calcipotriene and Dermatitis--Contact

Topics: Aged; Calcitriol; Dermatitis, Contact; Dermatologic Agents; Humans; Male

One hundred and sixty-eight individuals (psoriatic patients treated with calcipotriol with dermatitis due to calcipotriol, psoriatic patients treated with calcipotriol with no dermatitis, psoriatic patients never treated with calcipotriol, patients with eczema and healthy volunteers) were patch-tested (Finn chambers, back, 48 h) with dilutions of calcipotriol ointment (50, 10, 2, 0.4 micrograms/g) and an ointment vehicle. Test evaluation was based on clinical scoring and various non-invasive measuring methods. Doubtful (?+) and weak (1+) reactions were common, irrespective of patient group and history. Moderate (2+) reactions were uncommon and with no increased frequency among psoriatic patients with adverse dermatitis during calcipotriol treatment. The blood flow of test sites measured by laser Doppler flowmetry was, however, increased in psoriatics, who developed dermatitis during calcipotriol treatment as an isolated finding. Furthermore a 1-week repeated open application test (ROAT) was performed on all subjects. None of the persons having a strong reaction in the patch test showed any dermatitis in the ROAT test, indicating that they were not sensitized. Calcipotriol was found to be a mild irritant of the non-corrosive type, i.e. with no influence on the skin barrier. Reactions were dominated by redness (increased laser Doppler flow and chroma a*) and only oedema formation in advanced reactions. The calcipotriol dose-irritation curve was found to be scattered. Calcipotriol induced no increase of transepidermal water loss (TEWL) versus the ointment vehicle, but the ointment vehicle itself increased TEWL. The special ointment vehicle needed for calcipotriol for stability reasons may itself be irritant and cause some impairment of the skin water barrier, with increase in TEWL values. Future patch test studies for calcipotriol allergy should not be done with this vehicle. The non-irritant threshold concentration of calcipotriol in an appropriate test vehicle is still unknown.

Topics: Adult; Aged; Calcitriol; Dermatitis, Allergic Contact; Dermatitis, Contact; Dermatologic Agents; Double-Blind Method; Drug Eruptions; Female; Humans; Male; Middle Aged; Ointments; Patch Tests; Pharmaceutical Vehicles; Psoriasis; Skin

In this study, we investigated the effect of calcipotriol, prednicarbate and clobetasol 17-propionate on skin thickness over a treatment period of 6 weeks. The study was conducted as a controlled, randomized, double-blind comparison. The influence of these drugs on normal skin under occlusive conditions was assessed visually and by measuring skin thickness using 20 MHz B mode ultrasound. Both topically applied glucocorticosteroids lead to a significant decrease in skin thickness. In contrast to the glucocorticosteroid-induced atrophy, calcipotriol application on normal skin leads to an increase in skin thickness in all volunteers. The effect remains constant for the duration of treatment. The cause of this increase seems to be an irritative reaction of the skin which was histologically investigated in one volunteer. The histological features of this reaction are characteristic for a subacute dermatitis. The implications of these findings for the therapeutic mechanism of calcipotriol are discussed.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Atrophy; Calcitriol; Clobetasol; Dermatitis, Contact; Dermatologic Agents; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Middle Aged; Prednisolone; Skin; Ultrasonography

PD-1 is an immunoregulatory receptor that can bind PD-L1 or PD-L2 expressed on stimulated antigen-presenting cells. In this study, isolated antigen-presenting cells (macrophages and dendritic cells) were cultured with IFN-γ, IL-4, or IL-17A, and the expression of PD-L1 and PD-L2 was compared by flow cytometry. Strong upregulation of PD-L1 expression was observed on IFN-γ stimulation of both antigen-presenting cells as well as in response to IL-17A stimulation of macrophages compared with the expression in unstimulated controls. In contrast, only stimulation with IL-4 could upregulate PD-L2 expression on both antigen-presenting cells. Therefore, experiments were performed in murine models, including DNFB-induced contact hypersensitivity, calcipotriol-induced atopic dermatitis-like skin inflammation, and imiquimod-induced psoriasis-like dermatitis models, to trigger IFN-γ‒mediated T helper type (Th)1-, IL-4‒mediated Th2-, and IL-17A‒mediated Th17-type responses, respectively. In both Th1- and Th17-type immunity models, changes in ear thickness were more severe in Pd-l1‒deficient mice than in wild-type or Pd-l2‒deficient mice. In the Th2-type immunity model, changes in thickness in Pd-l2‒deficient mice were more severe than that in wild-type or Pd-l1‒deficient mice. Collectively, PD-L1 has predominant roles in Th1 and Th17 type immunity, whereas PD-L2 is involved in Th2-type immunity.

Topics: Animals; Antigen Presentation; B7-H1 Antigen; Calcitriol; Cells, Cultured; Cytokines; Dendritic Cells; Dermatitis, Atopic; Dermatitis, Contact; Dinitrofluorobenzene; Disease Models, Animal; Humans; Imiquimod; Inflammation; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Programmed Cell Death 1 Ligand 2 Protein; Psoriasis; Skin; Th1 Cells; Th17 Cells; Th2 Cells

Th2 immunity plays important roles in both protective and allergic responses. Nevertheless, the nature of antigen-presenting cells responsible for Th2 cell differentiation remains ill-defined compared with the nature of the cells responsible for Th1 and Th17 cell differentiation. Basophils have attracted attention as a producer of Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) expression and function as antigen-presenting cells are matters of considerable controversy. Here we revisited the MHC-II expression on basophils and explored its functional relevance in Th2 cell differentiation. Basophils generated in vitro from bone marrow cells in culture with IL-3 plus GM-CSF displayed MHC-II on the cell surface, whereas those generated in culture with IL-3 alone did not. Of note, these MHC-II-expressing basophils showed little or no transcription of the corresponding MHC-II gene. The GM-CSF addition to culture expanded dendritic cells (DCs) other than basophils. Coculture of basophils and DCs revealed that basophils acquired peptide-MHC-II complexes from DCs via cell contact-dependent trogocytosis. The acquired complexes, together with CD86, enabled basophils to stimulate peptide-specific T cells, leading to their proliferation and IL-4 production, indicating that basophils can function as antigen-presenting cells for Th2 cell differentiation. Transfer of MHC-II from DCs to basophils was also detected in draining lymph nodes of mice with atopic dermatitis-like skin inflammation. Thus, the present study defined the mechanism by which basophils display MHC-II on the cell surface and appears to reconcile some discrepancies observed in previous studies.

Topics: Amino Acid Sequence; Animals; Antigen Presentation; Antigen-Presenting Cells; Basophils; Calcitriol; Cells, Cultured; Coculture Techniques; Cytokines; Dendritic Cells; Dermatitis, Contact; Genes, MHC Class II; Histocompatibility Antigens Class II; Immunological Synapses; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Peptide Fragments; Specific Pathogen-Free Organisms; Th2 Cells; Tryptases

Vitamin D3 derivatives are new compounds used topically for the treatment of psoriasis. To get better insights into the mechanisms of action of these compounds, we studied the effect of local treatment with calcipotriol (vitamin D3 synthetic analogue) and compared it to that of betamethasone dipropionate in a murine contact sensitivity (CS) test, the Mouse Ear Swelling Test. Two haptens were used: oxazolone and paraphenylenediamine. Betamethasone and calcipotriol exerted a differential effect on the delayed-type hypersensitivity response. When drugs were applied to the abdomen (sensitization site) before sensitization, no effect was observed. When betamethasone was applied to the abdomen for 4 consecutive days after epicutaneous sensitization, a diminution of the CS response to the relevant hapten was observed, whereas calcipotriol given in the same conditions did not affect the reaction. Ointments were then administered to the ear (elicitation site) either for 4 consecutive days prior to the challenge, or for 4 days before and 2 days after the challenge. In both conditions, calcipotriol and betamethasone exerted a differential effect on elicitation, the latter inhibiting and the former increasing the CS response to oxazolone and paraphenylenediamine. From these results we conclude: (1) that vitamin D3 derivatives are devoided of immunosuppressive effects when applied topically, and (2) that clinical improvement of chronic inflammatory dermatoses observed with topical vitamin D3 derivatives and corticosteroids is due to different mechanisms.

Topics: Adrenal Cortex Hormones; Animals; Calcitriol; Dermatitis, Contact; Dermatologic Agents; Female; Hypersensitivity, Delayed; Immunosuppressive Agents; Lymphocyte Activation; Mice; Mice, Inbred BALB C; T-Lymphocytes

Topics: Calcitriol; Dermatitis, Contact; Female; Humans; Middle Aged; Patch Tests; Psoriasis

Topics: Acute Disease; Administration, Cutaneous; Aged; Calcitriol; Dermatitis, Contact; Female; Humans; Patch Tests; Psoriasis; Recurrence