Pathophysiology of Excessive Sweating
Sweat glands in patients with hyperhidrosis are not histopathologically different from those in normal patients, nor is there an increase in the number or size of glands. The condition is caused by hyperfunction of the sweat glands rather than hypertrophy. Patients with primary hyperhidrosis have a higher-than-normal basal level of sweat production as well as an increased response to normal stimuli such as emotional or physical stress. There is evidence that these patients have a reduced threshold for emotional sweating, but have normal thermoregulatory and drug-induced sweating. Other clinicians report that patients may be hyperreactive to thermal stimuli. And although emotional stimuli can be involved in primary hyperhidrosis, Stolman observes that it is a physiologic disorder as opposed to a psychological disease, noting the occasional onset of hyperhidrosis in the neonatal period as further evidence.
One of the underlying mechanisms for a lowered threshold and exaggerated response in hyperhidrosis patients may be excessive sympathetic activity. In research, patients with palmoplantar hyperhidrosis showed less reflex bradycardia in response to Valsalva maneuver or facial immersion than healthy controls, but a higher degree of vasoconstriction in response to finger immersion in cold water. This study suggested that increased sympathetic activity through the T2-T3 ganglia causes palmar hyperhidrosis.
There is a vicious cycle that can occur with excessive palmar and plantar sweating—the evaporative cooling of the skin increases sympathetic outflow through reflex action, in turn increasing sweat output.
A recent study of recovery of excitability of the sympathetic sudomotor skin response in patients with hyperhidrosis and in normal controls found significant differences. Patients with hyperhidrosis had enhanced recovery of excitability, implying a “hyperexcitable somatosympathetic polysynaptic pathway.” In another study, patients with primary palmoplantar hyperhidrosis and controls were asked to do mental arithmetic. During the activity, those with hyperhidrosis had markedly increased sympathetic nerve activity on the soles of the feet compared to controls.
If there is generalized sympathetic overactivity in primary hyperhidrosis, catecholamine levels in patients could be predicted to be elevated. However, a study of plasma catecholamine levels in patients before and after thoracic sympathectomy found preoperative norepinephrine and epinephrine levels to be normal. After sympathectomy, the norepinephrine level fell, but epinephrine was unchanged. It was thus concluded that primary hyperhidrosis is more likely due to sympathetic overactivity in the upper dorsal ganglia.
Cardiac autonomic response was studied in patients with primary focal hyperhidrosis and healthy controls using spectral analysis of heart rate variability. Interestingly, there were no differences between groups in the low-frequency band that represents sympathetic cardiac innervation, but the high-frequency band representative of parasympathetic innervation did show differences. These results led the investigators to suggest that primary hyperhidrosis may involve a more complex dysfunction of the autonomic nervous system than previously thought, involving parasympathetic pathway differences as well.
There may be additional mechanisms involved in primary hyperhidrosis. An EEG and PET scan study of patients with palmoplantar hyperhidrosis showed increased sharp wave bursts during hyperventilation and hyperperfusion of the frontal cortex.
In summary, although the exact pathophysiology of primary hyperhidrosis is yet to be determined, there is much evidence for abnormalities in autonomic nervous system function. Since hyperhidrosis often begins in childhood and can be familial, the physiologic basis for this disorder may be genetically determined. Indeed, nearly 66% of hyperhidrosis sufferers indicate other family members have hyperhidrosis too.*
* Ro KM, Cantor RM, Lange KL, Ahn SS. Palmar hyperhidrosis: evidence of genetic transmission. J Vasc Surg 35:2 (2002): 382-386.