The Autoimmune Polyendocrinopathy-
Candidiasis-Ectodermal Dystrophy Syndrome
Nicole LeBoeuf, M.D.,* Amit Garg, M.D., and Sophie Worobec M.D.
*Department of Medicine, University of Massachusetts, Worcester, Massachusetts, Division of Dermatology,
University of Massachusetts, Worcester, Massachusetts, Department of Dermatology, University of Illinois,
Chicago, Illinois
Abstract: The autoimmune polyendocrinopathy-candidiasis-ectodermal
dystrophy syndrome is characterized by the presence of chronic muco-
cutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism.
Almost all patients have skin or nail findings early in the course of the
disease. Therefore, the dermatologist is in the unique position of being able
to identify patients with this syndrome early in its course and to facilitate
careful monitoring of potentially lethal complications.
Autoimmune polyendocrinopathy-candidiasis-ecto-
dermal dystrophy (APECED) is an autosomal recessive
syndrome caused by mutations in the autoimmune reg-
ulator (AIRE) gene that is more frequent among the
Finnish, Sardinians, and Iranian Jews (1–3). Compo-
nents of the syndrome described in its appellation appear
to stem from direct autoimmune destruction of endo-
crine organs as well as impairment in cell-mediated
immunity. Since the recognition of the association bet-
ween mucocutaneous candidiasis and glandular dys-
function in 1929 (4), the APECED syndrome has been
reported uncommonly in the dermatology literature. An
affected child along with a review of integumentary and
systemic clinical findings of APECED are discussed.
CASE REPORT
A 17-year-old boy of Scandinavian descent with APE-
CED was seen by the in-patient consultation service for
evaluation of an abnormal appearing nevus. The patient
was admitted for seizure, muscle spasm, weakness, and
severe fatigue, for which he had been hospitalized mul-
tiple times since 7 years of age.At eachadmission, hehad
significant electrolyte abnormalities, particularly in
serum calcium. Initial workup confirmed diagnoses of
both hypoparathyroidism and adrenal insufficiency. The
patient reported visual sensitivity to bright light since
early childhood. He was also afflicted with recurrent
episodes of oral thrush and cutaneous candidiasis
involving the angles of the mouth and groin that were
refractory to topical treatments. Since adolescence, he
had noticed white patches surrounding some of his
nevi and over other cutaneous surfaces, as well as a
progressive loss of scalp, facial, and body hair. He had
abnormally shaped fingernails and toenails for as long as
he could remember.
At the time of our examination, the patient had sparse
scalp, facial (Fig. 1), and body hair. Scattered pustules
on an erythematous base were seen on the face. Ery-
thema and scale were noted along the nasolabial folds
and at the angles of themouth.Nowhitish exudateswere
noted in the oral cavity. He had several depigmented
Address correspondence to Dr. Amit Garg, Division of
Dermatology, University of Massachusetts Medical School, 281
Lincoln St., Dermatology, 4th Floor, Worcester, MA 01605, or
e-mail: garga@ummhc.org.
DOI: 10.1111/j.1525-1470.2007.00510.x
 2007 The Authors. Journal compilation  2007 Blackwell Publishing, Inc. 529
Pediatric Dermatology Vol. 24 No. 5 529–533, 2007

patches over the face, trunk, arms, and legs. Brown
papules, many of which had surrounding depigmenta-
tion (Fig. 2), were scattered over the scalp and trunk.
Fingernails and toenails showed scarring of the nail beds
with tenting (Fig. 3) or partial loss of nail plates.
After electrolyte adjustments and stabilization of the
patient, a team of physicians that included dermatolo-
gists, pediatricians, and endocrinologists followed him
on a regular basis as an outpatient. At the age of 20, the
patient died of sudden cardiac arrest. The exact cause of
this event was not determined, and it was presumed to
have been related to his disease.
DISCUSSION
Autoimmune polyendocrinopathy-candidiasis-ectoder-
mal dystrophy is diagnosed by the presence of at least
two of the three major criteria: chronic mucocutaneous
candidiasis, adrenal insufficiency, and hypoparathy-
roidism (5). In one series, 22% and 89% of patients ful-
filled the proposed criteria by the age of 5 and 20,
respectively (6). In other studies, approximately half
eventually fulfilled the triad (1,7). Our patient demon-
strated the triad by the age of 7. Notable is that almost
all patients have integumentary findings that are present
early in the course of disease (1). The sundry of integu-
mentary and systemic manifestations in APECED
(Table 1) are seldom described in the dermatology liter-
ature. Because some of the major presenting signs are
cutaneous, the dermatologist is in a position to identify
patients with APECED prior to the development of
potentially lethal complications resulting from electro-
lyte and hormone imbalances.
Autoimmune polyendocrinopathy-candidiasis-ecto-
dermal dystrophy syndrome is transmitted autosomal
recessively, and the AIRE gene responsible for the dis-
ease is localized to the short arm of chromosome 21
(21q22.3) (8). The gene product is thought to be anuclear
protein involved in transcriptional regulation (9). In
humans, the greatest transcription of the AIRE gene
occurs in the thymus, among other end organs (9).
Mutations in AIRE result in a partial defect in cell-
mediated immunity and in dysregulation of immune
function with loss of tolerance and subsequent destruc-
tion of endocrine tissues (10). Numerous mutations in
AIRE have been reported (11), and this may explain the
heterogeneity in disease expression. However, no corre-
lation has yet been found linking phenotypes to specific
mutations (12).
Immunodermatologic conditions reported in associ-
ation with APECED include vitiligo, alopecia, and
mucocutaneous candidiasis, all of which may be pre-
senting signs. Chronic mucocutaneous candidiasis may
Figure 1. Sparse eyebrow and eyelash hair.
Figure 2. One of many nevi with surrounding depigmenta-
tion (halo nevus).
Figure 3. Scarring of the nail beds with tenting of the
fingernails.
530 Pediatric Dermatology Vol. 24 No. 5 September ⁄October 2007