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.

Queratoacantoma tratado con metotrexato intralesional: una alternativa terapéutica efectiva en casos seleccionados / Keratoacanthoma treated with intralesional methotrexate: an effective therapeutic alternative in selected cases

El Queratoacantoma es un carcinoma de células escamosas de rápido crecimiento, cuyo tratamiento definitivo contempla la resección quirúrgica. El manejo se dificulta cuando las condiciones de la lesión implican cirugías extensas o las condiciones del paciente son riesgosas al plantear manejo invasivo. Se propone el uso de Metotrexato intralesional como estrategia terapéutica alternativa al tratamiento quirúrgico tradicional. Se exponen 2 casos en los cuales se usó este método. Primero es una paciente de 91 años con queratoacantoma en región frontal, de rápido crecimiento. Segundo, un paciente de 76 años, en tratamiento anticoagulante, con lesión en cuero cabelludo. Ambos pacientes reciben inyecciones de Metotrexato, las cuales muestran resultados significativos, en cuanto a reducción de tamaño. La inyección intralesional de Metotrexato demuestra utilidad como alternativa terapéutica o como manejo neoadyuvante previo a la cirugía

Keratoacanthoma is a rapidly growing squamous cell carcinoma, which definitive treatment includes surgical resection. Therapy becomes more complex when the lesion requires extensive surgeries or the patient's conditions are risky for invasive management. The use of intralesional methotrexate is proposed as an alternative therapeutic strategy to traditional surgical treatment. Two cases are presented where this method was used. First a 91-year-old patient with rapidly growing keratoacanthoma in the frontal region. Second a 76-year-old patient, undergoing anticoagulant treatment, with a scalp lesion. Methotrexate injections were applied to both patients, with significant lesion size reduction. Intralesional injection of Methotrexate proves useful as a therapeutic alternative or as neoadjuvant management prior to surgery.

Moderate to severe plaque psoriasis - treatment with drugs of the classic scheme

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Biosimilares: consenso de expertos de la Sociedad Latinoamericana de Psoriasis (SOLAPSO) en Argentina / Biosimilars: Expert consensus of the Latin American Society of Psoriasis (SOLAPSO) in Argentina

Con la aparición de los tratamientos biológicos, se ha modificado la terapéutica de muchas enfermedades, en especial las reumatológicas, dermatológicas y oncológicas. Debido al alto costo de estos productos y el vencimiento de las patentes, la industria farmacológica desarrolla los biosimilares, fármacos que son una versión (copia) de la sustancia de un medicamento biológico original, y que pueden facilitar el acceso a estos tratamientos. Son elaborados de acuerdo a exigencias específicas de organismos reguladores en cuanto a calidad, eficacia y seguridad, y debe demostrarse que son comparables al medicamento de referencia. Este trabajo revisa las normativas regulatorias internacionales y nacionales, las controversias que rodean a los biosimilares y presenta la posición de un grupo de expertos con respecto al uso de biosimilares.

With the appearance of biological treatments, therapeutics has changed in many rheumatological, dermatological and oncological diseases. Due to the high cost of these biological medicaments and the expiration of patents, the pharmacological industry develops biosimilars, drugs that are a version (copy) of the substance of the original biological medicine, with the aim of facilitating access to these treatments. These biosimilars are prepared according to the specific requirements of regulatory bodies in terms of quality, efficacy and safety, and must be shown they are comparable to the reference product. This paper reviews the international and national regulatory framework, the controversies surrounding biosimilars, and presents the position of a group of experts regarding the use of biosimilars.

Tazarotene gel with narrow-band UVB phototherapy: a synergistic combination in psoriasis

Abstract: BACKGROUND: Narrow-band UVB (NB-UVB) has been shown to be one of the most effective treatment modalities for psoriasis. Tazarotene, a known effective anti-psoriatic modality, when combined with NB-UVB may enhance the therapeutic success. OBJECTIVE: To study clinical efficacy and safety of combination of NB-UVB with topical tazarotene 0.05% gel in psoriasis. METHOD: Thirty patients with plaque psoriasis having symmetrical lesions were enrolled for 12 weeks. All patients were instructed to apply tazarotene gel on target plaque on left side of body once daily. In addition, the whole body was irradiated with NB-UVB twice weekly. Efficacy was assessed by target plaque scoring and number of treatment sessions for clearance. RESULT: Our study resulted in 3 key findings: Firstly, therapeutic efficacy of NB-UVB was enhanced by addition of tazarotene. This enhanced efficacy was more apparent in decreasing scaling and thickness as compared to decrease in erythema. Secondly, combination therapy showed faster clearance of target plaques, with reduction in mean number of treatment sessions. Thirdly, mean cumulative NB-UVB dose needed to achieve clearance of target plaques was significantly reduced with combination therapy. STUDY LIMITATIONS: The study was not randomized or controlled, but an open-label trial. The study period was relatively short, i.e., 12 weeks, without any follow-up period. CONCLUSION: Tazarotene gel significantly enhances the therapeutic efficacy of NB-UVB irradiation with faster clearance and without serious side effects.

Pneumocystis jirovecii pneumonia induced by low-dose methotrexate in a patient with chronic urticaria

Abstract Methotrexate has immunosuppressive effects and is administered for refractory chronic urticaria. We present a case of Pneumocystis jirovecii pneumonia in a patient with refractory chronic urticaria managed by low-dose weekly methotrexate treatment (total cumulative dose 195mg). Our study highlights the importance of providing prompt diagnosis and treatment of Pneumocystis jirovecii pneumonia in patients with chronic urticaria under methotrexate therapy.

Multicenter study for efficacy and safety evaluation of a fixeddose combination gel with adapalen 01% and benzoyl peroxide 2 5% (Epiduo® for the treatment of acne vulgaris in Brazilian population

Abstract: BACKGROUND: The current options for the treatment of acne vulgaris present many mechanisms of action. For several times, dermatologists try topical agents combinations, looking for better results. OBJECTIVES: To evaluate the efficacy, tolerability and safety of a topical, fixed-dose combination of adapalene 0.1% and benzoyl peroxide 2.5% gel for the treatment of acne vulgaris in the Brazilian population. METHODS: This is a multicenter, open-label and interventionist study. Patients applied 1.0 g of the fixed-dose combination of adapalene 0.1% and benzoyl peroxide 2.5% gel on the face, once daily at bedtime, during 12 weeks. Lesions were counted in all of the appointments, and the degree of acne severity, overall improvement, tolerability and safety were evaluated in each visit. RESULTS: From 79 recruited patients, 73 concluded the study. There was significant, fast and progressive reduction of non-inflammatory, inflammatory and total number of lesions. At the end of the study, 75.3% of patients had a reduction of >50% in non-inflammatory lesions, 69.9% in inflammatory lesions and 78.1% in total number of lesions. Of the 73 patients, 71.2% had good to excellent response and 87.6% had satisfactory to good response. In the first week of treatment, erythema, burning, scaling and dryness of the skin were frequent complaints, but, from second week on, these signals and symptoms have reduced. CONCLUSION: The fixed-dose combination of adapalene 0.1% and benzoyl peroxide 2.5% gel is effective, safe, well tolerated and apparently improves patient compliance with the treatment.

Oral isotretinoin in photoaging: objective histological evidence of efficacy and durability

AbstractBACKGROUND:The off-label use of oral isotretinoin in photoaging is a therapeutic tool that has been used by dermatologists. There are few studies to corroborate its effectiveness and durability.OBJECTIVES:To assess, both clinically and histologically, the changes caused by the use of oral isotretinoin in skin photoaging as well as the duration of the effects.METHODS:20 female patients, aged 45-50 years, with phototypes II-VI, none of whom had experienced menopause, were treated with 20mg oral isotretinoin, 3 days a week, for 12 weeks. They underwent clinical analysis and skin biopsies in the pre-auricular region, while histologic cuts enabled assessment of the solar elastosis level and morphologic analysis.RESULTS:Clinically, patients, as well as the researching and the assessor physicians, noticed improvement in skin quality. One patient presented severe solar elastosis, 11 manifested the moderate form, while 8 presented the discreet type. According to histological analysis, 65% of the patients revealed alteration in the distribution and thickness of the elastic fibers, which can be interpreted as a histological improvement, while 60% showed an increase in collagen density. We observed an increase in collagen density, from 51.2% to 57.4%, (p=0.004). At the end of the 12-week follow-up period, this density decreased to 54.7% (p=0.050). There was an increase in the density of elastic fibers, from 26.5% to 31.3%, (p=0.02), which had dropped to 27.5% at the end of the 12-week follow-up period.CONCLUSIONS:The study confirmed the role of oral isotretinoin in remodeling the extracellular matrix against photoaging, as well as its durability after 12 weeks, especially when we consider collagen fibers.

Combined acute interstitial pneumonitis and pancytopenia induced by low-dose methotrexate in a hemodialysis patient treated for bullous pemphigoid

Methotrexate has been widely used for many years in the treatment of a variety of diseases. Acute pneumonitis and bone marrow suppression are very serious side effects in methotrexate treatment. A 48-year-old man with end-stage renal disease undergoing chronic hemodialysis developed combined acute pneumonitis and pancytopenia after a cumulative dose of 20 mg methotrexate for bullous pemphigoid. Continuous renal replacement therapy (CRRT) can effi ciently decrease serum methotrexate concentration. A rapid improvement of clinical symptoms and resolution of pulmonary opacifi cation were found after CRRT. Blood cell counts returned to normal after component blood transfusion and cytokine supportive therapy. Patients with impaired renal function are at high risk of methotrexate toxicity, and low-dose methotrexate should be prescribed with great caution.

Pseudo-acne fulminans associated with oral isotretinoin

Acne fulminans is a rare and serious condition characterized by the sudden onset of nodular and ulcerative acne lesions associated with systemic symptoms. It has been recognized a subset of patients with a sudden worsening of acne, often during treatment with oral isotretinoin, but without the strong presence of systemic involvement. Recognized by some authors as "pseudo-acne fulminans" or " acne fulminans sine fulminans," we report a case with these features in order to draw attention to the recognition and early management of this manifestation.

A prospective, open, comparative study of 5% potassium hydroxide solution versus cryotherapy in the treatment of genital warts in men

BACKGROUND: Genital warts are caused by human papillomavirus infection and represent one of the most common sexually transmitted diseases. Many infections are transient but the virus may recur, persist, or become latent. To date, there is no effective antiviral treatment to eliminate HPV infection and most therapies are aimed at the destruction of visible lesions. Potassium hydroxide is a strong alkali that has been shown to be safe and effective for the treatment of genital warts and molluscum contagiosum. Cryotherapy is considered one of the most established treatments for genital warts. No comparative trials have been reported to date on the use of potassium hydroxide for genital warts. OBJECTIVE: A prospective, open-label, randomized clinical trial was conducted to compare topical potassium hydroxide versus cryotherapy in the treatment of genital warts affecting immunocompetent, sexually active men. METHODS: Over a period of 10 months, 48 patients were enrolled. They were randomly divided into two groups and selected on an alternative basis for either potassium hydroxide therapy or cryotherapy. While response to therapy did not differ substantially between both treatment modalities, side effects such as local pain and post-treatment hypopigmentation were considerably more prevalent in the groups treated using cryotherapy. Result: In our study, potassium hydroxide therapy proved to be at least as effective as cryotherapy and offered the benefit of a better safety profile. CONCLUSION: Topical 5% potassium hydroxide presents an effective, safe, and low-cost treatment modality for genital warts in men and should be included in the spectrum of therapies for genital warts. .

A randomized placebo-controlled double-blind pilot study of methotrexate in the treatment of H1 antihistamine-resistant chronic spontaneous urticaria.

Background: Chronic urticaria not responsive to antihistamines is a diffi cult disease to manage. Methotrexate has been used in diffi cult chronic urticarias with some benefi t. Objective: To evaluate the effi cacy of methotrexate in the treatment of chronic spontaneous urticaria poorly responsive to H1 antihistaminics. Methods: In a randomized double-blind trial at the Department of Dermatology and Venereology of a tertiary care centre, 29 patients with chronic spontaneous urticaria not responding well to H1 antihistaminics were recruited. Patients were randomly allocated to receive either a weekly dose of oral methotrexate 15 mg or placebo (calcium carbonate) for a total duration of 12 weeks, after which treatment was stopped and patients were followed up for relapse of urticaria. Each group also received levocetrizine 5 mg once daily for symptom control. Primary outcome measured was a reduction by >2/3rd of baseline urticaria scores after 12 week therapy. Secondary outcome was a reduction in antihistamine requirement after stopping therapy. Results: Fourteen patients were randomized to the methotrexate group and fi fteen patients to the placebo group. Out of 17 patients who completed therapy, the primary outcome was achieved by 3.5 ± 1.9 (out of 10) patients in the methotrexate group and by 3.67 ± 1.03 (out of 7) patients in the placebo group (P > 0.05). Ten patients followed up, after stopping therapy, for a mean period of 3.5 ± 2.4 months; 3 remained in remission and 7 had relapsed. One patient had uncontrollable nausea and vomiting after taking methotrexate and was withdrawn from the study. The placebo group did not experience any side effects. Conclusions: Methotrexate 15 mg weekly for 3 months did not provide any additional benefi t over H1 antihistamines in this study but an adequately powered study with longer follow up is required to assess its utility.

Actualización: uso de isotretinoína oral en rosácea / Update: use of oral isotretinoin in rosacea

La rosácea es una dermatosis facial inflamatoria crónica caracterizada por periodos intermitentes de exacerbación y remisión. La etiología es desconocida y factores genéticos y ambientales están involucrados en su desarrollo. El tratamiento tópico y sistémico controla la rosácea en forma parcial. La Isotretinoína oral es útil por sus propiedades antiinflamatorias,inmunomoduladoras y de reducción del flujo sanguíneo.

Rosacea is a chronic facial inflammatory dermatoses characterized by intermittent periods of clinical exacerbation and remission. The etiology is unkown. Genetic and external factors are involved in the pathogenesis. Topical and oral treatments partially control the disease. Oral Isotretinoin can be useful because of the antiinflammatory, inmumodulating actions and because it reduce the blood flow.

Comparative study of actinic keratosis treatment with 3% diclofenac sodium and 5% 5-fluorouracil / Estudo comparativo do tratamento de ceratoses actinicas com diclofenaco sodico 3% e 5-fluorouracil 5%

BACKGROUND: Actinic keratosis is a frequent lesion which occurs in sunlight exposed areas. Diclofenac sodium and 5-Fluorouracil are effective, non-invasive and easy-to-apply topical treatment options. OBJECTIVES: To assess and compare the effectiveness of 3% diclofenac sodium associated with 2.5% hyaluronic acid and of 5% 5-Fluorouracil for the treatment of actinic keratosis, as well as the patient's degree of satisfaction and tolerability. METHODS: 28 patients with a clinical diagnosis of actinic keratosis were randomized to receive diclofenac sodium or 5-Fluorouracil and were clinically assessed before and after treatment as well as 8 weeks after the end of treatment. Modified versions of the Investigator and Patient Global Improvement Scores were used. RESULTS: The average number of lesions in the diclofenac sodium group before and after treatment was 13.6 and 6.6 (p<0,001), respectively, while it was 17.4 and 3.15 (p<0.001) in the 5-Fluorouracil group. There was a significant reduction in the number of lesions in the 5-Fluorouracil group in relation to the diclofenac sodium group (p<0.001). To the non-blinded physician, there was a higher satisfactory therapeutic response in the 5-Fluorouracil group (p<0.001); to the blinded physician, there was a higher satisfactory response in this same group, although not statistically significant (p=0.09). There was a high degree of satisfaction in both groups (73% in the diclofenac sodium group and 77% in the 5-Fluorouracil group; p=0.827). Regarding adverse effects, the diclofenac sodium group presented a higher degree of satisfaction (93.3% vs 38.4%; p=0.008). Erythema, edema, crusts and itching were significantly higher in the 5-Fluorouracil group. CONCLUSION: We concluded that 5-Fluorouracil was more effective; however, it showed lower tolerability than diclofenac sodium. .

FUNDAMENTOS: Ceratose actínica é uma lesão frequente que ocorre em áreas de exposição solar. Diclofenaco sódico e 5-Fluorouracil são opções de tratamento tópico efetivo, não invasivo e de fácil aplicação. OBJETIVOS: Avaliar e comparar a efetividade do diclofenaco sódico 3% associado ao ácido hialurônico 2,5% e do 5-fluorouracil 5% no tratamento de ceratose actínica, assim como a tolerabilidade e o grau de satisfação do paciente. MÉTODOS: 28 pacientes com diagnóstico clínico de ceratoses actínicas foram randomizados para receber diclofenaco sódico ou 5-fluorouracil e foram avaliados clinicamente antes, ao término e após 8 semanas do tratamento. Utilizou-se o Escore de Melhora Global do Investigador e do Paciente, ambos modificados. RESULTADOS: A média de lesões no grupo do diclofenaco sódico antes e depois do tratamento foi de 13,6 e 6,6 (p<0,001) e no grupo do 5-fluorouracil foi de 17,4 e 3,15 (p<0,001). Houve uma diminuição significativa no número de lesões no grupo do 5-fluorouracil em relação ao grupo do diclofenaco sódico (p<0,001). Para o médico não cegado houve uma resposta terapêutica satisfatoriamente maior no grupo do 5-fluorouracil (p<0,001); para o cegado, houve uma maior resposta nesse mesmo grupo, porém não significativa (p=0,09). Houve alta satisfação com o tratamento em ambos os grupos (73% no diclofenaco sódico e 77% no 5-fluorouracil; p=0,827). Já em relação aos efeitos adversos, o grupo do diclofenaco sódico apresentou taxa de satisfação maior (93,3% vs 38,4%; p=0,008). Eritema, edema, crostas e prurido foram significativamente maiores no tratamento com 5-fluorouracil. CONCLUSÕES: Concluímos que o 5-fluorouracil foi mais efetivo, ...

Lípidos séricos y enzimas hepáticas en pacientes tratados con isotretinoína oral / Seric lipids and hepatic enzymes in patients treated with oral isotretinoin

La isotretinoína es un retinoide empleado en el tratamiento del acné. El objetivo de este estudio fue determinar colesterol, triglicéridos, transaminasa glutámico oxalacética, transaminasa glutámico pirúvica y fosfatasa alcalina, pretratamiento, trimestralmente durante el tratamiento y postratamiento en pacientes tratados con isotretinoína oral procedentes de consultas dermatológicas del Estado Carabobo. La edad Promedio de la muestra estudiada fue (19,4 ± 4,7 años), los valores de colesterol mostraron variación estadísticamente significativa para el primer trimestre (P=0,044), Los triglicéridos se incrementaron en el segundo trimestre (P=0,036) para ambos géneros, mientras que para el tercer trimestre solo el género masculino experimentó incremento. Transaminasa glutámico oxalacético en el primer trimestre se incrementó en el género femenino, sin embargo, no fue estadísticamente significativo. En los demás trimetres los valores de las enzimas hepáticas no superaron los valores de referencia. No se evidencian diferencias estadísticamente significativas entre los niveles del pretratamiento y postratamiento. Es recomendable monitorear los lípidos séricos y transaminasas durante el primer trimestre de tratamiento aunque los cambios observados fueron discretos en la mayoría de los pacientes

Isotretinoin is a retinoid used to treat acne. The aim of this sindy was to determine cholesterol, triglyceride, seric glutami oxalacetic transaminase, seric glutami pyruvic transaminase and alkaline phosphatase pretreatment, quarterly during treatment and post-treatment in patients treated with oral isotretinoin dermatological consultations from Carabobo State. The overage age of the sample was (19.4 ± 4.7 years), cholesterol values showed statistically significant variation in the first quarter (P=0.044). Triglycerides increased in the second quarter (P=0.036) for both genders, while for the third quarter only increase in male. Seric glutami oxalacetic transaminase in the first quarter increased in females, but was not statistically significant. In other quarters the liver enzyme values did not exceed reference values. No statistically significant differences are evident between the levels of pretreatment and postreatment. It is advisable to monitor serum lipids and transaminases during the first quarter of treatment although the observed changes were discrete in most patients

Infliximab: Efficacy in psoriasis.

Moderate to severe psoriasis often needs to be addressed with standard disease modifying therapies such as methotrexate, cyclosporine, acitretin or ultraviolet radiation, which have their potential benefits and limitations. The tumor necrosis factor-alpha (TNF-α) is elevated in psoriatic plaques compared to non lesional skin as well as in the plasma of patients with moderate to severe psoriasis. Infliximab, a TNF-α blocker, has been recommended for the treatment of moderate to severe plaque psoriasis in adults who have failed to respond to these therapies or who cannot tolerate them. Its specific action on the bound and membrane forms of the pro-inflammatory cytokine TNF-α has made it the molecule of choice for obtaining quicker and longer remission in recalcitrant cases. However, the widespread use of infliximab in the Indian subcontinent is limited by its cost. This article reviews the international guidelines for use of infliximab, its dosage patterns, and efficacy in chronic plaque psoriasis, nail psoriasis, erythrodermic psoriasis, and pustular psoriasis as well as Indian experience.