Psoriasis is a disease of the entire skin: non-lesional skin displays a prepsoriasis phenotype.

Psoriasis is a multifactorial skin pathology resulting from genetic susceptibility and environmental triggers that lead to epidermal and immune dysfunction. There is now strong evidence that non-lesional (NL) psoriatic skin, despite its normal appearance, represents an intermediate state between healthy and lesional skin. Changes observed in NL skin mainly affect the skin barrier, keratinocytes, innate and adaptive immune responses, the microbiota and neurogenic tissue innervation. Several epidermal barrier defects are commonly observed in NL skin compared to healthy skin, including an elevated pH, delayed barrier function repair after injury and lower expression of epidermal differentiation complex proteins. NL keratinocytes also show a predisposition for activation and proliferation, and an increased sensitivity to cytokine or microbial triggers, probably linked to their unique transcriptome and proteome, associated with their intermediate state between healthy and lesional cells. In addition, the accumulation of pathogenic IL-17-producing resident memory T cells, which can (re)instigate the formation of new lesions, characterises both the NL and never-lesional skin of patients with psoriasis. Although the contribution of NL skin dysbiosis to psoriasis pathophysiology remains to be clarified, the expression of numerous pruritogenic mediators appears to be involved in disease progression due to an iterative itch-scratch cycle. In summary, the NL skin of patients with psoriasis exhibits numerous hallmarks of dormant psoriasis. The fact that these alterations are mostly located in the epidermis suggests that they are readily accessible to topical treatments, which could prevent the recurrence/spread of this chronic disease.

Methotrexate Versus Cyclosporine in Adults with Moderate-to-Severe Atopic Dermatitis: A Phase III Randomized Noninferiority Trial.

BACKGROUND: Methotrexate is currently used to treat atopic dermatitis but has never been assessed versus cyclosporine in adults. OBJECTIVE: This study evaluated the efficacy and safety of methotrexate versus cyclosporine in patients with moderate-to-severe atopic dermatitis. METHODS: Patients were randomized to receive either oral methotrexate (15 mg/wk) or cyclosporine (2.5 mg/kg/d) for 8 weeks. The primary end point was a patient achieving 50% improvement in the SCORing Atopic Dermatitis index (SCORAD 50) at week 8. When the primary end point was not achieved, methotrexate was increased to 25 mg and cyclosporine to 5 mg during the next 16 weeks. The secondary end points were a patient achieving a 50% reduction in the Eczema Area Severity Intensity index (EASI 50) and SCORAD 50 at each visit (ClinicalTrials.gov no. NCT00809172). RESULTS: A total of 97 patients received methotrexate 15 mg (n = 50) or cyclosporine 2.5 mg (n = 47). Regarding the primary end point at week 8, methotrexate was inferior to cyclosporine because the proportion of patients with SCORAD 50 was 8% (4 of 50) in the methotrexate arm versus 42% (18 of 43) in the cyclosporine arm. The difference in percentages for the 2 treatment groups (2-sided 90% CI) was -34% (-48% to -20%). At week 8, methotrexate and cyclosporine dosages were increased in 56% and 49% of the patients, respectively. Regarding EASI 50, the noninferiority end point was reached at week 20 in 92% (22 of 24) of patients in the methotrexate arm and 87% (26 of 30) of patients in the cyclosporine arm. The treatment-related adverse events were more frequent with cyclosporine (P < .0001). CONCLUSIONS: Methotrexate 15 mg/wk was inferior to cyclosporine 2.5 mg/kg/d at week 8. Increasing the doses of methotrexate to 25 mg/wk induced a significant improvement versus cyclosporine at week 20.

Tolerance of oat-based topical products in cereal-sensitized adults with atopic dermatitis.

BACKGROUND: Few data suggest oat-based cosmetics may cause allergic reactions in atopic subjects, especially when sensitized to cereals. OBJECTIVES: To evaluate the risk of immediate and delayed allergic reactions to repeated and maximized applications (RMA) of oat-containing cosmetics and oat extracts and their tolerance in cereal-sensitized atopic adults. METHODS: Open-label pilot study in 12 cereal-sensitized atopic adults over 45 days. Open tests and RMA were performed with Rhealba oat-containing cosmetics at day 0 (D0) and D10, and from D10 to D31. Patch and prick tests were performed at D7 and D42 with wheat and Rhealba oat extracts and the study cream. RESULTS: The RMA of oat-based cosmetics in cereal-sensitized atopic adults did not induce any immediate or delayed allergic reaction and was well tolerated. No immediate or delayed positive skin test to oat extracts was observed. CONCLUSION: Sensitization to cereals does not increase the risk of allergic reactions to oat-containing cosmetics.

Safety and efficacy of transcutaneous vaccination using a patch with the live-attenuated measles vaccine in humans.

Transcutaneous immunisation (TCI) using a skin patch is a non-invasive vaccination route relevant to mass vaccination against infectious diseases. This phase I/II clinical study, documents that TCI of human adult volunteers with the live-attenuated measles vaccine ROUVAX((R)) is safe and poorly reactogenic. It promotes induction of measles-specific salivary IgA and a tendency to increased frequency of MV-specific IFNgamma-producing T cells. However, in contrast to the subcutaneous route, TCI failed to evoke neutralising MV-specific serum antibodies. Thus, alternative delivery methods and/or devices providing optimal uptake by skin DC should be considered for live-attenuated virus vaccines, such as the measles vaccine.

Echographic measurement of skin thickness in adults by high frequency ultrasound to assess the appropriate microneedle length for intradermal delivery of vaccines.

Skin thickness (epidermis-dermis) across the deltoid, suprascapular, waist and thigh as possible body sites for a new microdelivery system for intradermal (id) inoculation were evaluated using 20 MHz ultrasound echography in 205 women and 137 men aged 18-70 years, in three ethnic groups: Caucasian, Asian and Black. Mean skin thickness was 2.54 mm at the suprascapular, 2.02 mm at the deltoid, 1.91 mm at the waist and 1.55 mm at the thigh. A 1.5 mm microneedle length inserted perpendicularly to the skin surface would ensure the administration of the antigen into the dermal layer, irrespectively of subject gender, age, ethnicity and BMI. The deltoid, suprascapular and waist are the most appropriate body sites.

Improvement of atopic dermatitis skin symptoms by Vitreoscilla filiformis bacterial extract.

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease. The first line treatment of AD relies on the daily use of emollients to restore the skin barrier impairment associated with the disease. Vitreoscilla filiformis (V.f.) is a non photosynthetic bacterium and extracts of V.f. are endowed with properties which balance cutaneous immune-homeostasis. The aim of our study was to investigate the efficacy and safety of a 5% V.f. extract-containing ointment on mild to moderate AD in a randomised, double-blind, vehicle-controlled trial. Thirteen patients applied the treatment and the vehicle on symmetrical AD lesions (left versus right side of the body) twice daily for 4 weeks. The assessment of AD severity was done at each visit (Day 0, Day 14 and Day 28) using the modified eczema area and severity index (mEASI). Treatment with the ointment containing 5% V.f. extract significantly improved the AD skin symptoms. Beneficial effects were observed after two weeks of treatment and increased thereafter. These results suggest that V.f. extract could be favourably added to AD skin care emollients formulated for AD.

Methotrexate for the treatment of adult atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease mediated by allergen-specific T cells which are recruited and activated in lesional skin. Methotrexate (MTX) is an old systemic agent used at low dosage for the treatment of psoriasis, another T cell-mediated skin disorder. Since MTX has been shown to improve the clinical symptoms of eczema in a model of antigen-specific dermatitis in mice, we postulated that it could be an effective treatment of AD. In the present open retrospective study, we report our results on the treatment of moderate to severe AD by MTX. Twenty patients (17 to 68-years-old) with low responses to routine therapies were treated (three months to 2 1/2 years) with a weekly dose of MTX ranging from 7.5 to 25 mg. The evaluation was made on physician's global assessment after 3 months of MTX use, and showed that 75% (15/20) of patients improved after 3 months of MTX use, among which 13/20 with an improvement>70%. The beginning of improvement was observed between the fourth and the eighth week after MTX was initiated. Tolerance was good. However, nausea and increase of liver enzymes were observed in 5 patients and required discontinuation of MTX in 2 patients. In conclusion, MTX seems to be an effective and safe treatment of AD. Placebo-controlled clinical trials are needed to confirm our observations and to define more precisely the effectiveness and safety of MTX in adult AD.