title: Paradoxical psoriasiform reactions to anti-TNFα drugs are associated with genetic polymorphisms in patients with psoriasis.
abstract: Paradoxical psoriasiform reactions to anti-tumor necrosis factor α (TNFα) agents have been described. We aimed to study the association between these reactions and polymorphisms in genes previously associated with psoriasis or other autoimmune diseases. A total of 161 patients with plaque-type psoriasis treated with anti-TNFα drugs were genotyped for 173 single-nucleotide polymorphisms (SNPs) using the Illumina Veracode genotyping platform. Among the 161 patients, 25 patients developed a paradoxical psoriasiform reaction consisting of a change in morphology, mostly to guttate psoriasis (88%). These lesions developed 9.20±13.52 months after initiating treatment, mainly with etanercept (72%). Psoriasis type and a Psoriasis Area and Severity Index (PASI) 75 response to treatment were not associated with lesions. Multivariate logistic regression revealed that five SNPs (rs11209026 in IL23R, rs10782001 in FBXL19, rs3087243 in CTLA4, rs651630 in SLC12A8 and rs1800453 in TAP1) were associated with paradoxical reactions. This is the first study to show an association between genetic polymorphisms and paradoxical reactions in patients with psoriasis treated with anti-TNFα drugs.The Pharmacogenomics Journal advance online publication, 21 July 2015; doi:10.1038/tpj.2015.53.
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Cabaleiro
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Prieto-Pérez
authors.affiliation: Dermatology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Navarro
authors.affiliation: Dermatology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Solano
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Román
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Ochoa
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Abad-Santos
authors.affiliation: Dermatology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Daudén
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2 / Q000235:genetics; D000328:Adult; D000368:Aged; D060908:CTLA-4 Antigen / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003879:Dermatologic Agents / Q000009:adverse effects*; D003875:Drug Eruptions / Q000175:diagnosis / Q000235:genetics*; D044783:F-Box Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D018123:Receptors, Interleukin / Q000235:genetics; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004268:DNA-Binding Proteins; D003879:Dermatologic Agents; D044783:F-Box Proteins; C499971:FBXL19 protein, human; C515500:IL23R protein, human; D018123:Receptors, Interleukin; C073119:TAP1 protein, human; D014409:Tumor Necrosis Factor-alpha