Hyperhidrosis

Aka: Hyperhidrosis, Palmoplantar Hyperhidrosis, Generalized Hyperhidrosis, Craniofacial Hyperhidrosis, Primary Focal Hyperhidrosis, Localized Hyperhidrosis

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II. Definitions

  1. Hyperhidrosis
    1. Excessive sweating beyond physiologic need for Thermoregulation

III. Epidemiology

  1. Prevalence: 1-3% of U.S.
  2. Genetic predisposition
  3. Both genders affected equally (women report more often)

IV. Pathophysiology

  1. Eccrine Sweat Glands
    1. Most concentrated on the palms, soles, axillae and face
    2. Innervation by postganglionic autonomic nerve fibers
    3. Neurotransmitter: Acetylcholine
  2. Cerebral cortex releases stimuli secondary to emotion or physiologic stress
    1. Hypothalamus is hypersensitive to these stimuli
    2. Hyperhidrosis results from increased sympathetic stimulation
  3. Results in Eccrine Gland (Sweat Gland) hypersecretion
    1. Eccrine Glands are normal, but they are hyperstimulated

V. Types

  1. Primary Hyperhidrosis (90%)
    1. Idiopathic, bilateral, symmetric focal excessive sweating (see symptoms below)
  2. Secondary Hyperhidrosis
    1. Generalized or focal sweating due to underlying cause (medical condition, medication)
    2. See Hyperhidrosis Causes and Medication Causes of Hyperhidrosis

VI. Symptoms: Primary Hyperhidrosis

  1. Excessive focal sweating
    1. Axilla (50% of cases)
    2. Palms and soles
    3. Face
    4. Less common: Scalp, inguinal
  2. Exacerbated by stress or anxiety
  3. Only occurs while awake
    1. Contrast with Night Sweats

VII. Labs

  1. No labs needed unless secondary Hyperhidrosis is suspected by history, exam or lack of diagnostic criteria below

VIII. Differential Diagnosis: Secondary Hyperhidrosis

  1. See Hyperhidrosis Causes
  2. Night Sweats
  3. Medication Causes of Hyperhidrosis
  4. Vasomotor Symptoms of Menopause

IX. Diagnosis: Primary Hyperhidrosis

  1. Focal, visible, excessive sweating for longer than 6 months without secondary Hyperhidrosis cause AND
  2. At least 2 of the following criteria (using 4 criteria increases Test Specificity for primary Hyperhidrosis to 99%)
    1. Bilateral and symmetric sweating
    2. Daily activity Impairment
    3. Occurs at least once per week
    4. Onset at age <25 years old
    5. No occurrence during sleep
    6. Positive Family History

X. Grading: Hyperhidrosis Disease Severity Scale (HDSS)

  1. Grade 1
    1. Sweating not noticeable and does not interfere with daily activities
  2. Grade 2 (mild)
    1. Sweating is tolerable, but sometimes interferes with daily activities
  3. Grade 3 (severe)
    1. Sweating is barely tolerable and often interferes with daily activities
  4. Grade 4 (very severe)
    1. Sweating intolerable and always interferes with daily activities

XI. Management: Axillary Hyperhidrosis

  1. Step 1: Topical Aluminum Chloride 20-25% (Drysol)
  2. Step 2: Onabotulinum Toxin A (Botox Injection)
    1. May start at step 2 in severe cases (HDSS 3-4)
  3. Step 2 Alternative: QBrexza (moistened glycopyrronium disposable cloth)
    1. Expensive (nearly $600/month in 2019) and Anticholinergic adverse effects (see below)
    2. Another expensive option in 2024 is Sofpironium (Sofdra) Topical Gel
  4. Step 3: Oral Anticholinergics (e.g. Glycopyrrolate or Oxybutynin)
  5. Step 4: Consider microwave therapy
  6. Step 5: Consider local surgery
  7. Step 6: Consider sympathetic denervation (endoscopic thoracic sympathectomy)

XII. Management: Craniofacial Hyperhidrosis

  1. Step 1: Topical Aluminum Chloride 20% (Drysol) or topical glycopyrrolate 2%
  2. Step 2: Oral Anticholinergics (e.g. Glycopyrrolate or Oxybutynin)
  3. Step 3: Onabotulinum Toxin A (Botox Injection)
  4. Step 4: Consider sympathetic denervation (endoscopic thoracic sympathectomy)

XIII. Management: Palmar Hyperhidrosis

  1. Step 1: Topical Aluminum Chloride 20% (Drysol)
  2. Step 2: Onabotulinum Toxin A (Botox Injection) or Iontophoresis
    1. May start at step 2 in severe cases (HDSS 3-4)
  3. Step 3: Oral Anticholinergics (e.g. Glycopyrrolate or Oxybutynin)
  4. Step 4: Consider sympathetic denervation (endoscopic thoracic sympathectomy)

XIV. Management: Plantar Hyperhidrosis

  1. Step 1: Topical Aluminum Chloride 20% (Drysol)
  2. Step 2: Onabotulinum Toxin A (Botox Injection) or Iontophoresis
    1. May start at step 2 in severe cases (HDSS 3-4)
  3. Step 3: Oral Anticholinergics (e.g. Glycopyrrolate or Oxybutynin)

XV. Management: Methods - Topical Preparations

  1. Aluminum Chloride hexahydrate 20-25% (Drysol, Xerac)
    1. Obstruct Eccrine Gland pores
    2. Results in atrophy of Sweat Gland secretory cells
    3. OTC agents are less expensive and higher concentration than prescription preparations
  2. Expensive Topical Anticholinergics
    1. Glycopyrronium (Qbrexza) 2.4% wiped across each axilla daily
      1. Very expensive ($580/30 wipes in 2019)
      2. Anticholinergic effects (Blurred Vision, Dry Mouth) and local irritation
      3. References
        1. (2018) presc lett 25(11): 65-6
        2. Arnold (2019) Am Fam Physician 100(6):372-3 +PMID:31524358 [PubMed]
    2. Sofpironium (Sofdra) Topical Gel
      1. Similar to Glycopyrronium, both in structure and expense, used for axillary Hyperhidrosis
      2. FDA approved for age >9 years
      3. Avoid bathing for 30 minutes before or 8 hours after application
      4. Avoid shaving axilla for at least 8 hours after application
      5. References
        1. (2024) Presc Lett 31(11): 65
        2. Sofpironium (DailyMed)
          1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=78f86f4f-658c-468b-bd54-49182ddcc7ac
  3. Other agents with lower efficacy (or much higher expense)
    1. Antiperspirants containing aluminum zirconium trichlorohydrate (OTC)
      1. Swaite (2012) Br J Dermatol 166(suppl 1):22-6 [PubMed]
    2. Zeasorb Powder (Miconazole)
    3. Numerous others are not recommended (Formaldehyde, Glutaraldehyde, Boric Acid, tannic acid)
  4. Bedtime technique: First-line, preferred option
    1. Apply topical (Drysol) nightly for 6-8 hours until decrease in HDSS score
      1. Patients sweat less at night when topicals are more effective at blocking Eccrine Glands
      2. May then gradually space to 2-3 times per week at bedtime
    2. Apply Occlusive Dressing over night
    3. Remove in the morning and wash off
    4. May apply Baking Soda to skin to reduce irritation (Drysol may form HCL when combined with water)

XVI. Management: Methods - Systemic Preparations

  1. Anticholinergics (Not recommended for longterm use, Anticholinergic adverse effects)
    1. Glycopyrrolate (Robinul)
    2. Oxybutynin (Ditropan)
    3. Phenoxybenzamine (Dibenzyline), an Antihypertensive agent
  2. Medications to reduce anxiety (low efficacy)
    1. Serzone
    2. Imipramine
    3. Propranolol
    4. Benzodiazepines
      1. Not recommended due to dependency risk

XVII. Management: Methods - Procedural and Surgical Interventions (Refractory, severe cases)

  1. Botulinum Toxin Type A (Botox) local intradermal injection
    1. Safe and effective
    2. Binds synaptic Proteins and blocks Acetylcholine release
    3. Expensive ($1500 for both hands repeated q6-9 months)
    4. Regional Anesthesia (Median and Ulnar Nerve Block)
    5. Preferred option for axillary Hyperhidrosis
    6. Minor Starch-Iodine Test identifies area of injection
    7. Serial intradermal injections (0.1 ml aliquot/cm)
      1. Each injection spaced 0.5 to 2 cm apart
      2. Anhidrosis at each site persists 4-13 months
    8. Adverse Effects
      1. Injection site pain and Ecchymosis
      2. Decreased grip strength (palmar injection)
      3. Frontalis Muscle Weakness (forehead injection)
  2. Tap water Iontophoresis
    1. Direct current used to pass water (or other ionized substance) through the skin
      1. Safe, effective and well tolerated since the 1950s
      2. May be performed at home
    2. Galvanic current 15-20 mA applied to intact skin
      1. Hands and feet submerged in a device tray containing tap water
      2. Current applied to each distal extremity
      3. Apply current for 30 minutes on 3 days per week until improvement, and then weekly
    3. Adjuncts (increase efficacy)
      1. Aluminum Chloride hexahydrate (Drysol)
      2. Baking Soda (1 tbs)
      3. Glycopyrrolate (Robinul) 1-2 tabs crushed
      4. Atropine (limit to 1 mg per 30 cc tap water)
    4. Adverse Effects (mild)
      1. Skin erythema
      2. Skin vesiculation
      3. Paresthesias
  3. Microwave therapy (axillary Hyperhidrosis)
    1. Microwave technology destroys Eccrine Glands via heat induced cellular thermolysis
    2. Handheld transducer applied in the area identified with the Minor Starch-Iodine Test
    3. Used in the axilla and performed under Local Anesthesia
    4. Hong (2012) Dermatol Surg 38(5): 728-35 [PubMed]
    5. Jacob (2013) Semin Cutan Med Surg 32(1): 2-8 [PubMed]
  4. Fractionated microneedle radiofrequency (axillary Hyperhidrosis)
    1. Radiofrequency applied via microneedles inserted 2-3 mm under the skin
    2. Fatemi (2015) Australas J Dermatol 56(4): 279-84 [PubMed]
    3. Abtahi-Naeini (2016) Indian J Dermatol 61(2): 234 [PubMed]
  5. Endoscopic sympathectomy
    1. Surgical destruction of sympathetic ganglia
      1. Palmar: third thoracic ganglia (T3)
      2. Plantar: Not done due to Sexual Dysfunction
        1. Improves with 50% of T4 sympathectomy
        2. Consider iotophoresis as alternative
    2. Indications
      1. Method of last resort for severe Hyperhidrosis
      2. Case refractory to other measures
      3. Highly effective for palmar Hyperhidrosis
    3. Relative contraindications
      1. Axillary Hyperhidrosis (T4) due to poor efficacy
      2. Face, scalp Hyperhidrosis (T2)
        1. Due to very high risk of compensatory sweating
    4. Adverse effects and complications
      1. Compensatory sweating
        1. Trunk, groin, thighs and popliteal fossa
        2. Severe in 50% if T2 sympathectomy
        3. Severe in 19% if only T3 sympathectomy
        4. Clip removal may alleviate symptoms
      2. Gustatory sweating
        1. Sweating at back of neck when eating spicy food
        2. May follow T2 sympathectomy
        3. Also seen with Diabetic Autonomic Neuropathy
      3. Injury to adjacent structures during surgery
        1. Pneumothorax, Pneumonia, Pneumothorax
        2. Horner's Syndrome

XVIII. Resources

  1. International Hyperhidrosis Society
    1. http://www.sweathelp.org

XIX. References

  1. Rakel (2002) Family Practice, Saunders, p. 1003-4
  2. Ferri (2004) Clinical Advisor, p. 1069
  3. Hornberger (2004) J Am Acad Dermatol 51(2): 274-86 [PubMed]
  4. Linn (1998) Eur J Surg, Suppl 580:13 [PubMed]
  5. McConaghy (2018) Am Fam Physician 97(11): 729-34 [PubMed]
  6. Stolman (1998) Dermatol Clin 16:863-9 [PubMed]
  7. Thomas (2004) Am Fam Physician 69(5):1117-21 [PubMed]
  8. Wailing (2011) J Am Acad Dermatol 64(4): 690-5 [PubMed]

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