Chemotherapy-induced acral erythema: report of a case and immunohistochemical findings

Abstract

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.

Novel role of regulatory T cells in limiting early neutrophil responses in skin

“…This occurs partly through the influence of Treg cells on neutrophil survival, as evidenced by a significantly enhanced nuclear hypersegmentation in neutrophils recovered from mice with reduced Treg‐cell numbers. Nuclear hypersegmentation is strongly associated with non‐infectious inflammatory conditions 19–21 and is historically associated with older neutrophils and prolonged survival. More recently, hypersegmented neutrophils resulting from granulocyte colony‐stimulating factor treatment, 22 exhibited increased survival and increased phagocytic and cytolytic capacity 23,24 .…”

Acral Erythema with Oral Methotrexate in a Child

“…Histologic findings of patients in whom biopsies have been performed are generally nonspecific but include changes to the eccrine sweat glands (4,24). Vargas‐Diez et al (24) reported 15 patients who developed acral erythema in response to various chemotherapeutic regimens.…”

“…Acral erythema has been described as symmetric, painful erythema of the palms and soles with a prodrome of paresthesia and occasional bullous formation with desquamation upon resolution (1). It has been associated with a number of chemotherapeutic agents including 5‐fluorouracil (2,3), cytarabine (4–6), and cyclophosphamide (7). Methotrexate‐induced acral erythema was initially described in 1983 and since then over a dozen reports implicating MTX as the causative agent in the development of acral erythema have been published (8–15).…”

Bullous acral erythema: an additional consideration in the differential diagnosis of pauci‐inflammatory subepidermal bullae*

“…Excretion onto the skin surface may create a microenvironment in which the direct toxic effects of the chemotherapeutic agents may induce the skin lesions 23 . Others have speculated that the accumulation of chemotherapeutic agents within the sweat gland apparatus may trigger an immune response that in turn generates the cutaneous lesions 27 . Unfortunately, the superficial shave biopsy from our patient did not permit analysis of eccrine structures.…”