Interleukin-1 receptor antagonist allele 2 and familial alopecia areata.

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J Invest Dermatol 2002 Feb;118(2):335-7

Interleukin-1 receptor antagonist allele 2 and familial alopecia areata.

Alopecia areata affects 1%-2% of the population and is hypothesized to be an autoimmune, organ specific T-cell mediated reaction directed against the human hair follicle. It is characterized by loss of hair in patches (alopecia areata) with progression in some individuals to total loss of scalp hair (alopecia totalis) or to loss of all scalp and body hair (alopecia universalis). The interleukin-1 receptor antagonist (IL-1RN) gene was found to be associated with more severe clinical outcome in several chronic inflammatory diseases, including alopecia areata. The IL-1RN*2 allele was found to be associated with alopecia areata severity in a British case-control study. In this paper, we analyzed alopecia areata probands in a family-based sample (n = 131 parent-offspring trios) to study the association between alleles of the IL-1RN and various phenotypes of alopecia areata. In considering all patients with any form of alopecia areata, no association was found with IL-1RN. IL-1RN*2 allele was not associated with alopecia totalis and alopecia universalis. A borderline association was observed between IL-1RN and patchy alopecia areata but it was not statistically significant (p =0.06). We also observed an association between IL1-RN*1 allele and patchy alopecia areata (p =0.045).

J Cardiovasc Risk. 2003 Jun;10(3):227-31.

Hair loss, insulin resistance, and heredity in middle-aged women. A population-based study.

CONTEXTThe association of androgenic alopecia (AGA) with insulin resistance, coronary artery disease and hypercholesterolemia has been previously reported in men, but no such association has been reported in women with female androgenic alopecia (AGA). Female AGA has usually been linked with hyper-androgenism and hirsutism and, most recently, also with polycystic ovarian syndrome (PCOS), even though epidemiological documentation of the latter association is scanty. Polycystic ovarian syndrome is quite common among Caucasian women, and its association with insulin resistance is well documented.OBJECTIVES AND DESIGNThe aim of this study was to obtain a more precise estimation of the prevalence on female AGA and to describe its possible connections with insulin resistance linked parameters and with paternal and maternal family history of alopecia. A cross-sectional population based cohort survey was carried out in the City of Oulu, Finland in 1998.SETTING AND PARTICIPANTSAs a part of a population based cohort study the hair status of 324 women aged 63 years was assessed by a modification of Ludwig's scale. The background data consisting of anthropometric measures (weight, height, body mass index, waist, hip and neck circumferences), smoking status, chronic diseases and their medication as well as the family history of AGA were collected by questionnaires and interviews made by study nurses and in clinical examination. Blood samples for laboratory tests were taken on the same occasion.RESULTSThe prevalence of extensive loss of hair (at least grade II or III on Ludwig's scale) was quite high (31.2%). The insulin resistance associated parameters, such as waist and neck circumferences, abdominal obesity measured by waist-to-hip ratio, mean insulin concentration (11.3 mU/l versus 9.95 mU/l, p=0.02) or urinary albumin-to-creatinine ratio (1.80 versus 1.58, p=0.01), were significantly higher in women with extensive hair loss compared to those with normal hair or only minimal hair loss (grade I on Ludwig's scale). The women belonging to the highest quintiles of neck or waist circumferences had significantly increased risk for extensive hair loss compared to those with normal hair or minimal hair loss, the unadjusted ORs being 2.25 (95% CI, 1.26-4.03) and 1.75 (95% CI, 1.00-3.07), respectively. Similarly in women with hyperinsulinemia (fs-insulin >10 mU/l), microalbuminuria (urinary albumin-to-creatinine ratio exceeding the highest microalbuminuria decile (>2.5 mg/mmol) and paternal history of AGA the ORs for alopecia were increased being 1.65 (95% CI, 1.02-2.67), 2.39 (95% CI, 1.21-4.73) and 2.08 (95% CI, 1.26-3.44). All of these ORs, except those for highest quintiles of waist and neck circumferences remained significant in multiple adjusted models.CONCLUSIONSAccording to the results of this study, female AGA (grade II or III on Ludwig's scale) was quite common among Finnish women aged 63 years. Our results support the hypothesis that women with some markers of insulin resistance have significantly increased risk for female AGA. Paternal history of alopecia seemed to be more common in female AGA compared to women with normal or minimal loss of hair.

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).

Cancer Res. 2003 Jun 15;63(12):3037-42.

Inhibition of the Development of Metastatic Squamous Cell Carcinoma in Protein Kinase C epsilon Transgenic Mice by alpha-Difluoromethylornithine Accompanied by Marked Hair Follicle Degeneration and Hair Loss.

The role of 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated polyamine biosynthesis in the development of metastatic squamous cell carcinoma (mSCC) in protein kinase C epsilon (PKCepsilon) transgenic mice was determined. TPA treatment induced epidermal ornithine decarboxylase (ODC) activity and putrescine levels approximately 3-4-fold more in PKCepsilon transgenic mice than their wild-type littermates. Development of mSCC by the 7,12-dimethylbenz(a)anthracene (100 nmol)-TPA (5 nmol) protocol in PKCepsilon transgenic mice was completely prevented by administration of the suicide inhibitor of ODC alpha-difluoromethylornithine (DFMO, 0.5% w/v) in the drinking water during TPA promotion. However, DFMO treatment led to marked hair loss in PKCepsilon transgenic mice. DFMO treatment-associated hair loss in PKCepsilon transgenic mice was accompanied by a decrease in the number of intact hair follicles. These results indicate that TPA-induced ODC activity and the resultant accumulation of putrescine in PKCepsilon transgenic mice are linked to growth and maintenance of hair follicles, and the development of mSCC. Severe hair loss observed in PKCepsilon transgenic mice on DFMO during skin tumor promotion has not been reported before in the prevention of cancer in other animal models or in human cancer prevention trials.

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