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

Abstract

Background Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly Th2/“T22” immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate-to-severe AD. In psoriasis, NB-UVB has been found to suppress the Th1/Th17-polarization with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in AD. Objective To evaluate the effects of NB-UVB on immune and barrier abnormalities in AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. Methods 12 moderate-to-severe chronic AD patients received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and non-lesional skin biopsies were obtained before and after treatment and evaluated by gene-expression and immunohistochemistry studies. Results All patients had at least a 50% reduction in SCORing of AD (SCORAD) index with NB-UVB phototherapy. The Th2, “T22,” and Th1 immune pathways were suppressed and measures of epidermal hyperplasia and differentiation normalized. The reversal of disease activity was associated with elimination of inflammatory leukocytes, Th2/“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 Th2 and “T22” inflammation in chronic AD patients with reversal of barrier pathology. By showing reversal of the AD epidermal phenotype with a broad immune-targeted therapy, our data argues against a fixed genetic phenotype.

Estimation of Calcidiol Level in Serum of Atopic Dermatitis Patients before and after NB-UVB Phototherapy in Comparison to Oral Vitamin D Therapy

“…The improvement of clinical signs of atopic dermatitis by the NBUVBtreatment is well documented in literature [2,23,39,40] and is explained by the different mechanisms of actions of nB-UVB. UVB can improve the barrier function through increased expression of terminal differentiation proteins (filaggrin and involucrin) and antimicrobial peptides (AMPs) [41].…”

The role of emollients in pathogenetic therapy of atopic dermatitis in children

“…Несмотря на широкую распространенность данного заболевания, в настоящее время отсутствуют гарантированно эффектив-ные методы терапии, особенно тяжелых форм АтД [9,10,15,20,31,34]. Усугубляется это тем, что нередко врачи не учитывают весь комплекс патогенетических механизмов в формировании АтД.…”

Deciphering the complexities of atopic dermatitis: Shifting paradigms in treatment approaches

“…The arguments against a primary role of the barrier defect in triggering keratinocyte hyperplasia and secondary immune activation include: 1) The FLG mutation is absent in most AD patients (28,29,58); 2) The majority of children with AD outgrow their disease even in the presence of a FLG mutation (59); 3) Unlike ichthyosis vulgaris where the entire skin is affected at birth, in the same genetic background AD patients with FLG mutations have both lesional and non-lesional skin, and the disease develops at some later time-point and does not start at birth; 4) Both lesional and non-lesional AD skin exhibit a broad range of differentiation abnormalities beyond filaggrin (loricrin, involcucrin, corneodesmosin, claudins, etc), suggesting reactive epidermal differentiation/cornification alterations (60, 71); 5) treatment of keratinocytes with IL-4, IL-13, IL-22, IL-25 and IL-31 directly downregulate filaggrin expression and increases kallikrein function which can directly cause barrier dysfunction (21, 23, 42-44, 61, 62). IL-22 directly induces keratinocyte hyperplasia, and downregulation of filaggrin expression (63, 79); 6) mice that are genetically engineered to overexpress Th2 cytokines in their skin spontaneously develop AD and in vivo skin barrier defects (64-67); 7) Filaggrin expression is restored using anti-inflammatory regimens with either topical calcineurin inhibitors or topical corticosteroids (68); 8) Finally, the strongest argument is resolution of clinical AD disease activity in moderate to severe patients with broad based immunosuppressive therapies such as cyclosporine or narrow band UV phototherapy (69,70), and immune targeted therapeutics (dupilumab), that is coupled with resolution of the abnormal epidermal responses (20).…”