DOI: 10.1111/pde.

14550

Pediatric
CASE REPORT Dermatology

Alopecia totalis following hand-­foot-­and-­mouth disease

Sandra Oska BS1  | Lisa M. Bedford MD2 | Geoffrey A. Potts MD2

1
Oakland University William Beaumont
School of Medicine, Rochester, MI, USA Abstract
2
Department of Dermatology, Wayne State We present a case of a 13-­month-­old male patient with alopecia totalis that began
University, Dearborn, MI, USA
two months after an episode of hand-­foot-­and-­mouth disease. It is hypothesized that
Correspondence the viral infection triggered an autoimmune response, which lead to production of
Geoffrey A. Potts, MD, Department of
lymphocytes targeting an antigen present in the hair bulb. Future research is neces-
Dermatology, Wayne State University,
Dearborn, MI 48124, USA. sary to determine whether and how the pathophysiology of alopecia totalis may be
Email: gpotts@med.wayne.edu
triggered by viral infection.

KEYWORDS

alopecia totalis, hand-­foot-­and-­mouth disease, pediatric dermatology

1   | I NTRO D U C TI O N
Hand-­foot-­and-­mouth disease (HFMD) is a common childhood viral
infection caused most commonly by coxsackievirus A16.1 Enterovirus
71 may also cause HFMD with higher risk of subsequent cardiopul-
2
monary and neurologic complications. Classic presenting features
of HFMD include fever, oral enanthem, and acral papules and vesi-
cles, although lesions may present on the buttocks and extremities
in the atypical type. The oral enanthem consists of ulcerations of
the buccal and pharyngeal mucosa.3 Treatment is supportive, with
the vast majority of affected individuals recovering spontaneously
within 7-­10 days.3
Additional dermatologic findings may present after resolution of
primary HFMD lesions. Onychomadesis, or nail shedding, has been
described as a late complication of HFMD, occurring 1-­2 months
after infection. HFMD has also been associated with alopecia areata
(AA), with an increase in pediatric AA cases noted following HFMD
4
outbreaks. We present a case of alopecia totalis associated with
HFMD.
area. A family history of thyroid disease was found but no alopecia
areata, vitiligo, or other autoimmune conditions. Family history was
significant for atopic dermatitis, and the patient did have mild atopic
dermatitis of the arms and back. Prior to presentation, eyebrows,
eyelashes, and fingernails appeared normal. On physical examina-
tion, there was near complete loss of terminal hairs on the scalp
with few vellus hairs present (Figure 1). Thinning of the eyebrows
and eyelashes was found (Figure 2). Regular pitting was noted on
the fingernails (Figure 3). Teeth development was normal. Thyroid
function tests were within normal limits. Hydrocortisone cream
was prescribed for the eyebrows, and triamcinolone cream was pre-
scribed for the scalp with minimal improvement in hair growth after
2 months. Treatment for the scalp was changed to augmented beta-
methasone 0.05% ointment with temporary increase in terminal hair
growth on the occipital scalp after two months, followed by loss of
those terminal hairs five months later after a lapse in treatment due
to social factors. At nine months following initial presentation, there
were minimal terminal hairs scattered over scalp, although eyebrows
and eyelashes had an increased number of hairs.

2   |  C A S E PR E S E NTATI O N 3   |  D I S C U S S I O N

A 13-­month-­old male patient with otherwise normal development
and previously normal hair growth presented to the dermatology
clinic with asymptomatic hair loss affecting the scalp, eyebrows, and
eyelashes of two-­month duration. Past medical history was signifi-
cant for an episode of HFMD two months prior to the onset of hair
loss. His parents denied previous history of alopecia or trauma to the
Alopecia areata has previously been reported to be triggered by viral
infections such as H1N1 influenza and Epstein-­Barr virus infectious
mononucleosis.5,6 Alopecia universalis has been reported in patients
with HIV infection.7-­9 Also, acute diffuse and total alopecia of the
scalp has occurred in a 65-­year-­old female patient with Borrelia in-
fection (acrodermatitis chronica atrophicans).10

Pediatric Dermatology. 2021;00:1–3. wileyonlinelibrary.com/journal/pde© 2021 Wiley Periodicals LLC.     1 |

 |
2       Pediatric OSKA et al.
Dermatology
A previous epidemiological study demonstrated an increase in
pediatric AA cases following an outbreak of atypical HFMD.4 In that
study, 42 cases of HFMD were diagnosed within an eight-­week pe-
riod, followed by the diagnosis of four cases of AA in four weeks. In
the eleven months prior to the HFMD outbreak, only three alopecia
cases had been diagnosed.4 However, none of the children with AA in
that study had been diagnosed with HFMD in the previous months.
Given the known association of enteroviral infections and other dis-
eases such as type I diabetes, a common pathophysiology for entero-
viral infections triggering alopecia was found.4,11 It is thought that
the body's inflammatory response to the viral infection leads to ab-
errant proliferation of autoreactive T cells.12
The proximal anagen hair follicle is an immune privileged site.13
Immune privilege is maintained by the absence of (or minimal) MHC
I expression and local production of immunosuppressants, such
as TGF-­β1, interleukin (IL)-­10, and α-­melanocyte stimulating hor-
F I G U R E 1   Near complete loss of terminal hairs on scalp mone (MSH).14 Collapse of this immune privilege may lead to AA.
with few vellus hairs present
Interferon-­γ has specifically been shown to upregulate MHC I ex-
pression, and it is thought that the Th1 response induced by viral
infections activates this pathway.12 The “swarm of bees” is the cor-
responding characteristic histopathological feature in active AA le-
sions, in which there is peribulbar lymphocytic infiltration comprised
of CD8+ and CD4+ T cells.13 TGF-­β1, IL-­10, and α-­MSH have been
shown to decrease MHC I expression and restore immune privilege
to tissue; upregulation of these may serve as a future treatment op-
tion for AA.14 Downregulation of chemotactic cytokines could also
help reverse AA.12 These may be future directions for treatment of
alopecia, as well as other diseases with collapse of immune privilege
such as multiple sclerosis, autoimmune uveitis, and fetal or allograft
rejection.14
Although HFMD outbreaks have been linked to AA, we report
a case of alopecia totalis following HFMD. While it is possible that
the two diagnoses are coincidental, we believe that the presentation
of both within such a short time frame in a healthy child implies a
F I G U R E 2   Sparse hairs noted over frontal scalp with thinning
common pathophysiology. We hypothesize that the viral infection
of eyebrows and eyelashes
triggered a Th1 immune response, upregulating MHC I expression
on hair follicles. This cascade led to activation of autoreactive T cells
and alopecia. Future research is necessary to determine whether
and how alopecia totalis may be triggered by viral infection.

DATA AVA I L A B I LT Y S TAT E M E N T

Data sharing is not applicable to this article as no new data were cre-
ated or analyzed in this study.

AC K N OW L E D G M E N T
We would like to thank the patient's mother for permission to pub-
lish this case.

ORCID
Sandra Oska  https://orcid.org/0000-0002-5659-2864
Geoffrey A. Potts  https://orcid.org/0000-0002-1193-7339

F I G U R E 3   Regular pitting of scattered fingernails

OSKA et al. Pediatric |
      3
Dermatology
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