What is the cause of plantar palmar erythema (PPE), also known as palmoplantar erythema?

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From the Guidelines

Plantar palmar erythema, also known as palmar-plantar erythrodysaesthesia syndrome (PPES), is a disorder characterized by redness, discomfort, swelling, and tingling in the palms and soles, often associated with cytotoxic chemotherapy agents and targeted therapies, and its management should focus on addressing the underlying cause, such as adjusting chemotherapy agents or doses, as evidenced by the 2021 ESMO clinical practice guidelines 1.

Causes and Associations

The condition is linked to various chemotherapy agents, including 5-fluorouracil (5-FU), capecitabine, doxorubicin, and others, with the highest incidences reported for combinations of these agents 1. Additionally, BRAF inhibitors and multikinase vascular endothelial growth factor receptor (VEGFR) inhibitors can cause a similar condition known as hand-foot skin reaction (HFSR), characterized by painful hyperkeratosis 1.

Clinical Considerations

The occurrence and severity of PPES and HFSR have been correlated with therapy response, suggesting that managing these conditions is crucial for maintaining effective treatment regimens 1. Given the association with various medications and therapies, adjusting or switching these treatments under medical supervision is often necessary to alleviate symptoms.

Management Approach

Since plantar palmar erythema is typically a symptom of an underlying issue rather than a primary condition, treatment should prioritize addressing the root cause, whether it be chemotherapy-induced, related to targeted therapies, or due to other medical conditions 1. This approach ensures that the management strategy is tailored to the individual's specific needs, minimizing unnecessary interventions and maximizing the quality of life.

From the Research

Definition and Classification

  • Plantar palmar erythema, also known as palmar-plantar erythrodysesthesia (PPE), is a relatively common side effect of cytotoxic chemotherapy 2.
  • It is characterized by dysesthesia, tingling, and erythema in the palms and soles, which may progress to burning pain, dryness, cracking, desquamation, ulceration, and edema 2.
  • Palmar erythema (PE) can exist as a primary physiologic finding or as a secondary marker of systemic pathology, including liver cirrhosis, rheumatoid arthritis, thyrotoxicosis, and diabetes mellitus 3.

Causes and Triggers

  • Cytotoxic drugs, such as 5-fluorouracil (5FU), liposomal doxorubicin, and cytarabine, are commonly associated with PPE 2.
  • Smoking and upper respiratory infections have been suggested as main triggers of palmoplantar pustulosis (PPP), a rare and chronic inflammatory disease that affects the palms and soles 4.
  • Drug-induced PE has been documented with the use of amiodarone, gemfibrozil, and cholestyramine, while topiramate and albuterol have been reported to cause PE in the setting of normal liver function 3.

Diagnosis and Management

  • Effective and appropriate patient education from a specialist nurse prior to treatment is essential for early identification of PPE symptoms and prevention of treatment delays 2.
  • The treatment approach for PPP involves both topical and systemic therapies, as well as phototherapy and targeted molecules, with no gold standard therapy yet identified 4.
  • Identification of PE related to underlying disorders should be followed by treatment of the underlying condition, and discontinuation of the responsible medication if possible 3.
  • Erythema multiforme, an immune-mediated reaction that involves the skin and sometimes the mucosa, can be differentiated from urticaria by the duration of individual lesions, and managed with symptomatic treatment and treatment of the underlying etiology 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Palmar-plantar erythrodysesthesia (PPE): a literature review with commentary on experience in a cancer centre.

European journal of oncology nursing : the official journal of European Oncology Nursing Society, 2007

Research

Palmar erythema.

American journal of clinical dermatology, 2007

Research

Erythema Multiforme: Recognition and Management.

American family physician, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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