Fludroxycortide cream as an alternative therapy for actinic cheilitis.

OBJECTIVES: The objective of the study is to assess, by clinical follow-up, the efficacy of the dermatological cream Fludroxycortide 0.125 mg/g (Drenison®) in the treatment of actinic cheilitis (AC). MATERIAL AND METHODS: Twenty-three patients diagnosed with AC participated in the study. Fifteen were submitted to corticotherapy with Fludroxycortide, applied three times a day for up to 6 weeks, associated with lip sunscreen (LS) before sun exposure. In the control group of eight patients, only the use of LS was established. At each weekly return, a photographic record was made of the lesion. After treatment, images were evaluated and scores were assigned to verify clinical evolution. Also, patients treated with Fludroxycortide responded to a questionnaire, to assess drug tolerability and treatment satisfaction. RESULTS: In the group treated with Fludroxycortide (n = 15), five patients showed total improvement, seven presented partial improvement, and three showed no clinical change. Concerning the patients treated with LS (n = 8), one presented total remission of the clinical lesion characteristics, four exhibited partial improvement, and three exhibited no clinical lip alteration. No case presented symptom worsening. Of the 15 patients undergoing corticotherapy, 12 were satisfied and reported that the product was not irritating and contributed to lesion improvement. CONCLUSIONS: Conventional treatment with LS was effective in the remission of some AC lesions, but treatment responses were improved when associated with Fludroxycortide, especially in the more severe cases. CLINICAL RELEVANCE: As it is a non-invasive therapy leading, in most cases, to adequate clinical results, safety, and tolerability, Fludroxycortide can be considered an effective alternative treatment for AC.

Novel chemical suppressors of long QT syndrome identified by an in vivo functional screen.

BACKGROUND: Genetic long QT (LQT) syndrome is a life-threatening disorder caused by mutations that result in prolongation of cardiac repolarization. Recent work has demonstrated that a zebrafish model of LQT syndrome faithfully recapitulates several features of human disease, including prolongation of ventricular action potential duration, spontaneous early afterdepolarizations, and 2:1 atrioventricular block in early stages of development. Because of their transparency, small size, and absorption of small molecules from their environment, zebrafish are amenable to high-throughput chemical screens. We describe a small-molecule screen using the zebrafish KCNH2 mutant breakdance to identify compounds that can rescue the LQT type 2 phenotype. METHODS AND RESULTS: Zebrafish breakdance embryos were exposed to test compounds at 48 hours of development and scored for rescue of 2:1 atrioventricular block at 72 hours in a 96-well format. Only compounds that suppressed the LQT phenotype in 3 of 3 fish were considered hits. Screen compounds were obtained from commercially available small-molecule libraries (Prestwick and Chembridge). Initial hits were confirmed with dose-response testing and time-course studies. Optical mapping with the voltage-sensitive dye di-4 ANEPPS was performed to measure compound effects on cardiac action potential durations. Screening of 1200 small molecules resulted in the identification of flurandrenolide and 2-methoxy-N-(4-methylphenyl) benzamide (2-MMB) as compounds that reproducibly suppressed the LQT phenotype. Optical mapping confirmed that treatment with each compound caused shortening of ventricular action potential durations. Structure activity studies and steroid receptor knockdown suggest that flurandrenolide functions via the glucocorticoid signaling pathway. CONCLUSIONS: Using a zebrafish model of LQT type 2 syndrome in a high-throughput chemical screen, we have identified 2 compounds, flurandrenolide and the novel compound 2-MMB, as small molecules that rescue the zebrafish LQT type 2 syndrome by shortening the ventricular action potential duration. We provide evidence that flurandrenolide functions via the glucocorticoid receptor-mediated pathway. These 2 molecules and future discoveries from this screen should yield novel tools for the study of cardiac electrophysiology and may lead to novel therapeutics for human LQT patients.

Extensive keloid formation and progression after each vaccination.

Keloids are scars that extend beyond the original wound boundaries. They typically occur in darker skinned individuals with a familial tendency. Keloid formation has occurred after vaccination with bacilli Calmette-Guerin (BCG), small pox and hepatitis B vaccinations. We report the case of a 45-year-old female patient who developed extensive keloidal scars on her bilateral upper arms beginning in childhood after routine vaccinations. These keloids progressed with additional vaccines given at the same sites. Keloidal scars develop in anatomic areas exposed to increased skin tension as was seen in this patient. Treatment of these keloids is difficult but typically involves surgical excision, cryotherapy, radiation and intralesional and topical corticosteroids.

Linear cutaneous lupus erythematosus in the lines of Blaschko.

Eleven patients with linear cutaneous lupus erythematosus following the lines of Blaschko have been previously reported in the literature. We describe a child with this entity following Blaschko lines on the trunk. The patient responded to oral hydroxychloroquine therapy combined with topical flurandrenolide tape resulting in resolution with atrophic scarring. The clinical and histological features of linear cutaneous lupus erythematosus are discussed and a review of the literature is presented.

Lichen planus associated with milia.

The formation of milia is well recognized in both bullous and inflammatory dermatoses. There are several reports of milia developing in a rare variant of lichen planus pilaris known as lichen planus follicularis tumidus (LPFT), but the association of milia with other types of lichen planus (LP) has not been documented in the literature. We report five patients who developed milia during the course of either drug-induced or idiopathic LP and one in whom milia developed in a lichenoid tattoo reaction. Milia were noted to occur transiently during the resolving phase of LP. Most cases were severe enough to warrant treatment with systemic steroids. The association of milia with LP is not restricted to the rare clinical variant LPFT. We speculate that a severe lichenoid reaction with basal layer degeneration may precipitate the formation of milia in some cases of LP.

Treatment of recurrent earlobe keloids.

The use of complete surgical excision and postoperative pressure with steroid-impregnated tape has been evaluated in fifty-seven patients with recurrent earlobe keloids. All patients underwent conventional treatment previously, which was not curative. In a four-year follow-up of the method described here, four recurrences occurred. Patients' failure to use the recommended pressure earring and alteration in endocrine balance were noted in three of the four patients with recurrent keloids.

Estudo clínico com fluorandrenolida tópica oclusiva no tratamento de dermatoses que respondem a corticoterapia / Clinical study with topical occlusive flurandrenolide in the treatment of dermatosis responsive to corticotherapy

Um total de 30 pacientes, adultos e crianças de ambos os sexos, portadores de diversas dermatoses, foi tratado com corticoterapia oclusiva, usando-se uma fita plástica impregnada com fluorandrenolida. Os resultados finais constituíram-se em excelente e bom, num total de 30 casos (100%), näo havendo aparecimento de intolerância no uso do medicamento em qualquer dos pacientes. A segurança e comodidade da preparaçäo, evidenciadas pela ausência de reaçöes adversas e praticidade no uso, demonstradas pela boa aceitaçäo de todos os pacientes estudados, leva-nos a concluir que a fluorandrenolida em fita plástica adesiva constitui excelente e prático recurso terapêutico em dermatoses que respondem ao uso dos corticóides tópicos

Tratamento de dermatoses com o uso da fita plástica impregnada com fluorandrenolida / Treatment of dermatoses with the use of adhesive plastic tape impregnated with flurandrenolide

Um total de 30 pacientes adultos e crianças de ambos os sexos, portadores de variadas dermatoses, foram submetidos a terapêutica tópica com uma nova forma medicamentosa, constituída de fita plástica adesiva impregnada com fluorandrenolida na concentraçäo de 4 mcg/cm2. A aplicaçäo foi por períodos de 24 ou 48 horas, e os resultados obtidos foram considerados excelentes em 22 pacientes, bons em 5, melhora parcial em 2, havendo reaçäo discreta de hipersensibilidade em apenas um paciente, considerado como piora

[Anti-inflammatory activity of a topical glucocorticoid, fludroxycortide tape in experimental animals (author's transl)].

Fludroxycortide tape is a thin plastic tape which contains a synthetic glucocorticoid, fludroxycortide of 4 microgram/cm2. fludroxycortide tape with a topical application of 1 cm2 inhibited significantly contact hypersensitivities to oxazolone and picryl chloride in the ear skin of mice and PCA caused by IgE-like antibodies in the depilated abdominal skin of rats. Topical application of 1 to 4 cm2 of fludroxycortide tape produced a significant inhibition against histamine-induced vascular permeability, skin edema induced by intradermal injection of carrageenin into the depilated back and ear edema induced by topical application of croton oil in rats. Topical to oxazolone in dose-dependent manner, and had no thymolytic action, while in a dose of 100 microgram/ear, thymus atrophy occurred. Ear edema induced by croton oil was markedly inhibited by topical application of fludroxycortide (0.4 microgram/ear). Thus, fludorxycortide tape has topical anti-inflammatory activity against both allergic and non-allergic inflammation in mice and rats, and the topical anti-inflammatory activity of fludroxycortide appears to be favourably dissociated from its thymolytic action.

New cream vehicle for flurandrenolide.

New methods are now available to help select vehicles for topical corticosteroids. In the development of a new cream vehicle for flurandrenolide, the goal was a cream base with optimal solubility for release of the drug, minimal irritation potential, and no sensitizing preservatives. Vasoconstriction tests make selection much more scientific, and a newer method for such testing is described in detail. Irritation testing then helped determine the vehicle concentration that was least irritating. Final studies included double-blind comparisons with the previous formulation in the treatment of psoriatic patients.

Tumbleweed dermatitis.

Russian thistle (Salsola kali), the most common plant referred to as "tumbleweed" in the western United States, can cause a dermatitis in persons who come into direct contract with it. Tests were conducted to determine the mechanism of this dermatitis. Mechanical contact with plant branches, as well as scratch, patch, and photopatch tests with Russian thistle extract and scratch tests with 1.5% potassium nitrate, a plant constituent, were employed. These tests, along with transparent adhesive tape preparations and a skin biopsy, showed that in nonsensitized persons, dermatitis was due only to mechanical irritation of plant floral bracts. In sensitized individuals, Russian thistle floral bracts pierced the skin and stimulated an urticarial reaction.

A separation of clinical from epidermal thinning effect in the topical glucocorticoid clobetasone butyrate.

Clobetasone butyrate ointment has been shown to be more effective in treating psoriasis and eczema than flurandrenolone ointment yet to cause less epidermal thinning in a human experimental model. This is an indication that the clinical activity of topical glucocorticoids may not necessarily be inseparable from their propensity to cause atrophy of the skin.

The clinical assessment of topical corticosteroid activity.

Glucocorticoid-induced vasoconstriction of human skin has provided a useful guide to topical anti-inflammatory activity. The concentration and base in which a steroid is used influence this activity, and traditional greasy ointments are probably the most effective vehicles. Confirmation of clinical effectiveness should be by double-blind comparison in patients with bilateral skin lesions. Psoriasis provides a more discriminating test of steroidal activity than eczema; the use of occlusive dressings may mask differences between compounds. Short-term trials are informative but in patients with chronic diseases, longer studies should also be done.

A new model for human bioassay of topical corticosteroids.

The aiblity of topical corticosteroids to reduce the size of weals induced with histamine on human skin was used as a human bioassay model to assess their relative efficacy. Histamine was introduced by the pinprick method and various topical corticosteroids were assessed. It is a simple, easy and reliable procedure which can be used on both white and dark people. Even though it is a non-clinical assay, it possesses close similarity to processes involved in the development of clinical dermatoses.