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BACKGROUND: Palmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. Although the disease can present with concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets. OBJECTIVES: We sought to identify genetic determinants of PPP and investigate whether cigarette smoking contributes to disease pathogenesis. METHODS: We performed a genome-wide association meta-analysis of 3 North-European cohorts (n = 1,456 PPP cases and 402,050 controls). We then used the scGWAS program to investigate the cell-type specificity of the association signals. We also undertook genetic correlation analyses to examine the similarities between PPP and other immune-mediated diseases. Finally, we applied Mendelian randomization to analyze the causal relationship between cigarette smoking and PPP. RESULTS: We found that PPP is not associated with the main genetic determinants of plaque psoriasis. Conversely, we identified genome-wide significant associations with the FCGR3A/FCGR3B and CCHCR1 loci. We also observed 13 suggestive (P < 5 × 10-6) susceptibility regions, including the IL4/IL13 interval. Accordingly, we demonstrated a significant genetic correlation between PPP and TH2-mediated diseases such as atopic dermatitis and ulcerative colitis. We also found that genes mapping to PPP-associated intervals were preferentially expressed in dendritic cells and often implicated in T-cell activation pathways. Finally, we undertook a Mendelian randomization analysis, which supported a causal role of cigarette smoking in PPP. CONCLUSIONS: The first genome-wide association study of PPP points to a pathogenic role for deregulated TH2 responses and cigarette smoking.
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BACKGROUND: Systematic reviews suggest that narrowband ultraviolet B light combined with treatments such as topical corticosteroids may be more effective than monotherapy for vitiligo. OBJECTIVE: To explore the clinical effectiveness and cost-effectiveness of topical corticosteroid monotherapy compared with (1) hand-held narrowband ultraviolet B light monotherapy and (2) hand-held narrowband ultraviolet B light/topical corticosteroid combination treatment for localised vitiligo. DESIGN: Pragmatic, three-arm, randomised controlled trial with 9 months of treatment and a 12-month follow-up. SETTING: Sixteen UK hospitals - participants were recruited from primary and secondary care and the community. PARTICIPANTS: Adults and children (aged ≥ 5 years) with active non-segmental vitiligo affecting ≤ 10% of their body area. INTERVENTIONS: Topical corticosteroids [mometasone furoate 0.1% (Elocon®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) plus dummy narrowband ultraviolet B light]; narrowband ultraviolet B light (narrowband ultraviolet B light plus placebo topical corticosteroids); or combination (topical corticosteroids plus narrowband ultraviolet B light). Topical corticosteroids were applied once daily on alternate weeks and narrowband ultraviolet B light was administered every other day in escalating doses, with a dose adjustment for erythema. All treatments were home based. MAIN OUTCOME MEASURES: The primary outcome was self-assessed treatment success for a chosen target patch after 9 months of treatment ('a lot less noticeable' or 'no longer noticeable' on the Vitiligo Noticeability Scale). Secondary outcomes included blinded assessment of primary outcome and percentage repigmentation, onset and maintenance of treatment response, quality of life, side effects, treatment burden and cost-effectiveness (cost per additional successful treatment). RESULTS: In total, 517 participants were randomised (adults, n = 398; and children, n = 119; 52% male; 57% paler skin types I-III, 43% darker skin types IV-VI). At the end of 9 months of treatment, 370 (72%) participants provided primary outcome data. The median percentage of narrowband ultraviolet B light treatment-days (actual/allocated) was 81% for topical corticosteroids, 77% for narrowband ultraviolet B light and 74% for combination groups; and for ointment was 79% for topical corticosteroids, 83% for narrowband ultraviolet B light and 77% for combination. Target patch location was head and neck (31%), hands and feet (32%), and rest of the body (37%). Target patch treatment 'success' was 20 out of 119 (17%) for topical corticosteroids, 27 out of 123 (22%) for narrowband ultraviolet B light and 34 out of 128 (27%) for combination. Combination treatment was superior to topical corticosteroids (adjusted risk difference 10.9%, 95% confidence interval 1.0% to 20.9%; p = 0.032; number needed to treat = 10). Narrowband ultraviolet B light was not superior to topical corticosteroids (adjusted risk difference 5.2%, 95% confidence interval -4.4% to 14.9%; p = 0.290; number needed to treat = 19). The secondary outcomes supported the primary analysis. Quality of life did not differ between the groups. Participants who adhered to the interventions for > 75% of the expected treatment protocol were more likely to achieve treatment success. Over 40% of participants had lost treatment response after 1 year with no treatment. Grade 3 or 4 erythema was experienced by 62 participants (12%) (three of whom were using the dummy) and transient skin thinning by 13 participants (2.5%) (two of whom were using the placebo). We observed no serious adverse treatment effects. For combination treatment compared with topical corticosteroids, the unadjusted incremental cost-effectiveness ratio was £2328.56 (adjusted £1932) per additional successful treatment (from an NHS perspective). LIMITATIONS: Relatively high loss to follow-up limits the interpretation of the trial findings, especially during the post-intervention follow-up phase. CONCLUSION: Hand-held narrowband ultraviolet B light plus topical corticosteroid combination treatment is superior to topical corticosteroids alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated, but was effective in around one-quarter of participants only. Whether or not combination treatment is cost-effective depends on how much decision-makers are willing to pay for the benefits observed. FUTURE WORK: Development and testing of new vitiligo treatments with a greater treatment response and longer-lasting effects are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17160087. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 64. See the NIHR Journals Library website for further project information.
The Home Interventions and Light therapy for the treatment of vitiligo (HI-Light Vitiligo) trial aimed to find out whether or not treating vitiligo at home with a narrowband ultraviolet B light, either by itself or with a steroid ointment, is better than treatment using a steroid ointment only. We enrolled 517 children (aged ≥ 5 years) and adults who had small, active (i.e. recently changing) patches of vitiligo into the study. Participants received one of three possible treatment options: steroid ointment (plus dummy light), hand-held narrowband ultraviolet B light therapy (plus placebo ointment) or both treatments used together. We asked participants to judge how noticeable their target vitiligo patch was after 9 months of treatment. We considered the treatment to be successful if the participants' responses were either 'a lot less noticeable' or 'no longer noticeable'. The results showed that using both treatments together was better than using a steroid ointment on its own. Around one-quarter of participants (27%) who used both treatments together said that their vitiligo was either 'no longer noticeable' or 'a lot less noticeable' after 9 months of treatment. This was compared with 17% of those using steroid ointment on its own and 22% of those using narrowband ultraviolet B light on its own. All treatments were able to stop the vitiligo from spreading. Patches on the hands and feet were less likely to respond to treatment than patches on other parts of the body. The trial found that the vitiligo tended to return once treatments were stopped, so ongoing intermittent treatment may be needed to maintain the treatment response. The treatments were found to be relatively safe and easy to use, but light treatment required a considerable time commitment (approximately 20 minutes per session, two or three times per week). This trial showed that using steroid ointment and narrowband ultraviolet B light together is likely to be better than steroid ointment alone for people with small patches of vitiligo. Steroid ointment alone can still be effective for some people and remains a useful treatment that is able to stop vitiligo from spreading. The challenge is to make hand-held narrowband ultraviolet B light treatment available as normal care in the NHS for people with vitiligo.
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Fármacos Dermatológicos/uso terapéutico , Furoato de Mometasona/uso terapéutico , Terapia Ultravioleta/métodos , Vitíligo/terapia , Administración Cutánea , Adolescente , Niño , Preescolar , Terapia Combinada , Análisis Costo-Beneficio , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/economía , Femenino , Humanos , Masculino , Modelos Económicos , Furoato de Mometasona/administración & dosificación , Furoato de Mometasona/efectos adversos , Furoato de Mometasona/economía , Calidad de Vida , Método Simple Ciego , Evaluación de la Tecnología Biomédica , Terapia Ultravioleta/efectos adversos , Terapia Ultravioleta/economía , Reino UnidoRESUMEN
Importance: Although palmoplantar pustulosis (PPP) can significantly impact quality of life, the factors underlying disease severity have not been studied. Objective: To examine the factors associated with PPP severity. Design, Setting, and Participants: An observational, cross-sectional study of 2 cohorts was conducted. A UK data set including 203 patients was obtained through the Anakinra in Pustular Psoriasis, Response in a Controlled Trial (2016-2019) and its sister research study Pustular Psoriasis, Elucidating Underlying Mechanisms (2016-2020). A Northern European cohort including 193 patients was independently ascertained by the European Rare and Severe Psoriasis Expert Network (2014-2017). Patients had been recruited in secondary or tertiary dermatology referral centers. All patients were of European descent. The PPP diagnosis was established by dermatologists, based on clinical examination and/or published consensus criteria. The present study was conducted from October 1, 2014, to March 15, 2020. Main Outcomes and Measures: Demographic characteristics, comorbidities, smoking status, Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI), measuring severity from 0 (no sign of disease) to 72 (very severe disease), or Physician Global Assessment (PGA), measuring severity as 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). Results: Among the 203 UK patients (43 men [21%], 160 women [79%]; median age at onset, 48 [interquartile range (IQR), 38-59] years), the PPPASI was inversely correlated with age of onset (r = -0.18, P = .01). Similarly, in the 159 Northern European patients who were eligible for inclusion in this analysis (25 men [16%], 134 women [84%]; median age at onset, 45 [IQR, 34-53.3] years), the median age at onset was lower in individuals with a moderate to severe PGA score (41 years [IQR, 30.5-52 years]) compared with those with a clear to mild PGA score (46.5 years [IQR, 35-55 years]) (P = .04). In the UK sample, the median PPPASI score was higher in women (9.6 [IQR, 3.0-16.2]) vs men (4.0 [IQR, 1.0-11.7]) (P = .01). Likewise, moderate to severe PPP was more prevalent among Northern European women (57 of 134 [43%]) compared with men (5 of 25 [20%]) (P = .03). In the UK cohort, the median PPPASI score was increased in current smokers (10.7 [IQR, 4.2-17.5]) compared with former smokers (7 [IQR, 2.0-14.4]) and nonsmokers (2.2 [IQR, 1-6]) (P = .003). Comparable differences were observed in the Northern European data set, as the prevalence of moderate to severe PPP was higher in former and current smokers (51 of 130 [39%]) compared with nonsmokers (6 of 24 [25%]) (P = .14). Conclusions and Relevance: The findings of this study suggest that PPP severity is associated with early-onset disease, female sex, and smoking status. Thus, smoking cessation intervention might be beneficial.
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Psoriasis/diagnóstico , Índice de Severidad de la Enfermedad , Fumar/epidemiología , Adulto , Edad de Inicio , Comorbilidad , Estudios Transversales , Ex-Fumadores/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , No Fumadores/estadística & datos numéricos , Prevalencia , Psoriasis/epidemiología , Psoriasis/prevención & control , Calidad de Vida , Factores de Riesgo , Factores Sexuales , Fumadores/estadística & datos numéricos , Prevención del Hábito de FumarRESUMEN
The identification of disease alleles underlying human autoinflammatory diseases can provide important insights into the mechanisms that maintain neutrophil homeostasis. Here, we focused our attention on generalized pustular psoriasis (GPP), a potentially life-threatening disorder presenting with cutaneous and systemic neutrophilia. Following the whole-exome sequencing of 19 unrelated affected individuals, we identified a subject harboring a homozygous splice-site mutation (c.2031-2A>C) in MPO. This encodes myeloperoxidase, an essential component of neutrophil azurophil granules. MPO screening in conditions phenotypically related to GPP uncovered further disease alleles in one subject with acral pustular psoriasis (c.2031-2A>C;c.2031-2A>C) and in two individuals with acute generalized exanthematous pustulosis (c.1705C>T;c.2031-2A>C and c.1552_1565del;c.1552_1565del). A subsequent analysis of UK Biobank data demonstrated that the c.2031-2A>C and c.1705C>T (p.Arg569Trp) disease alleles were also associated with increased neutrophil abundance in the general population (p = 5.1 × 10-6 and p = 3.6 × 10-5, respectively). The same applied to three further deleterious variants that had been genotyped in the cohort, with two alleles (c.995C>T [p.Ala332Val] and c.752T>C [p.Met251Thr]) yielding p values < 10-10. Finally, treatment of healthy neutrophils with an MPO inhibitor (4-Aminobenzoic acid hydrazide) increased cell viability and delayed apoptosis, highlighting a mechanism whereby MPO mutations affect granulocyte numbers. These findings identify MPO as a genetic determinant of pustular skin disease and neutrophil abundance. Given the recent interest in the development of MPO antagonists for the treatment of neurodegenerative disease, our results also suggest that the pro-inflammatory effects of these agents should be closely monitored.
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Enfermedades Neurodegenerativas/genética , Peroxidasa/genética , Psoriasis/genética , Enfermedades de la Piel/genética , Ácido 4-Aminobenzoico/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular/efectos de los fármacos , Femenino , Genotipo , Humanos , Mutación con Pérdida de Función/genética , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/patología , Neutrófilos/efectos de los fármacos , Peroxidasa/antagonistas & inhibidores , Fenotipo , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Piel/efectos de los fármacos , Piel/patología , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/patologíaRESUMEN
Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes.
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Fármacos Dermatológicos/farmacocinética , Modelos Biológicos , Psoriasis/tratamiento farmacológico , Ustekinumab/farmacocinética , Adolescente , Adulto , Anciano , Teorema de Bayes , Fármacos Dermatológicos/administración & dosificación , Cálculo de Dosificación de Drogas , Monitoreo de Drogas/métodos , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psoriasis/sangre , Psoriasis/diagnóstico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Ustekinumab/administración & dosificación , Adulto JovenRESUMEN
IMPORTANCE: High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab. OBJECTIVE: To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis. DESIGN, SETTING, AND PARTICIPANTS: A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria. EXPOSURE: Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay. MAIN OUTCOMES AND MEASURES: Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less. RESULTS: A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5). CONCLUSIONS AND RELEVANCE: This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome.
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Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02.
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Alopecia/congénito , Sitios Genéticos , Predisposición Genética a la Enfermedad , Antígeno HLA-B7/genética , Transcriptoma/inmunología , Inmunidad Adaptativa , Alopecia/diagnóstico , Alopecia/genética , Alopecia/fisiopatología , Estudios de Casos y Controles , Estudios de Cohortes , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/inmunología , Femenino , Expresión Génica , Genoma Humano , Estudio de Asociación del Genoma Completo , Antígeno HLA-B7/inmunología , Humanos , Inmunidad Innata , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations. OBJECTIVE: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort. METHODS: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases. RESULTS: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P < .0005 for both), whereas the mean age of onset was earliest in GPP (31.0 vs 43.7 years in PPP and 51.8 years in ACH, P < .0001 for both). The percentage of female patients was greater in PPP (77.0%) than in GPP (62.5%; P = 5.8 × 10-5). The same applied to the prevalence of smokers (79.8% vs 28.3%, P < 10-15). Although AP1S3 alleles had similar frequency (0.03-0.05) across disease subtypes, IL36RN mutations were less common in patients with PPP (0.03) than in those with GPP (0.19) and ACH (0.16; P = 1.9 × 10-14 and .002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset in all forms of pustular psoriasis (P = .003). CONCLUSIONS: The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP.
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Psoriasis/genética , Adolescente , Adulto , Anciano , Niño , Femenino , Estudios de Asociación Genética , Humanos , Interleucinas/genética , Masculino , Persona de Mediana Edad , Mutación , Fumar/genética , Proteínas de Transporte Vesicular/genética , Adulto JovenRESUMEN
BACKGROUND: Biologic therapies can be highly effective for the treatment of severe psoriasis, but response for individual patients can vary according to drug. Predictive biomarkers to guide treatment selection could improve patient outcomes and treatment cost-effectiveness. OBJECTIVE: We sought to test whether HLA-C*06:02, the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologics for psoriasis: adalimumab (anti-TNF-α) and ustekinumab (anti-IL-12/23). METHODS: This study uses a national psoriasis registry that includes longitudinal treatment and response observations and detailed clinical data. HLA alleles were imputed from genome-wide genotype data for 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index score (PASI90) response status was observed after 3, 6, or 12 months of treatment. We developed regression models of PASI90 response, examining the interaction between HLA-C*06:02 and drug type (adalimumab or ustekinumab) while accounting for potentially confounding clinical variables. RESULTS: HLA-C*06:02-negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (most strongly at 6 months: odds ratio [OR], 2.95; P = 5.85 × 10-7), and the difference was greater in HLA-C*06:02-negative patients with psoriatic arthritis (OR, 5.98; P = 6.89 × 10-5). Biologic-naive patients who were HLA-C*06:02 positive and psoriatic arthritis negative demonstrated significantly poorer response to adalimumab at 12 months (OR, 0.31; P = 3.42 × 10-4). Results from HLA-wide analyses were consistent with HLA-C*06:02 itself being the primary effect allele. We found no evidence for genetic interaction between HLA-C*06:02 and ERAP1. CONCLUSION: This large observational study suggests that reference to HLA-C*06:02 status could offer substantial clinical benefit when selecting treatments for severe psoriasis.
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Adalimumab/uso terapéutico , Terapia Biológica/métodos , Biomarcadores Farmacológicos , Genotipo , Antígenos HLA-C/genética , Psoriasis/genética , Ustekinumab/uso terapéutico , Adulto , Alelos , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Valor Predictivo de las Pruebas , Pronóstico , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. OBJECTIVE: We sought to estimate the effectiveness of topical therapies in the treatment of patients with PG. METHODS: This was a prospective cohort study of UK secondary care patients with a clinical diagnosis of PG that was suitable for topical treatment (recruited between July 2009 and June 2012). Participants received topical therapy after normal clinical practice (primarily topical corticosteroids [classes I-III] and tacrolimus 0.03% or 0.1%). The primary outcome was speed of healing at 6 weeks. Secondary outcomes included the following: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality of life; treatment failure; and recurrence. RESULTS: Sixty-six patients (22-85 years of age) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28 of 66 (43.8%) ulcers healed by 6 months. The median time to healing was 145 days (95% confidence interval, 96 days to ∞). Initial ulcer size was a significant predictor of time to healing (hazard ratio, 0.94 [95% confidence interval, 0.88-1.00); P = .043). Four patients (15%) had a recurrence. LIMITATIONS: Our study did not include a randomized comparator. CONCLUSION: Topical therapy is potentially an effective first-line treatment for PG that avoids the possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone.
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Antiinflamatorios/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Piodermia Gangrenosa/tratamiento farmacológico , Administración Cutánea , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Clobetasol/administración & dosificación , Clobetasol/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Estudios Prospectivos , Piodermia Gangrenosa/complicaciones , Calidad de Vida , Recurrencia , Úlcera Cutánea/tratamiento farmacológico , Úlcera Cutánea/etiología , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéutico , Resultado del TratamientoRESUMEN
A 61-year-old man presented with erysipelas-like cutaneous leishmaniasis.
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Erisipela/diagnóstico , Enfermedades de los Párpados/diagnóstico , Dermatosis Facial/diagnóstico , Leishmaniasis Cutánea/diagnóstico , Gluconato de Sodio Antimonio/efectos adversos , Gluconato de Sodio Antimonio/uso terapéutico , Antiprotozoarios/efectos adversos , Antiprotozoarios/uso terapéutico , Celulitis (Flemón)/diagnóstico , ADN Protozoario/análisis , Diagnóstico Diferencial , Progresión de la Enfermedad , Enfermedades Endémicas , Enfermedades de los Párpados/tratamiento farmacológico , Enfermedades de los Párpados/parasitología , Enfermedades de los Párpados/patología , Dermatosis Facial/tratamiento farmacológico , Dermatosis Facial/parasitología , Dermatosis Facial/patología , Humanos , Hipopotasemia/inducido químicamente , Leishmania donovani/genética , Leishmania donovani/aislamiento & purificación , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/patología , Síndrome de QT Prolongado/inducido químicamente , Masculino , Persona de Mediana Edad , Pancitopenia/etiología , España , ViajeRESUMEN
The recommended systemic therapy of choice for discoid lupus erythematosus (DLE) is the 4-aminoquinolone antimalarial hydroxychloroquine. There is limited published information on the likelihood of clinical response and, in particular, what factors influence outcome. We conducted a multicenter observational and pharmacogenetic study of 200 patients with DLE treated with hydroxychloroquine. The primary outcome was clinical response to hydroxychloroquine. We investigated the effects of disease attributes and metabolizing cytochrome P450 (CYP) polymorphisms on clinical outcome. Although the majority of patients responded to hydroxychloroquine, a significant proportion (39%) either failed to respond or was intolerant of the drug. Cigarette smoking and CYP genotype did not have any significant influence on response to hydroxychloroquine. Moreover, multivariate analysis indicated that disseminated disease (odds ratio (OR): 0.21; 95% confidence interval (CI): 0.08-0.52; P<0.001) and concomitant systemic lupus erythematosus (SLE; OR: 0.06; 95% CI: 0.01-0.49; P = 0.009) were significantly associated with lack of response to hydroxychloroquine. These findings suggest that baseline lupus severity and SLE are predictors of response to hydroxychloroquine. A prospective study is now required to further investigate the relationship between disease activity and response to hydroxychloroquine. This will have the potential to further inform the clinical management of this disfiguring photosensitive disease.
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Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Discoide/tratamiento farmacológico , Lupus Eritematoso Discoide/genética , Farmacogenética/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Sistema Enzimático del Citocromo P-450/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo Genético , Estudios Retrospectivos , Fumar , Resultado del TratamientoAsunto(s)
Artritis/etiología , Lupus Eritematoso Sistémico/complicaciones , Mucinosis/complicaciones , Proteinuria/etiología , Artritis/diagnóstico , Biopsia , Diagnóstico Diferencial , Humanos , Lupus Eritematoso Sistémico/patología , Masculino , Persona de Mediana Edad , Mucinosis/patología , Proteinuria/diagnóstico , Articulación de la MuñecaRESUMEN
OBJECTIVES: To prospectively determine the wound complication rate for dermatology inpatients undergoing diagnostic skin biopsies during their admission and to determine significant host and procedural risk factors. DESIGN: Prospective assessment, by a single observer, of 100 postdiagnostic skin biopsy wounds in dermatology inpatients. The following data were recorded for each patient: age and sex, presence of comorbidities, smoking status, dermatologic diagnosis, use of immunosuppressive or antibiotic therapy, place of biopsy (whether in the operation theater or in the ward), grade of physician performing biopsy, biopsy site on the body, type of biopsy (whether elliptical incision, punch, shave, or curettage), and wound closure technique. MAIN OUTCOME MEASURE: Wounds were designated as having had no complication or as being complicated by infection, dehiscence, and/or hematoma. SETTING: A dedicated dermatology inpatient ward in a university teaching hospital. RESULTS: Wound complications occurred in 29 (29%) biopsies, 27 (93%) of which were the result of wound infection. Complications occurred significantly more frequently when biopsies were performed below the waist compared with above the waist (P < .02), in the ward compared with the outpatient operating theater (P < .001), in smokers compared with nonsmokers (P < .001), and in those taking corticosteroids compared with those who were not (P < .001). In addition, elliptical incisional biopsies developed complications more frequently when subcutaneous sutures were not used compared with when they had been used (P < .001). CONCLUSIONS: This study has demonstrated a high rate of wound complications after diagnostic dermatologic surgery on dermatology inpatients with significant host and procedural risk factors. These findings are relevant for other centers with inpatient units where diagnostic biopsies are performed.
Asunto(s)
Biopsia/efectos adversos , Pacientes Internos , Piel/patología , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/métodos , Femenino , Humanos , Incidencia , Masculino , Resistencia a la Meticilina , Persona de Mediana Edad , Quirófanos , Habitaciones de Pacientes , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Factores de Riesgo , Fumar , Infecciones Cutáneas Estafilocócicas/epidemiología , Infecciones Cutáneas Estafilocócicas/fisiopatología , Dehiscencia de la Herida Operatoria/epidemiología , Infección de la Herida Quirúrgica/complicaciones , Infección de la Herida Quirúrgica/epidemiologíaRESUMEN
Photocontact allergic reactions to sunscreen chemicals are investigated by photopatch testing. It has generally been assumed that for photocontact allergy to be shown, the putative pro-allergen must be in the skin at the time of ultraviolet A (UVA) exposure. However, this assumption has not, to our knowledge, been tested. The objective of this study was to determine whether positive photocontact responses can still be elicited when sunscreen chemicals are exposed to UVA prior to application onto the skin. 3 patients known to have positive photocontact reactions to a total of 6 sunscreen chemicals were studied. For conventional photopatch testing, patch test strips were applied onto the back and removed 1 D later, and the area was irradiated with UVA (5 J/cm(2)). For pre-irradiated testing, patches were exposed to the same dose of UVA immediately before application onto the back and then removed 1 D later. Skin responses were visually assessed by a blinded investigator 1 and 2 D after patch test removal. The same photocontact responses of the same magnitude, as previously documented for each patient, were seen at each of the conventional UVA-exposed patch test sites. However, in no patient was a positive response elicited at any of the sites where pre-irradiated patches had been applied. This study shows that positive photocontact responses to sunscreen chemicals do not occur when the putative pro-allergen is irradiated prior to application onto the skin. This suggests that for a photoallergic reaction to occur, the sunscreen chemical needs to be within the skin when activated by UVA.