Human and computational models of atopic dermatitis: A review and perspectives by an expert panel of the International Eczema Council.

Atopic dermatitis (AD) is a prevalent disease worldwide and is associated with systemic comorbidities representing a significant burden on patients, their families, and society. Therapeutic options for AD remain limited, in part because of a lack of well-characterized animal models. There has been increasing interest in developing experimental approaches to study the pathogenesis of human AD in vivo, in vitro, and in silico to better define pathophysiologic mechanisms and identify novel therapeutic targets and biomarkers that predict therapeutic response. This review critically appraises a range of models, including genetic mutations relevant to AD, experimental challenge of human skin in vivo, tissue culture models, integration of "omics" data sets, and development of predictive computational models. Although no one individual model recapitulates the complex AD pathophysiology, our review highlights insights gained into key elements of cutaneous biology, molecular pathways, and therapeutic target identification through each approach. Recent developments in computational analysis, including application of machine learning and a systems approach to data integration and predictive modeling, highlight the applicability of these methods to AD subclassification (endotyping), therapy development, and precision medicine. Such predictive modeling will highlight knowledge gaps, further inform refinement of biological models, and support new experimental and systems approaches to AD.

A randomized controlled study of combination therapy with alefacept and narrow band UVB phototherapy (UVB) for moderate to severe psoriasis: efficacy, onset, and duration of response.

BACKGROUND: Alefacept is an effective intermittent treatment for psoriasis that can provide long-lasting remissions. Combination therapy with narrow-band ultraviolet B (nbUVB) phototherapy may enhance treatment outcomes and accelerate the onset of clinical response. OBJECTIVE: To assess the efficacy of alefacept in combination with nbUVB phototherapy compared to alefacept alone in subjects with moderate to severe psoriasis. METHODS: Ninety-eight adults with moderate to severe psoriasis were randomized to treatment with alefacept 15 mg intramuscularly (i.m.) once weekly for 12 weeks alone or in combination with three times weekly nbUVB treatments in this prospective, open-label, assessor-blinded, randomized, multicenter, parallel-group, 36-week study. RESULTS: A statistically significantly greater proportion of subjects in the alefacept plus nbUVB arm achieved the primary endpoint of PASI 75 at week 16 compared to subjects in the alefacept alone arm (44.9% vs 22.5%, P=0.032). Secondary outcomes were also in favor of the alefacept plus nbUVB group, including the proportion of subjects achieving a Physician Global Assessment (PGA) score of clear or almost clear at any time during the study (59.2% vs 34.7%, P=0.026) and reduction in percent body surface area (BSA) involved with psoriasis at week 16 (13.4% vs 8.0%, P<0.001). The onset of clinical response was significantly faster in the combination therapy group compared to monotherapy (mean time to PASI 75: 82 vs 107 days, P=0.007). Both treatments were generally well tolerated. LIMITATIONS: Open-label, assessor-blinded study without a phototherapy-only treatment arm. CONCLUSION: The addition of nbUVB to treatment with alefacept significantly enhanced and accelerated the clinical benefits of alefacept therapy and was generally safe and well-tolerated.

Large surface photodynamic therapy with aminolevulinic acid: treatment of actinic keratoses and beyond.

Photodynamic therapy (PDT) with topical aminolevulinic acid (ALA) is currently approved in the US and Canada for the spot treatment of non-hypertrophic actinic keratoses of the face and scalp. Dermatologists are currently using ALA-PDT on larger skin surfaces for the treatment of extensive actinic keratoses, sun damage P and acne. This article reviews the safety and efficacy of large surface ALA-PDT for the treatment of actinic keratoses and photodamage. New data on the carcinogenic potential of weekly topical ALA-PDT in mice is also presented. Groups of hairless mice were treated weekly with either ALA alone, blue light alone or ALA-PDT using blue light for a total of 10 months followed by an additional 2 months or observation. Mice were examined weekly for the presence of skin tumors. Skin tumors were not observed in mice treated weekly with blue light alone, with topical application of ALA alone or with ALA-PDT.