What is the etiology of hyperhidrosis?

Etiology of Hyperhidrosis

Primary hyperhidrosis is believed to result from sympathetic overactivity without an underlying medical cause, while secondary hyperhidrosis is associated with specific endocrine, neurological, infectious, malignant, or medication-induced causes. 1

Primary Hyperhidrosis

Primary hyperhidrosis (PHH) accounts for approximately 93% of all hyperhidrosis cases 1 and has the following characteristics:

• Pathophysiology: Results from overactivity of the sympathetic nervous system controlling eccrine sweat glands, though the exact mechanism remains unclear 1

• Key clinical features:

  • Bilateral and symmetric sweating 2
  • Focal excessive sweating affecting specific areas (axillae, palms, soles, craniofacial region) 2
  • Absence of sweating during sleep 3
  • Onset typically in childhood or adolescence (≤25 years of age) 3
  • Episodes occurring at least weekly 3
  • Often has positive family history 3
  • Significantly impairs daily activities 3

• Hypohidrosis connection: In some cases, hypohidrosis (decreased sweating) may result from plugging of sweat ducts by hyperkeratosis, though it can also occur in mild forms of ichthyosis, suggesting additional functional defects 4

Secondary Hyperhidrosis

Secondary hyperhidrosis (SHH) has distinct clinical features that help differentiate it from primary hyperhidrosis:

• Clinical presentation:

  • Often unilateral or asymmetric (OR: 51; 95% CI: 12.6-208) 3
  • More likely to be generalized rather than focal (OR: 18; 95% CI: 7.3-47.6) 3
  • Frequently present during sleep (OR: 23.2; 95% CI: 4.3-126) 3
  • Later onset (>25 years of age) is common (OR: 8.7; 95% CI: 3.5-21.4) 3

• Common underlying causes:

  1. Endocrine disorders (57% of SHH cases) 3:

     • Diabetes mellitus
     • Hyperthyroidism
     • Hyperpituitarism
     • Pheochromocytoma

  2. Neurological conditions (32% of SHH cases) 3:

     • Peripheral nerve injury
     • Parkinson's disease
     • Reflex sympathetic dystrophy
     • Spinal injury
     • Arnold-Chiari malformation
     • Asymmetric presentation strongly favors neurologic etiology (OR: 63; 95% CI: 4.9-810) 3

  3. Other causes:

     • Malignancies
     • Respiratory diseases
     • Psychiatric disorders
     • Medications
     • Infections (particularly tuberculosis) 5

Diagnostic Approach

When evaluating a patient with hyperhidrosis, the following diagnostic criteria help distinguish primary from secondary forms:

1. For primary hyperhidrosis: Excessive sweating for ≥6 months with at least 4 of these features 3:

   • Primarily involving eccrine-dense sites (axillae/palms/soles/craniofacial)
   • Bilateral and symmetric distribution
   • Absent during sleep
   • Episodes occurring at least weekly
   • Onset at ≤25 years of age
   • Positive family history
   • Impairment of daily activities

   These criteria have excellent diagnostic performance (sensitivity: 0.99; specificity: 0.82; PPV: 0.99; NPV: 0.852) 3

2. For secondary hyperhidrosis, look for:

   • Asymmetric or unilateral sweating
   • Generalized distribution
   • Nocturnal sweating
   • Onset after age 25
   • Associated symptoms of underlying conditions

Clinical Implications

Understanding the etiology of hyperhidrosis is crucial for appropriate management:

• Primary hyperhidrosis treatment focuses on symptom control through:

  • Topical treatments (aluminum chloride, glycopyrrolate)
  • Iontophoresis for palmar/plantar hyperhidrosis
  • Botulinum toxin injections
  • Oral anticholinergics in severe cases
  • Surgical interventions for refractory cases 6

• Secondary hyperhidrosis management requires:

  • Identification and treatment of the underlying cause
  • Symptomatic treatment as needed

Common Pitfalls to Avoid

1. Misdiagnosis: Failing to distinguish between primary and secondary hyperhidrosis can lead to inappropriate treatment and missed underlying conditions

2. Overlooking asymmetric presentation: Unilateral or asymmetric sweating strongly suggests secondary hyperhidrosis, particularly neurologic causes 3

3. Ignoring nocturnal symptoms: Sweating during sleep is highly indicative of secondary hyperhidrosis 3

4. Age of onset: Late-onset hyperhidrosis (>25 years) should raise suspicion for secondary causes 3

5. Inadequate evaluation: Not performing a thorough assessment for potential underlying medical conditions in patients with clinical features suggestive of secondary hyperhidrosis

By understanding the distinct etiologies and clinical presentations of primary versus secondary hyperhidrosis, clinicians can provide appropriate diagnostic evaluation and targeted treatment approaches that address the underlying cause when present.