among college students (Buttery et al., 2015) and military trainees (Banta et al., 2016).
Exanthematous diseases are frequently of infectious origin, posing risks, especially for pregnant health care workers (HCWs) who treat them. The shift from cell-mediated (Th1 cytokine profile) to humoral (Th2 cytokine profile) immunity during pregnancy can influence the mother’s susceptibility to infection and lead to complications for both mother and fetus. The potential for vertical transmission must be considered when evaluating the risks for pregnant HCWs treating infected patients because fetal infection can often have devastating consequences. Given the high proportion of women of childbearing age among HCWs, the pregnancy-related risks of exposure to infectious diseases are an important topic in both patient care and occupational health. Contagious patients with cutaneous manifestations often present to dermatology or pediatric clinics, where female providers are particularly prevalent; a growing number of these physicians are female. Unfortunately, the risks of infection for pregnant HCWs are not well defined. To our knowledge, there is limited guidance on safe practices for pregnant HCWs who encounter infectious dermatologic diseases. In this article, we review several infectious exanthems, their transmissibility to pregnant women, the likelihood of vertical transmission, and the potential consequences of infection for the mother and fetus. Additionally, we discuss recommendations with respect to avoidance, contact, and respiratory precautions, as well as the need for treatment after exposure.
Hand-foot-mouth disease: Description of cases in Zaragoza
2020, Piel

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: Conflicts of interest: None declared.

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DermatopathologyClinicopathologic analysis of atypical hand, foot, and mouth disease in adult patients

Background

Objective

Methods

Results

Limitations

Conclusion

Section snippets

Methods

Results

Discussion

FEMS Microbiol Rev

J Am Acad Dermatol

J Clin Virol

J Clin Virol

Int J Infect Dis

J Microbiol Immunol Infect

Lancet Infect Dis

J Invest Dermatol

Two cases of hand, foot, and mouth disease involving the scalp

Acta Derm Venereol

Coxsackievirus A6 and hand, foot and mouth disease: three case reports of familial child-to-immunocompetent adult transmission and a literature review

Case Rep Dermatol

Dermatopathology
Clinicopathologic analysis of atypical hand, foot, and mouth disease in adult patients