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Vol. 99. Núm. 4.
Páginas 281-290 (mayo 2008)
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Vol. 99. Núm. 4.
Páginas 281-290 (mayo 2008)
Original articles
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Chemotherapy-Induced Acral Erythema: A Clinical and Histopathologic Study of 44 Cases
Eritema Acral Inducido Por Quimioterapia: Estudio Clínico e Histopatoló-Gico de 44 Casos
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L. Hueso, O. Sanmartín
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osanmartinj@gmail.com

Correspondence: Servicio de Dermatología, Instituto Valenciano de Oncología, C/ Profesor Beltrán Báguena, 8, 46009 Valencia, Spain.
, E. Nagore, R. Botella-Estrada, C. Requena, B. Llombart, C. Serra-Guillén, A. Alfaro-Rubio, C. Guillén
Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, Spain
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Abstract
Introduction

Acral erythema, also known as palmoplantar erythrodysesthesia or hand-foot syndrome, is a relatively common cutaneous reaction caused by a variety of chemotherapeutic agents. It presents during cancer treatment as painful erythema and paresthesia affecting the palms and soles. It seems to be dose dependent and its appearance is determined by both the peak plasma concentration and the cumulative dose of the chemotherapeutic agent. The symptoms and histopathology findings are suggestive of direct cytotoxicity affecting the epidermis of the extremities caused by high concentrations of chemotherapeutic agents. The most commonly implicated agents are doxorubicin, 5-fluoracil and its derivatives, cytarabine, and docetaxel.

Material and methods

We present the clinical and histologic characteristics of a series of patients diagnosed with chemotherapy-induced acral erythema. The study included all patients who developed acral erythema lesions following chemotherapy between January 2000 and December 2003.

Results and conclusions

Out of 2186 patients who underwent chemotherapy, 44 cases of acral erythema were identified, representing an incidence of 2.01% during the study period and 16.75% of all cutaneous lesions attributed to chemotherapy. The most commonly implicated drug was 5-fluoracil administered by continuous infusion and the highest incidence was observed in patients treated with liposomal doxorubicin. Acral erythema was a dose-limiting toxic effect in 29.5% of cases. The histologic findings varied according to the clinical severity of the lesions and included interface dermatitis with variable keratinocyte necrosis, dilation of the superficial vascular plexus, and limited inflammatory infiltrate. The most commonly used treatment was pyridoxine, along with topical treatments such as cold compresses, emollients, and topical corticosteroids.

Key words:
acral erythema
palmoplantar erythrodysesthesia
hand-foot syndrome
chemotherapy
adverse effects
Resumen
Introducción

El eritema acral (EA) es una reacción cutánea relativamente frecuente producida por diferentes agentes quimioterápicos. Otros términos con los que se le conoce son eritrodisestesia palmoplantar o síndrome pie-mano. Se presenta como un eritema doloroso en palmas y plantas asociado a parestesias en el contexto de un tratamiento oncológico. El EA parece ser dosis-dependiente, y tanto el pico plasmático como la dosis acumulada del quimioterápico determinan su aparición. La clínica y los hallazgos histopatológicos sugieren una citotoxicidad directa de la epidermis acral por las altas concentraciones de los quimioterápicos. Los agentes más frecuentemente implicados son doxorrubicina, 5-fluorouracilo y derivados, citarabina y docetaxel.

Material y métodos

Se presentan las características clínicas e histológicas de una serie de pacientes diagnosticados de eritema acral por quimioterápicos. Se incluyeron en el trabajo todos los pacientes sometidos a quimioterapia que desarrollaron lesiones de eritema acral durante un período de tiempo comprendido entre enero de 2000 y diciembre de 2003.

Resultados y conclusión

Se encontraron 44 casos entre los 2.186 pacientes sometidos a quimioterapia, lo que supuso una incidencia del 2,01% durante el período de estudio, y el 16,75% de todas las lesiones cutáneas atribuidas a la quimioterapia. El fármaco más frecuentemente relacionado fue el 5-fluorouracilo en infusión continua, y la mayor incidencia se dio en pacientes tratados con doxorrubicina liposomial. El EA fue toxicidad limitante de dosis en el 29,5% de los casos. Los hallazgos histológicos variaron según la intensidad clínica de las lesiones, encontrando una dermatitis de interfase con necrosis de queratinocitos variable, dilatación del plexo vascular superficial y un escaso infiltrado inflamatorio. El tratamiento más utilizado fue la piridoxina y las medidas locales como fomentos fríos, emolientes y corticoides tópicos.

Palabras clave:
eritema acral
eritrodisestesia palmoplantar
síndrome pie-mano
quimioterapia
efectos adversos
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References
[1.]
R.K. Zuehlke.
Erythematous eruption of the palms and soles associated with mitotane therapy.
Dermatologica, 148 (1974), pp. 90-92
[2.]
E. Nagore, A. Insa, O. Sanmartin.
Antineoplastic therapy-induced palmar plantar erythrodysesthesia (’hand-foot’) syndrome. Incidence, recognition and management.
Am J Clin Dermatol, 1 (2000), pp. 225-234
[3.]
S. Chiara, M.T. Nobile, C. Barzacchi, O. Sanguineti, M. Vincenti, C. Di Somma, et al.
Hand-foot syndrome induced by high-dose, short-term, continuous 5-fluorouracil infusion.
Eur J Cancer, 33 (1997), pp. 967-969
[4.]
R.A. Popescu, A. Norman, P.J. Ross, B. Parikh, D. Cunningham.
Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older.
J Clin Oncol, 17 (1999), pp. 2412-2418
[5.]
M.C. Fariña, J. Andrade, M.L. Soriano, R. Grillo, M. Domine, L. Martin, et al.
Eritema acral inducido por quimioterapia. Descripción de cuatro casos y revisión de la literatura.
Actas Dermosifiliogr, 89 (1998), pp. 385-391
[6.]
Z. Demircay, O. Gurbuz, T.B. Alpdogan, D. Yucelten, O. Alpdogan, O. Kurtkaya, et al.
Chemotherapy-induced acral erythema in leukemic patients: a report of 15 cases.
Int J Dermatol, 36 (1997), pp. 593-598
[7.]
A. Comandone, S. Bretti, G. LaGrotta, S. Manzoni, G. Bonardi, R. Berardo, et al.
Palmar-plantar erythrodysesthesia syndrome associated with 5-fluorouracil treatment.
Anticancer Res, 13 (1993), pp. 1781-1783
[8.]
C.J. Fabian, R. Molina, M. Slavik, S. Dahlberg, S. Giri, R. Stephens.
Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion.
Invest New Drugs, 8 (1990), pp. 57-63
[9.]
Meta-Analysis Group in Cancer.
Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors.
J Clin Oncol, 16 (1998), pp. 3537-3541
[10.]
J.L. Blum, S.E. Jones, A.U. Buzdar, P.M. LoRusso, I. Kuter, C. Vogel, et al.
Multicenter phase II study of capecitabine in paclitaxel refractory metastatic breast cancer.
J Clin Oncol, 17 (1999), pp. 485-493
[11.]
S.M. Gressett, B.L. Stanford, F. Hardwicke.
Management of hand-foot syndrome induced by capecitabine.
J Oncol Pharm Pract, 12 (2006), pp. 131-141
[12.]
I.O. Kara, B. Sahin, M. Erkisi.
Palmar-plantar erythrodysesthesia due to docetaxel-capecitabine therapy is treated with vitamin E without dose reduction.
[13.]
A. Sella, R. Kilbourn, R. Amato, C. Bui, A.A. Zukiwski, J. Ellerhorst, et al.
Phase II study of ketoconazole combined with weekly doxorubicin in patients with androgen-independent prostate cancer.
J Clin Oncol, 2 (1994), pp. 683-688
[14.]
L.J. Ayash, A. Elias, J. Ibrahim, G. Schwartz, C. Wheeler, E. Reich, et al.
High-dose multimodality therapy with autologous stem-cell support for stage IIIB breast carcinoma.
J Clin Oncol, 16 (1998), pp. 1000-1007
[15.]
H. Gabra, D.A. Cameron, L.E. Lee, J. Mackay, R.C. Leonard.
Weekly doxorubicin and continuous infusional 5-fluorouracil for advanced breast cancer.
Br J Cancer, 74 (1996), pp. 2008-2012
[16.]
K.B. Gordon, A. Tajuddin, J. Guitart, T.M. Kuzel, L.R. Eramo, J. VonRoenn.
Hand-foot syndrome associated with liposome-encapsulated doxorubicin therapy.
Cancer, 75 (1995), pp. 2169-2173
[17.]
M.A. Titgan.
Prevention of palmar-plantar erythrodysesthesia associated with liposome-encapsulated doxorubicin (Doxil®) by oral dexamethasone.
Proc Am Soc Clin Oncol, 16 (1997), pp. 82a
[18.]
M. Amantea, M.S. Newman, T.M. Sullivan, A. Forrest, P.K. Working.
Relationship of dose intensity to the induction of palmar-plantar erythrodysesthesia by pegylated liposomal doxorubicin in dogs.
Hum Exp Toxicol, 18 (1999), pp. 17-26
[19.]
B. Uziely, S. Jeffers, R. Isacson, K. Kutsch, D. Wei-Tsao, Z. Yehoshua, et al.
Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies.
J Clin Oncol, 13 (1995), pp. 1777-1785
[20.]
F.M. Cady, R. Kneuper-Hall, J.S. Metcalf.
Histologic patterns of polyethylene glycol-liposomal doxorubicin-related cutaneous eruptions.
Am J Dermatopatol, 28 (2006), pp. 168-172
[21.]
K.L. Molpus, L.B. Anderson, C.L. Craig, J.G. Puleo.
The effect of regional cooling on toxicity associated with intravenous infusion of pegylated liposomal doxorubicin in recurrent ovarian carcinoma.
Gynecol Oncol, 93 (2004), pp. 513-516
[22.]
I. Palaia, R. Angioli, F. Bellati, S. Basile, C. Rabitti, P.B. Panici.
Distal phalange necrosis: a severe manifestation of palmar plantar erythrodysesthesia.
Am J Obstet Gynecol, 195 (2006), pp. e1-e2
[23.]
J.F. Waltzer, F.P. Flowers.
Bullous variant of chemotherapy-induced acral erythema.
Arch Dermatol, 129 (1993), pp. 43-45
[24.]
J.A. Whitlock, R.J. Wells, J.D. Hord, R.L. Janco, J.P. Greer, J.C. Gay, et al.
High-dose cytosine arabinoside and etoposide: an effective regimen without anthracyclines for refractory childhood acute non-lymphocytic leukemia.
Leukemia, 11 (1997), pp. 185-189
[25.]
W.G. Peters, R. Willemze.
Palmar-plantar skin changes and cytarabine.
Ann Intern Med, 103 (1985), pp. 805
[26.]
R.H. Herzig, S.N. Wolff, H.M. Lazarus, G.L. Phillips, C. Karanes, G.P. Herzig.
High-dose cytosine arabinoside therapy for refractory leukemia.
Blood, 62 (1983), pp. 361-369
[27.]
E. Vargas-Díez, P. Abajo, J. Fraga, J. Fernández-Herrera, A. García-Díez.
Chemotherapy-induced acral erythema.
Acta Derm Venereol, 79 (1999), pp. 173-175
[28.]
B.R. Baack, W.H. Burgdorf.
Chemotherapy-induced acral erythema.
J Am Acad Dermatol, 24 (1991), pp. 457-461
[29.]
M. Katoh, M. Kadota, Y. Nishimura.
A case of docetaxel-induced erythrodysesthesia.
J Dermatol, 31 (2004), pp. 403-406
[30.]
S.M. Sorscher.
Penile involvement with hand-foot syndrome.
Am J Clin Dermatol, 5 (2004), pp. 209-210
[31.]
G.C. Zimmerman, J.H. Keeling, H.A. Burris, G. Cook, R. Irvin, J. Kuhn, et al.
Acute cutaneous reactions to docetaxel, a new chemotherapeutic agent.
Arch Dermatol, 131 (1995), pp. 202-206
[32.]
A. Kreuter, T. Gambichler, R. Schlottmann, P. Altmeyer, N. Brockmeyer.
Psoriasiform pustular eruptions from pegylatedliposomal doxorubicin in AIDS-related Kaposi's sarcoma.
Acta Derm Venereol, 81 (2001), pp. 224
[33.]
M. Lotem, A. Hubert, O. Lyass, M.A. Goldenhersh, A. Ingber, T. Peretz, et al.
Skin toxic effects of polyethylene glycol-coated liposomal doxorubicin.
Arch Dermatol, 136 (2000), pp. 1475-1480
[34.]
J.S. Beard, K.J. Smith, H.G. Skelton.
Combination chemotherapy with 5-fluorouracil, folinic acid, and alpha-interferon producing histologic features of graft-versus-host disease.
J Am Acad Dermatol, 29 (1993), pp. 325-330
[35.]
J.E. Mortimer, I. Anderson.
Weekly fluorouracil and high-dose leucovorin: efficacy and treatment of cutaneous toxicity.
Cancer Chemother Pharmacol, 26 (1990), pp. 449-452
[36.]
E. Díaz-Rubio, E. Aranda, M. Martín, R. González-Mancha, J. González-Larriba, I. Barneto.
Weekly high-dose infusion of 5-fluorouracil in advanced colorectal cancer.
Eur J Cancer, 26 (1990), pp. 727-729
[37.]
J.E. Fitzpatrick.
New histopathologic findings in drug eruptions.
Dermatol Clin, 10 (1992), pp. 19-36
[38.]
D. Tsuruta, K. Mochida, T. Hamada, M. Ishii, K. Wakasa, S. Hashimoto, et al.
Chemotherapy induced acral erythema: report of a case and immunohistochemical findings.
Clin Exp Dermatol, 25 (2000), pp. 386-388
[39.]
J. Bastida, C. Díaz-Cascajo, S. Borghi.
Chemotherapy-induced acral erythema due to Tegafur.
Acta Derm Venereol, 77 (1997), pp. 72-73
[40.]
D. Calista, C. Landi.
Cytarabine-induced acral erythema: a localized form of toxic epidermal necrolysis?.
J Eur Acad Dermatol Venereol, 10 (1998), pp. 274-275
[41.]
M.K. Crider, J. Jansen, A.L. Norins, M.S. McHale.
Chemotherapy-induced acral erythema in patients receiving bone marrow transplantation.
Arch Dermatol, 122 (1986), pp. 1023-1027
[42.]
D. De Argila, J.D. Domínguez, L. Iglesias.
Taxol-induced acral erythema.
Dermatology, 192 (1996), pp. 377-378
[43.]
D. De Argila, R. Rivera, J.L. López, A. Guerra, L. Iglesias.
Eritema acral inducido por 5-fluorouracilo en infusión continua. Presentación de un caso y revisión de la literatura.
Actas Dermosifiliogr, 84 (1993), pp. 315-318
[44.]
I. Portal, F. Cardenal, X. García-del-Muro.
Etoposide-related acral erythema.
Cancer Chemother Pharmacol, 34 (1994), pp. 181
[45.]
L. Ríos-Buceta, G.F. Buezo, P.F. Peñas, E. Dauden, J. Fernán-dez-Herrera, A. García-Díez.
Palmar-plantar erythrodysaesthesia syndrome and after treatment with Tegafur.
Acta Derm Venereol, 77 (1997), pp. 80-81
[46.]
F. Rongioletti, A. Ballestrero, F. Bogliolo, A. Rebora.
Necrotizing eccrine squamous syringometaplasia presenting as acral erythema.
J Cutan Pathol, 18 (1991), pp. 453-456
[47.]
F. Revenga, D.A. Fernández, C. Grande, J.L. Rodríguez, F. Vanaclocha.
Acute and painful erythema of the hands and feet. Acral erythema induced by chemotherapy.
Arch Dermatol, 133 (1997), pp. 502-503
[48.]
R. Valks, J. Fraga, J. Porras-Luque, A. Figuera, A. García-Díaz, J. Fernández-Herrera.
Chemotherapy-induced eccrine squamous syringometaplasia. A distinctive eruption in patients receiving hematopoietic progenitor cells.
Arch Dermatol, 133 (1997), pp. 873-878
[49.]
H. Tsuboi, K. Yonemoto, K. Katsuoka.
A case of bleomycininduced acral erythema (AE) with eccrine squamous syringometaplasia (ESS) and summary of reports of AE with ESS in the literature.
J Dermatol, 32 (2005), pp. 921-925
[50.]
J.J. Lokich, C. Moore.
Chemotherapy-associated palmar-plantar erythrodysesthesia syndrome.
Ann Intern Med, 101 (1984), pp. 798-800
[51.]
A.E. Werchniak, S. Chaffee, J.G.H. Dinulos.
Methotrexate-induced bullous acral erythema in a child.
J Am Acad Dermatol, 52 (2005), pp. s93-s95
[52.]
W.S. Susser, D.L. Whitaker-Worth, J.M. Grant-Kels.
Mucocutaneous reactions to chemotherapy.
J Am Acad Dermatol, 40 (1999), pp. 367-398
[53.]
G.C. Zimmerman, J.H. Keeling, M. Lowry, J. Medina, D.D. Von Hoff, H.A. Burris.
Prevention of docetaxel-induced erythrodysesthesia with local hypothermia.
J Natl Cancer Inst, 86 (1994), pp. 557
[54.]
H. Komamura, M. Higashiyama, K. Hashimoto, K. Takeda, H. Kimura, Y. Tani.
Three cases of chemotherapy-induced acral erythema.
J Dermatol, 22 (1995), pp. 116-121
[55.]
D. Vakalis, D. Ioannides, E. Lazaridou, G. Mattheou-Vakali, A. Teknetzis.
Acral erythema induced by chemotherapy with cisplatin.
Br J Dermatol, 139 (1998), pp. 750-751
[56.]
E. Esteve, Y. Schillio, L. Vaillant, P. Bensaid, F. Missonnier, E.H. Metman.
Efficacité de la corticothérapie séquentielle dans un cas d’érythème acral douloureux secondaire au 5-fluorouracile à fortes doses.
Ann Med Interne (Paris), 146 (1995), pp. 192-193
[57.]
S.J. Vukelja, F.A. Lombardo, W.D. James, R.B. Weiss.
Pyridoxine for the palmar-plantar erythrodysesthesia syndrome.
Ann Intern Med, 111 (1989), pp. 688-689
[58.]
J. Brown, K. Burck, D. Black, C. Collins.
Treatment of cytarabine acral erythema with corticosteroids.
J Am Acad Dermatol, 24 (1991), pp. 1023-1025
[59.]
E. Nagore, J.M. Sánchez-Motilla, A. Insa, M.I. Febrer.
Síndrome de eritrodisestesia palmo-plantar por 5-fluorouracilo: respuesta favorable al tratamiento con piridoxina.
Med Cutan Iber Lat Am, 26 (1998), pp. 35-38
[60.]
S.J. Vukelja, W.J. Baker, H.A. Burris III.
Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with taxotere.
J Natl Cancer Inst, 85 (1993), pp. 1432-1433
[61.]
D.M. Vail, R. Chun, D.H. Thamm, L.D. Garrett, A.J. Cooley, J.E. Obradovich.
Efficacy of pyridoxine to ameliorate the cutaneous toxicity associated with doxorubicin containing pegylated (Stealth) liposomes: a randomized, double-blind clinical trial using a canine model.
Clin Cancer Res, 4 (1998), pp. 1567-1571
[62.]
K.W. Becker, E.W. Kienecker, P. Dick.
A contribution to the scientific assessment of degenerative and regenerative processes of peripheral nerve fibers following axonotmesis under the systemic administration of vitamins B1, B6 and B12—light and electron microscopy findings of the saphenous nerve in the rabbit.
Neurochirurgia (Stuttg), 33 (1990), pp. 113-121
[63.]
A.M. López, L. Wallace, R.T. Dorr, M. Koff, E.M. Hersh, D.S. Alberts.
Topical DMSO treatment for pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia.
Cancer Chemother Pharmacol, 44 (1999), pp. 303-306
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