Chapter 84

Disorders of the
Eccrine Sweat Glands
and Sweating
Robert D. Fealey & Adelaide A. Hebert

IN VIVO METHODS OF
STUDYING SWEAT GLAND
FUNCTION
Sweat is readily visualized by a topical indicator
such as iodinated starch1,2 or sodium alizarin sulfonate (alizarin Red S).3 These techniques are used to
evaluate large body surfaces (Fig. 84-2). Iodinated
starch powder is prepared by adding 0.51.0 g of
iodine crystals to 500 g of soluble starch in a tightly
capped bottle. Sodium alizarin sulfate is mixed with
an equal amount (by weight) of sodium carbonate
anhydrous and twice the amount of cornstarch.
Both are applied to the skin and undergo a dramatic color change when moistened by the water
(sweat) from activated sweat glands. For smaller
body areas, a Minors starch-iodine test for excessive sweating may be performed by applying
betadine on Q-tips to the affected area. Once the
iodine solution has dried, cornstarch can be lightly
sprinkled on the area. Deep purple color change
will develop over time in the areas affected with
hyperhidrosis.
Sweat gland activity can be studied quantitatively
by a number of techniques including: filter paper
collection, weighing and analyzing of sweat, the
quantitative sudomotor axon reflex test (QSART),4
skin sympathetic potentials,5 silastic mold or
iodine-impregnated paper imprint after pilocarpine
stimulation,6 microcannulation of the sweat duct
or coil,7 collection into a WescorMacroduct coil
(Logan, CT),8 humidity sensors within ventilated
capsules measuring transepidermal water loss,9,10
and by determining total body surface anhidrosis
to a maximal thermoregulatory stimulus during a
thermoregulatory sweat test (TST).11,12 Other, more
sophisticated techniques use microdialysis membranes delivering minute quantities of transmitter
substances to the dermis13 or use confocal electron

microscopy and immunohistochemical analysis of

biopsied skin stained for peptides and proteins that
comprise the structure and innervation of the sweat
gland14 (Fig. 84-3).
It is desirable to combine several methods for
determining the integrity of the eccrine sweat
response. For example, a TST can be combined with
tests of the sweat gland and/or its peripheral nerve
innervation to localize a sweating disorder to the
peripheral or central nervous system. Alternatively,
a volumetric technique can be combined with a
sweat droplet distribution imprint to estimate the
sweat volume per active gland.
The composition of collected sweat can give critical information about eccrine function. For example,
sweat chloride ion concentration can determine the
integrity of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel and provide
diagnostic information for cystic fibrosis.15

SECONDARY CAUSES OF
LOCALIZED HYPERHIDROSIS
Cerebral Infarction
Hemispheric strokes, especially those affecting the
insular and opercular cortex, can produce contralateral hemihyperhidrosis primarily affecting the
face and upper extremities. Unilateral hypothalamic,
peduncular, pontine, and medullary infarcts can do
the same, even in the absence of ipsilateral Horner
syndrome. Bilateral pontine and cerebellar infarction can produce facial hyperhidrosis. The hyperhidrosis is acute and transient. Putative mechanisms
involve interruption of inhibitory pathways controlling contralateral sweating.

Spinal Cord Injury and

Autonomic Disreflexia
Patients with spinal cord injuries experience episodes of profuse sweating weeks, months, or years
after injury. The areas of hyperhidrosis are determined by the complex interaction of exaggerated
somatosympathetic reflexes, and the longitudinal
and transverse extent, level, and completeness of
the cord lesion. The lowest segment of cord injury is
usually above T6 and the segmental hyperhidrosis
involves the face, neck, and upper trunk most com-

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98

Chapter 84:

Disorders of the Eccrine Sweat Glands and Sweating

monly. Associated symptoms include facial flushing and nasal congestion, headaches, piloerection,
hypertension, and bradycardia. Stimuli, such as
distention of the bowel or bladder, skin and visceral
organ inflammation, and orthostatic hypotension,
stimulate uninhibited sympathetic preganglionic
neurons. Removing the stimulus is the most effective treatment, although antihypertensives (clonidine, blockers, and calcium channel blockers) and
anticholinergic agents (propantheline, glycopyrrolate) are sometimes needed.
Recent studies have shown that sprouting of afferent fibers in the dorsal horn of thoracolumbar cord
segments below the lesion and severe necrosis of
descending white matter tracts in the vicinity of the
lesion are associated with autonomic dysreflexia.
Novel treatments that inhibit nerve growth factorinduced sprouting and that suppress immunemediated responses to tissue injury are emerging
as therapeutic agents4145 that promise to limit
dysreflexia development.
Spontaneous syringomyelia with Chiaris I and
II malformations and incomplete or asymmetric
myelopathies may produce segmental hyperhidrosis not associated with other features of dysreflexia.
These represent examples of compensatory or
perilesional hyperhidrosis most times.

Other Central Nervous System

Disorders
COLD-INDUCED SWEATING SYNDROME.46,47
Cold-induced sweating syndrome is a genetically
heterogenous autosomal recessive condition associated with alterations of a composite cytokine,
which is composed of cardiotrophin-like cytokine
factor 1 (CLCF1) and cytokine receptor-like factor
1 (CRLF1).46 The cold-induced sweating involves
the upper body segments, which paradoxically do
not sweat in the heat. Cold-induced sweating is
associated with limited autonomic failure, motor
neuropathy, skeletal deformities, and abnormal
facies that include a high arched palate. Long-term
symptom control has been reported with a combination of low dose amitriptyline and clonidine.46
In olfactory hyperhidrosis syndrome,48 profuse facial
sweating is precipitated by perfume smells, but not
by gustatory or mental stimuli, and may respond to
amitriptyline.

Peripheral Nervous System

Disorders
INTRATHORACIC NEOPLASMS.
Abnormal thoracic sympathetic activity due to
encroachment of mass lesions (Pancoast tumor,
mesothelioma, lymphoma, osteoma, cervical rib)
on the sympathetic trunk or postganglionic fibers
can cause segmental hyperhidrosis.49 Sweating is
usually spontaneous and located in the distribution
of the involved sympathetic trunk or segmental
spinal nerve root. An area of anhidrosis may be
juxtaposed with the area of hyperhidrosis or the
hyperhidrosis is contralateral to the lesion. Nonmalignant causes of the same phenomenon include
diabetic and idiopathic immune-mediated truncal
neuropathy (see eFig. 84-3.4 in online edition).
COMPENSATORY SEGMENTAL
HYPERHIDROSIS.
Segmental or localized hyperhidrosis commonly
occurs postsympathectomy and in the primary autonomic disorders such as pure autonomic failure
(PAF) and Ross syndrome. The latter two disorders
are discussed in Section Primary Autonomic Disorders with Acquired Idiopathic Anhidrosis.

Lacrimal Sweating63
Continuous profuse sweating in the medial
supraorbital region associated with Raeder syndrome (Horner syndrome plus temporal and frontal
headache and paresthesia) is known as lacrimal
sweating. Sudomotor fibers to the medial forehead
traveling with the internal carotid artery presumably are damaged and parasympathetic fibers to
the lacrimal gland provide aberrant regeneration to
the nearby denervated sweat glands.

Harlequin Syndrome64
Harlequin syndrome (unilateral facial flushing
and sweating with heat and exercise) may develop
abruptly posttrauma or stroke or as an immunemediated ganglionopathy. The flushed, sweating
side attracts attention, but it is the contralateral
side with anhidrosis and loss of flushing that has
a sympathetic abnormality. Occasionally, tonic
pupils may occur, forming an overlap with Ross
syndrome.65,66

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Chapter 84:

Disorders of the Eccrine Sweat Glands and Sweating 99

Idiopathic, Localized
Hyperhidrosis
The involved area in idiopathic unilateral circumscribed hyperhidrosis is usually sharply demarcated
and no larger than 10 10 cm2.67 It occurs mainly
on the face and upper extremities of otherwise
healthy individuals. Profuse sweating, which is usually precipitated by heat, lasts 1560 minutes. Mental or gustatory stimulation also triggers sweating.
There is no accompanying sensory or motor neuropathy, flushing of the face, headaches, excessive
salivation, lacrimation, vasodilation, or piloerection.
The pathogenesis of circumscribed hyperhidrosis
is unknown. Sweating may be partially controlled
by local application of 20% aluminum chloride in
ethanol, topical anticholinergic agents, systemic
clonidine (which inhibits central sympathetic outflow), or by local injections of BTX.
PAROXYSMAL LOCALIZED HYPERHIDROSIS.
Older women, much more so than men, are occasionally troubled by a syndrome of daytime,
paroxysmal hyperhidrosis primarily affecting the
head, neck, and upper trunk. Hot flashes (head and
neck heat and flushing) are not commonly associated, and hormonal replacement therapy is usually
ineffective. Nevertheless, affected women are often
postmenopausal and have previously experienced
typical hot flashes. Sweating before menopause is
normal, distinguishing the syndrome from craniofacial essential hyperhidrosis. Normal whole body
thermoregulatory sweating rules out compensatory
hyperhidrosis. Alterations in hypothalamic set point
temperature range for sweating are suspect in
many cases. Symptomatic treatment with clonidine,
glycopyrrolate (0.5%2.0% topical or 38 mg/day
orally), or with other agents (scopolamine, phenobarbital, topiramate) may be effective. Whether
this syndrome is simply an aged version of typical
hot flashes or a late onset idiopathic primary focal
hyperhidrosis is uncertain.

Localized Hyperhidrosis
Associated with Skin Disorders
Localized hyperhidrosis has been reported to occur in the skin over a blue rubber bleb nevus, in the
perilesional skin of a glomus tumor (presumably
due to increased local temperature and/or pain),
and in POEMS (polyneuropathy, organomegaly,

endocrinopathy, M protein, and skin changes) syndrome, Gopalan disease (burning feet syndrome),
pachydermoperiostosis, and painful pretibial myxedema. Hyperhidrosis is also often associated with
eccrine angiomatous hamartoma, tufted angioma,
a vascular tumor, and with a nevoid proliferative
condition that shows increased numbers of eccrine
glands and dilated vascular channels in the deep
dermis and subcutaneous tissue on histologic
evaluation of lesional tissue.68 The hamartoma is
most commonly localized to an extremity, and
usually presents as a solitary, sometimes painful,
bluepurple, slow-growing nodule at birth or in
childhood, but may first be noted in adults.

SECONDARY CAUSES OF
GENERALIZED HYPERHIDROSIS
Central Autonomic Nervous
System Disorders
EPISODIC HYPOTHERMIA WITH
HYPERHIDROSIS.
Episodic hypothermia [core temperature <35C
(95F)] with hyperhidrosis (Shapiro syndrome) was
originally described in association with agenesis of
the corpus callosum,69 but has more recently been
reported in association with human immunodeficiency virus. However, it may occur without an
identifiable brain lesion or systemic illness, and can
affect both children and adults. The hypothermia
may be due to periodic dysfunction of the medial
preoptic hypothalamic region with lowering of the
set-point temperature, producing profuse sweating to lower core temperature. Treatment with anticonvulsants, oxybutynin, clonidine, and glycopyrrolate have been used with variable success.7072
GENERALIZED HYPERHIDROSIS WITHOUT
HYPOTHERMIA.
Generalized hyperhidrosis without hypothermia
has been reported in patients with episodic hypertension, tachycardia, flushing, and hypothalamicpituitary dysfunction after brain injury, infarction, or
tumor in the region of the hypothalamus. These autonomic storms or diencephalic epileptic events
are not true seizures but likely reflect overactivity or
disinhibition of the hypothalamic areas, which control the sympathoexcitatory stress reaction. Hyperhidrosis has also been reported with fatal familial
insomnia (an autosomal dominant prion disease

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100 Chapter 84: Disorders of the Eccrine Sweat Glands and Sweating

clinically characterized by inattention, sleep loss,

dysautonomia, and motor signs). Involvement of
the medial thalamic nuclei and connecting limbic
system pathways may be causative.73 In Parkinson
disease, hyperhidrosis is a frequent manifestation
during dopamine drug off states.74

Disorders with Central and

Peripheral Nerve Abnormalities
Familial dysautonomia (FD), also known as Riley
Day syndrome, is the best known and most intensively studied of the hereditary sensory-autonomic
neuropathies (designated as HSAN type III). This autosomal recessive disorder is caused by mutations
in the IKAP gene, located on chromosome 9. FD is
characterized by pronounced autonomic dysregulation with episodic orthostatic hypotension, arterial
hypertension, profuse sweating, skin blotching,
puffy hands, nausea, and behavioral abnormalities.
FD manifests only in children of Ashkenazi Jewish
ancestry. Cardinal findings are diminished deep
tendon reflexes, absence of overflow tears, absence
of fungiform papillae of the tongue, and of axon
flare response after intradermal histamine injection.
Thermal and vibratory testing shows pronounced
impairment of temperature and pain but also of
vibratory perception. Parasympathetic pupillary
denervation may occur.
Hilz and Axelrod have recently studied the
peripheral nervous system in ten patients, finding
elevated mean temperature thresholds and baseline sweat rate, although total sweat volume and
response time to acetylcholine (ACh) iontophoresis
did not differ from controls.82 The average density
of epidermal nerve fibers was greatly diminished
in the calf and back. There was also severe nerve
loss from the subepidermal neural plexus and deep
dermis. The few sweat glands present within the biopsies had reduced innervation density. Substance
P and calcitonin gene-related peptide immunoreactive nerves were virtually absent, but vasoactive
intestinal peptide immunoreactive nerves were
present. Such findings suggest greater involvement
of sensory than autonomic ganglion cells and secondary neurotransmitter depletions. Both central
sudomotor pathways and remaining peripheral
sudomotor axons appear hyperexcitable.
Acute episodes are treated with clonidine or
benzodiazepines, and a small study of 15 patients
showed that pregabalin taken daily was effective in
reducing the frequency and severity of episodes.83

Morvan fibrillary chorea is characterized by neuromyotonia, pain, hyperhidrosis, weight loss, severe
insomnia, and hallucinations. Voltage-gated potassium channel antibodies have been found in some
cases and may be responsible for the central and
peripheral nervous system manifestations. Areas of
hyperhidrosis and anhidrosis may be demonstrated
on testing.84

DISORDERS CAUSING
HYPOHIDROSIS AND
ANHIDROSIS
Anhidrosis is the absence of sweating in response
to an appropriate stimulus and can result from
poral occlusion, congenital or acquired absence
of sweat glands, damage to sweat gland function
by inflammation of the skin, or dysfunction at any
level of thermoregulatory nerve pathways (see
Table 84-1). Hypohidrosis or anhidrosis can be a
component of several forms of ectodermal dysplasias (related to developmental abnormalities of the
sweat glands; see Chapter 142) and disorders with
abnormal epidermal differentiation (related to poral
occlusion; see Chapter 49).

Primary Autonomic Disorders

with Acquired Idiopathic
Anhidrosis
Widespread loss of sweating can be caused by
isolated failure of sympathetic sudomotor activity,
a condition known as chronic idiopathic anhidrosis
(CIA)85 or acquired idiopathic generalized anhidrosis (AIGA).86 The main clinical features include
symptoms of heat intolerance: feeling hot, flushed,
dyspneic, light headed, and weak but not sweating
when the ambient temperature is high or when
exercising. Recent published reports have emphasized the heterogeneous features and subtypes of
this condition.87,88
ACQUIRED IDIOPATHIC GENERALIZED
ANHIDROSIS.
AIGA is a rare entity in which generalized anhidrosis occurs without any other neurologic or
autonomic dysfunction, and the majority of cases
reported are in Japanese patients. This disorder is
subcategorized into three groups: (1) sweat gland
failure in which a biopsy will reveal inflammation
or degeneration of the sweat glands; (2) sudomotor neuropathy in which sympathetic innervation

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Chapter 84:

Disorders of the Eccrine Sweat Glands and Sweating 101

of the sweat gland is absent or decreased; and (3)

the most common type, idiopathic pure sudomotor failure (IPSF).88 Clinical features of IPSF comprise
sudden onset, concomitant sharp pain, or cholinergic urticaria over the entire body, lack of autonomic
dysfunction other than generalized anhidrosis, elevated serum immunoglobulin E levels, and marked
response to parenteral corticosteroids. The clinical
findings suggest lesions on the postsynaptic side of
the nervesweat gland junction. The lesions in IPSF
may involve the muscarinic cholinergic receptors
of sweat glands, and an allergic mechanism may be
responsible.
CHRONIC IDIOPATHIC ANHIDROSIS.85
(See Fig. 84-1). Most patients present, in a subacute manner over weeks to months, with heat
intolerance and impaired thermoregulatory sweating as an isolated autonomic abnormality. Axon
reflex sweating (QSART) is usually impaired. Punch
biopsies of nonsweating skin infrequently show
perieccrine infiltration with small, CD3+ lymphocytes. IgE levels are usually normal. Ganglionic ACh
receptor antibodies are usually absent. The antigenic target of the CD3+ lymphocytes is unclear, but
may be the M3 ACh receptor. Oral corticosteroid,
parenteral methotrexate, and topical pimecrolimus
cream have not improved the anhidrosis; however,
such interventions are often many months after
onset. Spontaneous recovery over 1 to several years
may occur and the condition does not progress
to generalized autonomic failure. Examining skin
biopsies with electron and laser scanning confocal
fluorescence microscopy14 to discern the ultrastructural changes disrupting the neuroglandular
unit, determining cell surface markers of infiltrating
lymphocytes and searching for novel antibodies
(e.g., to the aquaporin-5 water channel) are among
current and proposed methods to better understand the neurobiology of these disorders.
SEGMENTAL TYPE OF ACQUIRED IDIOPATHIC
ANHIDROSIS.
(See eFig. 84-3.5 in online edition). Often included
as a subtype of CIA or AIGA, patients with the
segmental type of acquired idiopathic anhidrosis
develop asymmetric, slowly progressive sweat loss,
conforming to sympathetic dermatomal body segments. Exercise and heat intolerance also progressively worsens. The exact pathophysiology and
cause are unknown, but may begin as a preganglionic neuronal degenerative process.75,89

In the patient shown in eFig. 84-3.5 and other

reported cases, the areas of progressive loss (e.g.,
the left leg and foot) initially showed preservation
of the quantitative sudomotor axon reflex response,
strong evidence that the lesion was affecting a site
proximal to the sympathetic chain ganglion cells
(i.e., preganglionic axons or synapse or intermediolateral cell column neurons of the spinal cord). After
several more years, the peripheral sweat response
was lost in the left foot.

Ross Syndrome
Patients with Ross syndrome present with heat intolerance and striking segmental areas of anhidrosis and compensatory hyperhidrosis (see eFig. 843.6 in online edition). On examination, tonic pupils
and absent lower extremity deep tendon reflexes
are found. Sympathetic denervation of the pupils
and heart may occur. Symptomatic treatment of the
hyperhidrosis (topical glycopyrrolate or BTX injections) and heat intolerance is provided. Combined
TST and QSART studies suggest a postganglionic
neuronal lesion is responsible. Recent studies on 12
patients employing serial skin biopsies, sensory and
autonomic tests reveal a complex and progressive
involvement of cutaneous sensory and autonomic
innervation underlying the impairment of heat
production and heat dissipation through both
loss of sweating and loss of cutaneous blood flow
regulation.90Recently, a case of Ross Syndrome associated with a cytomegalovirus infection has been
reported.91

Pure Autonomic Failure

(Bradbury-Eggleston Syndrome)
and Autoimmune Autonomic
Neuropathy
PAF is now considered one of the synucleinopathies, a neurodegenerative disorder associated with
fibrillary aggregates of -synuclein in the cytoplasm
of specific populations of neurons and glia. Such
patients develop orthostatic hypotension, segmental to widespread loss of sweating, bowel bladder
and sexual dysfunction. Patients may present with
dry skin and heat intolerance or may be bothered
by an asymmetric, nonpalmoplantar compensatory
hyperhidrosis.
Shishido et al have now shown -synuclein
pathology in cutaneous nerves obtained by skin
biopsies taken from anhidrotic skin sites.92 It is

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102 Chapter 84: Disorders of the Eccrine Sweat Glands and Sweating

anticipated that skin biopsies stained to show

nerve fibers in the dermis around sweat glands,
hair follicles as well as the epidermis will become
increasing utilized to diagnose PAF and many other
neurologic disorders.

Autoimmune Autonomic
Ganglionopathy
This syndrome is increasingly recognized and is
characterized by severe anhidrosis, gastrointestinal
dysmotility, dry mouth, and neurogenic bladder.
Novel serum antibodies to the ganglionic ACh
receptor are found.93 The pattern of anhidrosis on
thermoregulatory sweat testing is consistent with
a ganglionopathy in the majority of patients (14
of 21) and a distal pattern in a minority of patients
(8 of 21). These patterns of anhidrosis indicate
lesions at both the ganglia and distal axon of the
postganglionic sudomotor sympathetic neuron.
Immunomodulatory treatment can be effective in
both seropositive and seronegative cases. Plasma
exchange or combined therapy with immunosuppressive agents should be considered in patients
who do not benefit from intravenous immunoglobulin alone.93,94

SECONDARY ANHIDROSIS
ASSOCIATED WITH NEUROLOGIC
DISORDERS
Disorders of the
Central Nerous System
Stroke, tumor, infection, infiltration, trauma at any
level of the ipsilateral descending thermoregulatory sweating pathway between hypothalamus
and spinal cord can cause a hemihypohidrosis or
asymmetric segmental anhidrosis that is preganglionic on testing (see eFig. 84-4.6 in online edition).
Combined TST and QSART confirm that the extensive anhidrosis is on a central or preganglionic basis.

Degenerative Disorders
Generalized anhidrosis is a common manifestation of multiple system atrophy (MSA) and sweat
testing has been used to help distinguish MSA from
Parkinson disease.95,96 The lesion is usually preganglionic involving the intermediolateral columns.

Progressive preganglionic and then postganglionic impaired sweating occurs. Diffuse Lewy body
disease has an associated autonomic impairment
that is more than Parkinson disease and less than
in MSA. Widespread autonomic neuronal involvement with Lewy bodies in brainstem, spinal cord,
and sympathetic ganglia have been described in
autopsy cases.97,98

Causing Anhidrosis
HEREDITARY SENSORY AND AUTONOMIC
NEUROPATHY TYPES I, II, AND IV.
HSANs I, II, IV (also known as congenital insensitivity to pain), and V are associated with distal or
more generalized anhidrosis and have differing
genetic mutations and phenotypes distinct from
HSAN III (FD, see Section Disorders with Central
and Peripheral Nerve Abnormalities). HSAN II is
characterized by distal mutilating acropathy and
anhidrosis, whereas HSAN type IV features congenital or infantile onset, repeated high fevers with
widespread anhidrosis, and widespread insensitivity to pain. Immunohistochemical analysis of skin
biopsy specimens reveals a lack of epidermal and
sweat gland innervation.99
GUILLAINBARR SYNDROME.
Acute inflammatory demyelinating polyneuropathy (GuillainBarr syndrome) produces regional
deficits of sweating in legs in 10%20% of patients.
Such involvement is overshadowed by the sensory
and motor involvement. Rarely, acute dysautonomia without much involvement of somatic nerves
occurs.
DIABETIC NEUROPATHY.
Diabetic neuropathy commonly involves distal
sensorimotor neuropathy, painful thoracolumbar
monoradiculopathy, and polyradiculopathy. Of 51
patients with diabetic neuropathy, 48 presented
with unequivocal abnormalities of thermoregulatory sweating.11 Focal deficits occur with lumbar
and thoracic radiculoplexus neuropathy, distal loss
with length dependent neuropathy, and, rarely,
global sweat loss in those with profound autonomic
neuropathy. Abnormal thermoregulatory sweating
in a patient with diabetes mellitus is shown in eFig.
84-3.8 in online edition.

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Chapter 84:

Disorders of the Eccrine Sweat Glands and Sweating 103

AMYLOID NEUROPATHY.
Amyloid (familial and primary systemic) neuropathy
often affects autonomic nerves, producing distal
and/or segmental sweating deficits, the latter commonly affecting the head and neck.100 Sudomotor
neuropathy can progress even after liver transplantation.
LEPROSY.
Leprosy (see Chapter 186) is due to an infection
with Mycobacterium leprae, which has a predilection for skin and peripheral nerves in cooler regions
of the body [organisms reproduce best at 32C
(95F)]. The tuberculoid form is associated with
a few skin lesions that are both anesthetic and
anhidrotic. Lepromatous leprosy is associated with
little immunity to the organisms that gain access
to cutaneous and intracutaneous nerve endings,
destroying these elements in a highly characteristic temperature-linked pattern. Intermediate or
borderline leprosy shows features between these
extremes.101 TST is one of the best ways to delineate
the extent and distribution of sudomotor nerve
involvement. Fig. 84-4 shows the TST result in a
patient with lepromatous leprosy. There were only
subtle skin changes (right inset) and only mild
sensory loss in distal lower extremities. However,
the TST (left inset) showed striking anhidrosis in the
cooler regions of the extremities. These skin areas
had reduced to absent axon reflex sweating, suggesting postganglionic axonal involvement. Skin
biopsy from the right forearm showed numerous
acid-fast bacilli (background photo) with Fite staining, diagnostic of lepromatous leprosy.
LAMBERTEATON MYASTHENIC SYNDROME.
The LambertEaton myasthenic syndrome is characterized by proximal muscle weakness, decreased
deep tendon reflexes and autonomic symptoms
(dry mouth, constipation, erectile failure). Widespread anhidrosis occurs. The disorder is caused
by a reduction in the quantal release of ACh from
motor and autonomic nerve terminals, caused by
autoantibodies to P/Q-type voltage-gated calcium
channels. LambertEaton myasthenic syndrome is
associated with malignancy in 60% of cases.102
ALCOHOLIC NEUROPATHY.
Alcoholic neuropathy typically affects small sensory
fibers. Unmyelinated, autonomic fibers are also
affected and sweat loss with trophic skin changes

is common in the feet.103 Early in the course, there

may be a period of excessive acral (distal) sweating.
Neuropathic ulcers, impairment of pain sensation,
and the neurogenic vasodilator flare response,
fissuring, and cracking of skin accompany intrinsic
foot muscle atrophy with high arches and claw toes.
These trophic skin changes are common in many
length-dependent neuropathies (e.g., in diabetic
neuropathy).
FABRY DISEASE.
Fabry Disease is an X-linked heritable disease in
which there is insufficient activity of the lysosomal
enzyme -galactosidase A, leading to the accumulation of glycolipids in multiple organs including
the nervous system that causes painful neuropathy
and autonomic dysfunction.104 Patients with Fabry
disease are known to have hypohidrosis which is
ameliorated by enzyme replacement therapy (see
Chapter 136).105
Lao has done electron microscopy on sweat
glands from a patient with typical Fabry disease
with anhidrosis and heat intolerance.106 He found
large vacuolar inclusions predominated in clear
cells of secretory coil: lesser vacuoles were also seen
in the coiled duct, and the basal cells of the straight
duct toward the coiled duct displayed mulberrylike figures. There were some clear cells showing
cell damage and necrosis in the secretory coil.
Lamellated inclusions were noted in the unmyelinated axons innervating the eccrine sweat glands.
The small blood vessels around the eccrine glands
were narrowed by swollen endothelial cells with
heavy inclusions.
IDIOPATHIC SMALL-FIBER NEUROPATHY.
Many cases of painful, distal neuropathy are of
the small-fiber type. Nerve conductions and
electromyography are usually normal, and patient
examinations only show subjective change in pain
and temperature sensation. Quantitative tests of
sweating and skin biopsies107 to determine epidermal nerve fiber density show diagnostic abnormalities in most patients. Postganglionic sympathetic
sudomotor fibers show axonal degeneration and
produce length-dependent loss of sweating, especially affecting the feet (see eFig. 84-4.1 in online
edition).108

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104 Chapter 84: Disorders of the Eccrine Sweat Glands and Sweating

ERYTHROMELALGIA.
The occurrence of small-fiber neuropathy in association with clinically diagnosed primary erythromelalgia has been recently highlighted.109 A relative
decrease in small nerve fiber density was noted in
skin biopsies from 13 of 16 patients.110 This finding
supports recent observations of deficient thermoregulatory and axon reflex sweating in primary
erythromelalgia.111
POSTSYMPATHECTOMY.
As noted in the hyperhidrosis treatment section,
surgical sympathectomy has been used to treat
palmar hyperhidrosis. The degree of anhidrosis resulting is related to the extent of sympathetic chain
resection and varies from 35% to only 1% or 2% on
TST postoperatively. The lower percentage is desirable as greater degrees may be associated with
unwanted compensatory hyperhidrosis of the trunk
just below the level of the sympathectomy.30 This
complication has been one of the main sources of
disappointment in outcome and diminished quality
of life for those treated surgically for hyperhidrosis
(see eFig. 84-3.3).
HARLEQUIN SYNDROME.
Patients with harlequin syndrome usually have
unilateral anhidrosis (of head and neck) and pharmacologic evidence of denervation of the pupil. It
is thought this precedes and is responsible for the
compensatory, contralateral excessive sweating
(see above) and vasodilatation characteristic of this
disorder.112,113

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