Hyperhidrosis is a disorder of excessive sweating due to over-stimulation of cholinergic receptors on eccrine glands. This pathologic disorder is characterized by sweating beyond what the body uses for homeostatic temperature regulation. Eccrine glands are concentrated in areas such as the axillae, palms, soles, and face, so these are the areas most commonly affected by hyperhidrosis. The acetylcholine negative feedback loop is likely impaired in these patient's which may help explain how a physiologic response can become pathologic. Studies have shown the prevalence of this disorder to be approximately 3% in the United States. It also has the potential to affect the mental status of an individual, particularly in social environments.
There are two types of hyperhidrosis, primary and secondary and the management and treatment can be quite different. Primary disease will typically present earlier in life with more localized symptoms; whereas, the secondary disease will commonly be due to adverse effects of medications or systemic disorders, particularly neurologic. The diagnosis will usually be made clinically; however, grading scales and tests available to assist in determining the severity and localization of the disorder. Laboratory workup may be indicated if a secondary cause is suspected to rule out infection, hyperthyroidism, diabetes mellitus, neurologic disorders, or a medication side-effect. There are several treatment options for hyperhidrosis including topical aluminum chloride and oral anticholinergic medications which are sufficient in most mild to moderate cases. Botulinum toxin A injections, sympathectomy, and local excision are also very effective but reserved for cases that are resistant to conservative therapy.
Hyperhidrosis can be categorized as either primary or secondary. This distinction is important to make because treatment and management may differ between the two groups. The etiology of primary hyperhidrosis remains unknown despite multiple literature reviews. Genetic factors are believed to play a role in excessive neural stimulation, although this is not well understood. Secondary causes are usually easier to identify because they are associated with medications such as dopamine agonists, SSRIs, antipsychotics, alcohol, and insulin, systemic disorders such as diabetes mellitus, hyperthyroidism, Parkinson disease, and other neurologic disorder, and tumors such as pheochromocytoma and lymphoma.
Almost any febrile illness can cause hyperhidrosis. Both chronic alcoholism and tuberculosis are also associated with hyperhidrosis.
Developing segmental or localized hyperhidrosis is rare. However, the condition can present on the forehead, axilla, palm, feet or forearm in some adults. Some postmenopausal women develop moderate to severe hyperhidrosis around the face and scalp. Unilateral hyperhidrosis tends to be more common on the right side of the face or arm, with anhidrosis on the left side.
Hyperhidrosis affects approximately 3% of the U.S. population and is most common in patients between the ages of 20 to 60. There has been no evidence showing that either men or women are at increased risk of this disorder. The palmar region is the most common area affected and females up approximately 50% to 60% of hyperhidrosis cases.
Hyperhidrosis affects all races, but data show that the Japanese are more affected than any other ethnic group.
Hyperhidrosis involves hyperactivity of the parasympathetic nervous system causing excessive release of acetylcholine from the nerve ending. Acetylcholine will innervate the epidermal eccrine sweat glands as a physiologic response to core body temperature control during times of physical or psychological stress. In hyperhidrosis, it is believed that the negative feedback mechanism to the hypothalamus may be impaired causing the body to sweat more than what is needed to cool down the body's temperature. This pathologic reaction can be triggered by medications which increase the release of acetylcholine from the neuron or systemic medical disorders which also upregulate a sympathetic response.
On histologic examination, eccrine glands appear to be normal in size and number compared to patients without the disorder. However, the sympathetic ganglia in these patients are usually larger. This supports the idea that hyperhidrosis is a disorder of excessive cholinergic stimulation as opposed to a problem with the eccrine glands themselves.
History and Physical
Patients with hyperhidrosis will report excessive sweating, usually in with a high amount of eccrine glands in the skin including the palms, soles, face, head and/or axillae. Primary hyperhidrosis is more commonly seen in the younger population, the patients who have symptoms for more than six months, those who have a family history of the disorder, and the patients with bilateral involvement. Symptoms that present later in life should be more concerning for a secondary cause and a workup to rule out adverse effects to medications or systemic diseases like diabetes mellitus or hyperthyroidism is warranted. Diagnosis is usually made from clinical assessment, so a visual inspection of the common sites is recommended. There are visual scales available that quantify the severity of palmar sweat, and when localization is questioned, an iodine-starch test can help localize the areas of concern which will also be beneficial at the time of treatment application.
Diagnostic criteria for primary hyperhidrosis:
- Excessive sweating for 6 or more months
- Sweating involves axilla, palms, soles, and/or face
- Sweating is bilateral and symmetric
- Decreased or no sweating at night
- Sweating episodes last at least 7 days
- The individual is 25 years or younger
- There is a family history
- Sweating impairs daily living activities
It is important first to determine whether the source is primary or secondary and a thorough history will help to differentiate that. If a secondary cause is suspected, providers should consider ordering a complete blood count, basic metabolic panel, thyroid-stimulating hormone, chest x-ray, sedimentation rate, ANA, Hemogblin A1C. These tests will assist in ruling out infection, kidney dysfunction, malignancy, diabetes mellitus, thyroid disease, an inflammatory disorder, or connective tissue disease which can all be associated with hyperhidrosis. Providers can also thoroughly evaluate the severity of the disease by assessing the amount of palmar involvement using a measuring scale or determining the pattern of disease using a starch-iodine. These are not widely used since visual assessment alone is usually sufficient to diagnose.
Treatment / Management
Treating hyperhidrosis has become easier for clinicians as more treatment options have become available and a stepwise approach is often effective. But despite many treatments being available, many do not work or work inconsistently. Patient dissatisfaction is very high. There are many topical and systemic agents available to treat hyperhidrosis.
First-line therapy for hyperhidrosis includes over the counter aluminum chloride hexahydrate 20% (Drysol) for 3 to 4 nights then nightly as needed. Mild skin irritation may result from the application; however, this is usually minimal.Drysol is best applied at night and should be washed off in the morning. Most patients are not able to tolerate the irritating in the long term,
Recently glycopyrronium tosylate topical cloth was approved to treat sweating.
Axillary sweating can be maned with aluminum chloride gel and while it does work, it is also a potent irritant.
All topical agents can cause skin sensitization and some like tannic acid and potassium permanganate can also cause skin discoloration. These agents appear to decrease sweating by denaturing keratin and thus occluding the pores of the sweat glands. The duration of the effect is very short.
If a patient does not respond to topical treatment or there are more generalized symptoms, oral anticholinergic medications which block the cholinergic receptors (including oxybutynin 5 mg to 10 mg per day or topical glycopyrrolate 0.5% to 2.0%) should be considered.
Every single anticholinergic agent has a very poor adverse risk profile and patients often develop dry eyes, dry mouth, urinary retention, and constipation.
Additionally, iontophoresis two to three times weekly and botulinum toxin A injections every 3 to 4 weeks are effective if patients fail topical and oral medication therapy.
Iontophoresis is a long term treatment and at best its effects are mild. Many agents can be added to the water but compliance with this treatment is low.
Botulinum toxin is effective but it is also expensive and repeat treatments are required every few months. Plus the toxin can cause nerve paralysis depending on where it was injected. Some experts recommend botulinum toxin plus lidocaine for injection into the axilla. Again the treatment benefits are temporary and costly.
More invasive therapeutic measures are available including sympathectomy or local excision as a last resort. Many types of surgical procedures have been developed to manage hyperhidrosis including sympathectomy, radiofrequency ablation, subcutaneous liposuction and surgical excision of affected areas. Of all these, sympathectomy appears to be the best treatment that is somewhat permanent. It involves the excision of the ganglia (T2-T4) responsible for sweating. Resection of T1 ganglia is done for facial sweating, T2 and T3 for palmar sweating and T4 ganglia is excised for axillary sweating. The procedure can be done thoracoscopically, but complications are also common. Compensatory sweating, gustatory sweating, horner syndrome, pneumothorax, pain, and intercostal neuralgia have all been reported.
If a secondary cause is suspected, treatment of the underlying disorder or discontinuing the suspected medication is recommended in addition to the regular therapy.
- Chronic alcoholism
The prognosis of hyperhidrosis is guarded. While not life-threatening, it can be cosmetically unacceptable and may even lead to difficulties with work. The quality of life for patients with severe hyperhidrosis is poor. There is no treatment that works reliably and the recurrence of hyperhidrosis is common with all of them. Newer surgical treatments offer hope but do not always cure the disorder.
- Social embarrassment
- Emotional distress
- Work or school-related disability
Pearls and Other Issues
Hyperhidrosis can affect not only a patient's physical health but also his or her psychological health. Patients, particularly those within the pediatric population, may suffer from social embarrassment leading to a lower quality of life compared to their peers. It is important for healthcare providers to screen for this condition.
Enhancing Healthcare Team Outcomes
Hyperhidrosis is a common complaint in clinical practice and while there are many treatments available, many are unsatisfactory. Thus, the disorder is best managed by an interprofessional team that includes the primary care provider, nurse specialist, thoracic surgeon, plastic surgeon, and the internist. The key is to reduce sweating with minimal complications.
The pharmacist should educate the patient on all the topical and systemic products available to manage sweating. The patient should be aware of the adverse effects and potential complications.
The dermatologist should be consulted if the cause is unknown.
For recalcitrant cases, a thoracic surgeon should be consulted.
A mental health nurse and psychiatrist should be involved as the condition to assist with mental health support as the disease can cause severe emotional distress.
Most topical and non-surgical treatments do not work reliably. Surgery can be done but recurrences are not uncommon. Patients need to be educated about all the potential treatments and select one which is the most effective and with the least morbidity. A team approach may help deliver the optimal treatment for hyperhidrosis and improve outcomes.