Gene array profiling and immunomodulation studies define a cell-mediated immune response underlying the pathogenesis of alopecia areata in a mouse model and humans.

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J Invest Dermatol 2002 Aug;119(2):392-402

Gene array profiling and immunomodulation studies define a cell-mediated immune response underlying the pathogenesis of alopecia areata in a mouse model and humans.

Alopecia areata is a suspected autoimmune hair loss disease. In a rodent model, alopecia areata can be induced in normal haired C3H/HeJ mice by transfer of skin grafts from mice with spontaneous alopecia areata. At weeks 2, 4, 6, and 10 after surgery, grafted mice were euthanized, skin collected and processed for histology, and RNA extracted. Age-matched sham-grafted mice, and mice with and without spontaneous alopecia areata, were similarly processed. For comparison, skin biopsies from alopecia areata and androgenetic alopecia affected humans were also collected. Skin mRNA processed to cDNA was analyzed using Affymetrix mouse 11K and human 6800 gene chip(R) array technology. Microarray results indicated 42 known genes upregulated or downregulated during onset of mouse alopecia areata consistent with an inflammatory cell-mediated disease pathogenesis involving antigen presentation, costimulation, and a T helper 1 lymphocyte response. In contrast, 114 genes, many regulating immunoglobulin response, were altered late in disease development. In alopecia areata affected humans, 95 genes were significantly modulated. As confirmation of microarray analysis results, lymph node and spleen cells from alopecia areata affected mice injected into normal haired littermates transferred the alopecia areata phenotype. Alopecia areata onset could be inhibited in skin-grafted mice by modulation with B7.1- and B7.2-specific monoclonal antibodies. In addition, depletion of CD4+ CD8+ expressing cells in chronic alopecia areata affected mice using monoclonal antibodies permitted hair regrowth. The results consistently demonstrated the importance of an immune cell-mediated disease mechanism in alopecia areata pathogenesis and suggested targeting antigen-presenting cells and reactive lymphocytes may be effective in alopecia areata treatment.

Br J Dermatol 2002 Aug;147(2):222-9

Langerhans cells that express matrix metalloproteinase 9 increase in human dermis during sensitization to diphenylcyclopropenone in patients with alopecia areata.

BACKGROUND: We know little of the initial events during the sensitization phase of contact allergy in humans. Alopecia areata (AA), a disease of unknown pathogenesis characterized by patchy hair loss, may be treated by inducing contact allergy to diphenylcyclopropenone (DPC), later followed by its topical application. OBJECTIVES: To learn more about the initial events during sensitization in human skin, we studied the early events during induction of contact allergy to DPC in patients with AA. METHODS: DPC 2% and sodium lauryl sulphate (SLS) 4% were applied on the backs of eight patients with AA. Punch biopsies were taken 6 and 24 h after application. The biopsies were snap-frozen and cryostat sections were evaluated with immunohistochemistry using antibodies against CD1a, HLA-DR, CD3, CD54 and matrix metalloproteinase 9 (MMP-9). RESULTS: After 24 h all subjects exhibited erythema on the DPC-treated areas. Histological evaluation of biopsies from these areas showed hydropic degeneration and a significantly increased number of MMP-9+ cells in the dermis (P < 0.0005). The MMP-9+ cells were identified with double immunofluorescence staining as CD1a + Langerhans cells. The expression of the other markers studied remained unaltered irrespective of treatment, including treatment with SLS. CONCLUSIONS: Our findings show that DPC induces an irritant reaction leading to an increased number of MMP-9+ CD1a+ cells in the dermis during the initial phase of sensitization.

Ther Umsch 2002 May;59(5):233-7

Alopecia areata

Alopecia areata is a frequent cause of hair loss. The origin of disease is not fully understood. However there are indications for a T-cell mediated autoimmune process. Genetic, immunologic and psychologic factors are important for the outbreak of disease. Most patients show localized patches of acute hair loss, where regrowth is observed spontaneously or with simple topical treatment within few months. In up to 15% of patients severe forms of disease can develop with total scalp (alopecia totalis) or scalp and body hair loss (alopecia universalis). There are only few known risk factors for development of a severe form. Although spontaneous remission is possible in these cases, it occurs rarely and treatment is difficult. Multifocal alopecia areata responds to intravenous high-dose corticosteroids. Topical immunotherapy with diphenylcyclopropenone (DPC) or PUVA therapy may be effective in longstanding and widespread disease. The unpredictable course of disease is a major handicap for clinical trials and treatment recommendations. Contact of patients with self-help organisations may be of help for coping with the disease.

J Eur Acad Dermatol Venereol 2000 Mar;15(2):137-9

The effect of hair loss on quality of life.

BACKGROUND: The aim of this study was to quantify the effect of hair loss on quality of life. Patients were recruited from an alopecia support group, and were assessed using the Dermatology Life Quality Index (DLQI) and an adapted version of the DLQI. Financial utility questions, an abbreviated version of the Center for Epidemiologic Studies Depression Scale and open-ended questions were also used. OBSERVATIONS: Seventy (90% response rate) questionnaires were returned. DLQI scores in responders with hair loss (mean score = 8.3, SD = 5.6, range 0-23, n = 70) were similar to those recorded in severe psoriasis. The hair loss continued to have a significant impact on life quality well after the initial event (median duration of hair loss = 138 months +/- 114; range 7-588, n = 70). Forty per cent of patients also felt dissatisfied with the way in which their doctor dealt with them. CONCLUSIONS: This study specifically identifies the feelings of loss of self-confidence, low self-esteem and heightened self-consciousness in people affected by hair loss.

Since hair growth is a complicated biological process, modern science has yet to grasp a complete picture. A number of traditional and alternative therapeutic methods that include drugs, surgery, and suppelements have been developed to help those who are losing hair. Unfortunately, none of these approaches are perfect for all hair loss problems due to the complexity of the phenomenon and diverse nature of the causes underlying hair loss. Also, most of chemical drugs and hair transplantation surgeries are accompanied by undesirable side effects.

DreamPharm offers Hair Million (have you heard?) to help treat hair loss problems. Numerous anecdotal cases have demonstrated that this herbal formula based on traditional Chinese herbs actually improves hair thinning and hair loss, a condition often associated with aging, for a significant fraction of people who take the formula regularly. It is not yet understood how Hair Million can stop hair loss and promote hair growth. No scientific research or placebo controlled clinical analysis has been performed on these herbs. Lack of scientific/clinical research is not uncommon in herbal arena. Nonetheless, there are two merits in this hair restoration herbal formula: Firstly, Hair Million is relatively inexpensive, and secondly, it is made of edible herbs that are known to be safe when consumed in regular quantities. Propecia is a clinically tested prescription medication.

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