Clinics in Dermatology (2015) 33, 483491

Hyperhidrosis, bromhidrosis, and chromhidrosis:

Fold (intertriginous) dermatoses
Kristina Semkova, MD a,, Malena Gergovska, MD b , Jana Kazandjieva, MD, PhD a ,
Nikolai Tsankov, MD, PhD c
a
St. John's Institute of Dermatology, London, Westminster Bridge Road, SE1 7EH, United Kingdom
b
Euro Derma Clinic, Sofia, Bulgaria
c
Tokuda Hospital, Sofia, Bulgaria

Abstract Human sweat glands disorders are common and can have a significant impact on the quality of life
and on professional, social, and emotional burdens. It is of paramount importance to diagnose and treat them
properly to ensure optimal patient care. Hyperhidrosis is characterized by increased sweat secretion, which
can be idiopathic or secondary to other systemic conditions. Numerous therapeutic options have been
introduced with variable success. Novel methods with microwave-based and ultrasound devices have been
developed and are currently tested in comparison to the conventional approaches. All treatment options for
hyperhidrosis require frequent monitoring by a dermatologist for evaluation of the therapeutic progress.
Bromhidrosis and chromhidrosis are rare disorders but are still equally disabling as hyperhidrosis.
Bromhidrosis occurs secondary to excessive secretion from either apocrine or eccrine glands that become
malodorous on bacterial breakdown. The condition is further aggravated by poor hygiene or underlying
disorders promoting bacterial overgrowth, including diabetes, intertrigo, erythrasma, and obesity.
Chromhidrosis is a rare dermatologic disorder characterized by secretion of colored sweat with a
predilection for the axillary area and the face. Treatment is challenging in that the condition usually recurs
after discontinuation of therapy and persists until the age-related regression of the sweat glands.
2015 Elsevier Inc. All rights reserved.

Human sweat glands (sudoriferous or sudoriparous glands)
are subdivided into three main typeseccrine, apocrine, and
apoeccrinebased on their different structure, anatomic distri-
bution, function, secretory products, and mechanism of excretion.
Eccrine glands
Eccrine glands are distributed with varying density over the
entire skin surface with the exception of the lips, ear canal,
Corresponding author.
E-mail address: kristina_semkova@yahoo.com (K. Semkova).
prepuce, glans penis, labia minora, and clitoris. The glands are
10 times smaller than apocrine glands and open with a duct
directly onto the skin surface. Eccrine sweat is a dilute salt
solution that contains mostly water and electrolytes. The total
volume of eccrine sweat depends on the number of functional
glands in the respective area and the size of the surface opening.
The degree of secretory activity is regulated by neural and
hormonal mechanisms. At their maximum capacity, eccrine
glands can produce more than three liters of secretions per
hour.1 Eccrine sweat has three primary functions: thermoreg-
ulation, excretion of electrolytes and exogenous substances,
and protection as an important part of the skin barrier.

http://dx.doi.org/10.1016/j.clindermatol.2015.04.013
0738-081X/ 2015 Elsevier Inc. All rights reserved.
484
Apocrine glands
Apocrine glands are found in limited areas over the body,
mostly in the axillary region, perineum, around the nipples,
in the ears, and on the eyelids. They secrete small amounts of
oily fluid that is excreted into the pilary canal of the hair
follicle and not directly onto the skin surface. Apocrine sweat
is initially odorless when excreted onto the skin but is soon
degraded by the resident bacteria. Its breakdown products are
responsible for the individual pheromonal body odor.24
Apoeccrine glands
Apoeccrine glands are a mixed type of sweat glands, as
they simultaneously show features of the other two well-
studied types.2 They presumably develop during puberty
from eccrine glands and can represent up to 50% of all
axillary glands. Apoeccrine glands continuously secrete a
thin, watery sweat with similar sodium and potassium
concentrations as eccrine sweat. These glands show a greater
responsiveness to cholinergic and adrenergic stimuli than
eccrine glands, and their overall sweat secretion rate is
higher than that of other types of sweat glands. Due to this
and to their abundance in the axillary region, it is believed
that apoeccrine glands are of paramount significance for
axillary sweating.
Hyperhidrosis
Hyperhidrosis (also polyhidrosis or sudorrhea) is a
common medical condition characterized by abnormally
increased sweating, defined as sweat secretion that largely
exceeds the quantity required for normal body thermoreg-
ulation. In patients with hyperhidrosis, sweat secretion may
occur at low temperatures or at rest. The disorder is
associated with a significant quality of life burden from a
psychological, emotional, and social perspective. Studies on
quality of life reveal that the negative effects of hyperhidrosis
are comparable to those of conditions such as severe
psoriasis, end-stage renal failure, rheumatoid arthritis, and
multiple sclerosis.5
Hyperhidrosis is primary (idiopathic) or secondary to
other diseases. It is generalized (involving the whole body)
or focal (involving specific body sites, most commonly the
axillae, palms, soles, and face).6 Hyperhidrosis can be further
distinguished by anatomic distribution of affected regions
and by laterality: unilateral versus bilateral and symmetric.7
Primary hyperhidrosis is idiopathic and focal.6 It affects
about 2.8% of the U.S. population.8 It shows no sexual
predilection and most commonly affects people between 25
and 64 years of age. Rarely, patients may be affected in early
childhood.8 Japanese individuals are reportedly affected by
K. Semkova et al.
hyperhidrosis more than 20 times more frequently than other
ethnic groups;911 however, all races can be affected.
Genetic predisposition is seen in about 30% to 50% of
people with an autosomal dominant mode of transmission,
incomplete penetrance, and variable phenotype.11 Only one
primary focal hyperhidrosis locus was mapped to chromo-
some 14q11.2-q13, but no disease-causing gene has been
identified.12
Secondary hyperhidrosis can be either generalized or
focal and results from an underlying condition such as
endocrine, neurologic, or infectious disorders.
Pathophysiology
Hyperhidrosis is observed in the areas with the highest
density of eccrine and apoeccrine sweat glands. Apocrine
glands have not been shown to contribute to excessive sweat
production.13 Axillary hyperhidrosis is the most common,
followed by palmar and plantar hyperhidrosis.
In the localized form, hyperhidrosis is due to an abnormal
regeneration of sympathetic nerves or a localized abnormal-
ity in the number or distribution of the eccrine glands.
Essential hyperhidrosis, which is a disorder of the eccrine
sweat glands, is usually associated with sympathetic
overactivity.14
Generalized hyperhidrosis may be a result of autonomic
dysregulation, or it may be a consequence of a systemic
disease, febrile illness, and adverse effects of medications or
malignancy. Hyperhidrosis beginning later in life requires
investigations for endocrine disorders (diabetes mellitus,
hyperthyroidism, and hyperpituitarism) or neurologic
conditions (including peripheral nerve injury, Parkinsons
disease, reflex sympathetic dystrophy, spinal injury, and
Arnold-Chiari malformation). Asymmetric hyperhidrosis
may also be a sign of neurologic disease.15 Additional
causes include pheochromocytoma, carcinoid syndrome,
respiratory disease, and psychiatric disease. Hyperhidrosis
may accompany hot flashes during menopause. Medica-
tions associated with excessive sweating include propran-
olol, physostigmine, pilocarpine, tricyclic antidepressants,
and serotonin reuptake inhibitors. It has been reported that
the temperament and character profile of patients with
essential hyperhidrosis 16 is not related to social phobia or
personality disorder.
Clinical presentation
Primary hyperhidrosis usually involves the hands, axillae,
feet, and the craniofacial region. The diagnostic criteria
include excessive sweating for at least 6 months with 4 or
more of the following present:
primary involvement of eccrine-dense (axillae/palms/
soles/craniofacial) sites
Hyperhidrosis, bromhidrosis, and chromhidrosis: Fold (intertriginous) dermatoses
bilateral and symmetric distribution
absence of signs at night
episodes at least weekly
onset at 25 years of age or younger
positive family history
impairment of daily activities.17
Localized unilateral or segmental hyperhidrosis is rare and
of unknown etiology. It usually occurs on the forearm or
forehead in otherwise healthy individuals with no evidence of
the typical triggering factors found in essential hyperhidrosis.
Hyperhidrosis affecting relatively small areas (less than
100 cm2)11 includes idiopathic unilateral circumscribed
hyperhydrosis, gustatory sweating, lacrimal sweating, Har-
lequin syndrome, and emotional hyperhidrosis. There are
reported associations of unilateral circumscribed hyperhy-
drosis with blue rubber bleb nevus, glomus tumor, POEMS
syndrome, burning feet (Gopalans) syndrome, trench foot,
causalgia, pachydermoperiostosis, and pretibial myxedema.
Gustatory sweating is associated with encephalitis, syringo-
myelia, diabetic neuropathies, herpes zoster, parotitis, and
auriculotemporal (Freys) syndrome. Lacrimal sweating is
due to postganglionic sympathetic deficit, often seen in
Raeders syndrome. Harlequin syndrome is described as a
unilateral hyperhidrosis and flushing that are predominantly
induced by exercise or heat.18 The sympathetic deficits are
usually limited to the face. Unilateral hyperhidrosis has been
described on the right sides of the forehead, the nose, and the
palmar surface of the right hand with anhidrosis on the left
hand.19
Hyperhidrosis affecting relatively large areas (generalized;
covering over 100 cm2)11 occurs in people with a past history
of spinal cord injuries, orthostatic hypotension, posttraumatic
syringomyelia and in association with peripheral neuropathies,
familial dysautonomia (Riley-Day syndrome), congenital
autonomic dysfunction with universal pain loss, and exposure
to cold, notably associated with cold-induced sweating
syndrome. It could also be associated with brain lesions,
episodic with hypothermia (Hines-Bannick syndrome) or
without hypothermia, olfactory conditions, or systemic
medical problems, such as pheochromocytoma, Parkinsons
disease, thyrotoxicosis, diabetes mellitus, fibromyalgia, or
congestive heart failure.
Laboratory investigations
The iodine starch test may be used if direct visualization
of the areas affected by hyperhidrosis is desired. This test
requires spraying the affected area with a mixture of 0.5 to 1
g of iodine crystals and 500 g of soluble starch. Areas with
increased sweat secretion turn black. There are many other
test methods, including the Minors starch-iodine test with
gravimetric analysis,20 dynamic sudorometry,21 thermoreg-
ulatory sweat test,17 and skin conductance.22
485
Additional tests to clarify a possible underlying pathology
include thyroid function, blood glucose, urinary catecholamines,
uric acid, and purified protein derivative. Chest radiography may
be used to rule out tuberculosis or a neoplastic condition.
In patients with hyperhidrosis, the eccrine glands have
normal morphologic structure and functions. In patients with
localized hyperhidrosis, an abnormal number and/or distri-
bution of otherwise normal eccrine glands may be found.
Treatment
Various therapeutic options can be used to treat axillary
hyperhidrosis: topical medications, systemic medications,
iontophoresis, botulinum toxin, and surgical procedures.
Each case must be evaluated separately, considering the
severity and extent of the clinical condition, as well as the
advantages and disadvantages of each method. The treatment
of axillary hyperhidrosis should follow a step-by-step strategy,
always beginning with conservative methods. All treatment
options for hyperhidrosis require frequent monitoring by a
dermatologist for evaluation of the therapeutic progress.
Topical treatments
Topical treatments include boric acid, topical anticholiner-
gics, 2% to 5% tannic acid solutions, resorcinol, potassium
permanganate, formaldehyde,23 glutaraldehyde, and methena-
mine. All of these agents have limited effectiveness or are
restricted due to side effects such as staining, contact
sensitization, and irritation. Aluminum salt solutions are the
most common antiperspirants in use.24 Aluminum chloride
works by blocking the openings of the sweat ducts. It is believed
that the metal ions precipitate with mucopolysaccharides,
damaging the epithelial cells along the lumen of the duct and
forming a plug that blocks sweat secretion. Sweat is still
produced, as evidenced by the appearance of miliaria during heat
stress, with sweat building up behind the obstruction created by
the metallic salt25; however, normal sweat gland function returns
with epidermal renewal, necessitating retreatment once or twice
a week. Aluminum chloride tends to work best in the axillae.
Products containing 10% to 20% aluminum chloride hexahy-
drate are the first line of treatment for underarm sweating. Some
patients may be prescribed a product containing a higher dose of
aluminum chloride, which is applied nightly onto the affected
areas; this approach may also work for sweating of the palms and
soles. Caution is advised when the face is treated as aluminum
chloride may cause severe eye irritation.
Systemic agents
Systemic agents, including anticholinergic medications
such as propantheline bromide, glycopyrrolate, oxybutynin,
and benztropine, are effective as they inhibit acetylcholine, the
486
preglandular neurotransmitter for sweat secretion.26,27 Oxy-
butynin is an antimuscarinic drug that was first associated with
the resolution of hyperhidrosis in 1988.28 Oxybutynin has
provided good results and is an alternative for treating
hyperhidrosis at both common and uncommon sites.29
According to one study,30 the dosing schedule is started at
2.5 mg daily for the first week, then 2.5 mg twice daily from
days 8 to 21, and 5 mg twice daily starting at day 22. More than
70% of patients in the oxybutynin group treated for palmar or
axillary hyperhidrosis noted significant improvement, whereas
only 27.3% of patients in the corresponding placebo group had
moderate improvement (P 0.001). Other systemic medications,
such as sedatives and tranquilizers, indomethacin, and calcium
channel blockers, have been reported effective in the treatment
of palmoplantar hyperhidrosis.
Iontophoresis
Iontophoresis was first introduced in 1952. The procedure
consists of passing a galvanic current across the skin.3133 The
mechanism of action remains unclear. Iontophoresis of tap
water and normal saline solution in idiopathic hyperhidrosis is a
relatively common treatment and is most effective for sweating
of the hands and feet. Multiple agents have been used; however,
treatment with anticholinergic iontophoresis is more effective
than tap water iontophoresis.34 According to one study,
iontophoresis or phonophoresis could be used to facilitate
percutaneous delivery of botulinum toxin A. Improvement of
hyperhidrosis lasted for 16 weeks after treatment.35
Botulinum toxin
Botulinum toxin (BTX) injections are an effective
treatment approach for hyperhidrosis due to their anticho-
linergic effects at the neuromuscular junction and in the
postganglionic sympathetic cholinergic nerves in the sweat
glands.3639 Botulinum neurotoxin-type A (BTX-A) is a
useful and safe treatment option for most areas of the body.
The application of 1 U/cm2 of BTX-A (50 to 100 U per
axilla) is recommended.40 The therapeutic effect lasts for 6 to
8 months. Injections of BTX must be repeated at varying
intervals to maintain long-term results. Side effects include
injection-site pain and flulike symptoms. Botox used for
sweating of the palms can cause mild, temporary weakness.
In addition to pharmacologic therapy, other treatments include
surgical sympathectomy, radiofrequency ablation,41 surgical
excision of the affected areas, and subcutaneous liposuction.
Sympathectomy
Sympathectomy has been used as a permanent effective
treatment since 1920, and it is usually reserved as a last
K. Semkova et al.
treatment option.42 In an endoscopic thoracic sympathecto-
my, cuts, burns, or clamps interrupt the thoracic ganglion on
the main sympathetic chain that runs alongside the spine.
Endoscopic thoracic sympathectomy is generally considered
a safe, reproducible, and effective procedure and most
patients are satisfied with the results of the surgery.42
Compensatory sweating is a severe and undesirable side
effect of this procedure.
Suction-curettage
Suction-curettage of sweat glands is a minimally invasive
surgical technique that is easy to perform and safe, with high
rates of success and relatively few side effects. It is generally
well tolerated by patients and requires shorter time away
from daily activities compared with other surgical modali-
ties. Considering the less serious complications (and lower
associated costs), better cosmetic outcome, and resolution of
symptoms, liposuction-curettage provides a promising option
for axillary hyperhidrosis.43
Laser technology
Laser technology has also been used externally for
glandular disruption in the treatment of hyperhidrosis. The
1064-nm neodymium-doped yttrium aluminum garnet
(Nd:YAG) laser was used for axillary hyperhidrosis in 17
patients and was determined to be safe and effective by
subjective and objective measures.44
Novel methods of microwave-based and ultrasound
devices have been developed. Microwave-based devices45
have recently been used to treat hyperhidrosis. Investigators
found that 94% of patients experienced at least a 1-point
decrease on the Hyperhidrosis Disease Severity Scale,
whereas 55% reported a 2-point or greater decrease.
Ultrasound technology has also been introduced as a new
method in the treatment of hyperhidrosis.46
Prognosis
Hyperhidrosis has physiologic and psychological con-
sequences, such as cold and clammy hands, dehydration,
and skin infections secondary to maceration of the skin. 47
Severe cases of hyperhidrosis significantly affect the
patients quality of life and can be disabling in profes-
sional, academic, and social aspects, causing embarrass-
ment and work-related disability and depressive
symptoms. 33 Hyperhidrosis is difficult to treat, but the
now available newer treatment options offer a better
prognosis for patients.
Hyperhidrosis, bromhidrosis, and chromhidrosis: Fold (intertriginous) dermatoses
Bromhidrosis
Bromhidrosis (from Greek: bromos [stench] and hidros
[sweat]) is a chronic condition that presents clinically with an
abnormal and excessively unpleasant body odor. It is also
known as osmidrosis, bromidrosis, ozochrotia, and malodor-
ous sweating or body odor. All sweat gland types could be
involved in bromhidrosis.
Bromhidrosis shows no racial predilection but is more
common in men. Apocrine bromhidrosis occurs after puberty,
reflecting the time of maturation of apocrine glands. Eccrine
bromhidrosis may develop at any age, including childhood.
Pathophysiology
Bromhidrosis occurs secondary to excessive secretion
from either apocrine or eccrine glands that becomes
malodorous on bacterial breakdown. The condition is further
aggravated by poor hygiene or underlying disorders
promoting bacterial overgrowth, including diabetes, inter-
trigo, erythrasma, and obesity.
Apocrine bromhidrosis
Apocrine bromhidrosis is the most common form of
bromhidrosis. Its pathogenesis is multifactorial. Studies have
shown that compared with control subjects, individuals with
bromhidrosis have more numerous and larger apocrine
glands.48 Apocrine secretions are decomposed by skin
surface bacteria into ammonia and short-chain fatty acids,
with their characteristic strong odors. The most abundant of
these acids is (E)-3-methyl-2-hexenoic acid (E3M2H).49,50
In the axillary region, bacterial flora have been shown to
transform non-odoriferous precursors in sweat to more
odoriferous volatile acids, thus creating the specific body
odor. A specific zinc-dependent N--acyl-glutamine ami-
noacylase (N-AGA) from Corynebacterium species releases
these acids (primarily E-3 M2 H and (RS)-3-hydroxy-3-
methylhexanoic acid [HMHA]) and other odoriferous
substances from glutamine conjugates in sweat and thus
creates the specific individual body odor.51
Various factors can affect eccrine sweat and cause eccrine
bromhidrosis. Bacterial degradation of sweat-softened ker-
atin; ingestion of some foods, including garlic, onion, curry,
and alcohol; ingestion of certain medications (eg, penicillin,
bromides) and toxins; underlying metabolic (disturbances in
amino acid metabolism; sweaty feet syndrome; cat odor
syndrome, isovaleric acidemia, and hypermethioninemia) or
endogenous causes and hyperhidrosis have all been
associated with bromhidrosis. The mechanism of hyperhi-
drosis-induced bromhidrosis is unclear, but excessive
apocrine secretion may create a favorable environment for
487
bacterial overgrowth, thus contributing to further keratin
degradation and odor enhancement.52,53 A foreign body in
the nasal cavity is a reported cause of generalized
bromhidrosis in the pediatric population.19,54
Bromhidrosis may affect more than one member of a
given family, and recent studies have proposed an autosomal
dominant pattern of inheritance, particularly in Asian
patients. A strong relationship between bromhidrosis and
wet earwax type associated with the single-nucleotide
polymorphism rs17822931 of the ABCC11 gene has been
found.55,56
Clinical presentation
Patients present with excessively strong and offensive
body odor, emanating primarily from the axillary region but
also from the genitals or feet. Physical examination in
apocrine bromhidrosis is usually unremarkable, as it is a
functional and not a morphologic disorder. In eccrine
bromhidrosis, bacterial degradation of keratin may result in
maceration and wet keratin accumulation, especially on the
plantar and intertriginous surfaces. In cases involving an
underlying disease, the examination may reveal its relevant
signs. Nasal passages should be examined in children with
generalized eccrine bromhidrosis, as a nasal foreign body is a
recognized and underlying cause for this condition.35,36
Laboratory investigations
Bromhidrosis is primarily a clinical diagnosis. Laboratory
investigations are needed only to elucidate a suspected
underlying cause or for academic purposes. The odor-produ-
cing chemicals may be found by chromatography or
spectroscopy, but this does not affect the therapeutic
approach. Metabolic amino acid disorders should be
diagnosed by specific testing of the urine or sweat for the
aberrant amino acid product. Histologic examination of
hematoxylin-eosinstained specimens may show an in-
creased number and size of apocrine glands, but this finding
is not invariable.29
Treatment
Improved hygiene, antibacterial agents, antiperspirant
agents, lasers, BTXs, and, ultimately, surgery can be tried,
taking into account the patients quality of life and
expectations. Mild cases can be treated conservatively, but
laser or surgical treatment is needed for a definitive cure.
Treatment of the concomitant underlying skin or systemic
conditions should be considered as well.
Improved hygiene and topical antiseptics and antibacterial
agents reduce bacterial overgrowth and the malodorous
products from the breakdown of bacterial fatty acids. Hair
removal may show an additional benefit by preventing sweat
488
and bacteria accumulation on the hair shaft; however, other
methods excluding laser surgery should be preferred, as
bromhidrosis has been reported as a potential adverse effect
of laser hair removal.57
Topical antibiotics for bromhidrosis include clindamycin
and erythromycin, but antiseptics should be tried first to limit
the risk of bacterial resistance. Antiperspirants containing
aluminum salts enhance drying, limit maceration, and may
improve both apocrine and eccrine bromhidrosis, particularly
when these occur in association with hyperhidrosis.58
Laser treatment has been effective in a number of patients.
A frequency-doubled, Q-switched Nd:YAG laser (1064 nm)
has been used in axillary bromhidrosis.59 Several studies
have shown the beneficial effect for a long-term cure with the
1444-nm Nd:YAG laser that destroys the apocrine glands by
subdermal coagulation.58,60 Transient pain and limitation of
mobility persisting for 1 to 4 weeks postoperatively are the
main side effects.
Another successful treatment modality BTX-A, which
denervates eccrine sweat glands and temporarily decreases
sweat production. BTX-A has been used effectively in
axillary61,62 and genital bromhidrosis.63 In a cohort study of
67 patients with axillary bromhidrosis, BTX-A inhibited
eccrine and apoeccrine sweating but no apocrine sweating,
demonstrating that a close positive correlation between
malodor and sweating is the indication for BTX-A
treatment.64
Different surgical methods have been tried with consis-
tent success.6569 Three main approaches are possible:
removing only subcutaneous tissue without removing skin
and with or without axillary superficial fascia removal70 ;
removing skin and subcutaneous tissue en bloc68 ; and
removing skin and subcutaneous tissue en bloc with
removing of the adjacent subcutaneous tissue.51,71 Regen-
eration of gland function over a period of years may be
observed, and this depends mainly on the depth and
extension of surgical excision. A novel surgical approach
has combined surgical intervention with additional carbon
dioxide laser vaporization for the residual apocrine glands.72
Advantages of this combined approach include a high
success rate, low complication rate, no admission treatment,
less scarring, and rapid recovery.
Superficial liposuction curettage is a minimally invasive
technique for outpatient treatment that is less traumatic than
open surgery. Suction is used to remove the subcutaneous
tissue through small incisions in the axilla. The advantages
of this technique are smaller scars, lower complication
rates, and minimal postoperative care.73,74 The disadvan-
tage of this method is the higher rate of recurrence.
Ultrasound-assisted suction aspiration is an alternative
option with better long-term results and similar cosmetic
benefits. 75,76 Its main mechanism is liquefaction of fat and
sweat glands.
Upper thoracic sympathectomy has been used in some
patients with a reported satisfaction rate of about 71%77;
however, this method is usually reserved for hyperhidrosis.
K. Semkova et al.
Chromhidrosis
Chromhidrosis (from Greek: chroma [color] and hidros
[sweat]) is a rare dermatologic disorder, characterized by
secretion of colored sweat with a predilection for the axillary
area and the face. The condition was first described by
Yonge in 1709, and the pathophysiology was elucidated in
1954 by Walter B. Shelley (1917-2009) and Harry J. Hurley
(1927-2009), who attributed the coloration to lipofuscin
granules in the apocrine glands.78
Lipofuscin is a yellowish brown pigment that is not
specific to the apocrine glands and is usually found in the
cytoplasm of cells that do not normally divide (eg, neurons).
In apocrine chromhidrosis, lipofuscin pigment granules in
apocrine glands occur in a higher-than-normal concentration
or a higher-than-normal state of oxidation. This leads to blue,
yellow, green, or black discoloration of the apocrine
secretions. Even though the pathophysiology is clear, the
etiology of and predisposing factors for accumulation of
lipofuscin granules accumulation is as of yet unknown.79
Substance P also plays a role in the pathogenesis, which is
evidenced by the efficacy of treatment with topical
capsaicin.80
Pathophysiology
Chromhidrosis is primarily apocrine in origin, but eccrine
chromhidrosis may also occur with ingestion of various dyes
and drugs (such as quinines81). Pseudochromhidrosis, on the
contrary, results from mixing of various compounds with
eccrine sweat that is initially secreted as colorless on the skin
surface. These compounds include extrinsic dyes, colorants,
fungi, or chromogenic bacteria such as Piedraia or
Cornynebacterium.82
Chromhidrosis usually develops in puberty with the
activation of apocrine secretion. The disease is chronic but
follows the natural evolution of apocrine glands and often
regresses with age. Although apocrine glands are found in
various body areas, including the genital, axillary, areolar
skin, and facial regions, chromhidrosis has been reported
only on the face,61,63 axillae,83 and the breast areola.84,85
There is no sexual predilection, but this disorder has been
reported more commonly in blacks with the exception of
facial chromhidrosis, which is exclusive in the white
population. In addition to its association with mature
apocrine glands, one case of chromhidrosis in an infant has
been reported in the literature.86
Clinical presentation
The clinical presentation is usually distinctive and does
not present a challenge to the dermatologist. Patients report
staining of their clothes or underwear in the axillary region
and, less commonly, areolar or facial staining. Some people
Hyperhidrosis, bromhidrosis, and chromhidrosis: Fold (intertriginous) dermatoses
note an aura of warmth or a prickly sensation provoked by
physical or emotional stress preceding the occurrence of
colored sweat. The apocrine sweat secretions are odorless,
turbid, and of variable color (yellow, green, blue, brown, or
black) with follicular accentuation and can be expressed
mechanically from the affected glands. Lucent, adherent,
colored scales form upon drying of these secretions.
Approximately 10% of the population without chromhidro-
sis may have colored sweat, a physiologic phenomenon that
is considered acceptable.
Laboratory investigations
Chromhidrosis is a clinical diagnosis, and tests to confirm
it are only rarely needed. Woods lamp examination is the
fastest and easiest confirmatory test for some cases. The
yellow, green, and blue apocrine secretions fluoresce in
yellow with a Woods lamp (ultraviolet wavelength 360 nm),
whereas the dark brown and black apocrine secretions
usually do not fluoresce. Sweat secretion could be stimulated
for the test with intradermal epinephrine or oxytocin.
Standard ultraviolet microscopy may show yellow-green
fluorescence of the clothes that were in contact with the
affected area.
On histologic examination the apocrine glands are normal
in size and morphology, but the number of glands varies.
Increased number of yellow-brown lipofuscin granules is
observed in the cytoplasm of secretory cells on standard
hematoxylin-eosin staining.87 The granules are positive with
periodic acidSchiff and Oil Red O staining and fluoresce
under an ultraviolet microscope with an excitation wave-
length of 360 to 395 nm.
Additional laboratory tests could be used to differentiate
apocrine chromhidrosis from exogenous causes for pigmen-
tation. These include urinary homogentisic acid levels to
exclude alkaptonuria, complete blood cell counts to exclude
bleeding diathesis, and relevant fungal and bacteriologic
cultures to exclude infectious pseudochromhidrosis.
Treatment
Treatment is only symptomatic. The condition usually
recurs after discontinuation of therapy and persists until the
age-related regression of the apocrine glands. Manual or
pharmacologically induced expression of the secretions
empties the glands, resulting in a symptom-free period of
48 to 72 hours.
Successful treatment of chromhidrosis has been reported
with capsaicin cream in a few patients.80,88 Capsaicin, an
alkaloid found in chili peppers, is commonly used in
medicine as a temporary analgesic for the treatment of
minor myalgias and arthralgias, rheumatoid arthritis, osteo-
arthritis, and peripheral neuropathy such as postherpetic
neuralgia caused by shingles. Capsaicin depletes neurons of
489
substance P, a neurotransmitter and a neuromodulator for
pain perception, responsible for the transmission of pain
information in the central nervous system. Substance P is
also an important factor for apocrine sweat production.71
Capsaicin should be applied once or twice daily for as long as
required, but chromhidrosis relapses several days after
discontinuation of treatment.62
BTX-A has also been effective for facial and axillary
chromhidrosis.8991 The mechanism by which BTX-A
suppresses apocrine chromhidrosis is still unclear. Various
mechanisms can be involved, including blockade of
cholinergic stimulation and inhibition of substance P
release.72,73 Although apocrine glands are less responsive
to cholinergic stimulation compared with eccrine glands,
cholinergic nerve fibers have been shown around their
secretory coils but with a lower density of innervation.74
Treatment results usually persist for 4 to 5 months, and the
course of treatment can be continued for as long as needed.
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