What is the etiology of intense diaphoresis (excessive sweating) without chest pain in a patient with Parkinson's disease (PD)?

From the Guidelines

Intense diaphoresis without chest pain in a patient with Parkinson's disease is most likely due to autonomic dysfunction, which is a common feature in approximately 70-80% of Parkinson's patients, as supported by the ESPEN guideline on clinical nutrition in neurology 1. This autonomic dysregulation occurs because alpha-synuclein deposits affect not only dopaminergic neurons but also the autonomic nervous system, disrupting normal thermoregulation and sweat gland function.

Potential Causes

• Autonomic dysfunction: The most common cause, affecting approximately 70-80% of Parkinson's patients, as mentioned in the ESPEN guideline 1.
• Medication side effects: Particular from levodopa therapy, dopamine agonists, and anticholinergics, which can disrupt the balance of neurotransmitters involved in sweat regulation.
• Hyperhidrosis: May represent "off" periods in Parkinson's when medication levels are suboptimal.

Management

• Optimizing Parkinson's medications to reduce motor fluctuations.
• Considering medication adjustments if the diaphoresis appears to be drug-induced.
• Implementing symptomatic treatments such as:
  • Antiperspirants containing aluminum chloride.
  • Anticholinergic medications like glycopyrrolate (1-2mg twice daily).
  • Botulinum toxin injections for localized sweating.
• Patients should also be advised to:
  • Wear light, breathable clothing.
  • Maintain hydration.
  • Avoid triggers like spicy foods and hot environments. It is essential to rule out other causes, including thyroid disorders, infections, malignancies, or cardiac conditions, particularly if the symptom is new or severe, as the ESPEN guideline highlights the importance of monitoring and managing nutritional and metabolic aspects in Parkinson's patients 1.

From the FDA Drug Label

Patients may develop postural (orthostatic) hypotension, with or without symptoms such as dizziness, nausea, fainting or blackouts, and sometimes, sweating.

The etiology of intense diaphoresis without chest pain in a patient with Parkinson's disease may be related to postural (orthostatic) hypotension, a known side effect of pramipexole. This condition can cause symptoms such as dizziness, nausea, fainting, and sweating. However, it is essential to note that the FDA drug label does not directly link pramipexole to intense diaphoresis without chest pain. Therefore, a conservative clinical decision would be to consider other potential causes of diaphoresis and monitor the patient closely. 2

From the Research

Etiology of Intense Diaphoresis without Chest Pain in a Patient with Parkinson's Disease

• Intense diaphoresis without chest pain in a patient with Parkinson's disease can be related to various factors, including autonomic dysfunction and medication side effects 3.
• Autonomic dysfunction in Parkinson's disease can lead to thermoregulatory symptoms, such as abnormal temperature sensation and sweating, which were first noted by Gowers in the late 19th century 3.
• Dopamine agonists, which are commonly used to treat Parkinson's disease, can also affect thermoregulatory symptoms and cause side effects such as orthostatic hypotension and excessive daytime somnolence 4, 5.
• The use of dopamine agonists can lead to excessive dopaminergic stimulation, which can cause dyskinesia-hyperpyrexia syndrome (DHS), a condition characterized by severe generalized athetotic dyskinesia, visual hallucinations, and hyperpyrexia 6.
• The pathophysiology of thermoregulatory dysfunction in Parkinson's disease encompasses both central and peripheral mechanisms, including the involvement of the brainstem and hypothalamus with alpha-synuclein pathology and peripheral neuropathy 3.

Medication-Related Factors

• Dopamine agonists, such as pramipexole, can cause neuropsychiatric events, including excessive daytime somnolence, impulse-control disorders, hallucinations, and delusions, which can severely affect patients 4.
• The risk of such neuropsychiatric complications should be considered when using dopamine agonists, and patients should be informed about the risk and actively detected at each consultation 4.
• The dosage of dopamine agonists should be increased gradually to minimize the risk of side effects, and the use of long-acting dopaminergic drugs should be done with caution to avoid excessive dopaminergic stimulation 4, 6.

Clinical Implications

• The diagnosis of dyskinesia-hyperpyrexia syndrome (DHS) should be considered in patients with Parkinson's disease who develop severe generalized athetotic dyskinesia, visual hallucinations, and hyperpyrexia, especially after switching to long-acting dopaminergic drugs 6.
• The treatment of DHS involves tapering the oral administration of dopaminergic drugs, including extended-release pramipexole, to avoid excessive dopaminergic stimulation 6.
• The management of thermoregulatory symptoms in Parkinson's disease requires a comprehensive approach, including the use of medications, lifestyle modifications, and close monitoring of autonomic function 3.