Background

Hyperhidrosis is a condition which causes people to sweat too much because their sweat glands are overstimulated. It causes the body to generate more sweat than is necessary for maintaining its temperature in a steady state. Sweat or eccrine glands are found in armpits, palms, feet, and the face, which are the areas usually related this condition. The negative feedback loop connected to acetylcholine might be altered in people suffering from this disorder making the physiologic duty to a pathologic response.  Research shows that about 3% of people in the United States have this condition. Hyperhidrosis can make life hard for people, affecting their feelings mental health social life, and work. 

This condition can be divided into primary as well as secondary. The treatment and management strategies depend on the type of condition. Primary condition is noticed in early stages of life characterized by localized symptoms whereas secondary condition occurs due to systemic disorders mainly neurological disorders or  medication side effects. Laboratory studies help to identify the causes such as diabetes mellitus, infection, hyperthyroidism etc. Treatment options include anticholinergic medications and aluminum chloride (topical). 

Epidemiology

Hyperhidrosis is a common condition that affects individuals of all ages. In the United Staes and the UK, its prevalence is 1- 1.6%, with 60% of the affected population being women. Among adolescents and young adults, the incidence rate is 0.6-1%. Japanese individuals are significantly more affected than any other ethnic group. Hyperhidrosis can affect both sexes and often begins in childhood or adolescence. A study of 850 patients with palmar, axillary, or facial hyperhidrosis found that 62% reported experiencing excessive sweating since early childhood, 33% since puberty, and 5% during adulthood. 

Anatomy

Pathophysiology

The sweat glands are innervated by sympathetic cholinergic fibers, which send signals to regulate the core body temperature in response to physical or psychological stress. The hypothalamus, specifically its thermoregulatory center, controls this sympathetic innervation. Sweating is induced by the excitation of muscarinic receptors via cholinergic systems. In hyperhidrosis, the sympathetic nervous system becomes hyperactive, leading to excessive release of acetylcholine from nerve endings. It is observed that the existence of the negative feedback mechanism prohibits the hypothalamus from sweating more than necessary for cooling. This pathological response may also be due to medications used to increase the release of the neurotransmitter, acetylcholine, alternatively, is the result of a systemic medical disorder, which intensifies sympathetic responses. 

Etiology

The analysis of primary condition remains unknown in spite of extensive research. Inheritance of factors is certain to be responsible for the excess stimulation of nerves, although it is not well understood. Secondary hyperhidrosis is generally easy to identify as it is related to medications like SSRIs, insulin, and dopamine agonists, systemic abnormalities that include hyperthyroidism, Parkinson disease, diabetes mellitus, tumors like lymphoma, pheochromocytoma and other neurologic disorders.  

Almost any delirious illness can lead to hyperhidrosis, and it is also linked to tuberculosis and prolonged consumption of excessive alcohol. There are very few cases of localized or segmental hyperhidrosis being developed. The condition can be seen on the foreheads, palms, forearms, axillas and feet in some adults. Post menopausal women may experience mediate to severe sweat around their scalp and face. Unilateral hyperhidrosis is often noticed on the right of the arm or face, often accompanied by anihidrosis on left side. 

Genetics

Prognostic Factors

This condition is challenging to treat effectively but is not associated with mortality. Severe cases can significantly impact the quality of a patient’s life. However, newer treatment options have improved the prognosis for patients. 

Clinical History

Primary hyperhidrosis is a skin and nerve condition described by extreme sweating from the sweat glands that produce perspiration. Generally, this starts in childhood or teenage and may be caused by other conditions within the body, the side effects of some drugs or disorders of metabolism. Harlequin syndrome presents as one-sided excessive perspiration and blushing, mainly evoked by warmth or physical activity. 

The character profile and temperament of patients with essential hyperhidrosis has been a topic of interest, but evidence suggests that this condition Is not associated with personality disorders or social phobia. Secondary causes of hyperhidrosis include endocrine diseases, psychiatric disorders, respiratory diseases and pheochromocytoma. 

The diagnostic criteria supporting primary hyperhidrosis are an onset of at least 6 months of excessive sweating which occurs in at least four of the following such as locations rich in eccrine glands, absence at night, happening once a week, bilateral with symmetrical distribution, starts before 25 years of age, and interferes with daily life. 

Physical Examination

The visible indication of hyperhidrosis can be typically noticed. Iodine starch test may be employed to directly visualize the affected areas. The affected area is sprayed with a mixture of 500g of soluble starch and 0.5-1g of iodine crystals in this test. Those areas which produce sweat turn black colour. 

Age group

Associated comorbidity

Emotional distress 

Work-related disability 

Irritation of affected skin 

Social embarrassment 

Associated activity

Acuity of presentation

Differential Diagnoses

POEMS syndrome 

Blue Rubber Bleb Nevus syndrome 

Pachydermoperiostosis 

Dermatologic symptoms of Glomus tumor 

Neuropathy 

Lymphoma 

Thryrotoxicosis 

Alcohol use disorder 

Menopause 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The choice of treatment depends on the severity of the condition, location, patient preference, response to prior treatments, etc., often requiring a combination of therapies for optimal results. 

First-line therapy involves the use of aluminum chloride hexahydrate for 3 to 4 days in the night followed by using glycopyrronium tosylate for axillary sweating. If the response to the treatment is inadequate, then oral anticholinergic drugs like oxybutynin or glycopyrrolate (topical) can be considered. 

If initial treatments fail, iontophoresis two to three times per week and injections of botulinum toxin A for every 3 to 4 weeks can be effective alternatives. However, these treatments can be costly and require ongoing sessions.  

More invasive treatment measures, such as local excision or sympathectomy, are considered as the last options for managing hyperhidrosis. Surgical procedures developed for this condition include sympathectomy, subcutaneous liposuction, surgical excision, and radiofrequency ablation of the affected areas. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Use of aluminum compounds

Aluminum chloride topical: This preparation is available over the counter and works best when applied on dry skin and covered overnight. 

Use of anticholinergic agents

Propantheline: This drug works by blocking the action of acetylcholine at postganglionic receptor sites of the parasympathetic system. 

Glycopyrrolate: This inhibits the activity of acetylcholine at the parasympathetic sites by acting on secretory glands, CNS and smooth muscles. 

Benztropine: this inhibits striatal cholinergic receptors and may help to balance the dopaminergic and cholinergic activity in straitum. 

Use of topical anticholinergics

Sofpironium topical: it is a competitive inhibitor of acetylcholine receptors that are located on few peripheral tissues like sweat glands. 

Glycopyrronium tosylate: This is applied topically to inhibit the activity of acetylcholine on sweat glands and indicated in treating primary axillary hyperhidrosis. 

Use of neuromuscular blocking agents

Onabotulinumtoxin A: This drug prevents the release of acetylcholine and causes a state of denervation at postganglionic sympathetic cholinergic nerves and neuromuscular junction. 

Sympathectomy:  

ETS (endoscopic thoracic sympathectomy) is a surgical procedure that cuts or clamps sympathetic nerves responsible for sweating, particularly effective for palmar and axillary hyperhidrosis. It can cause complications like compensatory sweating, intercostal neuralgia, Horner syndrome, gustatory sweating,pain, and pneumothorax which can lead to drowsiness, constricted pupils, and lung collapse. 

Radiofrequency inflation: 

Radiofrequency energy is used to destroy nerve tissue causing excessive sweating, providing long-term reduction, especially for axillary hyperhidrosis. Complications include temporary pain and numbness, less common than sympathectomy. 

Subcutaneous liposuction: 

Liposuction is a procedure that involves the removal of sweat glands in the underarms, which can significantly reduce sweating, but may also cause infection, bruising, and changes in the sensation of skin. 

Surgical excision: 

This involves the surgical removal of sweat glands directly and is highly effective for localized axillary hyperhidrosis. Disadvantages of this technique include infection, scarring and changes in the texture of the skin. 

use-of-phases-of-management-in-treating-hyperhidrosis

Hyperhidrosis is a common medical problem to which proper treatment is not available. It is effective only with interprofessional teamwork. Pharmacists should teach patients about the possible treatment options, their side effects, and the possible complications. Consult a dermatologist when the cause is unknown. Thoracic surgery is also recommended in difficult cases. Mental health support is crucial to overcome emotional distress caused by this disorder. Most treatments are not reliable, and recurrences are common.  

Medication

Future Trends

Media Gallary

References

Hyperhidrosis – StatPearls – NCBI Bookshelf (nih.gov)