tretinoin and Dermatitis--Irritant

An aqueous gel formulation containing solubilized clindamycin phosphate 1.2% and a stable combination of both solubilized and crystalline tretinoin 0.025% (clin/tret) has been evaluated in 3 pivotal phase 3 studies, among other studies including a 52-week trial. The pivotal studies enrolled 4550 participants 12 years and older with mild, moderate, and severe acne vulgaris. The combination clin/tret gel was effective in reducing both inflammatory and noninflammatory lesions and was well-tolerated. This article reviews important vehicle characteristics of the combination gel as well as formulation stability and tolerability data that are potentially clinically relevant.

Topics: Acne Vulgaris; Administration, Cutaneous; Anti-Bacterial Agents; Benzoyl Peroxide; Clindamycin; Dermatitis, Irritant; Dermatologic Agents; Drug Combinations; Drug Interactions; Drug Stability; Gels; Humans; Pharmaceutical Vehicles; Skin Absorption; Tretinoin

Topics: Acne Vulgaris; Administration, Cutaneous; Adolescent; Adrenal Cortex Hormones; Adult; Child; Dermatitis, Irritant; Dermatologic Agents; Double-Blind Method; Facial Dermatoses; Female; Humans; Lipids; Male; Middle Aged; Patient Satisfaction; Tretinoin; Triamcinolone; Young Adult

The efficacy of topical retinoids is well known according to several clinical studies conducted predominantly among Caucasian patients. This study aimed to evaluate the efficacy and safety profile of adapalene and tretinoin among Mexican patients.. To compare adapalene 0.1 and 0.3% and tretinoin 0.05% in Mexican subjects with acne vulgaris.. We enrolled 171 patients in this single-center, randomized, double-blinded, placebo-controlled clinical trial. The patients applied on the face either adapalene 0.1%, adapalene 0.3%, tretinoin 0.05%, or placebo for 90 days and were evaluated for the reduction in total lesion counts and for the level of irritation.. Tretinoin 0.05% and adapalene 0.3% were more effective than adapalene 0.1% and placebo in the reduction of both inflammatory and noninflammatory lesions. Most of adverse events to adapalene and many on tretinoin group were related to skin irritation, dry skin, scaling, pruritus, burning, and postinflammatory hyperpigmentation.. Adapalene 0.3% and tretinoin 0.05% are comparable in efficacy, and adapalene 0.1% offers a better safety profile in Mexican patients.

Topics: Acne Vulgaris; Adapalene; Adolescent; Adult; Child; Dermatitis, Irritant; Dermatologic Agents; Double-Blind Method; Female; Gels; Humans; Hyperpigmentation; Keratolytic Agents; Male; Mexico; Naphthalenes; Pruritus; Tretinoin; Young Adult

The most frequent side effect of topical retinoids is irritant contact dermatitis. It occurs in approximately 85% of patients; the percentage can reach up to 95% in patients treated with tretinoin. Severity of this dermatitis is moderate to severe in approximately 20% of patients. However, 15% of patients stop the treatment with tretinoin because of skin irritation. The authors used tretinoin as short contact therapy (SCT) in mild to moderate acne, in order to try to reduce the incidence and severity of irritant contact dermatitis. They present the final results of a sponsor-free, pilot, open, multicenter study. Seventy-four patients were treated with 0.05% tretinoin cream. It was applied once daily for 30 min. Treatment duration ranged from 8 to 32 weeks (mean duration: 12 weeks). Acne severity and treatment efficacy were evaluated by means of the Global Acne Grading System. A significant clinical improvement (≥50% from baseline) was observed in 41 patients (55.4%). Thirteen patients (17.6%) developed a mild skin irritation. Four patients (5.4%) stopped the treatment because of severe skin irritation. Efficacy of tretinoin used as SCT seems to be superimposable to that of tretinoin used according to standard modality. Tolerability of SCT with tretinoin is very good. This tolerability allows a high adherence of patients to the treatment and it markedly improves compliance.

Topics: Acne Vulgaris; Administration, Topical; Adolescent; Adult; Dermatitis, Irritant; Dermatologic Agents; Female; Humans; Male; Pilot Projects; Treatment Outcome; Tretinoin; Young Adult

Topical tretinoin [all-trans-retinoic acid (RA)] currently is widely used to treat photoaged skin. However, undesirable side effects such as erythema, irritation, and scaling are unavoidable and limit the use of tretinoin. To address these issues, the authors developed the tretinoin cyclodextrin complex (RA/CyD), which is tretinoin encapsulated by cyclodextrin. Cyclodextrins are cyclic oligosaccharides commonly used in food additives and fabric fresheners. This study aimed to evaluate the antiwrinkle effect of RA/CyD and alleviation of the side effects compared with RA treatment alone.. In this study, 12 photoaged patients completed an 8 week study using RA and RA/CyD in a double-blind manner. Before and after the treatment, the patients' evaluations, wrinkle scores, skin elasticity, and wrinkle area measurement using skin replica were evaluated. Three men were recruited for histologic analysis.. The patients reported that undesirable irritant reactions were more moderate with RA/CyD than with RA. In the assessment of wrinkle scores, skin elasticity, and wrinkle area measurement, RA/CyD demonstrated an antiwrinkle effect statistically equal to that of RA. In histology, both RA/CyD and RA demonstrated epidermal hyperplasia. In immunohistochemistry, inflammation induced by RA/CyD was more moderate than that induced by RA.. The findings show that RA and RA/CyD result in the equivalent clinical improvement for patients with photoaging. The use of RA/CyD overcomes the drawbacks of RA while possessing equal effect. It is expected that CyD will broaden tretinoin treatment.. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Cutaneous; Administration, Topical; Aged; beta-Cyclodextrins; Dermatitis, Irritant; Dermatologic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Middle Aged; Severity of Illness Index; Skin; Skin Aging; Treatment Outcome; Tretinoin

Vasodilation with increased cutaneous perfusion is an essential part of an irritant inflammatory response. The aim of the present study was to investigate the usefulness of the high-resolution laser Doppler perfusion imaging (HR-LDPI) technique for investigating irritant skin reactions. Irritants may elicit clinically different reactions due to different skin penetration profiles and different modes of irritant action on the exposed. Twelve subjects were tested on the forearms using 24 h occlusive application of three concentrations of the irritants sodium lauryl sulphate (SLS) and nonanoic acid (NON) and with the topical acne drug all-trans retinoic acid (RA). Cutaneous blood flow at baseline, the increase in cutaneous blood flow and the skin area having increased perfusion were measured on day 2, day 3 and day 5.. Based both on measurement of mean perfusion and area with increased perfusion, it was possible to differentiate between different clinical irritation grades on any study day. The area with increased perfusion exceeded the area with clinically visible skin reactions for irritant reactions of grade 1/2 and above. Irritant reactions for individual irritants could furthermore be typed using HR-LDPI. It was possible to differentiate between vehicle treatment and the different dose levels of the irritant compounds. A correlation was found between clinical scores for the individual irritants and the mean flow and the area with increased flow. The individual irritants could be differentiated due to different time courses of their skin irritation.. Laser Doppler imaging was found to be an important new method for characterization and grading of the inflammatory response of single exposure irritant reactions. However, standardised study procedures cannot be emphasised enough in order to obtain reliable and useful data.

Topics: Adult; Antifungal Agents; Dermatitis, Irritant; Double-Blind Method; Fatty Acids; Female; Forearm; Humans; Keratolytic Agents; Laser-Doppler Flowmetry; Male; Middle Aged; Skin; Skin Irritancy Tests; Sodium Dodecyl Sulfate; Surface-Active Agents; Tretinoin

This is a clinical, prospective, and longitudinal study comparing the efficacy and incidence of averse effects of topical isotretinoin against those of topical retinoic acid in the treatment of acne vulgaris. The 30 participants were recruited from the patients attending the outpatient clinic of the Department of Dermatology of "Dr Manuel Gea González" General Hospital in Mexico City. They belonged to either sex and any race, their ages ranged between 13 and 30 years, and they presented with 15 to 100 facial inflammatory lesions (papulo-pustules) and/or 15 to 100 noninflammatory lesions (comedones) and no more than three nodulo-cystic lesions. The criteria of exclusion were as follows: pregnancy or lactation, systemic treatment with steroids, antibiotics, antiandrogens, or oral retinoids in the preceding 24 months, treatment with ultraviolet radiation, hypersensitivity to retinoids, or a severe systemic illness. From 44 interviewed patients, 14 were excluded. A detailed clinical history was obtained from the remaining individuals, the degree of seborrhea was recorded, and acne lesions were counted. Each patient received either isotretinoin gel 0.05% or retinoic acid cream 0.05%. The patients were instructed to wash their faces in the mornings and evenings with a neutral soap, and to apply the product after the evening cleansing. The patients were examined again after 2, 4, 8, and 12 weeks of treatment and, at each appointment, the number of lesions was recorded and the severity of acne was graded according to the classification of Plewig and Kligman. The seriousness of the adverse effects, such as stinging, pruritus, erythema, xerosis, and desquamation, was evaluated blindly by an investigator who did not know what group the patient belonged to, and graded as 1 = mild, 2 = moderate, and 3 = severe. The efficacy of each drug was determined by the reduction in the number of lesions between weeks 0 and 12 of treatment. An excellent response corresponded to a 76%-100% reduction of the lesions, a good response to a 51%-75% reduction, a fair response to a 26%-50% reduction, and a poor response to a 0%-25% reduction. The results were analyzed statistically using the chi-square test, the exact test of Fisher and the test of Wilcoxon-Mann-Whitney. The changes in the numbers of lesions between weeks 0 and 12 were analyzed separately for each group of treatment, and the level of statistical significance was fixed at 0.05. The analysis was performed with the aid of a. The patients were assigned randomly to either Group I (isotretinoin) or Group II (retinoic acid). Each group was composed of 15 individuals and, as a coincidence, in each group there were nine women and six men. The clinical differences between the groups at the first visit were not statistically significant. In both groups, there was, in general, a good response to treatment (Fig. 1). Both drugs had a similar degree of efficacy on inflammatory lesions. At the first visit, grades III and IV predominated, whereas, after 12 weeks of treatment, most patients were classified in grades I or II (Fig. 2). Similar results were observed regarding noninflammatory lesions (Fig. 3). Ten of the patients of Group II complained of stinging associated with the treatment, especially at weeks 8 and 12, as well as erythema and desquamation at the 12th week. Erythema and stinging lasted for minutes or hours, whereas desquamation persisted for several days. Seven individuals receiving isotretinoin mentioned irritation, which was of a mild degree.

Topics: Acne Vulgaris; Administration, Topical; Adolescent; Adult; Dermatitis, Irritant; Erythema; Female; Humans; Isotretinoin; Keratolytic Agents; Longitudinal Studies; Male; Prospective Studies; Severity of Illness Index; Skin; Time Factors; Treatment Outcome; Tretinoin

Chronic exposure to a weak irritant leads to inflammatory changes which may be followed by pigmentary changes and accommodation. The inflammatory responses to acute exposure to an irritant have been extensively studied. This study investigated quantitatively the inflammatory reactions produced in photodamaged skin with chronic application of a weak chemical irritant (tretinoin cream 0.025%) over a period of 9 months (36 weeks). Forty-eight subjects with moderately to severely photodamaged skin were enrolled in a 36-week, double-blind placebo-controlled study. Tretinoin cream was applied nightly on the distal two thirds of one dorsal forearm and placebo on the other. The proximal third of each dorsal forearm received no treatment and served as control. Clinical assessments and diffuse reflectance measurements were made at 7 time points during treatment. Apparent concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin (Hb) and melanin were estimated by analysis of the diffuse reflectance spectra. No changes were observed in the apparent HbO2 or the Hb concentration of the placebo-treated or control sites, thus establishing a reliable baseline. The apparent HbO2 concentration of the tretinoin-treated sites increased significantly from baseline to a maximum at 12-18 weeks of treatment, then returned to baseline with continued applications. The changes in HbO2 concentration agreed closely with clinical assessments of erythema. The apparent melanin concentration, corresponding to diffuse hyperpigmentation, showed a large seasonal decrease in both the control and the treated sites, with an additional decrease in the treated sites between 12 and 18 weeks. Erythema appeared after repeated applications and eventually resolved under continuous treatment. The maximum decrease in hyperpigmentation occurred simultaneously with the maximum increase in erythema.

Topics: Administration, Oral; Adult; Aged; Chronic Disease; Dermatitis, Irritant; Double-Blind Method; Erythema; Hemoglobins; Humans; Keratolytic Agents; Melanins; Middle Aged; Oxyhemoglobins; Placebos; Skin Aging; Skin Pigmentation; Tretinoin; Ultraviolet Rays

Dermo-epidermal atrophy is one of the main side effects of long-term treatment with topical corticosteroids (TC). Retinoic acid (RA) may prevent and even reverse these effects in animals. It has been previously established that topical RA (TRA) does not inhibit corticosteroid-induced vasoconstriction in humans, thus suggesting that RA, combined with TC, does not interfere with its anti-inflammatory property. The next step was to test this association in patients with inflammatory skin disorders. In this symmetrical double-blind study, triamcinolone acetonide (TA) cream 0.1% and a cream containing TA 0.1% plus RA 0.025% (TARA) were compared in 18 subjects with eczema. No statistical difference between both treatments was observed after 1, 2 and 3 weeks, although on the TARA-treated sides the anti-inflammatory responses were slightly less pronounced. Subjective irritation was significantly more frequent in TARA-treated side (3/17, p = 0.05) but did not lead to interruption of the treatment. This indicates that addition of RA 0.025% to a medium-range potency topical steroid does not abrogate the anti-inflammatory property of the latter and that the association can be tolerated by inflamed skin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Dermatitis, Allergic Contact; Dermatitis, Atopic; Dermatitis, Irritant; Double-Blind Method; Drug Combinations; Drug Tolerance; Eczema; Female; Humans; Male; Middle Aged; Tretinoin; Triamcinolone Acetonide

Mice on a calorie-restricted (CR) diet (total calories restricted to 70% of ad libitum; AL) for periods of time ranging from 3 to 18 months were examined for response to topical treatment with all-trans retinoic acid (RA). Daily application of a 0.1% solution of RA to the shaved skin of UM-HET3 mice on an AL diet produced a severe irritation that was evident by day 4, maximal at day 7-8 and still detectable at day 14. Skin irritation was characterized by redness, dryness, flaking and failure of the hair to grow at the treated site. In CR mice, the same treatment produced little detectable irritation. Animals were sacrificed at the end of the retinoid-treatment period (day 7 or day 14) and skin from these animals was examined histologically. In both AL and CR mice, a similar degree of epidermal hyperplasia was observed. Numerous inflammatory cells (mononuclear cells and granulocytes) were present in the skin of both groups. Occasional S100-positive cells (presumably Langerhans cells) were also observed in the epidermis of skin from both groups. S100-positive cells were also observed in the dermis. When skin from CR and AL mice was incubated in organ culture for 3 days (on day 7 after initiation of RA treatment), similar levels of four different pro-inflammatory cytokines were found in the conditioned medium. Soluble type I collagen levels were also similar. In contrast, the level of matrix metalloproteinase-9 was lower in the conditioned medium of skin from CR mice than in conditioned medium from skin cultures of AL mice. Taken together, these studies suggest that CR may provide a way to mitigate the irritation that normally accompanies RA treatment without compromising the beneficial effects of retinoid use. CR appears to exert a protective effect at the target tissue level rather than by a reduction in pro-inflammatory events, per se.

Topics: Administration, Topical; Animals; Caloric Restriction; Cell Proliferation; Collagen; Collagen Type I; Cytokines; Dermatitis, Irritant; Female; Keratolytic Agents; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred Strains; Organ Culture Techniques; S100 Proteins; Skin; Time Factors; Tretinoin

The ability of the synthetic retinoid MDI-301, in which the carboxylic acid of 9- cis-retinoic acid (9-cis-RA) is replaced with an ester linkage, to induce epidermal and dermal thickening and skin irritation (erythema and flaking) in hairless (rhino) mice following its topical application was investigated in comparison with that of 14-all- trans-retinoic acid (14-all-trans-RA) and 9-cis-RA. MDI-301 induced epidermal proliferation leading to a thickened epidermis. Treated animals also demonstrated a prominent band of organized connective tissue immediately below the epidermis. In its ability to induce epidermal thickening, MDI-301 was quantitatively similar to 14-all-trans-RA and 9-cis-RA. However, unlike 14-all-trans-RA and 9-cis-RA, which produced skin irritation associated with a perivascular influx of mononuclear leukocytes into the dermis, there was no evidence of irritation with MDI-301 and little leukocyte infiltration. Intraperitoneal injection of either 14-all-trans-RA or MDI-301 also resulted in epidermal and dermal thickening. Irritation of skin was not observed in these animals but splenomegaly was prominent in animals treated with either agent.

Topics: Alitretinoin; Animals; Cells, Cultured; Dermatitis, Irritant; Dermis; Epidermis; Fibroblasts; Humans; Keratinocytes; Mice; Mice, Hairless; Retinoids; Tretinoin

Retinoids are natural and synthetic analogues of the hormone retinoic acid. Systemic retinoid agonist therapy is usually associated with toxic side effects, such as mucocutaneous toxicity, which may be alleviated by the use of topical retinoid antagonists. We report the synthesis and biological activity of a new series of potent, RAR-specific antagonists substituted with phenylcyclohexene and phenylcyclohexadiene groups.

Topics: Animals; Benzoates; Cyclohexanes; Dermatitis, Irritant; Disease Models, Animal; Mice; Receptors, Retinoic Acid; Retinoids

Non-invasive bioengineering methods are widely used in the assessment of irritant skin reactions.. To assess the ability of eight non-invasive measurement techniques to distinguish changes in skin conditions over time, these changes being induced by five different irritants.. The following techniques were compared in a multivariate analysis: laser-Doppler perfusion imaging (LDI), laser-Doppler flowmetry (LDF), transepidermal water loss (TEWL), visual scoring (VS), colorimetric measurements (Chromameter CR 200 a* and L* scales), Mexameter Hb scale (Mexa Hb) and capacitance (Corneometer CM 820). Irritants tested were sodium lauryl sulphate 2% (SLS), tape stripping (TS), tretinoin 0.05% (TRET), ultraviolet (UV) exposure to 30 W m(-2) UVB/95 W m(-2) UVA, and dithranol 0.5% (DIT). Measurements were performed at baseline and after 24, 48 and 72 h. The study was conducted on the upper back of 11 healthy volunteers of both sexes aged 27-51 years.. For DIT it was possible to discriminate over time with CR 200 a* and L*, VS, LDI, LDF and Mexa Hb. In SLS discrimination over time was seen with TEWL and LDF. Discrimination in TS was demonstrated for TEWL, VS, CR 200 a*, CM 820, LDF, LDI and Mexa Hb. In TRET discrimination ability was seen for LDI, LDF, Mexa Hb and VS. For UV it was possible to discriminate using VS, TEWL, LDF, LDI and Mexa Hb.. Different irritation patterns need different measurement modalities in order to give optimal discrimination over time.

Topics: Adult; Analysis of Variance; Anthralin; Calorimetry; Dermatitis, Irritant; Erythema; Female; Humans; Irritants; Laser-Doppler Flowmetry; Male; Middle Aged; Multivariate Analysis; Severity of Illness Index; Skin; Sodium Dodecyl Sulfate; Tretinoin; Ultraviolet Rays; Water Loss, Insensible

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

Topics: Allergens; Dermatitis, Allergic Contact; Dermatitis, Irritant; Diagnosis, Differential; Humans; Irritants; Patch Tests; Sodium Dodecyl Sulfate; Tretinoin

Topics: Animals; Body Water; Data Display; Dermatitis, Irritant; Edema; Erythema; Guinea Pigs; Laser-Doppler Flowmetry; Patch Tests; Regional Blood Flow; Severity of Illness Index; Skin; Sodium Dodecyl Sulfate; Tretinoin

Topics: Administration, Cutaneous; Adolescent; Adult; Child; Child, Preschool; Dermatitis, Irritant; Dermatologic Agents; Facial Dermatoses; Female; Humans; Irritants; Ointments; Salicylates; Salicylic Acid; Tretinoin; Warts