Rare Causes of Excessive Sweating

1. Shapiro’s syndrome

This is a very rare syndrome consisting of episodic temperature dysregulation with hyperhidrosis and hypothermia, associated with agenesis of the corpus callosum.  It may be associated with lethargy, confusion and weight loss during the abnormal episodes.  The exact mechanism is not known, although hypotheses include a resetting of the hypothalamic thermostat to a lower level secondary to neurochemical dysregulation, inflammation, neurodegeneration or autoimmunity.  Clonidine has been helpful in some reported cases.  Appropriate fluid resuscitation is also needed if there is dehydration.

2. Frey’s syndrome

Frey’s syndrome is focal gustatory sweating, i.e., sweating of the face during eating or drinking.  This occurs after damage to the facial nerve, such as following an operation or Bell’s palsy with aberrant reinnervation occurring such that the nerve fibres which would normally innervate the facial sweat glands through the parasympathetic chorda tympani nerve fibers being incorrectly replaced by fibers which should be innervating the salivary glands.  Thus when salivation is stimulated, so is sweating.

Botulinum is very effective for Frey’s syndrome.  Alternatives include topical antiperspirants or topical anticholinergics such as glycopyrrolate.

3. Harlequin’s syndrome

In Harlequin’s syndrome, erythema and hyperhidrosis develop unilaterally. Typically there is a compensatory reaction to decreased sweating because of damage to the sympathetic system on the opposite side of the body.  It may result from either central or peripheral sympathetic pathway damage.

4. Spinal cord lesions

Autonomic dysreflexia may occur with lesions of the spinal cord above T6, manifested by exaggerated autonomic responses to otherwise innocuous stimuli.  This may be a presenting feature of a syrinx or intramedullary tumour.

5. Serotonin syndrome

This is an important syndrome to be aware of as it is commonly overlooked and very variable in degree. It classically manifests with mental status changes, neuromuscular hyperactivity, and autonomic instability, in particular sweating and hyperthermia, but only a component may be present. Patients taking more than one agent acting on the serotonin system are particularly prone, for example an SSRI plus a tricylic. Other agents to have on the alert list when thinking about this diagnosis include monoamine oxidase inhibitors (MAOIs), trazodone (Desyrel), lithium, opioids, and amphetamine/stimulants, including methylphenidate (Ritalin), 3,4 methylenedioxymethamphetamine (MDMA, Ecstasy), SNRIs (e.g. Venlafaxine (Effexor) and duloxetine (Cymbalta)), cocaine, herbal supplements (St. John's Wort, ginseng), alpha-2 adrenergic heteroreceptor blocking agents (e.g. mirtazapine (Remeron)) that act by increasing noradrenaline and serotonin release and block serotonin receptors, Trazodone (Desyrel) and certain opioids. Less frequently, serotonin syndrome may be seen with the use of a single agent.

6. Stroke related sweating

Sweating associated with stroke may be mild or profuse, usually occurring early, either with the onset of stroke or a few days later, typically lasting two days to a couple of months.  Delayed onset six to eight months following a stroke as well as prolonged persistence of sweating has also been described.  The sweating may be spontaneous or precipitated by exercise or minor infection.  It involves one entire side of the body, although face and arm are more prominently affected.  Other associated autonomic features are not usually present.  The hemi-hyperhidrosis is contralateral.