Failure of leucovorin rescue to prevent reactivation of a solar burn after high dose methotrexate

Abstract

A 21-year-old patient with metastatic osteosarcoma was receiving methotrexate with leucovorin rescue every 2 weeks. After the second (of four) infusions of methotrexate, a prior solar burn on an area of skin was reactivated in spite of leucovorin rescue. An area of skin treated 5 months previously by radiation was spared the effects of the reactivation phenomenon. N o other toxicities appeared.T h e reactivation of the solar burn is a n example of "false photosensitization" and this cutaneous toxicity is not ameliorated by leucovorin. Methotrexate therapy should be delayed until the effects of generalized solar burns have resolved (approximately 1 week). A recent review' of the dermatologic toxicities of antineoplastic agents mentions that methotrexate is associated with reactivation of radiation dermatitis; however, no mention was made of reactivation of solar burns with methotrexate. Dermatitis is commonly described as a toxic effect of methotrexate but in most reports the character of the dermatitis is not specified or it is described as one of the following: (a) reactivation of a radiation dermatitis; (b) generalized maculopapular eruptions occasionally progressing t o bullous eruptions associated with other manifestations of methotrexate toxicity such as stomatitis, bone

Solar Burn Reactivation Induced by Methotrexate

“…Solar burn reactivation tends to occur during the subsiding phase of a sunburn following exposure to a medication and can occur up to 3-7 days after the original sun exposure occurred. [4][5][6][7] It has been proposed that exposure to the medication causes an enhancement of the inflammatory reaction, resulting in a reactivation and exaggeration of a sunburn in the areas that were exposed. Still other literature suggests the mechanism is believed to be associated with an increased rate of basal cell proliferation following solar erythema and the subsequent destruction of hyperproliferating basal cells following chemotherapy.…”

“…13 However, as Corder and Stone reported in 1976, the use of leucovorin rescue following a solar burn does not prevent a solar burn reactivation reaction. 5 Studies have also shown the combination of L-asparaginase with methotrexate have synergistic antileukemic activity when given on a particular schedule to maximize synergistic cytoxicity, while providing a means of methotrexate rescue. [14][15][16] When asparaginase is administered after methotrexate, it has been shown to stop both methotrexate's therapeutic and toxic effects by interfering with protein synthesis and decreasing methotrexate polyglutamation, thus decreasing toxicity.…”

Methotrexate Reactivation of Sunburn Reaction

“…This reaction is probably unrelated to the enzyme inhibi¬ tory effect of the methotrexate, since the reactivation phenomenon can be elicited by other chemically unrelated chemotherapeutic agents,5-6 and the administration of leu¬ covorin will not prevent reactivation of solar erythema. 7 Epidermal hyperplasia occurs one to three days after mild or moderate sunburn reaction. This is associated with an increased rate of basal cell proliferation after enhanced DNA, RNA, and protein synthesis.8 Damage to these hyperproliferating cells by methotrexate might, in some way, explain the increased cutaneous inflammation seen in our patient.…”