Palmar-plantar erythrodysesthesia

Causes and manifestations of palmar-plantar erythrodysesthesia

The development of palmar-plantar erythrodysesthesia is most characteristic of prolonged administration of fluorouracil (5-fluorouracil). This is a specific dermatological complication where the toxic effect of the drug manifests in the capillaries of the distal extremities.

Key clinical manifestations of the syndrome include:

• Purplish discoloration of the skin on the hands and feet;
• Marked local edema;
• Tenderness of the palms and soles.

In addition to skin reactions, fluorouracil has high toxicity to the gastrointestinal tract, often manifesting as ulcerative mucosal lesions with the development of severe stomatitis and enteritis.

General side effects of antineoplastic agents

Although palmar-plantar erythrodysesthesia is specific to a limited pool of drugs, most cytotoxics (including topoisomerase I and II inhibitors) share a similar toxicity profile due to their impact on rapidly dividing cells.

Typical systemic reactions:

1. Myelosuppression (bone marrow depression). Manifests as leukopenia (decreased leukocyte count leading to a high risk of infections), thrombocytopenia (triggers hemorrhagic syndrome), and anemia (drop in red blood cells and hemoglobin causing weakness and dyspnea).
2. Dyspeptic disorders. Include nausea and vomiting (both central and peripheral origin), diarrhea, and anorexia.
3. Dermatological reactions. In addition to specific syndromes, general dermatitis, rash, and alopecia (hair loss due to damage to hair follicles, which is reversible) are frequently observed.
4. Immunosuppression and allergies. Decreased immunity leads to the reactivation of latent viruses, while allergic responses range from skin rashes to anaphylaxis.

Specific organ toxicity of individual drugs

For the differential diagnosis of complications, it is important to remember the specific organ toxicity of other antineoplastic agents:

• Methotrexate: causes renal impairment (prophylaxis involves urine alkalinization), risk of liver cirrhosis with prolonged use, pulmonary toxicity (especially in children), and neurotoxicity (with intrathecal administration). To reduce overall toxicity, a specific antidote is used — leucovorin (folinic acid).
• Trastuzumab: extremely hazardous due to severe complications in the form of heart failure. Requires maximum caution in patients with baseline cardiac pathology. Additionally causes fever and dizziness.
• Cyclophosphamide: causes hemorrhagic cystitis (mesna is used for prevention), is teratogenic, and can lead to infertility with a prolonged course.

Mechanisms of tumor resistance

The efficacy of chemotherapy, including drugs that cause palmar-plantar erythrodysesthesia, is often reduced due to the development of resistance.

Specific resistance to fluorouracil develops via two pathways:

• The tumor cell's own ability to transform the administered drug into active metabolites decreases;
• A compensatory increase in the activity of the target enzyme (thymidylate synthase) occurs, which neutralizes the drug's effect.

Multiple drug resistance (general mechanism) is caused by tumor cells beginning to overexpress P-glycoprotein. This protein acts as a pump, actively pumping various antineoplastic drugs out of the cytoplasm, which drastically reduces the overall treatment efficacy.

Class and exam questions

What else to study on this topic

• Clinical manifestations and pathogenesis of myelosuppression (leukopenia, thrombocytopenia, anemia).
• Specific organ toxicity of methotrexate and the principles of leucovorin use.
• Features of cardiotoxicity during trastuzumab therapy.
• The role of P-glycoprotein in cellular resistance mechanisms.

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.