Hyperhidrosis: Five Things to Know

Hyperhidrosis

Eccrine sweat glands—concentrated in the scalp, axillae, inguinal folds, and acral skin—function to maintain normal thermal homeostasis and, to a lesser extent, eliminate toxins and drug metabolites. Hyperhidrosis is a disorder of eccrine sweat glands characterized by excessive production of sweat beyond physiologic levels. Anatomically, hyperhidrosis is either focal (localized) or generalized. Etiologically, the disorder is broadly divided into primary (idiopathic) or secondary (caused by drugs or an underlying metabolic, endocrine, infectious, or neurologic disease) types.^[1]

Secondary hyperhidrosis is best managed by treating the underlying disorder or discontinuing the causative medication. In contrast, primary hyperhidrosis seems to be genetically inherited, with normal eccrine glands producing too much sweat in response to aberrant autonomic neuronal stimulation, possibly because of pathology in the sympathetic ganglia of hyperhidrotic individuals.^[2] Primary hyperhidrosis often presents during childhood and can be a challenging, lifelong disorder associated with significant social, emotional, and occupational distress. Fortunately, public and professional awareness of hyperhidrosis is growing, along with improved therapeutic choices—both local and systemic.

Here are five important things to know about hyperhidrosis.

1. It's more common than you think. Primary hyperhidrosis affects roughly 4.8% of the US population,^[3] making it about as common as psoriasis. Among those with hyperhidrosis, 70% report severe excessive sweating in at least one body area, but only 51% have discussed their condition with a healthcare professional.^[3] Many suffer from hyperhidrosis, never asking their healthcare providers for help owing to the twin misconceptions that hyperhidrosis isn't a "real" medical condition and that there are no effective treatments.

Diagnosis is also frequently delayed. Half of those surveyed in a 2014 study conducted by the International Hyperhidrosis Society reported waiting at least 10 years before seeking medical help.^[4] In keeping with this idea of widespread underdiagnosis, prevalence estimates (2011-2013 data) showed that only 1.0% and 1.6% of United States and United Kingdom populations, respectively, were formally diagnosed hyperhidrosis.^[5]

Because the symptoms of primary hyperhidrosis typically begin in adolescence or young adulthood, an older adult presenting with new-onset hyperhidrosis should be assessed for secondary causes.

2. Topical antiperspirants will control most cases of mild to moderate primary hyperhidrosis—and not just in the axillae. Primary idiopathic hyperhidrosis is defined as at least 6 months of focal excessive sweating without secondary causes; sweating is typically exacerbated by stress, heat, and exertion and is absent during sleep. For mild to moderate primary hyperhidrosis, topical therapies are usually sufficient to alleviate symptoms. Aluminum and zirconium antiperspirants have been available for decades.

Antiperspirants such as aluminum chloride hexahydrate are safe and effective first-line treatments for mild to moderate focal primary hyperhidrosis of the palms, soles, and axillae; they work by precipitating in salt form to block distal eccrine sweat gland ducts^[6] and are available in both over-the-counter and prescription strengths. For optimal results, antiperspirants should be applied to dry skin, and applied less frequently when daily use causes significant irritation (redness, burning, itching, peeling).

Topical antiperspirants are safe and surprisingly effective, yielding long-term satisfaction rates of up to 87% in cases of mild axillary hyperhidrosis.^[6] Although prescription topical antiperspirants offer higher concentrations of the active ingredient, over-the-counter products are typically less irritating and may even be more effective, especially when treating sensitive areas, such as the axillae.^[7]

Just a note: if patients claim that underarm antiperspirants don't control their sweating, ask them the name of the product they are using, or better yet, ask them to bring it in. If it's a deodorant only, rather than an antiperspirant or combined product, that might explain the lack of efficacy. The International Hyperhidrosis society has a great resource on antiperspirants the right product.

3. A new topical therapy is a towelette for axillary hyperhidrosis, and more topicals are on the way. Glycopyrrolate and oxybutynin are oral anticholinergic drugs that have been used off-label to treat moderate to severe primary hyperhidrosis for decades.^[8,9] Small studies and case reports support the use of such topical anticholinergics as oxybutynin 10% gel and 1% glycopyrronium cream to treat primary focal hyperhidrosis.^[10,11] To date, however, only one topical anticholinergic—glycopyrronium tosylate (GT) 3.75%—has received US Food and Drug Administration (FDA) approval (June 29, 2018) to treat primary axillary hyperhidrosis.

FDA approval of GT 3.75% cloths (trade name Qbrexza™) for primary axillary hyperhidrosis was based largely on positive results from two large phase 3 clinical trials (ATMOS-1 and ATMOS-2).^[12] In these studies, 4 weeks of daily GT application yielded both reduced subjective (patient journal) axillary sweating (59.5% vs 27.6%) and gravimetrically assessed sweat production (-107.6 mg/5 min vs -92.1 mg/5 min) in the GT versus placebo groups. Treatment was well tolerated, with mild to moderate local skin irritation as the most common transient adverse event.^[12]

4. Sweating the details: tailor treatment to body part and severity. There's no shortage of management options, but the right one depends on which areas of the body are affected and the degree of sweating experienced by the patient. But beware: Some of these treatments have side effects that are worse than the condition itself.

The therapeutic "pyramid" for primary hyperhidrosis typically starts with topical antiperspirants (and/or anticholinergics, such as glycopyrronium tosylate for excessive axillary sweating). To this base, clinicians may need to add, either alone or in combination:

• Targeted botulinum A toxin injections (axillary, palms, soles)^[13,14];

• Iontophoresis for palmar and/or plantar hyperhidrosis^[15];

• Microwave thermolysis for axillary hyperhidrosis^[16]; and/or

• Oral anticholinergic drugs, such as glycopyrrolate and oxybutynin, prescribed off-label.^[8,9]

Each of these options comes with its own set of benefits and risks. Botulinum A toxin injections, for instance, are highly effective and yield markedly reduced sweating for 6-8 months^[14,15] but they are expensive and painful (especially for palms and soles) and may cause functional muscle weakness of the hands.

Microwave thermolysis reduces axillary hyperhidrosis in up to 89% of treated patients, with results lasting 12 months or longer, yet treatments are expensive and may cause swelling, tenderness, subcutaneous nodules, and/or numbness.^[16] Iontophoresis (which works by soaking hands or feet in tap water containing an ionized substance, then passing a weak electric current through the eccrine glands to temporarily inhibit sweat production) is safe even in children but the process is time-consuming, may cause significant discomfort, and delivers variable results.^[15]

Endoscopic thoracic sympathectomy continues to be performed for cases of refractory and severe primary hyperhidrosis. Although this procedure has been refined using video-assisted endoscopy to reduce potential cardiac, pulmonary, and neurologic complications^[17,18] compensatory hyperhidrosis (chronic excessive sweating in new areas) remains a major postoperative concern, occurring in up to 88% of those who underwent the procedure.^[18]

Finally, with respect to the systemic oral anticholenergics, the most common side effects are xerostomia, dry eyes, orthostatic hypotension, and (rarely) urinary hesitance and constipation. These are typically mild and dose-dependent.

5. Say "so long" to sweating in silence. Primary hyperhidrosis is both common and potentially debilitating, causing significant social, emotional, and occupational impact. Because primary hyperhidrosis typically presents early in life and affects up to 1.6% of adolescents and 0.6% of prepubertal children, the social and emotional damage can be severe, especially in children.^[19]

Fortunately, public perception of primary hyperhidrosis is changing. The International Hyperhidrosis Society continues to spearhead a multinational effort to provide resources to those with hyperhidrosis. Public awareness of hyperhidrosis is growing, thanks in large part to excellent educational resources for patients and healthcare providers,^[20] including those at https://www.sweathelp.org. With the introduction of new and effective topical treatments, such as glycopyrronium tosylate, more people will be exposed to the message that they don't have to sweat in silence.