Radiation Oncology/Toxicity/Skin

Skin Toxicity

Please see the skin care chapter for management

RTOG Scale

Grade Description
0 None or no change
I Scattered macular or papular eruption or erythema that is asymptomatic
II Scattered macular or papular eruption or erythema with pruritis or other associated symptoms
III Generalized symptomatic macular, papular, or vesicular eruption
IV Exfoliative dermatitis or ulcerating dermatitis

Grade Description
0 None or no change
I Faint erythema or dry desquamation
II Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema
III Moist desquamation other than skin folds and creases; bleeding induced by minor trauma or abrasion
IV Skin necrosis or ulceration of full thickness dermis; spontaneous bleeding from involved site

Dose Tolerances

  • Temporary erythema - 2 Gy - 1 day
  • Dry desquamation - 14 Gy - 4 weeks
  • Moist desquamation - 18 Gy - 4 weeks
  • Temporary epilation - 3 Gy - 3 weeks
  • Permanent epilation - 7 Gy - 3 weeks
  • Permanent alopecia- 43 Gy (PMID 15465206)

Phenytoin-Induced Syndromes

  • Can be seen after whole-brain radiation concurrent with phenytoin
    • Erythema Multiforme minor and Erythema Multiforme major
    • Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
  • Tentatively proposed to be classified under acronym EMPACT (Erythema Multiforme associated with Phenytoin And Cranial radiation Therapy)
  • A case report also describes similar interaction between carbamazepine and cranial irradiation

  • Madrid; 2007 (Spain) PMID 17669303 -- "[Toxic epidermal necrolysis induced by phenytoin and whole brain radiotherapy] [Article in Spanish]" (Fernandez FA, Actas Dermosifiliogr. 2007 Sep;98(7):483-5.)
    • Case report. 1 patient treated with phenytoin and whole brain RT developed TEN
  • Samsun; 2006 (Turkey) PMID 16684289 -- "Stevens-Johnson syndrome in two patients treated with cranial irradiation and phenytoin." (Aydin F, J Eur Acad Dermatol Venereol. 2006 May;20(5):588-90.)
    • Case report. 2 patients. Treated with cranial RT and phenytoin developed SJS
  • Vienna; 2005 (Austria) PMID 16353748 -- "EMPACT syndrome." (Wohrl S, J Dtsch Dermatol Ges. 2005 Jan;3(1):39-43.)
    • Case report. 1 patient treated with phenytoin and cranial RT. Treated with corticosteroids and immunoglobulins
    • Conclusion: Propose definition of EMPACT
  • Istanbul; 2004 PMID 15347896 -- "Toxic epidermal necrolysis after cranial radiotherapy and phenytoin treatment." (Oner Dincbas F, Onkologie. 2004 Aug;27(4):389-92.)
    • Case reports. 1 patient treated with phenytoin and cranial irradiation, progressed to 70% of whole body, leading to death
    • Conclusion: TEN should be considered during cranial irradiation and antiepileptic prophylaxis
  • Mayo Clinic; 2004 PMID 14693027 -- "Erythema multiforme associated with phenytoin and cranial radiation therapy: a report of three patients and review of the literature." (Ahmed I, Int J Dermatol. 2004 Jan;43(1):67-73.)
    • Review. 24 cases identified in literature. Mean age 44 (23-67). Phenytoin variable duration (mean 40 days, 16-80 days). Lesions during RT or soon thereafter. No relationship between extent and severity of skin lesions and phenytoin or RT dose. Complete recovery within 1-8 weeks of discontinuing RT
    • Propose acronym EMPACT (Erythema Multiforme associated with Phenytoin and Cranial radiation Therapy)
  • Riyadh; 1999 (Saudi Arabia) PMID 10090698 -- "Stevens-Johnson syndrome in patients on phenytoin and cranial radiotherapy." (Khafaga YM, Acta Oncol. 1999;38(1):111-6.)
    • Case report. 4 patients within 24 month period. Adverse reactions to phenytoin during cranial RT
    • Conclusion: In absence of seizure history, prophylactic phenytoin use may not be warranted
  • Catania; 1999 (Italy) PMID 10030773 -- "Increased risk of erythema multiforme major with combination anticonvulsant and radiation therapies." (Micali G, Pharmacotherapy. 1999 Feb;19(2):223-7.)
    • Case report and literature review. 1 patient. Identified 20 cases in literature of phenytoin + cranial irradiation. No relationship between phenytoin dose, RT dose, histology of brain tumor, age, or gender
    • Also identified a report describing carbamazepine. Gabapentin should be considered