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.

Am J Clin Dermatol 2000 May-Jun;1(3):151-8

Management of androgenetic alopecia.

Androgenetic alopecia is by far the most common cause of hair loss. It affects approximately 50% of men by the age of 50 and 20 to 53% of women by the age 50. Although it is a medically benign condition, it is a significant psychosocial issue for many patients. Various different treatment options are now available for androgenetic alopecia. The best treatment option for women with androgenetic alopecia Ludwig stage I and II is minoxidil 5% solution. If it is not effective after 1 year, antiandrogens can be tried, but there are no large studies showing their efficacy and they have considerable adverse effects. Also, for patients with alopecia that is unresponsive to treatment or with Ludwig stage III, hair transplantation can be offered if the occipital donor area is sufficient. For men, we always offer minoxidil or finasteride therapy and leave the choice of therapy to the patient. Some patients may prefer a systemic agent, whereas others may favor a topical agent. If the condition is not stabilized after 1 year or if the patient wants greater hair density, hair transplantation can be discussed. There have been tremendous advances in the treatment of hair loss in recent years and the future is very encouraging. As our knowledge of androgenetic alopecia pathophysiology increases, novel targeted treatments will potentially be developed.

Australas J Dermatol. 2003 May;44(2):106-9.

PUVA treatment of alopecia areata totalis and universalis: a retrospective study.

The results of PUVA treatment of alopecia areata (AA) totalis and universalis were reviewed in 26 adult patients. Eight of 15 patients with AA totalis and six of 11 patients with AA universalis achieved a complete response (>90% hair regrowth). Patients with AA totalis had a greater incidence of treatment failure (<25% hair regrowth) than those with AA universalis. Patients with a family history of AA were significantly less likely to have a positive response to PUVA than those with no family history. Sex, age at diagnosis and treatment, interval between diagnosis and treatment, and background of atopy were not significant determinants of outcome. Although unable to show significance for clinical response to treatment, this study demonstrates complete hair regrowth in patients with both AA totalis (53%) and universalis (55%) while reporting a low relapse rate among these patients (21%) within a long period of follow up (mean 5.2 years).

J Am Acad Dermatol. 2003 May;48(5):752-9.

Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice.

Human hair follicles were grafted onto 2 strains of immunodeficient mice to compare the regeneration potential of vellus (miniaturized, balding) and terminal (hairy, nonbalding) follicles from males and a female exhibiting pattern baldness. Each mouse had transplants of both types of follicles from a single donor for direct comparison. Grafted follicles from 2 male donors resulted in nonsignificant differences in mean length (52 mm vs 54 mm) and mean diameter (99 microm vs 93 microm) at 22 weeks for hairs originating from balding and hairy scalp, respectively, corresponding to 400% versus 62% of the mean pretransplantation diameters. Follicles from the female donor transplanted to several mice also resulted in nonsignificant differences in length (43 mm vs 37 mm) for hairs from balding and hairy scalp, respectively, during a period of 22 weeks. The mean diameter of the originally vellus hairs increased 3-fold, whereas the terminal hairs plateaued at approximately 50% of pretransplantation diameter, resulting in a final balding hair volume double that of the nonbalding hairs. This report shows that miniaturized hair follicles of pattern alopecia can quickly regenerate once removed from the human scalp and can grow as well as or better than terminal follicles from the same individual.

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