Skin protectant drug products for over-the-counter human use; final monograph; technical amendment. Final rule; technical amendment.
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The Food and Drug Administration (FDA) is amending the regulation that established conditions under which over-the-counter (OTC) skin protectant drug products are generally recognized as safe and effective and not misbranded as part of FDA's ongoing review of OTC drug products. This amendment revises several of the indications for OTC skin protectant drug products to provide additional labeling claims that should not have been excluded from the final monograph (FM). (+info)
Herbal creams used for atopic eczema in Birmingham, UK illegally contain potent corticosteroids.
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AIMS: To determine whether "herbal creams" reported as being effective for the treatment of childhood atopic eczema contained corticosteroids. METHODS: Patients attending the paediatric dermatology clinic at Birmingham Children's Hospital, April 2001 to March 2002, and who reported using "herbal creams" with good effect for atopic eczema were asked to submit the cream for analysis. Hydrocortisone, clobetasone butyrate, betamethasone valerate, and clobetasol propionate were analysed by HPLC. RESULTS: Twenty four creams from 19 patients, median (interquartile range) age 3.82 (0.69-7.98) years were analysed. All five creams labelled Wau Wa and the two labelled Muijiza cream contained clobetasol propionate. Thirteen of 17 unnamed creams contained corticosteroids: clobetasol proprionate (n = 4), clobetasol proprionate + hydrocortisone (n = 1), betamethasone valerate (n = 2), clobetasone butyrate (n = 3), and hydrocortisone (n = 2); there was an unidentified peak in one. Further analysis suggested Wau Wa cream contained approximately 20% proprietary Dermovate Cream in a paraffin base. No parents were aware that the creams contained steroid. CONCLUSIONS: The majority of herbal creams analysed illegally contained potent or very potent topical steroids. There is an urgent need for tighter regulation of herbal creams and for increased public education about the potential dangers of alternative therapies. (+info)
Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial.
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OBJECTIVE: To study the efficacy and tolerability of borage oil, which contains a high concentration of gamma linolenic acid, in children and adults with atopic eczema. DESIGN: Single centre, randomised, double blind, placebo controlled, parallel group trial. SETTING: Acute district general hospital in Nuneaton, England. PARTICIPANTS: 151 patients, of whom 11 failed to return for assessment, leaving an evaluable population of 140 (including 69 children). INTERVENTION: Adults received four capsules of borage oil twice daily (920 mg gamma linolenic acid), and children received two capsules twice daily, for 12 weeks. MAIN OUTCOME MEASURES: Change in total sign score at 12 weeks measured with the six area, six sign, atopic dermatitis (SASSAD) score (primary endpoint); symptom scores, assessed on visual analogue scales; topical corticosteroid requirement, assessed on a five point scale; global assessment of response by participants; adverse events and tolerability. RESULTS: The mean SASSAD score fell from 30 to 27 in the borage oil group and from 28 to 23 in the placebo group. The difference between the mean improvements in the two groups was 1.4 (95% confidence interval -2.2 to 5.0) points in favour of placebo (P = 0.45). No significant differences occurred between treatment groups in the other assessments. Subset analysis of adults and children did not indicate any difference in response. The treatments were well tolerated. CONCLUSION: Gamma linolenic acid is not beneficial in atopic dermatitis. (+info)
Epidermal overexpression of interleukin-19 and -20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine a or calcipotriol.
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Interleukin-19, 20, and 24 are new members of the IL-10 family binding and signaling through the IL-20R1/IL-20R2 heterodimer, while IL-20 and 24 also bind to the IL-20R2/IL-22R1 heterodimer. Using in situ hybridization we have studied mRNA expression of IL-19, 20, and 24 and their related receptor chains in skin from psoriatic patients before and during short-term treatment with either oral cyclosporine A or topical calcipotriol. In untreated lesions IL-19 and IL-20 mRNA was expressed focally in epidermis above the dermal papillae, whereas IL-24 was expressed in mononuclear cells in the dermal infiltrate. The expression of IL-19 and 20 mRNA was confined to the basal and suprabasal keratinocytes. No expression of IL-19 and 20 mRNA could be detected in uninvolved psoriatic skin. Treatment with cyclosporine A and calcipotriol resulted in disappearance of the IL-19 and 20 mRNA. Expression of mRNA for the receptor chains IL-20R1 and IL-20R2 was found throughout the psoriatic epidermal layer, whereas IL-22R1 mRNA was predominantly expressed in the superficial part of the psoriatic epidermis. These findings show that IL-19 and IL-20 are synthesized by a distinct population of keratinocytes. It remains to be clarified whether IL-19 and IL-20 are implicated in the pathogenesis of psoriasis. (+info)
Dimethylfumarate is a potent inducer of apoptosis in human T cells.
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Fumaric acid esters (FAE) have been used for the systemic treatment of psoriasis in Germany for almost 50 years. Recently, it has been shown that dimethylfumarate (DMF) as the main ingredient of the marketed FAE mixture is a potent inhibitor of the nuclear transcription factor NF-kappaB. DMF was also shown to induce apoptosis in various cells. Because T cells play a crucial role in psoriasis pathogenesis, we asked whether DMF and its main metabolite methylhydrogenfumarate (MHF) were able to induce apoptosis in these cells. Purified human T cells were treated with DMF and MHF (1-20 microg/mL) and stimulated with interleukin 2, anti-CD3 antibodies or both for 48 h, and apoptosis was subsequently determined by the expression of Apo2.7 as well as by terminal deoxynucleotide transferase nick end labeling. The expression of antiapoptotic protein Bcl-2 was simultaneously determined. The results showed a dose-and-time dependent up-regulation of Apo2.7 expression and DNA fragmentation by DMF preferable in stimulated T cells. MHF and the solvent dimethyl sulfoxide were without effect. DMF, but not MHF, led to a concentration-dependent decrease of Bcl-2 expression in interleukin-2-stimulated T cells. The data provide evidence that the effect of FAE treatment of psoriasis may at least in part be due to induction of apoptosis in activated T cells. (+info)
The health assessment questionnaire (HAQ) is strongly predictive of good outcome in early diffuse scleroderma: results from an analysis of two randomized controlled trials in early diffuse scleroderma.
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OBJECTIVE: Scoring poorly on the health assessment questionnaire (HAQ) has recently been shown to be a strong predictor of morbidity and mortality in rheumatoid arthritis (RA), while a good HAQ score is predictive of a better outcome. In patients presenting with early diffuse scleroderma prognosis is variable. Our goal was to determine possible baseline predictors of future good outcomes. METHODS: We used the raw data from two randomized controlled trials (RCTs) in early diffuse scleroderma: methotrexate (Pope et al.) and D-penicillamine (Clements et al.). Subjects in the methotrexate trial were divided into the following groups: (1) those with at least 20% improvement in the primary outcome measurements [patient global assessment, physician global assessment, UCLA skin tethering score, modified Rodnan skin score (MRSS), DLCO as % predicted and HAQ disability] at 1 yr vs (2) the others. Baseline factors (including age, gender, skin scores, physician and patient global assessments, HAQ disability and pain scores, DLCO and physical parameters) were analysed to find baseline variables strongly correlated with later improvement. These variables were explored in the D-penicillamine trial to determine if (in a separate trial) they were still predictive of improved outcome at 1 and 2 yr. Adjusted models were used to find baseline predictors of good outcome. The median HAQ-DI was 1.3 (methotrexate) and 1.0 (D-penicillamine). RESULTS: A baseline HAQ disability score of less than the median was predictive of at least a 20% improvement at 1 and 2 yr with odds ratios of 1.77 to 5.05, in four of the five outcome measurements (in both groups); with strongly significant P values for 3 of 5 outcomes (UCLA skin score, MRSS, patient global skin score; P<0.02) from the methotrexate study group. These three outcomes were strongly correlated with improvement (r between 0.25 and 0.35). Although data from the D-penicillamine trial were less convincing, in both trials the less than median HAQ-DI and HAQ pain scores showed a stronger association with improved outcome, more so than age, gender, skin score and baseline global assessment. CONCLUSION: A low baseline HAQ (defined as less than the median HAQ score) is predictive of improved outcome in diffuse scleroderma at 1 and 2 yr. (+info)
Topical treatment with 22-oxacalcitriol (OCT), a new vitamin D analogue, caused severe hypercalcemia with exacerbation of chronic renal failure in a psoriatic patient with diabetic nephropathy; a case report and analysis of the potential for hypercalcemia.
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Vitamin D has been used for topical treatment of psoriasis, and 22-oxacalcitriol (OCT), shown to be less calcemic, was developed for the topical treatment of psoriasis in Japan. Recently, we treated a psoriatic patient with diabetic nephropathy who developed severe hypercalcemia with exacerbation of chronic renal failure by the use of topical OCT. Analysis of the reported cases demonstrated that both the severity of psoriasis and renal dysfunction are critical factors in the induction of hypercalcemia in the topical treatment of psoriasis. Therefore, we must pay attention to the severity of psoriasis, especially when complicated by renal function impairment. Regular monitoring of Ca and renal function is essential to avoid life-threatening hypercalcemia from the topical treatment with vitamin D analogues. (+info)
A topical skin protectant against chemical warfare agents.
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BACKGROUND: Sulfur mustard and VX are potent chemical warfare agents that penetrate rapidly through the skin, causing severe prolonged injuries and sometimes death. OBJECTIVES: To develop a topically applied pretreatment that will act as a barrier and prevent the absorption of these agents through the skin, reducing morbidity and saving life. METHODS: Several formulations were developed and tested in preclinical animal studies in pigs. The protecting cream was applied as a single application (0.5-1 ml/100 cm2) prior to exposure (10 minutes to 12 hours) to sulfur mustard or VX. Assessment of sulfur mustard-induced skin damage was based on clinical and histologic evaluations. When tested against VX, clinical signs and blood cholinesterase activity were monitored. At the final stage of development, safety studies were conducted in animals and in human volunteers. RESULTS: The formulation that gave the best results, coded IB1 (under patent application), provided significant protection against a 1 hour exposure to sulfur mustard (droplets or vapor). All the pigs pretreated with IB1 cream survived a 1-4 hour challenge of 2xLD50 VX and did not exhibit any overt clinical signs. Protection was exhibited even when the cream was applied 12 hours (single application) prior to exposure. IB1 was found to be non-irritating in animals and humans. No adverse effects were found in a Phase I clinical study in young healthy volunteers when the cream was applied to around 20% of the skin surface (results presented elsewhere). CONCLUSIONS: IB1 cream has been shown to be a safe and effective topical skin protectant against the chemical warfare agents sulfur mustard and VX. (+info)