tretinoin and Erythema

Topical tretinoin has been a standard treatment for acne vulgaris for more than 4 decades. While tretinoin has demonstrated proven efficacy in the treatment of acne lesions, it also is associated with the potential for skin irritation. Newer formulations have been designed to optimize both the drug concentration and the delivery vehicle with the aim to enable clinicians to provide increasingly effective acne treatment that minimizes irritation. These therapies include formulations with varying concentrations of tretinoin and vehicles that utilize a microsponge delivery system, hydrogels and micronized tretinoin, or propolymers. The purpose of this review is to evaluate different formulations and combinations of tretinoin in the treatment of acne vulgaris. While these advanced formulations were designed for controlled release of active ingredient, and have the potential to reduce cutaneous irritation relative to standard tretinoin cream and gel formulations, there is a need for comparative studies to evaluate the relative benefits of each of these advanced tretinoin formulations in optimizing acne treatment.

Topics: Acne Vulgaris; Chemistry, Pharmaceutical; Drug Eruptions; Erythema; Humans; Hydrogels; Keratolytic Agents; Microspheres; Pharmaceutical Vehicles; Polypropylenes; Polyurethanes; Tretinoin

Topics: Administration, Topical; Child; Erythema; Follow-Up Studies; Glossitis, Benign Migratory; Humans; Male; Severity of Illness Index; Treatment Outcome; Tretinoin

Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by tender, red inflammatory nodules or papules that occur in association with infection, malignancy, connective tissue disease, or following exposure to certain drugs. Although drug-induced Sweet syndrome is rare, granulocyte colony-stimulating factor, all-trans-retinoic acid, and miscellaneous drugs have been implicated in causing this disorder in adults. In pediatric patients, granulocyte colony-stimulating factor, all-trans-retinoic acid, trimethoprim-sulfamethoxazole, and azathioprine have been implicated as potential causes of drug-induced Sweet syndrome. To date, six cases, including the patient reported here, have been reported in children.

Topics: Adult; Azathioprine; Child; Connective Tissue Diseases; Erythema; Fever; Granulocyte Colony-Stimulating Factor; Humans; Infections; Sweet Syndrome; Tretinoin; Trimethoprim, Sulfamethoxazole Drug Combination

Milia plaque is an unusual and rare variant of milia. We now report a Chinese man with numerous milia within an erythematous plaque of the upper and lower eyelids; histology confirmed the diagnosis and showed pericystic inflammation. All but one of the previous 10 reported cases affected the ear or adjacent sites, and to our knowledge, this is the first reported case of milia en plaque affecting the eyelids.

Topics: Adult; Anti-Bacterial Agents; Biopsy; Doxycycline; Erythema; Eyelid Diseases; Humans; Keratolytic Agents; Male; Skin Diseases; Treatment Outcome; Tretinoin

A patient with erythrokeratodermia variabilis (Mendes da Costa's disease) is presented, and the clinical and histological response to acitretin is described. An initial dose of 35 mg of acitretin and a maintenance dose of 25-35 mg resulted in a pronounced and sustained improvement. Further reduction of the dosage resulted in a relapse within a few days. At the histological level the extensive hyperkeratosis and the moderate dermal inflammatory infiltrate decreased during treatment with acitretin. In comparison with the other retinoids available so far, acitretin is the derivative of first choice in the treatment of erythrokeratodermia variabilis Mendes da Costa.

Topics: Acitretin; Adolescent; Erythema; Female; Humans; Keratosis; Tretinoin

Acne vulgaris is the most common dermatological disorder worldwide, causing significant physical and psychological morbidity. Topical combination therapy has shown superior efficacy compared to monotherapy, especially when combined with retinoids. Few studies have directly compared combined formulations. This evaluator-blinded pilot study compared the efficacy and tolerability of two marketed topical combination acne gels, clindamycin 1%-tretinoin 0.025% (CT) and benzoyl peroxide 2.5%-adapalene 0.1% (BA) in 20 patients with mild to moderate acne vulgaris. Gels were applied daily on opposite sides of the face for 21 days. The primary outcome was difference in transepidermal water loss (TEWL) at the end of treatment. Secondary endpoints were skin moisture content measurement, Investigators' Global Assessment, subject self-assessments (SSA) of burning/stinging, itching, erythema, and dryness/scaling, and Comparative Participant Satisfaction Questionnaire (CPSQ). Efficacy was assessed by inflammatory and non- inflammatory acne efflorescences counts. TEWL increased significantly for both CT and BA (+57.74%, P=0.002; +58.77%, P<0.001); skin moisture content significantly decreased only for BA (-16.47%, P=0.02). Only BA showed a significant increase in erythema and dryness/scaling (P=0.027 and P=0.014) and in SSA burning/stinging (P=0.04). Patient satisfaction evaluation also reflected the strong BA irritation. Although CT and BA both reduced acne lesions (P<0.001) and more patients preferred to continue with CT, subject perception of acne improvement was higher for BA. These findings suggest that CT and BA have similar efficacy in the treatment of mild to moderate papulopustular acne. However, CT was better tolerated than BA by both medical and subject evaluation. CT is an effective and tolerated treatment option.J Drugs Dermatol. 2021;20(3):295-301. doi:10.36849/JDD.2021.5641.

Topics: Acne Vulgaris; Adapalene, Benzoyl Peroxide Drug Combination; Administration, Cutaneous; Adolescent; Adult; Clindamycin; Dermatologic Agents; Drug Combinations; Erythema; Female; Gels; Humans; Male; Patient Satisfaction; Pilot Projects; Pruritus; Severity of Illness Index; Skin; Treatment Outcome; Tretinoin; Water Loss, Insensible; Young Adult

Striae gravidarum is a common skin condition resulting after pregnancy, caused by fibroblast dysfunction. Although not considered a disease, it may be considered cosmetically unpleasant to sufferers and remains as a therapeutic challenge to date.. To evaluate the efficacy and safety of a sublative bipolar fractional radiofrequency (FRF) system, associated with 0.1% topical tretinoin, in treating striae gravidarum.. Eighteen Chinese women with striae gravidarum on the abdomen were enrolled in the study. The target area of each patient was divided into 4 sites randomly: control, tretinoin, FRF, and tretinoin and FRF. Fractional RF was used 3 times, with 3-month intervals. Changes to striae gravidarum were evaluated through subjective scaling and objective measures, using both high-frequency ultrasound and histological study.. Both subjective assessment and skin thickness differences demonstrated significant improvement in the combination site (p < .001). Average optical density and density percentage of neocollagen and elastic fibers were also markedly increased in the combination site (p < .05). The adverse effects of FRF were limited to mild pain and transient erythema, edema, and microcrusts.. The combined therapy of FRF and topical tretinoin may be a potential method in treating striae gravidarum, with satisfactory efficacy and limited side effects.

Topics: Adult; Erythema; Female; Humans; Keratolytic Agents; Middle Aged; Pain; Pain Measurement; Patient Satisfaction; Pilot Projects; Pregnancy; Pregnancy Complications; Radiofrequency Therapy; Skin; Skin Cream; Striae Distensae; Treatment Outcome; Tretinoin; Ultrasonography

Topical retinoids are used to treat the visible signs of photoaging. While efficacious, they are irritating.. Evaluate the effectiveness and tolerability of a double-conjugate retinoid cream (AlphaRet Overnight Cream; AHA-Ret) in improving visible signs of photoaging vs 1.0% retinol or 0.025% tretinoin.. A 12-week, split-face, randomized trial was conducted in 48 female subjects, aged 30-65 years with mild to severe photodamage. AHA-Ret was applied to one side of the face and either retinol (n=24) or tretinoin (n=24) to the other side (PM). Expert blinded evaluation of images and Nova measurements occurred at 4, 8, and 12 weeks. Tolerability was assessed throughout the study.. Forty-seven subjects completed the study. AHA-Ret demonstrated significant reductions in average severity from baseline: Fine Lines/Wrinkles (P<.001; all time points); Erythema (P=.004, P<.0001; 8 and 12 weeks, respectively); Dyschromia (P<.0001; all time points); Skin Tone (P<.0001; all time points), and Pore Size (P=.035, P<.0001; 8 and 12 weeks, respectively). AHA-Ret induced less Erythema vs retinol at 8 (P=.008) and 12 (P<.02) weeks. AHA-Ret was noninferior to prescription tretinoin in all categories at 4 and 8 weeks, and for Fine Lines/Wrinkles, Erythema, Dyschromia, and Skin Tone at 12 weeks. Improvements in Hydration occurred at every time point with AHA-Ret only (P<.04, P<.03, P<.01). Less irritation was reported with AHA-Ret vs retinol or tretinoin.. Treatment with a double-conjugate retinoid cream demonstrated early reductions in photodamage and improvements in Hydration. AHA-Ret induced less Erythema vs retinol and was more tolerable vs retinol and tretinoin.

Topics: Adult; Aged; Erythema; Face; Female; Humans; Middle Aged; Single-Blind Method; Skin Aging; Skin Cream; Skin Physiological Phenomena; Skin Pigmentation; Tretinoin; Vitamin A

Quality-switched (QS) laser therapy is a safe and well-established treatment option for removing solar lentigines. Triple combination therapy (TCT) with the active pharmaceutical ingredients hydroquinone 5%, tretinoin 0.03%, and dexamethasone 0.03% is often used for skin-lightening.. This prospective, open-label trial compares the efficacy and safety of a QS Ruby laser (QSRL) and a TCT in the treatment of solar lentigines.. In total, 15 patients with symmetrically distributed solar lentigines on the back of both hands were included. The lesions on the back of the right hand were treated in one or 2 sessions with a QSRL, the ones on the back of the left hand with a TCT for 7 weeks accompanied by UV protection. Clinical results were evaluated 4 weeks, 8 weeks, and 20 weeks after baseline.. Treatment with QSRL provided significant lightening (p = .01) compared with TCT. Both procedures were generally well-tolerated. Comparing the side effects, the laser produced significantly more crusting and hyperpigmentation than the TCT.. Both QSRL and TCT were capable in reducing solar lentigines in Fitzpatrick skin Type I to IV with an acceptable side effect profile. The QSRL provides faster, superior, and long lasting lightening compared with TCT.

Topics: Aged; Dexamethasone; Drug Combinations; Erythema; Female; Hand Dermatoses; Humans; Hydroquinones; Lasers, Solid-State; Lentigo; Male; Middle Aged; Pain; Prospective Studies; Skin Cream; Skin Lightening Preparations; Tretinoin

Post-inflammatory hyperpigmentation is a frequent concern when treating solar lentigines.. To assess the safety and efficacy of a triple combination cream with fluocinolone acetonide 0.01%, hydroquinone 4% and tretinoin 0.05% as adjuvant to cryotherapy in the treatment of solar lentigines in hands dorsum, and in the prevention of post-inflammatory hyperpigmentation after cryotherapy.. This prospective, randomized, controlled, investigator-blinded, single-centre study enrolled 50 patients. Twenty-five patients received a 2-week daily triple combination cream plus sunscreen pre-treatment and 25 received sunscreen alone. After that, cryotherapy was performed in all patients followed by a 3-week recovery period. After this period, patients received the same initial treatment and were followed up for 8 weeks. Melanin and erythema levels of a target and a control lentigo were objectively measured using a narrowband reflectance spectrophotometer. Lentigines count, colour homogeneity and global improvement were also assessed.. The number of solar lentigines reduced in the first 2 weeks only in patients who used the triple combination 25 ± 7 vs. 22 ± 8 (P < 0.0001), and reduced at the end of the study for both groups (P < 0.0001). The melanin levels also reduced in the first 2 weeks only in patients who used the triple combination 297 ± 69 vs. 273 ± 66 (P < 0.0001) and reduced at the end of the study for both groups (P < 0.0001). Erythema and residual blisters from cryotherapy were the reported adverse reactions.. Triple combination cream can be used to enhance the resolution of solar lentigines, and to significantly reduce melanin levels and lentigines count, improving treatment results. It was well-tolerated and did not increase the occurrence of neither erythema nor other side-effects after the cryotherapy.

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Chemotherapy, Adjuvant; Cryotherapy; Drug Combinations; Erythema; Female; Fluocinolone Acetonide; Hand Dermatoses; Humans; Hydroquinones; Lentigo; Male; Melanins; Middle Aged; Prospective Studies; Single-Blind Method; Skin Cream; Sunlight; Tretinoin

A fixed-dose combination of clindamycin phosphate 1.2% and tretinoin 0.025% gel (VELTIN® (clindamycin phosphate and tretinoin) 1.2%/0.025% Gel [VELTIN]) (clindamycin/tretinoin gel) is currently available for the once-daily topical treatment of acne.. Two-phase I studies were conducted to evaluate the phototoxic and photoallergic potential of clindamycin/tretinoin gel.. Study 1 (phototoxic) (n=37) and Study 2 (photoallergic) (n=58) were single-center, evaluator-blinded, randomized, vehicle-controlled, phase 1 studies conducted in healthy volunteers. In Study 1, clindamycin/tretinoin gel patches, vehicle gel patches and blank patches (no gel) were applied concurrently for 24 hours to naïve sites. After patch removal, sites were irradiated with 16 joules/cm2 of ultraviolet A light (UVA) then 0.75 minimal erythema dose (MED) of UVA/ultraviolet B light (UVB), the same irradiation protocol followed by 15 joules/cm2 of visible light (VIS), or served as non-irradiated controls. Study 2 examined the effect of repeated drug exposure and involved an induction period (6 repeat phases at the same body sites during which clindamycin/tretinoin gel and vehicle gel patches were applied for 24 hours, removed and sites irradiated with UVB +/- VIS), followed by a rest period (10 to 17 days), then a challenge period that used the protocol described for Study 1. In both studies, inflammatory responses and other cutaneous effects were evaluated at 1, 24, 48, and 72 hours after patch removal.. No subject experienced any adverse events in Study 1 (phototoxic). One subject in Study 2 (photoallergic) experienced AEs (diffuse erythema; mild application site irritation at one each of UV/VIS-irradiated clindamycin/tretinoin gel and vehicle gel patch sites) considered definitely related to study product that resulted in discontinuation from the study. Data from Study 1 and the challenge phase from Study 2 showed most subjects had no visible inflammatory reaction to clindamycin/tretinoin gel after irradiation.. Clindamycin/tretinoin gel has a favorable safety profile following UV/visible irradiation and a low potential for phototoxicity and photoallergenicity.

Topics: Acne Vulgaris; Administration, Cutaneous; Adolescent; Adult; Aged; Anti-Bacterial Agents; Clindamycin; Dermatitis, Photoallergic; Dermatitis, Phototoxic; Drug Combinations; Erythema; Female; Humans; Keratolytic Agents; Male; Middle Aged; Treatment Outcome; Tretinoin; Young Adult

Melasma has a negative impact on quality of life since it typically occurs on the face.. To evaluate the erythema and pigmentation of melasma lesions and the surrounding areas in patients receiving triple combination (TC: hydroquinone, tretinoin, and fluocinolone acetonide) regimens.. Patients first received an 8-week daily TC treatment and were then randomized to twice weekly or tapering regimen with TC. Melanin and erythema levels of lesions and surrounding areas were objectively measured using a narrowband reflectance spectrophotometer.. Progressive reduction in the mean melanin levels was observed in the treatment phase. Following both maintenance regimens, there was no difference between melanin levels in the melasma lesions. Adverse effects were rare in both phases of the study and there was borderline reduction in erythema with regimen II.. Both maintenance regimens were effective in maintaining results obtained during the initial treatment phase, and were safe and well-tolerated. Erythema was less intense with the tapering regimen.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Antioxidants; Drug Therapy, Combination; Erythema; Fluocinolone Acetonide; Humans; Hydroquinones; Keratolytic Agents; Long-Term Care; Maintenance Chemotherapy; Melanins; Melanosis; Prospective Studies; Single-Blind Method; Skin; Skin Pigmentation; Tretinoin; Young Adult

Determinants of skin irritability are poorly understood. This study aims to assess differences in cutaneous safety/irritation based on Fitzpatrick skin type among patients with acne treated with tretinoin gel microsphere (TGM). This was a phase 4, 12-week, prospective, nonrandomized, open-label, multicenter study. Approximately 500 patients with mild to moderate acne were treated with TGM 0.04% or 0.1% and assessed for cutaneous irritation at baseline and weeks 3, 6, and 12. In this post hoc analysis of patients with Fitzpatrick skin type I-III vs Fitzpatrick skin type IV-VI, there was a general trend toward initial worsening of cutaneous adverse events (AEs) by week 3 across all variables and groups. This was followed by a trend toward improvement and resolution of skin-related AEs from week 3 to week 12 regardless of Fitzpatrick skin type, with a few exceptions. Erythema was the only cutaneous AE that consistently decreased among patients with darker skin. Results from a subsequent 3-group analysis (Fitzpatrick I-II vs Fitzpatrick III-IV vs Fitzpatrick V-VI) generally mirrored those from the 2-group study. Study limitations include patient nonadherence, lack of a placebo arm, and lack of data regarding the impact of concurrent medications on outcomes. There was no correlation between irritation and Fitzpatrick skin type. ABBREVIATIONS USED: adverse event (AE), analysis of variance (ANOVA), benzoyl peroxide (BP), case report form (CRF), modified Global Acne Grading Score (mGAGS), tretinoin gel microsphere (TGM).

Topics: Acne Vulgaris; Administration, Cutaneous; Adolescent; Adult; Child; Dermatologic Agents; Erythema; Female; Gels; Humans; Male; Microspheres; Prospective Studies; Skin Pigmentation; Time Factors; Tretinoin; Young Adult

The use of topical medications for acne vulgaris is often limited by their irritant properties. Newer combination preparations are available and offer convenience, but irritant potential may still be a hindrance, perhaps more so with the combination of 2 agents. Few studies have compared these formulations directly for tolerability.. We sought to compare the tolerability of 2 combination topical acne products, clindamycin 1.2%-tretinoin 0.025% (CLIN/RA) gel and benzoyl peroxide 2.5%-adapalene 0.1% (BPO/ADA) gel.. CLIN/RA and BPO/ADA were applied daily to opposite sides of a subject's face for 21 days in a double-blinded fashion. Investigators' Global Assessments and study subject self-assessments of burning/stinging, itching, erythema, and dryness/scaling were collected. Transepidermal water loss (TEWL) was also measured as an objective measure of skin irritation. A mixed model analysis and repeated-measures analysis of variance were used to compare outcomes for both acne formulations.. CLIN/RA produced significantly less burning/stinging than BPO/ADA (P<.001) as well as significantly less pruritus than BPO/ ADA (P<.001). BPO/ADA caused significantly more TEWL than CLIN/RA (P=.005). There was no significant difference in the amount of erythema or the amount of dryness/scaling caused by either formulation.. CLIN/RA produced significantly less skin irritancy and TEWL than BPO/ADA.

Topics: Acne Vulgaris; Adapalene; Adult; Anti-Bacterial Agents; Benzoyl Peroxide; Clindamycin; Dermatologic Agents; Diagnostic Self Evaluation; Double-Blind Method; Drug Combinations; Erythema; Female; Humans; Irritants; Keratolytic Agents; Linear Models; Male; Naphthalenes; Pruritus; Skin; Tretinoin; Water Loss, Insensible; Young Adult

Despite the many beneficial effects of dermatologic applications, most of the current treatments for acne cause local irritation. The objective of this study was to compare the ability of the epidermis to tolerate adapalene 0.1% cream and gel and tretinoin microsphere in concentrations of 0.04% and 0.1%. A total of 31 subjects were enrolled in the study. The test products were applied under occlusive dressings on the upper back for approximately 24 hours, 4 times a week, and for 72 hours, once a week, for a period of 3 weeks. Skin reactions (erythema score plus other local reactions) at the product application sites were assessed 5 to 30 minutes after dressing removal. Twenty-six subjects completed the study. A total of 10 subjects discontinued use of 1 or more of the test products because of irritation scores reaching severe or greater, all of these discontinuations were at sites treated with the tretinoin products. The mean 21-day cumulative irritancy indices for adapalene 0. 1% cream and gel were significantly lower (P<.01) than those for tretirnoin microsphere 0.04% and 0. 1% and not higher than that of the negative control product.

Topics: Adapalene; Adult; Dermatologic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Eruptions; Erythema; Female; Gels; Humans; Male; Microspheres; Middle Aged; Naphthalenes; Ointments; Pruritus; Skin; Tretinoin

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

Tretinoin is often prescribed before laser resurfacing in an attempt to enhance results.. We sought to assess the clinical and biochemical effects of preoperative tretinoin use before laser resurfacing.. Patients were randomized to apply tretinoin to one forearm and placebo to the other for 3 weeks. Patients' photodamaged forearms were focally treated by carbon-dioxide laser resurfacing. Biopsy specimens were obtained at baseline and various times posttreatment. Real-time polymerase chain reaction technology was used to quantify messenger RNA levels of types I and III procollagen and matrix metalloproteinases-1, 3, and 9. Wounds were assessed for degree of re-epithelialization using a computer graphics-generated template. A colorimeter was used to quantify postoperative erythema.. No substantial differences in either biochemical markers or clinical end points were identified between tretinoin and placebo pretreated forearms.. We found no evidence of enhanced collagen formation, accelerated re-epithelialization, or quicker resolution of postoperative erythema with tretinoin pretreatment before laser resurfacing.

Topics: Administration, Cutaneous; Combined Modality Therapy; Double-Blind Method; Erythema; Humans; Keratolytic Agents; Laser Therapy; Lasers; Matrix Metalloproteinases; Procollagen; Prospective Studies; RNA, Messenger; Skin; Skin Aging; Tretinoin

Forty-two subjects with normal skin were enrolled in a single-center study to assess the cumulative irritancy potential of adapalene (Differin gel 0.1% and Differin solution 0.1%) compared with tazarotene (Tazorac gels 0.05% and 0.1%), tretinoin (Retin-A Micro gel 0.1%, Avita cream 0.025%, and Avita gel 0.025%), and white petrolatum (negative control). All test materials were applied randomly, under occlusion, to sites located on either side of the midline--the mid thoracic area of the subjects' backs. All patches were applied daily, Monday through Friday, to the same sites, unless the degree of reaction to a test product or adhesive necessitated removal (grade 3). Thirty-eight of the 42 subjects (90.5%) completed the study. Thirty-four of those 38 subjects (89.5%) had to discontinue using both tazarotene concentrations due to intolerance. Patch discontinuations for the remaining test materials were as follows: 7 subjects discontinued use of tretinoin microsphere gel 0.1%, 3 discontinued tretinoin cream 0.025%, 1 discontinued tretinoin gel 0.025%, and 1 discontinued adapalene gel 0.1%. None of the subjects discontinued use of the white petrolatum or the adapalene solution 0.1%. Adapalene gel and solution 0.1% were statistically (P<.01) less irritating than both tazarotene gels 0.1% and 0.05%, tretinoin microsphere gel 0.1%, and tretinoin gel 0.025%, and they were not statistically different from tretinoin gel 0.025%.

Topics: Adapalene; Adult; Aged; Dermatologic Agents; Double-Blind Method; Drug Interactions; Erythema; Female; Gels; Humans; Male; Middle Aged; Naphthalenes; Nicotinic Acids; Probability; Sensitivity and Specificity; Skin Irritancy Tests; 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

Topics: Adult; Erythema; Facial Dermatoses; Female; Humans; Keratolytic Agents; Middle Aged; Skin; Skin Aging; Skin Physiological Phenomena; Treatment Outcome; Tretinoin; Water; Water Loss, Insensible

The percutaneous absorption of clindamycin was studied in healthy male volunteers, comparing two investigative clindamycin (% w/v)/tretinoin (0.025% w/v) gels, containing clindamycin phosphate ester and clindamycin HCl, respectively, relative to a clindamycin phosphate lotion (1% clindamycin; Dalacin T). Formulations were applied daily for 5 days on the face, according to a balanced complete block design. Redness of the skin was scored visually, and blood and urine were collected. Clindamycin plasma levels did not exceed the limit of quantification (5 ng mL(-1)) with the clindamycin phosphate formulations, but one volunteer who received the clindamycin HCl/tretinoin gel showed plasma levels of up to 13 ng mL(-1). Clindamycin urinary excretion for 12 h after application of the clindamycin phosphate/tretinoin gel was comparable to the values of the reference lotion, whereas the clindamycin HCl/tretinoin gel gave significantly higher values. Erythema appeared to be associated with increased urinary excretion. The formulations were tolerated well. In a separate clinical pilot study in acne patients, the transdermal uptake of tretinoin and clindamycin from the clindamycin phosphate/tretinoin gel was monitored. Plasma samples were collected after 4 and 12 weeks of daily treatment. None of the study plasma samples contained measurable tretinoin levels. Clindamycin levels were not quantifiable in the majority (87%) of samples, the highest plasma level was 11 ng mL(-1). The chemical form of clindamycin proved to modulate skin irritation and percutaneous uptake of clindamycin from a gel formulation in healthy subjects. There was no indications for a notable transdermal uptake of tretinoin during daily application of the gel in patients, nor for an enhancing effect of tretinoin on clindamycin uptake.

Topics: Acne Vulgaris; Administration, Cutaneous; Adult; Anti-Bacterial Agents; Chemistry, Pharmaceutical; Clindamycin; Drug Therapy, Combination; Erythema; Gels; Humans; Keratolytic Agents; Male; Pilot Projects; Skin Absorption; Tretinoin

A randomized, investigator masked, intra individual comparative study was conducted in 30 healthy volunteers to compare the cutaneous effects of adapalene 0.1% gel and adapalene 0.1% cream with their respective vehicles, using tretinoin 0.05% cream (n = 21) or tretinoin 0.1% cream (n = 9) and a tretinoin cream vehicle (n = 30) as controls. The products were applied to hip/buttock skin for 4 days under occlusive conditions. Cytosolic retinoic acid binding protein-II (CRABP-II) mRNA levels were measured using the RT-PCR technique in punch biopsies taken from 10 subjects. Epidermal thickness was assessed using image analysis of haematoxylin and eosin stained sections from another 11 subjects. Erythema was assessed in all subjects both by a visual scoring system and by chromameter. Adapalene 0.1% gel and adapalene 0.1% cream produced similar significant increases in CRABP-II mRNA levels compared to their vehicles (P < 0.01). The two tretinoin formulations also resulted in similar significant increases in CRABP-II compared to the cream vehicle (P < 0.001). However, only the two tretinoin formulations resulted in an increase in epidermal thickness and only the tretinoin 0.1% cream resulted in significant erythema. Adapalene 0.1% gel and adapalene 0.1% cream induce RAR-mediated gene expression to a similar degree in this model, without the irritant effects of tretinoin.

Topics: Adapalene; Anti-Inflammatory Agents, Non-Steroidal; Erythema; Gels; Humans; Keratolytic Agents; Naphthalenes; Ointments; Receptors, Retinoic Acid; Transcription, Genetic; 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

In clinical practice, the cutaneous exposure to chemical irritants such as surfactants and topical drugs is frequent. Topical all-trans retinoic acid (RA) is often associated with irritation and induces epidermal changes similar to those produced by sodium lauryl sulphate (SLS). Using bioengineering techniques, e.g. assessing transepidermal water loss (TEWL), capacitance and chromametry, we investigated the variations of the skin response to SLS and RA and to both chemicals applied sequentially, allowing different time periods (from 1 h to 2 weeks) between applications of SLS and RA. Both chemicals caused irritation as assessed by visual scoring, but the values from the objective variables differed at different time periods. TEWL increased dramatically shortly after applying SLS but the increase was delayed after RA. After applying SLS, the capacitance generally decreased then returned to basal values; treatment with RA produced an overall increase. Only the results from chromametry were similar. After tandem application, the drugs were synergistic for all variables except capacitance, showing an antagonistic interaction for skin hydration. These results suggest that non-specific skin irritation profoundly reflects different mechanisms of action at tissue level. With sequential application, SLS injury modified the response to RA for at least 1 week after applying SLS. These late effects of detergents should be considered when studying irritant chemical interactions and in developing strategies for the management of occupational and other irritant dermatitis.

Topics: Adult; Drug Administration Schedule; Drug Eruptions; Drug Interactions; Erythema; Female; Galvanic Skin Response; Humans; Keratolytic Agents; Male; Patch Tests; Sodium Dodecyl Sulfate; Surface-Active Agents; Tretinoin; Water Loss, Insensible

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

Adapalene is a new synthetic retinoid analogue developed for the topical treatment of acne vulgaris.. The study was designed to compare the efficacy and safety and adapalene gel 0.1% with tretinoin gel 0.025% in the treatment of grade II to II facial acne vulgaris.. Three hundred twenty-three patients were enrolled in this investigator-masked, randomized, parallel group, multicenter trial. Patients applied the test materials to the entire facial area daily, for a period of 12 weeks. Efficacy and cutaneous tolerance were assessed at baseline and weeks 2,4,8, and 12. Efficacy was determined by investigator counts of noninflammatory open and closed comedones, and inflammatory papules and pustules, as well as global improvement. Cutaneous tolerance was evaluated by erythema, scaling, and dryness, along with burning and pruritus.. Staring at weeks 2 and 4, adapalene gel produced numerically greater lesion reductions than did tretinoin gel for all lesion types. At week 12, the mean percent reduction in the different lesion counts was as follow: 49% versus 37% for total lesions (p<0.01); 46% versus 33% for noninflammatory lesions (p=0.02); 48% versus 38% for inflammatory lesions (p=0.06) in adapalene and tretinoin gel treatment groups, respectively. Cutaneous side effects were limited to a mild "retinoid dermatitis" occurring in both treatment groups; however, patients treated with adapalene gel tolerated this therapy significantly better than those treated with tretinoin gel. Laboratory test evaluations (hematology, blood chemistries, urinalysis) were performed in 54 patients before and after 3 months of treatment. No clinically significant changes were observed.. Adapalene gel 0.1% applied once daily was significantly more effective in reducing acne lesions and was better tolerated than tretinoin gel 0.025% in the treatment of acne vulgaris.

Topics: Acne Vulgaris; Adapalene; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Child; Drug Eruptions; Drug Tolerance; Erythema; Facial Dermatoses; Female; Gels; Humans; Keratolytic Agents; Male; Naphthalenes; Pruritus; Single-Blind Method; Skin Diseases; Tretinoin

Topically applied all-trans retinoic acid (RA) is often associated with skin irritation. A detailed quantification of RA-induced functional changes in stratum corneum is, however, still limited. Using non-invasive bioengineering techniques of measurements of transepidermal water loss (TEWL), stratum corneum hydration and cutaneous blood flow (CBF), we quantified the irritant effects of 0.05% and 0.1% RA in ethanol on normal skin compared with 1% sodium lauryl sulphate (SLS) in water as a model irritant in a 24-h occlusive patch-test assay. Additionally, in order to document data possibly related to the mechanism of action, skin responses to both compounds applied in tandem was also investigated over 18 days. The extent of the irritant response to 0.05 and 0.1% RA, respectively, were similar, implying analogous irritation potency. While RA caused more intense scaling than SLS, other skin responses to RA were significantly weaker than those due to SLS. An increase in TEWL, on day 7, in RA-exposed sites indicates a secondary delayed impairment of the stratum corneum (SC) barrier. In a tandem-design assay, pretreatment with RA appeared to reduce the irritant effects of SLS on SC hydration and CBF. In contrast, pre-exposure to SLS showed a synergestic response in erythema, scaling and TEWL. Our results demonstrate that RA, like SLS, is capable of impairing SC water barrier function, which may be responsible, in part, for the irritation associated with its topical use. However, the distinctive biological responses to these compounds suggest a different mode of action of RA and SLS. In addition, the precise reason for the unique results observed in the tandem-design assays is not clear.

Topics: Administration, Topical; Adult; Blood Flow Velocity; Cross-Over Studies; Drug Eruptions; Erythema; Female; Humans; Keratolytic Agents; Male; Skin; Sodium Dodecyl Sulfate; Surface-Active Agents; Tretinoin

We investigated the clinical, histologic, and molecular responses of normal human skin to all-trans-retinol (ROL) application, compared to those induced by topical all-trans-retinoic acid (RA), and measured ROL-derived metabolites. Up to 1.6% ROL, 0.025% RA in vehicle (70% ethanol/30% propylene glycol), or vehicle alone were applied in a double-blind fashion to normal buttock skin and occluded for 4 d. ROL produced from none to only trace erythema, which was clinically and statistically insignificant, whereas RA induced a significant 3.7-fold increase in erythema score compared to vehicle (n = 10, p < 0.01). However, ROL induced significant epidermal thickening (1.5-fold at 1.6% ROL, p < 0.01), similar to RA (1.6-fold at 0.025% RA, p < 0.01), relative to the vehicle. ROL, compared with vehicle, also increased mRNA levels of cellular retinoic acid binding protein (CRABP-II) and cellular retinol binding protein (CRBP) genes as determined by Northern analysis (5-6-fold and 6-7-fold, respectively) and riboprobe in situ hybridization. CRABP-II and CRBP protein levels were also higher following ROL than vehicle treatment, as measured by ligand binding (3.2-fold, p < 0.001; n = 7) and Western analysis (3.6-fold, p < 0.003; n = 6), respectively. Epidermal retinyl ester (RE) content, measured after removal of stratum corneum, rose 240-fold (p < 0.005, n = 5) by 24 h of ROL occlusion. RA content, however, was undetectable or detectable only at trace amounts in all samples obtained at 0, 6, 24, and 96 h after ROL occlusion. Detectability of RA was not correlated with ROL treatment (compared to untreated normal skin, p = 0.86) or baseline skin ROL levels (average r = -0.1, p > 0.3). These data demonstrate that ROL application 1) produces trace erythema not significantly different from vehicle, whereas RA causes erythema; 2) induces epidermal thickening and enhances expression of CRABP-II and CRBP mRNAs and proteins as does RA; 3) causes marked accumulation of retinyl ester; and 4) does not significantly increase RA levels. Taken together, the data are compatible with the idea that ROL may be a prohormone of RA, because it produces changes in skin similar to those produced by RA but without measurable RA or irritation.

Topics: Administration, Cutaneous; Adult; Dose-Response Relationship, Drug; Drug Eruptions; Epidermis; Erythema; Esters; Gene Expression Regulation; Humans; Hyperplasia; In Situ Hybridization; Occlusive Dressings; Receptors, Retinoic Acid; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Safety; Tretinoin; Vitamin A

Acute topical treatment of human skin with retinoic acid (RA) results in a pleiotropic response, some aspects of which are mimicked by non-specific irritants. To identify reliable cutaneous markers of retinoid action, it is important to determine which aspects of this response are specifically due to the presence of RA. We have previously demonstrated a rapid and pronounced increase in steady-state cellular RA-binding protein II (CRABP-II)mRNA levels after topical RA treatment. Here we characterize the dose dependence and kinetics of this response, and compare the effects of a well-known irritant, sodium dodecylsulfate (SDS), to those of RA and its vehicle. The induction of CRABP-II mRNA in response to 0.1% RA cream was maximal by 16 h (elevenfold relative to untreated skin), and persisted at near-maximal levels (eight-fold) for up to 4 d. RA was potent in eliciting this response, as approximately half-maximal stimulation was observed after 16 h of treatment with 0.001% RA. Treatment for 4 d with 0.1% RA cream versus 2% SDS in RA vehicle resulted in nearly identical levels of cutaneous erythema, spongiosis, and epidermal thickening. However, the CRABP-II mRNA response to 2% SDS was no greater than that observed in response to vehicle alone (2.9 times relative to occluded skin control at 4 d). SDS also had no effect upon either CRABP-II or RAR-beta mRNA levels in quiescent human dermal fibroblasts in vitro, whereas RA elicited both responses at 1000-times lower concentrations than SDS. Taken together, these data identify the CRABP-II mRNA response as a reliable, rapid, and selective marker for retinoid activity in human skin.

Topics: Carrier Proteins; Dose-Response Relationship, Drug; Erythema; Fibroblasts; Humans; Receptors, Retinoic Acid; RNA, Messenger; Skin; Skin Physiological Phenomena; Sodium Dodecyl Sulfate; Time Factors; Transcription, Genetic; Tretinoin

A new synthetic retinoid analogue, adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid, CD271), which is relatively selective for retinoic acid receptor beta, was noted to be an effective comedolytic agent in the rhino mouse model and to have clinical efficacy against acne. In pursuit of this observation, we studied the effects of CD271 on the development of erythema, spongiosis, and epidermal hyperplasia as well as other well-characterized markers of in vivo retinoid action after 4 d of occluded topical treatment. The objective of the study was to elucidate further those parameters associated with potential clinical efficacy. Twenty-five subjects were treated with 0.1% all-trans retinoic acid cream, all-trans retinoic acid vehicle, 0.1% CD271 gel, or CD271 vehicle under occlusion for 4 d. Only all-trans retinoic acid induced erythema (p < 0.01 versus all other treatments). Similarly, histologic analysis revealed that epidermal hyperplasia and spongiosis were induced only by all-trans retinoic acid (p < 0.01 versus all other treatments). By immunohistochemical analysis: all-trans retinoic acid increased expression of epidermal transglutaminase, involucrin, and calgranulin (p < 0.05 versus all other treatments). In contrast to these data, both CD271 and all-trans retinoic acid caused marked and significant (p < 0.05) elevation of cellular retinoic acid-binding protein-II (CRABP-II) messenger ribonucleic acid steady-state levels as judged by quantitative RNA blot analysis. Although CD271 treatment did not lead to erythema or affect epidermal morphology, its ability to induce a marker of retinoid action (i.e., CRABP-II) was 70% the potency of all-trans retinoic acid. This study suggests that CRABP-II gene expression may be a more sensitive indicator of retinoid biologic activity in skin than are erythema or changes in epidermal morphology and differentiation.

Topics: Adapalene; Administration, Topical; Blotting, Northern; Carrier Proteins; Erythema; Gene Expression; Humans; Immunohistochemistry; Naphthalenes; Receptors, Retinoic Acid; RNA, Messenger; Skin; Tretinoin

There is evidence that topical tretinoin promotes wound healing, especially when the wound area is pretreated. In our study, 5 patients were pretreated for 2 weeks with 0.05% tretinoin cream to one groin or axilla, followed by electroepilation to both sides. Electroepilation created small, superficial wounds. Healing was defined as complete re-epithelialization. In all patients the pretreated side showed a significantly decreased healing time as compared to the nonpretreated side. Pretreatment of skin with topical tretinoin may be useful in reducing healing times of patients undergoing electroepilation.

Topics: Administration, Topical; Adult; Erythema; Hair Removal; Humans; Tretinoin; Wound Healing

Topics: Administration, Cutaneous; Adult; Double-Blind Method; Erythema; Female; Humans; Male; Middle Aged; Prospective Studies; Skin Aging; Skin Diseases; Tretinoin

20% azelaic acid cream was compared clinically with it vehicle in a 3-month double-blind study of 92 patients with moderate inflammatory acne. In a single-blind study of 289 patients with comedonal acne, the topical azelaic acid preparation was compared with 0.05% tretinoin cream over a period of 6 months. In both controlled studies, 20% azelaic acid cream significantly reduced the number of acne lesions and yielded clinically relevant improvement rates. Azelaic acid cream was significantly and substantially more effective than its vehicle, indicating that the dicarboxylic acid itself is an active drug in acne treatment. In the study of comedonal acne, 20% azelaic acid cream was equally effective as 0.05% tretinoin cream in reducing the number of comedones and with respect to overall response. However, azelaic acid cream was better tolerated, causing fewer local side effects than the topical retinoid.

Topics: Acne Vulgaris; Administration, Topical; Adolescent; Adult; Child; Clinical Trials as Topic; Dicarboxylic Acids; Double-Blind Method; Drug Eruptions; Erythema; Female; Humans; Male; Middle Aged; Tretinoin

In a double-blind controlled multicenter trial consisting of 257 patients with acne vulgaris an 8-week topical treatment with the retinoic acid derivative Ro 11-1430 (0.1% lotion) was compared with vitamin A acid (0.05% lotion) and the lotion alone (placebo). In reducing the number of comedones vitamin A acid was superior to Ro 11-1430, which was significantly better than placebo. The reduction in number of papules and pustules was not statistically significant on either treatment. Local side effects, i.e. erythema, desquamation, burning and pruritus occurred more frequently and were more severe on vitamin A acid than on Ro 11-1430 and placebo which did not differ. No correlation was found between incidence and severity of local reactions and therapeutic effect.

Topics: Acne Vulgaris; Administration, Topical; Clinical Trials as Topic; Drug Eruptions; Drug Evaluation; Erythema; Humans; Pruritus; Tretinoin; Vitamin A

Neutrogena hand cream has been used to modify the erythema, dryness, and topical irritancy caused by topical tretinoin and other topical acne preparations in a study of fifty-two patients.

Topics: Acne Vulgaris; Administration, Topical; Adolescent; Adult; Erythema; Female; Humans; Male; Ointments; Tretinoin; Vitamin A

In a double-blind, randomized, group-comparative clinical trial, 31 patients with acne vulgaris received topical treatment for 6-8 weeks with a lotion containing either 0.05% retinoic acid or 0.1% of the retinoic acid derivative Ro 11-1430. The side-effects erythema, desquamation and burning were significantly less frequent with Ro 11-1430 than with retinoic acid. The treatments appeared to be approximately equally effective in reducing the number of acne elements, but due to the limited number of patients studied, the trial was admittedly not sufficient to detect differences with regard to therapeutic efficacy.

Topics: Acne Vulgaris; Administration, Topical; Clinical Trials as Topic; Drug Eruptions; Drug Evaluation; Erythema; Humans; Tretinoin; Vitamin A

Erythema-directed digital photography is a novel method for evaluating the efficacy and tolerability of topical acne treatments. Here, we describe three case reports in which erythema-directed digital photography was used to evaluate acne before and after up to 12 weeks of treatment with clindamycin 1%/tretinoin 0.025% (Clin-RA).. Erythema-directed digital photography was used to evaluate acne in three patients with mild-to-moderate facial acne, two of whom had refused to continue previous topical acne treatment (benzoyl peroxide 5% and clindamycin 1%/benzoyl peroxide 5%) due to persistent irritation. Acne lesions and erythema were evaluated using standard clinical photography and erythema-directed digital photography (VISIA-CR. Erythema-directed digital photography revealed background erythema from previous topical acne treatments that was not evident from standard clinical photographs and allowed a better visualization of both inflammatory and non-inflammatory lesions. In all patients, there was a clear improvement in background erythema and a reduction in acne lesions following treatment with Clin-RA.. This study has demonstrated for the first time that erythema-directed digital photography can enhance the evaluation of the efficacy and tolerability of topical acne treatments. These cases show that Clin-RA was associated with improved efficacy and tolerability vs previous treatments with topical monotherapy (benzoyl peroxide 5%) or a topical fixed-dose combination (clindamycin 1%/benzoyl peroxide 5%).

Topics: Acne Vulgaris; Administration, Cutaneous; Adolescent; Benzoyl Peroxide; Clindamycin; Dermatologic Agents; Drug Combinations; Erythema; Female; Humans; Male; Photography; Treatment Outcome; Tretinoin; Young Adult

Deep erythema and inflammation after re-epithelialization of superficial wounds is a sign of scar formation. Corticosteroids may prevent scarring by suppression of inflammation and fibroblast activity. Tretinoin may increase the efficacy of corticosteroids in this setting.. To evaluate the efficacy of corticosteroids plus tretinoin for prevention of scars after superficial wounds.. In a retrospective study of patients with superficial partial thickness thermal skin burn, we compared the patients who received clobetasol plus tretinoin after re-epithelialization with patients who did not receive any medication. Clobetasol propionate 0.05% ointment was used twice daily with overnight occlusive dressing in conjunction with twice weekly topical tretinoin 0.05% cream.. Among 43 patients who had light pink or no erythema after re-epithelialization and consequently did not receive clobetasol + tretinoin, no scar was developed. Among patients who had deep erythema after re-epithelialization, rate of scar formation was significantly higher in 14 patients who did not receive clobetasol + tretinoin than in 21 patients who received clobetasol + tretinoin (64% and 19%, respectively; p = 0.01).. Clobetasol + tretinoin can significantly decrease the incidence of scar formation in patients with inflammation after re-epithelialization of superficial wounds.

Topics: Adolescent; Adult; Aged; Burns; Child; Child, Preschool; Cicatrix; Clobetasol; Dermatologic Agents; Erythema; Female; Glucocorticoids; Humans; Male; Middle Aged; Occlusive Dressings; Re-Epithelialization; Retrospective Studies; Skin; Tretinoin; Ulcer; Young Adult

Actinic keratoses (AK) are premalignant lesions occurring mainly in sun-damaged skin. Current topical treatment options for AK and photo-damaged skin such as liquid nitrogen and electrosurgery are not suitable for field treatment. Otherwise, therapies suitable for field treatment bring along considerable patient discomfort. Non-ablative fractional resurfacing has emerged as a logical treatment option especially for field treatment of AK.. To evaluate the clinical efficacy of fractional laser therapy for clearing AK and improving skin quality. To compare patient friendliness of the "fractional" therapy with those reported for other field treatment modalities.. Ten patients with Fitzpatrick skin type I to III with multiple AK and extensive sun-damaged skin, received 5-10 sessions with a 4-week interval using a 1550 nm Erbium-Glass Fractionated laser (Sellas, Korea). Four weeks and 24 weeks after the last treatment the clinical results were evaluated by an independent physician.. The mean degree of improvement, in terms of reduction in the number of AK and improvement of skin texture, was 54% on a 4 point PGA scale, and persisted for approximately 6 months. The biggest advantage of fractional laser treatment, besides the eradication of AK and a clear rejuvenation effect, is the absence of "downtime".. Fractional non-ablative resurfacing induces significant reduction in the number of AK and improves the skin quality. Also all patients preferred fractional laser therapy above other AK treatment modalities.

Topics: Aged; Aged, 80 and over; Combined Modality Therapy; Edema; Erythema; Female; Humans; Keratolytic Agents; Keratosis, Actinic; Laser Therapy; Male; Middle Aged; Pain Measurement; Pilot Projects; Rejuvenation; Skin; Sunlight; Tretinoin

Novel drug delivery systems, such as solid lipid nanoparticles (SLN), have been proposed to reduce retinoic acid (RA)-induced skin irritation. However, one question still remains: could it be accomplished without reducing efficacy? To evaluate this question the comedolytic effects and epidermal thickening of RA-loaded SLN were compared to the conventional RA formulations (gel or cream), as well as the potential of these formulations to induce skin irritation. The comedolytic effects and epidermal thickening of these formulations, both containing RA at 0.01 or 0.05%, were investigated in a rhino mouse model, while the studies of RA-induced skin irritation were evaluated through rabbit skin irritation tests and in the rhino mouse model. RA-loaded SLN, as compared to the placebo, produced a comedolytic effect with a significant reduction of the utricle diameter, which proved to be similar to that observed for marketed gels or creams regardless of the RA concentration. RA formulations (SLN or marketed cream) also induced an epidermal proliferation leading to a thickened epidermis in treated animals. In both animals studied (rhino mice and rabbits), the RA-loaded SLN, when compared to conventional formulations, promoted a significant reduction in RA-induced skin irritation (erythema and scaling). Then, RA-loaded SLN represents an interesting alternative to reduce RA-induced skin irritation without reducing efficacy, and constitutes an innovative approach for the topical treatment of acne with RA.

Topics: Animals; Cell Proliferation; Dermatitis, Contact; Disease Models, Animal; Drug Delivery Systems; Epidermis; Erythema; Gels; Glutamates; Humans; Lipids; Mice; Nanoparticles; Rabbits; Skin Irritancy Tests; Tretinoin

Alitretinoin is a new drug for systemic treatment of chronic hand eczema. Previous functional tests of skin topically treated with retinoids have indicated impaired skin barrier function, but no data are available on barrier parameters after systemic alitretinoin treatment. To investigate the effect of systemic alitretinoin on skin barrier function and response to irritants, a secondary objective was to determine if changes occur in the lipid profile of stratum corneum after treatment with systemic alitretinoin. We conducted an open clinical intervention study on eight people ascribed to systemic alitretinoin treatment. The criteria for being ascribed to alitretinoin were chronic hand eczema and insufficient therapeutic response to potent topical corticosteroids. Before initiation and after 2 months of systemic treatment with 30 mg alitretinoin, a challenge with sodium lauryl sulphate (SLS) was performed on the volar forearm and evaluated by trans-epidermal water loss (TEWL), erythema, and a cyanoacrylate skin sample was obtained for lipid analysis. We found no significant changes in response to SLS irritation as evaluated by TEWL and erythema, after treatment with alitretinoin for 2 months. No significant changes in stratum corneum lipids were found after 2 months of treatment. In conclusion, systemic alitretinoin does not influence skin susceptibility to irritants or the ceramide profile of stratum corneum.

Topics: Alitretinoin; Ceramides; Chronic Disease; Disease Progression; Eczema; Epidermis; Erythema; Humans; Irritants; Retinoids; Sodium Dodecyl Sulfate; Tretinoin; Water Loss, Insensible

The aim of this investigation was to develop solid lipid nanoparticles (SLNs) from indigenous, natural solid lipids by using a simple microemulsion technique. Furthermore, the aim was to characterize these SLNs and evaluate its potential in the topical delivery of a lipophilic drug, tretinoin (TRN). The developed SLNs were characterized for particle size, polydispersity index, entrapment efficiency of TRN and morphology. TRN-loaded SLN-based topical gels were formulated and the gels were evaluated comparatively with the commercial product with respect to primary skin irritation, in vitro occlusivity and skin permeation. The results of the study showed mean particle size <100nm of the SLN dispersions with the novel lipids. Up to 46% of drug entrapment in the lipids was attained. Lesser skin irritancy, greater skin tolerance, occlusivity and slow drug release was observed with the developed TRN-loaded SLN-based gels than the commercial product. The research work could be concluded as successful production of SLNs using highly purified stearine fraction of natural solid lipids. The results of the characterization and evaluation established the safety for use, suitability and compatibility of indigenous natural lipids as a novel excipient.

Topics: Administration, Cutaneous; Animals; Delayed-Action Preparations; Dermatologic Agents; Drug Carriers; Drug Compounding; Edema; Erythema; Gels; Lipids; Nanoparticles; Particle Size; Permeability; Rabbits; Skin; Skin Absorption; Solubility; Surface Properties; Technology, Pharmaceutical; Tretinoin; Water Loss, Insensible

The objective of this investigation was to develop solid lipid nanoparticles (SLN) of tretinoin (TRE) with the help of facile and simple emulsification-solvent diffusion (ESD) technique and to evaluate the viability of an SLN based gel in improving topical delivery of TRE. The feasibility of fabricating SLN of TRE by the ESD method was successfully demonstrated in this investigation. The developed SLN were characterized for particle size, polydispersity index, entrapment efficiency of TRE and morphology. Studies were carried out to evaluate the ability of SLN in improving the photostability of TRE as compared to TRE in methanol. Encapsulation of TRE in SLN resulted in a significant improvement in its photostability in comparison to methanolic TRE solution and also prevented its isomerization. Furthermore, the skin irritation studies carried out on rabbits showed that SLN based TRE gel is significantly less irritating to skin as compared to marketed TRE cream and clearly indicated its potential in improving the skin tolerability of TRE. In vitro permeation studies through rat skin indicated that an SLN based TRE gel has permeation profile comparable to that of the marketed TRE cream.

Topics: Administration, Topical; Animals; Chemistry, Pharmaceutical; Diffusion; Drug Compounding; Drug Stability; Erythema; Hydrogen-Ion Concentration; Irritants; Keratolytic Agents; Lipids; Microscopy, Electron, Scanning; Nanoparticles; Particle Size; Rabbits; Rheology; Skin; Skin Absorption; Solvents; Tretinoin

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

Topics: Erythema; Glycolates; Humans; Hydroquinones; Keratolytic Agents; Laser Therapy; Lasers; Pigmentation Disorders; Radiation-Protective Agents; Randomized Controlled Trials as Topic; Time Factors; Tretinoin

An undesirable side-effect of retinoid treatment is skin fragility. As desmosomes are important in maintaining the cohesion of epidermal keratinocytes, we investigated whether all-trans-retinoic acid (RA) compromises desmosome expression in human epidermis, thereby predisposing skin to fragility. Solutions containing 0.025% RA, 5% sodium dodecyl sulphate (SDS) as an irritant control, or vehicle alone were applied to three sites on the buttocks of normal volunteers (n = 9). Treated sites were occluded for 4 days, and biopsies taken under local anaesthesia. Cryostat sections were stained with a panel of antibodies to desmosomal proteins and visualized by immunofluorescence microscopy. Stained sections were randomized and assessed for intensity of staining. The epidermal thickness of each treated site was quantified by image analysis. Western blots of epidermal desmocollins were quantified by densitometry. RA and SDS treatments significantly, but equivalently, increased epidermal thickness compared with vehicle. Immunohistochemically, both RA and SDS were shown to reduce epidermal staining for desmoplakin, desmoglein 1, plakophilin 1 and desmocollin 3 equally compared with vehicle-treated skin (P < 0.001). RA produced a greater reduction in desmocollin 1 staining compared with SDS (P < 0.001). Similar reductions in desmocollins were found by Western blot analysis. Reduced desmocollin expression may indicate compromised desmosomal adhesion, leading to the skin fragility that results from retinoid treatment.

Topics: Adult; Blotting, Western; Desmosomes; Erythema; Female; Humans; Immunohistochemistry; Irritants; Keratolytic Agents; Male; Middle Aged; Skin Diseases; Sodium Dodecyl Sulfate; Surface-Active Agents; Tretinoin

Eleven female patients are reported who underwent full-face resurfacing. Three patients were treated for cosmetic rhytids, five for residual acne scarring, and three for photoaging. There were no complications or side effects in this group of patients. Reepithelialization was achieved in an average of 9.3 days, and erythema disappeared in an average of 8.9 weeks. The UltraPulse carbon dioxide laser with computerized pattern generator (CPG) scanner allows a rapid, uniform laserbrasion. The sequence of the procedure involves close application of adjacent squares at 60 W, 200 to 300 ml, at moderate density. Skin preparation with Retin-A and bleaching agents is important for best wound healing. Postoperative wound care includes maintenance of a moist environment and Zovirax for herpes prophylaxis.

Topics: Acne Vulgaris; Acyclovir; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Antiviral Agents; Carbon Dioxide; Cicatrix; Dexamethasone; Epithelium; Erythema; Facial Dermatoses; Female; Follow-Up Studies; Glycolates; Herpesviridae Infections; Humans; Hydroquinones; Keratolytic Agents; Laser Therapy; Middle Aged; Radiation-Protective Agents; Rhytidoplasty; Skin Aging; Skin Care; Therapy, Computer-Assisted; Tretinoin; Wound Healing

We present a patient with atrophodermia vermiculata. A family tree study revealed an autosomal mode of inheritance with good penetrance. A slight improvement of the atrophic scars of the disease was noticed after local treatment with tretinoin cream, 0.05 percent, and cryotherapy.

Topics: Administration, Cutaneous; Atrophy; Child; Cicatrix; Cryotherapy; Epidermis; Erythema; Facial Dermatoses; Humans; Male; Pedigree; Tretinoin

The formation of all-trans retinoic acid is an oxidative process whereby retinol is converted to retinaldehyde and then to retinoic acid. Because retinol causes qualitative molecular changes similar to those produced by retinoic acid, we compared potency of retinol, retinaldehyde, and retinyl palmitate to retinoic acid and assessed the effects of occlusion. Retinoids were prepared in an experimental vehicle of 95% ethanol:propylene glycol (7:3) with anti-oxidant. Induction of retinoic acid 4-hydroxylase activity was the end point for comparison. Retinoic acid concentrations from 0.001% to 0.05% under occlusion produced a linear dose-response induction of 4-hydroxylase activity. The concentrations of the other retinoids under occlusion required to achieve significant induction of enzyme activity were 0.6% retinyl palmitate, 0.025% retinol, and 0.01% retinaldehyde. The linear dose-response was lost with retinoid concentrations in excess of 0.25% retinol or 0.5% retinaldehyde. Statistical analyses showed no difference in 4-hydroxylase activity between unoccluded and occluded retinol treated sites. By contrast, however, unoccluded sites treated with retinoic acid or retinyl palmitate had less induction of 4-hydroxylase activity than occluded sites. Retinol, retinaldehyde, and retinyl palmitate did not produce erythema but did increase epidermal thickness. Although retinol is a weaker retinoid than retinoic acid, the increased penetration of unoccluded retinol in comparison to unoccluded retinoic acid with this prototypic vehicle confers on retinol a more effective delivery of a retinoidal effect than unoccluded retinoic acid. Retinol at 0.25% may be a useful retinoid for application without occlusion because it does not irritate but does induce cellular and molecular changes similar to those observed with application of 0.025% retinoic acid.

Topics: Administration, Topical; Adult; Anticarcinogenic Agents; Antioxidants; Cell Membrane Permeability; Cytochrome P-450 Enzyme System; Diterpenes; Dose-Response Relationship, Drug; Enzyme Activation; Erythema; Humans; Hyperplasia; Retinoic Acid 4-Hydroxylase; Retinyl Esters; Skin; Tretinoin; Vitamin A

Separation of specific and nonspecific "irritant" effects of topical all-trans retinoic acid (RA) is a key to understanding the mechanism of retinoid action in skin. Cellular RA-binding protein (CRABP) II has been found to be a marker of RA activity in human skin. We have also previously identified a skin-specific gene (RIS-1/psoriasin) which is rapidly induced in human skin treated with RA. Here we compared the kinetics and time-course of RIS-1 and CRABP II gene activation by RA, sodium lauryl sulfate (SLS), a classical irritant, and their vehicle (VH), using a quantitative reverse transcription polymerase chain reaction. RIS-1 and CRABP II were both expressed at very low levels in untreated normal human skin, and in RA-treated skin the kinetics and time course of RIS-1 and CRABP II mRNA induction were similar. Relative to VH-treated skin, RA induced RIS-1 mRNA levels within 6 h, which further increased to 6.4-fold by 24 h (n = 4). Similarly, CRABP II mRNA levels increased from 2.6-fold at 6 h to 7.8-fold after 24 h. At 48 h the relative mRNA levels for both genes decreased towards the steady-state levels. Relative to SLS-treated skin, RIS-1 mRNA increased by 3.2-fold after 6 h and by 5.1-fold after 12 h (n = 3). Also, a 2.6-fold higher CRABP II mRNA observed after 6 h increased to 6-fold after 12 h. After 24 and 48 h RA treatment the relative mRNA levels for both genes decreased towards the steady-state levels. RA-induced skin erythema was not obvious until 24 to 48 h. We conclude, therefore, that induction of RIS-1 and CRABP II mRNA levels by topical RA in human skin are early, coordinated molecular events which precede the clinical cutaneous erythematous response to RA.

Topics: Administration, Topical; Base Sequence; Calcium-Binding Proteins; DNA Primers; Erythema; Gene Expression Regulation; Humans; Kinetics; Polymerase Chain Reaction; Receptors, Retinoic Acid; RNA, Messenger; S100 Calcium Binding Protein A7; S100 Proteins; Skin; Transcriptional Activation; 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

The area of UV erythema produced by a small beam head was found to increase with increasing doses. The aim was to investigate whether measurement of the area could be a more useful indicator of UV-induced damage than classic visual grading. Topical pretreatment with all-trans retinoic acid (tretinoin) and betamethasone valerate was used to test the applicability of the method in pharmacological studies. We used a round outlet head (5 mm2) connected by optical fibre to a monochromatic irradiator, and doses ranging from 0.05 to 0.2 Joule of 300 mm UV light were applied to the skin of 6 healthy subjects. Erythemal area was calculated by the measurement of two diameters, and intensity was graded visually (0-6 scale). The area of the erythema correlated with the increase in intensity up to score 6. Area measurement was less subject to intra-investigators' variability than the intensity score. By multiplying intensity by area, a good indicator of UV-induced reactivity was obtained. Pretreatment with betamethasone valerate decreased the area of erythema, as did tretinoin 12 h after irradiation. Thus, area measurement of erythema is a useful adjunct to visual grading of UV-induced skin reactions.

Topics: Administration, Cutaneous; Adult; Analysis of Variance; Betamethasone Valerate; Erythema; Female; Humans; Male; Pilot Projects; Radiation Dosage; Radiation Tolerance; Radiation-Protective Agents; Radiodermatitis; Skin; Tretinoin; Ultraviolet Rays

Topics: Drug Eruptions; Erythema; Granuloma; Humans; Male; Middle Aged; Minoxidil; Scalp Dermatoses; Tretinoin

Histologic and clinical improvement of sun-exposed skin following topical treatment with retinoic acid has been reported. Daily application of retinoic acid typically results within 2-5 d in an erythematous scaling reaction, which lessens with continued usage. The cellular, immunologic, and biochemical basis of this retinoid reaction and its role in the repair of photodamaged skin are not known. To investigate the retinoid reaction in man, we have treated non-sun-exposed skin with 0.1% retinoic acid cream (Retin-A, Ortho Pharmaceutical Corporation, Raritan, NJ) under occlusion for 4 d to induce erythema and then examined changes in 1) histology, 2) expression of cell-surface molecules, 3) the enzymes and second messengers of the phospholipase C/protein kinase C signal-transduction system, 4) levels of eicosanoids, and 5) levels of interleukin-1 protein and mRNA. These parameters were chosen for measurement both because they are indicators of epidermal function and previous studies suggest they may be responsive to retinoic acid treatment. Epidermal cell growth as judged by increased epidermal thickness and mitotic figures was significantly increased in retinoic acid-treated skin compared to vehicle-treated controls. Increased numbers of CD4+ T cells accompanied by prominence of dermal dendrocytes in the papillary dermis and focal keratinocyte expression of intercellular adhesion molecule-1 were observed in retinoic acid-treated biopsies. Phosphoinositide-specific phospholipase C activity and 1,2-diacylglycerol content were also elevated in retinoic acid-treated epidermis. Protein kinase C activity was reduced by one third in both the soluble and membrane fraction, suggesting down-regulation. Surprisingly, in view of the inflammatory nature of the retinoid reaction, no increases were observed in arachidonic acid, its metabolites, interleukin-1 alpha, or interleukin-1 beta. To examine the specificity of the retinoid reaction, subjects were treated with the irritant sodium lauryl sulfate, under conditions that resulted in a reaction clinically similar to that observed with retinoic acid. The histologic alterations induced by sodium lauryl sulfate were found to be indistinguishable from those induced by retinoic acid. These data indicate that, although a wide range of cellular and molecular alterations occur in retinoic acid-treated skin, these changes may not be necessarily specific or unique for retinoic acid.

Topics: Cell Adhesion Molecules; Eicosanoids; Erythema; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Interleukin-1; Protein Kinase C; RNA, Messenger; Signal Transduction; Skin; Tretinoin; Type C Phospholipases

The effects of retinoid treatment on wrinkling in the hairless mouse can be understood in the context of the repair of the dermal elastosis. The two isomers of retinoic acid do not differ qualitatively in their effects on the histological appearance of the tissue or on the wrinkling patterns produced. The all-trans isomer is slightly more potent in this system than the 13-cis isomer but substantially more irritating, which may limit the maximum degree of repair attainable. The "reconstructed" dermis is thickened, it contains new collagen as a result of the stimulation of gene expression, and the tangled, disorganized elastin is packed into a thin layer in the lower dermis. Thus, the framework within which a wrinkle had been established is eliminated, and the skin assumes a normal state, as observed. That the effacement is apparently permanent is additional evidence of the relationship between the integrity of the elastic fiber network and the surface appearance. The only difference in the repaired skin is the absence of filamentous surface features. The thickening effect of UVB and subsequent retinoid treatment on the epidermis does not contribute substantially to the overall thickness of the repaired skin. Nevertheless, despite having a minor role in the effacement of deep wrinkles, these epidermal changes evidently preclude the formation of fine surface features. The model is a valid one for the repair of photodamaged skin. From what is known about the role of elastin in maintaining skin integrity and from the association of wrinkling with excessive sun exposure, it is encouraging to observe the dual effect of retinoic acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Desmosine; Erythema; Female; Mice; Mice, Hairless; Reference Values; Skin; Skin Aging; Stereoisomerism; Tretinoin; Ultraviolet Rays

Topics: Collagen; Erythema; Humans; Injections, Subcutaneous; Tretinoin

Topics: Erythema; Humans; Keratosis; New York; North Carolina; Sunlight; Tretinoin

A 30-year-old woman with erythrokeratodermia variabilis was treated with oral isotretinoin for four months. Clinical and light and electron microscopic observations were made before and after treatment. A characteristic electron microscopic feature was subnormal numbers of keratinosomes within the stratum granulosum of hyperkeratotic plaques. Isotretinoin therapy resulted in almost complete clinical clearing of these plaques and restoration of normal numbers of epidermal keratinosomes. In addition, distinctive dyskeratotic cells containing clumped tonofilaments were observed within the stratum granulosum by electron microscopy. These cells persisted after retinoid treatment.

Topics: Adult; Biopsy; Epidermal Cells; Erythema; Female; Humans; Isotretinoin; Keratins; Keratoderma, Palmoplantar; Keratosis; Microscopy, Electron; Skin; Time Factors; Tretinoin

Six subjects taking isotretinoin were studied, none of whom had clinical or phototest evidence of photosensitivity. Of nine subjects taking etretinate, one had convincing clinical photosensitivity consisting of a burning erythema on sunlight exposure. His phototesting results showed a marked abnormality from 300 +/- 5 nm to 365 +/- 30 nm which returned close to normal limits within one month of stopping therapy. Although clinically normal, another subject taking etretinate had similar phototest evidence of abnormal photosensitivity. In vitro photohaemolysis studies demonstrated that tretinoin (all-trans-retinoic acid) and isotretinoin have a potential, while etretinate has none. However, the major metabolite of etretinate (Ro 10-1670) had a phototoxic potential greater than that of tretinoin. The apparently low incidence of photosensitivity suggests that an idiosyncrasy is responsible, perhaps due to a disorder of pharmacokinetics or metabolism. Clinical cases should use appropriate photoprotection against UVB and UVA wavebands.

Topics: Adult; Candida albicans; Erythema; Etretinate; Female; Humans; Isotretinoin; Male; Middle Aged; Photolysis; Photosensitivity Disorders; Retinoids; Tretinoin; Ultraviolet Rays

Topics: Acne Vulgaris; Adolescent; Adult; Erythema; Female; Humans; Isotretinoin; Male; Photosensitivity Disorders; Sunlight; Tretinoin

The effect of the aromatic retinoid, etretinate, has been evaluated in 17 patients suffering from moderate to severe Darier's disease (DD). The erythema, hyperkeratosis and number of papules as well as the extension of the lesions were scored before and at regular intervals during treatment. In the first treatment period a daily dose of 50 mg was given until healing but no longer than 10 weeks. In the majority of patients the effect was very good with almost complete clearing in 6 patients. In patients with severe DD a reduction of the initial score by more than 50% was seen in 7 out of 8 patients. Isomorphic reactions developed in 6 of 17 patients and was the most important side effect. In patients with moderate disease the remission periods without treatment exceeded 4 weeks. 8 patients were treated intermittently with a lower dose up to 4 treatment periods. Equally good results were obtained. The treatment of choice in DD seems to be etretinate at an intermittent regime with low doses (less than or equal to 0.5 mg/kg).

Topics: Adolescent; Adult; Aged; Darier Disease; Dose-Response Relationship, Drug; Erythema; Etretinate; Female; Humans; Lipoproteins; Male; Middle Aged; Pruritus; Tretinoin

Erythema anulare centrifugum with pustulation (EACP) is an unusual sterile pustulosis, which is believed to represent a rare type of pustular psoriasis. HLA-examination in this patient did not show, however, the typical pattern of vulgar of pustular psoriasis. No other signs of psoriasis were found either, except for the spongiform pustule. The EACP most likely corresponds to a special entity in the large group of psoriatic skin diseases. Oral retinoid therapy revealed full remission of the skin lesions.

Topics: Erythema; Etretinate; Female; Humans; Middle Aged; Psoriasis; Skin; Suppuration; Tretinoin

Forty-five patients suffering from various genodermatoses and erythematous, scaling, non-psoriatic dermatoses were treated orally with the aromatic derivative of retinoic acid, Ro 10-9359 (Tigason). In the genodermatoses the best results were obtained in ichthyosis, keratodermias and Darier's disease (95.6% good to excellent). Among the erythematous scaling diseases, treatment was effective in lichen planus, parapsoriasis and pityriasis rubra pilaris (53.3% good to excellent results). In comparison with therapies previously employed Ro 10-9359 was more effective. No serious side-effects were noted.

Topics: Administration, Oral; Adolescent; Adult; Aged; Child; Child, Preschool; Drug Evaluation; Erythema; Etretinate; Female; Humans; Male; Middle Aged; Skin Diseases; Tretinoin

The clinical and histologic features of lifelong reactive perforating collagenosis in a twenty-five year old woman are presented. Experimentally induced lesions showed the expected evolution and regression, although total time for the experimental lesion to develop and regress was shorter than the time necessary for those occurring spontaneously. Therapeutic trials with a wide variety of topical and systemic medications were without benefit, with the exception of tretinoin cream (0.1 percent), which was regularly effective in reducing the total number of lesions present.

Topics: Administration, Topical; Adult; Collagen Diseases; Erythema; Female; Humans; Keratosis; Skin; Tretinoin; Vitamin A

In a multicentre, cooperative study into the treatment of extensive psoriasis with a new aromatic retinoid (Ro 10--9359) trichogram, liver function tests and the light erythema threshold were investigated. In some of the patients hair loss occurred, usually in the fifth to eighth week after a total dose of 1.9 g retinoid. In all cases this improved an average of six weeks after dose reduction or cessation of treatment. The trichogram in 27 patients showed a diffuse toxic hair loss. In 70% the effluvium was telogenic, in 22% telogen-dystrophic. GPT, GOT, alkaline phosphatase and prothrombin index showed no significant alterations during retinoid treatment. However, in individual cases there was a rise in GOT and GPT up to 80 U/l. Furthermore there was a statistical tendency in rising bilirubin levels. Finally there was no evidence for an increase in light sensitivity after three weeks of retinoid treatment. Measurement of the erythema threshold showed rather more a reduction in light sensitivity under treatment.

Topics: Alanine Transaminase; Alkaline Phosphatase; Alopecia; Aspartate Aminotransferases; Erythema; Humans; Liver; Prothrombin; Psoriasis; Time Factors; Tretinoin; Vitamin A

Daily treatment of guinea-pig ear skin with topical 0.5% retinoic acid in acetone produced erythematous scaly dermatitis. Histologic sections revealed bandlike thickening of the epidermis on days 2 to 4, psoriasiform acanthosis, papillomatosis and increased mitotic activity on days 5 to 6. Also seen were dilatation of the upper dermal blood vessels and a fibroblastic, histiocytic reaction in the dermis. Prostaglandin E, cyclic AMP, and cyclic GMP levels were increased in the treated skin and thymidine incorporation was enhanced. Cyclic AMP and GMP levels peaked on day 5 simultaneous with maximal epidermal hyperplasia, increased mitotic activity and dermal reaction. Tritiated thymidine uptake peaked on days 4 and 5, and prostaglandin E levels continued to increase up to day 6. Cyclic AMP phosphodiesterase activity of treated skin on day 5 did not appear to be significantly different from control.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Administration, Topical; Animals; Cell Division; Cyclic AMP; Cyclic GMP; Disease Models, Animal; Erythema; Guinea Pigs; Male; Models, Biological; Prostaglandins E; Psoriasis; Skin; Skin Physiological Phenomena; Thymidine; Tretinoin; Vitamin A