edited for hair loss blog

Arch Dermatol Res. 2006;298:131

Induction of cellular immunity against hair follicle melanocyte causes hair loss.
Nagai H, et al

Hair loss due to Alopecia areata is an autoimmune disease. Although it has been hypothesized that the autoimmunity is mediated by T cells and that hair follicle melanocyte is one of the targets, definitive evidence is lacking. We here demonstrate that AA-like lesions can be induced in mice by inducing CD8(+) T-cell-mediated immunity to hair follicle melanocytes. We found that hair loss was induced in mice-bearing interleukin-12-producing B16 melanoma cells by the depletion of CD4(+) T cells, accompanied by vitiligo-like coat color change. The alopecic lesions varied in size from pachy to extensive. In many instances, hair loss developed and was followed by the regrowth of white hairs. Histological analysis revealed that mononuclear cells infiltrated in and around the bulb region of hair follicles. Furthermore, immunohistochemical examination clearly showed the intra-follicular infiltration of CD8(+) T cells. Neither the vitiligo-like coat color nor AA-like lesions were induced when CD8(+) T cells were codepleted. These observations indicate that the induction of CD8(+) T-cell-mediated immunity against hair follicle melanocytes causes alopecia. It is thought that there are many types of AA with different mechanisms, targets etc. Although hair follicle melanocytes have long been thought to be one of the targets of AA, evidence to support the hypothesis is sparse. Therefore, we believe that our observation is significant to support the hypothesis.

Proc Natl Acad Sci U S A. 1988;85:7739

Evidence that the effector mechanism of skin allograft rejection is antigen-specific.
Rosenberg AS, Singer A.

edited for hair loss blog

In vivo rejection responses are initiated by specific T-cell recognition of foreign antigens…., but it is not certain if the effector mechanism mediating the actual tissue injury is also antigen-specific. snip… Trunk skin from B6 in equilibrium with A/J allophenic mice was grafted onto immunoincompetent mice and allowed to heal and regrow hair that was both black and white, reflecting the genetic mosaicism of the allophenic grafts. One month after engraftment, the H-2b nude animals were reconstituted with syngeneic H-2b T cells reactive against H-2a allodeterminants. An obvious rejection response ensued involving antigen-nonspecific inflammatory destruction of the epidermis and complete hair loss. Despite the intensity of the nonspecific inflammatory response, the foreign skin grafts survived. Importantly, the allophenic grafts regrew hair and the predominant color of that hair was black, providing visual proof that syngeneic B6 melanocytes and hair follicle cells had not been destroyed. Thus, these results demonstrate that although the intense inflammatory component of skin graft rejection responses is capable of damaging superficial epidermal cells nonspecifically, it does not cause rejection of skin allografts. Rather, rejection of skin allografts is mediated by antigen-specific effector T cells that assess individual cells within the dermis of the graft for expression of foreign histocompatibility antigens.

Hair Loss Treatment at the Proctor Clinic

J Am Acad Dermatol. 2009;6:592.e1-9.

Comparison of topical bexarotene 1% gel for alopecia areata.

Talpur R, et al

Alopecia areata, hair loss caused by T-cell infiltrates, is refractory to therapy. Bexarotene, a retinoid X receptor is a selective retinoid, induces T-cell apoptosis. OBJECTIVE: We sought to determine the safety, including the dose-limiting toxicities with adverse events, and efficacy, ie, response rate, of bexarotene in alopecia areata. METHODS: We conducted a trial of 1% bexarotene gel applied twice daily for 6 months. RESULTS: In all, 42 patients with alopecia totalis , alopecia universalis, or alopecia areata applied 1% bexarotene gel for 24 weeks. Five of 42 had 50% or more partial hair regrowth on the treated side, and 6 of 42 on both sides including 3 complete responders. In all, 31 patients had mild irritation; 4 had grade-3 irritation. LIMITATIONS: This design cannot differentiate between drug-induced and spontaneous regrowth. Topical bexarotene 1% application is well tolerated and possibly effective. A randomized placebo-controlled trial should be conducted.

Exp Dermatol. 2008;17:793

The C3H/HeJ mouse and DEBR rat models for alopecia areata…

Jing Sun, M.D., et eal

The C3H/HeJ inbred mouse strain and the Dundee Experimental Bald Rat (DEBR) strain spontaneously develop hair loss due to adult onset alopecia areata (AA), a cell mediated disease directed against actively growing hair follicles. The low frequency of AA and the inability to predict the stage of AA as it evolves in the naturally occuring C3H/HeJ model of AA can be converted into a highly predictable system by grafting full thickness skin from AA affected mice to normal haired mice of the same strain. The rat DEBR model develops spontaneous AA at a higher frequency than in the mouse model but they are more expensive to use in drug studies due to their larger size. Regardless of the shortcomings of either model, these rodent models can be used succesfully to screen novel or approved drugs for efficacy to treat human AA. Since the pathogenesis of AA follows the canonical lymphocytic co-stimulatory cascade in the mouse AA model, it can be used to screen compounds potentially useful to treat a variety of cell mediated diseases. Efficacy of various agents can easily be screened by simply observing the presence, rate, and cosmetic acceptability of hair regrowth. More sophisticated assays can refine how the drugs induce hair regrowth and evaluate the underlying pathogenesis of AA. Some drugs commonly used to treat human AA patients work equally as well in both rodent models validating their usefulness as models for drug efficacy and safety for human AA.

Keywords: alopecia areata, hair loss treatment, animal model, review, diphenylcyclopropenone, squaric acid dibutyl esterase,

Alopecia areata targets hair follicles in the actively growing (anagen) phase of the hair cycle. It is often associated with other systemic cell mediated diseases (2)…..Human AA involves patchy hair loss from any hair-bearing region of the body that may progress to total body hair loss. AA may wax or wane on different sites, or the same site, or frequently it will spontaneously resolve with no treatment. AA most commonly affects the scalp but other body regions may also be affected. Extensive or total hair loss involving the scalp is termed alopecia totalis. AA affecting sites in addition to the bald scalp is termed AT/AU or alopecia universalis (AU) if the entire body is affected. This spontaneous, patchy, potentially reversible, non-scarring, hair loss has been the focus of medical research for over 100 years. Only recently however, with access to many new biomedical and molecular tools, have efforts been made to clarify the pathogenesis, and treatment of hair loss due to alopecia areata.

Changing trends in hair restoration surgery

Mysore Venkataram

edited exerpt: “…The term androgenetic alopecia (pattern baldness) has evolved from its dependence on the twin factors of androgens and genetic background. Pattern hair loss is probably multifactorial and may be inherited as an autosomal dominant trait with variable penetrance. The responsible genes have not yet been identified.

Although the term is used for both males and females, there are considerable differences between the sexes. Male pattern alopecia (hair loss) often presents in the first decade after puberty and is characterized by deep bitemporal recession and balding of the vertex, whereas female pattern hair loss is more diffuse, without bitemporal recession.

It is doubtful whether the hair loss seen in women is primarily androgen dependent and it is possible that several other factors may be responsible; hence the term ‘female pattern hair loss (FPHL)’ is preferred to the term androgenetic alopecia when referring to women with this type of alopecia. One noteworthy feature in both female and male pattern hair loss is that occipital scalp is spared of this process and the hairs in this region persist for life…”