Scientists May Have a New Explanation for Excessive Sweating

For people with hyperhidrosis, it always feels like the middle of August. New research brings us closer to understanding why — and the answer lies not in the sweat glands but deep within the autonomic nervous system.

In a study published in Science Advances, researchers from the Johns Hopkins University School of Medicine identified rare genetic variants that appear to hyperactivate the nerves controlling sweat production. The findings suggest that primary idiopathic hyperhidrosis — excessive sweating not caused by underlying conditions like thyroid disorders or malignancy — is a primary dysautonomia, a dysfunction of the autonomic nervous system present from birth. This insight could help researchers develop new treatments or repurpose existing ones to relieve excessing sweating in patients who aren’t benefiting from standard treatments. 

To pinpoint the root cause, senior author Malcolm Brock, MD, professor of surgery at Johns Hopkins, and his team used genetic sequencing to evaluate 32 people with hyperhidrosis from families in which people from multiple generations have been diagnosed with the condition.

The researchers discovered that nearly 19% of these patients carried rare variants in the SCN10A gene, which is responsible for encoding the sodium channel NaV1.8. In healthy sympathetic nerves, this channel acts as a precise regulator for sweat production. When mutated, however, it locks the sweat signaling pathway into overdrive.

To confirm the link, researchers engineered mice with the gene variants — and the rodents began dripping sweat, mirroring the human phenotype.

When Hyperhidrosis Is a Nervous System Problem

Because the autonomic nervous system innervates nearly every organ, this sympathetic overdrive could cause more problems than sweating. Patients — and their family members — frequently present with a cluster of multisystem symptoms, including chronic fatigue, brain fog, orthostatic intolerance, palpitations, and gastrointestinal disorders such as irritable bowel syndrome.

“One member of the family might have heart palpitations and chronic headaches, while another member might have hyperhidrosis and poor sleep and brain fog,” said Brock.

Often, these patients are dismissed or misdiagnosed with chronic anxiety. 

“Many of our patients are told that this is all in their heads, and I think that is probably the number one thing that we see,” said Brock. 

The new evidence suggests that for some patients, the issue originates in their DNA.

While these results don’t explain every case of hyperhidrosis, they could come as a relief for some patients, according to Joseph Lam, MD, a dermatologist and clinical professor of pediatrics at the University of British Columbia who was not involved in the study.

“Patients always want to know why — was it because I had an argument with my parents? Was it because I ate a wrong food?” he said. 

Having a clear genetic mechanism can confirm for patients that it wasn’t their fault, he added. 

The Future of Hyperhidrosis Treatment

Reframing hyperhidrosis as a systemic neurological condition explains why localized therapies — like clinical antiperspirants or botulinum toxin injections — often fall short: They target the end organ, not the origin.

Future treatments could target NaV1.8, the researchers said. In the mouse models, dampening sympathetic activity suppressed the hyperhidrosis.

For clinicians who have patients with severe hyperhidrosis, these insights could help guide drug selection, particularly when prescribing off-label systemic medications.

“If we’re going to choose a medication to treat, say, ADHD, we can choose one, like guanfacine, that might help for some of these patients,” said Lam. “This is still in the speculating and projecting-to-the-future stage, but this article gives us building blocks to think creatively.”

The implications may reach far beyond sweating.

“Sodium channels are probably just the tip of the iceberg,” said Brock. For example, dysfunction in calcium or potassium ion channels could play a role in hyperhidrosis and other autonomic nervous system problems, he said. 

Down the line, Brock envisions targeted gene therapies that directly address the underlying mutations — offering the potential to not just manage excessive sweating but correct it at its source.

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