tretinoin and calcipotriene

Porokeratos of Mibelli is a rare inherited disorder of epidermal keratinization, whose pathogenesis is not fully understood. The common clinical feature is a erythematous plaque surrounded by a hyperkeratotic border. The histopathologic hallmark is a parakeratotic cornoid lamella. An unusual case of porokeratosis gigantea, a morphological variant of classical porokeratosis of Mibelli, is reported. The pathogenesis, taking in account especially the clonal hypothesis and premalignant nature of porokeratosis, is discussed.

Topics: Acitretin; Aged; Calcitriol; Dermatologic Agents; Drug Combinations; Female; Fluorouracil; Humans; Porokeratosis; Tretinoin; Urea; Vitamin A

Various studies have shown the blocking effects of topical agents on UVB penetration, which can be used in combination with phototherapy. In this study, the photoprotective effects of 0.005% calcipotriol, 0.05% clobetasol-17-propionate, and 0.1% tretinoin, which can be used in combination with broad-band UVB, were investigated in an in vivo test. In a study group of 20 patients, phototests were performed to determine minimal erythema doses (MED) and the tests were repeated with thin (0.1 cc/25 cm2) and thick (0.3 cc/25 cm2) calcipotriol, clobetasol-17-propionate, and tretinoin in cream forms and sunscreen. After determining the MED, the test was repeated in another 20 patients with thin and thick calcipotriol and clobetasol-17-propionate in both cream and ointment forms and sunscreen. MED was increased with thin and thick applications of all agents. Moreover, the photoprotective effects of each agent increased with their thick applications compared with thin ones. The application of calcipotriol cream and ointment, clobetasol cream and ointment, and tretinoin cream, all of which can block UVB, is not recommended just before phototherapy.

Topics: Adult; Calcitriol; Clobetasol; Dermatologic Agents; Erythema; Humans; Ointments; Reference Values; Single-Blind Method; Tretinoin; Ultraviolet Rays

Topics: Adult; Aged; Calcitriol; Dermatologic Agents; Double-Blind Method; Drug Therapy, Combination; Humans; Keratosis; Kidney Transplantation; Middle Aged; Sunlight; Treatment Failure; Tretinoin

The aim of the current study was to evaluate, in an open trial, the clinical efficacy of topical calcipotriol compared with tretinoin in the therapy of hyperkeratotic oral lesions (leukoplakia). The study group consisted of 40 patients with histologically proven oral leukoplakias, 20 treated with calcipotriol, the other 20 with tretinoin. The treatment was for 5 weeks and follow-up at 4 months, with clinical assessments at 2, 4 and 5 weeks and regular laboratory assessments. The results showed a significant reduction in lesions (80%), in both calcipotriol and tretinoin groups, with no documented topical or systemic adverse reactions, results maintained at 4 months. Tretinoin however, potentially can induce erythema, angular cheilitis and xerostomia. The study suggests that topical calcipotriol is as effective in the therapy of oral leukoplakia as is topical tretinoin.

Topics: Administration, Topical; Adult; Antineoplastic Agents; Calcitriol; Female; Humans; Leukoplakia, Oral; Male; Middle Aged; Treatment Outcome; Tretinoin

The study was a single-centre, double-blind randomized, placebo-controlled within-subject comparison of 42 healthy volunteers. Occlusive patch test for 48 h was performed with solutions of 1 alpha,25(OH)2D3 (calcitriol), two vitamin D analogues (calcipotriol and KH 1060 (lexacalcitol)), all-trans retinoic acid and sodium lauryl sulphate (SLS) as reference irritant. Solution vehicles and an empty chamber was also included. Test evaluation was performed at day 2, day 3 and again on day 7. Test evaluation was based both on clinical scoring and on various non-invasive measuring methods. 1 alpha,25(OH)2D3, calcipotriol and KH 1060 all showed mild irritation in the concentrations tested. The number and severity of test reactions was found to be dose dependent based both on clinical scoring and on non-invasive measurements. Irritation of the vitamin D analogues mainly affected the vasculature with vasodilation and increased cutaneous blood flow. All-trans retinoic acid showed irritant reactions with some similarity to the tested vitamin D analogues; however, the reactions were more prolonged. Transepidermal water loss (TEWL) was affected neither after application of vitamin D analogues nor after application of all-trans retinoic acid and it was thus concluded that these substances are non-corrosive. SLS showed the known irritant mechanism with corrosion and increase in TEWL as the primary event.

Topics: Adult; Aged; Calcitriol; Dermatologic Agents; Double-Blind Method; Drug Eruptions; Erythema; Female; Humans; Male; Middle Aged; Patch Tests; Regional Blood Flow; Skin; Sodium Dodecyl Sulfate; Surface-Active Agents; Tretinoin; Water Loss, Insensible

TSLP is an important trigger and initiator for various atopic diseases mainly atopic dermatitis (AD). Activators of nuclear hormone receptors like bioactive vitamin A and D derivatives are known to induce TSLP up-regulation in the skin. In this study, various combinations of synthetic specific agonists and antagonists of the retinoic acid receptors (RARs), retinoid X receptors (RXRs) and vitamin D receptor (VDR) were topically administered to mice. The aim of the study was to elucidate via which nuclear hormone receptor pathways TSLP is regulated and how this regulation is connected to the development and phenotype of atopic dermatitis. TSLP expression was monitored using QRT-PCR and serum TSLP levels using ELISA. Synthetic agonists of the VDR and RARγ as well as the natural agonist all-trans retinoic acid (ATRA) increased TSLP expression in the skin, while an RXR agonist was not active. Treatments with antagonists of RXRs and RARs in addition to RARα-agonists reduced skin TSLP expression. Strong activation was found after a combination of a VDR and an RXR agonist (ca. 5 times induction) and even stronger by an RARγ and an RXR agonist treatment (ca. 48 times induction). We conclude that besides VDR-mediated signaling mainly RARγ-RXR mediated pathways in the skin are important patho-physiological triggers for increased skin TSLP expression. We conclude that topical synthesized retinoids stimulated by internal or external triggers or topically applied induce TSLP production and are thereby important triggers for atopic dermatitis prevalence.

Topics: Adolescent; Adult; Animals; Calcitriol; Coumaric Acids; Cytokines; Dermatitis, Atopic; Female; Gene Expression Regulation; Humans; Immunization; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Organic Chemicals; Ovalbumin; Receptors, Calcitriol; Receptors, Retinoic Acid; Retinoic Acid Receptor gamma; Retinoid X Receptors; Signal Transduction; Skin; Tetrahydronaphthalenes; Thymic Stromal Lymphopoietin; Tretinoin

To describe the clinical characteristics and treatments of children with psoriasis.. Retrospective, descriptive.. The medical records were studied of all 38 children with psoriasis who visited the outpatient clinic for Dermatology of the University Hospital/Wilhelmina Children's Hospital Utrecht, the Netherlands, for the first time between 1 January 1995 and 31 December 1997.. The 38 children accounted for 3.6% of all children in whom a diagnosis was made. There were 19 boys and 19 girls. 79% had psoriasis vulgaris and 11% psoriasis guttata. Average age of onset was 6.8 years for girls and 9.3 years for boys. Family history was positive in 42%. The limbs were affected most. Nail changes were seen in 11%. Provoking factors were stress, infections, summertime and injuries of the skin. In almost all patients in the outpatient department local mono- and/or combination therapy of corticosteroids in cream or ointment with salicylic acid and tar was given.

Topics: Adolescent; Adrenal Cortex Hormones; Anthralin; Anti-Inflammatory Agents; Aspirin; Calcitriol; Child; Cyclosporine; Dermatologic Agents; Female; Genetic Predisposition to Disease; Humans; Male; Phototherapy; Psoriasis; Retrospective Studies; Tars; Treatment Outcome; Tretinoin

An in vitro human reconstructed epidermis model (SkinEthic) used for screening acute and chronic skin irritation potential was validated against in vivo data from skin tolerability studies. The irritation potential of sodium lauryl sulfate (SLS), calcipotriol and trans-retinoic acid was investigated. The in vitro epidermis-like model consists of cultures of keratinocytes from human foreskin on a polycarbonate filter. The modulation of cell viability, the release and gene expression of proinflammatory cytokines, interleukins 1alpha and 8, and morphological changes were evaluated during 3 days as endpoints representative for an inflammatory reaction. The cumulative irritation potential of the topical products was evaluated in a human clinical study by visual scoring and biophysical measurement of inflammatory skin reaction after repeated 24 h applications over 3 weeks under Finn chamber patches. All topical products that were nonirritating in the human study were noncytotoxic and did not induce cytokine expression in the in vitro acute model (day 1 exposure). All irritating controls exhibited specific cell viability and cytokine patterns, which were predictive of the in vivo human data. The ranking of mild to moderate skin irritation potential was based on the lack of cytotoxicity and the presence of cytokine patterns including gene expression specific for each irritant, using the chronic in vitro model (up to 3 days exposure). The human reconstructed epidermis model SkinEthic was shown to be a reliable preclinical tool predicting the irritation potential of topical products. Moreover, it is a useful model in a two-step tiered strategy for screening acute and chronic irritation potential for the selection of vehicles for new topical drugs.

Topics: Adult; Calcitriol; Humans; Keratinocytes; Models, Biological; Skin; Sodium Dodecyl Sulfate; Tretinoin

Formaldehyde-releasing preservatives are well-known allergens found in many topical preparations including medications.. To analyze the relevance of a positive patch test to formaldehyde-releasing preservatives in medications containing these preservatives.. Patients were recruited with a history of allergy to one of these preservatives. Patch and use testing to the medications, vehicles, and preservatives were performed. The following medications and their respective preservatives were used: Renova 0.05% cream/quaternium-15, Dovonex 0.005% cream/diazolidinyl urea, and Temovate-E 0.05% cream/diazolidinyl urea.. Nine patients participated in the study. A positive patch test to the preservative was reproduced in six of nine patients, and a questionable reaction occurred in one. Two patients had a positive patch test to the topical medication and one a questionable reaction. There were no definitive positive patch tests to the vehicle but two questionable ones. Use testing revealed three positive reactions to Renova, one to Renova vehicle, and one to Temovate-E vehicle.. The concentration of the preservative in the commercial preparation was often below the threshold necessary to produce a clinical reaction. Use testing is a valuable tool in the complete evaluation of the patient with a positive patch test to a formaldehyde-releasing perservative found in topical medication.

Topics: Administration, Cutaneous; Anti-Infective Agents, Local; Anti-Inflammatory Agents; Calcitriol; Chemistry, Pharmaceutical; Clobetasol; Dermatitis, Allergic Contact; Dermatologic Agents; Double-Blind Method; Formaldehyde; Glucocorticoids; Humans; Keratolytic Agents; Methenamine; Patch Tests; Preservatives, Pharmaceutical; Tretinoin; Urea

This study examined the action of 9-cis retinoic acid and 1,25-dihydroxyvitamin D3 analogues (KH 1060, EB 1089 and MC 903) on the release of calcitonin (CT) and calcitonin gene-related peptide (CGRP) in the rat C cell line CA-77. This cell line mainly secretes CGRP. Using radioimmunoassays (RIAs) for CT and CGRP, we measured the release of both peptides in the culture medium as well as the amount of these proteins contained in the CA-77 C cells. 9-cis retinoic acid decreased the release of both CGRP and CT dose-dependently in the range between 1 nM and 1 microM. The half-effective dose was 10 nM. The treatment of CA-77 C cells with 0.1 microM calcitriol alone only slightly decreased the release of both CT and CGRP. The increase in the amount of CT and CGRP released by the action of 1 microM dexamethasone was reduced by 1 microM 9-cis retinoic acid, and this effect was enhanced by the addition of 0.1 microM calcitriol or KH 1060, EB 1089 and MC 903. When the C cells were continuously stimulated by dexamethasone, after 6 days of exposure to the combined treatment with calcitriol analogues + 9-cis retinoic acid, there was a greater decrease in the amount of CGRP contained in the C cells than after treatment with 9-cis retinoic alone. Our data suggested that combined treatment with retinoic acid and calcitriol analogues exerted a stronger inhibition on the amounts of the two peptides either contained in the cells or released in the medium than each hormone alone.

Topics: Alitretinoin; Animals; Calcitonin; Calcitonin Gene-Related Peptide; Calcitriol; Carcinoma, Medullary; Dexamethasone; Dose-Response Relationship, Drug; Drug Interactions; Kinetics; Rats; Thyroid Neoplasms; Tretinoin; Tumor Cells, Cultured

Exposure of the skin to sodium dodecyl sulfate (SDS) leads to disruption of barrier and skin irritation. We used repetitive short exposure to a low molarity SDS solution as an in vivo model to mimic the development of irritant contact dermatitis. In this model, we studied clinical (erythema), functional (transepidermal water loss(TEWL)) and cell biological changes. 24 healthy volunteers were patch tested with SDS (0.2%) for 4 h a day for 5 consecutive days. After removal of the patches, the exposed sites were treated 1 X daily either with a topical corticosteroid (triamcinolon acetonide cream 0.05%), a retinoid (tretinoin cream 0.025%), or a vitamin D3 derivative (calcipotriol ointment 50 micrograms/g). Irritant reactions were assessed by erythema scoring and measurement of barrier function with TEWL up to 14 days after the first challenge. Skin biopsies were taken for cell biological changes at day 4. Vehicle-treated sites served as controls. Repetitive exposure of human skin to SDS resulted in a gradual increase in erythema scoring and TEWL associated with the upregulation of proliferative cells as measured by the expression of Ki-67-antigen and of differentiation markers, visualized by increased expression of involucrin and epidermal-fatty-acid binding protein (E-FABP). Skin irritation as assessed by erythema scoring and TEWL was not significantly suppressed by triamcinolone cream. However, a significant reduction of the number of cycling keratinocytes and a decrease in involucrin positive cell layers was observed in this group. Neither treatment with calcipotriol ointment nor with tretinoin cream induced improvement of skin irritation as judged by visual scoring and TEWL. In contrast to steroid treatment, no significant effect of calcipotriol ointment or tretinoin cream treatment was observed with regard to the number of cycling cells and differentiation markers. Further studies are needed to assess whether treatment with topical corticosteroids is an effective modality in skin irritation and irritant contact dermatitis.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Biopsy, Needle; Calcitriol; Cell Division; Dermatitis, Irritant; Dermatologic Agents; Female; Glucocorticoids; Humans; Irritants; Keratolytic Agents; Male; Middle Aged; Ointments; Skin; Sodium Dodecyl Sulfate; Surface-Active Agents; Tretinoin; Triamcinolone Acetonide; Water Loss, Insensible

To develop a model for the study of oral epithelial differentiation, we reconstructed artificial buccal mucosa equivalents using keratinocytes and fibroblasts or de-epidermized dermis derived from non-cornifying buccal mucosa. The buccal mucosa equivalents reconstructed in this way showed a morphology closely mimicking that of their in vivo counterparts. There was no formation of horny layers and granular layers. The expression of various differentiation markers such as K13, involucrin and loricrin was consistent with that of the in vivo state, and indicative of the hyperproliferative state. We also demonstrated that the differentiation of oral epithelial cells was influenced by the de-epidermized dermis and subepithelial fibroblasts. The epidermis of buccal mucosa equivalents seemed to be less sensitive to retinoic acid than that of the skin. The effects of calcipotriol on the buccal mucosa equivalent and the skin epidermis were different. These results suggest that the pharmacological effects of retinoic acid and calcipotriol on the buccal mucosa are different from those on the skin. A useful model system for studies of oral keratinocyte differentiation and pharmacological research could be based on these artificial buccal mucosa equivalents.

Topics: Calcitriol; Cell Differentiation; Cheek; Dermatologic Agents; Epithelial Cells; Fibroblasts; Humans; Male; Mouth Mucosa; Tretinoin