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1.
Clin Exp Dermatol ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661219

RESUMO

Pyoderma gangrenosum (PG) is an ulcerative inflammatory disorder affecting the lower legs in 80% of cases. The use of biologic medications to treat PG is increasing although there is a limited evidence base to guide treatment choices. In some health systems, such as the UK NHS, limitations are placed on biologic prescribing for PG leading to wide variations in prescribing. A survey of mainly UK clinicians showed that prednisolone remains the first line treatment for PG (90%). Biologics have been used by 66% of clinicians as second line therapy but 19% have had prescribing requests declined. Further research is needed to determine optimal treatment strategies for PG.

3.
J Am Acad Dermatol ; 75(6): 1216-1220.e2, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27742168

RESUMO

BACKGROUND: Pyoderma gangrenosum is a rare inflammatory skin condition. Two prospective studies have evaluated treatments for pyoderma gangrenosum using a primary outcome of healing speed at 6 weeks. OBJECTIVE: Using data from both studies we assessed the predictive value of 3 early predictors for healing at 6 months: speed of healing, Investigator Global Assessment (IGA), and resolution of inflammation, recorded at 2 and 6 weeks. METHODS: Logistic regression models were applied and the effectiveness of the 3 measures was assessed through estimating the positive and negative predictive values and the area under the receiver operating characteristic curve. RESULTS: The positive and negative predictive value at 6 weeks were, respectively, 63.5% (95% confidence interval [CI] 52.4%-73.7%) and 74.6% (95% CI 62.5%-84.5%) for speed of healing; 80% (95% CI 68.7%-88.6%) and 74.2% (95% CI 64.1%-82.7%) for IGA; and 72.1% (95% CI 59.9%-82.3%) and 68.1% (95% CI 57.7%-77.3%) for resolution of inflammation. IGA had the best combined positive predictive value, negative predictive value, and area under the receiver operating characteristic curve at 2 and 6 weeks. LIMITATIONS: We were limited by data available from existing datasets. CONCLUSION: Speed of healing, IGA, and resolution of inflammation were all shown to be good predictors of eventual healing of pyoderma gangrenosum.


Assuntos
Pioderma Gangrenoso/tratamento farmacológico , Índice de Gravidade de Doença , Cicatrização , Adulto , Idoso , Área Sob a Curva , Determinação de Ponto Final , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Pioderma Gangrenoso/complicações , Curva ROC , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento
4.
J Am Acad Dermatol ; 75(5): 940-949, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27502313

RESUMO

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.


Assuntos
Anti-Inflamatórios/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Pioderma Gangrenoso/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Clobetasol/administração & dosagem , Clobetasol/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Prospectivos , Pioderma Gangrenoso/complicações , Qualidade de Vida , Recidiva , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/etiologia , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Resultado do Tratamento
5.
Cochrane Database Syst Rev ; (10): CD010081, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-26443004

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterised by recurrent painful boils in flexural sites, such as the axillae and groin, that affects about 1% of the population, with onset in early adulthood. OBJECTIVES: To assess the effects of interventions for HS in people of all ages. SEARCH METHODS: We searched the following databases up to 13 August 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched five trials registers and handsearched the conference proceedings of eight dermatology meetings. We checked the reference lists of included and excluded studies for further references to relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of all interventions for hidradenitis suppurativa. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and methodological quality and performed data extraction. Our primary outcomes were quality of life, measured by a validated dermatology-specific scale, and adverse effects of the interventions. MAIN RESULTS: Twelve trials, with 615 participants, met our inclusion criteria. The median number of participants in each trial was 27, and median trial duration was 16 weeks. The included studies were conducted over a 32-year time period, from 1983 to 2015. A single RCT that was underpowered to detect clinically meaningful differences investigated most interventions.There were four trials of anti-TNF-α (tumour necrosis factor-alpha) therapies, which included etanercept, infliximab, and adalimumab. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) score in participants with moderate to severe HS by 4.0 points relative to placebo (95% confidence interval (CI) -6.5 to -1.5 points), an effect size approximately equal to the DLQI minimal clinically important difference. We reduced the evidence quality to 'moderate' because the effect size was based on the results of only one study. In a meta-analysis of two studies with 124 participants, standard dose adalimumab 40 mg every other week was ineffective compared with placebo (moderate quality evidence). In a smaller study of 38 participants, of whom only 33 provided efficacy data, infliximab 5 mg/kg treatment improved DLQI by 8.4 DLQI points after eight weeks. Etanercept 50 mg twice weekly was well tolerated but ineffective.In a RCT of 200 participants, no difference was found in surgical complications (week one: risk ratio (RR) 0.78, 95% CI 0.58 to 1.05, moderate quality evidence) or risk of recurrence (after three months: RR 0.96, 95% CI 0.68 to 1.34, moderate quality evidence) in those randomised to receive a gentamicin-collagen sponge prior to primary closure compared with primary closure alone.RCTs of other interventions, including topical clindamycin 1% solution; oral tetracycline; oral ethinylestradiol 50 mcg with either cyproterone acetate 50 mg or norgestrel 500 mcg; intense pulsed light; neodymium-doped yttrium aluminium garnet (Nd:YAG) laser; methylene blue gel photodynamic therapy; and staphage lysate, were relatively small studies, preventing firm conclusions due to imprecision. AUTHORS' CONCLUSIONS: Many knowledge gaps exist in RCT evidence for HS. Moderate quality evidence exists for adalimumab, which improves DLQI score when 40 mg is given weekly, twice the standard psoriasis dose. However, the 95% confidence interval includes an effect size of only 1.5 DLQI points, which may not be clinically relevant, and the safety profile of weekly dosing has not been fully established. Infliximab also improves quality of life, based on moderate quality evidence.More RCTs are needed in most areas of HS care, particularly oral treatments and the type and timing of surgical procedures. Outcomes should be validated, ideally, including a minimal clinically important difference for HS.


Assuntos
Hidradenite Supurativa/terapia , Adulto , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Terapia de Luz Pulsada Intensa/métodos , Terapia a Laser/métodos , Masculino , Fotoquimioterapia/métodos , Fototerapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
6.
J Allergy Clin Immunol ; 129(6): 1554-61, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22502796

RESUMO

BACKGROUND: Many immune-mediated diseases are associated with low levels of vitamin D and sunlight. UV light or supplementation with vitamin D can increase regulatory T-cell activity and prevent animal models of autoimmune disease. Increasing population vitamin D levels may therefore alleviate the burden of human immune-mediated disease. OBJECTIVE: To determine the responses of circulating 25-hydroxyvitamin D [25(OH)D] levels, regulatory T-cell numbers, and immune function to UV light exposure in patients being treated for skin disease. METHODS: Twenty-four subjects with skin disease from the North of Scotland were recruited between December and March. At baseline, and after 2 and 4 weeks of narrowband UV light exposure, we measured peripheral blood 25(OH)D level, numbers of regulatory T cells (CD4(+)CD25(hi)FoxP3(+)), and T-cell proliferative and cytokine responses to anti-CD3/CD28 stimulation. RESULTS: Median (interquartile range) narrowband UV-B received during the study was 39.1 (30.9) as standard erythema dose, comparable to a quarter of the median summer sunlight exposure received locally. This increased the 25(OH)D level from a mean ± SD of 34 ± 17 nmol/L to 58 ± 16 nmol/L after 2 weeks and 78 ± 19 nmol/L after 4 weeks. The mean proportion of circulating regulatory T cells increased from 0.5% to 1.6% CD3(+) cells, which significantly correlated with the increased 25(OH)D level. UV treatment was also followed by reduced proliferative and IL-10 responses to anti-CD3/CD28 independent of the 25(OH)D level. CONCLUSION: Narrowband UV light reduces systemic immune responsiveness via the induction of regulatory T cells. Light and 25(OH)D levels may affect particular immune functions independently. The levels of serum 25(OH)D over which these effects are apparent should guide future interventions.


Assuntos
Imunidade/efeitos da radiação , Raios Ultravioleta , Vitamina D/análogos & derivados , Adulto , Idoso , Citocinas/biossíntese , Feminino , Humanos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Estações do Ano , Luz Solar , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Fatores de Tempo , Vitamina D/sangue , Vitamina D/efeitos da radiação , Adulto Jovem
7.
Contact Dermatitis ; 67(1): 9-19, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22500724

RESUMO

BACKGROUND: The pattern of contact sensitization to the supposedly most important allergens assembled in the baseline series differs between countries, presumably at least partly because of exposure differences. Objectives. To describe the prevalence of contact sensitization to allergens tested in consecutive patients in the years 2007 and 2008, and to discuss possible differences. METHODS: Data from the 39 departments in 11 European countries comprising the European Surveillance System on Contact Allergy network (www.essca-dc.org) in this period have been pooled and analysed according to common standards. RESULTS: Patch test results with the European baseline series, and country-specific or department-specific additions to it, obtained in 25 181 patients, showed marked international variation. Metals and fragrances are still the most frequent allergens across Europe. Some allergens tested nationally may be useful future additions to the European baseline series, for example methylisothiazolinone, whereas a few long-term components of the European baseline series, namely primin and clioquinol, no longer warrant routine testing. CONCLUSIONS: The present analysis points to 'excess' prevalences of specific contact sensitization in some countries, although interpretation must be cautious if only few, and possibly specialized, centres are representing one country. A comparison as presented may help to target in-depth research into possible causes of 'excess' exposure, and/or consideration of methodological issues, including modifications to the baseline series.


Assuntos
Alérgenos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Testes do Emplastro , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Metais/toxicidade , Doenças Profissionais/diagnóstico , Doenças Profissionais/epidemiologia , Perfumes/efeitos adversos , Prevalência
8.
Front Immunol ; 12: 763877, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35069536

RESUMO

Malignant melanoma is an aggressive form of cancer, which can be treated with anti-CTLA-4 and anti-PD-1 checkpoint inhibitor antibodies but while anti-CTLA-4 antibodies have clear benefits for some patients with melanoma, productive responses are difficult to predict and often associated with serious immune related adverse events. Antibodies specific to CTLA-4 bind two major isoforms of CTLA-4 in humans, the receptor isoform and a second naturally secretable, soluble isoform - sCTLA-4. The primary aim here was to examine the effect of selectively blocking the function of sCTLA-4 on in vitro immune responses from volunteer healthy or melanoma patient PBMC samples. Addition of recombinant sCTLA-4 to healthy PBMC samples demonstrated sCTLA-4 to have immunosuppressive capacity comparable to recombinant CTLA4-Ig, partially reversible upon antibody blockade. Further, we identified a mechanistic relationship where melanoma patient TGFß2 serum levels correlated with sCTLA-4 levels and provided the basis for a novel protocol to enhance sCTLA-4 production and secretion by T cells with TGFß2. Finally, a comparison of selective antibody blockade of sCTLA-4 demonstrated that both healthy and melanoma patient effector cytokine responses can be significantly increased. Overall, the data support the notion that sCTLA-4 is a contributory factor in cancer immune evasion.


Assuntos
Anticorpos Antineoplásicos/imunologia , Antígeno CTLA-4/imunologia , Inibidores de Checkpoint Imunológico , Melanoma , Proteínas de Neoplasias/imunologia , Fator de Crescimento Transformador beta2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Melanoma/imunologia , Melanoma/terapia , Camundongos , Pessoa de Meia-Idade
9.
Postgrad Med J ; 86(1018): 466-71, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20709768

RESUMO

Vitiligo is a common disease that causes a great degree of psychological distress. In its classical forms it is easily recognised and diagnosed. This review provides an evidence based outline of the management of vitiligo, particularly with the non-specialist in mind. Treatments for vitiligo are generally unsatisfactory. The initial approach to a patient who is thought to have vitiligo is to make a definite diagnosis, offer psychological support, and suggest supportive treatments such as the use of camouflage cosmetics and sunscreens, or in some cases after discussion the option of no treatment. Active therapies open to the non-specialist, after an explanation of potential side effects, include the topical use of potent or highly potent steroids or calcineurin inhibitors for a defined period of time (usually 2 months), following which an assessment is made to establish whether or not there has been a response. Patients whose condition is difficult to diagnose, unresponsive to straightforward treatments, or is causing psychological distress, are usually referred to a dermatologist. Specialist dermatology units have at their disposal phototherapy, either narrow band ultraviolet B or in some cases photochemotherapy, which is the most effective treatment presently available and can be considered for symmetrical types of vitiligo. Depigmenting treatments and possibly surgical approaches may be appropriate for vitiligo in selected cases. There is no evidence that presently available systemic treatments are helpful and safe in vitiligo. There is a need for further research into the causes of vitiligo, and into discovering better treatments.


Assuntos
Vitiligo/diagnóstico , Vitiligo/terapia , Inibidores de Calcineurina , Medicina Baseada em Evidências/métodos , Glucocorticoides/uso terapêutico , Humanos , Fototerapia/métodos , Guias de Prática Clínica como Assunto
10.
Contact Dermatitis ; 61(5): 287-90, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19878244

RESUMO

BACKGROUND: Propolis is widely used in 'natural' cosmetics, remedies, and over-the-counter products. The incidence of propolis allergy is increasing, and cross-reaction with fragrance mix I (FMII), colophonium, and Myroxylon pereirae can occur. OBJECTIVES: To find out the prevalence and clinical relevance of positive patch tests to propolis and assess cross-reactions with Myroxylon pereirae, colophonium, FMI, and beeswax. METHODS: Two thousand eight hundred and twenty-eight subjects in 10 UK centres were patch tested with propolis and beeswax. Generic data were acquired from British Contact Dermatology Society (BCDS) database and further relevant information was requested by survey of participating centres. RESULTS: The prevalence of propolis allergy was 1.9% (55/2828). Out of these 55 subjects, only 4 (7.2%) were allergic to beeswax, 22 (40%) to Myroxylon pereirae, 15 (27.2%) to colophonium, and 6 (10.9%) to FMI. Additional data for 41 propolis allergic subjects were collected by questionnaire. Hands were the most common sites of involvement, and cosmetics were the most common source of contact. Eight out of 12 subjects reported improvement in eczema following avoidance of propolis. CONCLUSIONS: Propolis is an important allergen of increasing frequency and its inclusion in BCDS baseline series is appropriate. Cross-sensitivity to beeswax is rare.


Assuntos
Anti-Infecciosos/efeitos adversos , Dermatite de Contato/epidemiologia , Própole/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Cosméticos/efeitos adversos , Cosméticos/química , Reações Cruzadas , Dermatite de Contato/etiologia , Feminino , Dermatoses da Mão/epidemiologia , Dermatoses da Mão/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Myroxylon/efeitos adversos , Testes do Emplastro , Perfumes/efeitos adversos , Fitoterapia/efeitos adversos , Resinas Vegetais/efeitos adversos , Reino Unido/epidemiologia , Ceras/efeitos adversos , Adulto Jovem
11.
Contact Dermatitis ; 61(1): 31-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19659962

RESUMO

BACKGROUND: Continual surveillance based on patch test results has proved useful for the identification of contact allergy. OBJECTIVES: To provide a current view on the spectrum of contact allergy to important sensitizers across Europe. PATIENTS/METHODS: Clinical and patch test data of 19 793 patients patch tested in 2005/2006 in the 31 participating departments from 10 European countries (the European Surveillance System on Contact Allergies' (ESSCA) www.essca-dc.org) were descriptively analysed, aggregated to four European regions. RESULTS: Nickel sulfate remains the most common allergen with standardized prevalences ranging from 19.7% (central Europe) to 24.4% (southern Europe). While a number of allergens shows limited variation across the four regions, such as Myroxylon pereirae (5.3-6.8%), cobalt chloride (6.2-8.8%) or thiuram mix (1.7-2.4%), the differences observed with other allergens may hint on underlying differences in exposures, for example: dichromate 2.4% in the UK (west) versus 4.5-5.9% in the remaining EU regions, methylchloroisothiazolinone/methylisothiazolinone 4.1% in the South versus 2.1-2.7% in the remaining regions. CONCLUSIONS: Notwithstanding residual methodological variation (affecting at least some 'difficult' allergens) tackled by ongoing efforts for standardization, a comparative analysis as presented provides (i) a broad overview on contact allergy frequencies and (ii) interesting starting points for further, in-depth investigation.


Assuntos
Alérgenos , Dermatite Alérgica de Contato/etiologia , Dermatite Atópica/etiologia , Dermatite Ocupacional/etiologia , Adulto , Dermatite Alérgica de Contato/epidemiologia , Dermatite Atópica/epidemiologia , Dermatite Ocupacional/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência
12.
J Invest Dermatol ; 138(3): 534-541, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29054603

RESUMO

Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts, respectively, and 3,421 participants were in the non-biologic cohort. A total of 283 patients had a serious infection; the incidence rates with 95% confidence intervals (CI) per 1,000 person-years were as follows: non-biologic, 14.2 (11.5-17.4); etanercept, 15.3 (11.6-20.1); adalimumab, 13.9 (11.4-16.6); and ustekinumab, 15.1 (10.8-21.1). No significant increases in the risk of serious infection were observed for etanercept (hazard ratio [HR] = 1.10, 95% CI = 0.75-1.60), adalimumab (HR = 0.93, 95% CI = 0.69-1.26), or ustekinumab (HR = 0.92, 95% CI = 0.60-1.41) compared with non-biologic systemic therapies or methotrexate-only (etanercept: HR = 1.47, 95% CI = 0.95-2.28; adalimumab: HR = 1.26, 95% CI = 0.86-1.84; ustekinumab: HR = 1.22, 95% CI = 0.75-1.99). The risk of serious infection should not be a key discriminator for patients and clinicians when choosing between non-biologic systemic therapies, etanercept, adalimumab, and ustekinumab for the treatment of psoriasis.


Assuntos
Terapia Biológica/efeitos adversos , Infecções/etiologia , Psoríase/tratamento farmacológico , Adulto , Humanos , Incidência , Infecções/epidemiologia , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Fator de Necrose Tumoral alfa/antagonistas & inibidores
15.
JAMA Dermatol ; 151(8): 854-61, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25922903

RESUMO

IMPORTANCE: Anogenital warts are a common disorder associated with significant physical and mental distress and a substantial cause of health care costs. OBJECTIVE: To assess the efficacy of the topical application of nitric oxide delivered using acidified nitrite. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, controlled, dose-ranging clinical trial was conducted in European genitourinary medicine clinics between December 20, 2001, and January 14, 2003. Analysis was by intent to treat for all individuals initiating therapy. Participants included male and female volunteers older than 18 years with between 2 and 50 external anogenital warts. A total of 299 individuals from 40 centers were randomized to a control arm and a treatment arm that received 3 doses of acidified nitrite applied topically for 12 weeks with an additional 12 weeks of follow-up, with the final follow-up visit on January 14, 2003. INTERVENTIONS: Placebo nitrite cream and placebo citric acid cream were applied twice daily. Active treatment was divided as low dose (sodium nitrite, 3%, with citric acid, 4.5%, creams applied twice daily), middle dose (sodium nitrite, 6%, with citric acid, 9%, creams applied once daily at night, with placebo applied in the morning), and high dose (sodium nitrite, 6%, with citric acid, 9%, creams applied twice daily). MAIN OUTCOMES AND MEASURES: The primary outcome was proportion of patients with complete clinical clearance of target warts; secondary outcomes were reduction in target wart area and safety. RESULTS: Complete clinical clearance at 12 weeks occurred in 10 of 74 patients (14%; 95% CI, 6%-21%) with placebo; 11 of 72 (15%; 95% CI, 7%-24%) with low-dose treatment; 17 of 74 (23%; 95% CI, 13%-33%) with middle-dose treatment; and 22 of 70 (31%; 95% CI, 21%-42%) with high-dose treatment (P = .01). Reduction in target wart area, time to clearance, and patient and investigator assessments supported the superiority of the high-dose therapy vs placebo. There were no systemic or serious adverse events associated with treatment. However, there was a dose-related increase in itching, pain, edema, and staining of the anogenital skin associated with the active treatment. Overall, 21 patients withdrew from active treatment because of adverse events compared with none using placebo. CONCLUSIONS AND RELEVANCE: Use of sodium nitrite, 6%, with citric acid, 9%, twice daily is more effective than placebo in the treatment of anogenital warts. Treatment was associated with local irritant adverse effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02015260.


Assuntos
Doenças do Ânus/tratamento farmacológico , Ácido Cítrico/uso terapêutico , Condiloma Acuminado/tratamento farmacológico , Nitrito de Sódio/uso terapêutico , Administração Tópica , Adulto , Doenças do Ânus/virologia , Ácido Cítrico/administração & dosagem , Ácido Cítrico/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nitrito de Sódio/administração & dosagem , Nitrito de Sódio/efeitos adversos , Resultado do Tratamento , Adulto Jovem
16.
BMJ ; 350: h2958, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-26071094

RESUMO

OBJECTIVE: To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management. DESIGN: Multicentre, parallel group, observer blind, randomised controlled trial. SETTING: 39 UK hospitals, recruiting from June 2009 to November 2012. PARTICIPANTS: 121 patients (73 women, mean age 54 years) with clinician diagnosed pyoderma gangrenosum. Clinical diagnosis was revised in nine participants after randomisation, leaving 112 participants in the analysis set (59 ciclosporin; 53 prednisolone). INTERVENTION: Oral prednisolone 0.75 mg/kg/day compared with ciclosporin 4 mg/kg/day, to a maximum dose of 75 and 400 mg/day, respectively. MAIN OUTCOME MEASURES: The primary outcome was speed of healing over six weeks, captured using digital images and assessed by blinded investigators. Secondary outcomes were time to healing, global treatment response, resolution of inflammation, self reported pain, quality of life, number of treatment failures, adverse reactions, and time to recurrence. Outcomes were assessed at baseline and six weeks and when the ulcer had healed (to a maximum of six months). RESULTS: Of the 112 participants, 108 had complete primary outcome data at baseline and six weeks (57 ciclosporin; 51 prednisolone). Groups were balanced at baseline. The mean (SD) speed of healing at six weeks was -0.21 (1.00) cm(2)/day in the ciclosporin group compared with -0.14 (0.42) cm(2)/day in the prednisolone group. The adjusted mean difference showed no between group difference (0.003 cm(2)/day, 95% confidence interval -0.20 to 0.21; P=0.97). By six months, ulcers had healed in 28/59 (47%) participants in the ciclosporin group compared with 25/53 (47%) in the prednisolone group. In those with healed ulcers, eight (30%) receiving ciclosporin and seven (28%) receiving prednisolone had a recurrence. Adverse reactions were similar for the two groups (68% ciclosporin and 66% prednisolone), but serious adverse reactions, especially infections, were more common in the prednisolone group. CONCLUSION: Prednisolone and ciclosporin did not differ across a range of objective and patient reported outcomes. Treatment decisions for individual patients may be guided by the different side effect profiles of the two drugs and patient preference. Trial registration Current Controlled Trials ISRCTN35898459.


Assuntos
Ciclosporina/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Prednisolona/administração & dosagem , Pioderma Gangrenoso/tratamento farmacológico , Úlcera Varicosa/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Pioderma Gangrenoso/patologia , Qualidade de Vida , Recidiva , Fatores de Tempo , Resultado do Tratamento , Reino Unido , Úlcera Varicosa/patologia
17.
J Invest Dermatol ; 135(11): 2632-2640, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26053050

RESUMO

Drug survival reflects a drug's effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09-1.37), being a current smoker (HR 1.19; 95% CI: 1.03-1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00-1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71-0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45-1.84) or infliximab (HR 1.56; 95% CI: 1.16-2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37-0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.


Assuntos
Produtos Biológicos/administração & dosagem , Dose Máxima Tolerável , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Sistema de Registros , Adalimumab/administração & dosagem , Adulto , Produtos Biológicos/farmacocinética , Terapia Biológica/métodos , Estudos de Coortes , Dermatologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Etanercepte/administração & dosagem , Etanercepte/farmacocinética , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/farmacocinética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sociedades Médicas , Ustekinumab/administração & dosagem , Ustekinumab/farmacocinética
18.
Curr Opin Investig Drugs ; 4(5): 608-13, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12833658

RESUMO

Alefacept is a lymphocyte function-associated antigen-3/IgG1 fusion protein that inhibits T-cells by antagonizing CD2, which has been developed and launched by Biogen for the potential treatment of psoriasis. In February 2003, Biogen launched alefacept in the US for use in adults with moderate-to-severe chronic plaque psoriasis, and by March 2003, the company was preparing for psoriasis trials to commence in Japan by the end of December 2003.


Assuntos
Proteínas Recombinantes de Fusão/uso terapêutico , Tecnologia Farmacêutica/métodos , Alefacept , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antígenos CD58/uso terapêutico , Humanos , Proteínas Recombinantes de Fusão/farmacologia , Tecnologia Farmacêutica/legislação & jurisprudência
19.
Am J Clin Dermatol ; 15(2): 77-86, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24425466

RESUMO

Acne is a common skin condition in adolescents. It is not uncommon in childhood and it persists into adulthood. A broad range of acne treatments are available and have been shown to be safe and effective in adolescents and adults. However, there is limited literature regarding acne treatment in childhood and its available therapeutic options. It seems reasonable to extrapolate findings of the various studies reported on treatment of acne in the adolescent and adult age group, with the exclusion of the use of tetracycline derivatives. As clinicians, we must be more familiar with the clinical presentation of acne and available treatment options in our younger patients. Early recognition of acne with prompt and appropriate initiation of therapy in childhood will help prevent severe scarring in children.


Assuntos
Acne Vulgar/tratamento farmacológico , Acne Vulgar/etiologia , Acne Vulgar/diagnóstico , Acne Vulgar/epidemiologia , Administração Tópica , Hiperplasia Suprarrenal Congênita/complicações , Adrenarca , Antibacterianos/uso terapêutico , Peróxido de Benzoíla/uso terapêutico , Criança , Pré-Escolar , Cicatriz/prevenção & controle , Fármacos Dermatológicos/uso terapêutico , Dermatomicoses/microbiologia , Quimioterapia Combinada , Dermatoses Faciais/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Malassezia/isolamento & purificação , Masculino , Síndrome do Ovário Policístico/complicações , Retinoides/uso terapêutico , Índice de Gravidade de Doença , Pele/microbiologia
20.
Am J Clin Dermatol ; 14(5): 351-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23996075

RESUMO

Acne vulgaris is a common condition in adolescence and also for many women of childbearing age. The management of acne in pregnancy is complicated by the lack of clinical studies and pharmacokinetic data in this patient population and safety concerns regarding retinoid use in pregnancy. Of primary concern to both patients and clinicians is the safety profile of medications used during pregnancy. This review seeks to clarify what management options are available to treat acne during pregnancy and what data are available to guide decision making. Topical treatments are considered the safest option during pregnancy. They have the best safety profile and minimize the levels of systemic absorption, and therefore the least risk of fetal exposure. If these are applied properly with a strong emphasis on adherence, excellent results can be achieved.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Acne Vulgar/terapia , Administração Cutânea , Administração Oral , Corticosteroides/uso terapêutico , Antibacterianos/administração & dosagem , Peróxido de Benzoíla/uso terapêutico , Feminino , Humanos , Terapia a Laser , Gravidez , Complicações na Gravidez/terapia , Retinoides/uso terapêutico
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