Botulinum toxin for the treatment of palmoplantar hyperhidrosis

Introduction: Epidemiology and pathophysiology

Hyperhidrosis (HH) is an excessive sweating disorder that affects at least 4.8% of the population in the United States, or 15.3 million individuals. This percentage is likely an underestimation, as this disorder is both underreported by patients and underdiagnosed by physicians. In fact, less than half of those affected discuss this with their physician, as many believe that HH is not a medical condition and that no treatment options exist. This underestimation is evident when we observe the reported prevalence of other countries, which range from 5.5% in Sweden, 12.8% in Japan, 16.7% in Canada, and 18.4% in China. By definition, HH is sweating beyond what is expected for environmental conditions and thermoregulation. In clinical practice, it is considered sweating that significantly interferes with daily life. Not only does palmoplantar HH cause anxiety and emotional distress, but it can increase the risk of cutaneous bacterial, viral and fungal infections, verruca infections, eczematous dermatitis, and muscle cramps. Most patients who have HH experience excess sweating in areas of high eccrine density, such as the axillae (51%), soles (30%), palms (24%), and occasionally in the craniofacial area (10%). Of patients with HH, 18% have both axillary and palmar involvement, whereas 15% have concurrent palmar and plantar involvement. Multiple modalities are available for treatment of primary focal HH, from topical medications such as aluminum chloride, non-surgical approaches such as iontophoresis, systemic medications such as clonidine or glycopyrrolate, botulinum toxin injections, and surgical sympathectomy. In this chapter, we will discuss the role of botulinum toxin (BTX) in the treatment of HH of the palms and soles.

Sweating is a complex mechanism regulated by the autonomic nervous system, which acts on three types of sweat glands: eccrine, apocrine, and apoeccrine. Eccrine glands are the most abundant among these three types, with approximately 3 million eccrine sweat glands unevenly distributed over the entire body surface area, particularly concentrated in the palms, soles, forehead, axilla, and cheeks. The primary function of eccrine sweat glands is thermoregulation, with cooling resulting from evaporation of eccrine sweat. Eccrine sweat glands are innervated by sympathetic cholinergic nerve fibers and thus use acetylcholine as the primary neurotransmitter, but they also respond to catecholamines (i.e., epinephrine, norepinephrine, and dopamine) in emotionally induced sweating. They secrete odorless, clear, thin and hypotonic sweat, with rates up to 10 L/day. The normal secretion rate of eccrine sweat glands is 0.5 to 1 mL/min, and only 5% of glands secrete sweat at any given time. In severe HH, secretion may exceed 40 mL/m ² /min.

Eccrine glands are the only sweat glands present on the palms, and thus it is believed that they are the source of over secretion in HH. In primary HH, neither the number, density, nor size of eccrine glands is abnormal, but rather there is overactivity of the postganglionic sympathetic cholinergic fibers innervating them. For this reason, BTX can be effective in treatment. BTX inhibits the presynaptic release of acetylcholine and binds to acetylcholine receptors at the postsynaptic membrane, thus disrupting the sympathetic input to eccrine glands. The resulting decrease in sweat output results in a clinically significant improvement of HH.