Background:
* Phototoxicity is a sunburn-like response associated with certain medications and is a phenomenon which is not completely understood. Although clinically similar to a typical sunburn reaction, the gene expression changes in phototoxic skin reactions may differ from those in typical sunburn.
* Doxycycline is a relatively well-tolerated and known phototoxic antimicrobial which can be used in healthy volunteers to increase susceptibility to phototoxicity.
* Characterizing potential risk factors to phototoxicity secondary to voriconazole, a broad-spectrum antifungal agent associated with potentially treatment-limiting phototoxicity, may allow identification of subjects at risk for the adverse reaction via pharmacogenetic evaluation and medical record review.
* Subjects at risk of phototoxicity may benefit from application of effective sunscreens.
Objectives:
* To determine the global gene expression profiles in skin exhibiting phototoxic reactions in healthy volunteers treated with doxycycline, and compare expression profiles in skin exposed to ultraviolet (UV) radiation occurring in the absence of doxycycline.
* To investigate the effects of the doxycycline alone in the skin of phototoxic and non-phototoxic healthy volunteers.
* To characterize voriconazole-related phototoxicity reactions in subjects with the use of phototesting and to determine if these subjects may receive reasonable phototoxic protection from the use of sunblock.
Eligibility:
* I \& II) Healthy volunteers with skin phototype II.
* III) Subjects scheduled to begin voriconazole therapy.
* IV) Subjects on chronic voriconazole with or without a history of phototoxicity reaction.
* Previously treated healthy volunteers (I \& II) who were evaluated to be either phototoxic
OR non-phototoxic.
Design:
* I) For the Screening visit arm, forty healthy volunteers will undergo screening with pertinent skin exam and blood work to evaluate ANA/ENA and liver function profile.
* II) For the Study visit arm, eligible healthy volunteers will undergo phototesting and will have skin biopsies prior to initiating a 3-day course of oral doxycycline 100 mg twice daily.
* After the last dose of doxycycline, healthy volunteers will undergo on-treatment MED testing.
* In those demonstrating phototoxicity, skin biopsies will be performed and submitted for processing for microarray analysis.
* III) Thirty-five subjects scheduled to begin voriconazole will undergo CYP450 genotyping and baseline phototesting prior to initiation of voriconazole.
* Adult subjects will be invited to undergo optional skin biopsies pre-drug and on-drug.
* Repeat phototesting will be performed in subjects after at least 7 days of voriconazole to determine if voriconazole predisposes to phototoxicity.
* Subjects with voriconazole phototoxicity will be invited to undergo sunscreen testing.
* IV) Seventy subjects with prior clinical history of voriconazole phototoxicity as well as known voriconazole phototoxicity non-reactors will undergo CYP450 genotyping and potential phototesting.
* To investigate the effects of the doxycycline alone in the skin of healthy volunteers previously categorized as phototoxic and non-phototoxic
