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dc.contributor.authorGuerra, Ricardo
dc.date.accessioned2019-12-05T09:00:01Z
dc.date.created2018-05
dc.date.issued2019-03-25
dc.date.submitted2018
dc.identifier.citationGuerra, Ricardo. 2018. Adverse Cutaneous Drug Eruptions: Review of Immunology, Pathogenesis, and Pharmacogenomics With Focus on HIV and TEN. Doctoral dissertation, Harvard Medical School.
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41973469*
dc.description.abstractPurpose: Immunologic principles behind antigen presentation inform the pathophysiologic basis of adverse cutaneous drug eruptions (ACDEs). We hypothesize that HIV predisposes to Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN), a severe ACDE, through decreased glutathione and regulatory T cells. Methods: Pubmed literature was reviewed including MESH terms “Anti-HIV Agents” and “Drug Eruptions” with other controlled vocabulary, synonyms, and truncated terms in addition to Boolean operators for more comprehensive and unambiguous searches. Results: HIV tropism for CD4+ in the circulating blood may decrease skin-directed CD4+, including CD4+ CD25+ T-regs that may prevent mild skin lesions from converting to TEN. HLA molecules play a crucial role in drug antigen presentation, and certain HLA alleles are present at higher frequency in patients who suffer from drug-specific ACDEs. Similarly, specific alleles related to glutathione synthesis, cytochrome P450 enzymes, and N-acetylatransferases important for drug metabolism appear in higher frequencies in patients with ACDEs and TEN induced by HIV-associated drugs. Conclusions: HIV and HIV-associated medications predispose patients to SJS/TEN through different, likely interacting mechanisms. SJS/TEN pathogenesis is multifactorial and involves interplay of cytotoxic T lymphocytes and various cytokines and cell signaling pathways. HIV associated-medications increase susceptibility to SJS/TEN and ACDEs at different rates, possibly attributed to variable forms of drug metabolism and antigen presentation. Further study in the immunology and pharmacogenomics of ACDEs can identify appropriate screening strategies, diagnostic biomarkers, and treatment targets, particularly in susceptible (e.g., virally infected) populations.
dc.description.sponsorshipScholarly Project
dc.format.mimetypeapplication/pdf
dc.language.isoen
dash.licenseLAA
dc.subjectDrug
dc.subjectEruption
dc.subjectHIV
dc.subjectTEN
dc.subjectPharmacogenomics
dc.titleAdverse Cutaneous Drug Eruptions: Review of Immunology, Pathogenesis, and Pharmacogenomics With Focus on HIV and TEN
dc.typeThesis or Dissertation
dash.depositing.authorGuerra, Ricardo
dc.date.available2019-12-05T09:00:01Z
thesis.degree.date2018
thesis.degree.grantorHarvard Medical School
thesis.degree.grantorHarvard Medical School
thesis.degree.levelDoctoral
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Medicine
thesis.degree.nameDoctor of Medicine
dc.type.materialtext
dash.identifier.vireo
dc.identifier.orcid0000-0001-6745-7521
dash.author.emailricardoguerra.rgu@gmail.com


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