- Chemotherapy-induced acral erythema
Chemotherapy-induced acral erythema Classification and external resources
Pictures of hands on capecitabine
ICD-10 Y43.1-Y43.3 ICD-9 693.0, E933.1 DiseasesDB 34044
Chemotherapy-induced acral erythema (also known as "palmar-plantar erythrodysesthesia" or "hand-foot syndrome") is reddening, swelling, numbness and desquamation on palms and soles that can occur after chemotherapy in patients with cancer. These skin changes usually are well demarcated. Acral erythema typically disappears within a few weeks after discontinuation of the offending drug. 
Synonyms for acral erythema (AE) include: hand-foot syndrome, palmar-plantar erythrodysesthesia, peculiar AE, chemotherapy-induced AE, toxic erythema of the palms and soles, palmar-plantar erythema, and Burgdorf’s reaction.
Hand-foot syndrome was first reported in association with chemotherapy by Zuehlke in 1974.
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).
The offending drug leading to acral erythema as an adverse drug reaction usually is a cytotoxic drug, very commonly fluorouracil, capecitabine, cytarabine, sorafenib, or pegylated liposomal doxorubicin.
New drugs: Targeted agents against cancer, especially two tyrosine kinase inhibitors, sorafenib and sunitinib, have also been associated with a high incidence of acral erythema. However, acral erythema due to tyrosine kinase inhibitors seems to differ somewhat from acral erythema due to classic chemotherapy drugs.
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).
Painful red swelling of the hands and feet in a patient receiving chemotherapy is usually enough to make the diagnosis. The problem can also arise 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).
The cooling of hands and feet during chemotherapy may help prevent PPE (Baack and Burgdorf, 1991; Zimmerman et al., 1995). Support for this and a variety of other approaches to treat or prevent acral erythema comes from small clinical studies, although none has been proven in a randomised controlled clinical trial of sufficient size.
The main treatment for acral erythema is discontinuation of the offending drug, and symptomatic treatment to provide analgesia, lessen edema, and prevent superinfection. However, the treatment for the underlying cancer of the patient must not be neglected. Often, the discontinued drug can be substituted with another cancer drug or cancer treatment. 
PPE invariably 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).
- ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.:132
- ^ Palmar-plantar rash with cytarabine therapy. Rosenbeck L, Kiel PJ. N Engl J Med. 2011 Jan 20;364(3):e5.
- ^ Erythematous eruption of the palms and soles associated with mitotane therapy. Zuehlke RL. Dermatologica. 1974;148(2):90-2.
- ^ Chemotherapy-induced acral erythema. Baack BR, Burgdorf WH. J Am Acad Dermatol. 1991 Mar;24(3):457-61.
- ^ Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib. Lacouture ME, Reilly LM, Gerami P, Guitart J. Ann Oncol. 2008;19(11):1955-61.
- ^ Cutaneous complications of conventional chemotherapy agents. Payne AS, Savarese DMF. In: UpToDate [Textbook of Medicine]. Massachusetts Medical Society, and Wolters Kluwer publishers. 2010.
- ^ Management of hand-foot syndrome induced by capecitabine. Gressett SM, Stanford BL, Hardwicke F. J Oncol Pharm Pract. 2006 Sep;12(3):131-41.
- ^ Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with taxotere. Vukelja SJ, Baker WJ, Burris HA 3rd, Keeling JH, Von Hoff D. J Natl Cancer Inst. 1993 Sep 1;85(17):1432-3.
- 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. doi:10.1001/archderm.122.9.1023. 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. doi:10.1046/j.1365-4362.1997.00040.x. 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. doi:10.1093/jnci/85.17.1432. 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. doi:10.1001/archderm.131.2.202. PMID 7857119.
- Zuehlke R (1974). "Erythematous eruption of the palms and soles associated with mitotane therapy". Dermatologica 148 (2): 90–2. PMID 4276191.
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