What is the cause of excessive sweating (hyperhidrosis) associated with a unilateral droopy eye (ptosis)?

Horner Syndrome: The Most Likely Diagnosis

The combination of excessive sweating (hyperhidrosis) with unilateral ptosis (droopy eye) is pathognomonic for Horner syndrome, a disorder of the sympathetic nervous system that requires urgent evaluation to identify potentially life-threatening underlying causes.

Clinical Presentation and Pathophysiology

Horner syndrome results from disruption of the oculosympathetic pathway at any point from the hypothalamus to the eye. The classic triad includes:

• Unilateral ptosis (drooping of the upper eyelid due to paralysis of Müller's muscle)
• Miosis (constricted pupil on the affected side)
• Anhidrosis (absence of sweating) OR hyperhidrosis (excessive sweating) depending on the lesion location

The sweating pattern is critical for localization. Lesions proximal to the superior cervical ganglion (first-order or second-order neurons) cause ipsilateral facial anhidrosis, while lesions distal to the ganglion (third-order neurons) spare facial sweating. However, compensatory hyperhidrosis can occur on the contralateral side or in other body regions as the body attempts to maintain thermoregulation.

Critical Differential Consideration: Myasthenia Gravis

While Horner syndrome is the primary diagnosis to consider, myasthenia gravis can present with unilateral ptosis and, importantly, excessive sweating during Tensilon (edrophonium) testing 1. The American Academy of Ophthalmology notes that Tensilon testing can cause "excess tearing, salivation, sweating, abdominal cramping, bradycardia, bronchospasm, hypotension, and syncope" due to muscarinic activity 1.

However, myasthenia gravis typically presents with:

• Variable ptosis that worsens with fatigue 1
• Bilateral involvement in many cases (though can be asymmetric) 1
• Normal pupillary responses 1
• Variable strabismus and diplopia 1

Urgent Evaluation Required

The presence of acute-onset Horner syndrome demands immediate neuroimaging to exclude life-threatening causes:

First-Order Neuron Lesions (Central)

• Brainstem stroke or hemorrhage
• Multiple sclerosis
• Brainstem tumors
• Syringomyelia

Second-Order Neuron Lesions (Preganglionic)

• Pancoast tumor (apical lung cancer) - most critical to exclude
• Thyroid carcinoma
• Mediastinal masses
• Cervical rib
• Trauma to neck or chest

Third-Order Neuron Lesions (Postganglionic)

• Carotid artery dissection (medical emergency)
• Cavernous sinus pathology
• Orbital apex lesions
• Cluster headaches

Diagnostic Approach

Immediate steps:

1. Confirm Horner syndrome clinically:

   • Document unilateral ptosis (typically 1-2 mm)
   • Assess for anisocoria (pupil asymmetry) that is more pronounced in dim lighting
   • Evaluate facial sweating pattern bilaterally
   • Check for iris heterochromia (if congenital)

2. Pharmacologic testing (if available):

   • Apraclonidine or cocaine eye drops can confirm the diagnosis
   • Hydroxyamphetamine testing can help localize the lesion

3. Urgent imaging:

   • MRI of brain, neck, and chest with contrast
   • CT angiography if carotid dissection suspected
   • Chest imaging to exclude Pancoast tumor

Common Pitfalls to Avoid

• Do not dismiss unilateral presentations as benign - asymmetric or unilateral disease always warrants thorough investigation 2
• Do not confuse with primary hyperhidrosis - primary hyperhidrosis is bilateral, symmetric, and not associated with ptosis 3, 4, 5
• Do not delay imaging - carotid dissection and Pancoast tumors require immediate intervention
• Do not overlook the sweating pattern - it provides crucial localization information

Secondary Hyperhidrosis Context

The research evidence confirms that secondary hyperhidrosis (as opposed to primary) is characterized by unilateral/asymmetric presentation, onset after age 25, and association with neurologic disease 3. This patient's presentation fits secondary hyperhidrosis criteria, with neurologic disease (Horner syndrome) being 63 times more likely when hyperhidrosis is asymmetric 3.

Bottom line: This clinical presentation demands immediate neurologic and oncologic evaluation to identify the underlying cause of sympathetic pathway disruption, as delay in diagnosis can result in significant morbidity or mortality.