Journal of the

American Academy of

DERMATOLOGYVOLUME 38 NUMBER 1 JANUARY 1998

CONTINUING MEDICAL EDUCATION

Nonneoplastic disorders of the eccrine glands
Frederick G. Wenzel, MD, and Thomas D. Horn, MD* Baltimore, Maryland

Eccrine glands are uniquely susceptible to a variety of pathologic processes. Alteration in

the rate of sweat secretion manifests as hypohidrosis and hyperhidrosis. Obstruction of
the eccrine duct leads to miliaria. The excretion of drugs into eccrine sweat may be a con-
tributory factor in neutrophilic eccrine hidradenitis (NEH), syringosquamous metaplasia
(SSM), coma bulla, and erythema multiforme (EM). Alterations in the electrolyte com-
position of eccrine sweat can be observed in several systemic diseases, most notably cys-
tic fibrosis. This article summarizes current knowledge of eccrine gland pathophysiology.
(J Am Acad Dermatol 1998;38:1-17.)

Eccrine sweat glands serve in a thermoregula-
tory capacity to maintain homeostasis in the pres-
ence of increased body temperature caused by a
hot environment or physical exertion. This is
accomplished primarily by the secretion of water
onto the skin surface and subsequent evaporative
cooling. Although other functions, such as prima-
ry excretion of waste products, have been ascribed
to eccrine glands, these appear to be of minor sig-
nificance except in disorders related to the excre-
tion of drugs. The rate of sweat secretion by
eccrine glands far surpasses that of other exocrine
glands, such as the salivary glands or pancreas,
and can reach up to several liters per hour.1
STRUCTURE AND FUNCTION OF ECCRINE
SWEAT GLANDS
Sato et al.2 provide a detailed review of the
structure and function of eccrine sweat glands.
From the Department of Dermatology, The Johns Hopkins School of
Medicine.
Reprint requests: Thomas D. Horn, MD, Department of
Dermatology, Division of Dermatopathology, The Johns Hopkins
University School of Medicine, Blalock 907, 600 N. Wolfe St.,
Baltimore, MD 21287.
*Dr. Horn is now at the Department of Dermatology, University of
Arkansas for Medical Sciences, Slot 576, 4301 W. Markham St.,
Little Rock, AR 72205-7199.
Copyright © 1998 by the American Academy of Dermatology, Inc.
0190-9622/98/$5.00 + 0 16/2/86471
Briefly, the eccrine secretory unit comprises (1)
simple tubular epithelium lining the secretory
coils, situated in the reticular dermis, and (2) the
eccrine ducts that conduct the sweat through the
dermis and epidermis onto the surface of the skin.
In the epidermis, the duct assumes a corkscrew
shape and is referred to as the acrosyringium (Fig.
1), terminating in an orifice approximately 15 µm
in width. Eccrine glands number from 2 to 4 mil-
lion per person and are nearly universal in distrib-
ution on the skin, but vary in density across the
body surface. They are most dense on the palms
and soles, in which they are the only cutaneous
appendage, and are found in decreasing order of
density on the head, trunk, and extremities.
The secretory coils are composed of a single
cell layer containing two cell types: clear cells and
dark cells. The clear cells are broader at the base
and contain periodic acid–Schiff (PAS)–positive
diastase-labile glycogen, whereas the dark cells
are broader at the lumen and and contain
basophilic granules.3 These granules contain both
neutral and nonsulfated acid mucopolysaccharides
that are PAS-positive diastase-resistant and stain
with alcian blue at pH 2.4.4 Surrounding the
secretory layer yet still within the basement mem-
brane are the myoepithelial cells, which exhibit a
contractile function that greatly enhances the

1

2 Wenzel and Horn
Fig. 1. Tortuous morphology of the eccrine acrosy-
ringium. (Original magnification ×200.)
delivery of sweat to the skin surface.5 The ductal
epithelium is composed of two layers of cuboidal
cells and is lined on the luminal surface by a PAS-
positive, diastase-resistant eosinophilic cuticle.
Eccrine gland cells stain for carcinoembryonic
antigen6 and epithelial membrane antigen.7 The
ductal epithelium and acrosyringium express S-
100 protein.8 The acrosyringial epithelial cells
constitutively express class II major histocompat-
ibility complex antigens.9
The primary constituents of eccrine sweat
include water, sodium, potassium, lactate, urea,
ammonia, and small quantities of various amino
acids and proteins. The formation of eccrine sweat
is a biphasic process that begins with the secretion
of precursor sweat from the clear cells in the
secretory coils. This isotonic or slightly hyperton-
ic solution of salt and water then passes through
the ducts, where sodium and potassium are prefer-
entially reabsorbed over water, resulting in a
hypertonic solution. Dark cells contribute the
mucinous contents of their metachromatic gran-
ules into sweat. Although eccrine glands are
innervated by the sympathetic nervous system,
acetylcholine is the principal neurotransmitter at
the nerve ending. The various types of sweating
(e.g., emotional, thermal) are controlled by reflex-
ive signals from corresponding higher neural cen-
ters in the central nervous system.
An unusual gland with features of both apo-
crine and eccrine glands, apoeccrine glands were
initially found in the axilla of a patient with hyper-
hidrosis.10,11 Like eccrine glands, the apoeccrine
gland has a long duct terminating directly onto the
skin surface. However, the secretory apparatus
Journal of the American Academy of Dermatology
January 1998
consists of two types of segments: a small-diame-
ter segment that closely resembles the eccrine
secretory coil and a larger diameter segment that
resembles apocrine secretory epithelium, which
lacks dark cells and intercellular canaliculi. The
innervation of the apoeccrine gland is similar to
eccrine glands, but the secretory rate is approxi-
mately 10 times higher.12 These glands may rep-
resent up to 50% of axillary glands in patients
with axillary hyperhidrosis and may contribute to
the pathophysiology of the condition.
HYPERHIDROSIS AND HYPOHIDROSIS
Disorders affecting eccrine function, causing
either increased or decreased secretion of sweat,
stem from many causes (Table I). These disorders
have been extensively reviewed by Sato et al.13,14
and are not a primary focus of this review.
Hyperhidrosis most commonly affects the axil-
lae, palms, and soles. Although the glands are
morphologically and functionally normal, there
appears to be an abnormal response to emotional
stimuli in the hypothalamic sweat centers.
Apoeccrine glands may be important in axillary
hyperhidrosis, which is precipitated by both emo-
tional and thermal stimuli. Treatment with topical
aluminum salts, tap water iontophoresis, or oral
anticholinergic medications is usually successful,
but sympathectomy may be necessary in extreme
cases. Other causes of localized hyperhidrosis
include causalgia, perilesional hyperhidrosis,
eccrine nevus, granulosis rubra nasi, and abnor-
mal gustatory sweating in response to diseases
affecting the sympathetic innervation of the face.
Generalized hyperhidrosis most commonly occurs
during a febrile illness, but can also be observed in
a variety of other systemic illnesses, such as
pheochromocytoma, thyrotoxicosis, congestive
heart failure, and diabetes mellitus. Nocturnal
hyperhidrosis has been classically associated with
Hodgkin's disease, but may also occur in other
chronic diseases. Hyperhidrosis of large areas
occurs in the setting of disorders affecting the ner-
vous system, such as spinal cord injuries, brain
lesions, and peripheral neuropathies. Finally,
paroxysmal unilateral hyperhidrosis may be asso-
ciated with an intrathoracic neoplasm or other dis-
ease.
Hypohidrosis or anhidrosis is most commonly
caused by poral occlusion associated with a vari-
ety of chronic dermatoses, such as psoriasis,
Journal of the American Academy of Dermatology
Volume 38, Number 1 Wenzel and Horn 3

Table I. Hyperhidrosis and hypohidrosis* Table I. Cont’d

Hyperhidrosis Generalized (cont’d)
Localized Fabry's disease
Emotional hyperhidrosis (palms, soles, axillae) Neuropathy
Gustatory sweating Congenital sensory neuropathy
Processes affecting sympathetic innervation Type II (Riley-Day syndrome)
Auriculotemporal or Frey's syndrome Type IV (congenital insensitivity to pain with
Eccrine nevus anhidrosis)
Granulosa rubra nasi Progressive segmental anhidrosis with Adie's tonic
Idiopathic unilateral circumscribed pupils (Ross syndrome)
Perilesional Autonomic insufficiency syndrome
Blue rubber bleb nevus Chronic idiopathic anhidrosis
Glomus tumor Diabetic neuropathy
Causalgia Guillain-Barré syndrome
POEMS syndrome Localized
Burning feet syndrome Local damage to glands
Pachydermoperiostosis Local denervation
Pretibial myxedema Follicular atrophoderma (Bazex syndrome)
Generalized Sjögren's syndrome
Spinal cord injuries
Peripheral neuropathies
Familial dysautonomia (Riley-Day syndrome)
Congenital autonomic dysfunction with universal
pain loss atopic dermatitis, or systemic sclerosis.
Cold exposure Neuropathies also represent an important cause of
Brain lesions hypohidrosis. Congenital sensory neuropathies,
Hypothermia (Hines-Bannick syndrome)
Posttraumatic hypertension such as familial dysautonomia (Riley-Day syn-
Olfactory hyperhidrosis drome) and congenital insensitivity to pain with
Intrathoracic processes anhidrosis, as well as those caused by diabetes
Paroxysmal unilateral hyperhidrosis mellitus or Guillain-Barré syndrome may affect
Systemic illnesses eccrine gland function. Progressive segmental
Febrile illnesses
hypohidrosis with tonic pupils (Ross syndrome) is
Pheochromocytoma
Parkinson's disease a specific type of hyperhidrosis. Eccrine glands
Thyrotoxicosis may be totally absent, as in anhidrotic ectodermal
Diabetes mellitus dysplasia, or dysfunctional, as in Fabry's disease
Congestive heart failure or systemic sclerosis. Localized hypohidrosis may
Anxiety be the result of local damage from inflammation
Menopause
Poisoning (insecticides, herbicides, mercury) or tumor, denervation, follicular atrophoderma, or
Night sweats Sjögren's syndrome.
Lymphoma (Hodgkin's disease)
Miscellaneous chronic diseases MILIARIA
Compensatory One of the most common disorders of the
After sympathectomy eccrine sweat glands, miliaria is a generic term
Associated with diffuse anhidrosis
Hypohidrosis and anhidrosis
denoting retention of eccrine sweat at various lev-
Generalized els of the skin. After the initial description by
Poral occlusion Robinson15 in 1884, observations on the clinical
Papulosquamous, ichthyosiform, dermatitic lesions manifestations of miliaria have led to a more
Xerosis refined classification based on the level of the
Tropical anhidrotic asthenia eccrine ductal obstruction. There are three types
Absence of sweat glands (anhidrotic ectodermal
dysplasia) of miliaria: miliaria crystallina, with ductal
Sweat gland dysfunction or atrophy obstruction in the stratum corneum; miliaria
Systemic sclerosis rubra, with obstruction within the stratum
*Adapted from Sato K, Kang WH, Saga K, Sato KT. J Am Acad malpighii; and miliaria profunda, with obstruction
Dermatol 1989;20:713-26. at or below the dermoepidermal junction.

4 Wenzel and Horn
Fig. 2. Erythematous papules of miliaria on the back of
a bed-bound patient.
Miliaria crystallina
Also known as sudamina, miliaria crystallina is
characterized by a diffuse eruption of 1 to 2 mm
superficial asymptomatic vesicles on a nonin-
flamed base, sometimes appearing as "drops of
water." These vesicles appear in crops, typically
on the trunk. The onset occurs after days to weeks
of excessive exposure to heat and humidity, espe-
cially in tropical areas or during summer
months.16,17 In addition, miliaria crystallina is fre-
quently seen with the profuse sweating accompa-
nying persistent febrile illnesses, or in response to
drugs that induce sweating, such as bethanechol.18
The individual vesicles are extremely fragile, rup-
turing spontaneously or with slight friction, and
resolve with a superficial branny desquamation.
Therapy is generally not required because the
eruption is self-limited.
Miliaria crystallina occurs in the neonatal peri-
od and can be confused with other vesicular dis-
orders in neonates. In this setting it occurs most
Journal of the American Academy of Dermatology
January 1998
Fig. 3. Miliaria pustulosa.
commonly on the head, neck, and upper trunk and
likely reflects a delay in patency of the sweat
ducts after birth.19 A large retrospective study of
5387 Japanese infants found miliaria crystallina in
4.5%, with a peak frequency at 1 week of age.20
Two patients with congenital miliaria crystallina
have also been described.21,22
Miliaria rubra
Miliaria rubra, or "prickly heat," is the most
clinically significant manifestation of eccrine
sweat retention. The primary lesion is an erythe-
matous nonfollicular macule or papule (Fig. 2)
that may contain a minute central vesicle. Pustule
formation in some of the lesions can occur, and if
widespread, the term miliaria pustulosa (Fig. 3)
can be employed. Unlike other forms of miliaria,
miliaria rubra characteristically is accompanied
by paroxysmal pruritus or a stinging sensation,
which are frequently exacerbated by stumili that
induce sweating.23 In adults, the eruption tends to
occur most commonly on the trunk and neck, but
can involve most other areas of the skin except the
face and volar areas. Miliaria rubra tends to occur
mainly in hot, humid environments, affecting up
to 30% of persons exposed to these condi-
tions.24,25 The incidence appears maximal at 2 to
5 months of exposure, but the process can begin
within only a few days in a tropical environment,
reflecting a wide individual susceptibility.25
Episodes of miliaria are typically followed by
periods of anhidrosis in affected sites, sometimes
lasting up to several weeks.23 Rarely, extensive
miliaria can lead to hyperpyrexia and heat exhaus-
tion.26
Journal of the American Academy of Dermatology
Volume 38, Number 1
Like miliaria crystallina, miliaria rubra affects
infants and occurs in up to 4% of neonates, with a
peak frequency at 11 to 14 days of life.20 In
infants, the eruption occurs most commonly in the
flexural areas and, unlike adults, frequently affects
the face and scalp.20
Treatment of miliaria consists of regulating the
heat and humidity of the patient's environment to
reduce sweating. After several days, the poral
obstructions are gradually relieved, although they
may persist for 2 to 3 weeks.26 Oral ascorbic acid,
1 gm daily,27 as well as the topical application of
lanolin, were reported to be helpful.28 Oral and
topical antibiotics are effective in preventing
experimentally induced miliaria, but their use in
the treatment of established miliaria has been dis-
appointing.29
Miliaria profunda
Miliaria profunda, or mamillaria, is usually
only seen in a tropical environment after repeated
episodes of miliaria rubra. The cutaneous findings
can be subtle and are characterized by pale or
flesh-colored, 1 to 3 mm papules located predom-
inantly on the trunk, but also on the extremities.16
These lesions are asymptomatic, and individual
papules may become more prominent when the
patient is stimulated to sweat because each papule
actually represents a deep-seated sweat retention
vesicle.26 Other common findings include com-
pensatory facial hyperhidrosis and inguinal and
axillary adenopathy.26
Because of widespread inactivation of eccrine
sweat glands, patients with miliaria profunda are
predisposed to the development of tropical
anhidrotic asthenia when exposed to prolonged
heat stress.30 In addition to the cutaneous findings
of miliaria profunda, these patients have malaise,
weakness, dyspnea, and tachycardia leading up to
hyperpyrexia and exhaustion.
Pathogenesis of miliaria
The characteristic histologic finding in miliaria
crystallina is an intracorneal or subcorneal vesicle
arising from the acrosyringium of the sweat
duct.31 Miliaria rubra is characterized by spongi-
otic vesicles in the stratum malpighii, also in com-
munication with sweat ducts, as well as a chronic
inflammatory infiltrate of the dermis surrounding
the ducts32,33 (Fig. 4). In addition, an amorphous
PAS-positive, diastase-resistant material can fre-
Wenzel and Horn 5
Fig. 4. Photomicrograph of biopsy specimen of mil-
iaria lesion shows subcorneal vesicle with epidermal
and periductal inflammation. (Original magnification
×100.)
quently be identified in the acrosyringium, which,
in older lesions, is followed by a parakeratotic
plug.34 In miliaria profunda, rupture of the intra-
dermal duct is present below the dermoepidermal
junction with marked lymphocytic infiltration of
the adjacent dermis, as well as spongiosis of the
intraepidermal portion of the duct.31
The origin of the PAS-positive material
obstructing the eccrine duct has been the subject
of debate. Dobson and Lobitz,34 who originally
described the phenomenon, postulated that this
material was a product of the eccrine secretory
coils. This view was later supported by Yanagawa,
Yokozeki, and Sato,35 who demonstrated that this
material was not derived from serum glycopro-
teins, but possibly from the dark cell secretory
granules, which also stain PAS-positive. O'Brien30
suggested an alternative hypothesis, in which
lipoid depletion of the keratinocytes lining the
eccrine pore leads to obstruction of the duct and
the parakeratotic plug. This idea was compatible
with his observations that lanolin application
quickly reverses the anhidrotic state in miliaria
induced by soap and other lipid solvents.
Subsequent studies28 led him to regard
Staphylococcus aureus as a key causative factor in
miliaria, supporting the view originally put forth
by Unna36 and Acton37 that miliaria is related to
bacterial colonization and overgrowth on the skin
surface. A threefold increase in the density of the
resident bacteria in patients with miliaria has been
documented,38 and several studies have shown the
efficacy of antimicrobial agents in suppressing

6 Wenzel and Horn
Fig. 5. Erythematous edematous papules and plaques
on a patient with neutrophilic eccrine hidradenitis.
experimentally induced miliaria.29,39,40 Hölzle
and Kligman29 demonstrated that the induction of
miliaria is proportional to the increase in density
of resident bacteria, most notably coagulase-nega-
tive cocci, presumably from some excreted bacte-
rial product. A complex, PAS-positive extracellu-
lar polysaccharide substance (EPS) produced
specifically by Staphylococcus epidermidis has
been described41 and is thought to represent a vir-
ulence factor.42 Mowad et al.43 confirmed the cen-
tral role of EPS in the pathogenesis of miliaria. By
using inocula of various strains of coagulase-neg-
ative cocci under occlusive dressings and thermal
stimulation, they found only S. epidermidis capa-
ble of producing EPS-induced miliaria under their
experimental conditions. Immunostaining of the
PAS-positive plugs in the eccrine ducts revealed
the presence of mannose, which is considered spe-
cific for EPS.44
DRUG-RELATED ECCRINE DISORDERS
Concentration of drugs in the eccrine glands
Journal of the American Academy of Dermatology
January 1998
and secretion into eccrine sweat is a well-recog-
nized phenomenon. Drugs known to be so secret-
ed include sulfaguanidine, sulfadiazine, anti-
pyrine, aminopyrine,45 amphetamines,46 iodide,47
phenytoin, phenobarbital, carbamazepine,48
ethanol,49 griseofulvin,50 ketoconazole,51 barbitu-
rates,52 ciprofloxacin,53 heroin, cocaine,54 flu-
conazole,55 nicotine,56 and triethylenephos-
phamide (thiotepa).57 Undoubtedly, many other
drugs that have not been studied are also secreted.
During the past few decades, drugs have been
increasingly implicated in the cause of various
eccrine disorders. As most of the information
comes mainly from case reports, a truly consistent
and thorough understanding of these observations
has yet to be achieved.
Neutrophilic eccrine hidradenitis
Chemotherapy-associated neutrophilic eccrine
hidradenitis. NEH was first described in 1982 by
Harrist et al.,58 and numerous case reports have
followed.59-76 The initial patient was a 38-year-
old man undergoing induction chemotherapy with
cytarabine, vincristine, and doxorubicin for acute
myelogenous leukemia. Subsequent reports have
emphasized antineoplastic chemotherapeutic
agents in the pathogenesis of this eruption.
A review of the literature reveals 28 cases of
NEH temporally linked to chemotherapy. Both
children and adults are affected. The most com-
mon malignant neoplasm is acute myelogenous
leukemia (64% of patients), followed by various
other leukemias and solid tumors. The eruption
typically consists of erythematous and edematous
papules and plaques (Fig. 5) that can also be pur-
puric and painful. Pustule formation was noted in
only one patient.65 The sites affected, in decreas-
ing order of reported frequency, are the extremi-
ties, trunk, periorbital region, neck, face, ears, and
palms. Unilateral or bilateral periorbital edema
and erythema can be the sole manifestation.75,76
Occurrence at sites of injections has also been
reported.76 Other unusual presentations include
bilateral painful edema of the ears74 and hyper-
pigmented plaques and linear papules in a patient
with typical bleomycin-induced flagellate hyper-
pigmentation.63 Excluding one case that occurred
5 months after chemotherapy, the eruption begins
approximately 10.6 days (mean, 8 days) after
institution of chemotherapy. The onset is often
associated with neutropenia and fever. When the
Journal of the American Academy of Dermatology
Volume 38, Number 1
duration of the eruption was reported, it lasted
from 6 to 33 days (mean, 10 days) and resolved
without therapy. Recurrence after subsequent
courses of chemotherapy have been reported in
three patients.58,72
Histologic examination reveals a variably
dense neutrophilic infiltrate surrounding the
eccrine coils and infiltrating the eccrine epitheli-
um (Fig. 6). Necrosis of the secretory coils,
including vacuolar degeneration and nuclear
pyknosis, is usually present. Neutrophils are also
found in the ductal lumina, with occasional
microabscess formation. The infiltrate can also
involve the eccrine ducts in which findings range
from minimal spongiosis to frank necrosis. In one
case involvement only of the ducts and not the
secretory coils was found.63 Variable findings
include dermal hemorrhage, edema, and mucinous
degeneration of the adipose tissue cuff and periad-
nexal dermis. In addition, perivascular infiltrates
have been reported in some cases, usually com-
posed of a mixture of lymphocytes, histiocytes,
and occasionally neutrophils.58,59,61,69,70,72
Coincident SSM of the ducts was noted in three
cases.58,59,63 Most cases reported that stains for
bacteria and fungi, as well as tissue cultures, were
negative.
Efforts to link NEH with specific chemothera-
peutic agents, particularly cytarabine, have been
unsuccessful. Although cytarabine is the most
common agent in the regimens of the reported
patients, it was almost always used in combination
with other agents, usually daunorubicin, doxoru-
bicin, vincristine, and mitoxantrone. In addition,
cytarabine was absent from the regimen of seven
patients, in which mitoxantrone, cyclophos-
phamide, and bleomycin were most commonly
employed. In the report of a case of NEH herald-
ing the onset of acute myelogenous leukemia, one
author has suggested that NEH may manifest
itself as a paraneoplastic phenomenon.77
However, further evidence for a link to
chemotherapy as the inciting cause was provided
by a study by Templeton, Solomon, and
Swerlick,78 in which the intradermal injection of
bleomycin in healthy volunteers resulted in the
histologic findings of NEH and SSM after 24
hours.
Several authors have suggested that NEH may
be just one part of a spectrum of chemotherapy-
related eccrine changes that include SSM and iso-
Wenzel and Horn 7
Fig. 6. Neutrophilic eccrine hidradenitis. Photomicro-
graph of biopsy specimen shows degeneration of the
eccrine coils associated with infiltrate of neutrophils.
(Original magnification ×400.)
lated eccrine necrosis. To support this argument,
several cases of chemotherapy-related eruptions
have been reported, in which histologic examina-
tion showed degenerative changes and necrosis of
the eccrine coils, but no significant infiltrate of
neutrophils.79,80 In addition, SSM was identified
in one of the cases.80
Infectious NEH. The eccrine glands are nor-
mally resistant to infection from agents found on
the skin surface and in the environment. However,
there are three reports of bacteria causing a
process at least histologically similar to NEH. The
first by Moreno et al.81 involved a 48-year-old
man who had been undergoing hemodialysis for 6
years because of renal failure from glomeru-
lonephritis. A recurrent, pruritic, papular eruption
developed on the extremities. A biopsy specimen
showed typical NEH involving the coils and ducts.
Bacterial culture of the specimen grew Serratia.
The eruption resolved in 3 months with topical
antibiotic therapy.
A similar case was reported by Allegue et al.,82
in which an otherwise healthy 49-year-old man
had a flu-like syndrome along with erythematous
and violaceous papules and pustules on the trunk
and extremities. The biopsy specimen showed
NEH of the secretory coils, with dermal hemor-
rhage and SSM of the ducts. Culture of a pustule
grew Enterobacter cloacae. The patient was treat-
ed with intramuscular amikacin and the eruption
resolved in 1 week.
NEH was also observed in the biopsy specimen
of a 47-year-old man with recurrent crops of

8 Wenzel and Horn
papules on his left wrist.83 The patient had under-
gone heart transplantation 4 years previously and
was receiving cyclosporine. Tissue cultures were
positive for S. aureus, and the patient was treated
with oral dicloxacillin with rapid resolution of the
papules. In none of these cases was the presumed
pathogen directly identified in lesional tissue by
light microscopy.
Palmoplantar hidradenitis. Recent reports of
NEH of the palms and soles of healthy children
and young adults have added to the spectrum of
this disorder. In 1994, Stahr, Cooper, and
Caputo84 described six patients, whose ages
ranged from 9 to 21 years, with painful papules
exclusively on the plantar surfaces. Biopsy speci-
mens showed an NEH, mainly centered on the
eccrine coils. The acrosyringia were involved in
two cases, and neutrophilic abscesses were pre-
sent in four cases. Stains for bacteria and fungi
were negative. The papules resolved in 1 to 2
weeks with oral or topical steroids. Only one
patient had a recurrence. An additional patient
with similar findings was described the same
year.85
Rabinowitz et al.86 described two additional
children with recurrent nodules on the palms and
soles. Biopsy specimens again showed NEH.
However, the infiltrate of neutrophils was present
in a focal nodular pattern in the reticular dermis,
with abscess formation.
Other causes of NEH. Two cases of NEH in
association with HIV were described by Smith et
al.87 Both patients were taking azidothymidine at
the time of the eruption.
NEH has also been described in a 12-year-old
girl with neonatal onset multisystem inflammato-
ry disease, a rare condition with features of juve-
nile rheumatoid arthritis and hyperimmunoglobu-
lin D syndrome, but with onset shortly after
birth.88 The only previous report noted a perivas-
cular eosinophilic infiltrate at the level of the
eccrine glands.89
Only one case has been reported of NEH in an
otherwise totally healthy adult, who had experi-
enced minor trauma to the knee and had been tak-
ing acetaminophen for 5 months before the erup-
tion. Stains of the biopsy specimen for bacteria
and fungi were negative, but tissue culture was not
performed. The acetaminophen was not discontin-
Journal of the American Academy of Dermatology
January 1998
ued, and the eruption resolved in 5 days without
recurrence.90
Syringosquamous metaplasia
Like NEH, the term syringosquamous metapla-
sia (SSM) is a histopathologic finding that has
been adapted to clinical use. The initial reports of
SSM viewed it as a reactive phenomenon in the
vicinity of chronic inflammation associated with
pressure necrosis and venous stasis ulcera-
tions.91,92 Although SSM has been linked to cer-
tain medications, its manifestation as a distinct
skin disease has become increasingly associated
with chemotherapy in recent years.
SSM most commonly appears as generalized
erythematous papules and vesicles, but may be
localized to the extremities or intertriginous
areas.93,94 Unusual presentations include occur-
rence in sun-exposed areas in association with
benoxaprofen use95 or in fields previously
exposed to ionizing radiation in a patient undergo-
ing systemic chemotherapy.96 The eruption typi-
cally appears during, or shortly after, the course of
chemotherapy and subsides slowly in several
weeks. The patients have had a variety of solid
and hematopoietic neoplasms. Among the
chemotherapeutic agents, cytarabine has been
most commonly implicated in the pathogenesis of
SSM.93,94 Hovever, several patients were taking
mixed drug regimens without cytarabine,93 and
one patient was receiving monotherapy with
suramin.97 Although no definite correlation of
SSM with specific drugs or tumors has been
established, evidence for a direct causative effect
of chemotherapy was provided by two cases of
extravasation of doxorubicin into the skin.98
Biopsy specimens revealed extensive SSM, along
with interface dermatitis and dermal reactive
changes analogous to radiation dermatitis.
The histopathologic hallmark of this disorder is
the transformation of the normal cuboidal ductal
epithelium cells into cells with an ample
eosinophilic cytoplasm and a larger more irregular
nucleus (Fig. 7). The ducts often appear as islands
of squamous epithelium mimicking squamous cell
carcinoma, or as dilated structures resembling
syringomas. Focal dyskeratosis or necrosis of the
ductal epithelium and fibrosis of the adjacent der-
mis are frequently noted.93 Typically the eccrine
coils are unaffected, and a sparse lymphoid infil-
trate may be present.
Journal of the American Academy of Dermatology
Volume 38, Number 1
Fig. 7. Transformation of the normal cuboidal ductal
epithelium in syringosquamous metaplasia. (Original
magnification ×200.)
SSM has also been reported as an associated
histologic finding in lobular panniculitis,99 pyo-
derma gangrenosum,99 cytarabine-related acral
erythema,100 and early chloracne lesions in chil-
dren exposed to 2,3,7,8-tetrachlorodibenzo-p-
dioxin during an industrial accident in Italy.101 A
2-year prospective study of the incidence of SSM
in all skin biopsy specimens taken in a hospital in
Barcelona, Spain found 21 cases of SSM.102 It
was seen most frequently in association with
ulcerations from ischemia or surgical excision (10
cases), but also with burn scars, neurodermatitis,
pyoderma gangrenosum, chemotherapy extravasa-
tion, furuncle, and thromboangiitis obliterans
(Buerger's disease). These numerous associations
suggest that SSM represents a nonspecific reactive
change to damaged eccrine ductal epithelium.
Drug-induced coma
Eccrine gland necrosis has been frequently
observed in patients with drug-induced coma.
Because many other structures in the skin are
affected as well, it is unclear whether eccrine
gland necrosis is the primary pathologic event and
is better considered as the most consistently
reported histopathologic finding. The question of
whether the ingested drugs play a direct role in the
pathophysiology of this phenomenon has been the
subject of much debate. Linear, erythematous, and
bullous lesions in comatose patients with carbon
monoxide poisoning were first described by
Larry103 in 1806. The first report of bullae in bar-
biturate-induced coma came in 1950.104 Although
barbiturates remain the most frequently reported
Wenzel and Horn 9
Fig. 8. Hemorrhagic bulla and macular erythema in a
patient with coma bulla.
drug,105-108 similar findings have been noted in
association with benzodiazepines,109-111 nar-
cotics,106,112-115 tricyclic antidepressants,110,116,117
as well as hypoglycemic coma118 and central ner-
vous system disorders.119-123
The unusual constellation of cutaneous find-
ings, including bullae, violaceous plaques, ero-
sions, and macular erythema (Fig. 8), has been
reported in 4% to 5% of patients hospitalized for
drug-induced coma115,124,125 and in 40% of such
patients at autopsy.126 The lesions typically occur
in pressure areas on the extremities and trunk after
several hours or days, but occassionally as early as
1 hour after acute intoxication.124 In addition,
areas not typically prone to pressure may be
involved.124
Based largely on the initial histopathologic
description by Adebahr,126 necrosis of the eccrine
secretory coils is considered the hallmark of drug-
induced coma (Fig. 9). Subsequent reports have
confirmed this finding,105,106,127,128 and others
have also described involvement of the eccrine
duct,105,106,108,109,129 with the inner cell layer of
the duct being more susceptible to necrosis.111
Although often uninvolved in earlier lesions, the
epidermis in later lesions may show spongiosis
and intraepidermal and subepidermal vesicles that
sometimes coalesce into subepidermal bullae.111
Occassionally, degenerative changes in the epider-
mis have been noted, ranging from mild vacuolar
alteration106,128 to massive necrosis of the blister
roof resembling toxic epidermal necrolysis.125
Necrosis of the pilosebaceous apparatus has also
been reported.108,111 A sparse inflammatory infil-

10 Wenzel and Horn
Fig. 9. Photomicrograph of biopsy specimen of coma
bulla shows necrosis of the eccrine coils with no
inflammatory infiltrate. (Original magnification ×200.)
trate may be present. Mild degenerative changes
in dermal blood vessels have been
described108,111,126,129 and immunofluorescence
studies have demonstrated IgM and C3 in vessel
walls,111,128 consistent with a reactive phenome-
non, although one report described massive gran-
ular deposits of IgM, C3, and fibrinogen in the
upper dermal vessels of two patients.130 Only one
immunofluorescence study has reported positive
findings in the epidermis, with IgG, IgA, and C3
in a patchy intercellular pattern in a bulla.131
The pathogenesis of the cutaneous changes in
drug-induced coma remains the subject of debate.
Location in pressure areas, linear pattern, unilater-
ality, and occurrence in comas not related to drugs
and in immobilized noncomatose patients all favor
pressure and hypoxia as causative factors.
However, appearance of some lesions in 1 to 2
hours after intoxication, occurrence in areas not
typically prone to pressure, and the occasional
widespread and irregular pattern of the eruption
implicate factors other than pressure.111 The fact
that the inner cell layer of the eccrine ducts is
affected earliest and most severely discounts the
involvement of hypoxia, which would affect the
more metabolically active outer cell layer.111
Whether the various case reports represent the
same entity is questionable because histologic
findings were often vague or not reported, and
investigation into other possible causes was not
mentioned.
Erythema multiforme
Erythema multiforme (EM) is related in most
Journal of the American Academy of Dermatology
January 1998
cases to herpes simplex virus (HSV) infection,
Mycoplasma pneumoniae infection, or drug
hypersensitivity.132 Assier et al.133 proposed that
drug-related EM manifested a pattern of atypical
flat targets or purpuric macules with diffuse
involvement, whereas HSV-related EM had an
acrally distributed pattern with more typical targe-
toid lesions. Some cases of EM display acrosy-
ringial concentration of necrotic keratinocytes his-
tologically. A retrospective histologic study of 23
cases of EM while blinded to clinical impressions
showed a strong correlation between drug-related
EM cases and acrosyringial concentration of
necrotic keratinocytes.134 None of the HSV-relat-
ed cases exhibited this histologic pattern. These
findings raise the possibility that drug-induced
EM relates in some way to eccrine concentration
of the inciting medication.
Hyperpigmentation
Concentration of a drug in the eccrine sweat
can produce epidermal damage. Hyperpigmenta-
tion from this phenomenon has been described in
five patients receiving thiotepa.57 The hyperpig-
mentation was limited to skin occluded by adhe-
sive bandages and electrocardiogram pads.
Measurement of thiotepa in gauze and bandages
containing sweat revealed concentrations several
times that of concurrent plasma levels, suggesting
that concentration of the drug by the eccrine
glands with subsequent occlusion caused the cuta-
neous findings. Although excretion of bleomycin
in sweat has not been documented, it may under-
lie the flagellate hyperpigmentation seen with this
drug.
Graft-versus-host reaction
Although eccrine involvement is not usually
seen in graft-versus-host reaction (GVHR), a
recent study of GVHR induced by roquinimex in
three of eight autologous bone marrow transplant
recipients found necrosis of the eccrine sweat
glands.135 Roquinimex is a carboxamide-
quinolone and acts as a potent immunomodulating
drug that increases the number and activity of nat-
ural killer cells, monocytes, and T lymphocytes,
but possesses no cytotoxic properties. The eccrine
necrosis occurred in the setting of histologic find-
ings compatible with typical grade II GVHR and
appeared 12 to 30 days after transplantation (2 to
11 days after initiation of roquinimex). This phe-
Journal of the American Academy of Dermatology
Volume 38, Number 1
nomenon might alternatively be explained by a
delayed reaction to the preparative chemothera-
peutic regimen.
Pathophysiology of drug-mediated eccrine dis-
orders
Whether the conditions described in the previ-
ous paragraphs represent separate, distinct reac-
tions to drugs or are simply a spectrum of related
drug-induced eccrine injury is debatable. Several
authors have suggested that the spectrum of
chemotherapy-related eccrine reactions range
from NEH to eccrine necrosis with no infiltrate to
SSM, depending on the individual host response
to injury. The most obvious hypothesis to explain
this injury is concentration of the drug in the
eccrine glands and its excretion into sweat. The
relative susceptibility to injury of the coils, ducts,
and acrosyringium would then determine which
reaction prevails. Host factors influencing such
reactions include the differential metabolism of
each drug in the various cell types of the eccrine
unit, as well as host immune and inflammatory
responses. The possibility of an immune-mediated
process participating in the pathogenesis of these
disorders must also be considered. The possibility
that the acrosyringial epithelium is immunologi-
cally "primed" through the constitutive expression
class II major histocompatibility complex anti-
gens was raised by a recent observation, although
this has not yet been confirmed by other investi-
gators.9 This observation may be of particular
consequence in drug-related EM, in which acrosy-
ringial concentration of necrosis appears to be
present. Supporting this possibility is the presence
of eosinophils in the infiltrate of drug-related
cases, which may represent an immunologic
process rather than direct toxicity only (unpub-
lished data). The possibility of a cross-reacting
antibody to a shared epitope between a drug and
the eccrine unit epithelium also exists. In addition,
because the eccrine coils are invested with a rich
vascular supply, it is possible that eccrine gland
damage may occur secondary to processes affect-
ing these vessels.
RADIATION-INDUCED ECCRINE INJURY
Although the effects of ionizing radiation on
the skin in general and on hair follicles in particu-
lar has been thoroughly studied, its effect on
eccrine glands has only recently been evaluated.
Wenzel and Horn 11
With pilocarpine stimulation tests, Morris,
Dische, and Mott136 studied six normal and 28
irradiated patients. All 11 patients who had
received high-dose radiation (> 50 Gy) had signs
of late radiation dermatitis and exhibited no func-
tional eccrine glands. In patients given lower
doses with no signs of skin changes, the results
ranged from normal numbers of eccrine glands to
partial and, rarely, complete loss of functional
glands. A follow-up study in mice confirmed that
eccrine glands are more radiosensitive than epi-
dermis.137 After irradiation, a loss of function as
measured by pilocarpine-induced sweat output
was noted within 2 weeks, which continued for 8
weeks at a dose-dependent rate. A dose-dependent
nadir was reached at 8 weeks, followed by a grad-
ual recovery in 30 weeks, but resulting in a final
dose-dependent residual deficit in function.
In addition to functional effects, radiation has
been implicated in the formation of a keratotic
miliaria-like eruption in a patient with non-
Hodgkin's lymphoma.138 After nine courses of
systemic chemotherapy, the patient received 40
Gy of radiation to the lower abdomen. Three
weeks after therapy had begun, an eruption
restricted to the radiation field was noted. The
lesions were characterized histologically by dilat-
ed eccrine orifices and ducts filled with lamellat-
ed keratin, as well as focal SSM. The eruption
resolved in several weeks after completion of the
radiotherapy.
ELECTROLYTE ABNORMALITIES IN
ECCRINE SWEAT
Abnormalities of electrolyte levels in eccrine
sweat can be observed in several systemic dis-
eases. This phenomenon was first described in
patients with cystic fibrosis (CF), in whom an ele-
vated sweat sodium chloride concentration has
become a diagnostic criterion. This abnormality is
consistent, persists throughout life, and varies lit-
tle with disease severity.26 Because the primary
sweat from the secretory coils in both patients
with CF and control subjects is isotonic to plasma,
the elevated sodium chloride concentration results
from defective reabsorption in the ductal epitheli-
um.139 Although the exact mechanism of this
defect remains unknown, the initial observation
that the electrical potential of the ductal lumen is
twice as negative in patients with CF as in control
patients has led to further investigations into regu-

12 Wenzel and Horn
Fig. 10. Periodic acid–Schiff–positive granules in the
eccrine ductal epithelium in Lafora's disease. (Periodic
acid–Schiff stain; original magnification ×400.)
lation of ion transport in the ductal epithelium.140
It appears that chloride ion transport, which
involves a voltage-dependent chloride channel,
responds abnormally to regulatory stimuli and is
abnormally slow across the luminal membrane.141
Unlike normal patients, neither cyclic adenosine
monophosphate (cAMP) nor the cAMP agonist
foskolin opens chloride channels in patients with
CF.142 The secretory coils show a similar unre-
sponsiveness to cAMP accumulated in response to
β-adrenergic stimulation.143 Thus the abnormal
ion transport seems to be related to defects in
intercellular regulatory pathways that are not yet
clearly defined. An understanding of the eccrine
pathophysiology in CF will likely explain the sys-
temic disease as well.
Measurement of electrolyte levels to establish
the diagnosis of CF is accomplished by means of
a standardized pilocarpine iontophoresis test.144
Sweat levels of sodium 60 mmol/L or higher or of
chloride 70 mmol/L or higher are required for the
diagnosis in children. In adults, sodium levels 80
mmol/L or higher are expected. However, normal
electrolyte levels do not absolutely exclude the
diagnosis of CF because a minority of mutations
do not cause the typical changes in electrolyte
concentrations.145,146
DIAGNOSTIC INCLUSIONS AND ALTER-
ATIONS IN ECCRINE GLANDS
Characteristic histologic alterations in eccrine
glands can be of diagnostic aid in several systemic
disorders. Eccrine glands are frequently involved
Journal of the American Academy of Dermatology
January 1998
in metabolic disorders that lead to abnormal accu-
mulation of material inside affected cells. In the
various mucopolysaccharidoses, such as Hurler's,
Hunter's, and Sanfillipo's syndromes, membrane-
bound vacuoles can be identified in the secretory
cells of the eccrine coils.147 Secretory cells may
also be characteristically affected by the intracyto-
plasmic accumulation of lipids in the lipid storage
diseases, such as those characterized by Sandhoff
and Neimann-Pick (cited in Drut148) as well as
those associated with angiokeratoma corporis dif-
fusum, such as Fabry's disease,149-151 fucosido-
sis,152 and Kanzaki disease.153 Other metabolic
diseases with intracytoplasmic inclusions in the
secretory cells include amaurotic idiocy, acid mal-
tase deficiency, and adrenoleukodystrophy.154 The
outer layer of eccrine ductal cells in patients with
Lafora's myoclonic epilepsy (Lafora's disease)
contain PAS-positive granules155 (Fig. 10).
In addition to metabolic disease, PAS-positive,
diastase-resistant granules may be observed in the
secretory cells of patients with hypothyroidism.156
A recent study of the eccrine glands in alcoholic
liver disease revealed deposits of IgA in the base-
ment membrane of the secretory coils with high
specificity and sensitivity.157 Finally, the relative
length of the eccrine duct compared with the
length of the secretory coil is reported to be help-
ful in distinguishing among trisomy D1, G1, and
18.158
MISCELLANEOUS ECCRINE GLAND
DISORDERS
Multiple sweat gland abscesses
Multiple sweat gland abscesses, sometimes
referred to as periporitis, represent a primary pyo-
derma of the eccrine sweat glands seen mainly in
infants. Although it has received little attention
recently, it was frequently reported earlier this
century in Europe,159 followed by several reports
in the United States.160 Chronically ill and debili-
tated infants are particularly susceptible, but
healthy infants may also be affected. The distinc-
tive eruption consists of multiple, dome-shaped,
cold, nontender nodules that most commonly
involve the occiput, back, and buttock.160 The
more superficial pustules that may precede these
findings are more appropriately called periporitis.
Later in the course, the abscesses commonly
break down, yielding thin pus. Fever is typically
Journal of the American Academy of Dermatology
Volume 38, Number 1
absent or mild. Bacteria, most commonly gram-
positive cocci, can usually be found in intact
lesions. Biopsy specimens reveal large focal
abscesses extending throughout the dermis into
the subcutaneous fat. Therapy consists of incision
and drainage of larger abscesses, as well as topi-
cal and systemic antibiotics.
Granulosa rubra nasi
Granulosa rubra nasi (GRN), first described in
1900, is a rare disease involving the eccrine glands
of the nose.161 Typically beginning in early child-
hood, the first manifestation is hyperhidrosis,
which after several years, leads to diffuse erythe-
ma.162 The tip of the nose is commonly involved
initially, but the erythema may spread to the rest
of the nose, as well as the cheeks, upper lip, and
chin. Fine erythematous papules and beads of
sweat are commonly seen in the erythematous
areas. Vesicles and small cysts have also been
noted occassionally. Mild pruritus is variably pre-
sent. Commonly associated conditions include
volar hyperhidrosis and poor peripheral circula-
tion. Although GRN usually resolves sponta-
neously at puberty, it sometimes persists indefi-
nitely, in which case telangiectasia becomes the
predominant feature.
Histopathologic examination reveals dilation of
dermal blood vessels and lymphatics with a mild
surrounding mononuclear cell infiltrate. These
changes are invariably accompanied by cystic
dilation of the eccrine ducts, sometimes even
resembling hidrocystoma. The pathogenesis of
GRN remains obscure. Some have suggested that
it represents a unique form of sweat retention.163
Family studies have indicated that most cases are
genetically determined, either in an autosomal
dominant or autosomal recessive pattern.164
Eccrine bromhidrosis and chromhidrosis
Eccrine sweat is usually odorless, but under
some circumstances it may assume an odor. The
most common form of this condition occurs in the
plantar and intertriginous regions and is caused by
bacterial degradation of macerated stratum
corneum, leading to odorogenic fatty acids.165
Predisposing factors include hyperhidrosis, obesi-
ty, intertrigo, and diabetes mellitus. The odor can
usually be diminished through control of hyper-
hidrosis, proper hygiene, and the use of absorbent
powders and antibacterial preparations.166
Wenzel and Horn 13
Excretion of certain ingested foods and drugs,
such as garlic and alcohol, into eccrine sweat may
impart an odor. In addition, certain systemic dis-
orders, such as various heritable amino-acidurias,
may produce odoriferous eccrine sweat.167 A "fish
odor" is reported to be characteristic of trimethy-
laminuria.168
Eccrine chromhidrosis is uncommon and is
almost always exogenous in nature. Chemicals,
dyes from clothing, or pigment production from
bacteria may lend a slight color to eccrine sweat,
but it is seldom striking.26
REFERENCES
1. Kuno Y. Human perspiration. Springfield (IL): Charles
C Thomas; 1956.
2. Sato K, Kang WH, Saga K, Sato KT. Biology of sweat
glands and their disorders. I. Normal sweat gland func-
tion. J Am Acad Dermatol 1989;20:537-63.
3. Montagna W, Chase HB, Lobitz WC Jr. Histology and
cytochemistry of human skin. IV. The eccrine sweat
glands. J Invest Dermatol 1963;20:415-23.
4. Headington JT. Primary mucinous carcimona of the
skin: histology and electron microscopy. Cancer 1977;
39:1055-63.
5. Hurley HJ, Witkowski JA. The dynamics of eccrine
sweating in man. J Invest Dermatol 1962;39:329-38.
6. Nadji M, Morales AR, Girtanner RE, et al. Paget's dis-
ease of the skin: a unifying concept of histogenesis.
Cancer 1982;50:2203-6.
7. Heyderman E, Graham RM, Chapman DV, et al.
Epithelial markers in primary skin cancer: an
immunoperoxidase study of the distribution of epithelial
membrane antigen (EMA) and carcinoembryonic anti-
gen (CEA) in 65 primary skin carcinomas. Histopatho-
logy 1984;8:423-34.
8. Kahn HJ, Baumal R, Marks A. The value of immuno-
histochemical studies using antibody to S-100 protein in
dermatopathology. Int J Dermatol 1984;23:38-44.
9. McGregor JM, Barker JN, Allen MH, et al. Antigenic
profile of human acrosyringium. Br J Dermatol 1991;
125:413-8.
10. Sato K, Leidal R, Sato F. Morphology and development
of an apoeccrine sweat gland in human axillae. Am J
Physiol 1987;252:R166-80.
11. Sato K, Sato F. Sweat secretion by human axillary
apoeccrine sweat gland in vitro. Am J Physiol 1987;252:
R181-7.
12. Sato K, Dobson RL, Mali JW. Enzymatic basis for the
active transport of sodium in the eccrine sweat gland:
localization and characterization of the Na-K-ATPase. J
Invest Dermatol 1971;57:10.
13. Sato K, Kang WH, Saga K, Sato KT. Biology of sweat
glands and their disorders. II. Disorders of sweat gland
function. J Am Acad Dermatol 1989;20:713-26.
14. Sato K, Ohtsuyama M, Samman G. Eccrine sweat gland
disorders. J Am Acad Dermatol 1991;24:1010-4.
15. Robinson AR. Miliaria and sudamina. J Cutan Venerol
Dis 1884;2:362.
16. Champion RH. Disorders of sweat glands. In:
Champion RH, Burton JL, Ebling FJG, editors.

14 Wenzel and Horn
Textbook of dermatology; vol 3. 5th ed. Oxford:
Blackwell; 1992. p. 1758-9.
17. Dobson RL, Lobitz W. Some histochemical observa-
tions on the human eccrine sweat glands: II. The patho-
genesis of miliaria. Arch Dermatol 1957;75:653.
18. Rochmis PG, Koplon BS. Iatrogenic miliaria crystallina
due to bethanochol. Arch Dermatol 1967;95:499-500.
19. Atherton DJ. The neonate. In: Champion RH, Burton
JL, Ebling FJG, editors. Textbook of dermatology; vol
1. 5th ed. Oxford: Blackwell; 1992. p. 387-8.
20. Hidano A, Purwoko R, Jutsukawa K. Statistical survey
of skin changes in Japanese neonates. Pediatr Dermatol
1986;3:140-4.
21. Straka BF, Cooper PH, Greer KE. Congenital miliaria
crystallina. Cutis 1991;47:103-6.
22. Arpey CJ, Nagashima-Whalen LS, Zaim MT, et al.
Congenital miliaria crystallina: case report and litera-
ture review. Pediatr Dermatol 1992;9:283-7.
23. Sulzberger MB, Harris DR. Miliaria and anhidrosis.
Arch Dermatol 1972;105:845-50.
24. Lyons RE, Levine R, Auld D. Miliaria rubra. Arch
Dermatol 1962;86:282-6.
25. Sanderson PH, Sloper JC. Skin disease in the British
army in SE Asia. Br J Dermatol 1953;65:252-64.
26. Hurley HJ. Diseases of the eccrine sweat glands. In:
Moschella SL, Hurley HJ, editors. Dermatology; vol 2.
3rd ed. Philadelphia: WB Saunders; 1992. p. 1514-37.
27. Hindson TC, Worsley DE. The effects of administration
of ascorbic acid in experimentally induced miliaria and
hypohidrosis in volunteers. Br J Dermatol 1969;81:226-
7.
28. O'Brien JP. The etiology of poral closure, I-IV. J Invest
Dermatol 1950;15:95-156.
29. Hölzle E, Kligman AM. The pathogenesis of miliaria
rubra: role of the resident microflora. Br J Dermatol
1978;99:117-37.
30. O'Brien JP. A study of miliaria rubra, tropical anhidro-
sis, and anhidrotic asthenia. Br J Dermatol 1947;59:
125-58.
31. Shelley WB, Horvath PN. Experimental miliaria in man.
J Invest Dermatol 1950;14:9-20.
32. Sulzberger MB, Zimmerman HM. Studies on prickly
heat. J Invest Dermatol 1946;7:61-8.
33. Loewenthal LJA. The pathogenesis of miliaria. Arch
Dermatol 1961;84:2-17.
34. Dobson RL, Lobitz WC. Some histochemical observa-
tions on the human eccrine sweat glands. Arch Dermatol
1957;75:653-66.
35. Yanagawa S, Yokozeki H, Sato K. Origin of periodic
acid-Schiff-reactive glycoprotein in human eccrine
sweat. J Appl Physiol 1986;60(Suppl 2):1615-22.
36. Unna PG. The histopathology of diseases of the skin.
Edinburgh: William F Clay; 1896. p. 908.
37. Acton HW. Prickly heat. Indian Med Gazette 1926;
61:321.
38. Lyons RE, Levine R, Auld D. Miliaria rubra: a manifes-
tation of staphylococcal disease. Arch Dermatol 1962;
86:282-6.
39. Lyons RE, Hunt JA. The treatment of miliaria rubra with
neomycin lotion. J Invest Dermatol 1954;24:557-9.
40. Stillman MA, Hindson TC, Maibach HI. The effect of
pre-treatment of skin in artificially induced miliaria
rubra and hypohidrosis. Br J Dermatol 1971;84:110-5.
41. Christensen GD, Simpson WA, Bisno AL, et al.
Adherence of slime-producing strains of Staphylococ-
Journal of the American Academy of Dermatology
January 1998
cus epidermidis to smooth surface. Infect Immun 1982;
37:318-26.
42. Davenport DS, Massanari RM, Pfaller MA, et al.
Usefulness of a test for slime production as a marker for
clinically significant infections with coagulase-negative
staphylococci. J Infect Dis 1986;153:332-9.
43. Mowad CM, McGinley KJ, Foglia A, et al. The role of
extracellular polysaccharide substance produced by
Staphylococcus epidermidis in miliaria. J Am Acad
Dermatol 1995;33:729-33.
44. Ludwicka AG, Uhlenbruck G, Peters G, et al.
Investigation on the extracellular slime substance pro-
duced by Staphylococcus epidermidis. Zentralbl
Bakteriol Microbiol Hyg (A) 1984;258:256-67.
45. Johnson H, Maibach HI. Drug excretion in human
eccrine sweat. J Invest Dermatol 1976;56:182-8.
46. Vree TB, Muskens AT, van Rossum JM. Excretion of
amphetamines in human sweat. Arch Int Pharmacodyn
Ther 1972;199:311-7.
47. Harden RM, Alexander WD. Quantitative aspects of
iodide secretion in human thermal sweat. Clin Sci 1963;
25:79-87.
48. Parnas J, Plachs H, Gram L, et al. Excretion of
antiepileptic drugs in sweat. Acta Neurol Scand 1978;
58:197-204.
49. Phillips M, McAloon MH. A sweat patch test for alco-
hol consumption: evaluation in continuous and episodic
drinkers. Clin Exp Res 1980;4:391-5.
50. Shah VP, Epstein WL, Riegelman S. Role of sweat in
accumulation of orally administered griseofulvin in the
skin. J Clin Invest 1974;53:1673-8.
51. Harris R, Jones HE, Artis WM. Orally administered
ketoconazole: route of delivery to the human stratum
corneum. Antimicrob Agents Chemother 1983;24:876-
82.
52. Wienig E, Jahn G. Die kriminalistiche Bedeutung der
Ausscheidung von Arzneimitteln im Schweiss. Dtsch Z
Ges Gerichtl Med 1954;43:370-3.
53. Høiby N, Johansen HK, Jarløv JO, et al. Ciprofloxacin
in sweat and antibiotic resistance [letter]. Lancet
1995;346:1235.
54. Cone EJ, Hillsgrove MJ, Jenkins AJ, et al. Sweat testing
for heroin, cocaine, and metabolites. J Anal Toxicol
1994;18:298-305.
55. Wildfeuer A, Faergemann J, Laufen H, et al.
Bioavailability of fluconazole in the skin after oral med-
ication. Mycoses 1994;37:127-30.
56. Balabanova S, Bühler G, Schneider E, et al. Über die
Ausscheidung von Nicotin mit dem apokrinen and
ekkrinen Schweiss bei Rauchern and Passiv-Rauchern.
Hautarzt 1992;43:73-6.
57. Horn TD, Beveridge RA, Egorin MJ, et al. Observations
and proposed mechanism of N,N´,N´´-triethylenethio-
phosphamide (thiotepa)-induced hyperpigmentation.
Arch Dermatol 1989;125:524-7.
58. Harrist TJ, Fine JD, Berman RS, et al. Neutrophilic
eccrine hidradenitis. Arch Dermatol 1982;118:263-6.
59. Flynn TC, Harrist TJ, Murphy GF, et al. Neutrophilic
eccrine hidradenitis: a distinctive rash associated with
cytarabine therapy and acute leukemia. J Am Acad
Dermatol 1984;11:584-90.
60. Beutner KR, Packman CH, Markowitch W.
Neutrophilic eccrine hidradenitis associated with
Hodgkin's disease and chemotherapy. Arch Dermatol
1986;122:809-11.
61. Fitzpatrick JE, Bennion SD, Reed OM, et al.
Journal of the American Academy of Dermatology
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Neutrophilic eccrine hidradenitis associated with induc-
tion chemotherapy. J Cutan Pathol 1987;14:272-8.
62. Katsanis E, Luke K-H, Hsu E, et al. Neutrophilic
eccrine hidradenitis in acute myelomonocytic leukemia.
Am J Pediatr Hematol Oncol 1987;9:204-8.
63. Scallan PJ, Kettler AH, Levy ML, et al. Neutrophilic
eccrine hidradenitis. Cancer 1988;62:2532-6.
64. Bailey DL, Barron D, Lucky AW. Neutrophilic eccrine
hidradenitis: a case report and review of the literature.
Pediatr Dermatol 1989;6:33-8.
65. Burg G, Bieber T, Langecker P. Lokalisierte neutrophile
ekkrine hidradenitis unter mitoxantron: eine typische
zytostatikanebenwirking. Hautarzt 1988;39:233-6.
66. Fernandez Cogolludo E, Ambrojo Antunez P, Aguilar
Martinez A, et al. Neutrophilic eccrine hidradenitis: a
report of two additional cases. Clin Exp Dermatol
1989;14:341-6.
67. Scherbenske JM, Benson PM, Lupton GP.
Asymptomatic erythematous papules in a leukemic
patient. Arch Dermatol 1990;126:528-9, 531-2.
68. Margolis DJ, Gross PR. Neutrophilic eccrine hidradeni-
tis: a case report and review of the literature. Cutis
1991;48:198-200.
69. Vion B, Alvero H. Neutrophilic eccrine hidradenitis.
Dermatologica 1991;183:70-1.
70. Scong VY, Appell ML, Sanders DY, et al. Annular
plaques on the dorsa of the hands. Arch Dermatol
1991;127:1397-9, 1400-2.
71. Cancelez Perez JA, Perez de Oteyza J, Megido M, et al.
Chemotherapy-induced neutrophilic eccrine hidradeni-
tis in acute myeloid leukemia. Acta Haematol 1992;87:
167-8.
72. Bernstein EF, Spielvogel RL, Topolsky DL. Recurrent
neutrophilic eccrine hidradenitis. Br J Dermatol 1992;
127:529-33.
73. Thorisdotter K, Tomecki K, Bergfeld WF, et al.
Neutrophilic eccrine hidradenitis. J Am Acad Dermatol
1993;28:775-7.
74. Ostlere LS, Wells J, Stevens HP, et al. Neutrophilic
eccrine hidradenitis with an unusual presentation. Br J
Dermatol 1993;128:696-8.
75. Bardenstein DS, Haluschak J, Gerson S, et al.
Neutrophilic eccrine hidradenitis simulating orbital cel-
lulitis. Arch Ophthalmol 1994;112:1460-3.
76. Aractingi S, Mallet V, Pinquier L, et al. Neutrophilic
dermatoses during granulocytopenia. Arch Dermatol
1995;131:1141- 5.
77. Pierson JC, Helm TN, Taylor JS, et al. Neutrophilic
eccrine hidradenitis heralding the onset of acute myel-
ogenous leukemia. Arch Dermatol 1993;129:791-2.
78. Templeton SF, Solomon AR, Swerlick RA. Intradermal
bleomycin injections into normal human skin. Arch
Dermatol 1994;130:577-83.
79. Greenbaum BH, Heymann WR, Reid CS, et al.
Chemotherapy- associated eccrine hidradenitis: neu-
trophilic eccrine hidradenitis reevaluated: the role of
neutrophilic infiltration. Med Pediatr Oncol 1988;16:
351-5.
80. Allegue F, Soria C, Rocamora A, et al. Neutrophilic
eccrine hidradenitis in two neutropenic patients. J Am
Acad Dermatol 1990;23:1110-3.
81. Moreno A, Barnadas MA, Ravella A, et al. Infectious
eccrine hidradenitis in a patient undergoing hemodialy-
sis. Arch Dermatol 1985;121:1106-7.
82. Allegue F, Rocamora A, Martin-Gonzalez M, et al.
Wenzel and Horn 15
Infectious eccrine hidradenitis. J Am Acad Dermatol
1990;22:1119-20.
83. Taira JW, Gerber HB. Eccrine hidradenitis. Int J
Dermatol 1992;31:433-4.
84. Stahr BJ, Cooper PH, Caputo RV. Idiopathic plantar
hidradenitis occurring primarily in children. J Cutan
Pathol 1994;21:289-96.
85. Manganoni AM, Facchetti F, Gavazzoni R, et al.
Neutrophilic eccrine hidradenitis in a healthy woman.
Dermatology 1994;189:211-2.
86. Rabinowitz LG, Cintra ML, Hood AF, et al. Recurrent
palmoplantar hidradenitis in children. Arch Dermatol
1995;131:817-20.
87. Smith KJ, Skelton HG, James WD, et al. Neutrophilic
eccrine hidradenitis in HIV-infected patients. J Am
Acad Dermatol 1990;23:945-7.
88. Huttenlocher A, Frieden IJ, Emery H. Neonatal onset
multisystem inflammatory disease. J Rheumatol
1995;22:1171-3.
89. Yarom A, Rennebohm RM, Levinson JE. Infantile mul-
tisystem inflammatory disease: A specific syndrome? J
Pediatr 1985;106:390-6.
90. Kuttner BJ, Kurban RS. Neutrophilic eccrine hidradeni-
tis in the absence of an underlying malignancy. Cutis
1988;41:403-5.
91. Freeman RG. On the pathogenesis of pseudoepithe-
liomatous hyperplasia. J Cutan Pathol 1974;1:231-7.
92. King DT, Barr RJ. Syringometaplasia: mucinous and
squamous variants. J Cutan Pathol 1979;6:284-91.
93. Bhawan J, Malhotra R. Syringosquamous metaplasia: a
distinctive eruption in patients receiving chemotherapy.
Am J Dermatopathol 1990;12:1-6.
94. Hurt MA, Halvorson RD, Friedman DJ, et al. Eccrine
squamous syringometaplasia. Arch Dermatol 1990;126:
73-7.
95. Lerner TH, Barr RJ, Dolezal JF, et al. Syringomatous
hyperplasia and eccrine squamous syringometaplasia
associated with benoxaprofen therapy. Arch Dermatol
1987;123:1202-4.
96. Rios-Buceta L, Penas PF, Dauden-Tello E, et al. Recall
phenomenon with the unusual presence of squamous
syringometaplasia. Br J Dermatol 1995;133:630-2.
97. Wong P, Bangert JL, Levine N. A papulovesicular erup-
tion in a man receiving chemotherapy for metastatic
melanoma. Arch Dermatol 1993;129:232-3, 235-6.
98. Bhawan J, Petry J, Rybak ME. Histologic changes
induced in skin by extravasation of doxorubicin (adri-
amycin). J Cutan Pathol 1989;16:158-63.
99. Metcalf JS, Maize JC. Squamous syringometaplasia in
lobular panniculitis and pyoderma gangrenosum. Am J
Dermatopathol 1990;12:141-9.
100. Rongioletti F, Ballestrero A, Bogliolo F, et al.
Necrotizing eccrine syringometaplasia presenting as
acral erythema. J Cutan Pathol 1991;18:453-6.
101. Caputo R, Monti M, Ermacora E, et al. Cutaneous man-
ifestations of tetrachlorodibenzo-p-dioxin in children
and adolescents. J Am Acad Dermatol 1988;19:812-9.
102. Serrano T, Amparo S, Moreno A. Eccrine squamous
syringometaplasia. J Cutan Pathol 1993;20:61-5.
103. Larry DJ. Mémoires de chirurgie militaire et cam-
pagnes; vol 3. Paris: Smith and Buisson; 1812. p. 13.
104. Bie J, Kirkegaard A. Traumatiske komplikationes ved
svaer akut barbiturate Fogiftning. Nord Med
1950;44:1680-1.
105. Leavell UW. Sweat gland necrosis in barbiturate poi-
soning. Arch Dermatol 1969;100:218-21.

16 Wenzel and Horn
106. Mandy S, Ackerman AB. Characteristic traumatic skin
lesions in drug-induced coma. JAMA 1970;213:253-6.
107. Gröschel D, Gerstein AR, Rosenbaum JM. Skin lesions
as a diagnostic aid in barbiturate poisoning. N Engl J
Med 1970;283:409-10.
108. Arndt KA, Mihm MC, Parrish JA. Bullae: a cutaneous
sign of a variety of neurologic diseases. J Invest
Dermatol 1973;60:312-20.
109. Varma AJ, Fisher BK, Sarin MK. Diazepam-induced
coma with bullae and eccrine sweat gland necrosis.
Arch Intern Med 1977;137:1207-11.
110. Herschtal D, Robinson MJ. Blisters of the skin in coma
induced by amitriptyline and clorazepate dipotassium.
Arch Dermatol 1979;115:499.
111. Sanchez Yus E, Requena L, Simon P, et al.
Histopathology of cutaneous changes in drug-induced
coma. Am J Dermatopathol 1993;15:208-16.
112. Lewis E. Bullous lesions. Br Med J 1965;1:995-8.
113. Katz S, Stein IM, Fulop M. Bullous eruption associated
with heroin pulmonary edema. JAMA 1971;216:145.
114. Carsuzaa F, De Jaureguiberry J-P, Carloz E, et al.
Nécrose sudorale en plaques au cours du SIDA. Ann
Dermatol Venereol 1993;120:448-9.
115. Sorensen BF. Skin symptoms in acute narcotic intoxica-
tion. Dan Med Bull 1963;10:130-1.
116. Ridley CM. Bullous lesions in nitrazepam overdosage.
Br Med J 1971;3:28.
117. Noble J, Matthew H. Acute poisoning by tricyclic anti-
depressants: clinical features and management of 100
patients. Clin Toxicol 1969;2:403-21.
118. Raymond LW, Cohen AB. "Barbiturate blisters" in a
case of severe hypoglycaemic coma. Lancet
1972;2:764.
119. Metz RJS, Cooper W. Salt retention and uremia in brain
injury. Br Med J 1958;1:435-8.
120. Robertson EE. Skin lesions in organic brain disease. Br
Med J 1953;1:291-5.
121. McLardy T. Uraemic and trophic deaths following
leukotomy: neuroanatomical findings. J Neurol
Neurosurg Psychiatry 1950;13:106-14.
122. Ziegler LH, Osgood CW. Edema and trophic distur-
bances of the lower extremities complicating prefrontal
lobotomy. Arch Neurol Psych 1945;53:262-8.
123. Judge TG, Nisbet NH. Trophoneurotic blisters in elder-
ly hemiplegics. Lancet 1967;1:811-2.
124. Holten C. Cutaneous phenomena in acute barbiturate
poisoning. Acta Derm Venereol (Stockh) 1952;32(Suppl
29):162-8.
125. Beveridge GW, Lawson AAH. Occurrence of bullous
lesions in acute barbiturate intoxication. Br Med J
1965;1:835-7.
126. Adebahr G. Hautveränderungen bei Schlafmittelvergif-
tung. Landarzt 1963;30:130-8.
127. Achten G, Ledoux-Corbusier M, Thys J-P. Intoxication
à l'oxyde de carbone et lésions cutanées. Ann Dermat
Syph (Paris) 1971;98:421-8.
128. Rocamora A, Matarredonda J, Sendagorta E, et al.
Sweat gland necrosis in drug-induced coma: a light and
direct immunofluorescence study. J Dermatol 1986;13:
49-53.
129. Brehmer-Anderson A, Pedersen WB. Sweat gland
necrosis and bullous skin changes in acute drug intoxi-
cation. Acta Derm Venereol (Stockh) 1969;49:157-62.
130. Taniguchi Y, Wada Y, Takahashi M, et al. Multiple bul-
lae and paresis after drug-induced coma. Acta Derm
Venereol (Stockh) 1991;71:536-8.
Journal of the American Academy of Dermatology
January 1998
131. Reilly GD, Harrington CI. Positive immunofluores-
cence in bullous lesions in drug-induced coma. Br J
Dermatol 1983;109:720.
132. Elias PM, Fritsch PO. Erythema multiforme. In:
Fitzpatrick TB, Eisen AZ, Wolff K, editors.
Dermatology in general medicine. 3rd ed. New York:
McGraw-Hill; 1987. p. 555-63.
133. Assier H, Bastuji-Garin S, Revuz J, et al. Erythema mul-
tiforme with mucous membrane involvement and
Stevens-Johnson syndrome are clinically different dis-
orders with distinct causes. Arch Dermatol 1995;131:
539-43.
134. Zohdi-Mofid M, Horn TD. Acrosyringial concentration
of necrotic keratinocytes in erythema multiforme: a clue
to drug etiology. J Cutan Pathol 1997;24:235-40.
135. Gaspari AA, Cheng SF, DiPersio JF, et al. Roquinimex-
induced graft-versus-host reaction after autologous
bone marrow transplantation. J Am Acad Dermatol
1995;33:711-7.
136. Morris WJ, Dische S, Mott G. A pilot study of a method
of estimating the number of functional eccrine sweat
glands in irradiated skin. Radiother Oncol 1992;25:49-
55.
137. Johns J, Morris WJ, Joiner MC. Radiation response of
murine eccrine glands. Radiother Oncol 1994;36:56-64.
138. Kossard S, Commens CA. Keratotic miliaria precipitat-
ed by radiotherapy. Arch Dermatol 1988;124:855-6.
139. Di Sant'Agnese PA, Davis PB. Research in cystic fibro-
sis. N Engl J Med 1976;295:481-5, 534-41, 597-602.
140. Quinton PM, Bijman J. Higher bioelectric potentials
due to decreased chloride absorption in the sweat glands
of patients with cystic fibrosis. N Engl J Med 1983;
308:1185-9.
141. Sato K, Saga K, Sato F. Membrane transport and intra-
cellular events in control and cystic fibrosis eccrine
sweat glands. In: Mastella G, Quinton PM, editors.
Cellular and molecular basis of cystic fibrosis. San
Francisco: San Francisco Press; 1988. p. 171-85.
142. Krauss RD, Rado TA. Current approaches to the molec-
ular and physiological basis of cystic fibrosis. Am J
Med Sci 1989;298:334-9.
143. Sato K, Sato F. Defective beta adrenergic response of
cystic fibrosis sweat glands in vivo and in vitro. J Clin
Invest 1984;73:1763-71.
144. Hall SK, Stableforth DE, Green A. Sweat sodium and
chloride concentrations: essential criteria for the diag-
nosis of cystic fibrosis in adults. Ann Clin Biochem
1990;27:318-22.
145. Stewart B, Zabner J, Shuber AP, et al. Normal sweat
chloride values do not exclude the diagnosis of cystic
fibrosis. Am J Respir Crit Care Med 1995;151:899-903.
146. Wilschanski M, Zielenski J, Markiewicz D, et al.
Correlation of sweat chloride concentration with class-
es of the cystic fibrosis transmembrane conductance
regulator gene mutations. J Pediatr 1995;127:705-10.
147. Belchin RW. Ultrastructure and function of eccrine
glands in the mucopolysaccharidoses. Arch Pathol
1973;96:339-44.
148. Drut R. Eccrine sweat gland involvement in GM gan-
gliosidosis. J Cutan Pathol 1978;5:35-40.
149. Ruiter M. Histologic investigation of the skin in angiok-
eratoma corporis diffusum in particular with regard to
the associated disturbance of phosphatid metabolism.
Dermatologica 1954;109:273-86.
150. Pittelkow RB, Kierland RR, Montgomery H.
Polariscopic and histochemical studies in angioker-
Journal of the American Academy of Dermatology
Volume 38, Number 1
atoma corporis diffusum. Arch Dermatol 1957;76:59-
64.
151. Nakamura T, Kaneko H, Nishino I. Angiokeratoma cor-
poris diffusum (Fabry disease): ultrastructural studies of
the skin. Acta Derm Venereol (Stockh) 1981;61:37-41.
152. Epinette WW, Norins AL, Drew AL, et al.
Angiokeratoma corporis diffusum with alpha-L-fucosi-
dase deficiency. Arch Dermatol 1973;107:754-7.
153. Yokota M, Koji M, Yotsumoto S. Histopathologic and
ultrastructural studies of angiokeratoma corporis dif-
fusum in Kanzaki disease. J Dermatol 1995;22:10-8.
154. Martin JJ, Cruterich C. Morphologic study of skin biop-
sy specimens: a contribution to the diagnosis of meta-
bolic disorders with involvement of the nervous system.
J Neurol Neurosurg Psychiatry 1978;41:232-6.
155. Carpenter S, Karpati G. Sweat gland cells in LaFora dis-
ease: diagnosis by skin biopsy. Neurology 1981;31:
1564.
156. Means M, Dobson RL. Cytologic changes in the sweat
gland in hypothyroidism. JAMA 1950;186:113.
157. Saklayen MG, Schroeter AL, Nafz MA, et al. IgA depo-
sition in the skin of patients with alcoholic liver disease.
J Cutan Pathol 1996;23:12-8.
158. Landing BH, Wells TR. Anatomy of eccrine sweat
glands in D1, G1, and 18 trisomy syndromes. J Invest
Dermatol 1968;50:475-82.
159. Lewandowsky F. Zur Pathogenese der multiplen
Wenzel and Horn 17
Abcesse in Säuglingsalter. Arch Dermatol Syphil
1906;108:179-92.
160. Maibach HI, Kligman AM. Multiple sweat gland
abscesses. JAMA 1960;174:124-6.
161. Maschkilleisson LN, Naradow LA. 33 Fälle von
Jadassohns Granulosis rubra nasi. Derm Z 1935;71:79-
84.
162. Grinoni F. Contributo clinico allo studio dell'etiopatoge-
nesi della Granulosis Rubra Nasi. G Dermatol Sif
1955;96:227.
163. Shelley WB. Granulosis rubra nasi. In: Pillsbury DM,
Shelley WB, Kligman AM, editors. Dermatology.
Philadelphia: WB Saunders; 1956. p. 835.
164. Touraine A. L'Heredite en medicine. Paris: Masson et
Cie; 1955. p. 551.
165. Kanda F, Yagi E, Fukuda M, et al. Elucidation of chem-
ical compounds responsible for foot malodour. Br J
Dermatol 1990;122:771-6.
166. Hurley HJ. Diseases of the apocrine sweat glands. In:
Moschella SL, Hurley HJ, editors. Dermatology; vol 2.
3rd ed. Philadelphia: WB Saunders; 1992. p. 1495-513.
167. Cone TE. Diagnosis and treatment: some diseases, syn-
dromes and conditions associated with an unusual odor.
Pediatrics 1968;41:993-5.
168. Marks R, Greaves MW, Prottey C, et al.
Trimethlyaminuria. Br J Dermatol 1977;96:399-402.
CME examination Identification No. 898-101

Instructions for Category I CME credit appear in the front advertising section. See last page of Contents for page number.

Questions 1-30, Wenzel FG, Horn TD. J Am Acad Dermatol 1998;38:1-17.

Directions for questions 1-30: Give single best a. familial dysautonomia (Riley-Day syndrome)
response. b. anhidrotic ectodermal dysplasia
1. Basophilic granules are present in which of the c. diabetes mellitus
following cells? d. pheochromocytoma
a. Clear cells e. systemic sclerosis
b. Dark cells 8. What percentage of neonates is affected by mil-
c. Ductal epithelium iaria rubra?
d. Myoepithelial cells a. 1%
e. Keratinocytes b. 4%
2. The principal neurotransmitter at the nerve end- c. 12%
ings innervating eccrine glands is d. 25%
a. acetylcholine e. 50%
b. norepinephrine 9. Tropical anhidrotic asthenia is caused by pro-
c. substance P longed episodes of
d. epinephrine a. neutrophilic eccrine hidradenitis
e. dopamine b. hypohidrosis
3. S-100 protein is expressed in c. miliaria crystallina
a. dark cells d. miliaria profunda
b. clear cells e. heat stroke
c. myoepithelial cells
10. A characteristic histopathologic finding in mil-
d. eccrine ductal epithelium
iaria is
e. lipocytes surrounding the eccrine coils
a. a tortuous eccrine duct
4. Each of the following is a constituent of eccrine b. necrosis of the eccrine coils
sweat except c. loss of eccrine units
a. lactate d. periodic acid–Schiff–positive plug in the
b. phosphate acrosyringium
c. urea e. abscess formation
d. sodium
11. Which of the following bacteria has been impli-
e. potassium
cated (under experimental conditions) in the
5. How many times higher is the secretory rate of pathogenesis of miliaria?
apoeccrine glands than eccrine glands? a. Staphylococcus aureus
a. 2 b. Propionibacterium acnes
b. 10 c. Corynebacterium minutissimum
c. 50 d. Micrococcus sedentarius
d. 100 e. Staphylococcus epidermidis
e. 1000
12. The most common malignancy associated with
6. Each of the following is considered effective in neutrophilic eccrine hidradenitis is
the treatment of hyperhidrosis except a. acute myelogenous leukemia
a. aluminum salts b. chronic lymphocytic leukemia
b. tap water iontophoresis c. Hodgkin's disease
c. anticholinergics d. neuroblastoma
d. sympathectomy e. carcinoma of the lung
e. antihistamines
13. The most common chemotherapeutic agent asso-
7. Each of the following is a cause of hypohidrosis ciated with neutrophilic eccrine hidradenitis is
except a. 5-fluorouracil

18
Journal of the American Academy of Dermatology
Volume 38, Number 1 CME examination 19

b. cyclophosphamide a. Doxorubicin
c. cytarabine b. Thiotepa
d. vincristine c. Ciprofloxacin
e. methotrexate d. Griseofulvin
e. Phenobarbital
14. Palmoplantar hidradenitis in healthy persons is
most frequently observed in which of the follow- 21. The most likely explanation of eccrine gland
ing age ranges? injury in drug-related eccrine disorders is
a. Up to 1 year a. direct blood vessel damage
b. 1 to 20 years b. immune complex–mediated damage
c. 21 to 40 years c. concentration of the drug in eccrine sweat
d. 41 to 60 years d. shared epitopes between eccrine epithelium
e. Older than 60 years and the drug
e. overgrowth of bacteria invading the eccrine
15. Syringosquamous metaplasia is most commonly
glands
observed in which of the following clinical situa-
tions? 22. Necrosis of the eccrine glands in graft-versus-
a. Antibiotic therapy host disease has been reported in association with
b. Radiation therapy a. granulocyte-macrophage colony-stimulating
c. Prolonged febrile episodes factor
d. UV light therapy b. bone marrow infusion
e. Systemic chemotherapy c. roquinimex
16. The histopathologic characteristics of syringo- d. cyclosporine
squamous metaplasia can mimic which of the fol- e. thalidomide
lowing? 23. After ionizing radiation, eccrine function is low-
a. Miliaria est at
b. Eccrine poroma a. 2 days
c. Squamous cell carcinoma b. 1 week
d. Neutrophilic eccrine hidradenitis c. 4 weeks
e. Eccrine hidrocystoma d. 8 weeks
17. Each of the following conditions has been e. 16 weeks
described in drug-induced coma except 24. Sweat sodium levels above which of the follow-
a. bullae ing levels are diagnostic of cystic fibrosis in chil-
b. violaceous plaques dren?
c. subcutaneous nodules a. 10 mmol/L
d. erosions b. 25 mmol/L
e. macular erythema c. 60 mmol/L
18. The histopathologic hallmark of drug-induced d. 100 mmol/L
coma is e. 120 mmol/L
a. necrosis of the eccrine coils 25. Periodic acid–Schiff–positive granules in the
b. dilation of the eccrine ducts outer layer of eccrine ductal cells can be
c. loss of eccrine units observed in
d. loss of fat investing the eccrine coils a. Niemann-Pick disease
e. neutrophilic infiltrate of the eccrine ducts b. Lafora's disease
19. Acrosyringeal concentration of keratinocyte c. Fabry's disease
necrosis has been observed in which of the fol- d. Hurler's syndrome
lowing disorders? e. Kanzaki syndrome
a. fixed drug eruption
26. IgA deposits in the basement membrane of
b. drug-induced coma
eccrine coils have been observed in patients with
c. graft-versus-host disease
a. alcoholic liver disease
d. septic emboli
b. inflammatory bowel disease
e. drug-related erythema multiforme
c. chronic sinusitis
20. Which of the following drugs excreted into sweat d. hyperthyroidism
has been reported to cause hyperpigmentation? e. Fabry's disease
 Journal of the American Academy of Dermatology
20 CME examination January 1998

27. Multiple sweat gland abscesses occur most com- 29. A "fish odor" of the sweat is characteristic of
monly in a. trimethylaminuria
a. immunocompromised patients b. Hartnup's disease
b. patients undergoing antibiotic therapy c. Fabry's disease
c. healthy adults d. alkaptonuria
d. bed-bound elderly e. Hurler's syndrome
e. chronically ill children
30. Eccrine chromhidrosis is usually caused by
28. The first manifestation of granulosa rubra nasi is a. excess lipofuscin granules in the dark cells of
a. erythema the secretory coils
b. edema b. ingestion of certain foods
c. pustules c. clothing dyes
d. tenderness d. metabolic disorders
e. hyperhidrosis e. minocycline

Answers to CME examination Identification No. 897-112

December 1997 issue of the Journal of the American Academy of Dermatology

Questions 1-33, Requena L, Sangueza OP. J Am Acad Dermatol 1997;37:887-920.

1. e 12. e 23. d
2. d 13. b 24. e
3. b 14. d 25. a
4. e 15. e 26. d
5. e 16. c 27. e
6. b 17. e 28. c
7. e 18. e 29. e
8. b 19. e 30. d
9. c 20. e 31. c
10. c 21. a 32. a
11. c 22. e 33. b