A comparative exploration of immunohistochemical markers in patients with papulopustular rosacea undergoing treatment with oral isotretinoin versus doxycycline.

BACKGROUND: Rosacea is a chronic inflammatory disease, and doxycycline is a widely recommended treatment for it due to its anti-inflammatory action. Oral isotretinoin reduces sebaceous gland activity and modulates toll-like receptors, reducing inflammation. Our aim was to investigate the effect of these two drugs on the expression of cutaneous immunohistochemical biomarkers related to etiopathogenic factors involved in rosacea. METHODS: We conducted a randomized, comparative, and evaluator-blinded trial, including 40 participants with moderate and severe papulopustular and ocular rosacea. Participants were treated with doxycycline (DOXY) 100 mg or isotretinoin (ISO) 0.3 mg/kg daily. Immunohistochemistry at baseline and after 4 months was used to demonstrate the expression of the biomarker on the affected skin. RESULTS: The following changes were detected: a reduction in the vessel count after using VEGF with DOXY (P = 0.010); a decrease in VEGF intensity with ISO (P < 0.001) and DOXY (P = 0.020); a reduction of nitric oxide synthase enzyme with both drugs in the inflammatory infiltrate (ISO P < 0.001; DOXY P = 0.003); however, only with ISO was there a significant (P = 0.030) decrease at the level of the sebaceous glands, indicating a reduction of nitric oxide synthesis; a reduction of TRPV-1 expression at the level of the sebaceous glands was observed only with DOXY (P = 0.041); a decrease of cathelicidin LL37 expression, a key antimicrobial peptide in the etiopathogenesis of rosacea, was noted with both drugs, although at the level of sebaceous glands, only with DOXY (P = 0.007). CONCLUSIONS: Oral isotretinoin and doxycycline have modified the expression of cutaneous biomarkers related to rosacea etiopathogenesis, demonstrating their role in controlling inflammatory and vascular processes.

Efficacy and safety of botulinum toxin for rosacea with positive impact on quality of life and self-esteem.

BACKGROUND: Rosacea is a prevalent chronic inflammatory skin disease with a multifactorial pathophysiology. It compromises several skin structures, including the proliferation and dilation of dermal blood vessels, primarily in the central areas of the face, accompanied by significant psychosocial impairment, leading to reduced quality of life (QoL) and self-esteem. There are consensus guidelines for its treatment, but few options for the erythema. This study hypothesizes that treating rosacea skin lesions with botulinum toxin (BTX) could improve signs and symptoms, resulting in enhanced QoL and self-esteem. METHODS: This interventional, open, uncontrolled, and prospective study, conducted at a single center, included 33 individuals diagnosed with rosacea, treated with standard therapeutic options according to the rosacea subtype plus superficial injections of BTX, and followed up for 90 days. Botulinum toxin injections were applied on Days 1 and 14. Clinical features and side effects were assessed at each visit; QoL, self-esteem, and medication adherence questionnaires were administered on Days 1 and 90. RESULTS: Treatment with BTX yielded improvement in the clinical signs of rosacea, registered by the investigators, and reported by 94% of the participants. Improved QoL scores (P < 0.05) and a notable increase in self-esteem scores (P < 0.001) were demonstrated. Rare adverse events were observed. CONCLUSIONS: The utilization of BTX superficial injections in patients with rosacea was safe and effective, improving the clinical appearance of the lesions. Despite some limitations, to our knowledge, this is the first study that showed the positive impact of this treatment modality on both QoL and self-esteem.

Long-term maintenance treatment of rosacea: experts' opinion.

BACKGROUND: Rosacea is a chronic inflammatory dermatosis characterized by remissions and flares. Although the rosacea active treatment phase is well established, the long-term maintenance phase is still challenging. OBJECTIVE: To discuss and make recommendations on how to treat patients during the long-term maintenance phase for the main rosacea phenotypes. METHODS: A panel of six board-certified Brazilian dermatologists and one American dermatologist gathered to compose a consensus based upon an initial statement on how to treat rosacea during the long-term maintenance phase based on the methodology Nominal Group Technique. The experts discussed each factor based upon an initial statement on how to treat rosacea patients in the long-term maintenance phase. A sequence of comprehensive narrative reviews was performed; a questionnaire preparation about the definition of the maintenance phase and its management was presented; an interpersonal discussion and ranking of the ideas were conducted. Recommendations were made if the specialists had 75% agreement. RESULTS: The maintenance treatment phase, which starts by achieving IGA 0 or 1 grades at the active phase, should be considered at least during the 9-month period after remission. The recommendations of all treatments target this period. Daily skincare regimen and sunscreen are crucial. Active treatment phase should be recommended if signs or symptoms reappear or worsen. CONCLUSION: Maintenance phase success depends on patient's adherence to daily skin care, appropriate treatments, continued follow-up with dermatologist, and self-assessment to identify new signs and symptoms indicating disease relapse.

Consensus on the use of oral isotretinoin in dermatology - Brazilian Society of Dermatology.

BACKGROUND: Isotretinoin is a synthetic retinoid, derived from vitamin A, with multiple mechanisms of action and highly effective in the treatment of acne, despite common adverse events, manageable and dose-dependent. Dose-independent teratogenicity is the most serious. Therefore, off-label prescriptions require strict criteria. OBJECTIVE: To communicate the experience and recommendation of Brazilian dermatologists on oral use of the drug in dermatology. METHODS: Eight experts from five universities were appointed by the Brazilian Society of Dermatology to develop a consensus on indications for this drug. Through the adapted DELPHI methodology, relevant elements were listed and an extensive analysis of the literature was carried out. The consensus was defined with the approval of at least 70% of the experts. RESULTS: With 100% approval from the authors, there was no doubt about the efficacy of oral isotretinoin in the treatment of acne, including as an adjunct in the correction of scars. Common and manageable common adverse events are mucocutaneous in nature. Others, such as growth retardation, abnormal healing, depression, and inflammatory bowel disease have been thoroughly investigated, and there is no evidence of a causal association; they are rare, individual, and should not contraindicate the use of the drug. Regarding unapproved indications, it may represent an option in cases of refractory rosacea, severe seborrheic dermatitis, stabilization of field cancerization with advanced photoaging and, although incipient, frontal fibrosing alopecia. For keratinization disorders, acitretin performs better. In the opinion of the authors, indications for purely esthetic purposes or oil control are not recommended, particularly for women of childbearing age. CONCLUSIONS: Approved and non-approved indications, efficacy and adverse effects of oral isotretinoin in dermatology were presented and critically evaluated.

Ocular surface changes in the treatment of rosacea: comparison between low-dose oral isotretinoin and doxycycline / Alterações da superfície ocular no tratamento da Rosácea: comparação entre isotretinoína oral em baixa dosagem e doxiciclina

ABSTRACT Purpose: To compare the impact of ocular changes between systemic treatment with doxycycline and low-dose oral isotretinoin in patients with moderate-to-severe papulopustular rosacea. Methods: Patients were randomized to receive either isotretinoin 0.3-0.4 mg/kg (group A) or doxycycline 100 mg/day (group B) for 16 weeks. Ocular symptoms were searched and evaluated, including best-corrected visual acuity (BCVA), Schirmer test, breakup time, rose bengal staining score, and meibomian gland dysfunction grading. The patients were retested at the end of treatment. Results: The present study included 39 patients (30 females and 9 males). Best-corrected visual acuity was > 20/30 in >90% of patients in both groups and did not change after treatment. After treatment, improvement in ocular symptoms and meibomian gland dysfunction was more pronounced in group B (p<0.05); the other parameters did not reach statistical significance. Conclusion: Doxycycline improved meibomian gland dysfunction, ocular symptoms, and ocular surface in patients with rosacea. Even though some patients experienced worsening meibomian gland dysfunction and symptoms, no subject experienced any serious complications after administration of low-dose isotretinoin.

RESUMO Objetivos: Comparar o impacto das alterações oculares entre o tratamento sistêmico de doxiciclina e isotretinoína em baixa dosagem em pacientes com rosácea papulopustulosa moderada a grave. Métodos: Os pacientes form randomizados para receber isotretinoína 0,3 a 0,4 mg/kg (grupo A) ou doxiciclina 100mg/dia (grupo B) por 16 semanas. Os sintomas oculares foram pesquisados e avaliados, incluindo melhor acuidade visual corrigida, teste de Schirmer, tempo de ruptura do filme lacrimal, coloração de rosa bengala e graduação da disfunção de glândula de Meibomius. Os pacientes foram novamente testados no final do tratamento. Resultados: O presente estudo incluiu 39 pacientes (30 mulheres e 9 homens). A melhor acuidade visual corrigida foi >20/30 em >90% dos pacientes em ambos os grupos e não se alterou após o tratamento. A melhora dos sintomas oculares e da disfunção de glândula de Meibomius foi mais pronunciada no grupo B (p<0,05) após o tratamento; as demais variáveis não atingiram significância estatística. Conclusão: A doxiciclina melhorou a disfunção de glândula de Meibomius, os sintomas oculares e a superfície ocular de pa cientes com rosácea. Mesmo que alguns pacientes tenham piorado a disfunção e os sintomas da glândula de Meibomius, nenhum indivíduo apresentou complicações graves após a admi nistração de baixas doses de isotretinoína.

Ocular surface changes in the treatment of rosacea: comparison between low-dose oral isotretinoin and doxycycline.

PURPOSE: To compare the impact of ocular changes between systemic treatment with doxycycline and low-dose oral isotretinoin in patients with moderate-to-severe papulopustular rosacea. METHODS: Patients were randomized to receive either isotretinoin 0.3-0.4 mg/kg (group A) or doxycycline 100 mg/day (group B) for 16 weeks. Ocular symptoms were searched and evaluated, including best-corrected visual acuity (BCVA), Schirmer test, breakup time, rose bengal staining score, and meibomian gland dysfunction grading. The patients were retested at the end of treatment. RESULTS: The present study included 39 patients (30 females and 9 males). Best-corrected visual acuity was > 20/30 in >90% of patients in both groups and did not change after treatment. After treatment, improvement in ocular symptoms and meibomian gland dysfunction was more pronounced in group B (p<0.05); the other parameters did not reach statistical significance. CONCLUSION: Doxycycline improved meibomian gland dysfunction, ocular symptoms, and ocular surface in patients with rosacea. Even though some patients experienced worsening meibomian gland dysfunction and symptoms, no subject experienced any serious complications after administration of low-dose isotretinoin.

Rosacea-specific quality of life questionnaire: translation, cultural adaptation and validation for Brazilian Portuguese

Abstract: Background: Brazil does not have a rosacea-specific quality of life questionnaire. Objectives: translation into Brazilian Portuguese, development of cultural adaptation, and validation of the RosaQoL disease-specific questionnaire for rosacea of any subtype. Methods: the recommended procedures for translation, cultural adaptation, and validation of an instrument were followed, and three interviews were conducted: baseline; seven to fourteen days after baseline; and at four to six months. The questionnaire was analyzed (with 95% confidence interval) for reliability by internal consistency (Cronbach's alpha); testretest reproducibility (intraclass correlation coefficient); responsiveness and validity. Results: terms of the original questionnaire were replaced to guarantee cultural and semantic equivalence. Validity was demonstrated by expressive correlations between the RosaQoL domains and by significance in the Jonckheere-Terpstra test (p≤0.05) between the scores of the RosaQoL domains and the participants' self-perception in relation to the disease. Reliability was acceptable; alpha coefficient ranged from 0.923 to 0.916 in the first and second applications of the RosaQoL, respectively, and the Intraclass Correlation Coefficient (ICC) ranged from 0.671 to 0.863 in the seven- to fourteen-day period. Responsiveness, measured by grouping participants into three categories based on self-perception of rosacea (better, worse or unchanged), was found for the "better" response group (p≤0.05). Study limitations: small sample; limited variety of screening sources. Conclusions: RosaQoL-BR (Brazil) was demonstrated as a reliable, valid and responsive questionnaire, with limitations, for individuals with any subtype of rosacea.

Rosacea-specific quality of life questionnaire: translation, cultural adaptation and validation for Brazilian Portuguese.

BACKGROUND: Brazil does not have a rosacea-specific quality of life questionnaire. OBJECTIVES: translation into Brazilian Portuguese, development of cultural adaptation, and validation of the RosaQoL disease-specific questionnaire for rosacea of any subtype. METHODS: the recommended procedures for translation, cultural adaptation, and validation of an instrument were followed, and three interviews were conducted: baseline; seven to fourteen days after baseline; and at four to six months. The questionnaire was analyzed (with 95% confidence interval) for reliability by internal consistency (Cronbach's alpha); testretest reproducibility (intraclass correlation coefficient); responsiveness and validity. RESULTS: terms of the original questionnaire were replaced to guarantee cultural and semantic equivalence. Validity was demonstrated by expressive correlations between the RosaQoL domains and by significance in the Jonckheere-Terpstra test (p≤0.05) between the scores of the RosaQoL domains and the participants' self-perception in relation to the disease. Reliability was acceptable; alpha coefficient ranged from 0.923 to 0.916 in the first and second applications of the RosaQoL, respectively, and the Intraclass Correlation Coefficient (ICC) ranged from 0.671 to 0.863 in the seven- to fourteen-day period. Responsiveness, measured by grouping participants into three categories based on self-perception of rosacea (better, worse or unchanged), was found for the "better" response group (p≤0.05). STUDY LIMITATIONS: small sample; limited variety of screening sources. CONCLUSIONS: RosaQoL-BR (Brazil) was demonstrated as a reliable, valid and responsive questionnaire, with limitations, for individuals with any subtype of rosacea.

Metabolic studies of a patient harbouring a novel S487L mutation in the catalytic subunit of AMPK.

AMP-activated protein kinase (AMPK) regulates many different metabolic pathways in eukaryote cells including mitochondria biogenesis and energy homeostasis. Here we identify a patient with hypotonia, weakness, delayed milestones and neurological impairment since birth harbouring a novel homozygous mutation in the AMPK catalytic α-subunit 1, encoded by the PRKAA1 gene. The homozygous mutation p.S487L in isoform 1 present in the patient is in a cryptic residue for AMPK activity. In the present study, we performed the characterization of mitochondrial respiratory properties of the patient, in comparison to healthy controls, through the culture of skin fibroblasts in order to understand some of the cellular consequences of the PRKAA1 mutation. In these assays, mitochondrial respiratory complex I showed lower activity, which was followed by a decrement in the mtDNA copy number, which is a probable consequence of the lower expression of PGC-1α and PRKAA1 itself as measured in our quantitative PCRs experiments. Confirming the effect of the patient mutation in respiration, transfection of patient fibroblasts with wild type PRKAA1 partially restore complex I level. The preliminary clinic evaluations of the patient suggested a metabolic defect related to the mitochondrial respiratory function, therefore treatment with CoQ10 supplementation dose started four years ago and a clear improvement in motor skills and strength has been achieved with this treatment.

Tratamento da acne vulgar moderada a grave com isotretinoína oral similar ao produto referência / Treatment of moderate to severe acne vulgaris with an oral isotretinoin similar to the reference product

Introdução: Acne vulgar é doença inflamatória crônica dos folículos pilossebáceos. O tratamento deve ser precoce e efetivo para evitar cicatrizes e repercussões psicossociais, sendo a isotretinoína droga de escolha para casos moderados ou graves. Objetivos: Avaliar eficácia, segurança e tolerabilidade de uma isotretinoína similar ao produto referência. Métodos: Estudo bicêntrico, de intervenção terapêutica, incluindo 50 participantes, de 13 a 35 anos de idade, com acne moderada ou grave, usando isotretinoína 0,5mg/kg/dia, até 120mg/kg. A eficácia foi avaliada por meio da contagem de lesões, escala de avaliação global do investigador (IGA), satisfação do paciente e aplicação do questionário de qualidade de vida específico para acne (Acne Qol). Segurança e tolerabilidade foram avaliadas pela análise de eventos adversos e por exames laboratoriais. Resultados: A idade média foi 20 anos, sendo 70% homens, com redução de 99% das lesões ao final do tratamento e remissão total das lesões em 91,5% dos participantes. A escala IGA reduziu 98% no escore ao final do tratamento. Todos os pacientes se declararam satisfeitos, com significativa melhora na qualidade de vida. Os eventos adversos foram semelhantes aos descritos na literatura. Conclusões: A isotretinoína avaliada mostrou-se igualmente eficaz, segura e bem tolerada quando comparada aos dados publicados referentes ao produto-padrão.

Introduction: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous follicles. Treatment should be early and effective to prevent scarring and psychosocial effects, and isotretinoin is the drug of choice for moderate or severe cases. Objective: To assess efficacy, safety and tolerability of an isotretinoin similar to the reference product. Methods: A bicentric study, with therapeutic intervention was conducted, including 50 participants aged 13 to 35 years, with moderate to severe acne, using isotretinoin 0.5 mg/kg/day up to 120 mg/kg. Efficacy was assessed through lesions counting, the investigator's global assessment (IGA) scale, patient satisfaction and application of the quality of life questionnaire specific for Acne (Acne Qol). Safety and tolerability were assessed by analysis of adverse events and laboratory tests. Results: Mean age was 20 years, 70% of participants were men, with a reduction of 99% of lesions after treatment and complete remission of lesions in 91.5% of participants. IGA scale reduced 98% in the score after treatment. Also, 100% of participants declared to be satisfied, with significant improvement in quality of life. Adverse events were similar to those described in the literature. Conclusion: The assessed isotretinoin was equally effective, safe and well-tolerated when compared with published data of the standard product.

Early chemabrasion for acne scars after treatment with oral isotretinoin.

BACKGROUND: Acne is an inflammatory disease of the pilosebaceous follicles. Oral isotretinoin is the treatment of choice for severe acne. Exaggerated cicatrization related to oral isotretinoin was reported in the 1980s and 1990s. Currently, dermabrasion for acne scar revision is only recommended 6 to 12 months after the completion of oral isotretinoin treatment. OBJECTIVE: To evaluate the evolution of healing from manual chemabrasion of depressed scars resulting from acne conducted within 1 to 3 months after oral isotretinoin treatment. METHODS AND MATERIALS: This was an interventional, prospective study involving 10 patients with depressed facial scars. A medium-depth chemical peel was applied to the entire face. Manual sandpaper dermabrasion was performed to areas of scarring until the appearance of bloody dew. A 6-month reepithelization follow-up was conducted. RESULTS: All of the patients presented with normal cicatrization, and neither hypertrophic scars nor keloids were observed. Depressed acne scar revision was satisfactory. CONCLUSION: Our observations may contribute to the discussion of the negative influence of oral isotretinoin on wound healing. Other studies are necessary to reevaluate the current recommendation of a 6- to 12-month waiting period after oral isotretinoin treatment before performing dermabrasion or fractional ablative laser for acne scar revision.

Avaliação do uso de colírio no paciente portador de glaucoma / Evaluation of the use of eye drops in patients with glaucoma

OBJETIVO: Identificação das principais variáveis que interferem na qualidade de instilação correta de colírio antiglaucomatoso. MÉTODOS: Realizou-se estudo transversal em 40 pacientes glaucomatosos sob tratamento clínico com uso de colírio, aplicando-se um questionário e realizando-se observações quanto à instilação. Foram investigadas as seguintes variáveis: sexo; escolaridade; idade; condições sócioeconômicas; lavagem das mãos; número de gotas por aplicação; alteração motora; pessoa que aplica o colírio; local da aplicação; contato do frasco com as pálpebras, a conjuntiva e a córnea; instrução pregressa; posição de aplicação; ardor, dor ou irritação ocular após a aplicação e acuidade visual. A partir do questionário e das observações, as variáveis citadas foram correlacionadas com a qualidade de instilação. O modelo de análise foi a regressão logística binária. RESULTADOS: Dentre todas as variáveis em questão, apenas a pessoa que aplica o colírio e a sensação de ardor, dor ou irritação ocular mostraram-se estatisticamente significativas para uma adequada instilação de colírio. CONCLUSÃO: A presença de um acompanhante e o ardor à instilação do colírio influenciaram significativamente na qualidade de instilação do mesmo.

PURPOSE:To identify the most important variables interfering with the correct topical administration of antiglaucomatous drugs. METHODS: Forty glaucomatous patients under clinical treatment were interviewed and observed while applying antiglaucomatous drugs. The following variables were analyzed: sex; age; income; washing of the hands; number of drops; motor abnormalities; availability of another person to apply the drug; place of the globe reached; bottle-eye contact; previous instruction; positioning for application; development of a burning sensation, pain or irritation. Using the questionary, the variables were correlated with the quality of instillation. RESULTS: Among all variables, only the availability of another person to apply the drug and the existence of a burning sensation, pain or eye irritation showed statistically important correlation to proper instillation. CONCLUSION: The presence of a companion and the development of burning sensation affected the quality of instillation.