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Chemotherapy-induced acral erythema (CIAE) is a cutaneous response to diverse chemotherapeutic drug administration. These drugs cause symmetrical and painful erythema of palmoplantar surfaces. Bulla formation, desquamation, and subsequent reepithelialization may occur. Commonly, the lesions slowly resolve over 7–15 days, through desquamation, followed by regeneration of the skin. Here, we described a case of CIAE, with involvement of face and neck in a patient treated for breast cancer using a number of chemotherapeutic agents. Face involvement in CIAE has not been previously reported in the literature.

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.

Chemotherapy induced acral erythema (CIAE) is an uncommon and dramatic reaction to high-dose chemotherapy. It is characterized by symmetrical, well-demarcated, painful erythema of the palms and soles which may progress to bullae formation and desquamation. Prompt recognition and discrimination from more serious conditions such as graft-vs-host disease or toxic epidermal necrolysis is essential. This paper describes the case of a 12-year-old boy who developed CIAE after high-dose methotrexate treatment and discusses the important clinical, histopathological, and therapeutic features of this condition.

Chemotherapy-induced acral erythema (CAE) is an uncommon and distinct reaction seen in patients receiving high-dose chemotherapy. The exact pathogenic mechanisms of this disorder are still unknown. We report a 27-year-old woman who presented with red, swollen and painful macules on both palms, clinically consistent with this disease. Histological examination demonstrated vacuolar degeneration of the basal cell layer and spongiotic blisters in the epidermis, especially in the atrophied eccrine ducts and papillary oedema with mild perivascular infiltration of mononuclear and hypersegmented neutrophils. Immunohistochemistry showed that the infiltrating mononuclear cells were CD3-CD16+CD56+ leucocyte function antigen-1+, possibly natural killer cells. The eccrine ducts expressed HLA-DR and intracellular adhesion molecule-1 (ICAM-1). Our findings suggest that cell-to-cell interaction between NK cells and keratinocytes in the eccrine apparatus may induce CAE and may be involved in the pathogenesis of the skin reaction in our patient and possibly in this disease.

Chemotherapy-induced acral erythema (CIAE) is a cutaneous response to a number of different chemotherapeutic agents. It causes a symmetrical, painful erythema of both the palms and soles which is self-limiting. CIAE with bullous reaction has been reported in relation to methotrexate, but it has been more commonly associated with cytosine arabinoside. We describe a case of CIAE with bullous reaction in a patient treated for Hodgkin's disease with a number of chemotherapeutic agents. We discuss the differential diagnosis of this condition which includes eccrine squamous syringometaplasia and acute graft vs. host disease

Background Chemotherapy-induced acral erythema is a distinct localized cutaneous response to certain systemic chemotherapeutic agents. Methods Between January 1990 and December 1994, from a total of 76 leukemic patients who have received combination chemotherapy consisting of cytosine arabinoside and anthracycline antibiotics, 15 patients developed chemotherapy-induced acral erythema. Fourteen of the patients had acute myelocytic leukemia, and one of them had chronic myelogenous leukemia in blast phase. Clinical features of these 15 patients have been analysed. Biopsy specimens obtained from eight of the patients were also evaluated for histopathologic alterations. Results The overall incidence of this reaction was found to be 19.7% in our group of patients receiving this chemotherapy protocol. The onset of reaction varied from the fourth to the seventeenth days of the chemotherapy and resolved within 2 weeks in most of the patients. Lesions appeared as well-defined erythema and edema involving the palmar surfaces in all of the patients. In nine of the patients the reaction recurred with subsequent chemotherapies. Scattered necrotic keratinocytes, vacuolar alterations of the basal layer, and mild to moderate perivascular lymphocytic infiltration in the dermis were the histopathologic findings observed in the biopsy specimens. Conclusions Chemotherapy-induced acral erythema is a frequent reaction in patients who are receiving high-dose chemotherapy. For patients in whom this self-limited condition develops, reassurance is the mainstay of therapy. Awareness of this reaction is also important to be able to differentiate it from acute graft versus host disease in patients who receive bone marrow transplants.

Three cases of chemotherapy-induced acral erythema are reported. All the patients had received cyclophosphamide, vincristine, adriamycin, prednisolone, and granulocyte-colony stimulating factor (G-CSF) for the treatment of leukemia or malignant lymphoma. From 35 to 45 days after the start of chemotherapy, painful erythematous lesions developed on their palms, soles, fingers, and toes, resulting in blister formation and desquamation. The recent higher incidence of chemotherapy-induced acral erythema may be correlated with the popularity of G-CSF, which allows the use of higher doses of chemotherapeutic drugs.

Chemotherapy-induced acral erythema has been described in association with several different chemotherapy regimens. We review the literature on this topic and suggest that different mechanisms may be responsible for the clinically heterogeneous array of acral changes.

Chemotherapy-induced acral erythema is a peculiar localized cutaneous response to several chemotherapeutic agents, mostly antimetabolites. Taxol is a recently developed antineoplastic drug that acts on the mitotic spindle and does not interfere with nucleic acid synthesis. We describe the first case of taxol-induced acral erythema and report on additional data concerning the pathogenesis of this kind of toxic eruptions.

Figure 1. Chemotherapy-Induced Acral Erythema. Acral cyanosis can be seen in a 61-year-old woman with non-Hodgkin's lymphoma. The lesions developed while the patient had severe neutropenia during a course of therapy consisting of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin. The disorder is characterized by intense, painful erythema of the palms and soles, often culminating in the formation of vesicles or bullae. Chemotherapeutic agents are one of the known causes.

To the Editor.— Chemotherapy-induced acral erythema (CIAE) is a rare response to cytotoxic agents that involves painful, well-demarcated erythematous plaques. These plaques usually occur on the palmar and dorsal surface of the hands and, less frequently, on the soles and dorsa of the feet. Some cases, however, progress to bullae formation with subsequent desquamation and sloughing. 1 After encountering a case of bullous CIAE, we discovered an interesting trend in our review of the literature. Patients in whom CIAE developed following treatment with cytarabine, alone or in combination with other agents, have a predilection to progress to the bullous form of CIAE. 2-6 Conversely, those patients receiving doxorubicin and/or fluorouracil are much more likely to have the nonbullous variation of acral erythema develop. Report of a Case.— A 31-year-old man with acute lymphocytic leukemia was admitted for an allogenic bone marrow transplantation. Induction therapy in preparation for undergoing the transplantation included cytarabine

To the Editor.— Chemotherapy-induced acral erythema is an uncommon and distinctive syndrome of painful, intense erythema of the palms and soles seen in patients treated with high-dose chemotherapy. Most of the reported cases were attributed to combination chemotherapy with cytarabine and doxorubicin for the treatment of acute myelogenous leukemia. 1,2 Various chemotherapeutic agents, including methotrexate, mercaptopurine, doxorubicin, and fluorouracil, have been incriminated as among the most logicble causes of this condition. Although the main histologie features of previously reported cases were most consistent with the morbilliform type of drug eruption, we herein describe a patient having the histologic features of leukocytoclastic vasculitis. Report of a Case.— A 59-year-old man was diagnosed as having lung cancer, small-cell type, in August 1988. He was treated with four cycles of the combination chemotherapy of cyclophosphamide, doxorubicin, and vincristine and achieved complete remission. The patient underwent a relapse in 4 months; a new regimen

Patients receiving very high doses of chemotherapeutic drugs, particularly cytarabine (cytosine arabinoside, ara-C, Cytosar), may develop chemotherapy-induced acral erythema, a painful toxic rash of the palmar surfaces of the hands that progresses to edema, blister formation, and desquamation. In more severe cases, the feet are involved, and they show similar changes. Plastic surgeons may be consulted because of the hand involvement and the clinical resemblance, after desquamation, to a very superficial second-degree burn. In patients who have had bone marrow transplantation, this diagnosis must be distinguished from graft-versus-host reaction--a desquamating skin lesion that can affect a similar anatomical area but that is progressive and productive of serious consequences. Acral erythema appears to be self-limited and requires only supportive treatment.

• Chemotherapy-induced acral erythema is an uncommon and distinctive syndrome of intense macular erythema of the palms and fingers seen in patients treated with high-dose chemotherapy. It is painful, may form bullae, and heals uneventfully with desquamation. The incidence (35%) of this complication in patients receiving bone marrow transplantation at our institution is quite high and probably reflects the exceptional doses of chemotherapy and concomitant total body irradiation these patients receive. Biopsy specimens showed vacuolar change, spongiosis, necrotic keratinocytes, and epidermal atypia. These findings probably result from direct toxic effect and mimic those of acute graft-vs-host disease. Awareness of chemotherapy-induced acral erythema is important to avoid its misdiagnosis as a cutaneous sign of acute graft-vs-host disease. This distinction can usually be made on clinical grounds. If necessary, serial skin biopsy specimens are helpful. ( Arch Dermatol 1986;122:1023-1027)