Exacerbation, then clearance, of mutation-proven Darier's disease of the skin after radiotherapy for bronchial carcinoma: a case of radiation-induced epidermal differentiation?

Abstract

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.

• Authors: M P Mac Manus, G Cavalleri, D L Ball, M Beasley, H Rotstein, M J McKay
• Journal: Radiation research (Radiat Res) Vol. 156 Issue 6 Pg. 724-30 (Dec 2001) ISSN: 0033-7587 [Print] United States
• PMID: 11741496 (Publication Type: Case Reports, Journal Article)

Chemical References

• DNA Primers
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• ATP2A2 protein, human
• Calcium-Transporting ATPases
• Cisplatin
• Hydroxyurea

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Base Sequence
• Calcium-Transporting ATPases (genetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, radiotherapy)
• Cell Differentiation (radiation effects)
• Cisplatin (administration & dosage)
• Combined Modality Therapy
• DNA Primers
• Darier Disease (etiology, genetics, pathology)
• Epidermal Cells
• Epidermis (radiation effects)
• Humans
• Hydroxyurea (administration & dosage)
• Lung Neoplasms (drug therapy, radiotherapy)
• Male
• Middle Aged
• Mutation
• Polymerase Chain Reaction
• Radiotherapy (adverse effects)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases