tretinoin and Dermatitis--Contact

Management of hand eczema is complex because of the broad range of different pathogeneses, courses, and prognoses. Furthermore, the efficacy of most available treatments is not well established and the more severe forms can have a major impact on the patient's quality of life. Patient education, preventive measures, and the use of emollients are the mainstays in the management of hand eczema. High-potency topical corticosteroids are the treatment of choice, with calcineurin inhibitors used for maintenance. Phototherapy or systemic treatments are indicated in patients who do not respond to topical treatments. Switching from topical treatments should not be delayed to avoid sensitizations, time off work, and a negative impact on quality of life. Alitretinoin is the only oral treatment approved for use in chronic hand eczema.

Topics: Adrenal Cortex Hormones; Alitretinoin; Calcineurin Inhibitors; Chronic Disease; Combined Modality Therapy; Dermatitis, Contact; Dermatologic Agents; Disease Management; Eczema; Emollients; Gloves, Protective; Hand Dermatoses; Humans; Immunosuppressive Agents; Occupational Diseases; Phototherapy; Practice Guidelines as Topic; Quality of Life; Tretinoin

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

Diphencyprone is a potent topical sensitizer, but is non-mutagenic in the Ames test (unlike dinitroclorobenzene) and remains relatively stable in solution (unlike squaric acid dibutyl ester). Seventeen patients with total loss of scalp hair (eight alopecia totalis, nine alopecia universalis) were treated by maintaining on one side of the scalp an allergic contact dermatitis induced by 2,3 diphenylcyclopropenone-I ('diphencyprone'), and on the other side an irritant contact dermatitis using tretinoin gel (Retin A). After 20 weeks, treatment with tretinoin was stopped and diphencyprone was applied bilaterally for a further 10 weeks. Satisfactory regrowth of terminal hair on the scalp was achieved in only one patient. Eyebrow, eyelash and beard regrowth was achieved in one individual whilst in another, moderate, but not cosmetically satisfactory, scalp regrowth took place. In no patient did regrowth take place at tretinoin treated sites until after diphencyprone was substituted.

Topics: Administration, Topical; Adolescent; Adult; Aged; Alopecia; Child; Child, Preschool; Cyclopropanes; Dermatitis, Contact; Female; Humans; Male; Middle Aged; Tretinoin

Topics: Administration, Cutaneous; Aging; Animals; Clinical Trials as Topic; Dermatitis, Contact; Double-Blind Method; Humans; Mice; Mice, Hairless; Middle Aged; Skin; Sunlight; Tretinoin

A 65-year-old women presented with sharply demarcated macules and small nodules on her face and neck for 2.5 years. They first appeared on her left face and gradually spread to her whole face and neck. The lesions were slightly pruritic. Her history was remarkable only for a high dose of topical tretinoin cream 0.025% dosage. On the basis of distribution and history, we made the diagnosis of contact dermatitis for the macules. A biopsy of a red papule from her neck revealed characteristics of pyogenic granuloma. However, white patches appear on his face at the third month follow-up after suspension of the tretinoin cream; Wood's lamp examination was consistent with vitiligo. It is the first report of a dose-response variant of this adverse reaction (Contact dermatitis combined with Pyogenic granulomas).

Topics: Aged; Dermatitis, Contact; Female; Granuloma, Pyogenic; Humans; Irritants; Tretinoin; Vitiligo

There is a major clinical need for new therapies for the treatment of chronic itch. Many of the molecular components involved in itch neurotransmission are known, including the neuropeptide NPPB, a transmitter required for normal itch responses to multiple pruritogens in mice. Here, we investigated the potential for a novel strategy for the treatment of itch that involves the inhibition of the NPPB receptor NPR1 (natriuretic peptide receptor 1). Because there are no available effective human NPR1 (hNPR1) antagonists, we performed a high-throughput cell-based screen and identified 15 small-molecule hNPR1 inhibitors. Using in vitro assays, we demonstrated that these compounds specifically inhibit hNPR1 and murine NPR1 (mNPR1). In vivo, NPR1 antagonism attenuated behavioral responses to both acute itch- and chronic itch-challenged mice. Together, our results suggest that inhibiting NPR1 might be an effective strategy for treating acute and chronic itch.

Topics: Animals; Behavior, Animal; Cell-Free System; Dermatitis, Contact; Disease Models, Animal; Ganglia, Spinal; Humans; Mice, Inbred C57BL; Mice, Knockout; Neurons; Pruritus; Receptors, Atrial Natriuretic Factor; Reproducibility of Results; Signal Transduction; Small Molecule Libraries

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

Novel drug delivery systems, such as solid lipid nanoparticles (SLN), have been proposed to reduce retinoic acid (RA)-induced skin irritation. However, one question still remains: could it be accomplished without reducing efficacy? To evaluate this question the comedolytic effects and epidermal thickening of RA-loaded SLN were compared to the conventional RA formulations (gel or cream), as well as the potential of these formulations to induce skin irritation. The comedolytic effects and epidermal thickening of these formulations, both containing RA at 0.01 or 0.05%, were investigated in a rhino mouse model, while the studies of RA-induced skin irritation were evaluated through rabbit skin irritation tests and in the rhino mouse model. RA-loaded SLN, as compared to the placebo, produced a comedolytic effect with a significant reduction of the utricle diameter, which proved to be similar to that observed for marketed gels or creams regardless of the RA concentration. RA formulations (SLN or marketed cream) also induced an epidermal proliferation leading to a thickened epidermis in treated animals. In both animals studied (rhino mice and rabbits), the RA-loaded SLN, when compared to conventional formulations, promoted a significant reduction in RA-induced skin irritation (erythema and scaling). Then, RA-loaded SLN represents an interesting alternative to reduce RA-induced skin irritation without reducing efficacy, and constitutes an innovative approach for the topical treatment of acne with RA.

Topics: Animals; Cell Proliferation; Dermatitis, Contact; Disease Models, Animal; Drug Delivery Systems; Epidermis; Erythema; Gels; Glutamates; Humans; Lipids; Mice; Nanoparticles; Rabbits; Skin Irritancy Tests; Tretinoin

1α,25-Dihydroxyvitamin D(3) (1,25D3), the active form of vitamin D(3), is an immunoregulatory hormone with beneficial effects on Th1 cell-mediated inflammatory diseases. Although IL-17-producing CD4(+) T helper (Th17) cells have been recently identified as novel effector cells, the immunomodulating effects of 1,25D3 on Th17 cells have not been well defined. We confirmed here that 1,25D3 inhibited the generation of Th17 cells in vitro. Interestingly, 1,25D3 synergistically suppressed the generation of Th17 cells by the combination with all-trans retinoic acid (ATRA). 1,25D3 and ATRA suppressed the development of allergen-induced contact hypersensitivity (CHS) in a mouse ear swelling model. In addition, we found that 1,25D3 and ATRA significantly inhibited the development of human Th17 cells from both naïve and memory human CD4(+) T cells. 1,25D3 and ATRA effectively suppressed mRNA expressions of IL-1R1, IL-21R, IL-23R, RORC, and AHR in human T cells. ATRA further suppressed IL-6R, whereas 1,25D3 did not. Finally, we found that 1,25D3 and ATRA remarkably blocked IL-22 as well as IL-17 mRNA expression in human memory CD4(+) T cells. Thus, we initially reveal that 1,25D3 and ATRA have synergistic effects on the generation of Th17 cells, suggesting that the combination with ATRA would provide a promising novel therapy for Th17 cell-related immune diseases including skin inflammation.

Topics: Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dermatitis, Contact; Drug Synergism; Flow Cytometry; Gene Expression; Humans; Interferon-gamma; Interleukin-17; Interleukin-22; Interleukins; Keratolytic Agents; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Receptors, Interleukin; Receptors, Interleukin-1; Reverse Transcriptase Polymerase Chain Reaction; Th17 Cells; Tretinoin; Vitamin D; Vitamins

Retinoids provide some protection against ultraviolet radiation-induced skin damage. We have previously shown that topical all-trans retinoic acid prevents ultraviolet light from reducing the density of epidermal Langerhans cells in the epidermis but does not inhibit the development of immunosuppression to a locally applied contact sensitizer. We therefore investigated the ability of all-trans retinoic acid to modulate Langerhans cell induction of allogeneic T-cell proliferation in the mixed epidermal cell lymphocyte reaction. Langerhans cells isolated from all-trans retinoic acid-treated mice induced an enhanced mixed epidermal cell lymphocyte reaction. This is similar to Langerhans cells cultured with granulocyte-macrophage colony stimulating factor. Retinoic acid treatment also enhanced the allogeneic cell-stimulating capability of Langerhans cells isolated from ultraviolet-irradiated mice. Langerhans cells from all-trans retinoic acid-treated, ultraviolet-irradiated mice which were "matured" by 3 days in culture induced a larger mixed epidermal cell lymphocyte reaction than mice treated with solvent and ultraviolet irradiation. Thus all-trans retinoic acid treatment of mice causes Langerhans cell maturation and inhibits ultraviolet light from reducing their density or impairing their allogeneic cell-stimulating capacity. However, these mice remained immunosuppressed upon application of a contact sensitizer to irradiated or unirradiated skin. It is thus likely that, whereas all-trans retinoic acid protects local Langerhans cell numbers and function, it does not inhibit the production of an ultraviolet radiation-induced photoproduct which causes immunosuppression.

Topics: Animals; CD4 Antigens; Cell Count; Cells, Cultured; Cellular Senescence; Dermatitis, Contact; Epidermal Cells; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Langerhans Cells; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred BALB C; Picryl Chloride; Tretinoin; Ultraviolet Rays

Topics: Administration, Topical; Adult; Dermatitis, Contact; Drug Eruptions; Female; Humans; Tretinoin

The influence of irritant contact dermatitis on percutaneous penetration was investigated for four 14C-labeled compounds with diverse physicochemical properties: hydrocortisone (HC), indomethacin (IM), ibuprofen (IB), and acitretin (AC). Hairless guinea pigs were pretreated in vivo for 24 h with either 0.5% sodium lauryl sulfate (SLS) to induce irritant contact dermatitis or with water (controls). Twenty-four hours after pretreatment animals were sacrificed. Percutaneous penetration was then measured using in vitro diffusion cells and the removed (pretreated) skin. The following parameters were determined: cumulative amount of compound penetrated, steady state flux, lag time, and permeability coefficient, skin concentration per unit area, and the relative amount of drug remaining in the skin (as a percentage of the cumulative amount of compound penetrated through the skin). SLS pretreatment resulted in moderate irritant dermatitis in all animals and increased in vivo transepidermal water loss 4.5 times. Flux was increased in SLS-pretreated skin as compared with controls for all four compounds, with the greatest enhancement for hydrocortisone (HC) (5.9 times), followed by indomethacin (IM) (4.6 times), ibuprofen (IB) (3.9 times), and acitretin (AC) (3.4 times). Skin concentrations increased to a smaller degree from 1.6 times (IB) and 2.6 times (HC) to 3.4 times (IM). However, AC skin concentrations were not different between the two groups. Thus, percutaneous penetration parameters were equivocally influenced by SLS-induced irritation. Increased skin concentrations were paralleled by even higher increases in flux.

Topics: Acitretin; Administration, Cutaneous; Administration, Topical; Animals; Anti-Inflammatory Agents; Body Water; Dermatitis, Contact; Female; Guinea Pigs; Hydrocortisone; Ibuprofen; Indomethacin; Skin Absorption; Sodium Dodecyl Sulfate; Tretinoin

The influence of sodium lauryl sulfate-induced irritant contact dermatitis on in vivo percutaneous penetration was investigated for four 14C-labeled compounds with diverse physicochemical properties: hydrocortisone (HC), indomethacin (IM), ibuprofen (IB), and acitretin (AC). Hairless guinea pigs were pretreated for 24 h with either 0.5% sodium lauryl sulfate (SLS) to induce irritant contact dermatitis or with water (controls). Twenty-four hours after pretreatment, 450 microliters saturated solutions of HC, IM, IB, or AC in isopropylmyristate were applied to the pretreated skin for 24 h. Systemic absorption was determined by urinary and fecal excretion of compounds. Drug concentrations in stratum corneum (obtained by tape cellophane stripping after decontamination of the application site) and in epidermis/dermis (punch biopsy) were also investigated. Systemic absorption of topically applied drugs (as evaluated by urinary and fecal excretion) in SLS-irritated skin was significantly increased for HC (factor 2.6) followed by IB (1.9 times) and IM (1.6 times) but not increased for AC. However, drug concentrations in the viable epidermis and dermis were 70% lower in SLS-irritated than normal skin for HC, but not different for IB, IM, and AC. Thus, the influence of the state of the skin (irritant dermatitis versus healthy) on percutaneous penetration was different for diverse drugs. The general assumption that percutaneous penetration and drug tissue concentrations were higher in diseased versus healthy skin was not found to be true in our irritated-skin model.

Topics: Acitretin; Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Contact; Female; Guinea Pigs; Hydrocortisone; Ibuprofen; Indomethacin; Skin; Skin Absorption; Sodium Dodecyl Sulfate; Tretinoin

Retinoic acid prevents the decrease in epidermal Langerhans' cell (LC) density which occurs upon application of the tumour promotor 12-O-tetradecanoylphorbol 13-acetate (TPA) to murine skin. This occurred very rapidly, after only 1 week, and was still observed after 4 weeks of treatment. Retinoic acid alone increased the LC density, indicating that it could affect LC density independently of TPA. The induction of a contact sensitivity response which was inhibited by prior treatment with TPA due to the low LC density was also protected by retinoic acid. The anti-carcinogenic activity of retinoic acid is partially the result of its ability to inhibit tumour promotion. The loss of LC may be one of the important steps in tumour promotion as this would allow developing tumours to escape immune destruction. Our studies suggest that the ability of retinoic acid to suppress tumour promotion may be in part by protecting local antigen-presenting cells, thus allowing an immune response to be generated against tumours.

Topics: Animals; Cell Count; Dermatitis, Contact; Langerhans Cells; Male; Mice; Mice, Inbred BALB C; Tetradecanoylphorbol Acetate; Tretinoin

Topics: Benzoyl Peroxide; Carbon Tetrachloride; Cosmetics; Dermatitis, Contact; Female; Humans; Peroxides; Tretinoin

A clinical trial using Airol cream (retinoic acid cream 0.05%), Panoxyl-5 and Panoxyl-10 (benzoyl-peroxide alcoholic gel 5% & 10%) in combination and alone as topical applications for 10 weeks was carried out on 150 ambulatory patients with acne vulgaris. The results based on efficacy, drug tolerance and treatment duration show that the combined use of Panoxyl and Airol is superior to the use of either drug alone and that the combination of Airol cream (0.05%) in the morning and Panoxyl gel (5%) before retiring was the most satisfactory.

Topics: Acne Vulgaris; Adolescent; Adult; Benzoyl Peroxide; Child; Dermatitis, Contact; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Male; Ointments; Peroxides; 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

Three patients treated daily with vitamin A acid cream experienced after one week, seven weeks and 14 weeks respectively sudden redness and itching at the treated sites. Patch testing with the cream (containing 0.05% vitamin A acid) and with vitamin A acid 0.05% in absolute alcohol produced strongly positive reactions in the patients but only slight erythema in some of the controls. Since patch testing with vitamin A acid 0.005% in absolute alcohol elicited no response in controls but positive reactions in the three patients, it is probable that these latter reactions were due to contact allergy. Histologically the test reaction showed intact epidermis and dense dermal infiltration by mononuclear cells, and thus resembled a response of the tuberculin type.

Topics: Biopsy; Dermatitis, Contact; Drug Eruptions; Humans; Hypersensitivity, Delayed; Ointments; Time Factors; Tretinoin; Vitamin A

The daily application of 0-3% retinoic acid to the back produced an acute irritant dermatitis which resolved to a near-normal clinical appearance within 40 days despite continued daily exposure. Hardened skin was markedly altered physiologically. The responses to DMSO, histamine and the histamine liberator, compound 48/80, were sharply enhanced. This reflected enhanced permeability resulting from reduction of the horny layer to less than one-half its normal thickness. Phototoxic and irritant substances produced exaggerated reactions owing to greater penetration. A paradoxical decrease in delayed sinsitivity to streptodornase-streptokinase was attributed to enhanced clearance of the antigen.

Topics: Adult; Dermatitis, Contact; Dimethyl Sulfoxide; Histamine; Humans; Hypersensitivity, Delayed; p-Methoxy-N-methylphenethylamine; Permeability; Skin; Tretinoin; Vitamin A

Two male prison volunteers had severe cutaneous reactions to the initial patch testing of All-trans-retinoic acid containing products being evaluated for irritancy. Muliple patch testing procedures performed throughout one year, along with leukocyte migration inhibition studies, speak strongly for delayed hypersensitivity reactions in these subjects. The failure to document a previous exposure in subjects living in a controlled environment suggests that these responses were cross-reactions to a prior sensitizer, perhaps unique to this environment.

Topics: Adult; Cell Migration Inhibition; Cross Reactions; Dermatitis, Contact; Humans; Hypersensitivity, Delayed; Leukocytes; Male; Middle Aged; Patch Tests; Tretinoin; Vitamin A