AA is difficult to treat. According to the guidelines of the British Association of Dermatologists, contact immunotherapy and corticosteroids are the most effective and best documented, but even these treatments often fail to induce hair growth6
. Therefore, the need exists for more efficient treatments.
The mechanism of topical calcipotriol in inducing hair regrowth in AA lesions is thought to regulate the differentiation of B cells, T cells, dendritic cells, and the expression of Toll-like receptors7
. Growing evidence suggests that use of vitamin D may be helpful in several autoimmune diseases like multiple sclerosis, type 1 diabetes mellitus, lupus, and rheumatoid arthritis8
Vitamin D has a multitude of biological effects that interact with the innate and adaptive immune system, most of which lead to its downregulation7
. Vitamin D has direct effects on T and B cells and shapes their responses to activation. The effect of 1, 25-dihydroxycholecalciferol [1, 25(OH)2
] on the acquired antigen-specific immune response is T lymphocyte proliferation inhibition, particularly of the Th1 arm9
. The addition of 1, 25(OH)2
to CD4 T cells inhibits Th1 cell proliferation and cytokine production10
and leads to decreased secretion of interleukin (IL)-2 and interferon-γ by CD4 T cells and promotes IL-5 and IL-10 production, which further tilts the T cell response toward Th2 dominance11
. Vitamin D has also been shown to inhibit antibody secretion and autoantibody production in B cells12
Dendritic cells play a central role in regulating immune activation and responses to self9
. Dendritic cell maturation is central to the outcome of antigen presentation to T cells9
. In vitro, 1, 25(OH)2
inhibits the differentiation of monocytes into dendritic cells and impedes T cell-induced stimulatory activity13
. It has been shown that 1, 25(OH)2
is one of the most powerful blockers of dendritic cell differentiation and of IL-12 secretion. IL-12 inhibition is achieved through the direct interaction of 1, 25(OH)2
bound to the VDR, which interferes with nuclear factor-kappaB-induced transcription of IL-1214
. Therefore, vitamin D is not the only factor affected by exposure to sunlight that has the capacity to modify immune function. A clinical trial of topical vitamin D analogs for the treatment of AA might be very helpful.
Another possible mechanism is that topical application of vitamin D might play a role in restoration of hair cycle dysfunction in AA. Recently, Xie et al.3
reported that VDR is required for the critical stage of secondary hair follicle development. The development of alopecia in the case of VDR deficiency but not vitamin D deficiency remains unexplained; however, it has been suggested that VDR has ligand-independent roles that are critical to hair follicle cycling3
. The biological actions of vitamin D3 derivatives include regulation of epidermal cell proliferation and differentiation and modulation of cytokine production15
. These effects might explain the efficacy of vitamin D3 derivatives for treating AA.
Our patient with AA did not respond to various treatments, including topical and intralesional corticosteroids. We tried calcipotriol as another treatment option to stimulate impaired function of VDR in AA. VDR is not expressed in only epidermal keratinocytes, but it is also found in the outer root sheath keratinocytes and dermal papilla cells of hair follicles1
. Furthermore, the enzyme for synthesizing 1, 25(OH)2
, 25-hydroxyvitamin D-1a-hydroxylase, is expressed in both the basal layer of the epidermis and the matrix cells of hair follicles in the dermis, suggesting that keratinocytes in hair follicles both make and respond to their own 1,25(OH)2
In this case, we have shown that AA presents with reduced VDR expression and that topical application of a vitamin D analog might be another treatment option upon failure of conventional therapies. To our knowledge, this is the first report of the successful treatment of AA with topical application of a vitamin D analog. Further studies are needed to assess the effectiveness of this therapeutic modality in a greater number of patients with AA.