RESUMO
Melasma is acquired hyperpigmentation that mainly affects the face, can cause negative changes in self-esteem, and mostly affects women. Treatment is difficult, and different drugs can be used in mono or combination therapy. In this article, we present a brief overview of melasma, how to evaluate it, and a synthesis of the most commonly used topical therapies and their indications, including sunscreens, pharmacological agents, and plant extracts. Hydroquinone (4%) in monotherapy or combined with corticosteroids (dexamethasone and fluocinolone acetonide) and retinoids (tretinoin); arbutin (1%); methimazole (5%); kojic (2%), azelaic (20%), and tranexamic (5%) acids are the pharmacological agents that stand out. Correct application of these substances determines a variable improvement in melasma but often causes adverse reactions such as erythema, itching, and burning at the application site. Vitamin C can contribute to the reduction of melasma and have little or no adverse effects while sunscreens are normally used as coadjuvant therapies. In conclusion, we have compiled specific topical therapies for treating melasma and discussed those that are the most used currently. We consider it important that prescribers and researchers evaluate the best cost-benefit ratio of topical therapeutic options and develop new formulations, enabling efficacy in the treatment with safety and comfort during application, through the reduction of adverse effects.
Assuntos
Melanose , Protetores Solares , Feminino , Humanos , Protetores Solares/uso terapêutico , Melanose/etiologia , Tretinoína/efeitos adversos , Retinoides/uso terapêutico , Fluocinolona Acetonida/efeitos adversos , Hidroquinonas/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is usually treated with corticosteroids, given their anti-inflammatory effects. Unlike the nasal administration, the oral and ocular use of tretinoin, an immunoregulatory drug, is well established. Therefore, tretinoin was thought to act on nasal polyps, and possible adverse and/or therapeutic effects were investigated. METHODS: A first-in-human open-label trial was conducted enrolling patients with CRSwNP randomized into: a control group (CTR, n = 15), treated with budesonide for 24 weeks; and an intervention group (TRT, n = 15), who received budesonide and 0.1% tretinoin in the last 12 weeks. Primary endpoint included histopathological analysis and tissue immunoassay (Multiplex) for tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-4, IL-5, IL-13, and matrix metalloproteinase 9 (MMP-9) at 12 and 24 weeks. Secondary endpoints were: adverse events report, endoscopy (modified Lund-Kennedy scoring system [LKS]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), and olfactory test (Connecticut Chemosensory Clinical Research Center) at baseline, at 12 weeks, and at 24 weeks, in addition to serum biochemistry and tomographic findings (Lund-Mackay computed tomography [CT] staging system [LMS]) at baseline and 24 weeks. RESULTS: TRT showed less microscopic edema (2/13 [15.4%] vs 8/13 [61.5%]; p = 0.044) as well as no increase in cytokines levels. All adverse events were categorized as "grade 1" (asymptomatic; mild). The most interesting part of this study was the improvement in smell between baseline (T0) and week 24 (T2) in TRT only (p = 0.041). CONCLUSION: Transnasal tretinoin associated with budesonide was safe and well tolerated, and it should be investigated as a treatment option for some CRSwNP endotypes. ©2021 ARSAAOA, LLC.
Assuntos
Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Humanos , Pólipos Nasais/tratamento farmacológico , Qualidade de Vida , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Tretinoína/efeitos adversosRESUMO
This study aimed to evaluate the effectiveness of isolated treatment with retinoic acid and its combination with the microneedling technique in facial melasma, seeking to associate these results with possible oxidative damage. This is a blinded randomized clinical trial with 42 women with facial melasma (skin phototype I-IV), randomized into Group A (microneedling and 5% retinoic acid) or Group B (5% retinoic acid alone). Four procedures were applied with 15 days intervals (4 blood collections). Clinical improvement was assessed using the Melasma Area Severity Index (MASI). Serum oxidative stress levels were evaluated by protein oxidation (carbonyl), lipid peroxidation (TBARS) and sulfhydryl groups, as well as enzyme activities of superoxide dismutase (SOD) and catalase (CAT). The statistical analyzes were performed by generalized estimation equation (GEE). There was a reduction in MASI scale and TBARS levels in both groups over time (p < 0.05), with no difference between groups (p = 0.416). There was also a substantial increase in the carbonyl levels at 30 days (p = 0.002). The SOD activity decreased after 30 days, regardless of group (p < 0.001), which was maintained after 60 days. In Group A, there was a reduction in sulfhydryl levels at 60 days (p < 0.001). It is important to highlight that both groups demonstrated efficacy in the clinical improvement of melasma within at least 60 days, reducing the MASI score by almost 50%. However, microneedling with retinoic acid seems to be the worst treatment because there is a reduction in the non-enzymatic antioxidant defense, which is important to protect against oxidative stress.
Assuntos
Agulhamento Seco/métodos , Dermatoses Faciais/terapia , Ceratolíticos/administração & dosagem , Melanose/terapia , Tretinoína/administração & dosagem , Administração Cutânea , Adulto , Terapia Combinada/instrumentação , Terapia Combinada/métodos , Agulhamento Seco/instrumentação , Dermatoses Faciais/sangue , Dermatoses Faciais/diagnóstico , Feminino , Humanos , Ceratolíticos/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Melanose/sangue , Melanose/diagnóstico , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Satisfação do Paciente , Índice de Gravidade de Doença , Resultado do Tratamento , Tretinoína/efeitos adversosRESUMO
BACKGROUND: Differentiation syndrome (DS) is the main life-threatening adverse event that occurs in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA). Cytokine imbalances have been reported to play role during the developing of acute promyelocytic leukemia differentiation syndrome (APL-DS). However, the relationship between the plasma cytokine levels and their prognostic value for the prediction of DS developing in patients with APL during the treatment with ATRA and anthracyclines has not been previously reported. METHODS: In this study, we followed an APL cohort (n = 17) over 7 days of ATRA therapy in DS (n = 6) and non-DS groups (n = 11). Interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were measured in the peripheral blood plasma from 17 patients with APL and 11 healthy adult controls by using the cytometric bead array method. RESULTS: In non-DS patients, IL-8 plasma levels were significantly reduced in the seventh day of ATRA treatment (34.16; 6.99 to 147.11 pg mL- 1 in D0 vs. 10.9; 0 to 26.81 pg mL- 1 in D7; p = 0.02) whereas their levels did not discriminate between DS and non-DS development during the entire induction period (all p > 0.05 in D0, D3, and D7). No significant differences were found in IL-6 levels between groups (p > 0.05 in D0-D7). Other cytokines tested were all undetectable in patients with APL or healthy controls. CONCLUSIONS: We demonstrated that the modulation of IL-8 following ATRA treatment may occur regardless of the development of DS and, therefore, does not appear to be a predictive biomarker to monitor the APL-DS.
Assuntos
Antineoplásicos/efeitos adversos , Diferenciação Celular/efeitos dos fármacos , Interleucina-8/sangue , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/efeitos adversos , Adulto , Idoso , Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/sangue , Feminino , Humanos , Interleucina-6/sangue , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome , Resultado do Tratamento , Tretinoína/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: Adapalene has been previously evaluated as a treatment for actinic keratosis (AK) and solar lentigines and shown to improve signs of photoaging. OBJECTIVES: To evaluate whether adapalene 0.3% gel is non-inferior to tretinoin 0.05% cream as treatment for photoaged skin. MATERIALS & METHODS: An investigator-blinded, parallel-group comparison study was conducted in Brazil. Subjects were randomised in a 1:1 ratio to receive, once daily, adapalene 0.3% gel or tretinoin 0.05% cream. Subjects were evaluated at Weeks 1, 4, 8, 12, 16, 20 and 24, based on clinical signs of cutaneous photoaging, histopathological and digital morphometric findings, as well as safety and tolerability. RESULTS: A comparison of clinical efficacy showed that both treatments did not differ significantly regarding clinical evaluation of the following criteria: global cutaneous photoaging, periorbital wrinkles, ephelides/melanosis, forehead wrinkles, and AK. CONCLUSION: Adapalene 0.3% gel showed non-inferior efficacy to tretinoin 0.05% cream as treatment for photoaged skin, with a similar safety profile. Adapalene 0.3% gel may therefore be considered a safe and effective option for the treatment of mild or moderate photoaging.
Assuntos
Adapaleno/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Tretinoína/administração & dosagem , Adapaleno/efeitos adversos , Adulto , Fármacos Dermatológicos/efeitos adversos , Estudos de Equivalência como Asunto , Feminino , Géis , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Envelhecimento da Pele/patologia , Creme para a Pele , Luz Solar/efeitos adversos , Tretinoína/efeitos adversos , Raios Ultravioleta/efeitos adversosRESUMO
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). All-trans retinoic acid (ATRA) is the first-choice therapy for the treatment of this disease, but has been associated with side effects, the most serious of which is retinoic acid syndrome (RAS). RAS is characterized by unexplained fever, dyspnea, pulmonary infiltrate, leukocytosis and nephropathy. Genital ulcers have been described in some cases, but only two cases of oral ulcers related to this syndrome have been described in the literature. This paper describes the third case of oral ulceration related to ATRA in a 32-year-old white man with diagnosis of APL. Clinicians should know the side effects of ATRA and identify oral ulcers resulting from this therapy. The prompt identification of these ulcers enables the institution of appropriate treatment and can therefore contribute to continuation of the patient's cancer treatment.
Assuntos
Antineoplásicos/efeitos adversos , Leucemia Promielocítica Aguda/tratamento farmacológico , Doenças Labiais/induzido quimicamente , Tretinoína/efeitos adversos , Úlcera/induzido quimicamente , Adulto , Humanos , MasculinoRESUMO
BACKGROUND: Topical tretinoin cream is the gold standard treatment for skin ageing, particularly photoaging. The purpose of tretinoin peel was to obtain similar results, but in a shorter time, however, there have been few controlled trials on its effectiveness. OBJECTIVE: To compare efficacy and safety of tretinoin 0.05% cream and 5% as a peeling agent on photoaging and field cancerization of the forearms. METHODS: Clinical trial with therapeutic intervention, prospective, randomized (computer-generated randomization list), parallel, comparative (intrasubject) and evaluator-blinded (except for histology and immunohistochemistry), including 24 women (48 forearms) aged over 60 years who have not undergone hormone replacement and categorized as Fitzpatrick skin phototype II or III. The forearms of the participants were randomized for treatment with 0.05% tretinoin cream three nights a week, or 5% tretinoin peel every 2 weeks. The opinion of the participant, severity of photoaging, corneometry, profilometry, high-frequency ultrasound, histology (haematoxylin-eosin and Verhoeff stainings) and immunohistochemistry (p53, bcl-2, Ki67 and collagen I) were assessed. RESULTS: One participant dropped out. The mean photoaging score reduced 20% and the mean actinic keratosis (AK) count reduced 60% with no difference between treatments. Three efficacy parameters showed opposite effects between the tretinoin treatments (P < 0.05%): (i) thickness of the corneal layer decreased with 0.05% tretinoin and increased by 5%; (ii) dermis echogenicity increased by 0.05% and decreased by 5% and (iii) Ki67 expression increased by 0.05% and decreased by 5%. There was good tolerability for both regimens. CONCLUSION: Tretinoin as a cream 0.05% or peeling (5%) is safe and effective for the treatment of moderate photoaging and forearm field cancerization. The cream was superior in improving ultrasonographic parameters of ageing. Peeling was shown a superior performance in the stabilization of field cancerization.
Assuntos
Antineoplásicos/administração & dosagem , Abrasão Química , Ceratose Actínica/tratamento farmacológico , Envelhecimento da Pele/efeitos dos fármacos , Creme para a Pele/administração & dosagem , Tretinoína/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Derme/diagnóstico por imagem , Epiderme/diagnóstico por imagem , Feminino , Antebraço , Humanos , Ceratose Actínica/metabolismo , Ceratose Actínica/patologia , Antígeno Ki-67/metabolismo , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Método Simples-Cego , Envelhecimento da Pele/patologia , Creme para a Pele/efeitos adversos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Tretinoína/efeitos adversos , Proteína Supressora de Tumor p53/metabolismo , UltrassonografiaRESUMO
BACKGROUND: The clinical efficacy of the topical tretinoin is widely studied and has been well established for many therapeutic interventions, among some, photoaging, acne, and melasma. However, the side effects, mainly cutaneous irritation, erythema, xerosis and peeling, remain major obstacle to the patient compliance. Besides, the insight regarding the drug delivery profile is essential to understand the therapeutic action of the drug. METHODS: Through bibliographic research in databases we highlight further advances and an update on tretinoin delivery systems such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrins, nanostructured polymers and other technological systems that reduce its side effects and improve the permeation profile to potentiate efficacy and drug safety on the skin. RESULTS: Pharmaceutical preparations were developed and evaluated for permeability in in vitro models using pig ear, snake, mouse and human skin, and potential for irritation was also verified using release systems for tretinoin and compared to available commercial formulations. Overall results indicated the composition, charge and size of the system influences the tretinoin delivery, modulating the type of release and its retention. Small unilamellar vesicles promoted greater cutaneous delivery of tretinoin. Negative charge, for both liposomes and niosomes, can improve pig skin hydration as well as the tretinoin retention. The quantity of solid lipids and the type of oil used in the composition of solid lipid nanoparticles and nanostructured lipid carriers affected percutaneous drug delivery. CONCLUSION: As evident from the literature, the tretinoin technological delivery systems consist an innovative and potential management for increasing the patient compliance presenting safety and efficacy.
Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Tretinoína/farmacologia , Administração Cutânea , Animais , Ciclodextrinas/química , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Nanotecnologia/métodos , Pele/metabolismo , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos , Lipossomas Unilamelares/químicaRESUMO
BACKGROUND/AIMS: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. METHODS AND RESULTS: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-ß, PI3K, AKT, NFκB, S6K, and ERK. CONCLUSION: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.
Assuntos
Coração/efeitos dos fármacos , Tretinoína/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Suplementos Nutricionais/efeitos adversos , Ecocardiografia , Metabolismo Energético/efeitos dos fármacos , Coração/fisiologia , Coração/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Tretinoína/efeitos adversosRESUMO
La leucemia promielocítica aguda (APL) es el subtipo de leucemia mieloide aguda de mejor pronóstico en niños. Su incidencia es menor a 10%. Desde el punto de vista citogenético se observa una translocación t (15;17). En la terapéutica la incorporación del ácido transretinoico ha logrado altas tasas de remisión completa debido a la rápida desaparición de la coagulopatía y, en consecuencia, disminución de la tasa de recaídas, en comparación con el tratamiento de monoterapia. En general es un fármaco bien tolerado pero puede tener reacciones adversas; el más grave es el síndrome de ácido transretinoico (ATRA), potencialmente mortal. Las manifestaciones clínicas son: fiebre, ganancia de peso, infiltrados pulmonares, síndrome de dificultad respiratoria, derrame pleural o pericárdico, hipotensión, insuficiencia hepática y renal. El tratamiento es con suspensión del ácido transretinoico, medidas de apoyo y altas dosis de esteroides. Se presenta un caso clínico del hospital del Niño DIF con APL y Síndrome de ATRA.
The leukemia promyelocytic acute (APL) is the subtype of leukemia myeloid acute of better prognosis in children. Its incidence is less than 10%. From the point of view cytogenetic is observed a translocation t (15; 17). The addition of the acid transretinoico has achieved high rates of complete remission because of the rapid disappearance of the coagulopathy and, consequently, decrease in the rate of relapses, compared with monotherapy treatment. In general it is a well-tolerated drug but can have adverse reactions; the most serious is transretinoico acid (ATRA), potentially fatal syndrome. The manifestations are: fever, weight gain, pulmonary infiltrates, syndrome of shortness of breath, hypotension, pleural effusion or pericardial, hepatic and renal insufficiency. The treatment is with suspension of the acid transretinoico, measures of support and high doses of steroids. It presents a case clinical of the Hospital del Niño DIF with APL and syndrome of ATRA.