What causes alopecia areata?

Abstract

The pathobiology of alopecia areata (AA), one of the most frequent autoimmune diseases and a major unsolved clinical problem, has intrigued dermatologists, hair biologists and immunologists for decades. Simultaneously, both affected patients and the physicians who take care of them are increasingly frustrated that there is still no fully satisfactory treatment. Much of this frustration results from the fact that the pathobiology of AA remains unclear, and no single AA pathogenesis concept can claim to be universally accepted. In fact, some investigators still harbour doubts whether this even is an autoimmune disease, and the relative importance of CD8(+) T cells, CD4(+) T cells and NKGD2(+) NK or NKT cells and the exact role of genetic factors in AA pathogenesis remain bones of contention. Also, is AA one disease, a spectrum of distinct disease entities or only a response pattern of normal hair follicles to immunologically mediated damage? During the past decade, substantial progress has been made in basic AA-related research, in the development of new models for translationally relevant AA research and in the identification of new therapeutic agents and targets for future AA management. This calls for a re-evaluation and public debate of currently prevalent AA pathobiology concepts. The present Controversies feature takes on this challenge, hoping to attract more skin biologists, immunologists and professional autoimmunity experts to this biologically fascinating and clinically important model disease.

Figure 1

How does round alopecia get formed in skin regions affected by AA? (a) Random autoreactive T cell diffusion hypothesis. (b) Cytokine (interferon c diffusion hypothesis).

Figure 2

Schematic representation of the findings in the GWAS performed by Petukhova et al., 2010 (31).

Figure 3

Suggested susceptibility genes for the development of alopecia areata and their presumed causal mechanism (,–64).

Figure 4

Transmission electron microscopic view of part of an affected hair bulb melanocyte in acute alopecia areata. Note (a) aberrant melanogenesis, as evidenced by the abnormal deposition of melanin in enlarged abnormal melanosomes (MS), and (b) swollen Golgi apparatus. Nu, melanocyte nucleus. Scale bar 0.5 μm.

Figure 5

Transmission electron microscopic view of part of an affected hair bulb in acute alopecia areata with a view through the follicular dermal papilla (DP). Note (a) relatively normal-appearing matrix (Mx) containing melanocytes (Mc), and (b) a more disrupted DP with an active plasma cell (Pc), fibroblasts (Fc) and other cells with immunocyte morphology (Ic). Scale bar 5 μm.

Figure 6

Possible pathomechanism of AA and effect of fexofenadine.