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 the 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.
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 makes up approximately 50% to 60% of hyperhidrosis cases.
Hyperhidrosis involves hyperactivity of the sympathetic 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.
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 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 which 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.
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.
Treating hyperhidrosis has become easier for clinicians as more treatment options have become available and a stepwise approach is often effective. 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. 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. Additionally, 0ontophoresis 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. More invasive therapeutic measures are available including sympathectomy or local excision as a last resort. If a secondary cause is suspected, treatment of the underlying disorder or discontinuing the suspected medication is recommended in addition to the regular therapy.
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.
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