tretinoin and Ichthyosis

Vitamin A is required for the proper functioning of many important metabolic and physiologic activities, including vision, gene transcription, the immune system and skin cell differentiation. Both excessive and deficient levels of vitamin A lead to poor functioning of many human systems. The biologically active form, retinoic acid, binds to nuclear receptors that facilitate transcription that ultimately leads to it's physiological effects. Retinoids are derivatives of vitamin A that are medications used to treat acne vulgaris, psoriasis, ichthyosis (and other disorders of keratinization), skin cancer prevention as well as several bone marrow derived neoplasias. Systemic retinoids are teratogenic and have to be prescribed with caution and close oversight. Other potential adverse events are controversial. These include the relationship of retinoid derivatives in sunscreens, their effects on bone mineral density, depression and suicidal ideation and inflammatory bowel disease. These controversies will be discussed in detail.

Topics: Acne Vulgaris; Bone and Bones; Cell Differentiation; Depression; Female; Humans; Ichthyosis; Inflammatory Bowel Diseases; Male; Nutrition Policy; Psoriasis; Retinoids; Sex Factors; Skin; Suicidal Ideation; Sunscreening Agents; Tretinoin; Vitamin A; Vitamins

Topics: Adult; Alitretinoin; Deafness; Female; Humans; Ichthyosis; Keratitis; Tretinoin

The ichthyoses constitute a large and heterogeneous group of disorders characterised by varying degrees of skin scaling. Most forms are rare but between them, they affect tens of thousands of people worldwide. Treatment presently consists primarily of topical keratolytic agents, aimed at removing the ichthyotic scales, and emollients. If an ichthyosis cannot be controlled by topical therapy alone, retinoids can be used. Although effective in several forms of ichthyosis, side effects and teratogenicity severely limit their use. The recent development of retinoic acid metabolism blocking agents (RAMBAs) offers new possibilities. With these drugs, retinoid effects may be obtained with less side effects and a shorter post-treatment teratogenicity period. This review discusses the RAMBAs that are now in clinical trials and outlines possible future developments.

Topics: Animals; Drug Design; Humans; Ichthyosis; Imidazoles; Keratolytic Agents; Molecular Structure; Tretinoin

Hereditary disorders of keratinization may be a considerable handicap. Oral treatment with retinoids has been shown to be effective in many of these diseases. In the group of ichthyoses, the best results can be obtained in the various types of nonbullous congenital ichthyosis (erythrodermic autosomal recessive lamellar ichthyosis, nonerythrodermic autosomal recessive lamellar ichthyosis, autosomal dominant lamellar ichthyosis). It should be borne in mind, however, that retinoid therapy alone cannot lead to a complete response of these forms of ichthyosis and that this treatment cannot replace an appropriate topical treatment. During continuous treatment with etretinate a reduction of the dosis to 0.5 mg/kg is often necessary. Etretinate treatment of bullous congenital ichthyosiform erythroderma is more difficult, and it is advisable to begin with a low dosis of 0.25-0.5 mg/kg. The epidermolytic form of palmoplantar keratoderma is in our opinion no indication for retinoid treatment which seems to result inevitably in large erosions. Good or excellent results have been seen in other forms of palmoplantar keratoderma including mal de Meleda, Papillon-Lefèvre syndrome, erythrokeratodermia variabilis, verrucous epidermal nevi, Darier disease and pityriasis rubra pilaris. In patients with Darier disease it is wise to begin with a relatively low dosage of 0.5 mg/kg and to adjust the dosage to the further course of the disease. The same is true for the ichthyosis seen in the Netherton syndrome, which may be either a diffuse hyperkeratosis or ichthyosis linearis circumflexa. In view of the fact that any inherited keratinization disorder requires long-term treatment, the risk of bone toxicity should be carefully weighed against the benefit of this therapy. The results so far obtained indicate that the effect of etretin is comparable to that of etretinate in the treatment of inherited keratinization disorders. Intermittent therapy should be tried whenever possible. A combination therapy seems reasonable in pityriasis rubra pilaris of the adult type. We have seen good results by combination with PUVA treatment. Autosomal dominant ichthyosis vulgaris and X-linked recessive ichthyosis are inappropriate to treat with oral retinoid therapy because these diseases are too mild. Papillomatous epidermal nevi should also be excluded because they do not respond to the drug. Hailey-Hailey disease may even be worsened by this treatment. According to our experience, oral retinoid

Topics: Acitretin; Adult; Etretinate; Humans; Ichthyosis; Keratoderma, Palmoplantar; Keratosis; Pityriasis; Tretinoin

Topics: Child; Etretinate; Female; Humans; Ichthyosis; Male; Retinoids; Skin Diseases, Vesiculobullous; Tretinoin; Vitamin A

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

Topics: Adrenal Cortex Hormones; Baths; Health Resorts; Humans; Ichthyosis; Infant; Ointments; Sodium Chloride; Tretinoin; Vitamin A

Topics: Acne Vulgaris; Administration, Oral; Adolescent; Dermatitis, Exfoliative; Half-Life; Humans; Ichthyosis; Isotretinoin; Neoplasms; Pityriasis Rubra Pilaris; Psoriasis; Tretinoin

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

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

The retinoid drugs have profound effects on many aspects of skin biology. The exact activity profile depends on the particular analog and its route of administration. The topical retinoids used at present have marked therapeutic effects on epidermal cell production and desquamation. All-trans-retinoic acid (tretinoin) also acts on dermal connective tissue and microvasculature in a way that is less well established but may also be of therapeutic benefit. We investigated both tretinoin and motretinide in normal subjects and in patients with ichthyosis. The quantitative dansyl chloride test has been particularly useful in monitoring the desquamatory action of these topically applied retinoids. Both compounds resulted in enhanced rates of epidermopoiesis and desquamation. Marked changes in the cytochemical profile of the epidermis were also detected, changes that differed somewhat from the alterations induced by the systemic administration of etretinate. Changes in dermal structure and vascularization were monitored by A-scan ultrasound and laser Doppler flowmetry. However, only minor changes were recorded, probably because of the comparatively short application time. These newer techniques for investigating skin structure and function offer considerable opportunities for delineating the action of retinoids.

Topics: Administration, Topical; Clinical Trials as Topic; Dansyl Compounds; Double-Blind Method; Humans; Ichthyosis; Lasers; Random Allocation; Skin; Tretinoin; Ultrasonography

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

A multicenter study of the effectiveness of 13-cis-retinoic acid (isotretinoin) in lamellar ichthyosis and epidermolytic hyperkeratosis has been conducted. A dose of the drug which produced maximum clearing with minimum side effects was chosen; this varied among different patients, the mean dose being about 2 mg/kg/day. Almost all of the patients in both groups were clearly improved, as evaluated both by the physicians and the patients. The degree of improvement seemed higher in the group of patients with lamellar ichthyosis.

Topics: Adolescent; Adult; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Ichthyosis; Infant; Isomerism; Isotretinoin; Male; Middle Aged; Skin Diseases, Vesiculobullous; Tretinoin

3 patients with lamellar ichthyosis have been treated orally with the aromatic retinoid Ro 10-9359 for periods of more than 2 years. This treatment resulted in a satisfactory improvement in the skin condition without any major side-effects. A light- and electron-microscopic study showed a marked decrease in the thickness of the lamellar stratum corneum without giving any clues concerning the mechanism of the therapeutic effect of this drug.

Topics: Administration, Oral; Adolescent; Adult; Child, Preschool; Clinical Trials as Topic; Etretinate; Female; Humans; Ichthyosis; Male; Skin; Tretinoin

In four medical centers, 40 patients with keratinizing dermatoses were treated with topical tretinoin (vitamin A acid) 0.1% cream and salicylic acid 2% cream in a short-term, double-blind study. Tretinoin was the more effective treatment for several of the keratinizing dermatoses with the exception of palmar-plantar hyperkeratosis, for which it was not effective in the concentration and method of application used. The most striking clinical responses occurred in patients with lamellar ichthyosis and ichthyosis vulgaris. Local adverse reactions-chiefly pruritus, erythema, burning, excoriation, and irritation-were not severe and could be controlled by modification of the treatment regimen.

Topics: Administration, Topical; Adolescent; Adult; Aged; Child; Child, Preschool; Double-Blind Method; Drug Evaluation; Female; Humans; Ichthyosis; Keratosis; Male; Middle Aged; Salicylates; Tretinoin; Vitamin A

The effect of urea-lactic acid ointment on the scales of ichthyotic skin was assessed using the 'cell swelling' technique of Christophers & Kligman. The thickness of the horny layer and of the scales was reduced both by the ointment and by the base. The formation of scales was shown to differ from that in psoriasis where the scale forms at the apex of th a rete peg and is symmetrical whereas in ichthyosis the separation of the scale may be at an entirely different depth at one margin. There is an increase in the number of 'T' cells in X-linked recessive ichthyosis.

Topics: Adolescent; Adult; Aged; Female; Humans; Ichthyosis; Lactates; Male; Middle Aged; Ointment Bases; Psoriasis; Skin; Tretinoin; Urea

Topics: Adolescent; Alitretinoin; Biopsy; Cellulitis; Deafness; Dermatologic Agents; Humans; Ichthyosis; Keratitis; Male; Scalp Dermatoses; Skin; Skin Diseases, Genetic; Treatment Outcome; Tretinoin

Lamin B receptor (LBR) is an integral protein of the inner nuclear membrane. Recent studies have demonstrated that genetic deficiency of LBR during granulopoiesis results in hypolobulation of the mature neutrophil nucleus, as observed in human Pelger-Huët anomaly and mouse ichthyosis (ic). In this study, we utilized differentiated early promyelocytes (EPRO cells) that were derived from the bone marrow of homozygous and heterozygous ichthyosis mice to examine changes to the expression of nuclear envelope proteins and heterochromatin structure that result from deficient LBR expression.. Wild-type (+/+), heterozygous (+/ic), and homozygous (ic/ic) granulocytic forms of EPRO cells were analyzed for the expression of multiple lamins and inner nuclear envelope proteins by immunostaining and immunoblotting techniques. The heterochromatin architecture was also examined by immunostaining for histone lysine methylation.. Wild-type (+/+) and heterozygous (+/ic) granulocytic forms revealed ring-shaped nuclei and contained LBR within the nuclear envelope; ic/ic granulocytes exhibited smaller ovoid nuclei devoid of LBR. The pericentric heterochromatin of undifferentiated and granulocytic ic/ic cells was condensed into larger spots and shifted away from the nuclear envelope, compared to +/+ and +/ic cell forms. Lamin A/C, which is normally not present in mature granulocytes, was significantly elevated in LBR-deficient EPRO cells.. Our observations suggest roles for LBR during granulopoiesis, which can involve augmenting nuclear membrane growth, facilitating compartmentalization of heterochromatin, and promoting downregulation of lamin A/C expression.

Topics: Animals; Biomarkers; Cell Differentiation; Cell Nucleus; Cells, Cultured; Centrosome; Gene Deletion; Granulocytes; Heterochromatin; Heterozygote; Homozygote; Ichthyosis; Lamin B Receptor; Mice; Nuclear Envelope; Receptors, Cytoplasmic and Nuclear; Tretinoin

We report a third family affected with ichthyosis bullosa of Siemens, and we further delineate the clinical spectrum of this mild type of epidermolytic hyperkeratosis. Erythroderma had never been present in any of the affected individuals. All of them exhibited a brownish, rimpled hyperkeratosis, the main characteristic sites being the joints, the shins and the periumbilical region. Blistering occurred after slight mechanical trauma and even after sweating, resulting in superficially denuded areas. Two affected family members also suffered from chronic, relapsing pustular eruptions surrounded by a transient erythematous flare. Light- and electron-microscopic examination revealed epidermolytic hyperkeratosis limited to the upper part of the epidermis. The pustular lesions were found to be subcorneal blisters filled with neutrophils. Ichthyosis bullosa of Siemens can be clearly distinguished from bullous ichthyosiform erythroderma. The observation of subcorneal pustular dermatosis occurring in this phenotype provides further evidence for the genetic heterogeneity of epidermolytic hyperkeratosis.

Topics: Acitretin; Adult; Epidermis; Etretinate; Female; Humans; Ichthyosis; Male; Microscopy, Electron; Middle Aged; Pedigree; Phenotype; Tretinoin

A young patient with Netherton's syndrome characterized by the classic triad of ichthyosis linearis circumflexa, trichorhexis invaginata and atopy was treated with Acitretin, a new retinoid preparation: 35 mg Acitretin/day resulted in a severe, erosive dermatitis which necessitated interruption of therapy. Even with 10 mg/day the patient had intolerable irritation of the integument. After a further dosage reduction to 5 mg/day there were no obvious side effects and a long-term treatment was possible, resulting in an obvious reduction of the ichthyotic lesions and improved hair growth. Electron microscopy in the active part of the skin lesions from untreated skin revealed granular, membrane-enclosed material intracellularly and in the intercellular spaces of the granular layer. Keratinization was almost completely suppressed. Therapy with Acitretin drastically reduced the deposition of intra- and extracellular material and normalized keratinization. Our results underline the importance of starting retinoid therapy in Netherton's syndrome at a low dosage and adjusting it carefully in each case with reference to the skin manifestations and the side effects.

Topics: Acitretin; Adolescent; Biopsy; Chromosome Aberrations; Chromosome Disorders; Dermatologic Agents; Female; Genes, Recessive; Humans; Ichthyosis; Skin; Syndrome; Tretinoin

A young female patient, expressing the symptom triad of Netherton's syndrome, i.e., ichthyosis linearis circumflexa Comèl, trichorrhexis invaginata and other hair shaft defects, and atopic diathesis, has been treated successfully with the new retinoid preparation Etretin. Our electron microscopical study especially focused on the ultrastructural effect on the characteristic, active part of the skin lesions, which is only found within a narrow borderline just preceding the lesion's margin. In untreated skin, this part is characterized by dermal inflammation, immigrating inflammatory cells, and specific keratinization disturbances: synthesis of keratinization proteins is suppressed, serum exudates invade the epidermis, either filling the intercellular spaces of the upper spinous and the granular layer as finely granular, amorphous material, or they are partly phagocytosed and lie within intracellular, round-oval inclusions. The portions of the lesions lying towards the center are unspecific and represent recovery stages, ultrastructurally resembling stages of normal wound repair. Oral therapy with Etretin did not heal the basic defect, but drastically reduced exoserosis and the deposition of intra- and extracellular material. Keratinization seemed to normalize. The condition of the hair was also improved.

Topics: Acitretin; Adolescent; Cell Differentiation; Female; Humans; Ichthyosis; Microscopy, Electron; Skin; Syndrome; Tretinoin

We study here the case of a male patient aged 22 years with antecedents of Down syndrome and X-linked ichthyosis. The results obtained from the administration of 13-cis retinoic acid are commented upon. The association with other diseases and the treatment are also reviewed.

Topics: Adult; Connective Tissue Diseases; Down Syndrome; Elastic Tissue; Humans; Ichthyosis; Male; Tretinoin

Eight men with severe recessive x-linked ichthyosis were treated with acitretin, the main metabolite of etretinate, during four months. All of the patients showed marked clinical improvement of scaling during therapy. Hypervitaminosis A-type adverse reactions were observed in all patients. Although the overall tolerance was good, therapy was interrupted in one atopic patient because of pruritus. There were no undesirable laboratory changes in values. Thirty-five milligrams of acitretin daily provided the best efficacy, with minimal side effects. The beneficial effect of this retinoid lasted between four and six weeks after therapy was stopped. These results suggest that acitretin is a useful agent in the symptomatic therapy of severe recessive x-linked ichthyosis resistant to topical therapeutic modalities. Good results with this agent can be achieved with interval therapy adjusted to seasonal variations of the skin symptoms.

Topics: Acitretin; Adult; Follow-Up Studies; Genetic Linkage; Humans; Ichthyosis; Male; Middle Aged; Pruritus; Tretinoin; X Chromosome

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

Topics: Acitretin; Adult; Dermatitis, Exfoliative; Diagnosis, Differential; Etretinate; Female; Humans; Ichthyosis; Keratosis; Optic Atrophy; Pedigree; Tretinoin

Topics: Acitretin; Humans; Ichthyosis; Infant, Newborn; Male; Prognosis; Tretinoin

Topics: Adult; Cornea; Female; Hearing Loss, Sensorineural; Humans; Ichthyosis; Isotretinoin; Keratitis; Neovascularization, Pathologic; Syndrome; Tretinoin

The problematic storage of etretinate in fat during chronic etretinate therapy prompted us to search for other "high-affinity" tissues in 3 patients studied at autopsy. Specimens from eleven organs were analysed for etretinate and its main metabolite, etretin, by high-performance liquid chromatography. The results confirmed an accumulation of etretinate in fat and to a lesser degree in liver. High levels of etretinate were also found in the adrenals and, in one case, this value exceeded that of the fat tissue. Low levels were observed in several other organs, notably the kidneys, brain and testis. With the possible exception of liver and gut, the metabolite did not accumulate in any particular organ. Although the available data is still limited, the risk that the accumulation of etretinate in the adrenals may adversely affect adrenal function must be examined.

Topics: Acitretin; Adipose Tissue; Adrenal Glands; Adult; Aged; Aged, 80 and over; Etretinate; Humans; Ichthyosis; Male; Psoriasis; Tissue Distribution; Tretinoin

Retinoids are natural and synthetic analogues of vitamin A. They have a marked influence on the differentiation of epithelial tissues by modifying membrane glycoconjugates and by acting through cytosolic and nuclear mechanisms like steroid hormones. Their clinical and biological toxic effects are numerous, but they are usually benign and reversible. However the possibility of teratogenic effects requires close monitoring of female patients. Etretinate is particularly effective in disorders of keratinisation (psoriasis, ichthyosis) whereas isotretinoin is the best known therapy of severe acne. Moreover the possible role of retinoids in the prevention and treatment of certain cancers gives hopeful prospects.

Topics: Acne Vulgaris; Chemical Phenomena; Chemistry; Etretinate; Humans; Ichthyosis; Isotretinoin; Neoplasms; Psoriasis; PUVA Therapy; Recurrence; Retinoids; Tretinoin

A 13-month-old child with lamellar ichthyosis and numerous cutaneous and systemic infections died following an abrupt episode of severe hypotension. Postmortem examination revealed white matter vacuolation in the brain stem tegmentum and cerebellar hemispheres similar to that seen in toxicity from hexachlorophene, to which our patient was not exposed. The patient had been treated with many commonly used medications, including 13-cis-retinoic acid, a relatively new drug with apparent therapeutic benefit in hyperkeratotic dermatoses. This had been given systemically during the patient's last week of life. Possible relationships between the white matter lesions and extrinsic toxic agents are discussed.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Brain Stem; Central Nervous System Diseases; Cerebral Ventricles; Drug Therapy, Combination; Female; Humans; Ichthyosis; Infant; Isotretinoin; Mycoses; Myelin Sheath; Skin Diseases, Infectious; Tretinoin; Vacuoles

Topics: Animals; Azacosterol; Cholesterol; Etretinate; Female; Ichthyosis; Isotretinoin; Mice; Mice, Hairless; Skin; Tretinoin

A case of miliaria crystallina occurring with isotretinoin therapy in a patient with lamellar ichthyosis is described. To our knowledge, the association of miliaria crystallina with isotretinoin therapy has not been previously reported.

Topics: Adolescent; Humans; Ichthyosis; Isotretinoin; Male; Miliaria; Skin; Tretinoin

Vitamin A and its synthetic congeners are known to produce a variety of skeletal abnormalities in patients on prolonged treatment with these medications. Two patients are described who developed posterior longitudinal ligament ossification following treatment with the synthetic retinoid 13-cis-retinoic acid. In both cases, this finding became apparent after other retinoid-induced skeletal abnormalities were observed and was less marked than the ossification of the anterior longitudinal ligament. Although spinal cord compression did not occur in our patients, patients on long-term retinoid therapy should be carefully observed for this complication.

Topics: Adolescent; Adult; Female; Humans; Ichthyosis; Isotretinoin; Ligaments, Articular; Ossification, Heterotopic; Spine; Time Factors; Tretinoin

Keratoderma hereditaria mutilans (KHM), or Vohwinkel's syndrome, is a rare genodermatosis consisting of hyperkeratosis of the palms and soles with a characteristic "honeycomb" appearance, keratotic structures taking the shape of a starfish and/or knuckle pads on the dorsal surfaces of the hands, and constricting bands (pseudoainhum) encircling digits of the hands and feet. We describe three cases of a variant of KHM with an associated ichthyosiform dermatosis in a pedigree consisting of 19 affected individuals through six generations. An autosomal dominant inheritance pattern for KHM was confirmed. One of the patients was successfully treated with isotretinoin, 0.6 mg/kg/day orally. We offer five hypothetical genetic models to account for the simultaneous expression of palmar-plantar keratoderma and ichthyosiform dermatosis.

Topics: Adult; Aged; Female; Genes, Dominant; Genetic Variation; Humans; Ichthyosis; Isomerism; Isotretinoin; Keratoderma, Palmoplantar; Male; Models, Genetic; Pedigree; Tretinoin

Although the new synthetic retinoids are effective when administered systemically, they have not been shown to be effective as topical agents. We compared the topical activity of six synthetic retinoids (two arotinoids, etretinate, all-trans- and 13-cis-tetrazole-retinamide, isotretinoin, and tretinoin) on tail skin in the diazacholesterol-fed mouse model of ichthyosis. Responses were assessed clinically and by measurement of stratum corneum thickness. Although the arotinoids dramatically reduced scaling, they were toxic at concentrations above 0.1%, as was etretinate at 1.0% or greater. Lower concentrations were effective without producing local or systemic toxic reactions. Clinical responses were paralleled by equivalent decrements in stratum corneum thickness, which also permitted quantitative comparisons. The order of potency for the retinoids was as follows: arotinoids, etretinate, tetrazole-retinamides, tretinoin = isotretinoin, vehicle. These results demonstrate that (1) the synthetic retinoids hold promise as topical agents; (2) irritation is not an absolute requirement for topical retinoid activity; and (3) the diazacholesterol-fed mouse offers a new assay of topical retinoid potency in a well-defined animal model of ichthyosis.

Topics: Administration, Topical; Animals; Azacosterol; Cholesterol; Dose-Response Relationship, Drug; Etretinate; Ichthyosis; Male; Mice; Mice, Hairless; Retinoids; Structure-Activity Relationship; Tretinoin

The ichthyosis of seven patients with the Sjögren-Larsson syndrome was treated with an aromatic retinoid, etretinate, during six months. Very good results were registered in six of the patients measured both as clinical improvement and as reduction in quantity of emollients needed. No unexpected side effects were noted.

Topics: Adolescent; Adult; Aged; Etretinate; Humans; Ichthyosis; Middle Aged; Pruritus; Sjogren's Syndrome; Time Factors; 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

Topics: Adolescent; Adult; Exostoses; Female; Humans; Ichthyosis; Isotretinoin; Long-Term Care; Male; Tretinoin

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

Topics: Adult; Etretinate; Female; Humans; Ichthyosis; Male; Middle Aged; Sweat Glands; Sweating; Tretinoin

A phase I study of 13-cis-retinoic acid was done in 16 patients with head and neck malignancies using a modified Fibonacci search scheme, with individual doses ranging from 20 to 120 mg/m2. Drug doses greater than 60 mg/m2 induced intense headaches, urethritis, desquamative dermatitis, vertigo, and ataxia. The severity of these side effects precludes the use of 13-cis-retinoic acid as a potential chemopreventive agent at doses greater than 60 mg/m2.

Topics: Adult; Aged; Cheilitis; Dose-Response Relationship, Drug; Drug Evaluation; Female; Head and Neck Neoplasms; Headache; Humans; Ichthyosis; Isomerism; Male; Middle Aged; Tretinoin; Urethritis

Topics: Adolescent; Dermatitis, Atopic; Etretinate; Female; Hair Diseases; Humans; Ichthyosis; Syndrome; Tretinoin

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

Topics: Administration, Oral; Corneal Opacity; Female; Humans; Ichthyosis; Infant; Isotretinoin; Tretinoin

The congenital ichthyosiform erythrodermas have become readily treatable with an aromatic retinoid. Satisfactory initial results over the first few months of treatment were achieved when the new preparation was given to Transvaal patients known to have these disorders and hitherto treated in vain. The pharmacology of the drug and therapeutic experiences in 6 cases are described.

Topics: Adult; Child; Etretinate; Female; Humans; Ichthyosis; Male; Skin; Skin Diseases, Vesiculobullous; Tretinoin

A thirty-one year old man and his ten year old daughter with the diagnosis of erythrokeratodermia variabilis, previously unresponsive to various topical agents and medication, were treated for seven weeks with oral retinoic acids. The response had been very good, particularly in the father. This is consistent with previous results obtained by other investigators in dermatosis characterized by accelerated or pathological keratinization, and perhaps enhances the possibility that the synthetic retinoids will be the future therapy of choice in controlling these conditions.

Topics: Administration, Oral; Adult; Child; Dermatitis, Exfoliative; Etretinate; Female; Humans; Ichthyosis; Male; Tretinoin

8 children with lamellar ichthyosis, 1 with epidermolytic hyperkeratosis and 5 with symmetrical progressive erythrokeratoderma were treated with a new aromatic retinoid (Ro 10-9359). Clinical improvement was dramatic. The children acquired an appearance never obtained before with other managements. The treatment had to be maintained to prevent recurrence. The tolerance to the drug was good. The side-effects were minimal and tended to disappear after several months of treatment. Our results suggest that because of its efficacy, good tolerance and easy administration, the oral retinoid Ro 10-9359 is at present the treatment of choice for the great ichthyotic disorders of children.

Topics: Child; Child, Preschool; Dermatitis, Exfoliative; Etretinate; Female; Humans; Ichthyosis; Infant; Keratosis; Male; Skin Diseases, Vesiculobullous; Tretinoin

A new synthetic oral retinoid, 13-cis retinoic acid, is fairly well tolerated in patients and appears to be effective in those with Darier's disease and lamellar ichthyosis. It is less effective in those with pityriasis rubra pilaris. The mechanism of action of 13-cis retinoic acid in disorders of keratinization is unknown at the present time; however, it does not appear to cause lysosomal proliferation in therapeutic doses.

Topics: Adolescent; Adult; Cheilitis; Child; Conjunctivitis; Darier Disease; Dose-Response Relationship, Drug; Evaluation Studies as Topic; Female; Humans; Ichthyosis; Isotretinoin; Male; Middle Aged; Pityriasis Rubra Pilaris; Tretinoin

A woman aged 54 years developed toxic necrosis of liver cells during treatment with aromatic retinoid (Ro 10-9359) for erythrodermia ichthyosiformis non-bullosa. Her skin was almost normalized when liver function tests and liver biopsy disclosed severe damage. The treatment was stopped, but 4 months later ALAT and ASAT were still elevated.

Topics: Chemical and Drug Induced Liver Injury; Etretinate; Female; Humans; Ichthyosis; Liver; Middle Aged; Tretinoin

Treatment with an oral aromatic all-trans retinoid (Ro 10-9359) resulted in clearing of the skin lesions in five patients with ichthyosis, four patients with Darier's disease and one patient with linear porokeratosis. No response to treatment was achieved in two patients with disseminated superficial actinic porokeratosis. Known side effects of retinoid treatment occurred in all patients in different intensity but disappeared when treatment was discontinued. Due to side effects (pruritus) treatment had to be discontinued only in one patient with Darier's disease and preexisting diabetes.

Topics: Administration, Oral; Adolescent; Adult; Child; Child, Preschool; Darier Disease; Etretinate; Female; Humans; Ichthyosis; Keratosis; Male; Middle Aged; Tretinoin

Topics: Humans; Ichthyosis; Tretinoin

Topics: Acne Vulgaris; Administration, Oral; Carcinoma, Basal Cell; Darier Disease; Drug Evaluation; Humans; Ichthyosis; Pityriasis Rubra Pilaris; Skin Neoplasms; Tretinoin; Vitamin A

Observations of 3 different great ichthyotic disorders, no longer responding to local keratolytics and to oral vitamin A are reported: a case of erythrokeratoderma variabilis, one of ichthyosiform erythroderma, and one of bullous ichthyosiform hyperkeratosis. After a week of oral treatment by the ethylester retinoid (Ro 10-9359), the hyperkeratotic component of each disease already improved dramatically. A maintenance treatment had to be continued. With equal or superior keratolytic effects, the retinoid has lower toxicity and less important side-effects than retinoic acid itself. The ethylester retinoid is nowadays the choice oral treatment in these great hyperkeratotic disorders.

Topics: Adolescent; Drug Evaluation; Female; Humans; Ichthyosis; Skin Diseases, Vesiculobullous; Tretinoin; Vitamin A

An aromatic retinoid (Ro-10/9359) was used for oral treatment of five cases of ichthyosis (three lamellar, two X-linked. Complete clearing of the skin lesions was achieved in all five patients within 24.2 +/- 3.2 days (X-linked 21.75 +/- 6.5, lamellar 23 days). Histopathology showed reduction of the hyperkeratosis, and thickening of the granular layer. Clinical side effects were of mild intensity and included cheilitis, conjunctivitis and pruritus. All side effects were reversible upon reduction of the daily dosage. In three patients treatment was discontinued after clearing of lesions. Fresh lesions re-appeared 6 weeks later. One patient with X-linked ichthyosis developed two recurrences during maintenance treatment; one patient with lamellar ichthyosis was kept in complete remission for 9 weeks on a reduced daily dosage.

Topics: Adolescent; Cheilitis; Child; Child, Preschool; Female; Humans; Ichthyosis; Male; Skin; Tretinoin; Vitamin A

Topics: Administration, Oral; Adult; Female; Humans; Ichthyosis; Skin; Skin Diseases, Vesiculobullous; Tretinoin; Vitamin A

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

In autosomal dominant ichthyosis, a permanent cure is impossible, and symptomatic treatment is most important. At present, known therapeutic procedures have had little or no influence in this disease. Following the application of 0.1% vitamin A acid ointment, especially in children, the skin became free of scales within a few weeks. After improvement, a maintenance dosage of one application per week in most cases was sufficient to avoid any recurrence. Possible side effects of this treatment are mentioned. Sereral possibilities regarding the mode of action of vitamin A acid are discussed.

Topics: Administration, Topical; Adolescent; Adult; Age Factors; Aged; Child; Child, Preschool; Female; Humans; Ichthyosis; Male; Middle Aged; Time Factors; 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: Administration, Oral; Adolescent; Adult; Aged; Child; Darier Disease; Female; Humans; Ichthyosis; Keratoderma, Palmoplantar; Keratosis; Leukoplakia; Male; Middle Aged; Pityriasis Rubra Pilaris; Psoriasis; Skin Neoplasms; Tretinoin; Vitamin A

Topics: Adult; Child; Female; Humans; Ichthyosis; Male; Ointments; Skin Diseases, Vesiculobullous; Tretinoin; Vitamin A

Oral retinoic acid has been therapeutically beneficial for three patients with congenital ichthyosiform erythroderma and one with congenital bullous ichthyosifrom erythroderma. Response to therapy was slow but definite with suppression of scale formation, marked reduction of painful cracking of the underlying epidermis and disappearance of skin irritation. Side effects have not occurred. Therapy had to be maintained to prevent recurrence of symptoms.

Topics: Administration, Oral; Adolescent; Adult; Child; Female; Humans; Ichthyosis; Male; Skin Diseases, Vesiculobullous; Tretinoin; Vitamin A