A Pilot of Pediatric/Adult Study of Gene Expression Profiling and Clinical Characterization of Phototoxicity

INCLUSION CRITERIA: Subjects who are scheduled to begin voriconazole Subjects with any skin phototype who are scheduled to begin voriconazole therapy. Availability of unexposed skin for testing. Test sites for ssUVR, UVA, and visible light exposures should be devoid of sunburn, suntan, scars, active dermal lesions, prior radiotherapy exposure, and uneven skin tones. The presence of nevi will be acceptable if in the physician's judgment they will not interfere with the study results. (Excess hair is acceptable if clipped or shaved.) Ages greater than or equal to 8 years old. Ability to participate fully and comply with the procedures of the protocol in the opinion of the investigator. Ability of subjects or guardians to understand and sign the consent form. Children must give assent for participation in addition to parental consent. OR Subjects currently on or previously on chronic voriconazole Subjects with any skin phototype who have received or are currently receiving chronic voriconazole therapy. Ages greater than or equal to 8 years old. Ability to participate fully and comply with the procedures of the protocol in the opinion of the investigator. Ability of subjects or guardians to understand and sign the consent form. Children must give assent for participation in addition to parental consent. OR Healthy volunteers I) Screening visit arm. Healthy adults aged 18-45 years old of skin phototype II (age and skin phototype limits selected to simulate subjects evaluated in protocol 04-C-0120). No history of allergy to tetracyclines. No systemic medications, herbal supplements or vitamins that are known to be associated with abnormal light response or effect on cytochrome P450 enzymes taken concurrently or within 7 days or 7 half-lives (whichever is longer) of phototesting. No history of liver disease or hepatitis. Willing to undergo screening dermatologic examination and bloodwork. Ability to understand and sign the consent form. II) Study visit arm Anti-nuclear antibodies (ANA) less than 3 EU; Negative extractable nuclear antigen (ENA); and negative history of idiopathic abnormal response to sunlight, such as polymorphic light eruption or solar urticaria. Prior remote history of phototoxicity reactions acceptable. Availability of unexposed skin for testing. Test sites for ssUVR, UVA, and visible light exposures should be devoid of sunburn, suntan, scars, active dermal lesions, prior radiotherapy exposure, and uneven skin tones. The presence of nevi will be acceptable if in the physician's judgment they will not interfere with the study results. (Excess hair is acceptable if clipped or shaved.) Liver function profile must be within limits of normal. Ability to participate fully and comply with the procedures of the protocol in the opinion of the investigator. EXCLUSION CRITERIA: Subjects who are scheduled to begin voriconazole Does not meet the inclusion criteria. Extensive skin disease and no testable skin area available. History of allergic reactions to lidocaine for the adults who will undergo the modified shave biopsy. History of idiopathic abnormal response to sunlight, such as polymorphic light eruption or solar urticaria. Prior remote history of phototoxicity reaction allowed. Unable to comply with the requirements of the protocol. Any confounding past or present medical illness that in the judgment of the investigators would pose added risk for study participants (i.e. subjects with history of graft-versus-host disease; subjects on concurrent chemotherapy or completed chemotherapy within the preceding two weeks with known photoexacerbating agents such as alkylating agents, doxorubicin, methotrexate, or cisplatin; or subjects with previous radiotherapy to the intended sites for phototesting). Pregnancy. History of keloid formation in the adults who will undergo the modified shave biopsy. OR Subjects currently on or previously on chronic voriconazole Does not meet the inclusion criteria. Unable to comply with the requirements of the protocol. Any confounding past or present medical illness that in the judgment of the investigators would pose added risk for study participants. OR Healthy volunteers I) Screening visit arm. Does not meet the Screening visit arm inclusion criteria. History of allergic reactions to lidocaine. Any confounding past or present medical illness that in the judgment of the investigators would pose added risk for study participants (i.e. subjects with history of graft-versus-host disease; subjects on concurrent chemotherapy with known photoexacerbating agents such as alkylating agents, doxorubicin, methotrexate, or cisplatin; or subjects with previous radiotherapy to the intended sites for phototesting). Pregnancy. History of keloid formation. II) Study visit arm Does not meet the Study visit arm inclusion criteria. Extensive skin disease and no testable skin area available. Anti-nuclear antibodies (ANA) greater than or equal to 3 EU or positive extractable nuclear antigen (ENA); prior history of idiopathic abnormal response to sunlight, such as polymorphic light eruption or solar urticaria. Prior remote history of phototoxicity reaction allowed. Unable to comply with the requirements of the protocol.