Hyperhidrosis: A Central Nervous Dysfunction of Sweat Secretion

Hyperhidrosis (HH) is a central nervous dysfunction characterized by abnormally increased sweating due to a central dysregulation of sweat secretion. HH significantly affects the quality of life of patients in their private, social and professional environments. Physiologically, sweating is a mechanism that regulates body temperature, but it may also be triggered by emotional or gustatory stimuli. There are two main types of sweat glands: eccrine and apocrine glands. The central nervous system controls sweat secretion through the release of neurotransmitters into the autonomous nervous system (ANS) that activate the sweat glands. The hypothalamus has two separate neuronal pathways, one for thermoregulation and one for emotions. HH may thus be due to either a neuronal dysfunction of ANS regulation leading to a hyperactivity of the sympathetic nervous system, or to abnormal central processing of emotions. Crucially, there is no dysfunction of the sweat glands themselves. Various pathogenic mechanisms have been proposed to be involved in pathological sweat secretion in HH, ranging from structural changes within the ANS to increased expression of aquaporin 5 and upregulation of activin A receptor type 1 in eccrine sweat glands. Although a genetic predisposition has been demonstrated, it remains unclear exactly which genes are involved. To identify new, potential therapeutic targets and to improve treatment options, a good understanding of the signaling pathways involved, the underlying mechanisms, and the genetic components is essential. In this review we discuss the various aspects of sweat physiology and function that are necessary to explain pathological sweating. Our aim is to raise awareness of the complexity of HH to promote a better understanding of the disorder.