The Evolving Evidence Base in Hyperhidrosis Care

Hyperhidrosis remains a prevalent yet historically under-recognized disorder, characterized by excessive eccrine sweat production disproportionate to thermoregulatory needs. While diagnostic criteria and disease mechanisms are well established, recent literature continues to emphasize gaps in recognition, patient engagement, and long-term disease management.¹ Contemporary research has increasingly focused on patient-reported outcomes, real-world disease burden, and refinement of topical therapeutic strategies, particularly for primary axillary hyperhidrosis (PAH).²

Disease Burden and Patient Impact

Recent reviews and survey-based studies reaffirm that hyperhidrosis exerts a substantial and sustained impact on quality of life (QoL), often beginning in adolescence and persisting for decades. Epidemiologic analyses summarized by Litchman et al and others describe PAH as comparable in prevalence to psoriasis, yet far less likely to be documented as a primary reason for dermatology visits.³ Patients frequently adapt behaviors, altering clothing choices, limiting social interaction, and modifying occupational activities, well before seeking medical care.

Psychosocial burden remains a dominant theme across studies. Anxiety, embarrassment, and perceived stigma continue to drive underreporting, with a significant proportion of patients never initiating discussions with healthcare providers. Importantly, these findings are consistent across adult and pediatric populations, reinforcing the concept of hyperhidrosis as a lifelong disease with cumulative psychosocial consequences rather than a transient cosmetic concern.²

Diagnostic Assessment and Outcome Measures

For clinicians familiar with hyperhidrosis, the recent literature offers less novelty in diagnostic criteria and more emphasis on standardization of outcome measurement. The Hyperhidrosis Disease Severity Scale (HDSS) remains widely referenced, but newer patient-reported outcome instruments, such as the Hyperhidrosis Disease Severity Measure–Axillary (HDSM-Ax-7), have been validated and incorporated into contemporary clinical trials.⁴

Publications by Del Rosso et al. and Pariser et al. highlight the increasing regulatory and scientific importance of patient-reported outcomes that capture daily functional impairment rather than relying solely on gravimetric sweat production.^3-4 A one-point improvement on these validated scales is consistently defined as clinically meaningful, aligning statistical outcomes with patient-centered benefit.

Advances in Topical Anticholinergic Therapy

Recent phase 3 data have expanded the evidence base for topical anticholinergic agents in PAH. The Cardigan I and II trials, reported in the Journal of the American Academy of Dermatology by Pariser et al evaluated sofpironium topical gel 12.45% in randomized, vehicle-controlled, double-blind studies. Pooled analyses demonstrated statistically significant improvements in both patient-reported severity scores and objective gravimetric sweat production compared with vehicle.

Notably, treatment effects were observed early, with separation from vehicle as soon as the first post-baseline assessment, and were sustained throughout the treatment period. Secondary endpoints—including combined thresholds of symptom score improvement and sweat reduction—also favored active treatment. These findings are consistent with earlier phase 2 investigations and support the role of topical anticholinergics as a noninvasive option for patients who have failed or cannot tolerate antiperspirants.

Safety and Tolerability Considerations

Safety data from recent trials reinforce known class effects of anticholinergic therapies. In the phase 3 studies, treatment-emergent adverse events were primarily mild to moderate and included dry mouth, blurred vision, mydriasis, and application-site reactions. Rates of systemic anticholinergic effects were lower than those historically reported with oral agents, though discontinuations due to adverse events did occur.³

Importantly, investigators emphasize appropriate patient selection and counseling, particularly for individuals with conditions that may be exacerbated by anticholinergic exposure. Long-term extension studies referenced in the literature suggest that adverse event incidence may decrease over time with continued use, though ongoing pharmacovigilance remains warranted.^3-4

The Current “State of the State”

Collectively, recent research characterizes hyperhidrosis as a well-defined yet persistently undertreated condition, despite growing therapeutic options and validated outcome measures. Advances in topical therapy design, particularly agents engineered for localized activity and rapid metabolism, represent a meaningful evolution in treatment strategy rather than a paradigm shift.

For clinicians, the current state of hyperhidrosis management emphasizes 3 key themes:

• Earlier recognition and proactive inquiry, especially in younger patients and those presenting for unrelated dermatologic concerns;
• Use of validated patient-reported outcomes to guide treatment decisions and assess response; and
• Individualized therapy selection, balancing efficacy, tolerability, adherence, and patient preference.

While recent trials have strengthened the evidence base for topical anticholinergics in PAH, ongoing research is needed to clarify long-term outcomes, comparative effectiveness across treatment classes, and strategies to address nonadherence. Ultimately, improving hyperhidrosis care will depend as much on clinician awareness and patient engagement as on continued therapeutic innovation.

References

1. Brackenrich J, Medeus CF. Hyperhidrosis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; October 3, 2022.
2. Litchman G, Hicks A, Bhatia N, Cartwright M. Clinical best practices and insights toward improving recognition, diagnosis and treatment of primary axillary hyperhidrosis (PAH). J of Skin. 2025;9(6):s718. doi:10.25251/0qds5b91
3. Pariser D, Glaser DA, Del Rosso J, et al. Sofpironium topical gel, 12.45%, for the treatment of axillary hyperhidrosis: Pooled efficacy and safety results from 2 phase 3 randomized, controlled, double-blind studies. J Am Acad Dermatol. 2025;93(1):82-88. doi:10.1016/j.jaad.2025.02.086
4. Del Rosso J, Hebert A, Cartwright M. Sofpironium targets M3 receptors in vitro and shows early clinically meaningful improvement in primary axillary hyperhidrosis symptoms. J of Skin. 2025;9(6):s717. doi:10.25251/kvstvq23