tretinoin and Skin-Diseases

Chemical peeling, or chemexfoliation, has been used for centuries to improve signs of ultraviolet light-induced sun damage. Over the last 30 years, the science behind chemical peeling has evolved, increasing our understanding of the role of peeling ingredients and treatment indications. The depth of peels is directly related to improved results and to the number of complications that can occur. Key principles for superficial and medium depth peeling are discussed, as well as appropriate indications for these treatments.

Topics: Caustics; Chemexfoliation; Drug Combinations; Ethanol; Glycolates; Humans; Keratolytic Agents; Lactic Acid; Phenol; Resorcinols; Salicylates; Salicylic Acid; Skin Diseases; Tretinoin; Trichloroacetic Acid

Topics: Administration, Cutaneous; Dermatologic Agents; Humans; Isotretinoin; Keratosis; Laser Therapy; Nicotinic Acids; Randomized Controlled Trials as Topic; Skin Aging; Skin Diseases; Sunlight; Tretinoin

Topics: Animals; DNA; Metabolic Diseases; Neoplasms; Receptors, Cytoplasmic and Nuclear; Receptors, Retinoic Acid; Retinoid X Receptors; Signal Transduction; Skin Diseases; Tretinoin

Topical tretinoin has been approved for use in dermatology for 40 years and is currently approved for the treatment of acne vulgaris and photodamage. During this time, topical tretinoin has accumulated significant efficacy and safety data in the treatment of acne and photodamaged skin and demonstrated clinical potential for treating a range of other dermatologic conditions. The diverse effects may be due to complex underlying mechanisms of action associated with tretinoin, including keratolytic activity, collagenesis, and other mechanisms associated with the activation of nuclear retinoic acid receptors (RARα, RARβ, and RARγ). In this article, we review the history of topical tretinoin use to date and outline emerging research suggesting that topical tretinoin may have potential clinical use for treating a multitude of other dermatological conditions when used either as monotherapy or in combination with other agents. We also describe newer formulations of topical tretinoin that have been designed to reduce irritation potential. In light of the substantial history of safety and efficacy of topical tretinoin in acne and photodamage, we speculate that it holds promise in treating many additional dermatological conditions, which may be explored in future research.

Topics: Acne Vulgaris; Administration, Cutaneous; Humans; Keratolytic Agents; Skin Aging; Skin Diseases; Tretinoin; Ultraviolet Rays

A Cochrane systematic review of 30 randomised clinical trials assessed the effects of current treatments for adults with mild-to-severe changes in facial and forearm skin that occurred as a result of prolonged exposure to the sun ('photodamage'). Topical tretinoin > or = 0.02% improved the appearance of mild-to-severe photodamage. Tazarotene 0.01-0.1% and isotretinoin 0.1% provided benefit to patients with moderate photodamage. The treatment duration was 4-11 months. Adverse effects were pain and redness. Both the efficacy and adverse effects were dose-dependent. Other treatments, such as polysaccharides, hydroxy acids, surgical procedures and laser, cannot be recommended.

Topics: Administration, Cutaneous; Dermatologic Agents; Dose-Response Relationship, Drug; Humans; Nicotinic Acids; Randomized Controlled Trials as Topic; Skin Aging; Skin Diseases; Sunlight; Tretinoin

The naturally occurring retinoids and their synthetic analogs play a key role in differentiation, proliferation, and apoptosis, and their use/potential in oncology, dermatology and a variety of diseases are well documented. This review focuses on the role of all-trans-retinoic acid (ATRA), the principal endogenous metabolite of vitamin A (retinol) and its metabolism in oncology and dermatology. ATRA has been used successfully in differentiated therapy of acute promyelocytic leukemia, skin cancer, Kaposi's sarcoma, and cutaneous T-cell lymphoma, and also in the treatment of acne and psoriasis. However, its usefulness is limited by the rapid emergence of acquired ATRA resistance involving multifactoral mechanisms. A key mechanism of resistance involves ATRA-induced catabolism of ATRA. Thus, a novel strategy to overcome the limitation associated with exogenous ATRA therapy has been to modulate and/or increase the levels of endogenous ATRA by inhibiting the cytochrome P450-dependent ATRA-4-hydroxylase enzymes (particularly CYP26s) responsible for ATRA metabolism. These inhibitors are also referred to as retinoic acid metabolism blocking agents (RAMBAs). This review highlights development in the design, synthesis, and evaluation of RAMBAs. Major emphasis is given to liarozole, the most studied and only RAMBA in clinical use and also the new RAMBAs in development and with clinical potential.

Topics: Animals; Antineoplastic Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dermatologic Agents; Enzyme Inhibitors; Humans; Neoplasms; Retinoic Acid 4-Hydroxylase; Skin Diseases; Tretinoin

Retinoid is a collective term for compounds which bind to and activate retinoic acid receptors (RARalpha, beta, gamma and RXRalpha, beta, gamma), members of nuclear hormone receptor superfamily. The most important endogeneous retinoid is all-trans-retinoic acid (ATRA) which is an RARalpha, beta and gamma ligand. ATRA and its mimics have been in clinical use for treatment of acute promyelocytic leukemia (APL) and some skin diseases. Many synthetic retinoids have been developed and attempts to improve their medicinal properties have been made. Among them, tamibarotene (Am80) is an RARalpha- and RARbeta-specific (but RARgamma- and RXRs-nonbinding) synthetic retinoid that is effective in the treatment of psoriasis patients and relapsed APL. Experimentally, this compound is also active in animal models of rheumatoid arthritis and experimental autoimmune encephalomyelitis. On this background, possible application of retinoids for the treatment of autoimmune diseases was discussed. In particular, Th1 dominant autoimmune diseases may be the targets of the retinoids.

Topics: Animals; Arthritis, Rheumatoid; Autoimmune Diseases; Benzoates; Humans; Leukemia, Promyelocytic, Acute; Receptors, Retinoic Acid; Retinoids; Skin Diseases; T-Lymphocytes; Tetrahydronaphthalenes; Tretinoin

The most widely used retinoids include topical tretinoin (Retin-A), adapalene (Differin), topical tazarotene (Tazorac), isotretinoin (Accutane), and acitretin (Soriatane). This article will review new uses and developments in tazarotene (its failure to secure FDA approval in oral form for psoriasis), adapalene (its new 0.3% gel form and use in rosacea), alitretinoin (its use in photoaging), bexarotene (its use for psoriasis and chronic hand dermatitis), isotretinoin (the IPledge program, its use for neuroblastoma and branded formulation pharmacological superiority to generics), and retinoic acid metabolism-blocking agents (RAMBAs) (liarazole use for ichthyosis and psoriasis).

Topics: Adapalene; Humans; Isotretinoin; Keratolytic Agents; Naphthalenes; Nicotinic Acids; Retinoids; Skin Diseases; Tretinoin

Retinoid is a term for compounds that bind to and activate retinoic acid receptors (RARalpha, RARbeta, and RARgamma), members of the nuclear hormone receptor superfamily. The most important endogenous retinoid is all-trans-retinoic acid. Retinoids regulate a wide variety of essential biological processes, such as vertebrate embryonic morphogenesis and organogenesis, cell growth arrest, differentiation and apoptosis, and homeostasis, as well as their disorders. This review summarizes the considerable amount of knowledge generated on these receptors.

Topics: Animals; Binding, Competitive; Gene Expression; Humans; Mutation; Neoplasms; Receptors, Retinoic Acid; Retinoids; Skin Diseases; Tretinoin

Photodamage describes skin changes such as fine and coarse wrinkles, roughness, freckles and pigmentation changes that occur as a result of prolonged exposure to the sun. Many treatments are available to reverse the damage, but it is unclear which work and at what cost in terms of unwanted side effects.. To assess the effects of topically applied treatments, tablet treatments, laser and surgical procedures for photodamaged skin.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Issue 1 2002, MEDLINE (1966-June 2002), EMBASE (1974-June 2002), Health Periodicals (1976-June 2002). We checked references of articles and communicated with authors and the pharmaceutical industry.. Randomised controlled trials which compared drug or surgical interventions with no treatment, placebo or another drug, in adults with mild, moderate or severe photodamage of the face or forearms.. Two reviewers independently extracted data and assessed trial quality.. Thirty studies of variable quality were included. Eight trials showed that topical tretinoin cream, in concentrations of 0.02% or higher, was superior to placebo for participants with mild to severe photodamage on the face and forearms (although losses to follow-up were relatively high in most studies). For example, the relative risk of improvement for 0.05% tretinoin cream, compared to placebo (three studies), at 24 weeks, was 1.73 (95% confidence interval 1.39 to 2.14). This effect was not seen for 0.001% topical tretinoin (one study) or 0.01% (three studies). A dose-response relationship was evident for both effectiveness and skin irritation. One small within-patient study showed benefit from topical ascorbic acid compared with placebo. Tazarotene (0.01% to 0.1%) and isotretinoin (0.1%) both showed significant improvement over placebo for moderate photodamage (one study each). There is limited evidence (one trial), to show that the effectiveness of 0.05% tretinoin, is equivalent to the effects of 0.05% and 0.1% tazarotene. One small study showed greater improvement in upper lip wrinkles with CO2 laser technique compared to Baker's phenol chemical peel, at 6 months. Three small RCTs comparing CO2 laser with dermabrasion found no difference in wrinkle score at 4 to 6 months, suggesting that both methods are equally efficacious, but more erythema was reported with the laser. The effectiveness of other interventions such as hydroxy acids and natural polysaccharides was not clear.. There is conclusive evidence that topical tretinoin improves the appearance of mild to moderate photodamage on the face and forearms, in the short term. However erythema, scaling/dryness, burning/stinging and irritation may be experienced initially. There is limited evidence that tazarotene and isotretinoin benefit patients with moderate photodamage on the face: both are associated with skin irritation and erythema. The effectiveness of other interventions remains uncertain.

Topics: Administration, Cutaneous; Dermatologic Agents; Humans; Isotretinoin; Keratosis; Laser Therapy; Nicotinic Acids; Randomized Controlled Trials as Topic; Skin Aging; Skin Diseases; Sunlight; Tretinoin

Routine everyday care of skin is an essential part of optimal patient management. Common problems such as xerosis, dermatitis, eczema, psoriasis, acne, rosacea, and photodamage leave the skin vulnerable to external insults, partly as a result of varying levels of barrier dysfunction. Cosmetic surgery procedures also typically damage the stratum corneum (SC) and leave skin with a very weak barrier during recovery phase. Cleansing is an important aspect of any skin care, since it not only removes unwanted dirt, soil, and bacteria from skin, but also removes dead surface cells, preparing skin to better absorb topically applied drugs/medication. Care must be taken to minimize any further weakening of the SC barrier during cleansing. Cleansers based on mild synthetic surfactants and/or emollients that cause minimal barrier perturbation are ideal for these patients. The present paper is a brief review of four clinical trials that evaluated the efficacy and compatibility of either mild syndet bars or cleansers in patients with atopic dermatitis, acne, rosacea, or patients who had received chemical peels or Retin-A(R) (tretinoin) treatment for sustained photodamage.

Topics: Acne Vulgaris; Clinical Trials as Topic; Dermatitis, Atopic; Detergents; Humans; Hydroxy Acids; Rosacea; Severity of Illness Index; Skin Care; Skin Diseases; Surface-Active Agents; Tretinoin

Retinoids have been in sharp focus ever since their introduction 30 years ago. They include any drug (s) that bind to retinoid receptors and elicit a biological response. Enormous information on the subject seems to embroil the recent literature. Practically it is impossible to clearly comprehend the undercurrents. The meticulously dispensing text envisages surmounting the perspective reader's predicaments. Accordingly, retinoids and their related facets namely retinoid receptors, classification, mode of action, and the pharmacological diversity have been precisely defined. Commonly used systemic retinoids too have been given a substantial fresh look along with their monitoring. Overall, adverse effects and relative and absolute contraindications have been scrupulously incorporated. Human immuno deficiency virus (HIV) and isoretinoid for acne, in particular, have been highlighted. Micronized isotretinoin formulations have also been taken care so also commonly used topical retinoids. Tretinoin and their newer formulation have also been accounted for along with tretinoin polymer cream. Adapalene, a new chemical entity possessing a unique physico-chemical activity similar to that of tretinoin has also been dealt with. Newer retinoids are likely to be a subject of intrigue. A focus on future potentials of retinoids is its special ingredient. The inclusion of details of rexinoid the most recent introduction in their purview is likely to invoke interest to further consolidate its reckoning in future. All in all the text of the paper should provide an insight into the current rumbling around retinoids.

Topics: Acne Vulgaris; Adapalene; Administration, Cutaneous; Administration, Oral; Chemistry, Pharmaceutical; Humans; Isotretinoin; Naphthalenes; Psoriasis; Receptors, Retinoic Acid; Retinoids; Skin Diseases; Tretinoin

Multiple miliary osteoma cutis of the face represents primary extra-skeletal bone formation that arises within the skin of the face.. A 60-year-old woman with multiple miliary osteoma cutis of the face was treated by application of 0.05% tretinoin (all-trans-retinoic acid) cream nightly.. After 3 months of therapy there were fewer papules and a decrease in size of remaining lesions. In a literature search, it was found that local application of tretinoin was successful and achieved a decrease in the number of papules over the face in all patients with multiple miliary osteoma cutis of the face; however, the length of time to achieve response varied from a few weeks to 6 months.. It is suggested that local application of tretinoin cream should be considered in the therapy of multiple miliary osteoma cutis of the face, particularly when the lesions are small and superficial.

Topics: Administration, Topical; Facial Dermatoses; Female; Humans; Keratolytic Agents; Middle Aged; Ossification, Heterotopic; Skin Diseases; Tretinoin

Premature skin aging, or photoaging, results largely from repeated exposure to ultraviolet (UV) radiation from the sun. Photoaging is characterized clinically by wrinkles, mottled pigmentation, rough skin, and loss of skin tone; the major histologic alterations lie in dermal connective tissue. In recent years, a great deal of research has been done to explain the mechanism by which UV induces dermal damage. This research has enabled the identification of rational targets for photoaging prevention strategies. Moreover, studies that have elucidated photoaging pathophysiology have produced significant evidence that topical tretinoin (all-trans retinoic acid), the only agent approved so far for the treatment of photoaging, also works to prevent it. This article summarizes evidence mainly from studies of human volunteers that provide the basis for the current model of photoaging and the effects of tretinoin.

Topics: Collagen; Humans; Keratolytic Agents; Skin Aging; Skin Diseases; Tretinoin; Ultraviolet Rays

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

Repeated exposure to UV radiation from the sun causes premature skin aging. This photoaging is characterized by wrinkles, mottled pigmentations, dry and rough skin, and loss of skin tone. Since the clinical demonstration that the use of topical tretinoin can improve photoaged skin, a great deal of knowledge that may explain wrinkle effacement has been acquired. Central to this pursuit has been dermal collagen. In this article, we summarize evidence (mainly from humans) that implicates a deficiency of superficial dermal collagen as the cause of the dermal aspects of photoaging. In addition, a mechanism through which UV radiation can lead to reduced collagen is presented. Through our understanding of the pathophysiological mechanism of photoaging, our ability to treat and possibly prevent this skin condition is enhanced.

Topics: Administration, Cutaneous; Collagen; Humans; Keratolytic Agents; Skin; Skin Aging; Skin Diseases; Skin Pigmentation; Sunlight; Tretinoin; Ultraviolet Rays

Cytochromes P-450 (CYPs) are the most versatile and important class of drug-metabolizing enzymes which are induced in mammalian skin in response to xenobiotic exposure. CYPs are the target of special interest in the development of pharmaceuticals for skin diseases because most, if not all, drugs available in the armamentarium of the dermatologist are substrates, inducers or inhibitors of this enzyme family. The functional significance of drug metabolism in the skin and the implication of CYP in skin pathology and therapy is an area for future investigation. A detailed insight into the mechanism of action of various cutaneous CYPs, being capable of modulating the drug bioavailability, will be helpful in the development of better strategies for novel therapy against constantly increasing skin disorders. This brief review puts some of these perspectives together and suggests additional research in the area of CYPs with regard to their expression and modulation in mammalian skin as well as their implication in dermatological disorders and the therapy of skin diseases.

Topics: Aryl Hydrocarbon Hydroxylases; Humans; Pharmaceutical Preparations; Skin Diseases; Tretinoin

The molecular structure of the biological active form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 (VD), and the vitamin A derivatives all-trans and 9-cis retinoic acid (RA) are not related. The nuclear receptors for VD (VDR) and retinoids (RAR and RXR), however, are members of the same superfamily of ligand-activated transcription factors. We observed stable VDR-RXR and VDR-RAR heterodimers in solution and their transcriptional activity on different types of response elements. Both heterodimeric complexes are activated by VD, but, depending on the relative expression of the nuclear receptors, retinoids can have either co-stimulating or repressing effects. This demonstrates that VD and retinoid signaling are linked at the level of gene regulation and may explain the similar effects of both hormones on cell proliferation and differentiation. This concept may be applied for treating skin diseases, with the hope that a synergism will be observed, allowing better responses with lower doses of each compound. Preliminary observations suggest that psoriasis, cutaneous T-cell lymphomas, and actinic keratoses might be potential targets for VD-retinoid associations.

Topics: Calcitriol; Drug Therapy, Combination; Gene Expression; Humans; Receptors, Calcitriol; Receptors, Retinoic Acid; Skin Diseases; Tretinoin

Tretinoin (all-trans-retinoic acid) is a retinol (vitamin A) derivative which has been evaluated as a topical treatment for the symptoms of photodamaged skin. In several well-controlled clinical trials, the proportion of patients showing improvement was significantly higher with 0.01 or 0.05% tretinoin cream than with placebo for criteria such as global assessment, fine and coarse wrinkling, pigmentation and roughness. Improvements in the overall severity of photodamage were also significantly greater with tretinoin than with placebo. The extent of clinical improvement with tretinoin has generally been moderate, but cytological and histological studies have shown that extensive changes in the epidermis and dermis occur during treatment. However, the permanency and clinical significance of these changes has yet to be fully evaluated. Topical tretinoin has also demonstrated potential for the treatment and eradication of premalignant skin growths such as actinic keratoses, and may be useful as combination therapy with fluorouracil in this indication. Dermatitis (the retinoid skin reaction) is the most common adverse event experienced by patients receiving topical tretinoin; this condition may persist for up to 3 months, but is usually mild or moderate in nature. Thus, topical tretinoin has been shown to be an effective form of treatment for the characteristic signs of photodamaged skin. Its ability to produce significant, albeit moderate, clinical improvements in symptoms such as fine wrinkling, roughness and pigmentation, together with its relatively mild or moderate adverse event profile, suggests that it is likely to be of considerable value in this indication. The treatment and eradication of potentially malignant growths such as actinic keratoses may also prove to be an important application for topical tretinoin.

Topics: Administration, Topical; Animals; Cell Transformation, Neoplastic; Clinical Trials as Topic; Drug Therapy, Combination; Fluorouracil; Humans; Skin; Skin Diseases; Sunlight; Tretinoin

Topics: Animals; Cells, Cultured; Humans; Keratins; Mice; Molecular Structure; Point Mutation; Skin Diseases; Tretinoin

Topics: Animals; Humans; Skin Diseases; Tretinoin

The retinoids provide an important new way of treating dermatologic disorders. They have also proved to have a role in the prevention of new lesion formation. New retinoids, of which adapalene is one, have recently been synthesized in order to obtain similar or better efficacy while reducing skin irritation potential. These new molecules are currently under clinical investigation. Preliminary results are encouraging. In the near future, an expanded range of topical retinoids should be available.

Topics: Adapalene; Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Humans; Isotretinoin; Mice; Models, Biological; Naphthalenes; Psoriasis; Retinoids; Skin Aging; Skin Diseases; Tretinoin

This is a review of the efficacy of etretinate/acitretin in the treatment of psoriasis and of the currently reported side-effects. The data indicate that retinoids bring significant improvement (if not total clearing) with frequent low-morbidity but rarely serious side-effects. The most serious side-effect of etretinate/acitretin is teratogenicity.

Topics: Abnormalities, Drug-Induced; Acitretin; Adult; Aged; Bone Diseases; Chemical and Drug Induced Liver Injury; Etretinate; Eye Diseases; Female; Humans; Lipids; Male; Middle Aged; Psoriasis; Risk Factors; Skin Diseases; Tretinoin

Skin changes associated with aging often manifest as cosmetic disabilities. As the population of elderly persons continues to rise, these aging skin changes and patients' dissatisfaction with them will increasingly command the attention of the primary care physician. The cosmetic aging changes and management strategies addressed here include wrinkles, hair changes, common benign neoplasms, dyspigmentation, and telangiectasias. While none of these conditions is a direct threat to the physical well being of the patient, their psychological impact, particularly with regard to self-perception, can be significant and even profound. They therefore merit a response from physicians caring for such patients.

Topics: Aged; Alopecia; Collagen; Cryosurgery; Dermabrasion; Humans; Minoxidil; Skin Aging; Skin Diseases; Tretinoin

The topical tretinoin epoch began almost 30 years ago in the laboratories of Stüttgen where he first recognized that a vitamin A derivative, tretinoin, had the potential to be a truly significant form of dermatological therapy. His early clinical trials in a variety of skin disorders provided the first indication of topical activity for the retinoids. Kligman evaluated further the utility of topical tretinoin; focusing his attention on acne. Through these initial studies, topical tretinoin became a fundamental treatment modality for acne. Soon after topical tretinoin was made available, elderly patients using it to treat acne noted a general improvement in the quality of their skin. Kligman began open clinical trials to investigate the effects of topical tretinoin on treatment of photodamaged skin. Positive findings from these trials led to double-blind, vehicle-controlled pilot studies which supported the concept that topical tretinoin could improve the fine wrinkling, mottled hyperpigmentation and tactile roughness which are characteristic of photodamaged skin. These results were verified in two large double-blind, multicentre studies of approximately 700 patients that used not only clinical and patient evaluations but also biopsies and skin surface replicas.

Topics: Administration, Topical; History, 20th Century; Humans; Skin Aging; Skin Diseases; Tretinoin

Tretinoin has previously been used for the treatment of acne. Recent studies, however, demonstrating the efficacy of topical tretinoin in the treatment of photodamaged skin have led to its widespread use for this entirely new indication. When prescribing tretinoin for photodamaged skin rather than acne, physicians must take into consideration a new set of issues. Patients must be selected based on their commitment to a total sun-avoidance regimen. Evaluation of photodamage must be careful and thorough prior to initiating topical tretinoin therapy. Global assessment of a patient's photodamaged skin should be made before therapy and at all follow-up visits. The patient population treated for photodamage tends to be older than that using topical tretinoin for acne; therefore, the treatment regimen must account for the different clinical and physiological characteristics of older patients' skin.

Topics: Humans; Research Design; Skin Aging; Skin Diseases; Tretinoin

Oral retinoids are now well-established drugs for the systemic treatment of skin diseases. For etretinate to be effective on a long-term basis it is recommended that maintenance therapy should be continued for 3-6 months after clinical signs of the disease have disappeared. In "non-responders" with psoriasis the blood levels of etretinate may be low and increasing the dose to 1.5 mg/kg body weight per day will be necessary and helpful in some cases. The interaction of drugs should also be considered carefully in non-responding individuals. Children usually respond well to treatment, but they also often require higher dose levels. Bone toxicity with premature epiphyseal closure and hyperostoses may be seen during isotretinoin administration and, more rarely, in patients receiving etretinate, but the risk is relatively low. Teratogenicity is a major concern in young females being treated for acne with isotretinoin, since 70 embryopathies have been recorded worldwide.

Topics: Acitretin; Adult; Bone and Bones; Child; Humans; Intestinal Absorption; Long-Term Care; Retinoids; Skin Diseases; Tretinoin

The retinoids, a group of compounds consisting of vitamin A and its derivatives, have been the subject of intense investigation over the past 30 years. These molecules have shown beneficial effects in the areas of acne, psoriasis, neoplastic processes and, most recently, reversal of extrinsically aged skin. Additional retinoids are currently under development. Adverse reactions to these drugs include mucocutaneous irritation, hyperlipidemia, and profound teratogenicity. Appropriate patient selection is imperative before beginning therapy with these medications. An overview of retinoid metabolism and the currently available compounds is presented. The newest class of retinoids, the arotinoids, is also discussed.

Topics: Abnormalities, Drug-Induced; Etretinate; Female; Humans; Isotretinoin; Pregnancy; Retinoids; Skin Diseases; Tretinoin

Tretinoin cream has been used extensively to reverse the changes of photoaging. It is the first topical therapy to undergo controlled clinical testing and proved to be efficacious. These results have been substantiated with photography, histopathologic examination, and skin surface replicas. The mechanism of action of retinoic acid is unknown, but it may bind to a specific receptor that alters the gene expression of the cell. Therapy is most successful when a liberal amount of tretinoin 0.1% cream is applied to the skin daily. Tretinoin cream has an excellent safety record; a local cutaneous hypervitaminosis A reaction is the only common problem.

Topics: Administration, Topical; Aging; Humans; Skin Diseases; Tretinoin; Ultraviolet Rays

The synthetic retinoids, the vitamin-D-derivatives etretinate and isotretinoin, have substantially enlarged the therapeutic arsenal in dermatology. They are primarily used in severe cases of acne and cornification disorders. In the majority of cases, long-term treatment is necessary. Certain side effects in the skeletal system can occur, e.g., osteoporosis, premature epiphyseal closure, and changes similar to DISH (diffuse idiopathic skeletal hyperostosis). We discuss the reports in the literature and our own observations in 31 patients treated at the Westphalian Wilhelms University in Muenster, as well as at the Technical University in Munich. In 3 out of 31 patients treated by retinoids on a long-term basis, skeletal changes were found radiologically as a result of the retinoid medication.

Topics: Adolescent; Adult; Calcinosis; Child; Etretinate; Female; Humans; Hyperostosis, Diffuse Idiopathic Skeletal; Isotretinoin; Male; Middle Aged; Osteoporosis; Radiography; Skin Diseases; Spinal Osteophytosis; Time Factors; Tretinoin

In addition to well-accepted indications, etretinate has a beneficial effect in a variety of other dermatoses such as the hyperkeratotic eczema of the palms and soles, prurigo nodularis, and other nonpsoriatic, sterile, pustular eruptions. Due to its influence on dermal inflammatory processes and immunomodulation of the tissue response, etretinate is effective in cutaneous lupus erythematosus, certain bullous disorders like pemphigus herpetiformis, the persistent variant of Grover's disease, dermatitis herpetiformis, and bullous pemphigoid. Isotretinoin is reported to be effective in cutaneous sarcoidosis, disseminated granuloma annulare, systemic sclerosis and tumors of the cutaneous appendages. New synthetic retinoids have been developed. Etretin, the main metabolite of etretinate, was shown to be effective and to have a short elimination half-life of approximately equal to 50 h. Arotinoid ethyl ester and arotinoid-free carboxylic acid are effective in minimal doses 500-fold lower than etretinate. Arotinoid ethyl ester was shown not to increase serum lipids. Arotinoid ethyl sulfone is the first retinoid without bone toxicity in animal experiments. Motretinide is the ethylamide of tretinoin and is reported to be effective in the local treatment of acne. Some of the new polyaromatic retinoids appear to have sebosuppressive, antikeratinizing and/or anti--inflammatory effects via topical application.

Topics: Administration, Cutaneous; Etretinate; Humans; Isotretinoin; Retinoids; Skin Diseases; Tretinoin

The bioavailability, plasma transport and tissue distribution of various retinoids are largely determined by their physicochemical properties; some are extremely lipidsoluble whereas others are relatively hydrophilic. Isotretinoin, a 1st generation retinoid, lacks the problematic affinity for fat. Etretinate, a 2nd generation aromatic retinoid, has been shown to accumulate in both fat tissues and in the adrenals. Etretin, the main free-acid metabolite of etretinate, is less lipophilic and is presently being tested as an alternative drug. Arotinoid ethyl ester, a 3rd generation aromatic retinoid which has as yet only undergone limited trials, is extremely potent making pharmacological evaluation difficult. The search for more potent retinoids has not so far resulted in a complete resolution of the efficacy and toxicity of the drugs.

Topics: Animals; Benzoates; Etretinate; Humans; Retinoids; Skin Diseases; Tretinoin

Topics: Adult; Benzoates; Bowen's Disease; Carcinoma, Basal Cell; Child; Etretinate; Female; Humans; Isotretinoin; Male; Precancerous Conditions; Psoriasis; Retinoids; Skin Diseases; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Since topical retinoic acid was first used for acne in 1959, many additional uses have been described for lesions on the skin, oral mucosa, and ocular surface epithelia. The topical application of retinoic acid has been shown to be effective in the treatment of several disorders of keratinization, keloids and hypertrophic scars, and various infections and inflammatory, pigmentation, and malignant and premalignant disorders. This article briefly reviews the use of topical retinoic acid for selected cutaneous conditions.

Topics: Administration, Topical; Humans; Mouth Diseases; Pigmentation Disorders; Precancerous Conditions; Skin Diseases; Skin Neoplasms; Tretinoin

Topics: Acitretin; Administration, Oral; Benzoates; Eczema; Etretinate; Humans; Isotretinoin; Psoriasis; Retinoids; Skin Diseases; Skin Diseases, Vesiculobullous; Tretinoin

The potential of vitamin A, or retinol, in the treatment of a variety of skin diseases has long been recognized, but because of serious toxic effects this substance generally could not be used. The recent development and marketing of two relatively non-toxic synthetic analogues, which are known as retinoids, has made it possible to treat some of the diseases that are resistant to standard forms of therapy. Isotretinoin is very effective in cystic and conglobate acne, while etretinate is especially useful in the more severe forms of psoriasis. Good results have also been obtained in other disorders of keratinization. Vitamin A and its derivatives apparently have an antineoplastic effect as well and may come to be used in both the prevention and the treatment of epithelial cancer. In many of these diseases the retinoids act by enhancing the normal differentiation and proliferation of epidermal tissues, but the exact mechanisms are not well understood. Their influence on the intracellular polyamines that control the synthesis of nucleic acids and proteins may be an important factor. Although the retinoids have few serious systemic effects, they are teratogenic, and because they persist in the body their use in women of childbearing potential is limited.

Topics: Acne Vulgaris; Bone Diseases; Chemical and Drug Induced Liver Injury; Etretinate; Female; Humans; Isomerism; Isotretinoin; Keratosis; Kinetics; Psoriasis; Skin Diseases; Skin Neoplasms; Tretinoin; Triglycerides; Vitamin A

Topics: Adolescent; Adult; Aged; Child; Drug Administration Schedule; Etretinate; Female; Humans; Isotretinoin; Retinoids; Skin Diseases; Tretinoin; Vitamin A; Vitamin A Deficiency

The retinoids are synthetic derivatives of vitamin A. Isotretinoin (13-cis-retinoic acid) is now being widely used in the United States for severe acne and etretinate is available in Europe and other countries for psoriasis. These drugs are also effective for a number of other skin diseases. This is an attempt to review basic knowledge of retinoids with which the practicing dermatologist should be familiar, to review the current status of studies, and to speculate on the present and future roles of these drugs in dermatology.

Topics: Acne Vulgaris; Etretinate; Humans; Inflammation; Isotretinoin; Keratins; Psoriasis; Retinoids; Sebum; Skin Diseases; Skin Neoplasms; Sweat Gland Diseases; Tretinoin; Vitamin A

Isotretinoin is a new orally active retinoic acid derivative for the treatment of severe refractory nodulocystic acne. The pharmacological profile of isotretinoin suggests that it acts primarily by reducing sebaceous gland size and sebum production, and as a result alters skin surface lipid composition. Bacterial skin microflora is reduced, probably as a result of altered sebaceous factors. Isotretinoin 1 to 2 mg/kg/day for 3 to 4 months produces 60 to 95% clearance of inflammatory lesions in patients with severe, recalcitrant nodulocystic acne, with evidence of continued healing and prolonged remissions in many patients after treatment withdrawal. Doses as low as 0.1 mg/kg/day have also proven successful in the clearance of lesions; however, with such low doses the duration of remission after discontinuation of therapy is usually shorter. Encouraging results have also been seen in small numbers of patients with rosacea, Gram-negative folliculitis, Darier's disease, ichthyosis and pityriasis rubra pilaris, the response in keratinising disorders resembling that with the related drug etretinate. While long term follow-up studies in these patients have not been reported, prolonged remission after withdrawal of isotretinoin in disorders of keratinisation is unlikely, as with other drugs used in these conditions. Isotretinoin is only partially effective in psoriasis, in contrast to etretinate which is very effective in psoriasis but ineffective in severe acne. Some encouraging results have also been reported with isotretinoin in patients with squamous and basal cell carcinomas, but isotretinoin has proven unsuccessful in non-squamous cell epithelial and non-epithelial cancer. Side effects affecting the mucocutaneous system occur in nearly all patients receiving isotretinoin, but rarely lead to drug withdrawal. Raised serum triglyceride levels are also commonly reported. The possibility of long term spinal or skeletal bone toxicity may restrict the use of isotretinoin in severe disorders of keratinisation requiring prolonged administration. Isotretinoin is strictly contraindicated in women of childbearing potential due to its severe teratogenic properties, unless an effective form of contraception is used. Thus, isotretinoin offers an effective advance on the treatment options available in a difficult therapeutic area - those patients with severe, nodulocystic acne not responding to 'traditional' therapy.

Topics: Acne Vulgaris; Animals; Anti-Inflammatory Agents; Carcinogens; Cell Differentiation; Cell Division; Humans; Immunity; Isotretinoin; Kinetics; Mutagens; Psoriasis; Rosacea; Sebaceous Glands; Skin; Skin Absorption; Skin Diseases; Skin Neoplasms; Teratogens; Tissue Distribution; Tretinoin

Topics: Animals; Cell Differentiation; Humans; Liver; Male; Neoplasms; Nutritional Requirements; Retinoids; Retinol-Binding Proteins; Skin Diseases; Tretinoin; Vitamin A; Vitamin A Deficiency

Topics: Animals; Cell Differentiation; Chemical Phenomena; Chemistry; Growth; Humans; Kinetics; Neoplasms; Skin Diseases; Tretinoin

Topics: Baths; Calcinosis; Cat-Scratch Disease; Child; Diabetes Mellitus, Type 1; Folliculitis; Foot Dermatoses; Herpes Simplex; Humans; Hyperhidrosis; Isomerism; Isotretinoin; Joint Diseases; Lyme Disease; Skin Diseases; Tinea; Tretinoin

Topics: Acne Vulgaris; Adolescent; Child; Child, Preschool; Darier Disease; Etretinate; Female; Humans; Ichthyosis; Infant; Isomerism; Isotretinoin; Keratins; Keratoderma, Palmoplantar; Male; Pityriasis Rubra Pilaris; Psoriasis; Skin Diseases; Skin Diseases, Vesiculobullous; Tretinoin

Oral retinoids obviously influence dermal components such as cutaneous capillaries and dermal inflammatory cells in addition to their well-known action on keratinizing epithelia. On this basis, they act as an anti-inflammatory drug. In particular, they reduce the elevated skin temperature, inhibit the motility of neutrophils and eosinophils and their migration into the epidermis, decrease DNA synthesis of human lymphocytes by blocking their response to lectins and stimulate Langerhans cells, monocytes and macrophages in various in vitro and in vivo models. These data indicate that oral retinoids may not only normalize disorders of keratinization but also exert distinct therapeutic effects on various skin diseases with dermal inflammatory involvement regardless of their particular aetiology. In some respects, retinoids resemble corticosteroids, acting as a modified hormone. Preliminary clinical experiences with oral retinoid treatment in skin diseases such as cutaneous disseminated LE, bullous pemphigoid, Duhring's disease, pemphigus, Behçet's disease and necrotizing vasculitis with eosinophilia support these data. Monotherapy or combined administration of oral retinoids with corticosteroids in low doses seems therapeutically beneficial in these disorders.

Topics: Acitretin; Administration, Oral; Animals; Anti-Inflammatory Agents; Etretinate; Granulocytes; Humans; Isotretinoin; Leukocyte Count; Lymphocytes; Macrophages; Mice; Psoriasis; Skin Diseases; Skin Temperature; Tretinoin

Etretinate (Ro 10-9359) is a new aromatic retinoic acid derivative for the treatment of severe psoriasis and other dyskeratoses. The pharmacological profile of etretinate suggests that it acts by normalizing pathological changes in epidermal and dermal skin, particularly inhibiting hyperkeratinization and cell differentiation, although its specific mode of action in different disorders remains to be elucidated. Etretinate is rapidly and presystemically metabolised to an active metabolite which appears in plasma at about the same time as parent drug. A 'deep' storage compartment with a very extended elimination half-life gives rise to detectable plasma levels of drug for at least 3 to 4 months after discontinuation of long term therapy. Studies suggest that etretinate at an initial dose of 1 mg/kg/day, reducible during maintenance therapy, is an effective alternative to PUVA and other conventional therapy in severe psoriasis. Its greatest immediate value is in the control of eruptive and treatment-resistant psoriasis, and in its potential for use in combination with other therapy to improve the response. In Darier's disease it appears to be the treatment of choice, and preliminary studies also suggest its usefulness in ichthyosis, and most other dyskeratoses and possibly in basal cell carcinoma. Side effects affecting the mucocutaneous system occur in nearly all patients, but rarely lead to drug withdrawal. When withdrawal does become necessary, the primary reason is usually hair loss. A few paradoxical observations of raised and lowered liver enzyme levels have been reported, and also a few cases of suspected liver damage. Etretinate is strictly contraindicated in women of child-bearing potential due to its severe teratogenic properties.

Topics: Acne Vulgaris; Alanine Transaminase; Antineoplastic Agents; Cell Division; Etretinate; Humans; Lipids; Liver; Neoplasms, Experimental; Psoriasis; PUVA Therapy; Skin; Skin Diseases; Tretinoin

In the one year since isotretinoin has been available in the United States for the treatment of severe, recalcitrant, nodulocystic acne, there has been extensive clinical verification of the reports of its dramatic efficacy in the treatment of this troublesome disease. Proper selection of patients, as well as treatment with adequate doses of drug for 3 to 5 months, will most often result in significant clinical improvement or total clearing. Although dosages of less than 1 mg/kg/day may produce a nearly equivalent degree of improvement with somewhat fewer or less severe side effects, the recommended daily dose remains 1 mg/kg/day because lower dosages are associated with more frequent relapses. In severe cases, the daily dosage may be increased to 2 mg/kg/day. Teratogenicity, elevation of serum triglycerides, liver function abnormalities, pancreatitis, and pseudotumor cerebri may all be associated with isotretinoin therapy and require close monitoring of the patient.

Topics: Abnormalities, Drug-Induced; Acne Vulgaris; Adolescent; Adult; Animals; Central Nervous System; Chemical and Drug Induced Liver Injury; Folliculitis; Humans; Isotretinoin; Middle Aged; Mucous Membrane; Musculoskeletal System; Rats; Skin Diseases; Sweat Gland Diseases; Tretinoin

The synthetic retinoids are a new class of drugs which are highly effective in the treatment of a broad spectrum of dermatologic disease. In this report 15 patients with chronic disorders of keratinization and one patient with severe cystic acne were treated with oral isotretinoin. The degree of clinical response and duration of post-treatment remission varied with the different disorders. Acute side effects were predominantly limited to the skin and mucous membranes and were reversible after discontinuation of treatment in these patients. Acute retinoid toxicity and the potential for developing chronic toxicity are reviewed. In an attempt to facilitate the monitoring of dermatologic patients treated with oral synthetic retinoids, we present our current guidelines for the use of these agents.

Topics: Acne Vulgaris; Adolescent; Animals; Bone Diseases; Child; Child, Preschool; Etretinate; Humans; Isomerism; Isotretinoin; Joint Diseases; Keratosis; Mice; Psoriasis; Skin Diseases; Tretinoin

Topics: Animals; Carrier Proteins; Cell Differentiation; Chemical Phenomena; Chemistry; Epithelium; Female; Growth; Humans; Isomerism; Male; Neoplasms; Pregnancy; Receptors, Retinoic Acid; Reproduction; Retinal Pigments; Retinaldehyde; Retinol-Binding Proteins; Skin Diseases; Structure-Activity Relationship; Tretinoin; Vitamin A; Vitamin A Deficiency

Topics: Animals; Antineoplastic Agents; Cell Division; Chemical Phenomena; Chemistry; Humans; Neoplasms; Ornithine Decarboxylase Inhibitors; Phenotype; Skin; Skin Diseases; Tretinoin; Vitamin A

The Vitamin A. derivatives known as Retinoids, are among the most exciting pharmacological agents used in the last few years. They strongly influence the keratinizing epithelia, have an antipromoting effect upon experimentally induced tumors and have immunomodulatory activities. Teratogenicity seems to be the most worrisome effect of the retinoids. However, it is reasonable to assume their release for physicians prescription in the near future. This review is intended to provide a general background for their correct use by dermatologists.

Topics: Animals; Carcinogens; Darier Disease; Humans; Ichthyosis; Mice; Neoplasms; Psoriasis; Rats; Skin Diseases; T-Lymphocytes; Tretinoin; Vitamin A; Vitamin A Deficiency

Topics: 4-Aminobenzoic Acid; Coloring Agents; Furocoumarins; Humans; Hydroquinones; Phenothiazines; Photosensitivity Disorders; Pigmentation Disorders; Radiation-Protective Agents; Salicylanilides; Skin Diseases; Stilbenes; Sulfonamides; Tars; Tretinoin; Ultraviolet Rays

Topical therapy of the skin begins with the liberation from a carrier substance and results in a subsequent diffusion of the drug into the horny layer, depending on the physical and chemical properties of the respective agents. By permeating the epidermis the drug may be taken up by the inner compartment, namely the blood. A rediffusion to the skin is possible following systemic application. Although equivalent processes are induced by systemic and topical application, the latter application form limits the permeability including the first pass effect to the skin and its microcirculation. The characteristics are influenced by the type of dermatoses and by the condition of the horny layer as a barrier. The binding of these drugs to the skin's fibers and cells as well as the intensity and degree of permeation in the microcirculation is also of importance. The topical application of antihistamines, corticosteroids, heparin, coffein and nicotinic acid esters are used to describe the relationship between pharmacokinetics and effectiveness in view of clinical-experimental aspects. This pharmacoanalysis is based for the most part on factors which influence the microcirculation, namely the development of erythema, edema and thermography. The pharmacokinetics of topically applied substances are altered by the therapeutic effectivity of these agents and by the resulting changes in the structures of the skin.

Topics: Adrenal Cortex Hormones; Caffeine; Dermatologic Agents; Estrogens; Heparin; Histamine H1 Antagonists; Humans; Kinetics; Skin Absorption; Skin Diseases; Tretinoin

Topical vitamin A acid (VAA) has various mechanisms of action which may be responsible for its therapeutic success in many different disorders. Although the absorption, metabolism, and excretion of VAA are not completely understood, VAA appears to remain mainly on the skin surface. The question of carcinogenicity is unresolved, and more research is needed to clarify this problem. This article reviews the literature regarding the therapeutic uses of VAA and summarizes various investigators' experiences with VAA.

Topics: Acne Vulgaris; Animals; Callosities; Cocarcinogenesis; Fox-Fordyce Disease; Humans; Ichthyosis; Keloid; Keratoacanthoma; Keratosis; Lichen Planus; Melanoma; Melanosis; Molluscum Contagiosum; Nevus; Psoriasis; Skin Absorption; Skin Diseases; Skin Neoplasms; Tretinoin

Vitamin A and its newly developed synthetic analogues recently have been demonstrated to have profound effects on disorders of keratinization, sebaceous gland function, and cancer. In separate sections of this article, we review the history, chemistry, metabolism, mechanism of action, toxicity, and clinical applications of both the naturally occurring and synthetic retinoids.

Topics: Antineoplastic Agents; Carrier Proteins; Cell Membrane; Chemical Phenomena; Chemistry; Cytosol; Humans; Nutrition Disorders; Reproduction; Retinol-Binding Proteins; Skin; Skin Diseases; Tretinoin; Vision, Ocular; Vitamin A

Topics: Breast Neoplasms; Etretinate; Humans; Isomerism; Isotretinoin; Skin Diseases; Skin Neoplasms; Tretinoin

Topics: Acne Vulgaris; Adolescent; Adult; Age Factors; Aged; Anti-Bacterial Agents; Child; Child, Preschool; Dermatologic Agents; Diagnosis, Differential; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Sebaceous Glands; Sebum; Skin Diseases; Tretinoin; Vitamin A

A review of recent investigations in the retinoid field is presented. Retinoic acid exerts a prophylactic and a therapeutic effect on chemically induced benign and malignant epithelial tumors in mice. In clinical studies positive therapeutic results have been obtained in patients with preneoplastic and neoplastic epithelial lesions. However, treatment with retinoic acid is limited by serious side effects (hypervitaminosis A syndrome). Therefore, the synthesis of analogs of retinoic acid (retinoids) possessing a more favorable therapeutic ratio has been initiated. Among a large series of synthesized compounds, certain aromatic analogs proved to have a particularly favorable therapeutic ratio. The structure-activity relationship of the most active retinoids is discussed including some biological data concerning prophylaxis and therapy of epithelial tumors. The total synthesis of retinoids according to various building schemes is discussed in detail. Methods for the synthesis of the cyclic end group, of the polyene chain component, and of the full retinoid skeleton are described. Metabolic studies of retinoic acid and of the most active retinoid, as well as the synthesis of some isolated metabolites are outlined. Suggestions concerning the mechanism of action of retinoids are made. Some clinical results on the treatment of acne, psoriasis and precancerous conditions are reported.

Topics: Animals; Carcinoma; Humans; Neoplasms, Experimental; Papilloma; Retinaldehyde; Skin Diseases; Skin Neoplasms; Structure-Activity Relationship; Tretinoin; Vitamin A

Topics: Acne Vulgaris; Animals; Female; Haplorhini; Humans; Maternal-Fetal Exchange; Mice; Pregnancy; Rats; Skin Diseases; Tretinoin; Vitamin A

Vitamin A acid (retinoic acid: tretinoin) is a vitamin A derivative used in the topical treatment of acne. It acts by 'unseating' comedones, improvement developing slowly over a period of 2 to 3 or more months, and is also said to prevent the formation of new lesions. About three-quarters of patients with acne vulgaris benefit from treatment. In controlled studies, results achieved after a 3 to 4 months course of treatment were superior to those with sulphur-resorcinol-salicylic acid. When compared with benzoyl peroxide, results were variable and appear to depend on the length of treatment, the types of formulations used, and the concentrations compared. Application of vitamin A acid should be continued until the patient has been free of new lesions for several months. Further continued application at a less frequent interval or using a less active dosage form may help to prevent exacerbations of acne. A systemic antibacterial agent such as tetracycline can be given as well as in patients with moderate to severe lesions. Vitamin A acid is used in conjunction with gentle washing (to remove surface oil) but should be applied to a dry skin to avoid unnecessary irritation. Patient education and encouragement are crucial during the initial phase of treatment when microcomedones may be converted to pustules prior to desquamation.

Topics: Acne Vulgaris; Humans; Kinetics; Liver; Prostaglandins; Skin; Skin Absorption; Skin Diseases; Steroids; Tretinoin; Vitamin A

The fields of cutaneous pharmacology and toxicology existed as long as man used topical therapy; some medicaments were helpful and others harmful. This review documents recent progress in these fields in terms of the experimental method. Emphasis has been given to conceptual and methodologic progress rather than a list of new molecules. As signs of the advent of the maturity of these fields, a graduate school course has recently been completed, one text has been published (7), and at least two are in preparation. It is likely that the next review of this topic in this series will reflect this considerable progress in terms of relevance to man.

Topics: Animals; Dermatitis, Contact; Drug Hypersensitivity; Guinea Pigs; Humans; Irritants; Methods; Perfusion; Photosensitivity Disorders; Rabbits; Skin; Skin Diseases; Skin Tests; Swine; Tretinoin

The future of a drug depends upon what it can do in the hands of the practitioner. Medicine is practiced on the basis of probabilities, and treatment must be selected which has the best chance of helping the patient, with the least amount of harm. There are many new drugs available for dermatologic therapy in other developed countries which are not available in this country, due to peculiarities of federal drug regulations.

Topics: Acne Vulgaris; Adrenal Cortex Hormones; Antifungal Agents; Antineoplastic Agents; Carotenoids; Dermatologic Agents; Fluorouracil; Herpesviridae Infections; Humans; Keratolytic Agents; Photosensitivity Disorders; Psoriasis; Skin Diseases; Tretinoin; United States; United States Food and Drug Administration; Vitamin E; Vitiligo

The efficacious acne treatment adapalene gel 0.1% is significantly less irritating than tretinoin of various concentrations and formulations, according to several clinical studies conducted predominantly in Caucasian patients.. To confirm the lower irritation potential of adapalene gel 0.1% compared to tretinoin gel 0.025% among volunteers of various ethnic origins and to explore the difference in the irritant susceptibility among ethnic groups.. The study was a single-centre, randomized, investigator-masked and intra-individual comparison. Healthy volunteers applied adapalene and tretinoin daily to the face for 21 days and to the forearms for 4 days, and were then evaluated for the level of irritation.. The irritation potential of adapalene gel 0.1% was significantly lower than that of tretinoin gel 0.025% in all tolerability assessments, irrespective of the volunteers' ethnic origins. The between-treatment differences were similar among various ethnic groups. Statistically significant but small inter-ethnicity differences were observed in the evaluation of facial signs, with Caucasians being less susceptible than Chinese, Asian Indians and Malays.. Adapalene gel 0.1% was significantly better tolerated than tretinoin gel 0.025% among various ethnic groups. The patients' ethnic origins had no impact on the difference between adapalene and tretinoin treatments in terms of tolerability.

Topics: Adapalene; Administration, Cutaneous; Adolescent; Adult; Aged; Dermatologic Agents; Gels; Humans; Middle Aged; Naphthalenes; Single-Blind Method; Skin Diseases; Skin Irritancy Tests; Tretinoin; Young Adult

The utility of topical tretinoin as a treatment for improving the appearance of photodamaged skin is limited by irritation that occurs during the early phases of facial retinization. The observed side effects are consistent with stratum corneum barrier compromise. This paired double-blinded study was conducted to determine if preconditioning the skin with a barrier-enhancing cosmetic facial moisturizer before beginning tretinoin therapy and continuing moisturizer application during therapy would mitigate these side effects. Women with facial photodamage were recruited and randomly assigned to apply one cosmetic moisturizer to one side of the face and the other cosmetic moisturizer to the other side of the face twice daily for 10 weeks. One moisturizer contained a mixture of vitamins (niacinamide, panthenol, and tocopheryl acetate) to enhance stratum corneum barrier function, and the other moisturizer contained similar moisturizing ingredients but no vitamins. Daily full-face treatment with tretinoin cream 0.025% commenced 2 weeks into the study. Subjects' facial skin condition was monitored via investigator assessments, instrumental measurements, and subject self-assessments. The results show that improving stratum corneum barrier function before beginning topical tretinoin therapy and continuing use of a barrier-enhancing cosmetic moisturizer during therapy facilitates the early phase of facial retinization and augments the treatment response.

Topics: Administration, Cutaneous; Adult; Double-Blind Method; Drug Therapy, Combination; Emollients; Epidermis; Female; Humans; Keratolytic Agents; Middle Aged; North Carolina; Ohio; Skin Aging; Skin Diseases; Sunlight; Treatment Outcome; Tretinoin

Tretinoin microsphere gel (TMG) 0. 1% was evaluated as a treatment of photodamaged skin. The study included a 6-month, randomized, double-blinded, placebo-controlled phase and an additional 6-month open-label phase during which all subjects received TMG 0. 1%. Forty-five subjects with moderate to severe photodamaged facial skin applied study gel topically to the face once nightly (22 subjects received TMG 0.1% and 23 subjects received placebo). At 6 months, TMG 0. 1% was found to be superior to placebo in improving overall severity of photodamage (P=.0003) and in the investigator's global assessment of clinical response (P<.0001). Statistically significant improvement relative to placebo was observed in fine wrinkling (P<.0001), mottled hyperpigmentation (P=.0002), yellowing/ sallowness (P<.0001), and lentigines (P=.0054). The improvements observed after 6 months of open-label therapy were consistent with the results observed in TMG 0. 1%-treated subjects during double-blinded treatment. Most signs and symptoms of cutaneous irritation were mild throughout the treatment period. At one month, a higher proportion of subjects in the TMG 0. 1% group relative to the placebo group experienced an increase in severity of cutaneous irritation. After 6 months, the difference between treatment groups was statistically significant only for peeling (P=.001) and dryness (P=.007).

Topics: Administration, Topical; Adult; Aged; Cross-Over Studies; Double-Blind Method; Female; Humans; Keratolytic Agents; Male; Microspheres; Middle Aged; Skin Aging; Skin Diseases; Treatment Outcome; Tretinoin; Ultraviolet Rays

Topics: Adult; Antineoplastic Agents; Humans; Leukemia-Lymphoma, Adult T-Cell; Skin Diseases; Tretinoin

To determine the maximum tolerated dose and describe the toxicities of 9-cis-retinoic acid (9cRA, ALRT1057) administered p.o. tid in pediatric patients with refractory cancer and to study the pharmacokinetics of 9cRA and determine whether systemic drug exposure changes with chronic dosing.. Children with refractory cancer (stratified by age, < or =12 and >12 years) were treated with p.o. 9cRA for 28 consecutive days. The starting dose was 50 mg/m(2)/day divided into 3 doses with planned escalations to 65, 85, and 110 mg/m(2)/day. Pharmacokinetic sampling was performed on days 1 and 29 of the first cycle.. Of the 37 patients entered, 18 patients < or =12 years of age and 11 patients >12 years of age were evaluable for toxicity. In patients >12 years of age, dose-limiting headache occurred in 2/2 patients at the 110 mg/m(2)/day dose level; 1/8 patients at 85 mg/m(2)/day developed dose-limiting pseudotumor cerebri. In patients < or =12 years of age, 3/5 patients at the starting dose level of 50 mg/m(2)/day developed dose-limiting pseudotumor cerebri; and 0/6 patients experienced dose-limiting toxicity at 35 mg/m(2)/day. Reversible non-dose-limiting hepatotoxicity was observed in 15 patients across all of the dose levels. There was considerable interpatient variability in 9cRA plasma concentrations. Peak plasma concentrations of 9cRA occurred at a median of 1.5 h after a p.o. dose, and the harmonic-mean terminal half-life was 43 min. By day 29 of 9cRA administration, the plasma 9cRA area under the curve declined by an average of 65% from day 1 values.. The dose-limiting toxicity of 9cRA in pediatric patients was neurotoxicity, primarily pseudotumor cerebri. Younger children tolerate significantly lower doses of 9cRA than older children. Similar to all-trans-retinoic acid, the pharmacokinetics of 9cRA demonstrated a wide degree of interpatient variability and decreased over time when administered on a daily basis. The recommended Phase II dose of 9cRA in patients < or =12 and >12 years of age is 35 and 85 mg/m(2)/day, respectively.

Topics: Adolescent; Adult; Age Factors; Alitretinoin; Antineoplastic Agents; Area Under Curve; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Headache; Humans; Liver; Male; Nausea; Neoplasms; Skin Diseases; Transaminases; Treatment Outcome; Tretinoin; Triglycerides; Vomiting

Studies comparing purported antiaging compounds are rare.. To compare in a randomized, placebo-controlled double-blind study 10% glycolic acid (GA), 2% 2-hydroxy-5-octanoyl benzoic acid (beta-lipohydroxy acid, LSA) and 0.05% all-trans-retinoic acid (RA).. Women volunteers treated one forearm twice daily with one of the active products and the other one with the vehicle. Comparative evaluations of efficacy were made using histochemistry and quantitative immunohistochemistry.. Improvement in the various epidermal compartments was the most prominent finding at the RA-treated site. The LSA-treated site also exhibited similar positive changes, although to a lesser degree. GA showed no significant effect.. In the presently tested concentrations and formulations, RA had a beneficial impact upon the aging epidermis. LSA mimicked RA but with somewhat lesser efficacy. By contrast, GA appeared almost inactive.

Topics: Double-Blind Method; Epidermis; Female; Filaggrin Proteins; Glycolates; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Keratolytic Agents; Ki-67 Antigen; Lectins; Middle Aged; Plant Lectins; Salicylates; Skin; Skin Diseases; Transglutaminases; Treatment Outcome; Tretinoin

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

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

To study the use of topical tretinoin for treating vulvar lichen sclerosus.. An open, uncontrolled clinical study on 22 patients affected by histologically confirmed vulvar lichen sclerosus. Topical 0.025% tretinoin was applied once a day, five days a week, for one year. Clinical and histologic parameters were evaluated before and after therapy, and statistical analysis was performed.. Symptoms, gross appearance and histopathologic features improved in a highly significant manner (P < .001). Cutaneous side effects were observed but rapidly disappeared, and no patient left the study for this reason. Maintenance of results was observed at the 4-13-month follow-up visits.. Topical tretinoin seems feasible for use in the topical treatment of vulvar lichen sclerosus.

Topics: Administration, Topical; Adult; Aged; Biopsy; Dose-Response Relationship, Drug; Female; Humans; Keratolytic Agents; Lichen Sclerosus et Atrophicus; Middle Aged; Skin Diseases; Time Factors; Tretinoin; Vulva; Vulvar Diseases

Prompted by recent demonstrations that all-trans-retinoic acid (all-trans-RA) had efficacy in acute promyelocytic leukemia, a phase I trial of all-trans-RA was conducted to establish the maximum-tolerated dose (MTD) before phase II testing.. Forty patients with a histologic or cytologic diagnosis of malignancy other than leukemia were treated with single daily oral doses of all-trans-RA ranging from 45 mg/m2 to 200 mg/m2. Doses of all-trans-RA were escalated in the next cohort of patients until the MTD was determined if the preceding dose level was not associated with significant toxicity.. Lung cancer was the most common type of tumor included in the study (26 cases) followed by head and neck squamous cell carcinomas (three cases), and squamous cell carcinoma of the skin (two cases); other miscellaneous solid tumors were also represented. Toxicities included cheilitis, skin reactions, headache, and nausea and vomiting, as well as transient elevations of liver enzymes and triglyceride levels. Skin toxicities, consisting of erythema with desquamation and paronychia, were considered to be the dose-limiting toxicity, and were observed in two of six patients who received 175 mg/m2/d, and in two of five patients who received 200 mg/m2/d. Of the 30 patients with assessable lesions, response was evaluated in 26 patients and no major objective tumor response was observed. Two patients were able to receive the drug for longer than 1 year without significant toxicities. There was considerable variation in individual patients' peak plasma all-trans-RA levels, and a decrease in the area under the curve of all-trans-RA plasma concentration was observed in all four patients evaluated.. For phase II study of adult patients, we recommend 150 mg/m2 of all-trans-RA administered orally once a day. However, for better optimization of drug administration schedules, further studies are needed.

Topics: Adult; Aged; Alkaline Phosphatase; Cheilitis; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Female; Headache; Hearing Disorders; Humans; Liver; Liver Diseases; Male; Middle Aged; Nausea; Neoplasms; Skin Diseases; Tretinoin; Vomiting

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

The clinical and histologic effects of a new emollient cream formulation of topical tretinoin at concentrations of 0.05% and 0.01% were examined in 251 subjects with mild to moderate photodamaged facial skin in a randomized, double-blind, vehicle-controlled, multicenter study. Seventy-nine percent of the subjects who received 0.05% tretinoin for 24 weeks showed overall improvement in photodamaged skin compared with improvement in 48% of the vehicle-treated control subjects. Significant reductions were found in fine wrinkling, mottled hyperpigmentation, roughness, and laxity after 0.05% tretinoin therapy when compared with controls. In addition, histologic changes of increased epidermal thickness, decreased melanin content, and stratum corneum compaction provide independent evidence supporting clinical improvement. Side effects of erythema, peeling, and stinging were usually mild and well tolerated.

Topics: Administration, Cutaneous; Adult; Dose-Response Relationship, Drug; Double-Blind Method; Face; Female; Humans; Lentigo; Male; Middle Aged; Pigmentation Disorders; Placebos; Skin; Skin Aging; Skin Diseases; Telangiectasis; Tretinoin

A 6-month, randomized, double-blind, vehicle-controlled study was conducted with 0.05% tretinoin cream once daily in the treatment of photodamaged facial skin. Significant amelioration of many of the signs of photodamage were achieved with minimal side effects. Clinical grading showed significant improvement both in the assessments based on changes in clinical scores and in pre- and posttreatment comparisons of standardized photographs. Fine wrinkling, coarse wrinkling, sallowness, looseness, and hyperpigmentation were significantly improved with tretinoin therapy. Furthermore, a self-appraisal questionnaire indicated that tretinoin-treated patients, but not vehicle-treated patients, were able to perceive improvement in their facial appearance. An objective method based on digital image processing of silicone rubber casts obtained from the crow's-feet area also indicated that the skin surface topography was smoother and less wrinkled in the tretinoin-treated group compared with the vehicle-control group.

Topics: Adult; Aging; Clinical Trials as Topic; Double-Blind Method; Face; Female; Humans; Image Processing, Computer-Assisted; Middle Aged; Random Allocation; Skin Diseases; Tretinoin; Ultraviolet Rays

A double-blind, placebo-controlled randomized trial of 13-cis retinoic acid was performed to determine if the drug has a therapeutic effect in patients with myelodysplastic syndromes (MDS). Sixty-eight evaluable patients with MDS were randomized to receive a single, daily oral dose of either 13-cis retinoic acid (13-CRA, 100 mg/m2) or matching placebo. Treatment was continued, when possible, for a period of 6 months. Determination of response to treatment was based on clinical course, repeat bone marrow biopsies, and aspirates and blood counts (CBC) with WBC differential, platelet, and reticulocyte numbers at specified intervals. No significant difference was noted between the two treatment groups in response to test drug (P = .66). One patient (3%) in the 13-CRA group and two patients (6%) in the placebo group had a minor response. Approximately 30% of patients in both groups had progression of their disease, and progression-free survival was nearly identical. Greater than 90% of the patients receiving 13-CRA developed mild or moderate skin toxicity that was reversible with decreasing or discontinuing the drug. Our study did not find that 13-CRA exerts a beneficial therapeutic effect in patients with MDS.

Topics: Clinical Trials as Topic; Double-Blind Method; Hematopoiesis; Humans; Myelodysplastic Syndromes; Random Allocation; Skin Diseases; Sleep Stages; Tretinoin

Responses have been reported in patients with myelodysplastic syndromes (MDS) after low-dose cytarabine (Ara-C) or 13-cis-retinoic acid (13-CRA) therapy. Recently, combination of these two substances in vitro was shown to produce a synergistic effect on differentiation of leukemic cells. We conducted a phase II trial with low-dose Ara-C (5 mg/m2 per 12 h s.c.) and 13-CRA (60 mg/m2 per day orally) in 14 patients with MDS, six of whom had refractory anemia with excess of blasts (RAEB), seven had RAEB in transformation (RAEBt) and one chronic myelomonocytic leukemia (CMML). The drugs were administered from day 1 to 14 and the treatment courses repeated every 4 to 8 weeks. One partial response and one minor response could be achieved. Major toxicity included dry skin, mucositis and cheilitis in 11 of the 14 patients. The response rate is no better than the results reported in the literature with either drugs alone. As yet there is no satisfactory treatment for MDS.

Topics: Adult; Aged; Cell Differentiation; Clinical Trials as Topic; Cytarabine; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Skin Diseases; Tretinoin

Topics: Administration, Topical; Amyloidosis; Azathioprine; Clinical Trials as Topic; Colchicine; Dimethyl Sulfoxide; Double-Blind Method; Etretinate; Humans; Skin Diseases; Tretinoin

Daily topical application of 0.05% tretinoin in a cream base was compared with its vehicle with regard to moderation of photoaging changes of the face and forearms. In comparison with the control tissue, tretinoin-treated tissue examined by light and electron microscopy showed the following effects: replacement of the atrophic epidermis by hyperplasia, elimination of dysplasia and atypia, eradication of microscopic actinic keratoses, uniform dispersion of melanin granules, new collagen formation in the papillary dermis, new vessel formation (angiogenesis), and exfoliation of retained horn in the follicles. Physiologic studies demonstrated: increased blood flow and dermal clearance, increased transepidermal water loss, and greater permeability and reactivity. It was concluded that topical tretinoin is capable of at least partly reversing the structural damages of excessive sunlight exposure and may be useful in decelerating the photoaging process.

Topics: Administration, Topical; Aged; Face; Female; Forearm; Humans; Microscopy, Electron; Middle Aged; Skin; Skin Diseases; Sunlight; Tretinoin

Etretinate and isotretinoin were compared with respect to their clinical effects and changes in serum lipoprotein concentrations. Sixteen patients with hyperkeratotic and pustular disorders of hands and feet (mainly palmoplantar pustulosis) underwent a double-blind cross-over study. The daily doses of etretinate and isotretinoin were 50 and 40 mg, respectively. Each drug was given for 2 months with a 2-month intermission. The clinical score was reduced both by isotretinoin (P less than 0.05) and etretinate (P less than 0.001). Both drugs affected the lipoprotein concentrations. Isotretinoin increased the cholesterol concentration in low-density lipoprotein (LDL) by 20% and the triglyceride concentration in very low-density lipoprotein (VLDL) by 35%, but decreased the high-density lipoprotein cholesterol by 12%. Etretinate elevated LDL-cholesterol by 10%. These changes had reverted to normal 8 weeks after the end of treatment. The data suggest that in the diseases studied, etretinate is preferable to isotretinoin with regard to both clinical effect and serum lipid side-effects.

Topics: Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Etretinate; Female; Humans; Hyperlipoproteinemias; Isotretinoin; Lipoproteins; Male; Middle Aged; Skin Diseases; Tretinoin

Topics: Clinical Trials as Topic; Humans; Ichthyosis; Isotretinoin; Keratosis; Pityriasis Rubra Pilaris; Skin Diseases; Tretinoin

A total of 40 patients with palmoplantar pustulosis (PPP) were initially treated with oral etretinate (Tigason) in an open trail with a maximum treatment period of 16 weeks. Remission, with only slight residual changes in some cases, was achieved in 26 patients (65%) who were randomized to either a low dose of Tigason or placebo. In the Tigason group, 7 of 11 patients were still in remission afer 6 months while in the placebo group, remission persisted in 4 of the 10 patients who stayed in the study throughout the whole 6 months' period. Alopecia led to stopping the treatment in 6 patients and desquamation of the healthy skin in 2 patients. Other side-effects were only mild. As a conclusion, Tigason shows a beneficial effect in the majority of patients with PPP and is better than placebo in preventing relapse of the disease but intolerable side-effects restrict its use in many patients.

Topics: Adult; Alopecia; Clinical Trials as Topic; Double-Blind Method; Etretinate; Female; Humans; Male; Middle Aged; Random Allocation; Skin; Skin Diseases; Suppuration; Tretinoin

5 patients with palmoplantar pustulosis (PPP) were randomized to 8 weeks of daily treatment with either oral etretinate, 1 mg/kg b.w. or placebo. Good or moderate effect was obtained in 18 or 20 patients on etretinate compared o 6 of 21 patients on placebo (p less than 0.001). Etretinate proved to be significantly superior to placebo with regard to influence on the individual symptoms and signs of pustulosis. All patients on etretinate experienced some side effects from the mucous membranes, but they were generally mild. Treatment was discontinued after 4 weeks in 3 patients for reasons unrelated to treatment, in 4 for lack of effect (all on placebo) and in 2 for side effects (both or etretinate). Etretinate is a good alternative to other systemic treatments of PPP.

Topics: Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Etretinate; Female; Humans; Male; Middle Aged; Mucous Membrane; Random Allocation; Skin Diseases; Suppuration; Tretinoin

Orally administered retinoids are synthetic derivatives of vitamin A. This new group of drugs (not yet available for general use in the United States) has been effective in experimental trials for treatment of a wide range of skin diseases. The current status of two of these drugs, isotretinoin (13-cis-retinoic acid) and etretinate (Ro 10-9359), is herein reviewed.

Topics: Acne Vulgaris; Administration, Oral; Child; Clinical Trials as Topic; Facial Dermatoses; Female; Humans; Isomerism; Isotretinoin; Keratins; Keratitis; Neoplasms; Psoriasis; Skin Diseases; Tretinoin; Xerostomia

Topics: Clinical Trials as Topic; Humans; Isomerism; Isotretinoin; Keratins; Skin Diseases; Tretinoin

Topics: Administration, Oral; Clinical Trials as Topic; Etretinate; Humans; PUVA Therapy; Skin Diseases; Tretinoin

Topics: Abnormalities, Drug-Induced; Australia; Clinical Trials as Topic; Etretinate; Female; Humans; Isotretinoin; Neoplasms; Pregnancy; Skin Diseases; Tretinoin; Vitamin A

Vitamin A acid (retinoic acid) is less toxic than vitamin A and seems to be an important advance in dermatology. Its therapeutic effect was investigated in clinical studies involving 405 patients. Biochemical investigations have shown that the administration of vitamin A acid is associated with elevation of serum levels of retinol and carotene and after high dosage symptoms develop identical with hypervitaminosis A. Several possibilities regarding the mode of action of vitamin A acid are discussed.

Topics: Administration, Topical; Animals; Female; Humans; Injections; Mouth Diseases; Mouth Mucosa; Placebos; Pregnancy; Rats; Skin Diseases; Tretinoin; Vitamin A

Innate immune defense against deep tissue infection by

Topics: Acne Vulgaris; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Humans; Mice; Propionibacterium acnes; Skin Diseases; Staphylococcus aureus; Tretinoin

Topics: Administration, Topical; Alopecia; Animals; Biological Transport; Drug Therapy, Combination; Hydrogels; Keratolytic Agents; Liposomes; Male; Minoxidil; Rats; Rats, Sprague-Dawley; Skin; Skin Diseases; Tretinoin; Vasodilator Agents

Topics: Administration, Cutaneous; Administration, Oral; Cell Differentiation; Cell Proliferation; Drug Combinations; Drug Compounding; Germany; Humans; Keratinocytes; Skin Diseases; Tretinoin

Thicker nasal skin blunts the definition of the underlying osseocartilaginous frame and the delicate topography of the nose posing additional challenges in producing desirable tip definition. Despite the recognized challenge in this patient population, there is a paucity of literature on how to overcome this problem.. The goal of this article is to provide a systematic algorithm to manage patients with thick nasal skin.. Approach to the thick nasal skin patient begins with an evaluation of the etiology of their skin thickness. Skin thickness secondary to sebaceous overactivity is diminished with the use of retinoic acid derivatives, lasers or isotretinoin (Accutane), commonly under the advice of the dermatologist. Rhinoplasty maneuvers include open technique, raising a healthy and reasonably thick skin flap overlying the tip, removing the remaining fat overlying and between the domes, creating a firm cartilaginous frame and eliminating dead space using the supratip suture reported by the senior author, and trimming redundant nasal skin envelope when indicated.. This systematic approach has been greatly effective in achieving often predictable and aesthetically pleasing rhinoplasty results.. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Topics: Algorithms; Female; Humans; Keratolytic Agents; Nasal Cartilages; Nose; Rhinoplasty; Skin; Skin Diseases; Tretinoin

Topics: Aged; Anthracenes; Antioxidants; Benzoates; Bronchi; Diterpenes; Epithelial Cells; Female; Humans; In Vitro Techniques; Male; Middle Aged; Naphthols; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Retinoic Acid Receptor gamma; Retinyl Esters; Skin Diseases; Smoking; Tetrahydronaphthalenes; Thiophenes; Tretinoin; Uteroglobin; Vitamin A

Topics: Animals; Cell Differentiation; Cell Proliferation; Epidermis; Gene Knockout Techniques; Keratin-6; Keratinocytes; Mice; Mice, Inbred Strains; PPAR gamma; PPAR-beta; Signal Transduction; Skin Diseases; Tretinoin; Tumor Suppressor Protein p53; Up-Regulation

Retinoid-X receptor (RXR)- and retinoic acid receptor (RAR)-mediated signaling is induced by retinoic acids (RA), which are involved in the regulation of skin permeability, differentiation and immune response. Dysregulation of retinoid signaling is present in various skin disorders. Topically and systemically administered synthetic RAR or RXR agonists might influence retinoid-mediated signaling in the skin of RARE reporter animals and gene expression analysis for retinoid, skin homeostasis and skin inflammation marker genes and local retinoid concentrations. Mice were treated orally and topically with synthetic ligands and bioimaging, QRT-PCR and retinoid analysis were performed. Topical application of the synthetic RAR ligand AM580 significantly enhanced retinoid signaling in skin while topical application of the RXR ligand LG268 did not influence retinoic acid receptor response elements (RARE)-mediated signaling. Systemic treatments with LG268 decreased the expression of genes involved in skin homeostasis, RA synthesis and skin RA concentrations, while it increased various markers for skin inflammation and RA degradation, which corresponds to decreased skin RARE signaling. We conclude from these observations that increased systemic concentrations of an RXR -ligand may be one reason for reduced retinoid signaling, -reduced all-trans RA levels in the skin, reduced epidermal homeostasis and increased skin inflammation marker expression with potential relevance for various skin disorders, like atopic dermatitis.

Topics: Administration, Oral; Administration, Topical; Animals; Benzoates; Chromatography, High Pressure Liquid; Female; Ligands; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Animal; Organic Chemicals; Real-Time Polymerase Chain Reaction; Receptors, Retinoic Acid; Response Elements; Retinoid X Receptors; RNA, Messenger; Signal Transduction; Skin; Skin Diseases; Tandem Mass Spectrometry; Tetrahydronaphthalenes; Tretinoin; Vitamin A

Simple and efficient gene transfer to the skin would facilitate many local and systemic gene therapy applications. This study reports a novel approach that allows expression of plasmid DNA in epidermis and hair follicle cells with dimethyl sulfoxide (DMSO) after pre-treatment with depilation and retinoic acid (RA) for the purposes of gene therapy. This study investigated the transdermal efficacy of gene to mouse skin when utilizing DMSO after RA pre-treatment. Retinoic acid pre-treatment can increase the efficiency of transfection. This finding indicates that one can more effectively and much less expensively make use of genes therapy to treat diseases of the hair and skin.

Topics: Administration, Cutaneous; Animals; Cell Proliferation; Dimethyl Sulfoxide; Epidermis; Gene Expression Regulation; Genes, Reporter; Genetic Therapy; Hair Follicle; Mice; Osmolar Concentration; Permeability; Pharmaceutical Vehicles; Plasmids; Premedication; Skin; Skin Diseases; Transfection; Transgenes; Tretinoin

There are numerous acquired elastic tissue disorders, several of which present cutaneously with small yellow-to-white papules resembling plucked chicken skin. Differential diagnoses depend on the abnormalities within the network of elastic tissues. We report a case with distinct histologic features, which may represent a unique elastic tissue disorder or a variant of pseudoxanthoma elasticum-like papillary dermal elastolysis. Our patient's clinical presentation includes scattered 1-2 mm white-to-yellow papules without surface change on the upper back and neck region. Histology is characterized by foci of clumped, granular elastic tissue, which have replaced the oxytalan and elaunin fibers, alternating with foci of decreased concentrations of normal-appearing elastic fibers within the papillary dermis. Given its characteristics, we have termed this novel entity 'papillary dermal elastosis'.

Topics: Adult; Elastic Tissue; Female; Humans; Keratolytic Agents; Pseudoxanthoma Elasticum; Skin Diseases; Tretinoin

Topics: Acne Vulgaris; Administration, Topical; Combined Modality Therapy; Cysts; Humans; Keratolytic Agents; Laser Therapy; Male; Skin Diseases; Tretinoin; Young Adult

Topics: Administration, Topical; Adolescent; Biopsy; Diagnosis, Differential; Epidermal Cyst; Female; Humans; Keratolytic Agents; Ointments; Skin; Skin Diseases; Tretinoin

Topics: Autoimmune Diseases; Clinical Trials as Topic; Humans; Skin Diseases; Tretinoin

Novel potent C-4 azolyl retinoic acid metabolism blocking agents (RAMBAs)-VN/14-1, VN/50-1, VN/66-1, VN/67-1, and VN/69-1, have been synthesized and investigated for their in vitro and in vivo effects against breast and prostate cancers. These RAMBAs, in addition to being potent inhibitors of all-trans-retinoic acid (ATRA) metabolism have potent anti-cancer properties and in vivo anti-tumor efficacies as characterized in breast and prostate cancer models. Here we determined the toxicity and pharmacokinetics (PK) of these various RAMBAs.. Preliminary acute toxicity studies of these RAMBAs were carried out using Swiss NIH mice. The toxicity profile of the RAMBAs was evaluated relative to ATRA. Three different doses (8.3, 33, and 100 micromol/kg/day) of ATRA and RAMBAs were administered on a daily basis subcutaneously for 14 days to the mice. Clinical signs of toxicity alopecia, scaly skin, and loss of body weight in the mice were observed during the study and the maximum tolerated dose was determined. PK of selected agents (VN/14-1, VN/50-1, and VN/66-1) was studied in Balb/C mice after a single dose subcutaneous administration. Plasma concentrations of the agents were quantitatively determined using a high-performance liquid chromatographic method with ultraviolet detection. Plasma concentration versus time profiles were fit to various PK structural models and relevant PK parameters were estimated.. VN/66-1 and VN/69-1 were found to be the least toxic even at the highest doses when compared to the other RAMBAs and ATRA. VN/66-1 had the longest half-life, the slowest clearance, and the greatest exposure.. Based on PK characteristics and toxicity studies, VN/66-1 appeared to be the most favorable agent. However, both VN/14-1 and VN/66-1 are our leads based on the fact that VN/14-1 has been found to be highly effective in endocrine-sensitive and -resistant breast cancer cells and tumors with little toxicity. Our findings provide valuable information that will be used to select RAMBAs and establish therapeutic regimens that provide optimal efficacy with minimal toxicity.

Topics: Alopecia; Animals; Antineoplastic Agents; Area Under Curve; Body Weight; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Half-Life; Imidazoles; Injections, Subcutaneous; Mice; Mice, Inbred BALB C; Skin Diseases; Tissue Distribution; Tretinoin

The kinase IKK1 (also known as IKKalpha) was previously reported to regulate epidermal development and skeletal morphogenesis by acting in keratinocytes to induce their differentiation in an NF-kappaB independent manner. Here, we show that mice with epidermal keratinocyte-specific IKK1 ablation (hereafter referred to as IKK1(EKO)) develop a normally differentiated stratified epidermis, demonstrating that the function of IKK1 in inducing epidermal differentiation is not keratinocyte-autonomous. Despite normal epidermal stratification, the IKK1(EKO) mice display impaired epidermal-barrier function and increased transepidermal water loss, due to defects in stratum corneum lipid composition and in epidermal tight junctions. These defects are caused by the deregulation of retinoic acid target genes, encoding key lipid modifying enzymes and tight junction proteins, in the IKK1-deficient epidermis. Furthermore, we show that IKK1-deficient cells display impaired retinoic acid-induced gene transcription, and that IKK1 is recruited to the promoters of retinoic acid-regulated genes, suggesting that one mechanism by which IKK1 controls epidermal-barrier formation is by regulating the expression of retinoic acid receptor target genes in keratinocytes.

Topics: Animals; Animals, Newborn; Cell Differentiation; Cell Proliferation; Cells, Cultured; Chromatin Immunoprecipitation; Epidermal Cells; Epidermis; Female; Forelimb; Gene Expression Profiling; I-kappa B Kinase; Keratinocytes; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron, Transmission; Mutation; Reverse Transcriptase Polymerase Chain Reaction; Skin Diseases; Transcription, Genetic; Tretinoin

A number of dermatology conditions including skin photodamage, atopic dermatitis, and rosacea involve skin barrier impairment and first line therapies for these conditions including retinoids and steroids further impair skin barrier function. We have evaluated the compatibility of myristyl nicotinate, an agent that enhances skin barrier function, with drugs used to treat conditions where skin barrier impairment is present including photodamage (retinoic acid), atopic dermatitis (hydrocortisone, triamcinolone acetonide), rosacea (metronidazole), and seborrheic dermatitis (ketoconazole). Myristyl nicotinate was found to be compatible with each of the drugs examined when formulated together and also was shown to be photocompatible with retinoic acid. Our results suggest that the combination of myristyl nicotinate with these drugs is a feasible therapeutic development strategy.

Topics: Chemistry, Pharmaceutical; Dermatologic Agents; Humans; Hydrocortisone; Ketoconazole; Metronidazole; Niacin; Skin; Skin Diseases; Tretinoin; Triamcinolone Acetonide

Retinoids are widely used in the treatment of photoaging to stimulate dermal repair. However, retinoids also induce epidermal hyperplasia, which can lead to excessive scaling. Scaling is the major deterrent to topical retinoid therapy. Keratinocyte growth is strongly stimulated via ligand activation of EGFR. We examined regulation of EGFR ligands by retinoids and the role of EGFR in retinoid-induced hyperplasia in human skin in vivo. Topical treatment of human skin with all-trans retinoic acid (tRA) induces EGFR ligands heparin-binding (HB)-EGF and amphiregulin (AR), and reduces betacellulin mRNA levels. Laser capture microdissection-coupled real-time reverse transcription-PCR reveals that tRA increases HB-EGF mRNA throughout the epidermis, whereas AR induction is limited to basal keratinocytes. Topical tRA activates extracellular signal-regulated kinase 1/2 (Erk1/2) downstream EGFR effectors in human skin in vivo. tRA increases the soluble forms of AR and HB-EGF proteins, and induces epidermal hyperplasia, in human skin organ culture. Neutralization of HB-EGF or AR with specific antibodies strongly reduces tRA-induced epidermal hyperplasia. Finally, inhibition of EGFR activation by genistein reduces epidermal hyperplasia caused by topical retinoid treatment. These data demonstrate the central role of EGFR activation in retinoid-induced epidermal hyperplasia, and suggest that EGFR inhibitors can mitigate retinoid-induced scaling.

Topics: Amphiregulin; Antibodies; Cells, Cultured; EGF Family of Proteins; Epidermal Growth Factor; Epidermis; ErbB Receptors; Glycoproteins; Heparin-binding EGF-like Growth Factor; Humans; Hyperplasia; Intercellular Signaling Peptides and Proteins; Ligands; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Retinoids; RNA, Messenger; Skin Diseases; Tretinoin

Matrix metalloproteinase (MMP)-21 and MMP-26 (matrilysin-2) are two recently cloned epithelial metalloproteases. Here we examined their expression in various benign skin disorders, in which macrophages and fibroblasts have been implicated as well as in cultures of these cells. Expression of MMP-21 was detected by immunohistochemistry in a subset of macrophages of granulomatous skin lesions and in fibroblasts in dermatofibromas. MMP-21 mRNA was found in THP-1, U937, HEL 299 and Hs68 cells. Furthermore, MMP-21 protein was detected by immunohistochemistry in cultures of the same cell lines. In culture MMP-21 was upregulated by phorbol myristate acetate in THP-1 cells and by retinoic acid (RA) in U937 cells, and downregulated by transforming growth factor beta 1 (TGF-beta1) in HEL 299 as assessed by Taqman quantitative polymerase chain reaction (PCR). Expression of MMP-26 was detected by immunohistochemistry in granulomatous skin diseases and actinic elastosis. MMP-26 at both mRNA and protein levels was only found in HEL 299 cells. In culture it was downregulated by TGF-beta1, RA and IL-1beta as assessed by Taqman quantitative PCR. Our results suggest these two novel MMPs are not only associated with cancer but may be important in connective tissue remodelling and pathobiology of various benign skin disorders.

Topics: Cell Line; Fibroblasts; Gene Expression Regulation; Humans; Immunohistochemistry; Interleukin-1beta; Keratolytic Agents; Macrophages; Matrix Metalloproteinases, Secreted; Monocytes; RNA, Messenger; Skin Diseases; Tetradecanoylphorbol Acetate; Transforming Growth Factor beta1; Tretinoin

Topical tretinoin is used in the treatment of acne and other dermatoses. The most common side-effects are itching, dryness and reddening of the skin. We report an additional cutaneous reaction, which occurred in patients using topical tretinoin. Pyogenic granulomas developed in two patients with acne and in one with dermatofibroma following application of tretinoin. The granulomas grew on the lesions after 2-3 weeks of therapy initiation. All patients were men and the granulomas developed in their trunk. The lesions resolved when topical tretinoin was ceased. Although the number of patients reported is too small to estimate the true incidence of this reaction, it is likely that dermatologists will encounter similar reactions in patients treated with topical tretinoin for acne or other reasons.

Topics: Acne Vulgaris; Administration, Topical; Adolescent; Adult; Biopsy, Needle; Granuloma, Pyogenic; Humans; Immunohistochemistry; Keratolytic Agents; Male; Prognosis; Risk Assessment; Sampling Studies; Severity of Illness Index; Skin Diseases; Tretinoin

Topics: Chemexfoliation; Face; Humans; Keratolytic Agents; Skin Diseases; Tretinoin

Topics: Chemexfoliation; Clinical Trials as Topic; Humans; Skin Diseases; Tretinoin

Treatment of a linear verrucous epidermal nevus using topical 0.1% tretinoin cream and 5% 5-fluorouracil in a young patient is described. In 1994, successful topical therapy using this combination was described in the management of an inflammatory linear verrucous epidermal nevus. We report another case in which treatment of a noninflamed epidermal verrucous nevus with 0.1% tretinoin and 5% 5-fluorouracil resulted in significant improvement. An updated summary of the literature discussing management of epidermal nevi is presented.

Topics: Antimetabolites; Child; Drug Combinations; Fluorouracil; Hamartoma; Humans; Keratolytic Agents; Male; Skin Diseases; Tretinoin

Comedo naevi are usually well circumscribed, and although extensive cases have been reported individual lesions crossing the midline are rare. Associated neurological, skeletal and ophthalmological abnormalities are also recognized. thus, the patient now reported is unusual in that she had an extensive systematized comedo naevus with crossing of the midline but no associated abnormalities. Topical tretinoin was helpful in improving the texture and appearance of the comedones, and various larger lesions responded to curettage.

Topics: Adult; Female; Humans; Keratolytic Agents; Nevus; Skin Diseases; Tretinoin

Topics: Child; Humans; Laser Therapy; Male; Porokeratosis; Precancerous Conditions; Skin; Skin Diseases; Skin Neoplasms; Tretinoin

Topics: Female; Gels; Humans; Keratolytic Agents; Middle Aged; Ossification, Heterotopic; Remission Induction; Skin Diseases; Tretinoin

Topics: Administration, Topical; Humans; Keratinocytes; Keratolytic Agents; Retinoids; Skin; Skin Diseases; Tretinoin

Topics: Acne Vulgaris; Administration, Topical; Anti-Inflammatory Agents; Dermatology; Drug Therapy, Combination; Forecasting; Glucocorticoids; Humans; Isotretinoin; Keratolytic Agents; Prospective Studies; Retinoids; Retrospective Studies; Skin Diseases; Tretinoin

Topics: Animals; Humans; Keratolytic Agents; Retinoids; Skin; Skin Aging; Skin Diseases; Tretinoin; Vitamin A; Wound Healing

Topics: Administration, Topical; Humans; Keratolytic Agents; Severity of Illness Index; Skin Aging; Skin Diseases; Time Factors; Treatment Outcome; Tretinoin

Topics: Administration, Topical; Aged; Asia, Eastern; Asian People; Drug Evaluation; Female; Humans; Keratolytic Agents; Male; Middle Aged; Retinoids; Skin; Skin Aging; Skin Diseases; Treatment Outcome; Tretinoin

The utility of topical tretinoin in combination with sun protection has now been formally established as a useful approach to the treatment of sun-damaged skin. The early observations of our group have been confirmed in numerous well controlled clinical trials. Moreover, a great deal is known about structural and even molecular changes induced by topical tretinoin, which account for the clinical benefits achieved by this agent. A great deal has been learned in a very short period of time, and these findings represent another major use of retinoid therapy in dermatologic disease.

Topics: Administration, Topical; Humans; Keratolytic Agents; Patient Selection; Skin Diseases; Sunlight; 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

Optimization of the therapeutic ratio of analogs of the topically active 11-cis, 13-cis-12-hydroxymethylretinoic acid, delta-lactone (1) relative to antihyperproliferation and antihyperkeratinization vs. toxicity.. Nine analogs of 1, in which variations were made in the lipophilic cyclohexenyl moiety or in the lactone ring, were evaluated for topical activity against hyperkeratinization, inhibition of TPA-induced DNA synthesis and for skin irritation.. Although more potent lactones than the parent lactone 1 were identified, none possessed the favorable therapeutic ratio associated with 1.. The delta-lactone 1 possesses unique molecular features responsible for its desirable therapeutic ratio as an antihyperproliferative and antihyperkeratotic agent. In view of its very low systemic retinoid toxicity and the absence of any systemic toxicity, this lactone may be a good candidate for use in the topical treatment of acne.

Topics: Administration, Topical; Animals; Drug Evaluation, Preclinical; Keratins; Lactones; Mice; Retinoids; Skin; Skin Diseases; 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

Evaluation of 13-cis-12-substituted analogues of retinoic acid in a series of dermatologic screens has revealed that structural modifications can lead to selectivity and specificity. An analogue, 11-cis,13-cis-12-hydroxymethylretinoic acid, delta-lactone, has been found to have good activity and to be devoid of topical and systemic toxicity.

Topics: Administration, Topical; Animals; Cricetinae; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Guinea Pigs; Hypervitaminosis A; Male; Mesocricetus; Mice; Mice, Hairless; Rabbits; Skin; Skin Diseases; Structure-Activity Relationship; Tretinoin

Topics: Administration, Topical; Child; Fluorouracil; Hamartoma; Humans; Male; Neck; Occlusive Dressings; Skin Diseases; Tretinoin

Topics: Emollients; Humans; Photography; Skin Diseases; Tretinoin

Loricrin, the major component of the cornified envelope, is normally expressed in the granular layer of epidermis during the last steps of keratinocyte differentiation. Using an antiloricrin antiserum (A8-73), an increased expression of this envelope precursor was found in some disorders of hyperorthokeratosis (ichthyosiform erythroderma; lichen ruber), but not in others (keratodermia ichthyosis vulgaris). In disorders accompanied by parakeratosis, a sign of incomplete differentiation (psoriasis, prurigo nodularis) loricrin was not detected, whereas the tissue expressed filaggrin. Treatment of normal skin with retinoic acid, increasing epidermal thickness in some subjects, led to an increased expression of loricrin. Loricrin might be a useful indicator of the extent of terminal epidermal differentiation in skin disorders.

Topics: Biopsy; Filaggrin Proteins; Humans; Immunohistochemistry; Membrane Proteins; Skin Diseases; Tretinoin

We prospectively analyzed skeletal changes of 16 patients who were treated with acitretin for various disorders of keratinization at doses of 10-50 mg/day (overall mean 0.4 mg/kg/day) for 7-12 months (mean 11.4 months). Skeletal changes from pretherapy findings were observed in 5 patients. In 4 of 5 patients they appeared to be linked to a preexisting degenerative pathology and could not be attributed to acitretin therapy. However, in 1 patient a spinal osseous side effect could not be excluded. No retinoid-induced extraspinal tendon or ligament calcifications were observed.

Topics: Acitretin; Adolescent; Bone and Bones; Bone Diseases; Female; Humans; Male; Middle Aged; Prospective Studies; Skin Diseases; Spinal Diseases; Tretinoin

There is no doubt that modern retinoids are a two-edged sword. While they appear to normalize many abnormal biologic processes, i.e. modulate cellular differentiation and cellular proliferation, at the same time they can severely "abnormalize" other processes, i.e. embryonic organogenesis. Pharmaceutical ingenuity in separating their toxicity from their efficacy will determine their ultimate value to the therapist.

Topics: Cell Differentiation; Female; Humans; Pregnancy; Retinoids; Skin Diseases; Tretinoin

Topics: British Columbia; Clinical Trials as Topic; Dermatology; Histamine H1 Antagonists; Humans; Photography; Skin Aging; Skin Diseases; Tretinoin; Urticaria

Dithranol-induced skin irritation and the modulatory effects of different pharmacological agents were studied using the mouse ear model. A single topical application of dithranol caused a dose-dependent skin irritation which resulted in delayed swelling of the mouse ear with two separate peak responses, 1-2 and 6-10 days after application. The irritation was most effectively and persistently inhibited by topical treatment with corticosteroids, the free radical scavenger DL-alpha-tocopherol (DLAT) and the serotonin antagonist metergoline. The effect of corticosteroids, however, was slightly diminished during the second peak irritation. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), the dual lipoxygenase and cyclo-oxygenase inhibitor tolfenamic acid and the cyclo-oxygenase inhibitor indomethacin as well as trifluoperazine retained their inhibitory activity. Of these compounds, indomethacin was active only during the first irritation peak, NDGA during both peaks and trifluoperazine principally during the second peak. Retinoic acid did not inhibit the ear swelling. The results confirm and extend the observations that the formation of free radicals is essential for dithranol inflammation. The inflammation can also be suppressed by inhibiting the formation of arachidonic acid or its pro-inflammatory metabolites.

Topics: Administration, Topical; Adrenal Cortex Hormones; Animals; Anthralin; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Dose-Response Relationship, Drug; Ear; Edema; Female; Hyperplasia; Indomethacin; Inflammation; Masoprocol; Mice; ortho-Aminobenzoates; Skin Diseases; Time Factors; Tretinoin; Trifluoperazine

The ultrastructure of hairless mouse skin exposed to UVB radiation and followed by retinoic acid treatment was studied to identify alterations induced in both epidermis and dermis. Female mice were irradiated 3 times weekly for 5-6 months; a group of these mice was then treated topically 3 times weekly for 10 weeks with either 25 micrograms all-trans-retinoic acid dissolved in acetone or with acetone alone. Age-matched, unexposed, untreated mice served as controls. Cutaneous changes induced by UVB radiation included keratinocyte mitochondrial inclusions often accompanied by damaged cristae, duplication of basement membrane, increased number of dermal fibroblasts, inflammatory cells and elastic fibers, and abnormal elastic fibers. Subsequent retinoic acid treatment resulted in more prominent mitochondrial inclusions which sometimes coalesced to form irregular contoured bodies. Also observed were lipid droplets in the stratum corneum, glycogen deposits in keratinocytes and granular material in dilated keratinocyte endoplasmic reticulum. Poorly differentiated epidermis with necrotic or apoptotic cells was present in some specimens. Elastic fibers were fewer and usually morphologically normal. Skin exposed to UVB and treated with vehicle appeared similar to control except for the presence of excess basement membrane and occasional small mitochondrial inclusions. Because of the heightened concern regarding UV radiation-induced damage to the human skin and the current topical use of retinoids, the cutaneous changes described are considered worthy of attention.

Topics: Animals; Female; Mice; Mice, Hairless; Radiation Injuries, Experimental; Skin Diseases; Tretinoin; Ultraviolet Rays

Topics: Alopecia; Cosmetics; Dermatologic Agents; Humans; Minoxidil; Nonprescription Drugs; Photosensitivity Disorders; Skin Diseases; Tretinoin

Chronic graft-versus-host disease (GVHD) of the skin is a common complication of allogeneic bone marrow transplantation. It can be resistant to common methods of systemic immunosuppression. We report successful treatment of a patient with progressive cutaneous GVHD that was resistant to cyclosporine and steroids after allogeneic marrow transplantation for acute myelogenous leukemia using topical tretinoin (Retin-A).

Topics: Administration, Topical; Adult; Bone Marrow Transplantation; Female; Graft vs Host Disease; Humans; Skin Diseases; Transplantation, Homologous; Tretinoin

Plasma concentrations of etretinate (E), acitretin (A) and 13-cis-acitretin (13-cis A) were measured using a reverse phase HPLC assay in patients with psoriasis during 24h after the first dose (0.8 mg/kg) and after 3 weeks (group A), and in a second group with various skin diseases (B) under long-term treatment after 3 months. Group A (n = 8) showed median peak plasma concentration levels (Cmax) 578 ng/ml for E. and 161 ng/ml for A 4h after dosing (tmax). The plasma concentration profile of 13-cis A. was plateau-like with Cmax-levels of 138 ng/ml after 4 to 10 hours. In group B treated with 0.3 to 0.4 mg/kg etretinate a trend to increased Cmax-values with 123 ng/ml for E., 44 ng/ml for A. and, more pronounced, 210 ng/ml for 13-cis A. occurred (steady state). In a third group C (n = 17) it was found that after an eight month treatment free period measurements of the 13-cis A. plasma concentration are more sensitive than that of E. or A. Comparing the pharmacokinetics in two patients with the same clinical conditions under E. and A., resp., two fold higher Cmax-values of A. after A. were found than for A. after E. However, 13-cis A. values were higher after E. than after A. Our observations have shown that the metabolisation of A. to 13-cis A. may be disturbed and the clinical efficacy may appear only after dramatic increase of the oral doses. Routine monitoring of plasma concentration profiles of oral retinoids and their metabolites under short or long-term treatment enable us to early identify and understand better the so-called "non-responders", either due to a disturbed metabolism of retinoids or to non-compliance. Furthermore, monitoring of 13-cis A in plasma after cessation of treatment with E. or A. in women in childbearing age seems to be more sensitive than measurement of plasma levels of E. or A. These measurements are helpful for defining the strategy of oral retinoid therapy and for reliable information of females who wish to become pregnant after interrupting the drug.

Topics: Acitretin; Administration, Oral; Adult; Aged; Chromatography, High Pressure Liquid; Etretinate; Female; Humans; Long-Term Care; Male; Middle Aged; Psoriasis; Skin Diseases; Tretinoin

Topics: Acitretin; Aged; Drug Interactions; Etretinate; Female; Humans; Male; Middle Aged; Skin Diseases; Tretinoin

We report the case of a 50-year-old female who suffered from severe palmar and plantar pustulosis. During treatment with acitretin, a novel oral retinoid, which is the main derivative of etretinate, the patient developed a severe hepatotoxic reaction. Subsequent histological studies strongly suggested the development of liver cirrhosis. Reversible elevation of serum aminotransferase values during treatment with acitretin has been reported. However, the present observation indicates that severe hepatotoxic injury may also follow treatment with this agent.

Topics: Acitretin; Female; Humans; Liver; Liver Cirrhosis; Microscopy, Electron; Middle Aged; Skin Diseases; Tretinoin

Topics: Humans; Skin Diseases; Sunlight; Tretinoin; Ultraviolet Rays

Multiple eruptive keratoacanthoma of Witten and Zak is a rare disorder characterized by numerous small, eruptive tumors and larger, more typical keratoacanthomas. Affected patients have features of Grzybowski-type keratoacanthomas and Ferguson Smith type. Two patients with multiple keratoacanthomas were treated with oral retinoids. Both patients had hundreds of follicular papules on the trunk and extremities. Less common lesions included nodules with central horn-filled craters more characteristic of classic keratoacanthomas. Retinoid therapy resulted in regression of the larger, more typical keratoacanthomas in both patients. The small follicular keratoacanthomas remained unaffected. Thus oral retinoids are only partially beneficial for the treatment of the Grzybowski type or the Witten and Zak type of multiple eruptive keratoacanthomas.

Topics: Administration, Oral; Aged; Etretinate; Female; Humans; Keratoacanthoma; Male; Skin Diseases; Tretinoin

When cells from normal human epidermis and from the human squamous cell carcinoma line SCC-13 were seeded on floating rafts of collagen and fibroblasts, they stratified and underwent terminal differentiation. Although the program of differentiation in SCC-13 cells was morphologically abnormal, the cultures resembled normal epidermal raft cultures by expressing the terminal differentiation-specific keratins, K1/K10, and by restricting their proliferative capacity to the basal-like cells of the population. In addition, the differentiating cells of both normal and SCC-13 raft cultures expressed keratins K6 and K16, which are not normally expressed in epidermis, but are synthesized suprabasally during wound-healing and in various epidermal diseases associated with hyperproliferation. While the behavior of normal and SCC-13 rafts was quite similar when they were cultured over normal medium, significant biochemical differences began to emerge when the cultures were exposed to retinoic acid. Most notably, while the SCC-13 cultures still stratified extensively, they showed a marked inhibition of both abnormal (K6/K16) and normal (K1/K10) differentiation-associated keratins, concomitantly with an overall disappearance of differentiated phenotype. Surprisingly, the reduction in K6/K16 in retinoid-treated SCC-13 cultures was not accompanied by a decrease in cell proliferation. Using immunohistochemistry combined with [3H]thymidine labeling, we demonstrate that while the expression of K6 and K16 are often associated with hyperproliferation, these keratins are only produced in the nondividing, differentiating populations of proliferating cultures. Moreover, since their expression can be suppressed without a corresponding decrease in proliferation, the expression of these keratins cannot be essential to the nature of the hyperproliferative epidermal cell.

Topics: Blotting, Northern; Carcinoma, Squamous Cell; Cell Division; DNA; Electrophoresis, Gel, Two-Dimensional; Epidermal Cells; Epidermis; Gene Expression Regulation; Humans; Hyperplasia; Keratins; Molecular Weight; Skin Diseases; Tretinoin; Tumor Cells, Cultured

Topics: Humans; Retinoids; Skin Aging; Skin Diseases; Tretinoin

We tested the ability of all-trans-retinoic acid to prevent corticosteroid-induced skin atrophy without lessening the anti-inflammatory effect of the steroids. Histologic study and skin-fold thickness in hairless mice treated topically with various steroids, followed by topical all-trans-retinoic acid, were used to measure prevention of atrophy. By both assessments, all-trans-retinoic acid prevented atrophy. Noninterference with the anti-inflammatory property of steroids was tested in a phorbol ester-induced mouse ear edema model and by histologic assessment of croton oil-induced inflammation of mouse dermis. We found that all-trans-retinoic acid did not interfere with steroid suppression of either edema or dermal inflammation. Thus all-trans-retinoic acid was effective in preventing steroid-induced atrophy without affecting the steroid's anti-inflammatory property.

Topics: Administration, Topical; Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Female; Inflammation; Mice; Skin Diseases; Steroids; Tretinoin

The hairless mouse is proving to be a relevant model for the systematic study of photoaging. As in humans, with chronic ultraviolet radiation, these mice develop elastic fiber hyperplasia, followed by elastosis and ultrastructural degradation. Collagen is damaged and its metabolism is altered, while the normally low levels of proteoglycans and glycosaminoglycans are greatly increased. With this model we have described the effects on dermal connective tissue of UVB (290 to 320 nm), UVA (320 to 400 nm), and the combination of the two. We have also assessed the protective effects of sunscreens. We found that a significant amount of photodamage was repaired when ultraviolet radiation was stopped. Subepidermally in a former region of elastosis, a band of new normal dermis was laid down. Enhancement of the repair was achieved with topical all-trans-retinoic acid in a time- and dose-dependent manner. Retinoic acid was also found to induce angiogenesis in unirradiated mice.

Topics: Aging; Animals; Disease Models, Animal; Mice; Mice, Hairless; Skin; Skin Diseases; Sunscreening Agents; Tretinoin; Ultraviolet Rays

Topical tretinoin (Retin-A) enhances the appearance of photoaged skin by effacing fine wrinkles, bleaching pigmented "age spots," improving surface texture, and inducing a rosy glow. A media blitz about Retin-A has resulted in a rush of patients to physicians, many of whom have had little experience with this drug. As a result, many patients receive too little information and often improper instructions regarding the best way to apply tretinoin. Misuse and misconceptions are common. Tretinoin is not a cosmetic preparation to be applied according to individual whims. Patients require detailed instructions to obtain maximal benefits, as well as an appreciation of the time frame for these to appear. This article presents current guidelines for the proper use of Retin-A.

Topics: Aging; Humans; Patient Education as Topic; Skin Diseases; Sunscreening Agents; Tretinoin; Ultraviolet Rays

We evaluated the effects of long- and short-term isotretinoin therapy on the skeletons of patients. Eight patients who were treated with isotretinoin for disorders of keratinization received frequent radiographic evaluations for 4 to 9 years. Seven patients developed multiple hyperostoses at the spine and extremities. Hyperostoses increased in size and number over the course of therapy, although relatively few sites were symptomatic. Hyperostoses typically developed first in the spine and later in the extremities, where both bilaterally symmetric and asymmetric involvement was observed. After 5 years of therapy one patient did not develop hyperostosis. In a group of nine patients who received a relatively high dose of isotretinoin in 1982 for the treatment of acne, two patients developed tiny, asymptomatic hyperostoses. One patient had hyperostoses 1 year after isotretinoin therapy, which remained unchanged 3 years later, whereas the other patient had one hyperostosis 4 years after therapy had been stopped. Although we suspect that these hyperostoses were retinoid induced, they should not be of concern for the patient needing routine isotretinoin therapy for the treatment of cystic acne.

Topics: Acne Vulgaris; Adolescent; Adult; Bone Diseases; Child; Female; Follow-Up Studies; Humans; Ichthyosis; Isomerism; Isotretinoin; Male; Radiography; Skin Diseases; Spinal Diseases; Time Factors; Tretinoin

The major plasma metabolite of acitretin (trans-acitretin) is its 13-cis isomer, cis-acitretin. Interconversion of cis-acitretin to trans-acitretin was demonstrated in man following administration of a single oral dose of cis-acitretin. Plasma concentrations of Ro 13-7652 (cis-acitretin) and Ro 10-1670 (trans-acitretin) were much higher after cis-acitretin administration than after trans-acitretin administration. Surprisingly, these high concentrations were not associated with a clear therapeutic effect in dermatoses (e.g. psoriasis) which are usually responsive to oral retinoids. Interactions between the cis and trans isomers formed in vivo may explain the difference in therapeutic activity of each stereoisomer when administered orally.

Topics: Acitretin; Adult; Aged; Animals; Biotransformation; Dermatitis; Female; Half-Life; Humans; Male; Middle Aged; Psoriasis; Rats; Skin Diseases; Stereoisomerism; Tretinoin

Topics: Child; Etretinate; Humans; Isotretinoin; Retinoids; Skin Diseases; Teratogens; Tretinoin

Topics: Adult; Aged; Aging; Humans; Middle Aged; Skin Diseases; Sunlight; Tretinoin

Topics: Aspirin; Humans; Myocardial Infarction; Skin Diseases; Tretinoin

The characteristics of chronologically aged skin should be differentiated from the features of photoaging, which is marked by yellowed, leathery, sagging, wrinkled, elastic skin, as well as underlying connective tissue damage and various benign, premalignant, and malignant neoplasms. Laboratory experiments with the hairless mouse exposed to varying doses of ultraviolet radiation have demonstrated the protective effects of sunscreens, the repair of ultraviolet damage when the skin is no longer bombarded by photons, and the enhancement of that repair by retinoids.

Topics: Aging; Animals; Humans; Mice; Mice, Hairless; Skin; Skin Diseases; Sunlight; Sunscreening Agents; Tretinoin; Ultraviolet Rays

Topics: Acne Vulgaris; Etretinate; Humans; Isotretinoin; Keratins; Papillon-Lefevre Disease; Skin Diseases; Tretinoin

Thirty patients, 13 female and 17 male, have been followed from 3 months to 22 years (mean, 81 months; median, 63 months) and special studies have been performed on a proportion of these in order to try to predict malignant evolution. Age at onset was from 20 to 70 years (mean, 43 years; median, 42 years). Duration of disease was from 1 to 30 years (mean, 119 months; median 161 months). Seven patients also had parapsoriasis en plaque or plaque-stage mycosis fungoides at the time of diagnosis and one patient had erythroderma. None of the 22 uncomplicated lymphomatoid papulosis patients developed malignant cutaneous lymphoma during the period of observation, while the remaining 8 patients who had concurrent parapsoriasis en plaque, mycosis fungoides, or erythroderma did not deteriorate further. Single-cell deoxyribonucleic acid (DNA) measurements on the dermal infiltrate were done in 13 patients and were abnormal in 7 patients. Two of these had greatly abnormal DNA histograms and at the same time an abnormal clinical presentation with multiple nodules and tumors. The remaining five patients had DNA histograms that indicated a potential for malignancy. Monoclonal antibody studies were performed on skin biopsy specimens of 10 patients. The dermal infiltrate was dominated by T-helper lymphocytes and some Hodgkin and Reed-Sternberg cells could be detected by the antibodies Ki-1, Ki-24, and Ki-27. Human T-lymphotropic virus type I (HTLV-I) antibodies were found in 3 of 18 patients examined. Treatment with psoralens plus ultraviolet A (PUVA) was effective (partial or complete remission) in six patients but they relapsed at cessation of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Viral; Deltaretrovirus; Deltaretrovirus Antibodies; DNA; Female; Follow-Up Studies; Humans; Isotretinoin; Male; Methotrexate; Middle Aged; Precancerous Conditions; PUVA Therapy; Skin Diseases; Skin Neoplasms; Tretinoin

The effect of oral isotretinoin (13-cis-retinoic acid) on in vivo chemotactic responses was studied longitudinally in 7 patients with cystic acne. As measured in a microchamber chemotaxis assay, both monocyte and neutrophil chemotaxis were inhibited 98% (p less than 0.001) during isotretinoin treatment. In vivo chemotactic responses returned to normal within 2 months of cessation of treatment. Biopsies of skin chamber sites from patients on isotretinoin showed no significant dermal or epidermal leukocytic accumulation in response to autologous zymosan-activated serum, whereas chambers from controls showed extensive neutrophilic infiltrates even in the epidermis. In contrast, in vitro chemotactic responses of neutrophils and monocytes from patients on isotretinoin were not diminished. Sera and plasma from patients on isotretinoin contained no inhibitors of chemotaxis, and activated sera from these patients were excellent attractants for normal monocytes. We postulate that isotretinoin produces significant anti-inflammatory effects by inhibition of monocyte and neutrophil chemotaxis across intact biologic barriers in vivo.

Topics: Acne Vulgaris; Chemotaxis; Chemotaxis, Leukocyte; Cysts; Humans; Isotretinoin; Monocytes; Neutrophils; Skin Diseases; Tretinoin

A case of excess granulation tissues in a patient treated with isotretinoin by a severe cystic acne is reported. Other cases described in the literature are reviewed.

Topics: Acne Vulgaris; Adolescent; Granulation Tissue; Granuloma; Humans; Isotretinoin; Male; Skin Diseases; Tretinoin

Using the sebum-absorbent tape technique, we have disclosed five different patterns of follicular sebum excretion rate (SER). These are the infantile, pubertal, acne, adult and aging patterns, distinguished by different densities of active sebaceous follicles, by distinct levels of follicular SER and by the relative stability in time of the overall SER.

Topics: Acne Vulgaris; Adolescent; Adult; Aged; Aged, 80 and over; Aging; Benzoyl Peroxide; Child; Child, Preschool; Cytodiagnosis; Hair; Humans; Image Processing, Computer-Assisted; Infant; Isotretinoin; Middle Aged; Sebaceous Glands; Sebum; Skin Diseases; Tretinoin

The roentgenographic changes noted in 13 patients, who had been treated with long-term 13-cis-retinoic acid for inherited scaling disorders, are presented. These patients were aged 13-16 years and had received this therapy for 16-87 months (mean, 58 months). The most pronounced abnormality was osteophyte formation, particularly in the cervical spine. Other changes which were noted included ossification of the anterior longitudinal and atlanto-occipital ligaments, proliferative enthesopathies, diminished bone density, premature fusion of epiphyses, and modeling abnormalities. Six of the 13 patients were asymptomatic and the osseous manifestations of this therapy were identified only by roentgenographic evaluation.

Topics: Adult; Bone Diseases; Bone Diseases, Metabolic; Child; Child, Preschool; Epiphyses; Female; Humans; Male; Middle Aged; Ossification, Heterotopic; Radiography; Skin Diseases; Spinal Osteophytosis; Time Factors; Tretinoin

We report the case of a young man with extreme sebaceous gland hyperplasia that occurred in a diffuse pattern of aggregated papular lesions involving the entire face, neck and upper chest, together with marked seborrhoea oleosa. Oral therapy with 13-cis-retinoic acid (isotretinoin) resulted in remarkable improvement within a few weeks. Parallels from our case are drawn to familial sebaceous hyperplasia, reported by Dypre et al. in 1980 [6], and to a case of a young man with severe sebaceous gland hyperplasia and facial seborrhoea, reported by de Villez et al. in 1982. We suggest that these types of seboglandular proliferative disorders be classified as diffuse (presenile) sebaceous gland hyperplasia in contrast to the well-defined senile circumscribed variant, and that they be regarded as a separate entity.

Topics: Adult; Humans; Hyperplasia; Isotretinoin; Male; Sebaceous Glands; Skin Diseases; Tretinoin

Topics: Cysts; Humans; Isotretinoin; Skin Diseases; Tretinoin

Retinoids are vitamin A derivatives that have therapeutic benefit in the treatment of hyperkeratotic genodermatosis, psoriasis, and acne. Isotretinoin (Accutane), a first-generation retinoid, is used in the treatment of cystic acne. Etretinate (Tegison), a second-generation retinoid, is used in the treatment of severe psoriasis. Third-generation drugs are currently being tested. Side effects and long-term toxicity are of concern. Etretinate in combination with ultraviolet B and psoralen-ultraviolet A (PUVA) is especially beneficial in the treatment of psoriasis.

Topics: Etretinate; Humans; Isotretinoin; Retinoids; Skin Diseases; Tretinoin

A 20-year old man with steatocystoma multiplex and pseudofolliculitis barbae was treated unsuccessfully with oral isotretinoin. Consistent with findings from previous reports, treatment with isotretinoin should be reserved for patients with steatocystoma multiplex suppurativum.

Topics: Adult; Epidermal Cyst; Folliculitis; Humans; Isomerism; Isotretinoin; Male; Skin Diseases; Tretinoin

We have previously found an important increase of cellular retinoic acid-binding protein (CRABP) in psoriatic plaques whereas the cellular retinol-binding protein (CRBP) was not elevated compared to normal human skin and nonlesional psoriatic skin. In the present study we analyzed CRABP and CRBP levels in a panel of dermatoses in order to address several questions raised by the above findings. Three observations were made: CRBP showed little or no variations whereas CRABP was either normal (seborrheic keratosis, lichenification, nonlesional psoriatic and nonlesional Darier disease skin) or elevated (psoriatic plaques, lamellar ichthyosis, lesional Darier disease, pityriasis rubra pilaris, keratosis pilaris); high levels of CRABP might indicate a greater sensitivity of the lesions to systemic synthetic retinoids with a carboxyl group in the C15 position, and systemic administration of etretin increased the levels of CRABP but not CRBP. These observations suggest that CRABP might be the receptor for synthetic retinoids in the skin and that its analysis might be useful in monitoring retinoid therapy.

Topics: Acitretin; Adsorption; Carrier Proteins; Charcoal; Chromatography, Gel; Dextrans; Female; Humans; Male; Psoriasis; Receptors, Retinoic Acid; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Skin; Skin Diseases; Tretinoin

Four weeks after the introduction of a therapeutic regimen with 80 mg 13-cis-retinoic acid/day, a 16-year-old male patient developed oozing hypergranulation with vulnerable masses within acne lesions. These local symptoms were accompanied by fever, fatigue, weight loss, polyarthralgia and myalgia, similar to acne fulminans. In spite of these unusual reactions treatment was continued. Local steroid ointments were additionally applied. Within a short period of time regression of granulations and normalization of the general health condition was observed. After 4 months, therapy was discontinued. The patient's acne had totally healed and did not relapse within an observation period of 2 years.

Topics: Acne Vulgaris; Administration, Topical; Adolescent; Granulation Tissue; Granuloma; Humans; Isotretinoin; Male; Skin Diseases; Tretinoin; Wound Healing

Topics: Acne Vulgaris; Humans; Isomerism; Isotretinoin; Skin Diseases; Teratogens; Tretinoin

Topics: Adult; Humans; Isotretinoin; Male; Middle Aged; Papillomaviridae; Skin Diseases; Tretinoin; Tumor Virus Infections

A patient with steatocystoma multiplex (SM) with severe inflammation was treated with oral isotretinoin. Inflamed cysts markedly improved with treatment. However, after eight weeks of therapy, many pre-existing cysts rapidly enlarged and new cysts occurred. Therapy was then discontinued. Isotretinoin may have exacerbated or worsened this condition.

Topics: Adult; Cysts; Female; Humans; Isotretinoin; Skin Diseases; Tretinoin

Topics: Abnormalities, Drug-Induced; Etretinate; Female; Humans; Infant, Newborn; Isotretinoin; Pregnancy; Retinoids; Skin Diseases; Teratogens; Tretinoin

Topics: Endocarditis, Bacterial; Epidermis; Humans; Isomerism; Isotretinoin; Retinoids; Risk; Skin; Skin Diseases; Tretinoin

Isotretinoin, a synthetic retinoid that has been prescribed for over 500,000 patients with cystic acne, has been associated with both spinal hyperostosis and a disorder similar to diffuse idiopathic skeletal hyperostosis. We describe a syndrome of tendon and ligament calcification, primarily in extraspinal locations, that we have observed after long-term therapy for psoriasis and disorders of keratinization with etretinate, another synthetic retinoid. Of 38 patients who had received etretinate (average dose, 0.8 mg per kilogram of body weight per day; average duration, 60 months), 32 (84 percent) had radiographic evidence of extraspinal tendon and ligament calcification. The most common sites of involvement were the ankles (29 patients [76 percent]), pelvis (20 patients [53 percent]), and knees (16 patients [42 percent]); spine involvement was uncommon in this group of etretinate-treated patients. Involvement tended to be bilateral and multifocal. Fifteen (47 percent) of the 32 affected patients had no bone or joint symptoms at the sites of radiographic abnormality. Thus, tendon and ligament calcification can occur without vertebral involvement as well as in association with it (for example, as part of the spectrum of diffuse idiopathic skeletal hyperostosis). We have identified extraspinal tendon and ligament calcification as a toxic effect that is commonly associated with long-term etretinate therapy.

Topics: Adult; Aged; Calcinosis; Etretinate; Female; Humans; Isotretinoin; Knee Joint; Ligaments; Lupus Erythematosus, Systemic; Male; Middle Aged; Pelvis; Prospective Studies; Psoriasis; Radiography; Skin Diseases; Spinal Diseases; Tendons; Tretinoin

A patient with multiple keratoacanthomas was successfully treated with oral isotretinoin. The treatment resulted in clearing of existing keratoacanthomas and prevented the development of new lesions. An induction dose of 1.5 mg/kg/day was necessary to initiate the response. This is the third report of successful treatment of multiple keratoacanthomas with isotretinoin.

Topics: Administration, Oral; Adult; Humans; Isotretinoin; Keratoacanthoma; Male; Skin; Skin Diseases; Tretinoin

Topics: Etretinate; Humans; Isotretinoin; Killer Cells, Natural; Skin Diseases; Tretinoin

The vitamin A acid story began when topical application of vitamin A (retinol) produced no therapeutic results in dyskeratotic conditions. It was logical to try metabolites of retinol topically. I published results of studies in 1962 that showed that topical tretinoin was beneficial in ichthyosis, actinic keratoses, and other hyperkeratotic conditions. It was reported in 1969 that topical tretinoin was effective in acne vulgaris, principally by preventing and dislodging comedones. It was subsequently demonstrated that tretinoin produced a distinctive kind of hyperplasia of human epidermis that was associated with early shedding of horny cells. Knowledge that the keratinization process was being profoundly altered stimulated interest in synthesizing retinol derivatives (retinoids) that could be administered orally. The development of 13-cis-retinoic acid was an outcome of this interest, a compound that astonished dermatologists by often producing permanent clearing of acne conglobata. The antitumor effects of tretinoin were already demonstrated by 1974, when it was shown to cause regression in many basal cell cancers. Today the cancer chemopreventive capability of retinoids is being intensively investigated in various organs. An international symposium held in Flims, Switzerland in 1975 demonstrated keen awareness of the therapeutic potential of tretinoin and the rapid growth of basic knowledge of the pharmacology of retinoids. From extensive clinical experience new applications for topical tretinoin came to light, ranging from the treatment of flat warts, lichen planus, and Darier's disease, and most recently in retarding photoaging. Perhaps for the first time in history, dermatologists can take credit for pioneering a drug development program that has had a profound influence on medical practice.

Topics: Germany, West; History, 20th Century; Humans; Skin Diseases; Tretinoin

A total of 261 adverse ocular reactions occurred in 237 patients who received isotretinoin, a commonly used drug in the treatment of severe cystic acne. Blepharoconjunctivitis, subjective complaints of dry eyes, blurred vision, contact lens intolerance, and photodermatitis are reversible side effects. More serious ocular adverse reactions include papilledema, pseudotumor cerebri, and white or gray subepithelial corneal opacities; all of these are reversible if the drug is discontinued. Reported cases of decreased dark adaptation are under investigation. Isotretinoin is contraindicated in pregnancy because of the many reported congenital abnormalities after maternal use (including microphthalmos, orbital hypertelorism, and optic nerve hypoplasia).

Topics: Acne Vulgaris; Cataract; Conjunctivitis; Cysts; Eye; Eye Diseases; Eyelid Diseases; Humans; Inflammation; Isotretinoin; Photosensitivity Disorders; Skin Diseases; Tretinoin; Vision Disorders

Hyperplasia of sebaceous glands is a common cause of papulonodular facial lesions that occur in middle-aged and older patients. Recently, several cases of premature sebaceous gland hyperplasia have been reported. In these patients the lesions had persisted despite vigorous attempts at therapy. We present a case of premature sebaceous gland hyperplasia that was successfully treated with isotretinoin.

Topics: Adult; Dermatologic Agents; Humans; Hyperplasia; Isotretinoin; Male; Sebaceous Glands; Skin Diseases; Tretinoin

The neutrophil function and plasma leukotactic activity of a patient with Sweet's syndrome and cystonodular acne were evaluated during a 2 1/2-year period. These studies demonstrated that chemotaxis was frequently slightly increased, especially during an exacerbation of Sweet's syndrome, but showed some decrease during isotretinoin therapy. Other functions, such as phagocytosis, metabolic activation, and bacterial killing, also were slightly increased. In addition, the patient's serum contained a heat-stable, nonlipid chemoattractant that was present at all times except during a course of isotretinoin. Although his symptoms responded to aspirin, the plasma continued to show this chemoattractant. These findings are consistent with the hypothesis that excess chemoattractant in Sweet's syndrome attracts neutrophils, which then mediate an inflammatory response. In addition, aspirin may be used to control Sweet's syndrome symptoms, although it does not suppress the plasma chemoattractant.

Topics: Adult; Aspirin; Chemotaxis, Leukocyte; Dialysis; Hot Temperature; Humans; Isotretinoin; Leukocytosis; Male; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Pentose Phosphate Pathway; Phagocytosis; Plasma; Skin Diseases; Syndrome; Tretinoin; Zymosan

Grover's disease (transient acantholytic dermatosis; TAD), a disorder of unknown etiology, may resemble Darier's disease and frequently resists conventional therapies. The lesions can be extensive and pruritus can be a prominent feature. Four patients with Grover's disease were treated with isotretinoin. Three patients with relatively acute disease responded with remissions of up to 10 months after treatment. One patient with disease of 8 months' duration obtained partial relief but experienced a relapse when medication was stopped.

Topics: Acantholysis; Female; Humans; Isotretinoin; Male; Middle Aged; Skin Diseases; Tretinoin

Topics: Etretinate; Humans; Isotretinoin; Psoriasis; PUVA Therapy; Retinoids; Skin Diseases; Tretinoin

Disseminated granuloma annulare is often a chronic disorder that may prove refractory to treatment and lead to prolonged cosmetic disfigurement. In a patient with disseminated granuloma annulare that was unresponsive to multiple therapeutic regimens, administration of isotretinoin resulted in rapid clearing of nearly all lesions. To our knowledge this is the first reported case in which this agent was used to treat disseminated granuloma annulare.

Topics: Female; Granuloma; Humans; Isotretinoin; Middle Aged; Skin; Skin Diseases; Tretinoin

Topics: Child; Humans; Isotretinoin; Male; Skin Diseases; Syndrome; Tretinoin

Peripheral blood natural killer (NK) cell activity was screened in patients with non-malignant disorders of the skin who took oral etretinate or 13-cis-retinoic acid for up to 11 months. Compared to pretreatment values, the basic NK activity rose during the first 2 months of treatment, but thereafter returned to starting values. Interferon reactivity (IFN-alpha, IFN-gamma) was essentially unaltered by the treatment. It is concluded that moderate oral retinoid doses cause a mild, transient stimulation of this natural immune surveillance system in man.

Topics: Administration, Oral; Adult; Aged; Etretinate; Female; Humans; Isotretinoin; Killer Cells, Natural; Male; Middle Aged; Skin Diseases; Stimulation, Chemical; Tretinoin

Isotretinoin is remarkably effective in the treatment of severe cystic acne, however, many complications have been observed during treatment and new toxic effects have been reported. Hypertriglyceridemia associated with decreases in high density lipoprotein (HDL) cholesterol has occurred in 25 percent of patients and requires monitoring during treatment. Painful erosions with granulation tissue recently have been reported in patients with severe acne. Other complications have included corneal opacities, pseudotumor cerebri, hypercalcemia, photosensitivity reactions, abnormal liver function tests, and skeletal hyperostosis. Isotretinoin is teratogenic and should be avoided during pregnancy. With the increasing acceptance and use of isotretinoin for cystic acne, as well as related disorders (inflammatory papulopustular acne with scarring, gram-negative folliculitis, and acne rosacea), a reevaluation of isotretinoin aimed at reducing complications is in order. Patient selection criteria and guidelines directed at reducing these complications are presented.

Topics: Acne Vulgaris; Female; Humans; Isotretinoin; Mucous Membrane; Pregnancy; Skin Diseases; Teratogens; Tretinoin; Triglycerides

Topics: Acne Vulgaris; Adolescent; Chronic Disease; Follow-Up Studies; Granuloma; Humans; Isotretinoin; Male; Skin Diseases; Tretinoin

Topics: Acne Vulgaris; Humans; Isotretinoin; Retinoids; Skin Diseases; Tretinoin

The authors have studied--in the plasma--the changes of zinc, retinol binding protein (RBP), retinol and retinoic acid with reference to the dermatological status of fifty chronically haemodialysed renal insufficiency patients divided into four subgroups (normal skin, dry skin, dry skin with keratosis, and only keratosis). The results of these groups were compared to those of thirty healthy subjects. The values of these variables do not show any significant difference in function of the dermatological subgroups; but, despite the considerable rise in the retinol binding protein and retinol levels in comparison with the controls (haemodialysis patients: RBP = 11.77 +/- 2.83 mumol X l(-1), retinol = 7 +/- 2.57 mumol X l(-1); controls; RBP = 2.76 +/- 0.62 mumol X l(-1), retinol = 2.16 +/- 0.53 mumol X l(-1] the electromicroscopic examination of skin biopsy samples from some of the patients did not reveal any sign of hypervitaminosis A in the lesions.

Topics: Humans; Hypervitaminosis A; Keratosis; Renal Dialysis; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Skin; Skin Diseases; Tretinoin; Vitamin A; Zinc

Topics: Animals; Etretinate; Humans; Isotretinoin; Mice; Rabbits; Rats; Retinoids; Skin Diseases; Tretinoin

Topics: Adolescent; Granuloma; Humans; Isomerism; Isotretinoin; Male; Paronychia; Skin Diseases; Tretinoin

Frequent symptoms of back and neck stiffness led to a radiographic investigation of the vertebral spine in patients receiving synthetic retinoids, isotretinoin and etretinate. X-ray examination of fifty patients with various skin disorders who received retinoids for at least 2 years were compared with seventy-two age- and sex-matched untreated patients. Differences in frequencies of defined abnormalities, which included anterior spinal ligament calcification and presence of osteophyte at two or more vertebral levels in the absence of joint space narrowing, were determined for treated and untreated patients. When the entire group of treated patients was compared with the entire group of those untreated, no statistically significant differences were observed. When only patients with basal cell nevus syndrome ( BCNS ) or basal cell carcinoma (BCC) who had never received retinoid were compared with those who received isotretinoin, the frequency of the defined abnormalities was significantly higher in the treated group (P less than 0.01). This study suggests that the ingestion of isotretinoin at mean total dose of 150,060 mg for an average of 2.9 years is associated with a statistically significant increase in developing an associated ossifying diathesis in patients with BCNS or BCC, when compared with matched, untreated controls.

Topics: Adult; Calcinosis; Dose-Response Relationship, Drug; Etretinate; Female; Humans; Isotretinoin; Male; Middle Aged; Radiography; Skin Diseases; Spinal Diseases; Spinal Osteophytosis; Spine; Tretinoin

The effects of four retinoids, all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), aromatic retinoid, and arotinoid ethyl ester ( arotinoid ) were examined on the skin of the rhino mouse. Rhino mouse skin is characterized by the presence of keratin-containing utricles attached to the epidermis, and subcutaneous cysts, both of which are derived from hair follicles. The utricles were examined in horizontal sheets of epidermis, and in vertical histologic sections. After applications of 0.1 ml of 0.1% RA, 0.1% 13-cis-RA, 0.1% aromatic retinoid, or 0.001% arotinoid in acetone to the dorsal skin for 5 days a week for 2 weeks, there was a reduction of utricle diameter to 45%, 52%, 30%, and 31% of acetone-treated controls, respectively. Histologic examination of the epidermis revealed that a dose-dependent hyperplasia and thickening of the epidermis and the stratum granulosum was induced by the retinoids when given at subtoxic doses, being most marked after arotinoid or RA. The thickness of the walls of the utricles also increased with increasing dose of retinoid, paralleling the changes in the epidermis. After doses of 0.1% RA and 0.001% arotinoid , the utricles resembled the hair follicles of hairless mice. Hyperplasia of the epidermis appears to be a primary effect of retinoids or rhino mouse skin. Hyperproliferation of the utricle wall is accompanied by a reduction in the size of the utricle lumen, preceding eventual differentiation of the utricles to normal-looking pilar units.

Topics: Animals; Benzoates; Dermatologic Agents; Etretinate; Isomerism; Isotretinoin; Keratolytic Agents; Mice; Mice, Mutant Strains; Retinoids; Skin; Skin Diseases; Tretinoin

Two cases of diffuse multiple lesions of sebaceous hyperplasia of the face are reported. The results of both medical and surgical therapies had been unsatisfactory. The patients were treated with low dose systemic isotretinoin (13-cis-retinoic acid) which resulted in complete clearing in one case and substantial clearing in the second. We suggest that in those patients cosmetically bothered by diffuse multiple lesions of sebaceous hyperplasia, for which other therapies are unsuccessful or unamenable to the patient, isotretinoin offers a safe, rational therapeutic option.

Topics: Aged; Facial Dermatoses; Humans; Hyperplasia; Isotretinoin; Male; Middle Aged; Sebaceous Glands; Skin Diseases; Tretinoin

An 83-year-old woman with multiple squamous cell carcinomas and keratoacanthomas of the legs was treated with orally administered isotretinoin (13 cis-retinoic acid). Complete regression of the tumors was noted during the initial six-month treatment period. In the subsequent 36 months, four new cutaneous tumors were excised. There have been no recurrences of lesions that regressed while the patient was receiving retinoid therapy.

Topics: Administration, Oral; Aged; Carcinoma, Squamous Cell; Female; Humans; Isotretinoin; Keratoacanthoma; Leg; Skin Diseases; Skin Neoplasms; Tretinoin

A patient with steatocystoma multiplex with multiple ruptured draining cysts and abscesses was treated with a twenty-week course of isotretinoin. Abscesses involuted and inflamed cysts shrank. The remission persisted for ten weeks after discontinuing therapy; subsequently cysts and abscesses occurred in multiple sites.

Topics: Adult; Epidermal Cyst; Humans; Isotretinoin; Male; Skin Diseases; Tretinoin

Topics: Chemical Phenomena; Chemistry; Humans; Isotretinoin; Neoplasms; Precancerous Conditions; Retinaldehyde; Skin Diseases; Tretinoin; Vitamin A; Vitamin A Deficiency

13-cis-Retinoic acid (Accutane) is an effective new agent for the treatment of severe cystic acne. The most encouraging feature associated with use of this drug is the persistence of remissions even after administration has been discontinued. The cutaneous side effects are mild to moderate and are usually well tolerated. Careful monitoring of the serum lipids is necessary. In 4 of our 10 patients, the levels of triglycerides became elevated. Of these four patients, three had lowering of the high-density lipoprotein fraction. In three of our most severely affected patients, nonhealing erosions with heaped-up granulation tissue developed at the sites of large acne cysts, which healed promptly after therapy was completed. For the present, we emphasize that use of Accutane should be reserved for severe acne that is unresponsive to conventional treatment; in such cases, careful clinical and laboratory monitoring is imperative.

Topics: Acne Vulgaris; Adolescent; Adult; Animals; Humans; Isotretinoin; Male; Rabbits; Rats; Skin Diseases; Tretinoin; Triglycerides

Synthetic and natural retinoids were analysed in epidermis, dermis, subcutis and serum of twenty-seven patients treated with etretinate (0.6-1.0 mg/kg/day) for 1-36 months. The concentrations of etretinate (including its major metabolite) in serum and normal-appearing epidermis were 150-600 ng/ml and 50-350 ng/g, respectively. The serum and epidermal values were significantly correlated (P less than 0.05). The drug progressively accumulated in the subcutis attaining a maximum value of 15,500 ng/g. After the treatment, etretinate disappeared from the epidermis within 1 week. By contrast, the drug remained in the subcutis for several months after cessation of treatment. The epidermal composition of endogenous retinoids changed during etretinate therapy as reflected in an increased ratio of 3-dehydroretinol to all-trans retinol.

Topics: Acitretin; Adipose Tissue; Adolescent; Adult; Aged; Biological Availability; Child; Etretinate; Female; Humans; Male; Middle Aged; Skin; Skin Diseases; Tretinoin

In our clinical trials of isotretinoin therapy for cystic acne and etretinate treatment of psoriasis, eight patients had growth of excessive granulation tissue. The granulation tissue was found in resolving acne lesions in one patient taking isotretinoin. Among the psoriatic patients taking etretinate, the granulation tissue usually was seen adjacent to nail plates. In two patients, the side effect caused them to stop retinoid therapy. The tissue response did not appear to be related to the daily or cumulative retinoid dose.

Topics: Acne Vulgaris; Adolescent; Adult; Aged; Granulation Tissue; Granuloma; Humans; Isotretinoin; Male; Middle Aged; Psoriasis; Skin Diseases; Tretinoin

The naturally occurring retinoids (vitamin A alcohol = retinol and all-trans-retinoic acid) have been largely replaced by synthetic retinoids in recent years as systemic drugs for use in dermatology. At the present time, two synthetic retinoids are commercially available: etretinate (Tigason) and isotretinoin (Accutane). These compounds-which have a more favourable therapeutic index than the naturally occurring retinoids-ushered in a new era of dermatological therapy by their potent antikeratinizing, antiseborrhoeic (only isotretinoin) and antineoplastic action. The broadest indications for the use of these retinoids are psoriasis (etretinate) and cystic acne (isotretinoin), whereas the most dramatic effects are encountered in a number of severe ichthyosiform disorders. Another important, although at present not clearly defined role of the retinoids is in the prophylaxis of skin tumours.

Topics: Acne Vulgaris; Etretinate; Humans; Ichthyosis; Isotretinoin; Psoriasis; Retinoids; Skin Diseases; Skin Neoplasms; Tretinoin

A patient with chronic cutaneous and pulmonary sarcoidosis, unresponsive to oral corticosteroid therapy, was treated with isotretinoin. The patient's cutaneous manifestations of sarcoidosis showed consistent improvement during the course of retinoid therapy. The lesions that responded earliest either resolved or showed the greatest reduction in size. The patient's WBC count increased and her angiotensin-converting enzyme level decreased during the first two months of isotretinoin therapy; both returned to pretreatment levels during the third month of therapy. Pulmonary function tests were unchanged after four months of treatment. Isotretinoin may be a useful therapeutic agent for cutaneous sarcoidosis. However, the possibility of spontaneous remission of the disease during the course of therapy cannot be excluded.

Topics: Adult; Female; Humans; Isotretinoin; Sarcoidosis; Skin; Skin Diseases; Time Factors; Tretinoin

Topics: Etretinate; Humans; Isotretinoin; Keratosis; Psoriasis; Skin; Skin Diseases; Tretinoin

Topics: Etretinate; Humans; Ichthyosis; Psoriasis; Skin Diseases; Tretinoin

Persisting human papilloma virus (HPV) 2 induced common warts of a chronic lymphatic leukemia patient were orally treated with aromatic retinoid Ro 10-9359 (Tigason). Clinically, the lesions improved rapidly. Virus-specific cytopathogenic effects (CPE), virus particles and viral DNA were no longer detectable. Therapy was discontinued because of the development of a liposarcoma, which led to a complete relapse of the cutaneous lesions. HPV-2 specific parameters, CPE and viral DNA, were restored. Comparison of the restriction enzyme cleavage patterns revealed that warts before and after therapy contained the same HPV-2 subtype. The implications of the observation on the effect of Tigason on virus-induced papillomas are discussed.

Topics: Administration, Oral; Aged; Etretinate; Hand; Humans; Leukemia, Lymphoid; Male; Skin Diseases; Tretinoin; Warts

59 patients with keratinisation diseases have been received RO 10 9359. There is a clinical medicum tolerance. Biologic controls have been carried out before and after a 3 month treatment. There is a good biological tolerance for the hematopoietic, glucidic, renal and thyroid functions. Thus the hepatic tolerance is poor for the patients with a predisposition for hepatic diseases (plethorics, alcoholics).

Topics: Carotenoids; Etretinate; Hematopoiesis; Humans; Kidney; Skin Diseases; Thyroid Gland; Tretinoin

A trial of etretinate (Tigason) for keratinizing disorders of the skin yielded prolonged improvements beyond any results hitherto obtained. The disorders included psoriasis of severe degree, keratosis obturans, ichthyosis vulgaris, follicular ichthyosis, porokeratosis of Nékam, disseminated superficial actinic porokeratosis. Darier's disease, palmoplantar keratoderma, Oudtshoorn disease, lamellar ichthyosis, 'badpak' ichthyosis, epidermolytic hyperkeratosis, the 'half-baby' syndrome, exfoliative dermatitis, hair dystrophy and selected precancerous conditions. A method of management which worked well under local conditions is outlined.

Topics: Adolescent; Adult; Child; Etretinate; Female; Humans; Male; Skin Diseases; Tretinoin

Topics: Administration, Oral; Child; Etretinate; Humans; Keratosis; Skin Diseases; Tretinoin

Topics: Acne Vulgaris; Humans; Isotretinoin; Keratins; Psoriasis; Skin Diseases; Skin Neoplasms; Tretinoin; Vitamin A

Topics: Dermatologic Agents; Humans; Keratins; Skin Diseases; Tretinoin

Topics: Acne Vulgaris; Adolescent; Adult; Anti-Inflammatory Agents; Female; Folliculitis; Humans; Isotretinoin; Male; Rosacea; Skin Diseases; Tretinoin

Topics: Acne Vulgaris; Humans; Neoplasms; Psoriasis; Skin Diseases; Tretinoin; Vitamin A

Retinoids possess regulatory influences on growth and differentiation of epithelial tissues. They induce a population of keratinozytes with normal pattern of differentiation, they have antiproliferative properties, and they show antineoplastic effects by inhibition of malignant transformation of cells in vitro. Also the dermis undergoes distinct alterations under oral administration of retinoids. By stimulating T-lymphocytes and by inhibition of neutrophil migration retinoids seem to develop immunmodulating and antiinflammatory effects. The aromatic retinoid Etretinate is therapeutically used in severe forms of psoriasis and in various genodermatoses with disorders of keratinization as for example ichthyosis, dyskeratosis follicularis Darier, and pityriasis rubra pilaris.

Topics: Acne Vulgaris; Administration, Oral; Etretinate; Humans; Isomerism; Isotretinoin; Psoriasis; Rosacea; Skin Diseases; Tretinoin

Topics: Acne Vulgaris; Adult; Cysts; Female; Humans; Isotretinoin; Male; Skin; Skin Diseases; Tretinoin

Topics: Adult; beta Carotene; Canthaxanthin; Carotenoids; Cell Transformation, Neoplastic; Child; Child, Preschool; Electrosurgery; Eye Diseases; Female; Humans; Infant; Male; Neurologic Manifestations; Skin Diseases; Tretinoin; Xeroderma Pigmentosum

Both auricles of 21 domestic rabbits were painted with dimethylbenzanthracene (DMBA). Eleven animals of this group were additionally fed aromatic retinoid (AR) by an esophageal tube. Two control animals were not treated at all. Eight or 9 weeks after the beginning of the study six of the seven remaining animals, which had only been painted with DMBA, developed a total of 25 keratoacanthoma-like tumors (KA). On the other hand, none of the seven animals left, which were painted with DMBA and fed AR showed any tumor by this time. The systemic effect of AR was studied in biopsies from the snout and the back. The epidermis of the snout showed 'mucous mataplasia' by histochemical and electron-microscopic criteria, whereas the epidermis of the back was not significantly altered. The production of intra- and extracellular lamellated material indicated an additional effect of AR on epidermal lipid metabolism. The effect of AR in the prevention of DMBA-induced tumors was characterized by 'mucoid cytolysis' and karyolysis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benz(a)Anthracenes; Esophagus; Etretinate; Intubation; Keratoacanthoma; Microscopy, Electron; Neoplasms, Experimental; Rabbits; Skin; Skin Diseases; Skin Neoplasms; Tretinoin

Topics: Female; Humans; Hyperplasia; Isotretinoin; Middle Aged; Sebaceous Glands; Skin Diseases; Tretinoin

This study reports comparative results of the effects of an aromatic retinoid, etretinate (RO 10-9359), on various disorders of the skin and mucous membranes. One hundred thirteen patients suffering from psoriasis, lichen planus, keratosis follicularis, and various other disorders were treated and examined. The patients received 25 to 100 mg/day of oral etretinate for up to 30 months. Patients with erythrodermic psoriasis, pustular psoriasis, and keratosis follicularis showed the best response. The conditions of patients with psoriasis vulgaris, palmoplantar psoriasis, and lichen planus also improved, but less impressively. The mucous membrane lesions of lichen planus and leukoplakia showed only moderate improvement. The most striking adverse clinical reactions observed were cheilitis (70%), dryness of the mucous membranes (27%), and hair loss (27%).

Topics: Administration, Oral; Adolescent; Adult; Darier Disease; Etretinate; Female; Humans; Lichen Planus; Male; Middle Aged; Mucous Membrane; Psoriasis; Skin Diseases; Tretinoin

Topics: Chemical Phenomena; Chemistry; Etretinate; Female; Humans; Male; Skin Diseases; Tretinoin

In a retrospective study clinical and hepatotoxic side effects caused by Tigason treatment are investigated. The material consists of data on 27 patients with normal liver function tests at the beginning of treatment. The clinical side effects encountered were: dryness of lips and mucous membranes (n = 14), diffuse hair loss (n = 5), epistaxis (n = 1) and conjunctivitis (n = 1). Abnormal liver function tests (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase lactate dehydrogenase and alkaline phosphatase) were found in 7 patients: 3 developed slight transient elevation of parameter during treatment, 2 transient elevation of more parameters, normalizing despite continued therapy in 1 and in the other normalizing after discontinuation. Finally 2 patients developed persistent elevation of one or more parameters. In the last 2 patients liver biopsy showed changes of toxic hepatitis.

Topics: Adolescent; Adult; Aged; Chemical and Drug Induced Liver Injury; Etretinate; Female; Humans; Liver Function Tests; Male; Middle Aged; Retrospective Studies; Skin Diseases; Tretinoin

Topics: Animals; Black or African American; Disease Models, Animal; Ear; Humans; Male; Rabbits; Salicylates; Salicylic Acid; Skin Diseases; Tretinoin

Topics: Administration, Oral; Adult; Cell Count; Eczema; Epidermis; Etretinate; Female; Humans; Langerhans Cells; Lichen Planus; Male; Middle Aged; Psoriasis; Skin Diseases; Tretinoin

26 patients with psoriasis and 23 patients with other dermatoses were treated for 28 days with oral retinoid Ro 10-9359. Intradermal tests to seven recall antigens were carried out before and after therapy. Dinitrochlorobenzene (DNCB) sensitization was started at the initiation of retinoid therapy and challenge tests made after 28 days. There was a significant increase in the reactions to recall antigens in all groups after 28 days' retinoid therapy. The reaction to DNCB was increased only in the non-psoriatic group compared with controls. These results demonstrate that the retinoid Ro 10-9359 stimulates cell-mediated immunity in vivo.

Topics: Dinitrochlorobenzene; Etretinate; Female; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Immunoglobulins; Intradermal Tests; Male; Middle Aged; Psoriasis; Skin Diseases; Tretinoin

Topics: Administration, Oral; Humans; Skin Diseases; Tretinoin

Topics: Etretinate; Humans; Isotretinoin; Skin Diseases; Tretinoin

Topics: Adult; Drug Evaluation; Etretinate; Humans; Male; Skin Diseases; Tretinoin

Topics: Acne Vulgaris; Darier Disease; Humans; Ichthyosis; Psoriasis; Skin Diseases; Tretinoin; Vitamin A

Topics: Acne Vulgaris; Animals; Cocarcinogenesis; Etretinate; Humans; Immunity; Isomerism; Isotretinoin; Keratosis; Polyamines; Psoriasis; Skin; Skin Diseases; Teratogens; Tretinoin; Triglycerides; Vitamin A

The origin and frequency of skin fragility, a frequent side effect of oral synthetic retinoids, was studied in ten patients receiving isotretinoin (13-cis-retinoic acid) for disorders of keratinization and in hairless mice treated with isotretinoin and the aromatic retinoid, etretinate (RO 10-9359). Clinical skin fragility occurred in eight of ten patients, and experimental friction blisters could be induced by pencil eraser abrasion in nine of nine patients and in the hairless mice. Light and electron microscopy of friction blisters showed fraying or loss of the stratum corneum and outer layers of the viable epidermis, loss of desmosomes and tonofilaments, and intracellular and intercellular deposits of amorphous material that did not stain with stains for mucin. The skin fragility produced by oral synthetic retinoids is epidermal in origin, since (1) retinoids induce profound disruption of epidermal morphologic appearance, (2) an intraepidermal split is produced by experimental friction blisters, and (3) urinary hydroxyproline excretion in patients receiving retinoids, a measure of collagen catabolism, was not increased.

Topics: Adolescent; Adult; Animals; Blister; Child; Etretinate; Female; Humans; Hydroxyproline; Isomerism; Isotretinoin; Lectins; Male; Mice; Mice, Hairless; Skin; Skin Diseases; Tretinoin; Water Loss, Insensible

The serum lipid levels were repeatedly controlled in 25 patients with various skin diseases treated orally with retinoid Ro 10-9359 in different doses. In 19 cases serum lipid values before onset of treatment were taken. 6 additional patients were controlled after long-term intake of the drug over 6-8 months. Pathological elevations of triglycerides were seen in 5 patients, in 4 of them 2-12 weeks after onset of oral treatment. All patients with elevated values had additional risk factors: Manifest or asymptomatic diabetes, alcoholic abuse with fatty liver, adipositas, and/or preexisting disorders of lipid metabolism. The observed changes seemed dose-dependent. The values were lowered or returned to normal after dose reduction or after discontinuation of treatment (one case). The cholesterin levels also showed some elevated values during the time of observation, however, there was no clear relation to the administration of the drug and the daily dose. The changes were also seen preferably in patients with risk factors. Controls of serum lipid levels seem, therefore, indicated before and under administration of oral retinoid. In patients with the additional risk factors mentioned above strict indication for oral retinoid therapy is needed and lower doses should be rather administered.

Topics: Administration, Oral; Adolescent; Adult; Aged; Cholesterol; Dose-Response Relationship, Drug; Etretinate; Female; Humans; Male; Middle Aged; Skin Diseases; Tretinoin; Triglycerides

Ten patients with disorders of keratinization were treated with oral isotretinoin (13-cis-retinoic acid) on an investigational protocol to test the efficacy, safety, and optimal dosage schedule for using the drug in these rare disorders. Elevations of serum triglyceride levels above the highest normal levels developed in seven of the ten patients, while they maintained normal levels of serum cholesterol. This effect was found to be dose and/or time related and reversible. Moderate elevations of serum triglyceride levels have not been clearly established as a risk factor for the development of coronary artery disease. High levels, however, may precipitate acute pancreatitis. For this reason, the conditions of patients receiving retinoids must be carefully monitored for triglyceride abnormalities throughout their courses of treatment.

Topics: Administration, Oral; Adolescent; Adult; Child; Cholesterol; Darier Disease; Female; Humans; Isotretinoin; Keratins; Keratosis; Male; Middle Aged; Skin; Skin Diseases; Tretinoin; Triglycerides

Topics: Acne Vulgaris; Humans; Psoriasis; Skin Diseases; Tretinoin; Vitamin A

Topics: Adult; Anti-Bacterial Agents; Aspirin; Child; Cimetidine; Cyclophosphamide; Dipyridamole; Female; Humans; Infant; Isotretinoin; Pruritus; Skin Diseases; Tretinoin; Ultraviolet Therapy

The need for safe and effective topical treatments is underlined by several clinical trials over the years treating miscellaneous dermatosis with many and heterologous drugs, sometimes on a simple empirical basis. In a recent study Robinson and Kligman claimed to have obtained satisfactory results treating several cases of actinic keratosis with an alternate regimen of retinoic acid and 5-FU. We wish to report an open-label pilot study using a simple and readily accessible combination of commercially formulated and available agents as 0,05% retinoic acid cream and 5% 5-FU cream over two groups of patients. Treatment consisted of bid application of sparing amounts of an equal parts combination of retinoic acid and 5-FU. The first group consisted of 7 patients affected by skin diseases associated with an altered epidermal keratinization (actinic keratosis, Darier's disease, seborrheic keratosis, phrynoderma and epidermodysplasia verruciformis). The patients were followed up for a period of 15 to 60 days and, as it might be expected, the results were quite good. The second group, on the contrary, consisted of 6 patients affected mainly by dermatosis involving the corium (LED, milium, colloid pseudomilium). The patients were followed up for the same period of time as the first group was, but the results were much less rewarding. Only a partial resolution of the process, which was followed soon after by a relapse, was noted. Finally we believe that this modified regimen of equal parts of retinoic acid and 5-FU has to be recommended in the topical treatment of the above mentioned dermatosis associated with an altered keratinization.

Topics: Drug Combinations; Fluorouracil; Humans; Keratosis; Ointments; Radiation Injuries; Skin Diseases; Syndrome; Tretinoin

Topics: Animals; Carcinoma, Squamous Cell; Humans; Lipoproteins, VLDL; Rats; Skin Diseases; Tretinoin; Triglycerides; Vitamin A; Vitamin A Deficiency

Topics: Etretinate; Humans; Skin Diseases; Tretinoin

Beneficial effects of oral retinoids in prophylaxis of epithelial neoplasias have been demonstrated by experimental works. In this study oral retinoid (RO 10-9359) was used in human dermatosis with high frequency of cutaneous malignancies: xeroderma pigmentosum with or without malignant neoplasias, Mibelli's porokeratosis with multifocal malignant degeneration, basal cell naevus syndrome with basal cell carcinomas, familial epithelioma of Ferguson-Smith and actinic keratosis. This work started in december 1977. Visible epitheliomas have been treated before trial. Initial dose of retinoid was 1 mg/kg daily, decreased depending on individual tolerance. Results were appreciated by comparising number of epitheliomas observed in years preceding retinoid therapy and number of them appearing during treatment; in two familial cases (basal cell naevus syndrom in twins and xeroderma pigmentosum in two brothers) comparison was made between treated and untreated patients. First results are very promising: an excellent response on solar keratosis is noted; epitheliomas occurrence seems actually to be prevented or delayed by oral retinoid therapy. Of course more numerous cases, a longer time, periods without treatment are necessary to confirm these interesting first results. On the other hand drug is not with this dose active on already constituted carcinomas.

Topics: Adolescent; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Etretinate; Female; Humans; Keratosis; Male; Precancerous Conditions; Skin Diseases; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

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

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epithelium; Etretinate; Humans; Skin Diseases; Skin Neoplasms; Tretinoin; Vitamin A

The ever increasing expenditures in health service urgently call for a critical revision of the therapy habitually practiced so far. This also includes the complete utilization of ambulatory therapeutic approaches. Moreover, after many years of clinical practice, the dermatologist in general practice should not forego the manifold therapeutic methods in which he had been trained and by the application of which he has gained particular experience. The dermatologist's small office consisting of a desk and couch must be a matter of the past once and for all. It is just the dermatologist who has the opportunity to try many forms of clinical treatment in general practice.

Topics: Family Practice; Humans; Keratosis; Methotrexate; Methoxsalen; Patient Care Team; Photochemotherapy; Psoriasis; Skin Diseases; Tretinoin

The anti-inflammatory effect of the new topical corticosteroid fluocortin butyl ester is approximately equal to that of hydrocortisone acetate but it has the advantage that systemic side-effects are lacking. Vitamin A acid and benzoyl peroxide have brought significant advances in the topical treatment of acne. For the treatment of chloasma and other hyperpigmentations the combination of vitamin A acid and hydroquinone with a corticoid is considerably more effective than any of the single components alone. Povidone-iodine with its extraordinarily low sensitization rate has proved useful for external antimicrobial treatment. Extensive or multiple precancerous lesions are effectively treated with 5-fluorouracil. New hair growth can be induced in alopecia areata by the local application of DNCB.

Topics: Acne Vulgaris; Administration, Topical; Alopecia; Benzoyl Peroxide; Dinitrochlorobenzene; Fluocortolone; Fluorouracil; Humans; Hydroquinones; Pigmentation Disorders; Precancerous Conditions; Skin Diseases; Tretinoin

Blepharoconjunctivitis developed as a side-effect of treatment of patients with basal cell carcinomas, keratinizing dermatoses, and cystic acne with oral 13-cis-retinoic acid. Forty-two of the 97 dermatologic patients had signs and symptoms of blepharoconjunctivitis that were dose related and abated one week after discontinuation of the medication. About half of the patients had a history of similar symptoms prior to treatment. Staphylococcus aureus was present in eye cultures of 73% to 79% of the patients, whether symptomatic or not. Patients whose clinical appearance was that of staphylococcal blepharoconjunctivitis and whose cultures grew S aureus were successfully treated with topical erythromycin ointment to the lids even while being treated with the 13-cis-retinoic acid.

Topics: Acne Vulgaris; Blepharitis; Carcinoma, Basal Cell; Conjunctivitis; Erythromycin; Eyelid Diseases; Humans; Keratosis; Skin Diseases; Skin Neoplasms; Staphylococcal Infections; Tretinoin

Topics: Adolescent; Aged; Anti-Bacterial Agents; Child; Cryosurgery; Darier Disease; Elastic Tissue; Epidermolysis Bullosa; Female; Humans; Impetigo; Larva Migrans; Lichen Planus; Male; Middle Aged; Papilloma; Pemphigus; Skin Diseases; Tongue Neoplasms; Tretinoin

Topics: Humans; Psoriasis; Skin Diseases; Tretinoin; Vitamin A

Twenty eight patients with various dermatological conditions were treated orally with the new aromatic derivate of retinoic acid, Ro 10-9359. The initial average dose was 48,3 mg/day and the maintenance dose was 26,6 mg/day. Duration of treatment ranged between 3 to 6 months. Evolution of erythema, infiltration and hyperkeratosis showed changes statistically significant (p < 0,05) and excellent to good results were obtained in 23 out of the 28 treated patients. On the basis of this study it is concluded that Ro 10-9359 is a promising drug for the treatment of several skin diseases, specially ichthyosis, Darier's disease, oral lichen planus, erythrokeratoderma variabilis and psoriasis. No serious side effects were reported; dryness of the lips, scaling of palms and soles, pruritus and thinning of the skin were the most common. In no case treatment was discontinued due to side effects. Laboratory controls did not show deviations from the normal values.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Male; Middle Aged; Skin Diseases; Tablets; Tretinoin

Topics: Adolescent; Adult; Carcinoma, Basal Cell; Humans; Middle Aged; Skin Diseases; Skin Neoplasms; Tretinoin; Vitamin A

Topics: Administration, Oral; Humans; Skin Diseases; Tretinoin; Vitamin A

The administration of anti-androgens brings favourable results especially in such skin diseases showing unsatisfactory therapeutic results, i.e. all severe forms of acne, seborrhoea, androgenic alopecia and hirsutism. Exact knowledge of the oestrogen and gestagen effect is essential. Also of fundamental importance is the observation and consideration of side effects besides the contraceptive efficacy and therapeutic results in dermatology.

Topics: Acne Vulgaris; Alopecia; Androgen Antagonists; Contraceptives, Oral; Contraceptives, Oral, Hormonal; Dermatitis, Seborrheic; Female; Hirsutism; Humans; Hypertrichosis; Skin Diseases; Tetracycline; Tretinoin

Topics: Acute Disease; Administration, Oral; Diethylstilbestrol; Female; Fetus; Gonadal Steroid Hormones; Hepatic Encephalopathy; Humans; Ichthyosis; Infant, Newborn; Male; Maternal-Fetal Exchange; Pregnancy; Research; Skin Diseases; Steroids; Tretinoin; Vitamin A

Topics: Animals; Carcinoma, Basal Cell; Humans; Neoplasms, Experimental; Papilloma; Precancerous Conditions; Skin Diseases; Skin Neoplasms; Tretinoin; Vitamin A; Vitamin A Deficiency

Topics: Adolescent; Adult; Female; Humans; Male; Middle Aged; Skin Diseases; Tretinoin; Vitamin A

Thirteen patients with keratinising dermatoses were treated for 2-17 weeks with oral 13-cis retinoic acid. There was near complete clearing of the skin lesions beginning within 2 weeks of starting treatment in all five patients with lamellar ichthyosis (including two cases of non-bullous congenital ichthyosiform erythroderma), in two of the three patients with Darier's disease, and in one patient with pityriasis rubra pilaris. The patients with psoriasis and naevus comedonicus did not improve. The main form of toxicity was cheilitis. These results indicate that 13-cis retinoic acid may be more effective and is less toxic than naturally occurring retinoic acid (all-trans vitamin A acid), and that the synthetic retinoids may represent a potent new class of drugs in the treatment of cutaneous disease.

Topics: Administration, Oral; Adult; Cheilitis; Child; Child, Preschool; Darier Disease; Drug Evaluation; Female; Follow-Up Studies; Humans; Ichthyosis; Male; Middle Aged; Pityriasis Rubra Pilaris; Skin Diseases; Tretinoin; Vitamin A

Topics: Acne Vulgaris; Humans; Skin Diseases; Tretinoin; Vitamin A

Topics: Acne Vulgaris; Animals; Congresses as Topic; Humans; In Vitro Techniques; Neoplasms, Experimental; Skin Diseases; Skin Neoplasms; Switzerland; Tretinoin; Vitamin A

Topics: Administration, Topical; Adult; Aged; Alopecia; Animals; Diarrhea; Female; Humans; Male; Middle Aged; Rats; Skin Diseases; Tretinoin; Vitamin A

Topics: Humans; Skin Diseases; Tretinoin; Vitamin A