stilbenes and Dermatitis--Contact

Tapinarof cream is a topical aryl hydrocarbon receptor-modulating agent under investigation for the treatment of psoriasis. Tapinarof modulates the expression of interleukin-17 and the skin-barrier proteins filaggrin and loricrin.. We conducted two identical phase 3 randomized trials of tapinarof in patients with mild-to-severe plaque psoriasis. Adults with a baseline Physician's Global Assessment (PGA) score of 2 (mild) to 4 (severe) (on a scale from 0 to 4, with higher scores indicating more severe psoriasis) and a percent of total body-surface area affected of 3 to 20% were randomly assigned in a 2:1 ratio to use tapinarof 1% cream or vehicle cream once daily for 12 weeks. The primary end point, PGA response, was a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points at week 12. Secondary efficacy end points at week 12 were a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) score, a PGA score of 0 or 1, the mean change from baseline in the percent of body-surface area affected, and a reduction of at least 90% in the PASI score. Patient-reported outcomes were the mean changes from baseline to week 12 in the proportion of patients who had a decrease of at least 4 points in the Peak Pruritus Numeric Rating Scale (PP-NRS) score (range, 0 [no itch] to 10 [worst imaginable itch]), the PP-NRS total score, the Dermatology Life Quality Index total score, and the Psoriasis Symptom Diary score.. In trials 1 and 2, a total of 692 and 674 patients, respectively, were screened, with 510 and 515 patients being enrolled. A PGA response occurred in 35.4% of the patients in the tapinarof group and in 6.0% of those in the vehicle group in trial 1 and in 40.2% and 6.3%, respectively, in trial 2 (P<0.001 for both comparisons). Results for secondary end points and patient-reported outcomes were generally in the same direction as those for the primary end point. Adverse events with tapinarof cream included folliculitis, nasopharyngitis, contact dermatitis, headache, upper respiratory tract infection, and pruritus.. Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks but was associated with local adverse events and headache. Larger and longer trials are needed to evaluate the efficacy and safety of tapinarof cream as compared with existing treatments for psoriasis. (Funded by Dermavant Sciences; PSOARING 1 and 2 ClinicalTrials.gov numbers, NCT03956355 and NCT03983980, respectively.).

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Contact; Double-Blind Method; Female; Headache; Humans; Intention to Treat Analysis; Interleukin-17; Male; Middle Aged; Patient Reported Outcome Measures; Psoriasis; Receptors, Aryl Hydrocarbon; Resorcinols; Severity of Illness Index; Skin Cream; Stilbenes

In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells.

Topics: Animals; Apoptosis; Cell Cycle Checkpoints; Dermatitis, Contact; Female; Immunosuppressive Agents; Lymphocyte Activation; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Resveratrol; Stilbenes; T-Lymphocytes

Eighty-three cases of dermatitis caused by wood or sawdust have been seen at St John's Hospital for Dieases of the Skin, London, in the last 20 years. The clinical details and results of patch tests are reported. The literature on dermatitis, mucosal irritation, asthma and other toxic effects of woods of some 300 botanical species is reviewed at length, with an index of scientific, trade and vernacular names, chemical formulae of the known sensitizing substances, and a table of the 28 toxic woods most often encountered. Pathogenesis, diagnosis and prophylaxis are discussed.

Topics: Adolescent; Adult; Coumarins; Dermatitis, Contact; Dermatitis, Occupational; Dust; Female; Humans; Male; Middle Aged; Patch Tests; Plants, Toxic; Protective Clothing; Quinones; Respiratory Tract Diseases; Stilbenes; Terpenes; Urticaria; Wood

Topics: Allergens; Benzimidazoles; Caustics; Clothing; Dermatitis, Contact; Detergents; Fluorescence; Humans; Hypersensitivity, Delayed; Laundering; Pharmaceutical Vehicles; Photosensitivity Disorders; Skin Tests; Stilbenes; Triazines

Topics: Abnormalities, Drug-Induced; Carcinogens; Caustics; Coumarins; Dermatitis, Contact; Environmental Exposure; Fluorescent Dyes; Naphthalenes; Neoplasms, Experimental; Photosensitivity Disorders; Pyrazoles; Stilbenes