Exacerbation, then clearance, of mutation-proven Darier's disease of the skin after radiotherapy for bronchial carcinoma: a case of radiation-induced epidermal differentiation?
We investigated a radiotherapy-induced flare and subsequent clearance of skin lesions of a patient with the rare, dominantly inherited genodermatosis, Darier's disease (DD). The DD gene, ATP2A2, was recently isolated and shown to be a cation pump responsible for regulating intracellular calcium homeostasis. A severe exacerbation of Darier's skin lesions developed within the radiation field when 40 Gy of palliative thoracic external-beam radiation therapy and concurrent chemotherapy (cisplatin and hydroxyurea) were delivered for non-small cell lung cancer. The DD lesions subsequently completely cleared from irradiated skin, as they did when a subsequent course of radiation alone was given for a loco-regional tumor recurrence. The two radiation therapy-treated areas of skin remained free from lesions of the skin disorder until the patient's death from progressive lung cancer 9 months later. The nucleotide sequence of the patient's ATP2A2 gene was determined by PCR-based cycle sequencing. We identified four nucleotide sequence variants in the ATP2A2 gene in this patient. Three were probable polymorphisms and the other appeared to be a novel disease-causing mutation (R751Q), situated in the transmembrane portion of the ATP2A2 protein. This finding confirmed the clinical diagnosis. Since epidermis turns over every 3-4 weeks, total and persistent clearance of the DD lesions by chemoradiotherapy suggests that this treatment induced sustained differentiation of the DD-affected skin by an unknown mechanism. Oncologists treating malignant disease in patients with DD should anticipate temporary deterioration in DD-involved irradiated skin. Radiation therapy has therapeutic potential in severe DD.
Mac Manus
M P
MP
Department of Radiation Oncology, Peter MacCallum Cancer Institute, Melbourne, Victoria, Vic 8006, Australia. mmanus@petermac.unimelb.edu.au
Cavalleri
G
G
Ball
D L
DL
Beasley
M
M
Rotstein
H
H
McKay
M J
MJ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D000252:Calcium-Transporting ATPases / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy*; D002454:Cell Differentiation / Q000528:radiation effects; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D017931:DNA Primers; D007644:Darier Disease / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D000078404:Epidermal Cells; D004817:Epidermis / Q000528:radiation effects*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011878:Radiotherapy / Q000009:adverse effects; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D017931:DNA Primers; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D000252:Calcium-Transporting ATPases; D002945:Cisplatin; D006918:Hydroxyurea