Palmar plantar erythrodysesthesia

Palmar plantar erythrodysesthesia (PPE) is a swelling and numbness of the hands and feet that occurs with chemotherapy, usually with fluorouracil, capecitabine, cytarabine, and doxorubicin.

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Synonyms

Other names for PPE include acral erythema (AE), palmoplantar erythema, hand-foot syndrome, peculiar AE, and Burgdorf reaction.

History

First reported in association with chemotherapy by Zuehlke in 1974 (Zuehlke, 1974).

Epidemiology

PPE occurs in 6-42% of patients receiving chemotherapy.

Pathogenesis

The cause of PPE is unknown. Existing theories are based on the fact that only the hands and feet are involved and posit the role of temperature differences, vascular anatomy, differences in the types of cells (rapidly dividing epidermal cells and eccrine glands).

Clinical symptoms

The symptoms can occur anywhere between days to months after administration of the offending medication, depending on the dose and speed of administration (Baack and Burgdorf, 1991; Demirçay, 1997;). The patient first experiences tingling and/or numbness of the palms and soles that evolves into painful, symmetric, and well-demarcated swelling and red plaques. This is followed by peeling of the skin and resolution of the symptoms (Apisarnthanarax and Duvic 2003).

Diagnosis

Painful red swelling of the hands and feet in a patient receiving chemotherapy is usually enough to make the diagnosis. The problem arises in patients after bone marrow transplants, as the clinical and histologic features of PPE can be similar to cutaneous manifestations of acute (first 3 weeks) graft-versus-host disease. It is important to differentiate PPE, which is benign, from the more dangerous graft-versus-host disease. As time progresses, patients with graft-versus-host disease progress to have other body parts affected, while PPE is limited to hands and feet. Serial biopsies every 3 to 5 days can also be helpful in differentiating the two disorders (Crider et al, 1986).

Prevention

The cooling of hands and feet may help prevent PPE (Baack and Burgdorf, 1991; Zimmerman et al, 1995).

Treatment

The goal is to continue chemotherapy while reducing symptoms of PPE. Symptomatic treatment includes pyridoxine, wound care, elevation, and pain medication (Vukelja et al 1993). Corticosteroids have also shown some efficacy in relieving symptoms.

Prognosis

PPE variably recurs with resumption of chemotherapy. Long-term chemotherapy may also result in reversible palmoplantar keratoderma. Symptoms resolve 1-2 weeks after cessation of chemotherapy (Apisarnthanarax and Duvic 2003).

References

• Apisarnthanarax, N and Duvic MM. Dermatologic Complications of Cancer Chemotherapy in Holland-Frei Cancer Medicine - 6th Ed., Ch. 147, Kufe, DW et al editors, BC Decker Inc, Hamilton, Ontario. 2003.
• Baack B, Burgdorf W (1991). "Chemotherapy-induced acral erythema". J Am Acad Dermatol 24 (3): 457-61. PMID 2061446.
• Crider M, Jansen J, Norins A, McHale M (1986). "Chemotherapy-induced acral erythema in patients receiving bone marrow transplantation". Arch Dermatol 122 (9): 1023-7. PMID 3527075.
• Demirçay Z, Gürbüz O, Alpdoğan T, Yücelten D, Alpdoğan O, Kurtkaya O, Bayik M (1997). "Chemotherapy-induced acral erythema in leukemic patients: a report of 15 cases". Int J Dermatol 36 (8): 593-8. PMID 9329890.
• Vukelja S, Baker W, Burris H, Keeling J, Von Hoff D (1993). "Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with taxotere". J Natl Cancer Inst 85 (17): 1432-3. PMID 8102408.
• Zimmerman G, Keeling J, Burris H, Cook G, Irvin R, Kuhn J, McCollough M, Von Hoff D (1995). "Acute cutaneous reactions to docetaxel, a new chemotherapeutic agent". Arch Dermatol 131 (2): 202-6. PMID 7857119.
• Zuehlke R (1974). "Erythematous eruption of the palms and soles associated with mitotane therapy". Dermatologica 148 (2): 90-2. PMID 4276191.