Guidelines for the diagnosis and treatment of male-pattern and female-pattern hair loss, 2017 version.

Male-pattern hair loss (MPHL, androgenetic alopecia) is a slowly progressive form of alopecia which begins after puberty. In 2010, we published the first Japanese edition of guidelines for the diagnosis and treatment of MPHL. It achieved the original goal of providing physicians and patients in Japan with evidence-based information for choosing efficacious and safe therapy for MPHL. Subsequently, new therapeutic drugs and treatment methods have been developed, and women's perception of MPHL has undergone change and the term "female-pattern hair loss (FPHL)" is becoming more common internationally. Thus, here we report a revised version of the 2010 guidelines aimed at both MPHL and FPHL. In these guidelines, finasteride 1 mg daily, dutasteride 0.5 mg daily and topical 5% minoxidil twice daily for MPHL, and topical 1% minoxidil twice daily for FPHL, are recommended as the first-line treatments. Self-hair transplantation, irradiation by light-emitting diodes and low-level lasers, and topical application of adenosine for MPHL are recommended, whereas prosthetic hair transplantation and oral administration of minoxidil should not be performed. Oral administration of finasteride or dutasteride are contraindicated for FPHL. In addition, we have evaluated the effectiveness of topical application of carpronium chloride, t-flavanone, cytopurine, pentadecane and ketoconazole, and wearing a wig. Unapproved topical application of bimatoprost and latanoprost, and emerging hair regeneration treatments have also been addressed. We believe that the revised guidelines will improve further the diagnostic and treatment standards for MPHL add FPHL in Japan.

Combination therapy with oral PUVA and corticosteroid for recalcitrant alopecia areata.

Alopecia areata (AA) is regarded as a tissue-specific autoimmune disease for which several therapies have been suggested to modify the immune reaction against HFs, such as contact immunotherapy, psoralen plus ultraviolet A (PUVA), corticosteroids, cyclosporine, minoxidil, and dithranol. However, severe type AA, such as alopecia totalis (AT) and alopecia universalis (AU), often show resistance against these therapies. We applied a combination therapy with oral corticosteroid and oral PUVA for intractable cases of AT and AU. These patients took 20 mg/day corticosteroid and were irradiated with UVA on the whole body 2 h after taking methoxsalen for 1 month. In all patients, the terminal hair on the whole scalp regrew after 2 months. Two patients had a relapse of hair loss 3 months after the termination of the treatment. FACS analysis revealed that the CD4+CD25(high) and CD4+CD25+FOXP3+ Treg population in PBMC was increased after the combination therapy. Furthermore, the number of infiltrating cells decreased and FOXP3+ cells were often found in lesion skin after the combination therapy. Mitogen-induced proliferation tests showed low responses against PHA and Con A after the combination therapy. Taken together, the combination therapy may modify the systemic immune system and increase the number of Treg cells, resulting in improvement of recalcitrant AA.

Anti-allergic Psidium guajava extracts exert an antitumor effect by inhibition of T regulatory cells and resultant augmentation of Th1 cells.

Th1 polarization is one of the mechanisms underlying the therapeutic effects of herbal medicine. The action of anti-allergic agents from Psidium guajava (P. guajava) on T cell immunity in mice was investigated. The addition of P. guajava extracts blocked IL-10-mediated, in vitro induction of T regulatory (Tr) cells from CD4+ splenocytes of C57BL/6 mice, whereas the extracts exerted only a weak or no effect on the development of Th1 and Th2 cells. Accordingly, Tr cells were not induced from splenocytes of mice administered orally with the extracts. Furthermore, P. guajava extracts shifted the Th1/Th2 balance to a Th1 dominant status by directly attenuating Tr cell activity. In a study of tumor immunity, mice pretreated with the extracts exhibited retarded growth of s.c. inoculated B16 melanoma cells. These findings suggest that P. guajava extracts are efficacious for the prevention of tumor development by depressing Tr cells and subsequently shifting to Th1 cells.

Unique therapeutic effects of the Japanese-Chinese herbal medicine, Sairei-to, on Th1/Th2 cytokines balance of the autoimmunity of MRL/lpr mice.

Sairei-to, one of the Japanese-Chinese herbal medicines has been used for the treatment of various diseases, especially collagen disease and edema in nephrotic syndrome. However, the mechanism of the therapeutic effects remains uncertain. Therefore, we investigated the immunological changes of skin, kidney, spleen cells and serum in autoimmune-prone MRL/lpr, MRL/n and C57BL/6J mice treated with Sairei-to. In MRL/lpr mice treated with Sairei-to, the improvement of proteinuria, reduction in the number of hematoxylin bodies in kidney, and reduced serum levels of blood urea nitrogen were observed. These results indicate that Sairei-to can improve or inhibit the progression of lupus nephritis. The proportion of CD19 and the serum levels of IgG1, which is one of the pathogenesis of lupus dermatoses and lupus nephritis, were significantly reduced in Sairei-to-treated MRL/lpr mice. Therefore, it is suspected that the B cell function was suppressed by Sairei-to. In addition, CD4/8 ratio in spleen cells and the degree of lymphoproliferation in MRL/lpr mice also decreased. Interestingly, IL-4 producing spleen cells were increased significantly by ELISPOT assay, and IFN-gamma mRNA expressions were reduced in Sairei-to-treated MRL/lpr mice. Regarding the Th balance, an imbalance towards Th1 predominance may play a significant role in MRL/lpr mice, and the Th1 axis was suppressed and the Th2 axis became predominant in Sairei-to-treated MRL/lpr mice. On the other hand, Th2 cell type immunoglobulins (IgG1) were suppressed. These results suggested that Sairei-to is potential for impairing shifted Th1/Th2 balance and hypergammaglobulinemia resulting in therapeutic effects.