tretinoin and Atrophy

Striae distensae, better known as stretch marks, are a common disfiguring skin disorder of significant cosmetic concern. Many sources have reported the use of lasers to diminish the appearance of striae. Controlled clinical studies of the various treatment modalities available for striae are relatively uncommon, and much of the clinical data are anecdotal. The use of lasers alone or in combination with other therapeutic modalities can provide a safe and effective reduction in the appearance of both red and white striae distensae. Many of these therapies require special measures for darker skin phototypes. This article reviews the historical use of laser therapy for this disorder and discusses current therapeutic options.

Topics: Administration, Topical; Atrophy; Connective Tissue Diseases; Epidermis; Female; Humans; Laser Therapy; Prognosis; Treatment Outcome; Tretinoin

In recent years there has been a growing awareness that many of the so-called attributes of aging skin are, instead, a reflection of environmental assault upon exposed areas of the body. Of special import are the deleterious effects of solar radiation on dermal connective tissue, leading to the visible manifestations of photoaging. Often termed "premature aging," the salient features of the process are distinctly different from those found in normal intrinsic aging. In general, chronically irradiated skin is metabolically hyperactive with epidermal hyperplasia and neoplasia, increased production of elastic fibers, GAGs, accelerated breakdown and synthesis of collagen, and enhanced inflammatory processes. In contrast, protected aged skin is usually characterized by a slow decline in many of these components. Experimental studies with animal models have confirmed the notion that the shorter, more energetic portion of the ultraviolet spectrum (UVB) is responsible for the dermal connective tissue destruction observed in photoaged skin. More recently, it has been shown that UVA and infrared radiation contribute significantly to photoaging, producing, among other changes, severe elastosis. Because the three broad wavebands are inseparably linked in terrestrial sunlight, all are of concern in the photoaging of human skin. Photoaged skin has been thought to be irreversibly damaged. However, our findings indicate that destruction and repair go on simultaneously under continued assault by actinic radiation. The balance is shifted toward repair when the radiation stress is relieved. Both epidermis and dermis are capable of moderate self-restoration when exogenous injury ceases, either by avoidance of sunlight or by the use of broad-spectrum, high-SPF sunscreens. Repair of the dermis, characterized by broad regions of new collagen deposited subepidermally, can be pharmacologically enhanced by topical application of retinoic acid. Although early protection from sunlight, before severe photodamage occurs, is most desirable, it is deemed advisable to counsel even older persons with photoaged skin to adopt protective measures, thereby allowing repair processes to occur.

Topics: Aging; Animals; Atrophy; Dose-Response Relationship, Radiation; Drug Evaluation, Preclinical; Elastic Tissue; Guinea Pigs; Humans; Hypertrophy; Infrared Rays; Mice; Skin; Sunlight; Sunscreening Agents; Tretinoin; Ultraviolet Rays

Melasma is a common disorder affecting a significant percentage of the population, particularly those with skin of color. Therapy with hydroquinone, a depigmenting agent, as a single agent or in combination with other agents has been used with variable success. A triple-combination (TC) cream combining hydroquinone 4% with tretinoin 0.05% and fluocinolone acetonide 0.01% was developed for the treatment of melasma. We studied the use of TC cream for 24 weeks and had tissue samples for all time points in 62 patients with moderate to severe melasma. The atrophogenic potential of TC cream was evaluated through serial histopathologic examination of skin biopsies. No statistically significant histopathologic signs of atrophy of the epidermis or dermis were noted at any time point throughout the study. There was a marked reduction in epidermal melanin in treated subjects; however, we did not observe any significant difference in baseline and treated samples in the amount of perivascular inflammatory infiltrate, dermal mucin, keratinocyte and melanocyte atypia, or mast cells, consistent with findings of previous studies where topical retinoids were used. An increase in the mean number of blood vessels per square millimeter of tissue was observed in 2 study cohorts between baseline and week 24. These results suggest that the risk of skin atrophy with 24-week use of TC cream for the treatment of melasma is very low.

Topics: Administration, Cutaneous; Adult; Atrophy; Dermatologic Agents; Drug Combinations; Female; Fluocinolone Acetonide; Humans; Hydroquinones; Male; Melanosis; Middle Aged; Skin; Tretinoin

Cutaneous atrophy arising from prolonged use of potent topical corticosteroids has long been a concern. Thus, it would be advantageous to find an agent which protects against atrophy produced by corticosteroids but at the same time does not impair their anti-inflammatory effects. Recent work shows that topical all-trans retinoic acid (tretinoin) prevents skin atrophy in mice treated with topical corticosteroids, but such studies have not been performed in humans. We performed an 8-week clinical, histological and biochemical study to test the ability of tretinoin to enhance efficacy and inhibit atrophogenicity of topical corticosteroids, when used in the treatment of psoriasis. In each of 20 psoriasis patients, one plaque, and its perilesional skin, was treated once daily with betamethasone dipropionate and tretinoin 0.1%, and one plaque, and its perilesional skin, treated with once daily betamethasone dipropionate and tretinoin vehicle. There was no difference in the speed or degree of improvement in plaques treated with either the topical corticosteroid/tretinoin combination or with corticosteroid alone. Light microscopy revealed a 19% reduction in epidermal thickness, in corticosteroid-treated perilesional skin, as compared with a slight (1%) increase in corticosteroid/tretinoin-treated perilesional areas (P = 0.067). Western blot analysis showed a 55% reduction in procollagen I aminopropeptide in perilesional skin treated corticosteroid alone, as compared with a 45% reduction in corticosteroid/tretinoin-treated perilesional skin. These data indicate that the addition of tretinoin does not impair the efficacy of a topical corticosteroid, in the treatment of psoriasis, and partially ameliorates epidermal atrophy produced by the topical corticosteroid.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Atrophy; Betamethasone; Blotting, Western; Double-Blind Method; Drug Therapy, Combination; Epidermis; Female; Glucocorticoids; Humans; Male; Middle Aged; Psoriasis; Tretinoin

Common treatment of atrophic acne scars consists of invasive methods such as dermabrasion, chemopeeling, or implantation of bovine collagen. In our study a new noninvasive treatment method consisting of local iontophoresis is demonstrated. Local iontophoresis was performed with either estriol--a mainly topically active estrogen--or with tretinoin.. Eighteen women were treated with estriol iontophoresis twice weekly for a period of 3 months. In addition to photographic and clinical documentation of the skin, venous blood for determination of serum levels of prolactin and estradiol according to standard radioimmunoassay methods was obtained monthly. Tretinoin iontophoresis was performed according to the same time schedule in 28 patients (19 women and 9 men) with atrophic acne scars.. Improvement of acne scars was observed in 93% of patients treated with tretinoin iontophoresis and in 100% of the group treated with estriol iontophoresis. No hormonal changes were noted in the estrogen group. Side effects involving the skin appeared in the tretinoin group in 4 cases and consisted of increased dryness and of retinoid dermatitis.. Both treatments were shown to be clinically effective in decreasing acne scars and persistence of effects. This promising new therapeutic approach may thus replace invasive treatment methods in many patients.

Topics: Acne Vulgaris; Administration, Cutaneous; Adult; Atrophy; Cicatrix; Drug Eruptions; Estradiol; Estriol; Facial Dermatoses; Female; Follow-Up Studies; Humans; Iontophoresis; Male; Prolactin; Skin; Skin Diseases; Tretinoin

Scars are problematic for thousands of patients. Scarring is a natural part of the healing process after an injury. However, the appearance of a scar and its treatment depend on multiple factors and on the experience of the therapist and the options available. Despite a plethora of rapidly evolving treatment options and technical advances, the management of atrophic and hypertrophic scars remains difficult. Innovative technologies provide an attractive alternative to conventional methods in the treatment of scars. The purpose of this trial was to determine the clinical and histological results of a method of treatment that combines radiofrequency, ultrasound, and transepidermal drug delivery. This was a prospective study conducted on 14 patients with scars of different sizes, types, and characteristics. All patients underwent six treatment sessions with the Legato device. Atrophic scars were treated with retinoic acid and hypertrophic scars with triamcinolone. Photographs and biopsies were taken before treatment and at 6 months after the last treatment session. The scars improved significantly (P < 0.0001). The mean attenuation in the severity of scars was 67% (range: 50-75%), where 100% indicates complete disappearance of the scar. Clinical and histological images of scar tissue in six patients in whom attenuation in the range of 55-75% was achieved are shown. Biopsies show regenerative changes in the scar tissue, in both the epidermis and dermis. The method makes it possible to treat extensive, heterogeneous scars on different sites with good results that are similar and predictable.

Topics: Adult; Aged; Atrophy; Biopsy, Needle; Cicatrix; Cicatrix, Hypertrophic; Cohort Studies; Combined Modality Therapy; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Immunohistochemistry; Laser Therapy; Male; Middle Aged; Prospective Studies; Risk Assessment; Treatment Outcome; Tretinoin; Triamcinolone; Ultrasonic Therapy; Young Adult

Retinoic acid is a widely used drug in the treatment of cystic acne. It has teratogenic effects that depend on the gestational period in which it is used. We report a seven months old female whose mother was exposed to retinoic acid in both pre-gestational and gestational periods. She had a retardation of psychomotor development and a brain MRI showed frontal atrophy and a malformation of the posterior fossa. We discuss the mechanisms of the teratogenic effects of retinoic acid.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Acne Vulgaris; Atrophy; Cranial Fossa, Posterior; Craniofacial Abnormalities; Female; Frontal Lobe; Humans; Infant; Isotretinoin; Keratolytic Agents; Maternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Psychomotor Disorders; Teratogens; Tretinoin

Neonatal stroke presents with seizures and results in neurologic morbidity, including epilepsy, hemiparesis, and cognitive deficits. Stem cell-based therapy offers a possible therapeutic strategy for neonatal stroke. We developed an immature mouse model of stroke with acute seizures and ischemic brain injury. Postnatal day 12 CD1 mice received right-sided carotid ligation. Two or 7 days after ligation, mice received an intrastriatal injection of B5 embryonic stem cell-derived neural stem cells. Four weeks after ligation, hemispheric brain atrophy was measured. Pups receiving stem cells 2 days after ligation had less severe hemispheric brain atrophy compared with either noninjected or vehicle-injected ligated controls. Transplanted cells survived, but 3 out of 10 pups injected with stem cells developed local tumors. No difference in hemispheric brain atrophy was seen in mice injected with stem cells 7 days after ligation. Neural stem cells have the potential to ameliorate ischemic injury in the immature brain, although tumor development is a serious concern.

Topics: Animals; Atrophy; Brain Ischemia; Brain Neoplasms; Carotid Arteries; Cell Survival; Ligation; Mice; Neurons; Seizures; Stem Cell Transplantation; Stem Cells; Stereotaxic Techniques; Stroke; Teratoma; Tretinoin

Previously we demonstrated the stimulation of collagen synthesis in triiodothyroacetic acid (TRIAC)-topically treated human and mice. In the present study, we have evaluated the dose response effect of thyroid hormone (TH) analogues and tretinoin on glucocorticoid-induced skin atrophy in a haired mouse model. For this investigation, we treated haired mice twice daily for 7 days with various topically administered doses of TRIAC, triiodothyronine-sodium salt (T(3)-Na), diiodothyroacetic acid (DIAC), 3,5-diiodothyropropionic acid (DITPA), and tretinoin with 0.2 mM betamethasone17-valerate (BM), or with the vehicle as a control group. We also investigated a combination of commercial betamethasone dipropionate (BD) 0.05% cream and various doses of TRIAC on mouse skin. TRIAC was able to reverse the skin atrophy by 25% in a daily dose of 1 nmol/cm(2) in the presence of 0.2 mM BM (p < 0.05). Neither other TH analogues nor TRIAC in lower and higher concentrations had a significant inhibitory effect on dermal atrophy (p > 0.05). A combination of 0.2 mM BM and 10 nmol/cm(2) TRIAC was able to prevent dermal atrophy by 18%. The addition of TRIAC to 0.05% BD cream in a final concentration of 0.1% was able partially to reverse the dermal atrophy by 15% (p < 0.05). TRIAC alone in a concentration of 1,000 nmol/cm(2) stimulated dermal proliferation by 34% (p < 0.05). Other TH analogues alone had no stimulatory effect on dermal proliferation. Tretinoin 0.8 mM was able to inhibit dermal atrophy by 20% (p < 0.05) and had an effect on dermal thickness of 85% (p < 0.05). However, severe side effects with edema, erythema, and scaling were commonly observed in all tretinoin-treated mouse skin, which could partly explain the increase in dermal thickness. In contrast, no skin side effects were observed after treatment with TRIAC. This study indicates that TRIAC may have a therapeutic effect on BM-induced dermal atrophy in mouse skin and a direct stimulatory effect on dermal proliferation when given alone.

Topics: Acetates; Animals; Atrophy; Betamethasone Valerate; Diiodothyronines; Female; Glucocorticoids; Male; Mice; Mice, Inbred BALB C; Propionates; Skin; Tretinoin; Triiodothyronine

Alcohol dehydrogenase (ADH) participates in the formation of retinoic acid from retinol in various organs including the gastric mucosa. However, its clinical significance still remains to be clarified. In this study, we identified the ADH isoforms responsible for the retinoic acid formation among various ADH isoforms and examined associations among the ADH activities, the retinoic acid formation level, and morphological changes in the human gastric mucosa. Human gastric samples were endoscopically obtained from 67 male subjects. Morphological changes were assessed by the Sydney system and activities of class I, III, and IV ADH isoforms were determined in each specimen. In 26 cases, levels of all-trans retinoic acid (ATRA) formation from all-trans retinol were examined. Among activities of the three ADH isoforms, class IV ADH activity was solely associated with the ATRA formation level. This association was found even when subjects' age and Helicobacter pylori infection status were adjusted. As the degrees of inflammation, atrophy, and intestinal metaplasia increased, the class IV ADH activity as well as the potential for the ATRA formation decreased. Class IV ADH is a major enzyme in the retinoic acid supply in the human gastric mucosa, and the reduction of its activity was associated with decreasing retinoic acid supply and progression of inflammation, atrophy, and intestinal metaplasia in the gastric mucosa. In that retinoic acid is a key molecule for maintaining normal morphology, the reduction of class IV ADH activity may be involved in the pathogenesis of these morphological changes in the human gastric mucosa.

Topics: Alcohol Dehydrogenase; Atrophy; Gastric Mucosa; Humans; Inflammation; Male; Protein Isoforms; Tretinoin; Vitamin A

Atrophic acne scars are a frequent problem after acne. Hitherto, mainly invasive treatment measures were possible. In a recent paper, we demonstrated the positive effects of iontophoresis with 0.025% tretinoin gel vs. estriol 0.03%.. In this further study, the recording of the clinical effects of iontophoresis with 0.025% tretinoin gel in atrophic acne scars was supplemented by immunohistochemistry investigations of collagen I and III, proliferation markers, and the estimation of epidermal thickness.. The treatment was performed twice weekly in 32 volunteer patients for a period of 3 months by application of the substance under a constant direct current of 3 mA for 20 min. Skin biopsies prior to and at the end of treatment were performed in 32 voluntary patients in order to investigate collagen I/III and proliferation markers by immunohistochemistry methods.. Clinically, at the end of treatment, in 94% of patients a significant decrease in the scar depth was observed. Neither epidermal thickness nor proliferation markers revealed a significant increase at the end of treatment. Furthermore, collagen I and collagen III showed no common trend, as expressed statistically by a lack of significance. In some cases, increases in collagen III became evident at the end of treatment.. Tretinoin-iontophoresis is an effective, noninvasive treatment of atrophic acne scars without causing disturbing side-effects.

Topics: Acne Vulgaris; Administration, Cutaneous; Adolescent; Adult; Atrophy; Cicatrix; Collagen; Female; Humans; Immunohistochemistry; Iontophoresis; Keratolytic Agents; Ki-67 Antigen; Male; Middle Aged; Skin; Treatment Outcome; Tretinoin

Topical treatment of striae rubra with 0.1% tretinoin and laser treatment of striae rubra and alba with the 585-nm pulsed dye laser are proven therapeutic options. However, little efficacy has been shown for treatment of striae alba topically, and the laser is currently not a suitable treatment option for darker ethnic skin types.. The purpose of this study was to demonstrate that selected commercial topical agents can improve the appearance of striae alba.. Ten patients of varying skin types (I-V) having straie distensae alba on the abdomen or thighs were selected to evaluate the effectiveness of two topical treatment regimens. Patients were placed on daily topical application of 20% glycolic acid (MD Forte) to the entire treatment area. In addition, the patients applied 10% L-ascorbic acid, 2% zinc sulfate, and 0.5% tyrosine to half to the treatment area and 0.05% tretinoin emollient cream (Renova) to the other half of the treatment area. The creams were applied on a daily basis for 12 weeks. Improvement was evaluated at 4 and 12 weeks in an objective unblinded fashion at the follow-up visits, a objective blinded fashion by visual grading at the conclusion of the study, and in an objective blinded fashion with profilometry. Additionally, histopathologic analysis was performed.. Analysis of these data reveals: 1) both regimens can improve the appearance of stretch marks; 2) these topical therapy regimens are safe and effective in study patients with minimal irritation; 3) elastin content within the reticular and papillary dermis can increase with topical 20% glycolic acid combined with 0.05% tretinoin emollient cream therapy; 4) both regimens increased epidermal thickness and decreased papillary dermal thickness in treated stretch marks when compared with untreated stretch marks; 5) combined epidermal and papillary dermal thickness in stretch marks treated with either topical regimen approaches that of normal skin; and 6) profilometry can objectively measure differences in skin texture associated with striae treatments when compared to controls, however, it is not sensitive enough to justify comparison or quantitative improvements between similarly effective treatments.

Topics: Abdomen; Administration, Cutaneous; Adult; Ascorbic Acid; Astringents; Atrophy; Connective Tissue Diseases; Dermatologic Agents; Drug Combinations; Elastic Tissue; Elastin; Emollients; Female; Follow-Up Studies; Glycolates; Humans; Keratolytic Agents; Middle Aged; Safety; Single-Blind Method; Skin; Thigh; Tretinoin; Tyrosine; Zinc Sulfate

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

Recently, there has been an exponential increase in the use of alpha-hydroxy acids in dermatologic practice. Their inclusion in a myriad of cosmetic preparations underscores their popularity. Among the clinical effects of alpha-hydroxy acids are their ability to prevent the atropy resulting from potent topical corticosteroids, improve the appearance of photoaged skin, and correct disorders of keratinization. Despite this range of desirable effects, very little is known about the specific changes produced by various alpha-hydroxy acid preparations in the epidermis and dermal extracellular matrix. Previous work by others has demonstrated the ability of another alpha-hydroxy acid to increase viable epidermal thickness, and dermal glycosaminoglycans.. In this study, we examined the effect of 20% citric acid lotion, as compared with vehicle alone, on skin thickness, viable epidermal thickness, and dermal glycosaminoglycan content. Biopsy samples were harvested after 3 months of treatment.. Image analysis of biopsy sections revealed increases in viable epidermal thickness and dermal glycosaminoglycans in treated skin.. Topical citric acid produces changes similar to those observed in response to glycolic acid, ammonium lactate, and retinoic acid including increases in epidermal and dermal glycosaminoglycans and viable epidermal thickness. Further studies of citric acid and other alpha-hydroxy acids are warranted to clarify their clinical effects and mechanisms of action.

Topics: Administration, Cutaneous; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Atrophy; Biopsy; Chondroitin Sulfates; Citric Acid; Dermatologic Agents; Epidermis; Extracellular Matrix; Female; Follow-Up Studies; Glucocorticoids; Glycolates; Glycosaminoglycans; Humans; Hyaluronic Acid; Hydroxy Acids; Image Processing, Computer-Assisted; Keratins; Keratolytic Agents; Lactates; Pharmaceutical Vehicles; Quaternary Ammonium Compounds; Skin; Skin Aging; Tissue Survival; Tretinoin

Strie distansae have been studies since the last century. However, many aspects like oxitalanic fiber variations in the striae, were still to be studied. This was the purpose of our work. Our results showed that in the striae, there is a decrease in the number of oxitalanic fibers when compared to normal skin. We also found a reduction in the arborecent aspect of these fibers as well as tissular fragility. The pathogenesis of striae distansae is still obscure, but the study of oxitalanic fibers can contribute to the understanding of its treatment as well as the compression of cutaneous aging.

Topics: Adult; Aged; Atrophy; Biopsy; Contractile Proteins; Elastic Tissue; Extracellular Matrix Proteins; Female; Humans; Middle Aged; RNA Splicing Factors; Skin; Skin Diseases; Tretinoin

In an earlier study we showed that tretinoin could prevent corticosteroid-induced skin atrophy in hairless mice. In this study, we examined the histochemical, biochemical, and immunochemical changes that accompanied the atrophy and its prevention. Mice were treated dorsally for 3 weeks in the morning and afternoon (AM:PM) as follows: 1) vehicle:vehicle, 2) steroid:vehicle, 3) steroid:tretinoin. Tretinoin concentration was 0.05% in an ethanol:propylene glycol vehicle. The steroid was clobetasol propionate (0.05%). The normally sparse dermal glycosaminoglycans were further reduced by steroid:vehicle treatment and increased to greater than vehicle:vehicle amounts by steroid:retinoid. Mast cells were similarly affected. Biochemical quantification of glycosaminoglycans confirmed the histochemical findings. Collagen, non-collagenous protein, and total protein content were reduced by the steroid. The latter two were returned to more normal levels by tretinoin whereas with collagen there was only a trend toward normal levels. Fibronectin, which was increased by the steroid:vehicle treatment, was reduced to more normal levels by steroid:tretinoin. We conclude that tretinoin has the ability to prevent the major steroid-induced biomechanical changes in hairless mouse dermal connective tissue that contribute to atrophy.

Topics: Adrenal Cortex Hormones; Animals; Atrophy; Clobetasol; Collagen; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Fibronectins; Glycosaminoglycans; Histocytochemistry; Image Processing, Computer-Assisted; Immunohistochemistry; Iron; Mast Cells; Mice; Mice, Hairless; Retinoids; Skin; Tolonium Chloride; Tretinoin

Topics: Administration, Cutaneous; Animals; Atrophy; Croton Oil; Drug Eruptions; Ear, External; Edema; Female; Fibronectins; Glucocorticoids; Glycosaminoglycans; Inflammation; Mice; Mice, Hairless; Skin; Tetradecanoylphorbol Acetate; Tretinoin

Etretinate 0.5 mg/kg body weight combined with 0.1% triamcinolone acetonide and 5% salicylic acid in an O/W cream gave more than 70% improvement in 62% of 75 patients. Of this satisfactorily improved group, at least 41% were still in the same condition after 3 years on a maintenance dose of, on average, 0.3 mg/kg body weight etretinate daily and 20 g weekly of a relatively strong corticosteroid cream. The side effects were acceptable and the convenience for the patients is great as compared with other treatment.

Topics: Administration, Oral; Administration, Topical; Alopecia; Atrophy; Etretinate; Follow-Up Studies; Humans; Psoriasis; Skin; Tretinoin

This paper describes toxic lesions induced in the hamster testes by 3 different retinoids. Groups of 13 Syrian Golden hamsters were fed diets containing 120 mg/kg 13-cis-retinoic acid (CRA), 327 mg/kg ethyl retinamide (ER), or 343 mg/kg 2-hydroxyethyl retinamide (HER) for 6 months. The germinal epithelium of the testicular tubules was completely atrophic in the groups fed ER and HER. Mean testicular weights were 0.8 g and 0.7 g respectively as compared to 3.3 g in the control group. No alterations in testicular weights or morphological characteristics, at the light microscopic level, were found in the group fed CRA. At the ultrastructural level, however, asymmetrical head caps and deformed acrosomes were observed in the spermatids.

Topics: Animals; Atrophy; Cricetinae; Isotretinoin; Male; Mesocricetus; Organ Size; Testis; Tretinoin