tretinoin and Dermatitis

Vitamin A is a fat-soluble vitamin that plays an important role in skin immunity. Deficiencies in Vitamin A have been linked to impaired immune response and increased susceptibility to skin infections and inflammatory skin disease. This narrative review summarizes recent primary evidence that elucidates the role of vitamin A and its derivatives on innate immune regulators through mechanisms that promote skin immunity and sustain the skin microbiome.

Topics: Animals; Dermatitis; Humans; Immunity, Innate; Microbiota; Skin; Staphylococcus aureus; Tretinoin; Vitamin A; Vitamin A Deficiency

Postinflammatory hyperpigmentation (PIH) has posed a substantial challenge for patients with higher Fitzpatrick skin types, specifically types III to VI. Treatment modalities pose a number of limitations due to the number of treatments required, potential side effects, and overall efficacy. Fortunately, multiple therapies have been delineated that can be moderately to highly efficacious in treating PIH in patients with skin of color. This article will review some of these modalities and procedures for this common patient concern.

Topics: Chemexfoliation; Dermatitis; Dermatologic Agents; Dicarboxylic Acids; Drug Combinations; Ethanol; Glycolates; Humans; Hydroquinones; Hyperpigmentation; Inflammation; Keratolytic Agents; Lactic Acid; Pyrones; Resorcinols; Salicylates; Salicylic Acid; Skin Pigmentation; Tretinoin

Dermal dendrocytes represent a population of resident cells of the dermis identified recently by virtue of the immunohistochemical expression of the coagulation factor XIIIa (fXIIIa). These dendritic cells of bone-marrow origin bear particular histoenzymatic and immunohistochemical features, some of which are shared with antigen-presenting cells; however, they are clearly distinct from epidermal Langerhans cells. Dermal dendrocytes could act as macrophages, antigen-presenting cells or participate in the homeostasis of macromolecules of the dermis. These cells give rise to some cutaneous tumours and seem involved in inflammatory dermatoses where they act by means of cytokine production; they could even represent targets of HIV infection. Future functional studies will hopefully lead to a better understanding of their precise role in normal and diseased skin, which remains presently partly speculative.

Topics: Acquired Immunodeficiency Syndrome; Cytokines; Dermatitis; Granuloma; Histiocytoma, Benign Fibrous; HLA-DR Antigens; Humans; Sarcoma, Kaposi; Skin; Skin Neoplasms; Skin Physiological Phenomena; Transglutaminases; Tretinoin; Ultraviolet Rays; Vasculitis, Leukocytoclastic, Cutaneous

Environmental stimuli responsible for inducing cutaneous inflammation include contact allergens and ultraviolet light. We postulate that these diverse stimuli trigger a cutaneous inflammatory response by directly inducing epidermal keratinocytes to elaborate specific pro-inflammatory cytokines and adhesion molecules. The consequences are activation of dermal microvascular endothelial cells and selective accumulation of specific mononuclear cells in the dermis and epidermis. Thus, keratinocytes may act as "signal transducers", capable of converting exogenous stimuli into the production of cytokines, adhesion molecules, and chemotactic factors (acting in an autocrine and paracrine fashion) responsible for initiation of "antigen-independent" cutaneous inflammation. The initiation phase may facilitate or promote an amplification phase with additional production of tumour-necrosis factor alpha and interferon gamma via an "antigen-dependent" pathway, and keratinocyte/T cell/antigen-presenting dendritic cellular associations. The direct activation of keratinocytes, with their ability to produce the complete repertoire of pro-inflammatory cytokines, can profoundly influence endogenous and recruited immunocompetent cells, thereby providing the critical trigger responsible for the swift and clinically dramatic alterations that occur following contact between the epidermis and a host of "noxious" agents.

Topics: Catechols; Cell Communication; Cell Division; Cells, Cultured; Cytokines; Dermatitis; Humans; Keratinocytes; Leukocytes, Mononuclear; Tretinoin; Ultraviolet Rays

Post-inflammatory hyperpigmentation (PIH) is a common occurrence in patients with acne vulgaris, particularly in those with skin of colour.. A previous study has demonstrated the benefit of tretinoin (retinoic acid) in the treatment of PIH; however, there is currently no standard protocol to evaluate change in PIH following treatment. Based on these findings, we performed a pilot, exploratory, blinded, intraindividual-controlled methodology study that consisted of a photographic assessment protocol with facial mapping..   The study was based on a secondary analysis of a phase 4, community-based trial of 544 acne patients who were treated with tretinoin gel microsphere 0.04% or 0.1%. Only patients with Fitzpatrick types III-V (skin of colour) were included in the study; subjects with Fitzpatrick skin type VI were excluded because the photographic assessment did not allow for proper evaluation.. Despite the small number of subjects evaluated (n=25), the results revealed consistent assessment of improvement in PIH between two independent graders (weighted κ=0.84).. Further study with a larger population is recommended to validate the accuracy of this method.

Topics: Acne Vulgaris; Dermatitis; Dermatologic Agents; Humans; Photography; Pigmentation Disorders; Pilot Projects; Tretinoin

The development of a hydrogel to stabilize and solubilize clindamycin and tretinoin provides a single, once-daily treatment for acne vulgaris.. Our aim was to compare the efficacy and safety of the combination of clindamycin (1%) and tretinoin (0.025%) with each agent alone and vehicle.. Two randomized, double-blind, active drug- and vehicle-controlled 12-week studies evaluated inflammatory and noninflammatory lesion counts and the Investigator's Static Global Assessment in 2219 subjects with acne vulgaris.. The combination demonstrated superior efficacy to clindamycin, tretinoin, and vehicle. Combination hydrogel was significantly more effective in reducing inflammatory (P < .005), noninflammatory (P < or = .0004), and total (P < .0001) lesion counts than the other treatments and vehicle. The proportion of subjects with clear or almost clear skin on the Investigator's Static Global Assessment was greater with the combination (P < .0001).. A majority of subjects (82.6%) had grade 2-3 acne vulgaris at baseline; therefore these overall results may not be representative of the response in the subjects (17.4%) with grade 4-5 acne.. The combination clindamycin/tretinoin hydrogel was well tolerated and significantly more effective than clindamycin, tretinoin, or vehicle for the treatment of acne vulgaris.

Topics: Acne Vulgaris; Adolescent; Anti-Bacterial Agents; Clindamycin; Dermatitis; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Male; Severity of Illness Index; Treatment Outcome; Tretinoin

Treatment of postinflammatory hyperpigmentation in patients of Fitzpatrick skin types IV, V, and VI is difficult. Glycolic acid peels are useful for pigment dyschromias in caucasians; however, there are no controlled studies examining their safety and efficacy in dark-complexioned individuals.. To determine if serial glycolic acid peels provide additional improvement when compared with a topical regimen of hydroquinone and tretinoin.. Nineteen patients with Fitzpatrick skin type IV, V, or VI were randomized to a control or peel group. The control group applied 2% hydroquinone/10% glycolic acid gel twice daily and 0.05% tretinoin cream at night. The peel patients used the same topical regimen and, in addition, received six serial glycolic acid peels (68% maximum concentration). Patients were evaluated with photography, colorimetry, and subjectively.. Sixteen patients completed the study. Both treatment groups demonstrated improvement, but the patients receiving the glycolic acid peels showed a trend toward more rapid and greater improvement. The peel group also experienced increased lightening of the normal skin.. This pilot study demonstrates that serial glycolic acid peels provide an additional benefit, with minimal adverse effects, for the treatment of postinflammatory hyperpigmentation in dark-complexioned individuals.

Topics: Administration, Topical; Adult; Black People; Chemexfoliation; Dermatitis; Drug Combinations; Female; Glycolates; Humans; Hydroquinones; Hyperpigmentation; Keratolytic Agents; Middle Aged; Pilot Projects; Tretinoin

Irregular disfiguring skin hyperpigmentation due to inflammation may develop in black persons. We investigated the treatment of this hyperpigmentation with topical tretinoin (0.1 percent retinoic acid cream). Fifty-four subjects completed a 40-week randomized, double-blind, vehicle-controlled study. Twenty-four subjects applied tretinoin daily to the face, arms, or both areas, and 30 subjects applied vehicle cream. At base line and after 40 weeks of treatment, each subject's post-inflammatory hyperpigmented lesions and normal skin were assessed by clinical and colorimetric evaluations and by analysis of biopsy specimens.. The facial post-inflammatory hyperpigmented lesions of the tretinoin-treated subjects were significantly lighter after the 40 weeks of therapy than those of the vehicle-treated subjects (P < 0.001); overall improvement was first noted after four weeks of tretinoin treatment. At the end of treatment, colorimetry demonstrated a 40 percent lightening of the lesions toward normal skin color in the tretinoin-treated lesions, as compared with an 18 percent lightening in vehicle-treated lesions (P = 0.05). The epidermal melanin content in the lesions decreased by 23 percent with tretinoin and by 3 percent with vehicle (P = 0.24). Normal skin was minimally lightened by tretinoin as compared with vehicle, according to both clinical evaluation (0.1 vs. -0.1 unit change on an 8-point scale; P = 0.055) and colorimetry (P < 0.001). Retinoid dermatitis developed in 12 of the 24 tretinoin-treated subjects who completed the study (50 percent) and in 1 tretinoin-treated subject who withdrew from the study, but diminished as the study progressed.. Topical application of tretinoin significantly lightens post-inflammatory hyperpigmentation and, to a clinically minimal but statistically significant degree, lightens normal skin in black persons.

Topics: Administration, Cutaneous; Adult; Black People; Dermatitis; Double-Blind Method; Female; Humans; Hyperpigmentation; Male; Middle Aged; Skin; Tretinoin

Twenty-one patients were enrolled in a randomized, double-blind study that examined the effects of topical 0.05% tretinoin (all-trans-retinoic acid; vitamin A acid; Retin-A) solution on dysplastic nevi. Following histologic confirmation of the diagnosis of dysplastic nevus in three representative lesions, patients applied either tretinoin or a placebo containing 50% alcohol to selected dysplastic nevi once a day under tape occlusion, or twice a day unoccluded, for 4 months. Immediate posttreatment comparative photographs showed marked fading or elimination of some dysplastic nevi clinically, and histologic examination of excisional biopsy specimens showed disappearance or reversion to benign nevi in many of the treated lesions. There were no clinical or histologic changes in those dysplastic nevi treated with placebo. This study shows a definite biological effect of topical tretinoin on some dysplastic nevi.

Topics: Administration, Cutaneous; Adolescent; Adult; Bandages; Dermatitis; Double-Blind Method; Dysplastic Nevus Syndrome; Ethanol; Female; Humans; Male; Middle Aged; Placebos; Random Allocation; Skin; Skin Neoplasms; Tretinoin

Eighteen patients developed Staphylococcus aureus infection during or shortly after a five-month course of therapy with isotretinoin. Staphylococcus aureus was recovered both from lesions and from the anterior nares. In a prospective study, 4% of control patients treated with isotretinoin alone developed S aureus infection, while none who applied topical antibiotic to the anterior nares developed infection. Control patients had a 64% prevalence of anterior nares colonization with S aureus, compared with 18% in the topical antibiotic group.

Topics: Administration, Topical; Anti-Bacterial Agents; Dermatitis; Humans; Isotretinoin; Ointments; Staphylococcal Infections; Staphylococcus aureus; Tretinoin

Long-term ultraviolet (UV) exposure can cause inflammation, pigmentation and photoaging. All-trans retinoic acid (ATRA/tretinoin) is a commonly used retinoic acid receptor (RAR) agonist in the clinical treatment of UV-induced skin problems. However, the use of such drugs is often accompanied by systemic adverse reactions caused by nonspecific activation of RARs. Therefore, this study was designed to screen for a novel RAR-γ-selective agonist with high safety.. Molecular docking, dynamic simulation and Biacore were used to screen and identify novel RAR-γ-selective agonists. RT-PCR, ELISA, western blotting, immunofluorescence staining, flow cytometry and proteomic analysis were used to detect the effects of these novel RAR-γ selective agonists on UVA-induced inflammation and photoaging cell models. UVA-induced mouse models were used to evaluate the effects of tectorigenin on skin repair, ageing and inflammation.. Tectorigenin is a novel RAR-γ-selective agonist, which inhibits UV-induced oxidative damage, inflammatory factor release and matrix metalloproteinase (MMP) production. Tectorigenin can also reverse the UVA-induced loss of collagen. The results of the signalling pathway research showed that tectorigenin mainly affects the MAPK/JNK/AP-1 pathway. In animal experiments, tectorigenin showed better anti-inflammatory and anti-photoaging effects, and caused less skin irritation than ATRA. Nano-particle loaded tectorigenin significantly improved the utilization of tectorigenin.. Tectorignen is a non-retinol RAR-γ-selective agonist that can inhibit UV-induced skin damage and could be developed as a safe pharmaceutical component for the prevention of photoaging and skin inflammation.

Topics: Animals; Dermatitis; Inflammation; Isoflavones; Mice; Molecular Docking Simulation; Proteomics; Receptors, Retinoic Acid; Tretinoin; Ultraviolet Rays

Retinoic acid (RA)-induced dermatitis is the most frequent side-effect limiting its widespread use. However, the exact mechanisms triggering dermatitis are not fully understood, including the role of skin mast cells. The newly discovered Mas-related G-protein-coupled receptor-X2 (MRGPRX2) in mast cells mediates pseudoallergic drug reactions in several types of dermatitis. A possible contribution of MRGPRX2 to contact dermatitis induced by RA has hitherto not been examined.. To investigate whether all-trans-RA (ATRA) activates mast cells via MRGPRX2/MrgprB2 (the mouse orthologue), contributing to the pathogenesis of retinoid-induced dermatitis.. Wild-type (WT) and MrgprB2. As compared with WT mice, MrgprB2. ATRA-induced dermatitis could be achieved by activating mast cells via MRGPRX2/MrgprB2, which may provide a potential therapy target to reduce the side-effect.

Topics: Animals; beta-N-Acetylhexosaminidases; Calcium; Cell Degranulation; Cell Line; Dermatitis; Dermatitis, Contact; Gene Knockdown Techniques; Histamine; Humans; Male; Mast Cells; Mice; Nerve Tissue Proteins; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Tretinoin

Mast cells (MCs) mature locally, thus possessing tissue-dependent phenotypes for their critical roles in both protective immunity against pathogens and the development of allergy or inflammation. We previously reported that MCs highly express P2X7, a receptor for extracellular ATP, in the colon but not in the skin. The ATP-P2X7 pathway induces MC activation and consequently exacerbates the inflammation. Here, we identified the mechanisms by which P2X7 expression on MCs is reduced by fibroblasts in the skin, but not in the other tissues. The retinoic-acid-degrading enzyme Cyp26b1 is highly expressed in skin fibroblasts, and its inhibition resulted in the upregulation of P2X7 on MCs. We also noted the increased expression of P2X7 on skin MCs and consequent P2X7- and MC-dependent dermatitis (so-called retinoid dermatitis) in the presence of excessive amounts of retinoic acid. These results demonstrate a unique skin-barrier homeostatic network operating through Cyp26b1-mediated inhibition of ATP-dependent MC activation by fibroblasts.

Topics: Adenosine Triphosphate; Animals; Cell Degranulation; Cytochrome P-450 Enzyme System; Dermatitis; Fibroblasts; Imidazoles; Immunity, Innate; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Microbiota; Receptors, Purinergic P2X7; Retinoic Acid 4-Hydroxylase; Skin; Toll-Like Receptor 2; Tretinoin

Nuclear receptor-mediated signaling via RARs and PPARδ is involved in the regulation of skin homeostasis. Moreover, activation of both RAR and PPARδ was shown to alter skin inflammation. Endogenous all-trans retinoic acid (ATRA) can activate both receptors depending on specific transport proteins: Fabp5 initiates PPARδ signaling whereas Crabp2 promotes RAR signaling. Repetitive topical applications of ovalbumin (OVA) in combination with intraperitoneal injections of OVA or only intraperitoneal OVA applications were used to induce allergic dermatitis. In our mouse model, expression of IL-4, and Hbegf increased whereas expression of involucrin, Abca12 and Spink5 decreased in inflamed skin, demonstrating altered immune response and epidermal barrier homeostasis. Comprehensive gene expression analysis showed alterations of the cutaneous retinoid metabolism and retinoid-mediated signaling in allergic skin immune response. Notably, ATRA synthesis was increased as indicated by the elevated expression of retinaldehyde dehydrogenases and increased levels of ATRA. Consequently, the expression pattern of genes downstream to RAR was altered. Furthermore, the increased ratio of Fabp5 vs. Crabp2 may indicate an up-regulation of the PPARδ pathway in allergen-induced dermatitis in addition to the altered RAR signaling. Thus, our findings suggest that ATRA levels, RAR-mediated signaling and signaling involved in PPARδ pathways are mainly increased in allergen-induced dermatitis and may contribute to the development and/or maintenance of allergic skin diseases.

Topics: Allergens; Animals; ATP-Binding Cassette Transporters; Dermatitis; Fatty Acid-Binding Proteins; Female; Gene Expression Regulation; Heparin-binding EGF-like Growth Factor; Intercellular Signaling Peptides and Proteins; Interleukin-4; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Ovalbumin; PPAR delta; Protein Precursors; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Serine Peptidase Inhibitor Kazal-Type 5; Serpins; Signal Transduction; Tretinoin

  Retinoids have been used for the treatment of skin disorders such as acne, psoriasis, and photoaging. However, despite their beneficial effects, topical retinoids often cause severe local irritation called retinoid dermatitis. We previously developed a novel vitamin A derivative, retinyl retinoate, which induces less irritation and affords excellent tolerance. In this study, we examined whether co-treatment with topical peroxisome proliferator-activated receptor-α (PPARα) agonists (e.g. WY14643) reduce retinoid dermatitis in hairless mouse skin..   The effect of concomitant treatment with a PPARα agonist on retinoid dermatitis in hairless mouse epidermis was evaluated by measuring transepidermal water loss, epidermal histology, and cytokine expression..   Retinyl retinoate induced less severe retinoid dermatitis than retinoic acid. Topical application of a PPARα agonist improved the stratum corneum structure and function, reduced mRNA expression of interleukin (IL)-1α, tumor necrosis factor-α and IL-8, and inhibited ear edema induced by retinoic acid or retinyl retinoate..   Our results indicate that PPARα agonists can potentially be used to improve retinoid dermatitis. We suggest that co-treatment with retinyl retinoate and a PPARα agonist may reduce or prevent detrimental alterations in retinoid-treated skin.

Topics: Administration, Topical; Animals; Cell Differentiation; Cell Proliferation; Dermatitis; Enzyme Inhibitors; Epidermis; Female; Interleukin-1alpha; Interleukin-8; Keratolytic Agents; Liver X Receptors; Mice; Mice, Hairless; Orphan Nuclear Receptors; Palmitic Acid; PPAR alpha; Pyrimidines; Retinoids; Retinyl Esters; RNA, Messenger; Tretinoin; Tumor Necrosis Factor-alpha; Water Loss, Insensible

Allograft inflammatory factor-1 (AIF-1) is an evolutionarily conserved, inflammatory protein produced by activated macrophages during chronic transplant rejection and in inflammatory brain lesions. Since T-cell-mediated inflammation is common to various dermatoses and nothing is known about AIF-1 in skin, we studied its protein expression at the tissue level and regulation in monocytic cell lines by various agents. Using immunohistochemistry, we found that AIF-1 is expressed at low levels in normal skin, but is highly upregulated in various inflammatory skin disorders, such as psoriasis, lichen planus, graft-versus-host disease and mycosis fungoides. The main cell types expressing AIF-1 in affected skin are macrophages and Langerhans' cells. We also show by real-time PCR that AIF-1 mRNA levels in monocytic THP-1 and U937 cell lines are significantly upregulated by retinoic acid as well as a number of cytokines. We conclude that AIF-1 may mediate survival and pro-inflammatory properties of macrophages in skin diseases.

Topics: Anti-Inflammatory Agents; Calcium-Binding Proteins; Cell Line; Cytokines; Dendritic Cells; Dermatitis; Dexamethasone; DNA-Binding Proteins; Graft vs Host Reaction; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Keratolytic Agents; Langerhans Cells; Macrophages; Microfilament Proteins; Polymerase Chain Reaction; RNA, Messenger; Skin; Tretinoin; Up-Regulation

Access of T effector cells to sites of inflammation is a prerequisite for an efficient action in immune defense and is mediated by different, partly tissue-specific sets of adhesion molecules. To what extent lymphocytes memorize the site of initial priming and develop organ-specific homing properties is still a matter of debate. Notably, data on the stability of homing receptor expression on T cells in vivo are largely lacking. We approached this question by the adoptive transfer of CD4(+) T cells sorted for the expression of P-selectin ligands, which contribute to migration into inflamed sites in skin and other tissues. We observed long-term expression of P-selectin ligands on roughly one-third of effector cells. On those cells that had lost P-selectin ligands, re-expression upon Ag challenge was observed but only within pLNs, similar to the organ-selective induction upon the primary activation of naive T cells. The frequency of cells stably expressing P-selectin ligands was higher when cells were repeatedly stimulated under permissive conditions in the presence of IL-12, indicating a gradual fixation of this phenotype. In line with that finding, isolated P-selectin ligand positive memory T cells showed the highest frequency of long-term expressing cells. A tissue-specific environment was not required for the long-term maintenance of P-selectin ligand expression on the subfraction of effector cells. These data indicate that the expression of selectin ligands can become clonally imprinted under certain conditions, but also that a major fraction of the cells remains flexible and subject to environmental modulation upon restimulation.

Topics: Animals; CD4-Positive T-Lymphocytes; Cell Movement; Cells, Cultured; Dermatitis; Immunologic Memory; Inflammation; Integrins; Membrane Glycoproteins; Mice; T-Lymphocyte Subsets; Tretinoin

In this study, the anti-inflammatory effects of tretinoin (all-trans-retinoic acid) 0.1% cream and adapalene 0.1% gel were compared in rats to determine whether there was a difference between these agents. Thirty-six rats of either sex were divided into six groups (two control groups, and an etodolac, indomethacin, tretinoin and adapalene group) of six animals each. Each group was given different drugs or chemicals. The inhibitory activities of the drugs were determined on carrageenan-induced rat-paw oedema. The inhibition rate (53.48%) in the tretinoin group was found to be higher than adapalene and controls (P < 0.05). Adapalene was found to have an inhibition rate of 10.28%, and when compared with the other groups, was found to have no statistically significant anti-inflammatory activity. We conclude that tretinoin has a higher anti-inflammatory activity than adapalene and thus should be preferred for the treatment of inflammatory lesions.

Topics: Adapalene; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Dermatitis; Edema; Female; Male; Naphthalenes; Rats; Rats, Sprague-Dawley; Tretinoin

The effect of a phospholipase A2 (PLA2) inhibitor on leukotriene, prostaglandin and platelet activating factor (PAF) biosynthesis in isolated cells and in vivo was determined. BMS-181162, [4(3'-carboxyphenyl)-3,7-dimethyl-9(2",6",6"-trimethyl-1"- cyclohexenyl)2Z,4E,6E,8E-nonatetraenoic acid], reversibly inhibited the 14-kdalton PLA2 purified from human synovial fluid with an IC50 of 8 microns. In A23187-stimulated human polymorphonuclear leukocytes (PMNs), BMS-181162 blocked arachidonic acid release with an IC50 of 10 microns. Leukotriene B4 and PAF biosynthesis in these cells was also inhibited. In a phorbol ester-induced chronic mouse skin inflammation model, topically applied BMS-181162 markedly lowered the tissue levels of leukotriene B4 and prostaglandin E2 and dose-dependently inhibited leukocyte infiltration (ED50 = 180 micrograms per ear). BMS-181162 is an inhibitor of PLA2 and may prove to be a useful tool in the delineation of the role of PLA2 in the inflammatory process.

Topics: Administration, Topical; Anti-Inflammatory Agents; Arachidonic Acid; Dermatitis; Eicosanoids; Humans; Neutrophils; Phospholipases A; Phospholipases A2; Platelet Activating Factor; Tetradecanoylphorbol Acetate; Tretinoin

Topics: Black People; Dermatitis; Humans; Hyperpigmentation; 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

An update is presented of bone changes taking place in association with oral treatment with the two most relevant synthetic retinoids, 13-cis-retinoic acid (isotretinoin; Roaccutan, Accutane) and etretinate (aromatic retinoid; Tigason, Tegison). All of the important clinical studies are reviewed, including our own results concerning etretinate-associated bone changes. While there are no more doubts about the potential bone toxicity of 13-cis-retinoic acid, the possibility of etretinate-induced bone changes probably occurring within a longer latency period cannot be conclusively assessed at present. The available clinical data concerning the potential skeletal toxicity of 13-cis-retinoic acid and etretinate should be carefully taken into consideration when determining the risk/benefit ratio, especially for long-term oral retinoid treatment.

Topics: Administration, Oral; Bone and Bones; Bone Diseases; Dermatitis; Etretinate; Humans; Isotretinoin; Retinoids; Risk; Tretinoin

Topics: Adult; Cysts; Dermatitis; Humans; Isotretinoin; Male; Tretinoin