Diseases of the Eccrine and Apocrine Sweat Glands

Disorders associated with cortical (emotional) hyperhidrosis

Isolated sweating of the palms and soles is primarily due to cortical excitation by emotional or sensory stimuli. Excessive volar sweating associated with certain inherited palmoplantar keratodermas is assumed to be cortical in nature, although the pathogenic relationship between the abnormal keratinization and hyperhidrosis has not been precisely delineated. Many palmoplantar keratodermas are malodorous, likely related to sweat-induced maceration of the thickened stratum corneum and bacterial degradation of keratin. Other genodermatoses affecting the volar skin, such as epidermolysis bullosa simplex, can also have associated palmoplantar hyperhidrosis. Additional causes of cortical hyperhidrosis are listed in Table 39.3 .

Hypothalamic (thermoregulatory) hyperhidrosis

The hypothalamus is responsible for many autonomic activities, including thermoregulation. Elevation of the temperature of the blood by 0.5°F or more excites the hypothalamic nuclei and results in vascular dilation and generalized sweating responses aimed at dissipating body heat .

Febrile illnesses are among the most common pathologic states that cause hypothalamic sweating. At the height of the fever, notably with temperatures of 39–40°C (102–104°F) or above, sweating is absent, the apparent result of inhibition of the hypothalamic center for sweating. With defervescence, sweating characteristically ensues. Lymphomas and chronic infections (e.g. tuberculosis) can present with episodic thermoregulatory sweating, which may be described as “night sweats” (that actually follow unperceived mild febrile pulses).

Generalized sweating of hypothalamic origin can also be seen in a number of metabolic and endocrine disorders ( Table 39.4 ). Patients with diabetes mellitus may exhibit hypohidrosis as well as various forms of hyperhidrosis. For example, hyperhidrosis is a characteristic sign of insulin-induced hypoglycemia (but not diabetic ketoacidosis), and compensatory hyperhidrosis of the trunk can develop in the setting of diabetic neuropathy affecting the extremities (see below). In addition, diabetics may exhibit gustatory hyperhidrosis, primarily of the face and neck. Troublesome sweating of the scalp can also be seen in poorly controlled diabetics, and, with regulation of the hyperglycemia, the hyperhidrosis often improves.

Disorders with vasomotor instability, such as Raynaud phenomenon, autoimmune connective tissue diseases, frostbite and other cold injuries, and reflex sympathetic dystrophy, may be associated with excessive sweating because of disturbed autonomic function . A synchronous discharge of vasoconstrictor and sudomotor impulses evokes a “cold sweat”, usually of the hands and feet, producing macerated, soggy wet, violaceous skin known as symmetrical lividity.

Cerebral cortex lesions, such as a tumor, abscess or cerebrovascular accident, may be associated with a contralateral hyperhidrosis due to an impairment of the inhibitory cortical influence that normally regulates hypothalamic sudomotor activity . Hypothalamic sweating is also observed in Parkinson disease and occurs as the “sweating sickness” following encephalitis. Harlequin syndrome, characterized by unilateral flushing and hyperhidrosis in association with contralateral anhidrosis, may be due to peripheral or central nervous system (CNS) abnormalities .

Episodic release of catecholamines from pheochromocytomas directly stimulates the hypothalamus and may elicit sweating . Exposures to toxins and medications can also lead to hypothalamic hyperhidrosis, and a number of drugs that act on the CNS have increased sweating as a potential side effect (see Table 39.2 ). Additional causes of hypothalamic hyperhidrosis are presented in Table 39.4 .

Pressure and postural hyperhidrosis may be due to hypothalamic or possibly cortical stimulation. With changes in posture or the application of pressure to one side of the supine individual, a variety of sweating patterns have been described, such as lateral hyperhidrosis, horizontal hemihidrosis, and crossed hemihidrosis. Idiopathic localized unilateral hyperhidrosis of the face and neck or forearm has been reported as an episodic disorder triggered by heat, emotional, or gustatory stimuli .

Medullary (gustatory) hyperhidrosis

Pathologic medullary hyperhidrosis

This disorder arises after disruption of nerves. During healing, nerve fibers mediating sweating aberrantly connect to nerves that mediate salivation. Impulses in parasympathetic fibers normally supplying the salivary glands are now misdirected to the sweat glands. As a result, salivary stimulation elicits sweating. Of note, thermal sweating in the areas of affected skin is reduced.

The parotid form appears weeks to months following surgery, trauma, or other disorder (e.g. abscess, herpes zoster) affecting the parotid gland. These patients experience vasodilation and sweating on the cheek and adjacent neck when salivary stimulation is induced by eating, drinking, or even chewing ( Fig. 39.3 ). Sweating most often occurs in the distribution of the auriculotemporal nerve; at times there is also unilateral localized pain .

Auriculotemporal syndrome (Frey syndrome) is common after parotid surgery, developing in 40% or more of patients, although many are not aware of it. It can also occur during infancy (frequently as a consequence of trauma to the parotid region in a forceps-assisted delivery), presenting with gustatory flushing, but usually no obvious sweating, that is often erroneously attributed to food allergy. Another variant of gustatory hyperhidrosis is the chorda tympani syndrome in which salivary stimuli to the submandibular gland induce sweating on the chin and lower jaw line.

Patients with cluster headaches can have sympathetic deficits that result in impaired thermoregulatory sweating on the affected side of the forehead. In addition, ipsilateral hyperhidrosis and flushing may occur together with excessive lacrimation during headache attacks. This is due to misdirection of parasympathetic fibers, which normally supply the lacrimal glands, to sweat glands and blood vessels. Patients with Raeder syndrome (Horner syndrome [ptosis, meiosis ± anhidrosis] plus unilateral temporofrontal headaches and pain) may also have excessive supraorbital sweating (lacrimal sweating).

Any condition that injures the vagus nerve and sympathetic trunk, as they lie close together in the thorax, may cause a pathologic medullary hyperhidrosis ( Table 39.5 ). Cholinergic fibers from the vagus nerve sprout into the adjacent sympathetic trunk during the healing process and can result in a gustatory hyperhidrosis with sweating on the face, neck, and portions of the trunk and upper extremities.

Table 39.5

Other causes of secondary hyperhidrosis.

Gustatory lacrimation (“crocodile tears” syndrome) is due to transposition of autonomic fibers for lacrimation and salivation after facial nerve injury.

Adapted from Moschella S, Hurley HV. Dermatology. Philadelphia: WB Saunders, 1992.

OTHER CAUSES OF SECONDARY HYPERHIDROSIS
Medullary (gustatory)	Spinal cord	Axon reflex	Abnormal blood vessels or eccrine glands (non-neural)
Physiologic gustatory sweating Frey syndrome Chorda tympani syndrome Cluster headaches Sympathectomy Sympathetic trunk and vagus nerve injury (e.g. by lung carcinoma, mesothelioma, thyroidectomy, subclavian aneurysm) Encephalitis Syringomyelia	Spinal injury Syringomyelia Tabes dorsalis	Inflammatory skin diseases Drugs (see Table 39.2 )	Aquagenic palmoplantar keratoderma Eccrine nevi Eccrine angiomatous hamartoma ( Fig. 39.5 ) Maffucci syndrome Arteriovenous fistula Klippel–Trenaunay syndrome Glomuvenous malformation Blue rubber bleb nevus syndrome Cold erythema Granulosis rubra nasi Pretibial myxedema

In patients with syringomyelia or encephalitis, gustatory hyperhidrosis is occasionally seen on the face and upper trunk. It involves the glossopharyngeal and vagus nerves. Disturbances in the brainstem apparently lead to transposition of the central medullary nuclei for salivation and sweating. There is no peripheral crossing of sympathetic and parasympathetic nerve fibers as is seen in other forms of pathologic gustatory hyperhidrosis.

Spinal (cord transection) sweating

Any injury or disease process that severs or interferes with the reticulospinal tracts of the cord can disrupt the sweating reflex (see Table 39.5 ). Lack of a sweat response to thermal stimulation usually occurs below the level of the injury. Abnormal patterns of segmental sweating may occur in conjunction with other autonomic, sensory, and motor alterations. Onset and duration are unpredictable. Sweating can be excessive, drenching the patient in the regions involved. Bouts of “mass reflex sweating” are initiated in the skin below the level of the cord interruption. It is most intense in skin segments close to the level of the transection. Mass reflex sweating does not occur in transections below T8–T10.

Autonomic dysreflexia

Autonomic dysreflexia is a syndrome that may occur with spinal injuries at or above T6 . Massive episodic sympathetic discharge results in sweating above the level of the transection accompanied by headache, hypertension, facial flushing, bradycardia or tachycardia, piloerection, and paresthesias.

Direct stimulation of a cutaneous sympathetic axon with electrical and physical impulses or injections of drugs with nicotine-like effects on autonomic ganglia can induce sweating in an area ~4 cm in diameter . Mediators from inflammatory skin conditions (e.g. psoriasis, dermatitis) can also elicit localized hyperhidrosis. Substance P and a number of other mediators, including kinins, dopamine, prostaglandins, angiotensin and adenine, may be involved .

Compensatory hyperhidrosis

The coordinated functioning of the body's eccrine sweat glands is illustrated by the phenomenon of compensatory hyperhidrosis, in which the sweat glands of one area become hyperactive in an effort to compensate for hypo- or anhidrosis in another. Apparently, a threshold number of sweat glands must be non-functional in order for the compensatory response to occur. The nature or type of the underlying process that produces the anhidrosis also appears to be important. For example, compensatory hyperhidrosis does not seem to develop secondary to the anhidrosis produced by lymphomas.

The best-known clinical forms of compensatory hyperhidrosis occur in the following three situations:

• Miliaria : longstanding or recurrent miliaria rubra or profunda typically results in numerous non-functional sweat glands within large areas of the trunk. This induces compensatory hyperhidrosis of the face ( Fig. 39.4A ), especially in response to ambient heat or exercise.

  

• In diabetes mellitus , disturbance of the autonomic nervous system due to peripheral neuropathy and microangiopathy often causes anhidrosis or hypohidrosis of the affected skin, particularly the legs. With the loss of sweating on the lower extremities, these patients may develop compensatory increases in thermal sweating on the trunk, especially the back. A second type of compensatory hyperhidrosis, gustatory in character and usually on the face and neck ( Fig. 39.4B ), may also be seen in diabetic patients with peripheral neuropathy of the lower extremities.

• Post-sympathectomy : with the loss of sweating that results from cervicothoracic sympathectomies, a thermal hyperhidrosis, usually on the trunk, is common. Sympathectomized patients may also experience gustatory hyperhidrosis.

Non-neural hyperhidrosis

Direct stimulation of eccrine sweat glands by heat or sudomimetic drugs can lead to localized sweating. Even denervated skin sweats when heat is applied . Table 39.5 outlines additional non-neural causes of localized hyperhidrosis, including increased activity of eccrine glands overlying vascular lesions such as eccrine angiomatous hamartoma ( Fig. 39.5 ). The rare disorder “cold erythema” affects the skin and gastrointestinal tract – exposure to cold produces local cutaneous erythema and intense pain along with a central area of hyperhidrosis. As with other entities in which local pain is a clinical feature (e.g. glomuvenous malformations), increased blood flow or an axon reflex (secondary to the pain) may be the casual mechanism for this sweating.