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. 2011 Sep;128(3):583-93.e1-4.
doi: 10.1016/j.jaci.2011.05.042. Epub 2011 Jul 16.

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

Suzanne Tintle  1 , Avner Shemer, Mayte Suárez-Fariñas, Hideki Fujita, Patricia Gilleaudeau, Mary Sullivan-Whalen, Leanne Johnson-Huang, Andrea Chiricozzi, Irma Cardinale, Shenghui Duan, Anne Bowcock, James G Krueger, Emma Guttman-Yassky
Affiliations

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

Suzanne Tintle et al. J Allergy Clin Immunol. 2011 Sep.

Abstract

Background: Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly T(H)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 T(H)1/T(H)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 T(H)2, T22, and T(H)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 T(H)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 T(H)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.

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Figures

Figure 1
Figure 1. Genomic differences in atopic dermatitis (AD) before and after narrowband-UVB (NB-UVB) phototherapy
A, Differentially expressed genes (DEGs) in non-lesional (ANL) and lesional (AL) AD skin before and after NB-UVB (red: gene up-regulation; blue: gene down-regulation). B, A scatterplot of gene-expression values in pre-NB-UVB (x-axis) and post-NB-UVB (y-axis) samples illustrates the substantial reduction (78%) in the AD disease phenotype with NB-UVB.
Figure 2
Figure 2
Immunohistochemistry of non-lesional (ANL) and lesional (AL) atopic dermatitis skin before (pre-) and after (post-) NB-UVB. Staining of hematoxylin and eosin (H&E) (A) and proliferation marker K16 (B) display reductions in epidermal hyperplasia and abnormal proliferation following NB-UVB. C-E; Reductions in dermal (CD3+) T-cells, myeloid (CD11c+) dendritic cells and Langerhans (CD1a+) cells. Scale bar=100 um.
Figure 3
Figure 3
Reductions in epidermal thickness and immune cell infiltrates, quantified by immunohistochemistry, in lesional (AL) (red lines) and non-lesional (ANL) (blue lines) atopic dermatitis following NB-UVB (asterisks above lines: significance of the change). Black error bars and asterisks represent standard error of the mean in normal skin samples and significance of difference in AL or ANL versus normal (when available), respectively. *p<0.05, **p<0.01, ***p<0.001.
Figure 4
Figure 4
RT-PCR expression of selected genes in lesional (AL) (red lines) and non-lesional (ANL) (blue lines) atopic dermatitis following NB-UVB UVB (asterisks above lines: significance of the change). Associated inflammatory pathways (Th1, Th2, Th17, or “T22”) are indicated for each cell type. Black error bars and asterisks represent standard error of the mean in normal skin samples and significance of difference in AL or ANL versus normal (when available), respectively. *p<0.05, **p<0.01, ***p<0.001.
Figure 5
Figure 5
Immunohistochemistry of non-lesional (ANL) and lesional (AL) atopic dermatitis skin before and after NB-UVB. Staining of the terminal differentiation proteins loricrin (LOR) (A), filaggrin (FLG) (B) and involucrin (IVL) (C) displays increased and more continuous granular layer staining following NB-UVB therapy. Scale bar=100 um.
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