tretinoin and Dermatitis--Atopic

Systemic therapy is required in patients with severe atopic dermatitis (AD) refractory to adequate topical therapy. The aim of a systemic therapy is the rapid and efficient improvement of skin symptoms and pruritus in acute exacerbation and/or the long-term control of severe chronic disease. A number of immunosuppressive and immunomodulating substances are available that may efficiently reduce skin inflammation and thus lead to a relief of symptoms including pruritus. The excellent effects of cyclosporine as short-term as well as maintenance therapy have been documented in several studies in children and adults. Furthermore, other immunosuppressive substances such as azathioprine, mycophenolate mofetil and methotrexate are effective in patients with moderate to severe AD. Intravenous immunoglobulins and γ-interferon exert immunomodulatory effects and thus may improve severe AD. Biological agents are a new approach in AD therapy since they may specifically target cells, cytokines or mediators involved in the pathogenesis of AD.

Topics: Adrenal Cortex Hormones; Adult; Alitretinoin; Antibodies, Monoclonal; Azathioprine; Child; Cyclosporine; Dermatitis, Atopic; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Interferon-gamma; Methotrexate; Mycophenolic Acid; Recombinant Proteins; 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

Dermo-epidermal atrophy is one of the main side effects of long-term treatment with topical corticosteroids (TC). Retinoic acid (RA) may prevent and even reverse these effects in animals. It has been previously established that topical RA (TRA) does not inhibit corticosteroid-induced vasoconstriction in humans, thus suggesting that RA, combined with TC, does not interfere with its anti-inflammatory property. The next step was to test this association in patients with inflammatory skin disorders. In this symmetrical double-blind study, triamcinolone acetonide (TA) cream 0.1% and a cream containing TA 0.1% plus RA 0.025% (TARA) were compared in 18 subjects with eczema. No statistical difference between both treatments was observed after 1, 2 and 3 weeks, although on the TARA-treated sides the anti-inflammatory responses were slightly less pronounced. Subjective irritation was significantly more frequent in TARA-treated side (3/17, p = 0.05) but did not lead to interruption of the treatment. This indicates that addition of RA 0.025% to a medium-range potency topical steroid does not abrogate the anti-inflammatory property of the latter and that the association can be tolerated by inflamed skin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Dermatitis, Allergic Contact; Dermatitis, Atopic; Dermatitis, Irritant; Double-Blind Method; Drug Combinations; Drug Tolerance; Eczema; Female; Humans; Male; Middle Aged; Tretinoin; Triamcinolone Acetonide

TSLP is an important trigger and initiator for various atopic diseases mainly atopic dermatitis (AD). Activators of nuclear hormone receptors like bioactive vitamin A and D derivatives are known to induce TSLP up-regulation in the skin. In this study, various combinations of synthetic specific agonists and antagonists of the retinoic acid receptors (RARs), retinoid X receptors (RXRs) and vitamin D receptor (VDR) were topically administered to mice. The aim of the study was to elucidate via which nuclear hormone receptor pathways TSLP is regulated and how this regulation is connected to the development and phenotype of atopic dermatitis. TSLP expression was monitored using QRT-PCR and serum TSLP levels using ELISA. Synthetic agonists of the VDR and RARγ as well as the natural agonist all-trans retinoic acid (ATRA) increased TSLP expression in the skin, while an RXR agonist was not active. Treatments with antagonists of RXRs and RARs in addition to RARα-agonists reduced skin TSLP expression. Strong activation was found after a combination of a VDR and an RXR agonist (ca. 5 times induction) and even stronger by an RARγ and an RXR agonist treatment (ca. 48 times induction). We conclude that besides VDR-mediated signaling mainly RARγ-RXR mediated pathways in the skin are important patho-physiological triggers for increased skin TSLP expression. We conclude that topical synthesized retinoids stimulated by internal or external triggers or topically applied induce TSLP production and are thereby important triggers for atopic dermatitis prevalence.

Topics: Adolescent; Adult; Animals; Calcitriol; Coumaric Acids; Cytokines; Dermatitis, Atopic; Female; Gene Expression Regulation; Humans; Immunization; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Organic Chemicals; Ovalbumin; Receptors, Calcitriol; Receptors, Retinoic Acid; Retinoic Acid Receptor gamma; Retinoid X Receptors; Signal Transduction; Skin; Tetrahydronaphthalenes; Thymic Stromal Lymphopoietin; Tretinoin

Eotaxins and their receptor CCR3 have a definitive role for tissue accumulation of eosinophils both under homeostatic and pathologic conditions. However, physiological stimuli that can up-regulate CCR3 in blood-derived human eosinophils have not been recognized. As a prior gene microarray study revealed up-regulation of CCR3 in eosinophils stimulated with retinoic acids (RAs), the expression of functional CCR3 was examined. We found that 9-cis RA and all-trans RA (ATRA) significantly induced surface CCR3 expression regardless of the presence of IL-3 or IL-5. Pharmacological manipulations with receptor-specific agonists and antagonists indicated that retinoic acid receptor-α activation is critical for CCR3 up-regulation. RA-induced CCR3 was associated with its functional capacity, in terms of the calcium mobilization and chemotactic response to eotaxin-1 (CCL11). Our study suggests an important role of vitamin A derivatives in the tissue accumulation of eosinophils.

Topics: Cells, Cultured; Chemokine CCL24; Chemotactic Factors, Eosinophil; Chemotaxis, Leukocyte; Dermatitis, Atopic; Eosinophils; Gene Expression Regulation; Humans; Receptors, CCR3; Sensitivity and Specificity; Signal Transduction; Tretinoin; Up-Regulation

Atopic dermatitis (AD) is one of the most common skin diseases. Various features present in AD like inflammation, reduced apoptosis, altered epidermal differentiation and hyperproliferation as well as permeability dysfunction are also regulated by retinoids. The aim of our study is to identify the retinoid signalling pathways and retinoid concentration profiles in AD skin. Human skin biopsies were obtained from healthy volunteers (HS) (n=6) and patients with AD (n=6), with both affected (AS) and non-affected (NAS) skin. The gene expression of retinoid receptors, retinoid-binding proteins and retinoid-metabolizing enzymes was investigated by QRT-PCR. Retinoid concentrations in serum and skin were measured via high performance liquid chromatography mass spectrometry-mass spectrometry. Our results show that the target gene expression of retinoid receptor regulated pathways is significantly decreased in AS and NAS of patients with AD. CYP26A1, transglutaminase 2 and retinoic acid receptor responder 1 decreased in NAS and AS in comparison with HS. The main retinoic acid synthesizing enzyme, retinal dehydrogenase 1, was significantly lower expressed in NAS (0.1%) and AS (1%) in patients with AD. Analysis of retinoid concentration in serum and skin showed comparable all-trans retinoic acid (ATRA) and retinol (ROL) concentrations from AD and healthy serum, but strongly reduced ATRA and ROL concentrations in affected and non-affected skin in comparison with healthy skin. Our data indicate that retinoid transport, synthesis, concentrations and signalling are strongly decreased in the affected but also in non-affected skin of patients with AD suggesting a general intrinsic influence on skin retinoid signalling pathway in patients with AD.

Topics: Adolescent; Adult; Cytochrome P-450 Enzyme System; Dermatitis, Atopic; Female; Gene Expression; Gene Expression Profiling; GTP-Binding Proteins; Humans; Male; Membrane Proteins; Middle Aged; Protein Glutamine gamma Glutamyltransferase 2; Retinal Dehydrogenase; Retinoic Acid 4-Hydroxylase; Retinoids; RNA, Messenger; Signal Transduction; Skin; Transglutaminases; Tretinoin; Vitamin A; Young Adult

Topics: Administration, Oral; Adult; Alitretinoin; Chronic Disease; Dermatitis, Atopic; Dermatologic Agents; Female; Hand Dermatoses; Humans; Male; Middle Aged; Treatment Outcome; Tretinoin; Young Adult

Psoriasis is a type I interferon-driven T cell-mediated disease characterized by the recruitment of plasmacytoid dendritic cells (pDC) into the skin. The molecules involved in pDC accumulation in psoriasis lesions are unknown. Chemerin is the only inflammatory chemotactic factor that is directly active on human blood pDC in vitro. The aim of this study was to evaluate the role of the chemerin/ChemR23 axis in the recruitment of pDC in psoriasis skin. Prepsoriatic skin adjacent to active lesions and early lesions were characterized by a strong expression of chemerin in the dermis and by the presence of CD15(+) neutrophils and CD123(+)/BDCA-2(+)/ChemR23(+) pDC. Conversely, skin from chronic plaques showed low chemerin expression, segregation of neutrophils to epidermal microabscesses, and few pDC in the dermis. Chemerin expression was localized mainly in fibroblasts, mast cells, and endothelial cells. Fibroblasts cultured from skin of psoriatic lesions expressed higher levels of chemerin messenger RNA and protein than fibroblasts from uninvolved psoriatic skin or healthy donors and promoted pDC migration in vitro in a chemerin-dependent manner. Therefore, chemerin expression specifically marks the early phases of evolving skin psoriatic lesions and is temporally strictly associated with pDC. These results support a role for the chemerin/ChemR23 axis in the early phases of psoriasis development.

Topics: Adult; Antibodies, Monoclonal; Antigens, CD; Blotting, Western; Calcitriol; CD8-Positive T-Lymphocytes; Cells, Cultured; Chemokine CXCL10; Chemokines; Chemotaxis, Leukocyte; Culture Media, Conditioned; Dendritic Cells; Dermatitis, Atopic; Extracellular Signal-Regulated MAP Kinases; Fibroblasts; Gene Expression; Humans; Intercellular Adhesion Molecule-1; Intercellular Signaling Peptides and Proteins; Lectins, C-Type; Membrane Glycoproteins; Neutrophils; Psoriasis; Receptors, Chemokine; Receptors, Immunologic; Reverse Transcriptase Polymerase Chain Reaction; Skin; Tretinoin

A case of molluscum contagiosum arising on the face and neck of a woman using topical tacrolimus over a period of 6 weeks for the treatment of atopic dermatitis is presented. Of particular note, these lesions remained confined to areas treated with tacrolimus and did not extend to adjacent regions treated with topical corticosteroids.

Topics: Administration, Topical; Adult; Betamethasone Valerate; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Molluscum Contagiosum; Ointments; Tacrolimus; Treatment Outcome; Tretinoin

Molluscum contagiosum is a viral disease frequently observed in children and adolescents with atopic dermatitis, in whom it poses a special therapeutic challenge. A 3-year-old girl presented with atopic eczema and disseminated molluscum contagiosum on her buttocks and upper legs. Topical application of 0.05% tretinoin resulted in a steady regression of the lesions. Other therapeutic options include topical anti-viral agents, cryosurgery, laser treatment, and curettage. Further, the therapeutic outcome is highly dependent on an adequate therapy of the concomitant atopic eczema.

Topics: Administration, Oral; Administration, Topical; Child, Preschool; Dermatitis, Atopic; Drug Therapy, Combination; Female; Humans; Molluscum Contagiosum; Prednisolone; Superinfection; Tretinoin

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

This study was designed to investigate the effects of increased or decreased epidermal turnover on the morphology of human corneocytes. The desquamating portion of the stratum corneum was sampled with the detergent scrub technique using Triton X-100. The following parameters were measured: size (surface micron2), shape (regular, irregular), nuclear inclusions, trabeculae, and numerical counts. Specimens were obtained from adult males with allergic contact dermatitis (N=18); with tretinoin-induced dermatitis (N=11); after cellophane stripping (N=11); and after treatment of these conditions with topical steroids (N=40). Data from 250,000 cells were analyzed statistically. The reproducibility of the method is good (r=0.934). Corneocytes from skin of patients with allergic contact dermatitis differed from those of normal skin: they were 15% smaller and of irregular shape with asymmetrical trabeculae; 50% were nucleated and about 3 times as many cells were collected per cm2 skin surface. Tretinoin and stripping produced similar but more pronounced effects. Topical steroids significantly improved all parameters (p less 0.01). Betamethasone-17-dipropionate was more effective than the valerate. This bioassay permits sensitive measurements of corneocyte morphology in conditions with altered epidermal cellular kinetics. It provides a method to evaluate steroid effectiveness.

Topics: Adult; Aged; Betamethasone; Betamethasone Valerate; Cell Count; Cell Division; Cell Nucleus; Dermatitis, Atopic; Dermatitis, Contact; Humans; Male; Middle Aged; Skin; Time Factors; Tretinoin