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1.
J Drugs Dermatol ; 19(9): 889-892, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026746

RESUMO

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.


Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fármacos Dermatológicos/efeitos adversos , Erupção por Droga/etiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Antivirais/uso terapêutico , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Erupção por Droga/epidemiologia , Erupção por Droga/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Incidência , Masculino , Pandemias , Prognóstico , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia
2.
Medicine (Baltimore) ; 99(33): e21266, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871985

RESUMO

Chronic spontaneous urticaria (CSU) is a common dermatologic disease that seriously affects patient quality of life. The choice of therapy to control the disease and prevent its recurrence has always presented a difficult clinical issue. Previous studies have shown that traditional Chinese medicine is a safe and effective treatment for CSU. Recently, the temporal rhythms of CSU, a disease characterized by intermittent flares of active disease and periods of little or no disease, have attracted the attention of traditional Chinese medicine researchers. We designed a multicenter, randomized, controlled study to evaluate the efficacy and safety of combining a Chinese herbal formulation with acupuncture using shu-stream acupoints applied on the corresponding time meridians during disease exacerbations. We plan to recruit 111 outpatients with CSU aged 18 to 65 years. Participants will be randomized to 1 of the 3 groups: group A, which will be given basic acupuncture and the herbal formulation dangui yinzi; group B, which will be given danggui yinzi and shu-stream acupuncture; and a control group, which will be given danggui yinzi alone. Patients will be treated for 4 weeks and followed for 8 additional weeks. Investigators will evaluate the following parameters: the symptoms and side effects of treatment, quality of life (using the chronic urticaria quality of life questionnaire), and overall patient condition. Each week, patients will also complete the measurement of 7-day urticarial activity score. This is the first use of a combination of shu-stream acupoints and Chinese herbal medicine in the treatment of CSU. If successful, it will prove to be a simple, inexpensive, treatment strategy for solving a difficult clinical problem.


Assuntos
Terapia por Acupuntura , Urticária Crônica/terapia , Fármacos Dermatológicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Pontos de Acupuntura , Terapia por Acupuntura/efeitos adversos , Terapia por Acupuntura/métodos , Adolescente , Adulto , Idoso , Assistência Ambulatorial , Terapia Combinada , Fármacos Dermatológicos/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Seleção de Pacientes , Resultado do Tratamento , Adulto Jovem
3.
Cochrane Database Syst Rev ; 9: CD013206, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32927498

RESUMO

BACKGROUND: Eczema is a common and chronic, relapsing, inflammatory skin disorder. It seriously impacts quality of life and economic outcomes, especially for those with moderate to severe eczema. Various treatments allow sustained control of the disease; however, their relative benefit remains unclear due to the limited number of trials directly comparing treatments. OBJECTIVES: To assess the comparative efficacy and safety of different types of systemic immunosuppressive treatments for moderate to severe eczema using NMA and to generate rankings of available systemic immunosuppressive treatments for eczema according to their efficacy and safety. SEARCH METHODS: We searched the following databases up to August 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. SELECTION CRITERIA: All randomised controlled trials (RCTs) of systemic immunosuppressive agents for moderate to severe atopic eczema when compared against placebo or any other eligible eczema treatment. DATA COLLECTION AND ANALYSIS: We synthesised data using pair-wise analysis and NMA to compare treatments and rank them according to their effectiveness. Effectiveness was assessed primarily by determining the proportion of participants who achieved at least 75% improvement in the Eczema Area and Severity Index (EASI75) and improvement in the Patient-Oriented Eczema Measure (POEM). Safety was evaluated primarily by considering the proportion of participants with serious adverse events (SAEs) and infection. We deemed short-term follow-up as ≤ 16 weeks and long-term follow-up as > 16 weeks. We assessed the certainty of the body of evidence from the NMA for these primary outcomes using six domains of CiNEMA grading. MAIN RESULTS: We included a total of 74 studies, with 8177 randomised participants. Approximately 55% of participants were male, with average age of 32 years (range 2 to 84 years), although age and gender were unreported for 419 and 902 participants, respectively. Most of the included trials were placebo controlled (65%), 34% were head-to-head studies (15% assessed the effects of different doses of the same drug), and 1% were multi-armed studies with both an active comparator and a placebo. All trials included participants with moderate to severe eczema, but 62% of studies did not separate data by severity; 38% of studies assessed only severe eczema. The total duration of included trials ranged from 2 weeks to 60 months, whereas treatment duration varied from a single dose (CIM331, KPL-716) to 60 months (methotrexate (MTX)). Seventy studies were available for quantitative synthesis; this review assessed 29 immunosuppressive agents from three classes of interventions. These included (1) conventional treatments, with ciclosporin assessed most commonly; (2) small molecule treatments, including phosphodiesterase (PDE)-4 inhibitors, tyrosine kinase inhibitors, and Janus kinase (JAK) inhibitors; and (3) biological treatments, including anti-CD31 receptors, anti-interleukin (IL)-22, anti-IL-31, anti-IL-13, anti-IL-12/23p40, anti-OX40, anti-TSLP, anti-CRTH2, and anti-immunoglobulin E (IgE) monoclonal antibodies, but most commonly dupilumab. Most trials (73) assessed outcomes at a short-term duration ranging from 2 to 16 weeks, whereas 33 trials assessed long-term outcomes, with duration ranging from 5 to 60 months. All participants were from a hospital setting. Fifty-two studies declared a source of funding, and of these, pharmaceutical companies funded 88%. We rated 37 studies as high risk; 21, unclear risk, and 16, low risk of bias, with studies most commonly at high risk of attrition bias. Network meta-analysis suggests that dupilumab ranks first for effectiveness when compared with other biological treatments. Dupilumab is more effective than placebo in achieving EASI75 (risk ratio (RR) 3.04, 95% confidence interval (CI) 2.51 to 3.69) and improvement in POEM score (mean difference 7.30, 95% CI 6.61 to 8.00) at short-term follow-up (high-certainty evidence). Very low-certainty evidence means we are uncertain of the effects of dupilumab when compared with placebo, in terms of the proportion of participants who achieve EASI75 (RR 2.59, 95% CI 1.87 to 3.60) at longer-term follow-up. Low-certainty evidence indicates that tralokinumab may be more effective than placebo in achieving short-term EASI75 (RR 2.54, 95% CI 1.21 to 5.34), but there was no evidence for tralokinumab to allow us to assess short-term follow-up of POEM or long-term follow-up of EASI75. We are uncertain of the effect of ustekinumab compared with placebo in achieving EASI75 (long-term follow-up: RR 1.17, 95% CI 0.40 to 3.45; short-term follow-up: RR 0.91, 95% CI 0.28 to 2.97; both very low certainty). We found no evidence on ustekinumab for the POEM outcome. We are uncertain whether other immunosuppressive agents that targeted our key outcomes influence the achievement of short-term EASI75 compared with placebo due to low- or very low-certainty evidence. Dupilumab and ustekinumab were the only immunosuppressive agents evaluated for longer-term EASI75. Dupilumab was the only agent evaluated for improvement in POEM during short-term follow-up. Low- to moderate-certainty evidence indicates a lower proportion of participants with SAEs after treatment with QAW039 and dupilumab compared to placebo during short-term follow-up, but low- to very low-certainty evidence suggests no difference in SAEs during short-term follow-up of other immunosuppressive agents compared to placebo. Evidence for effects of immunosuppressive agents on risk of any infection during short-term follow-up and SAEs during long-term follow-up compared with placebo was of low or very low certainty but did not indicate a difference. We did not identify differences in other adverse events (AEs), but dupilumab is associated with specific AEs, including eye inflammation and eosinophilia. AUTHORS' CONCLUSIONS: Our findings indicate that dupilumab is the most effective biological treatment for eczema. Compared to placebo, dupilumab reduces eczema signs and symptoms in the short term for people with moderate to severe atopic eczema. Short-term safety outcomes from clinical trials did not reveal new safety concerns with dupilumab. Overall, evidence for the efficacy of most other immunosuppressive treatments for moderate to severe atopic eczema is of low or very low certainty. Given the lack of data comparing conventional with newer biological treatments for the primary outcomes, there remains high uncertainty for ranking the efficacy and safety of conventional treatments such as ciclosporin and biological treatments such as dupilumab. Most studies were placebo-controlled and assessed only short-term efficacy of immunosuppressive agents. Further adequately powered head-to-head RCTs should evaluate comparative long-term efficacy and safety of available treatments for moderate to severe eczema.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Eczema/tratamento farmacológico , Imunossupressores/uso terapêutico , Metanálise em Rede , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Ustekinumab/uso terapêutico , Adulto Jovem
4.
Croat Med J ; 61(4): 333-337, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32881431

RESUMO

AIM: To assess C-reactive protein to albumin ratio (CAR) before and after treatment with biological agents in patients with psoriasis to determine whether CAR can be used as an inflammation biomarker. METHODS: Medical records of patients with psoriasis treated with biological agents at the Department of Dermatology, Gazi University Hospital were retrospectively evaluated between June 2018 and August 2019. The patients were divided into four groups based on the type of treatment (adalimumab, ustekinumab, infliximab, secukinumab). CAR was evaluated before and three months after treatment. RESULTS: The study enrolled 157 patients with psoriasis vulgaris (91 male) aged between 18 and 85. CAR significantly decreased in all treatment groups (adalimumab group P<0.001; ustekinumab P=0.006; infliximab P=0.007; secukinumab P<0.001). The most prominent decrease in CAR was observed in patients treated with secukinumab (median CAR before treatment 1.52 [1.01-3.04] and after treatment 0.84 [0.62-0.99]). CONCLUSION: CAR may be a good indicator of systemic inflammation in psoriasis patients treated with biological agents.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Fármacos Dermatológicos/uso terapêutico , Inflamação/sangue , Psoríase/tratamento farmacológico , Albumina Sérica/metabolismo , Adalimumab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Psoríase/sangue , Estudos Retrospectivos , Resultado do Tratamento , Ustekinumab/uso terapêutico , Adulto Jovem
5.
Mayo Clin Proc ; 95(8): 1684-1695, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32753140

RESUMO

OBJECTIVE: To characterize the clinicopathologic findings, comorbidities, and treatment outcomes of women with lichen planopilaris (LPP). METHOD: In this retrospective review of women with LPP at Mayo Clinic from 1992 to 2016, we searched for scarring alopecia in all female patients aged 1 to 100 years from January 1, 1992, through December 31, 2016. Men were excluded from this study to more accurately determine the association of hormonal factors in LPP pathogenesis. Two hundred thirty-two patients were included as they met diagnostic criteria for LPP based on clinicopathologic correlation, with 217 having confirmatory biopsies. RESULTS: We identified 232 women with LPP (mean age, 59.8 years). Of those, 92.7% (215) presented with hair loss; 23.7% (55) had preceding inflammation; 30.6% (71) had thyroid disease, including hypothyroidism (23.2%; 54); and 9.4% (22) had vitamin D deficiency. Incidence of depression and anxiety was 45.7% (106) and 41.8% (97), respectively. History of total abdominal hysterectomy/bilateral salpingo-oophorectomies and hormone replacement therapy was found in 16.8% (39) and 16.4% (38), respectively. Lichen planus at other body sites occurred in 16.4% (38) of patients; and 53.2% (123) had slowing of disease progression or disease stabilization, often requiring combination therapies. In those who achieved slowing or stabilization of disease, mean time to recurrence was 1.8 year. The mean time to remission was 1.1 year. CONCLUSION: The typical LPP patient is a 60-year-old female with vertex scarring alopecia who presents with burning, erythema, inflammation, and scale. Almost half of patients will have comorbid autoimmunity. As previously reported, LPP is associated with thyroid disease. We also found higher rates of depression, anxiety, nutritional deficiencies, and skin cancer than reported in the general population.


Assuntos
Líquen Plano/patologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Alopecia/patologia , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Líquen Plano/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele/patologia , Adulto Jovem
7.
PLoS One ; 15(7): e0235500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614886

RESUMO

INTRODUCTION: Clinical trials often suffer from significant recruitment barriers, poor adherence, and dropouts, which increase costs and negatively affect trial outcomes. The aim of this study was to examine whether making it virtual and reward-based would enable nationwide recruitment, identify patients with variable disease severity, achieve high adherence, and reduce dropouts. METHODS: In a siteless, virtual feasibility study, individuals with atopic dermatitis (AD) were recruited online. During the 8-week study, subjects used their smartphones weekly to photograph target AD lesions, and completed patient-oriented eczema measure (POEM) and treatment use questionnaires. In return, subjects were rewarded every week with personalized lifestyle reports based on their DNA. RESULTS: Over the course of the 11 day recruitment period, 164 (82% women and 18% men) filled in the form to participate, of which 65 fulfilled the inclusion criteria and signed the informed consent. Ten were excluded as they did not complete the mandatory study task of returning the DNA sample. 55 (91% women, 9% men) subjects returned the DNA sample and were enrolled throughout Denmark, the majority outside the Copenhagen capital region in rural areas with relatively low physician coverage. The mean age was 28.5 (SD ±9.5 years, range 18-52 years). The baseline POEM score was 14.5±5.6 (range 6-28). Based on the POEM, 7 individuals had mild, 28 had moderate, 17 had severe, and 3 had very severe eczema. The retention rate was 96% as 53 out of 55 enrolled completed the study. The adherence was very high, and more than 90% of all study tasks were completed. Follow up of 41 subjects showed that 90% would take part again or continue if the study had been longer. CONCLUSION: A virtual trial design enables recruitment with broad geographic reach and throughout the full spectrum of disease severity. Providing personalized genetic reports as a reward seems to contribute to high adherence and retention.


Assuntos
Dermatite Atópica/psicologia , Eczema/patologia , Recompensa , Cooperação e Adesão ao Tratamento , Adolescente , Adulto , DNA/análise , Dermatite Atópica/genética , Dermatite Atópica/patologia , Dermatite Atópica/terapia , Fármacos Dermatológicos/uso terapêutico , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fototerapia , Índice de Gravidade de Doença , Smartphone , Inquéritos e Questionários , Adulto Jovem
8.
Dermatol Online J ; 26(3)2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32609453

RESUMO

Pityriasis rubra pilaris is a rare psoriasiform dermatitis. Treatment has been adopted from psoriasis protocols, with topical corticosteroids and systemic retinoids as first-line agents, followed by escalation to biologics for recalcitrant disease. We report a patient with resistant pityriasis rubra pilaris who dramatically improved with acitretin and ustekinumab, a combination not well documented in the literature. The purpose of this letter is to emphasize the potential benefit of dual therapy in patients who fail traditional pityriasis rubra pilaris treatment regimens.


Assuntos
Acitretina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Pitiríase Rubra Pilar/tratamento farmacológico , Ustekinumab/uso terapêutico , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Humanos , Ceratolíticos/uso terapêutico , Masculino
9.
J Med Chem ; 63(13): 7163-7185, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32511913

RESUMO

Dermatologic disorders such as atopic dermatitis arise from genetic and environmental causes and are complex and multifactorial in nature. Among possible risk factors, aberrant immunological reactions are one of the leading etiologies. Immunosuppressive agents including topical steroids are common treatments for these disorders. Despite their reliability in clinical settings, topical steroids display side effects, typified by skin thinning. Accordingly, there is a need for alternate effective and well-tolerated therapies. As part of our efforts to investigate new immunomodulators, we have developed a series of JAK inhibitors, which incorporate novel three-dimensional spiro motifs and unexpectedly possess both excellent physicochemical properties and antidermatitis efficacy in the animal models. One of these compounds, JTE-052 (ent-60), also known as delgocitinib, has been shown to be effective and well-tolerated in human clinical trials and has recently been approved in Japan for the treatment of atopic dermatitis as the first drug among Janus kinase inhibitors.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/farmacologia , Desenho de Fármacos , Inibidores de Janus Quinases/farmacologia , Janus Quinases/antagonistas & inibidores , Pirróis/farmacologia , Fármacos Dermatológicos/uso terapêutico , Humanos , Concentração Inibidora 50 , Inibidores de Janus Quinases/uso terapêutico , Janus Quinases/química , Modelos Moleculares , Conformação Proteica , Pirróis/uso terapêutico
10.
Medicine (Baltimore) ; 99(22): e20391, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481426

RESUMO

INTRODUCTION: Acquired reactive perforating collagenosis (ARPC) is a rare skin disorder, which is associated with various internal diseases and even malignant neoplasms. A comprehensive knowledge of the concomitant diseases in ARPC patients is helpful to decrease the misdiagnosis. Although the treatment of ARPC is challenging, systemic assessment of existing regimens is not available. PATIENT CONCERNS: A 50-year-old woman was admitted to the hospital due to cutaneous pruritus and papules all over the body. DIAGNOSIS: Physical examination showed various sized papules on the lower limbs, buttocks, back, chest, and upper arms with keratotic plugs in the center. Histopathology showed typical collagenous fiber perforation. The diagnosis of ARPC was made according to histopathology, onset age and typical skin lesions. Type 2 diabetes mellitus (T2DM), chronic renal failure (CRF), and hypothyroidism simultaneously presented in this patient. INTERVENTIONS: This patient was initially treated with topical corticosteroids and oral antihistamines for the skin lesion and pruritus. Medications for glucose control and recovery of renal and thyroid functions were also applied. On the second admission, the combined therapy of topical retinoic acid, Chinese medicinal herb-Qingpeng ointment, and Zinc oxide ointment was added. OUTCOMES: Papules and pruritus were improved significantly after the second hospitalization. CONCLUSION: We present a case of ARPC associated with T2DM, CRF, and hypothyroidism, which has rarely been described. There is no standardized treatment for ARPC. Co-administration of two or more agents for dermatologic interventions and treatment for associated diseases may help to improve skin symptoms.


Assuntos
Doenças do Colágeno/diagnóstico , Dermatopatias/diagnóstico , Doenças do Colágeno/tratamento farmacológico , Doenças do Colágeno/etiologia , Doenças do Colágeno/patologia , Fármacos Dermatológicos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Falência Renal Crônica/complicações , Pessoa de Meia-Idade , Pele/patologia , Dermatopatias/tratamento farmacológico , Dermatopatias/etiologia , Dermatopatias/patologia
11.
Rev Fac Cien Med Univ Nac Cordoba ; 77(2): 94-99, 2020 06 09.
Artigo em Espanhol | MEDLINE | ID: mdl-32558511

RESUMO

Introduction: Severe atopic dermatitis (AD) treatment is an unmet need, given the limited efficacy and safety of classical systemic treatments (CSTs). Dupilumab is a monoclonal antibody that blocks the signaling of the interleukins that mediate the inflammatory response involved in AD. Methods: the clinical response of a group of patients from Argentina with severe AD and insufficient response and/or toxicity to CSTs who were treated with dupilumab before commercial availability was analyzed. EASI, SCORAD, DLQI scales and analog visual scales of pruritus and sleep were evaluated, during a median follow-up of 189 days. In addition, the incidence of adverse events was analyzed. Results: 20 patients (13 male) were included; median age: 37.5 years; median AD evolution: 20 years; atopic comorbidity: 70%. 100% had received systemic corticosteroids (serious complications: 20%). Main reasons for discontinuation of CSTs were lack of efficacy and occurrence of adverse events. All scores were significantly and steadily reduced, with identifiable clinical response at the second month of treatment. At the end of the follow-up, only 3 patients required concomitant systemic immunosuppressive treatment. Dupilumab was well tolerated, with mild and controllable adverse events. Discussion: Dupilumab is the only biological agent with high efficacy demonstrated in clinical and observational studies. In this case series, its effectiveness was confirmed in difficult-to-treat patients with severe AD and inadequate response to CSTs. The safety profile was favorable and consistent.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Adolescente , Adulto , Idoso , Argentina , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
13.
Cochrane Database Syst Rev ; 5: CD011368, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32356369

RESUMO

BACKGROUND: Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the topical acne treatments azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha-hydroxy acid is unclear. OBJECTIVES: To assess the effects of topical treatments (azelaic acid, salicylic acid, nicotinamide, zinc, alpha-hydroxy acid, and sulphur) for acne. SEARCH METHODS: We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers. SELECTION CRITERIA: Clinical randomised controlled trials of the six topical treatments compared with other topical treatments, placebo, or no treatment in people with acne. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Key outcomes included participants' global self-assessment of acne improvement (PGA), withdrawal for any reason, minor adverse events (assessed as total number of participants who experienced at least one minor adverse event), and quality of life. MAIN RESULTS: We included 49 trials (3880 reported participants) set in clinics, hospitals, research centres, and university settings in Europe, Asia, and the USA. The vast majority of participants had mild to moderate acne, were aged between 12 to 30 years (range: 10 to 45 years), and were female. Treatment lasted over eight weeks in 59% of the studies. Study duration ranged from three months to three years. We assessed 26 studies as being at high risk of bias in at least one domain, but most domains were at low or unclear risk of bias. We grouped outcome assessment into short-term (less than or equal to 4 weeks), medium-term (from 5 to 8 weeks), and long-term treatment (more than 8 weeks). The following results were measured at the end of treatment, which was mainly long-term for the PGA outcome and mixed length (medium-term mainly) for minor adverse events. Azelaic acid In terms of treatment response (PGA), azelaic acid is probably less effective than benzoyl peroxide (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.95; 1 study, 351 participants), but there is probably little or no difference when comparing azelaic acid to tretinoin (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 289 participants) (both moderate-quality evidence). There may be little or no difference in PGA when comparing azelaic acid to clindamycin (RR 1.13, 95% CI 0.92 to 1.38; 1 study, 229 participants; low-quality evidence), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). Low-quality evidence indicates there may be no differences in rates of withdrawal for any reason when comparing azelaic acid with benzoyl peroxide (RR 0.88, 95% CI 0.60 to 1.29; 1 study, 351 participants), clindamycin (RR 1.30, 95% CI 0.48 to 3.56; 2 studies, 329 participants), or tretinoin (RR 0.66, 95% CI 0.29 to 1.47; 2 studies, 309 participants), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). In terms of total minor adverse events, we are uncertain if there is a difference between azelaic acid compared to adapalene (1 study; 55 participants) or benzoyl peroxide (1 study, 30 participants) (both very low-quality evidence). There may be no difference when comparing azelaic acid to clindamycin (RR 1.50, 95% CI 0.67 to 3.35; 1 study, 100 participants; low-quality evidence). Total minor adverse events were not reported in the comparison of azelaic acid versus tretinoin, but individual application site reactions were reported, such as scaling. Salicylic acid For PGA, there may be little or no difference between salicylic acid and tretinoin (RR 1.00, 95% CI 0.92 to 1.09; 1 study, 46 participants; low-quality evidence); we are not certain whether there is a difference between salicylic acid and pyruvic acid (1 study, 86 participants; very low-quality evidence); and PGA was not measured in the comparison of salicylic acid versus benzoyl peroxide. There may be no difference between groups in withdrawals when comparing salicylic acid and pyruvic acid (RR 0.89, 95% CI 0.53 to 1.50; 1 study, 86 participants); when salicylic acid was compared to tretinoin, neither group had withdrawals (both based on low-quality evidence (2 studies, 74 participants)). We are uncertain whether there is a difference in withdrawals between salicylic acid and benzoyl peroxide (1 study, 41 participants; very low-quality evidence). For total minor adverse events, we are uncertain if there is any difference between salicylic acid and benzoyl peroxide (1 study, 41 participants) or tretinoin (2 studies, 74 participants) (both very low-quality evidence). This outcome was not reported for salicylic acid versus pyruvic acid, but individual application site reactions were reported, such as scaling and redness. Nicotinamide Four studies evaluated nicotinamide against clindamycin or erythromycin, but none measured PGA. Low-quality evidence showed there may be no difference in withdrawals between nicotinamide and clindamycin (RR 1.12, 95% CI 0.49 to 2.60; 3 studies, 216 participants) or erythromycin (RR 1.40, 95% CI 0.46 to 4.22; 1 study, 158 participants), or in total minor adverse events between nicotinamide and clindamycin (RR 1.20, 95% CI 0.73 to 1.99; 3 studies, 216 participants; low-quality evidence). Total minor adverse events were not reported in the nicotinamide versus erythromycin comparison. Alpha-hydroxy (fruit) acid There may be no difference in PGA when comparing glycolic acid peel to salicylic-mandelic acid peel (RR 1.06, 95% CI 0.88 to 1.26; 1 study, 40 participants; low-quality evidence), and we are uncertain if there is a difference in total minor adverse events due to very low-quality evidence (1 study, 44 participants). Neither group had withdrawals (2 studies, 84 participants; low-quality evidence). AUTHORS' CONCLUSIONS: Compared to benzoyl peroxide, azelaic acid probably leads to a worse treatment response, measured using PGA. When compared to tretinoin, azelaic acid probably makes little or no difference to treatment response. For other comparisons and outcomes the quality of evidence was low or very low. Risk of bias and imprecision limit our confidence in the evidence. We encourage the comparison of more methodologically robust head-to-head trials against commonly used active drugs.


Assuntos
Acne Vulgar/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Adapaleno/efeitos adversos , Adapaleno/uso terapêutico , Adolescente , Adulto , Antibacterianos/uso terapêutico , Peróxido de Benzoíla/uso terapêutico , Viés , Criança , Clindamicina/efeitos adversos , Clindamicina/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Ácidos Dicarboxílicos/efeitos adversos , Ácidos Dicarboxílicos/uso terapêutico , Eritromicina/efeitos adversos , Eritromicina/uso terapêutico , Feminino , Glicolatos/uso terapêutico , Humanos , Ceratolíticos/uso terapêutico , Masculino , Ácidos Mandélicos/uso terapêutico , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Ácido Pirúvico/efeitos adversos , Ácido Pirúvico/uso terapêutico , Qualidade de Vida , Ácido Salicílico/uso terapêutico , Enxofre/uso terapêutico , Tretinoína/uso terapêutico , Adulto Jovem , Zinco/uso terapêutico
14.
Hautarzt ; 71(7): 511-517, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32399669

RESUMO

Pruritus is a common and stressful symptom in medicine with cutaneous manifestation. Therapy remains a challenge for physicians and patients because there are many causes/triggers and approved systemic therapies are lacking. Basically, there are two different options of treatment: topical treatment is selected for every degree of severity, while patients with severe symptoms and chronic disease course have to be treated with systemic and topical options. This article provides a summary of current topical therapeutic options and offers tips for daily practice.


Assuntos
Antipruriginosos/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Prurido/tratamento farmacológico , Administração Cutânea , Administração Tópica , Antipruriginosos/uso terapêutico , Doença Crônica , Fármacos Dermatológicos/uso terapêutico , Humanos , Prurido/diagnóstico , Resultado do Tratamento
17.
J Med Chem ; 63(9): 4776-4789, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32302115

RESUMO

Toll-like receptor 7 (TLR7) is an established therapeutic target in myriad autoimmune disorders, but no TLR7 antagonist is available for clinical use to date. Herein, we report a purine scaffold TLR7 antagonist, first-of-its-kind to our knowledge, which was developed by rationally dissecting the structural requirements for TLR7-targeted activity for a purine scaffold. Specifically, we identified a singular chemical switch at C-2 that could make a potent purine scaffold TLR7 agonist to lose agonism and acquire antagonist activity, which could further be potentiated by the introduction of an additional basic center at C-6. We ended up developing a clinically relevant TLR7 antagonist with favorable pharmacokinetics and 70.8% oral bioavailability in mice. Moreover, the TLR7 antagonists depicted excellent selectivity against TLR8. To further validate the in vivo applicability of this novel TLR7 antagonist, we demonstrated its excellent efficacy in preventing TLR7-induced pathology in a preclinical murine model of psoriasis.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Purinas/uso terapêutico , Receptor 7 Toll-Like/agonistas , Receptor 7 Toll-Like/antagonistas & inibidores , Animais , Sítios de Ligação , Células CACO-2 , Fármacos Dermatológicos/síntese química , Fármacos Dermatológicos/metabolismo , Fármacos Dermatológicos/farmacocinética , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Estrutura Molecular , Psoríase/tratamento farmacológico , Psoríase/patologia , Purinas/síntese química , Purinas/metabolismo , Purinas/farmacocinética , Pele/patologia , Relação Estrutura-Atividade , Receptor 7 Toll-Like/metabolismo
19.
An Bras Dermatol ; 95(3): 320-325, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32291095

RESUMO

BACKGROUND: Higher skin pH in atopic dermatitis contributes to impaired epidermal barrier. A moisturizer compatible with physiological pH could improve atopic dermatitis. OBJECTIVE: To determine the effect of a physiologically compatible pH moisturizer in atopic dermatitis. METHODS: A randomized half body, double blind, controlled trial involving patients with stable atopic dermatitis was performed. pH-modified moisturizer and standard moisturizer were applied to half body for 6 weeks. RESULTS: A total of 6 (16.7%) males and 30 (83.3%) females participated. Skin pH reductions from week 0, week 2 and 6 were significant at the forearms (5.315 [0.98] to 4.85 [0.54] to 5.04 [0.78], p=0.02) and abdomen (5.25 [1.01], 4.82 [0.64], 5.01 [0.59], p=0.00) but not at the shins (5.01 [0.80], 4.76 [0.49], 4.85 [0.79], p=0.09) with pH-modified moisturizer. Transepidermal water loss (TEWL) at the forearms decreased (4.60 [2.55] to 3.70 [3.10] to 3.00 [3.55], p=0.00), abdomen (3.90 [2.90] to 2.40 [3.45] to 2.70 [2.25], p=0.046). SCORAD improved from 14.1±12.75 to 10.5±13.25 to 7±12.25, p=0.00. In standard moisturizer group, pH reductions were significant at the forearms (5.29 [0.94] to 4.84 [0.55] to 5.02 [0.70], p=0.00) and abdomen (5.25 [1.09], 4.91 [0.63], 5.12 [0.66], p=0.00). TEWL at the forearm were (4.80 [2.95], 4.10 [2.15], 4.60 [3.40], p=0.67), shins (3.80 [1.40], 3.50 [2.35], 4.00 [2.50], p=0.91) and abdomen (3.70 [2.45], 4.10 [3.60], 3.40 [2.95], p=0.80). SCORAD improved from 14.2±9.1 to 10.9±10.65 to 10.5±11, p=0.00. Reduction in pH was observed with both moisturizers while TEWL significantly improved with pH-modified moisturizer. pH-modified moisturizer resulted in greater pH, TEWL and SCORAD improvements however the differences were not significant from standard moisturizer. STUDY LIMITATION: Skin hydration was not evaluated. CONCLUSION: Moisturization is beneficial for atopic dermatitis; use of physiologically compatible pH moisturizer is promising.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/química , Fármacos Dermatológicos/uso terapêutico , Creme para a Pele/química , Creme para a Pele/uso terapêutico , Adolescente , Adulto , Criança , Método Duplo-Cego , Epiderme/química , Epiderme/efeitos dos fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
BMJ Case Rep ; 13(4)2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32332045

RESUMO

An 80-year-old woman presented with a several-year history of progressive hair loss and scalp pruritus. No other rashes or muscle weakness were noted on examination. Scalp biopsy showed interface dermatitis, dense perivascular and periadnexal lymphocytic infiltrate, mucin and scarring alopecia. Laboratory analysis did not show evidence of myositis. The patient was started on hydroxychloroquine for possible cutaneous lupus erythematosus. On follow-up, she presented with a new violaceous rash on the superior eyelids and a well-defined oval patch on the mid-hard palate suspicious for dermatomyositis. Myositis-specific autoantibodies revealed presence of anti-transcriptional intermediary factor-1γ (anti-TIF1γ) in the serum. Anti-TIF1γ autoantibody-positive dermatomyositis is a newly recognised subtype of dermatomyositis that is highly associated with amyopathic disease and has an increased risk of malignancy, making prompt diagnosis crucial. This case highlights the utility of a thorough oral exam in patients suspected to have connective tissue disease as the distinctive ovoid palatal patch is nearly pathognomonic for anti-TIF1γ dermatomyositis.


Assuntos
Autoanticorpos/sangue , Dermatomiosite/diagnóstico , Eritema/patologia , Exantema/patologia , Palato Duro/patologia , Idoso de 80 Anos ou mais , Fármacos Dermatológicos/uso terapêutico , Dermatomiosite/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Humanos , Metotrexato/uso terapêutico , Fatores de Transcrição/imunologia
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