Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response

• Published in: Journal of allergy and clinical immunology 2011-09, Vol.128 (3), p.583-593.e4
• Main Authors: Tintle, Suzanne, BS, Shemer, Avner, MD, Suárez-Fariñas, Mayte, PhD, Fujita, Hideki, MD, PhD, Gilleaudeau, Patricia, MSN, FNP, Sullivan-Whalen, Mary, MSN, FNP, Johnson-Huang, Leanne, PhD, Chiricozzi, Andrea, MD, Cardinale, Irma, MSc, Duan, Shenghui, MSc, Bowcock, Anne, PhD, Krueger, James G., MD, PhD, Guttman-Yassky, Emma, MD, PhD
• Format: Article
• Language: English
• Subjects: Adult; Allergic diseases; Allergy and Immunology; Atopic dermatitis; Biological and medical sciences; biomarker; Biomarkers; Biopsy; Chronic Disease; Cytokines; Defects; Dermatitis, Atopic - immunology; Dermatitis, Atopic - pathology; Dermatitis, Atopic - therapy; Disease; Drug therapy; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; Histocompatibility Antigens Class I - immunology; Humans; Hypotheses; Immunopathology; Inflammation - therapy; Ligands; Light therapy; Male; Medical sciences; Methods; Middle Aged; Mutation; narrow-band UVB; Patients; phototherapy; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin; Skin - immunology; Skin - pathology; Skin allergic diseases. Stinging insect allergies; T H2; T22; Th1 Cells - immunology; Th2 Cells - immunology; Treatment Outcome; Ultraviolet Therapy; Variables; Young Adult
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2011.05.042

Background Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly TH 2/“T22” immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate-to-severe AD. In patients with psoriasis, NB-UVB has been found to suppress TH 1/TH 17 polarization, with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in patients with AD. Objective We sought to evaluate the effects of NB-UVB on immune and barrier abnormalities in patients with AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. Methods Twelve patients with moderate-to-severe chronic AD received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and nonlesional skin biopsy specimens were obtained before and after treatment and evaluated by using gene expression and immunohistochemistry studies. Results All patients had at least a 50% reduction in SCORAD index scores with NB-UVB phototherapy. The TH 2, T22, and TH 1 immune pathways were suppressed, and measures of epidermal hyperplasia and differentiation normalized. The reversal of disease activity was associated with elimination of inflammatory leukocytes and TH 2/T22- associated cytokines and chemokines and normalized expression of barrier proteins. Conclusions Our study shows that resolution of clinical disease in patients with chronic AD is accompanied by reversal of both the epidermal defects and the underlying immune activation. We have defined a set of biomarkers of disease response that associate resolved TH 2 and T22 inflammation in patients with chronic AD with reversal of barrier pathology. By showing reversal of the AD epidermal phenotype with a broad immune-targeted therapy, our data argue against a fixed genetic phenotype.