ABSTRACT
Recent genome-wide association studies (GWASs) have identified >20 new loci associated with the susceptibility to psoriasis vulgaris (PsV) risk. We investigated the association of PsV and its main clinical subphenotypes with 32 loci having previous genome-wide evidence of association with PsV (P < 5e-8) or strong GWAS evidence (P < 5e-5 in discovery and P < 0.05 in replication sample) in a large cohort of PsV patients (n = 2005) and controls (n = 1497). We provide the first independent replication for COG6 (P = 0.00079) and SERPINB8 (P = 0.048) loci with PsV. In those patients having developed psoriatic arthritis (n = 955), we found, for the first time, a strong association with IFIH1 (P = 0.013). Analyses of clinically relevant PsV subtypes yielded a significant association of severity of cutaneous disease with variation at LCE3D locus (P = 0.0005) in PsV and nail involvement with IL1RN in purely cutaneous psoriasis (PsC, P = 0.007). In an exploratory analysis of epistasis, we replicated the previously described HLA-C-ERAP1 interaction with PsC. Our findings show that common genetic variants associated with a complex phenotype like PsV influence different subphenotypes of high clinical relevance.
Subject(s)
Genetic Variation , Phenotype , Psoriasis/genetics , Adaptor Proteins, Vesicular Transport/genetics , Adaptor Proteins, Vesicular Transport/metabolism , Alleles , Aminopeptidases/genetics , Aminopeptidases/metabolism , Case-Control Studies , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , HLA-C Antigens/genetics , HLA-C Antigens/immunology , Humans , Interleukin 1 Receptor Antagonist Protein/genetics , Male , Minor Histocompatibility Antigens , Skin/immunology , Skin/metabolismABSTRACT
OBJECTIVE: To describe the use of systemic therapy for psoriasis (biologic and nonbiologic [classic] drugs) in patients not adequately represented in randomized controlled trials (RCTs) and the risk of serious adverse events (SAEs) in these patients. DESIGN: A registry inception cohort was used. SETTING: Thirteen dermatology departments in Spain participated. PATIENTS: A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy were evaluated. A total of 1042 patients (2179 person-years) were included. EXPOSURE: Inadequate representation in trials was defined as the presence of any of the following factors: elderly age (>70 years); type of psoriasis other than chronic plaque psoriasis; history of infection caused by hepatitis B, hepatitis C, or human immunodeficiency virus; history of cancer (excluding nonmelanoma skin cancer); and chronic renal or hepatic disease. MAIN OUTCOME MEASURES: Serious adverse events as defined by the International Conference on Harmonization were evaluated. RESULTS: In all, 29.8% of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs. These individuals had an increased risk of SAEs (incidence rate ratio, 2.7; 95% CI, 1.5-4.7). Patients exposed to biologics had an adjusted increased risk of SAEs (incidence rate ratio, 2.3; 95% CI, 1.1-4.8) that was similar in patients eligible and ineligible for RCTs. CONCLUSIONS: Patients ineligible for RCTs are an important proportion (30%) of those receiving systemic therapy for psoriasis. These patients have a higher risk of SAEs and should be closely monitored. Patients exposed to biologics (whether these patients are eligible for RCTs or ineligible) are susceptible to the same increase in risk of SAEs, but biologics add to a higher baseline risk in patients who are ineligible for RCTs. The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients.
Subject(s)
Anti-Inflammatory Agents/adverse effects , Biological Products/adverse effects , Patient Selection , Psoriasis/classification , Psoriasis/drug therapy , Adult , Age Factors , Aged , Antibodies, Monoclonal/adverse effects , Female , Humans , Immunosuppressive Agents/adverse effects , Keratolytic Agents/adverse effects , Male , Middle Aged , PUVA Therapy/adverse effects , Proportional Hazards Models , Randomized Controlled Trials as Topic , Risk Assessment , SpainABSTRACT
Lichen sclerosus is an uncommon, chronic inflammatory skin disorder of unknown origin. It is clinically characterized by sclerotic, whitish, atrophic-type lesions. The most frequent site of the lesions is generally the genital region, with about 15-20% having additional extragenital involvement. We present the case of a 62-year-old woman with a very extensive extragenital lichen sclerosus who showed great clinical and subjective improvement with 0.1% tacrolimus ointment and psoralen plus UVA (PUVA), without any topical or systemic adverse effects. Combined treatment of 0.1% tacrolimus ointment and PUVA may be a good option in extensive cases of lichen sclerosus or when other treatment options have failed, and has a good tolerability and safety profile.
