Role of the Autoimmune Regulator (AIRE) gene in alopecia areata: Strong association of a potentially functional AIRE polymorphism with alopecia universalis.

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Tissue Antigens 2002 Dec;60(6):489-95

Role of the Autoimmune Regulator (AIRE) gene in alopecia areata: Strong association of a potentially functional AIRE polymorphism with alopecia universalis.

On screening the AIRE coding sequence, we identified 20 variants. Two of these at positions, G961C and T1029C, give rise to amino acid changes, S278R and V301A, located in the DNA-binding segment (SAND) and PHD1 zinc finger motif, respectively. We found no difference in the frequency of the AIRE T1029C polymorphism between the control and patient groups. We genotyped 202 alopecia areata patients and 175 matched Caucasian controls for the AIRE G961C alleles. The frequency of the rare allele (961G) was 0.08 in the controls and there was a significant increase to 0.13 in alopecia areata overall and 0.20 in severe disease (alopecia universalis). We found no association between the AIRE G961G variant and mild (patchy) alopecia areata or alopecia totalis. However, the AIRE 961G allele is a potent risk factor (> 3) for the severest form of alopecia areata, and for disease of early age at onset (at 30 years). The change from serine to arginine in the SAND domain of AIRE protein may have a significant effect on AIRE DNA-binding activity. Moreover, our results could provide a rational explanation of the unusually high frequency of AA in APECED patients, supporting the concept of AA as an autoimmune disease.

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.

J Altern Complement Med 2002 Apr;8(2):143-52

A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is characterized by the structural miniaturization of androgen-sensitive hair follicles in susceptible individuals and is anatomically defined within a given pattern of the scalp. Biochemically, one contributing factor of this disorder is the conversion of testosterone (T) to dihydrotestosterone (DHT) via the enzyme 5-alpha reductase (5AR). This metabolism is also key to the onset and progression of benign prostatic hyperplasia (BPH). Furthermore, AGA has also been shown to be responsive to drugs and agents used to treat BPH. Of note, certain botanical compounds have previously demonstrated efficacy against BPH. Here, we report the first example of a placebo-controlled, double-blind study undertaken in order to examine the benefit of these botanical substances in the treatment of AGA. OBJECTIVES: The goal of this study was to test botanically derived 5AR inhibitors, specifically the liposterolic extract of Serenoa repens (LSESr) and beta-sitosterol, in the treatment of AGA. Subjects: Included in this study were males between the ages of 23 and 64 years of age, in good health, with mild to moderate AGA. RESULTS: The results of this pilot study showed a highly positive response to treatment. The blinded investigative staff assessment report showed that 60% of (6/10) study subjects dosed with the active study formulation were rated as improved at the final visit. CONCLUSIONS: This study establishes the effectiveness of naturally occurring 5AR inhibitors against AGA for the first time, and justifies the expansion to larger trials.

Eur J Dermatol 2002 Jan-Feb;12(1):38-49

Long-term (5-year) multinational experience with finasteride 1 mg in the treatment of men with androgenetic alopecia.

BACKGROUND: Finasteride 1 mg (Propecia) is indicated for the treatment of men with androgenetic alopecia (male pattern hair loss, MPHL). However, the long-term (> 2 years) efficacy and safety of finasteride in this population has not been previously reported. Objectives. To assess the efficacy and safety of finasteride in men with MPHL compared to treatment with placebo over five years. METHODS: In two 1-year, Phase III trials, 1,553 men with MPHL were randomized to receive finasteride 1 mg/day or placebo, and 1,215 men continued in up to four 1-year, placebo-controlled extension studies. Efficacy was evaluated by hair counts, patient and investigator assessments, and panel review of clinical photographs. RESULTS: Treatment with finasteride led to durable improvements in scalp hair over five years (p 3/4 0.001 versus placebo, all endpoints), while treatment with placebo led to progressive hair loss. Finasteride was generally well tolerated and no new safety concerns were identified during long-term use. CONCLUSIONS: In men with MPHL, long-term treatment with finasteride 1 mg/day over five years was well tolerated, led to durable improvements in scalp hair growth, and slowed the further progression of hair loss that occurred without treatment.

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