Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata

Abstract

Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However, the immunological aspects of AA in relation to AD are still poorly understood. Therefore, we aim to clarify the immunological properties of AD-associated AA. In this study, we performed comparative analysis of the expression of intracytoplasmic cytokines (IFN-γ, IL-4, and IL-13), chemokine receptors (CXCR3 and CCR4) in peripheral blood which were taken from healthy controls, non-atopic AA patients, AA patients with extrinsic AD, and AA patients with intrinsic AD by flowcytometric analysis. We also compared the scalp skin samples taken from AA patients with extrinsic AD before and after treatment with dupilumab. In non-atopic AA patients, the ratios of CD4+IFN-γ+ cells to CD4+IL-4+ cells and CD4+IFN-γ+ cells to CD4+IL-13+ cells were higher than those in AA patients with extrinsic AD. Meanwhile, the ratio of CD8+IFN-γ+ cells to CD8+IL-13+ cells was significantly higher in the non-atopic AA than in the healthy controls. In AA patients with extrinsic AD, the skin AA lesion showed dense infiltration of not only CXCR3+ cells but also CCR4+ cells around hair bulb before dupilumab treatment. However, after the treatment, the number of CXCR3+ cells had no remarkable change while the number of CCR4+ cells significantly decreased. These results indicate that the immunological condition of AA may be different between atopic and non-atopic patients and between extrinsic and intrinsic AD patients. Our study provides an important notion that type 2 immunity may participate in the development of AA in extrinsic AD patients. It may be considered that the immunological state of non-atopic AA is different from that of atopic AA.

Dupilumab for the treatment of alopecia areata in children with atopic dermatitis

“…While the mechanism of action of dupilumab in AA remains unknown, it has been hypothesized that some patients with AA and AD may exhibit more Th2 skewing. 10,11 Prior reports have suggested that those with more severe and long-standing AD may be more likely to experience hair regrowth with dupilumab; however, that is not a trend that we observed. 6,10 Additional studies will be necessary…”

Baricitinib improved alopecia areata concomitant with atopic dermatitis: A case report

“…4 Recent findings suggest that AA is involved in not only the Th1-driven process but also the Th2 pathway, especially in extrinsic AD patients. 5 Dupilumab, an inteleukin (IL)-4Ra antibody, improved concomittant AA in some AD patients, whereas AA developed after initiating dupilumab in others. Since…”

Alopecia areata: Current understanding of the pathophysiology and update on therapeutic approaches, featuring the Japanese Dermatological Association guidelines

“…In contrast, exacerbation of AA in dupilumab‐treated AD patients has also been reported, 135 thus the efficacy of dupilumab for AA remains controversial. The differences in the response to dupilumab in AA has been speculated to be associated with the characteristics of comorbid AD, intrinsic or extrinsic 52,136 . Kageyama et al 136 reported that dupilumab would be effective for AA patients with extrinsic AD, but not for those with intrinsic AD.…”