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PubMed2003

Analysis of genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 genes in Korean men with androgenetic alopecia.

BACKGROUND: Genetic polymorphisms of steroid 5alpha-reductase have been studied in androgenetic alopecia in Caucasians, but the genes encoding the two isoenzymes were not associated with male pattern baldness. Genetic polymorphisms and ethnic variations have not been studied for Asians, although it is suggested that racial difference could exist and influence clinical phenotypes. OBJECTIVE: The purpose of our study is to investigate the genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 (SRD5A1 and SRD5A2) genes in Korean population, and to study the association of these polymorphisms with the development, clinical types (female or male pattern) and therapeutic response of androgenetic alopecia. METHODS: Sixty-six patients with androgenetic alopecia and controls consisted of 92 healthy men were included. Twenty-four patients were treated with finasteride for at least 6 months, and clinical responses were assessed by a simple classification. For type 1 isoenzyme, HinfI and NspI restriction fragment length polymorphisms (RFLPs) were detected using polymerase chain reaction method. For type 2 isoenzyme, RsaI RFLPs detected valine/leucine polymorphisms at codon 89, and MowI RFLPs detected alanine/threonine polymorphisms at codon 49. RESULTS: We could not find any significant associations of the genetic polymorphisms of these two isoenzyme genes with androgenetic alopecia in Koreans (P>0.05). These polymorphisms were not associated with the clinical types of baldness or the response to finasteride (P>0.05). CONCLUSION: These results suggest that polymorphisms of SRD5A1 and SRD5A2 genes may not be directly associated with the development of baldness or generation of different clinical phenotypes.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2003

The extract of Thujae occidentalis semen inhibited 5alpha-reductase and androchronogenetic alopecia of B6CBAF1/j hybrid mouse.

BACKGROUND: The conversion of testosterone to dihydrotestosterone; 5alpha-androstan-17beta-ol-3-one by 5alpha-reductase plays a crucial role in hair baldness and prostatomegaly. Recent approach showed specific inhibitors for 5alpha-reductase type 2 such as finasteride promoted hair growth in male pattern alopecia. OBJECTIVE: In order to search for effective medicinal plant extracts applied topically for androgenetic alopecia, we screened natural plant extracts having inhibitory activities of 5alpha-reductase type 2 and demonstrated its biological function in androgen-related animal models. METHODS: We evaluated the inhibition activities of numerous plant extracts by contact cell based metabolic method using a stable HEK 293 cell line expressing human 5alpha-reductase (type 2). To elucidate the biological activity in vivo, the Thujae occidentalis semen (TOS) extract was topically applied to fuzzy rat and androchronogenetic alopecia (AGA) mouse, respectively. The secreted sebum and the size of sebaceous glands of fuzzy rat were measured after 6 weeks. Also, after the topical treatment with TOS extract and androgen receptor antagonist (cyproterone acetate) simultaneously with subcutaneous injection of testosterone (1 mg/mice/day), hair loss patterns of female B6CBAF1/j hybrid mouse were observed. RESULTS: TOS extract showed higher inhibition activity of 5alpha-reductase type 2(IC(50) value=2.6 microg/ml) than that of gamma-linolenic acid, but lower than that of finasteride. When applied to fuzzy rat, the amount of sebum and sebaceous gland size decreased remarkably. In AGA model, alopecia degrees of two groups, treated with TOS extract (P<0.015) or cyproterone acetate (P<0.01), were lower than that of vehicle (propylene glycol:ethanol=7:3) and there was no difference between above two groups. CONCLUSION: We have demonstrated the inhibitory activity of TOS extract for 5alpha-reductase type 2 and its biological action in two animal models, suggesting that TOS extract would be used as an effective agent for male pattern baldness by modifying androgen conversion.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2002

[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.

Adrenal Cortex Hormones↗
PubMed2001

Insights from the asebia mouse: a molecular sebaceous gland defect leading to cicatricial alopecia.

The primary cicatricial alopecias have proven to be challenging for the clinician, dermatopathologist and the researcher--let alone the patient. If we are to improve our diagnostic and therapeutic tools for these very difficult disorders, we will need greater insight into their etiology. Recent work with the mouse mutant, asebia, provides a model for cicatricial alopecia. In this model the pathology--perifollicular inflammation, sebaceous gland "destruction", hair shaft granuloma, and cicatricial follicle drop-out--results from the mutation of one very important sebaceous gland gene. In the absence of this gene, the sebaceous gland is hypoplastic and normal sebum production is minimal to absent. In this paper the relevance of this mutant to human alopecias is discussed and the point emphasized that the pathogenesis of some forms of human cicatricial alopecia could involve the sebaceous gland.

Alopecia↗
PubMed2003

Scarring alopecia associated with mastocytosis.

BACKGROUND: Mastocytosis is comprised of a group of heterogeneous diseases involving various organs. Urticaria pigmentosa is the most common manifestation of cutaneous mastocytosis; others include mastocytoma, diffuse mastocytosis, and telangiectasia macularis eruptiva perstans. METHODS: We describe a case of indolent mastocytosis presenting as scarring alopecia. The scalp biopsy revealed a perifollicular and dermal inflammatory infiltrate composed predominantly of mast cells, which was confirmed by tryptase and Giemsa stains. RESULTS: The preponderance of mast cells in the biopsy prompted testing for urine N-methylhistamine levels, which were elevated and confirmed the diagnosis of mastocytosis. This is the first report of mastocytosis presenting as scarring alopecia. CONCLUSIONS: This case suggests that the diagnosis of mastocytosis should be entertained in patients presenting with scarring alopecia accompanied by an intense mast cell infiltrate on scalp biopsy and also supports the notion that mast cells may be involved in the pathogenesis of alopecia.

Alopecia↗
PubMed2003

Alopecia areata: autoimmunity--the evidence is compelling.

There is strong evidence indicating that alopecia areata is a tissue-specific, autoimmune disease. Hair loss is associated with a perifollicular lymphocytic infiltrate made up primarily of CD4+ cells, along with a CD8+ intrafollicular infiltrate. Evidence of immune activation includes expression of HLA-DR; HLA-A,B,C; and ICAM-1 on the follicular epithelium. It is likely that the follicular expression of HLA-DR and ICAM-1 is induced by interferon-gamma produced by T cells. Antibodies to follicular epithelium are often present, but their significance is not known. Lesional scalp from alopecia areata patients grafted onto nude mice regrows hair coincident with a loss of infiltrating lymphocytes from the graft. Hair loss can be transferred to human scalp explants on SCID mice by injection of lesional T cells. It is necessary to activate the T cells by culture with follicular autoantigens. Melanocyte-associated antigens are also capable of activating T cells to induce hair loss, suggesting that they are capable of functioning as autoantigens for alopecia areata. Parallel evidence in rodent models of spontaneous alopecia areata also strongly supports a role for T cells in the pathogenesis of this condition.

Alopecia Areata↗
PubMed2003

Neurotrophins and their role in pathogenesis of alopecia areata.

Neurotrophins comprise a family of structurally and functionally related proteins that are critical for the development and maintenance of cutaneous innervation. They also fulfill multiple non-neurotrophic functions in skin, including regulation of epidermal proliferation and apoptosis, control of hair follicle development and cycling, and melanogenesis. Numerous indications suggest that neurotrophins play an important role in the pathogenesis of a variety of autoimmune diseases. In this review, we focus on the role of neurotrophins in the pathogenesis of alopecia areata, an autoimmune disorder that affects actively growing hair follicles. Recent data suggest that neurotrophins and their receptors are differentially expressed among the subsets of immune cells in alopecia areata-affected skin. Experimental data suggest that neurotrophins may regulate both the cyclic activity of the hair follicle and the functions of immune cells of inflammatory infiltrates. Additional research is required to bridge the gap between our current knowledge of neurotrophin functions in skin affected by alopecia areata and our knowledge of their potential clinical applications. Progress in this area of research will hopefully lead to the development of multiple applications for neurotrophins and their agonists/antagonists in alopecia areata and other hair growth disorders.

Alopecia Areata↗
PubMed1999

Alopecia neoplastica in a patient with gastric carcinoma.

A well-recognized but rare presentation of scalp metastasis is alopecia neoplastica, which occurs as a single or multiple areas of cicatricial alopecia. Alopecia neoplastica is usually a presentation of metastasis from breast cancer, and other primary sites are extremely rare. We report a 36-year-old woman with alopecia neoplastica due to metastasis from gastric carcinoma. She also had pelvic metastases. An asymptomatic erythematous alopecic plaque had developed 10 months before presentation and biopsy was consistent with scalp metastasis. Total abdominal hysterectomy and salphingo-oophorectomy was performed and chemotherapy was proposed.

Adult↗
PubMed2001

Strategies of coping and quality of life in women with alopecia.

BACKGROUND: Measurements of the quality of life (QoL) have recently become an integral part of dermatological studies. Our hypothesis is that QoL in patients with certain diseases can be affected by strategies of coping behaviour, as well as by personality traits. OBJECTIVES: The aim of this study was to explore the particular correlation between QoL and strategies of coping in female patients with alopecia. PATIENTS: Fifty female patients, diagnosed with either diffuse or androgenetic alopecia, were evaluated by the use of Hairdex, an instrument developed to measure QoL in patients with hair loss. Most patients also underwent additional psychological assessments. RESULTS: Findings indicated that patients with highly visible hair loss reported a more negative impact on four Hairdex dimensions (functioning, emotions, self-confidence and stigmatization) than patients whose hair loss was only slightly visible. However, a subgroup of patients, with non-visible symptoms of hair loss, showed striking signs of psychological disturbance. These disturbed patients displayed either dysmorphophobic or affective disorder tendencies. CONCLUSIONS: Future studies using QoL as an instrument in research on patients with alopecia should consider that in cases of female alopecia these measurements may be affected by psychological disturbances.

Adaptation, Psychological↗
PubMed2003

Female alopecia: the mediating effect of attachment patterns on changes in subjective health indicators.

BACKGROUND: The interrelationship between female alopecia and psychological disorders is complex, with a range of psychosocial consequences, but also antecedents. Psychosocial antecedents are to a large extent interpersonal and can be assumed to have a mediating effect on health care utilization and subjective health. OBJECTIVES: To analyse whether changes in health-related quality of life (QoL) are mediated by relational or attachment styles and whether these styles are associated with a particular, dysmorphophobic type of alopecia. METHODS: Seventy-four women with androgenetic and diffuse alopecia underwent psychological assessment at the first consultation at a university clinic and at 2 months' follow-up. Attachment styles were evaluated by an observer rating scale. As a primary endpoint a disease-specific QoL instrument was employed. RESULTS: Findings indicated an association between patients with nonvisible hair loss and the ambivalent attachment style. Global clinical impressions and attachment indicators, e.g. attachment security and coping strategies, showed significant contributions in predicting changes in the QoL scales 'self-esteem' and 'emotions'. CONCLUSIONS: These findings suggest that attachment security may be one of the underlying mechanisms mediating subjective health and that a specific attachment vulnerability can be identified in a subgroup of patients with female alopecia. Future studies will have to focus on the relevance of attachment patterns in the doctor-patient relationship and on psychotherapeutic interventions.

Adaptation, Psychological↗
PubMed2002

Disappearance of pili annulati following an episode of alopecia areata.

Pili annulati is a distinctive autosomal dominant hair shaft disorder that produces alternating light and dark bands that can give a spangled appearance to the hair. The literature contains three case reports of patients in whom the condition has disappeared following recovery from alopecia totalis. None of these reports contain a direct microscopic comparison of pre- and post-regrowth hairs. We report a 6-year-old girl who was first noted to have pili annulati at the age of 2 years and who developed alopecia totalis at the age of 3 years. When the hair regrew spontaneously, 18 months later, the pili annulati was no longer visible. Hair samples obtained before and after the episode of alopecia areata were compared by normal and cross-polarized light microscopy. While not apparent on careful clinical examination, banding was present on light microscopy in 20% of the hairs. Eighty per cent of the affected hairs displayed banding throughout their entire length. In contrast, prior to the episode of alopecia totalis, when the pili annulati was clearly visible, 50% of the hair obtained was banded on microscopy and 90% of the affected hairs showed banding throughout their microscopic length.

Alopecia Areata↗
PubMed2001

Association analysis of IL1A and IL1B variants in alopecia areata.

Alopecia areata is an inflammatory hair loss disease with a major genetic component. The disease is characterized by focal inflammatory lesions with perifollicular T-cell infiltrates, reflecting the role of local cytokine production in the development of patchy hair loss. IL-1 alpha and IL-1 beta are important inhibitors of hair growth in vitro. Their effect is opposed by the interleukin-1 receptor antagonist, IL-1ra. Genes of the IL-1 cluster are candidate genes in the pathogenesis of alopecia areata. To investigate the role of the IL-1 system in alopecia areata we examined three biallelic polymorphisms within the IL-1 gene cluster (IL1A+4845, IL1B+3954 and IL1B-511) in 165 patients and a large number of matched controls (n=1150). There was no significant association of IL1B-511 or IL1B+3954 genotypes with the overall dataset, or with disease severity or age at onset, in contrast with a previous report. The results suggested the possibility of an association with IL1A+4845 in the overall dataset [OR 1.39 (95% CI 1.00, 1.93)] although this was not statistically significant. This was due mainly to the contribution from mild cases of alopecia areata [OR 1.48 (0.96, 2.29)], suggesting that IL-1 alpha may have a particular role in the pathogenesis of this subgroup.

Adult↗
PubMed1998

Severe alopecia areata treated with systemic corticosteroids.

BACKGROUND: Treatment of severe alopecia areata is difficult, and most efforts to successfully treat this condition have been disappointing. Systemic corticosteroids have been demonstrated as an effective treatment of severe alopecia areata. METHODS: Eighteen patients with alopecia areata (extensive patchy and totalis universalis types) were treated with systemic corticosteroids. RESULTS: Satisfactory hair regrowth was achieved in seven patients (38.9%). Hair fall subsequently occurred in all of these patients on discontinuation or tapering of corticosteroid therapy. CONCLUSIONS: Systemic corticosteroid therapy does not prevent the spread or relapse of severe alopecia areata and, when complete regrowth is obtained, it is rarely maintained off therapy.

Adolescent↗
PubMed2002

Lupus panniculitis clinically simulating alopecia areata.

A 27-year-old woman with a known history of lupus erythematosus presented with two circumscribed patches of non-scarring alopecia closely resembling alopecia areata. Scalp biopsy showed a predominantly subcutaneous and deep dermal lymphocytic infiltrate that surrounded the deep follicular segments and hair bulbs, as well as the eccrine glands. There was associated hyaline fat sclerosis. The epidermis, infundibular and isthmus segments of follicles were relatively spared and lacked the lichenoid inflammation and fibrosis seen with lupus erythematosus. The biopsy findings illustrate that the deep variant of lupus panniculitis may be concentrated around the hair bulbs and deep temporary segments of hair follicles and spare the permanent stem cell-rich follicular segments. This pattern is capable of producing a temporary hair-loss, clinically simulating alopecia areata. The clinical history, presence of subtle erythema and scalp tenderness on physical examination, as well as the biopsy findings, were important clues in distinguishing our case from a true combination of alopecia areata and lupus erythematosus.

Adult↗
PubMed2003

Androgenetic alopecia in a postmenopausal woman as a result of ovarian hyperthecosis.

A 65-year-old woman presented with an 8-year history of progressive frontotemporal alopecia and hirsutism. She had elevated serum levels of testosterone, androstenedione and estradiol. Ultrasound and computed tomography imaging suggested a right ovarian mass, while bilateral ovarian venous sampling demonstrated increased testosterone levels originating from both ovarian veins. Histology obtained following bilateral oophorectomy demonstrated bilateral ovarian hyperthecosis. Six months after surgery, the patient remains well with no progression of the alopecia. Ovarian hyperthecosis is a rare cause of androgenetic alopecia in postmenopausal women. The role of hyperthecosis and its relationship to androgenetic alopecia is reviewed.

Aged↗
PubMed2003

Turner's syndrome associated with psoriasis and alopecia areata.

Turner's syndrome is a sex chromosomal abnormality characterized by gonadal failure, short stature, skeletal and medical anomalies due to structural defects or monosomy of the X chromosome. The association between this syndrome and autoimmune diseases has been reported in the literature. This case report highlights the finding of two immunological skin diseases, alopecia areata and psoriasis, in an 18-year-old girl with Turner's syndrome. By the time of her referral to the Department of Dermatology, Verona University (Italy) the girl had suffered from psoriasis on the scalp for 5 years and alopecia for 6 months; the diagnoses were confirmed by histological evaluation. Topical therapy was useful for the treatment of the psoriatic lesions but not for the alopecia areata. Alopecia areata and psoriasis occurring together in Turner's syndrome may indicate some genetic relationship and could support the concept that these patients have the tendency to develop autoimmune or immunological diseases. Anxiety, depression and unsatisfactory relationships could have been important trigger factors in our patient. Multidisciplinary management, including psychological, educational and behavioural techniques, in addition to other therapies, could be useful in treating these conditions.

Adolescent↗
PubMed2003

Topical mechlorethamine restores autoimmune-arrested follicular activity in mice with an alopecia areata-like disease by targeting infiltrated lymphocytes.

Alopecia areata is an autoimmune disease targeted at hair follicles with infiltrated T lymphocytes probably playing an important role in the pathogenesis. It was reported in 1985 that mechlorethamine was effective on alopecia areata patients. This has never been confirmed since. The aims of the study were to investigate the effects of mechlorethamine on balding C3H/HeJ mice affected with an alopecia-areata-like disease and to study the underlying mechanisms. Mice were treated on half of the dorsal skin with mechlorethamine and the contralateral side was treated with the vehicle ointment. After 10 wk of mechlorethamine therapy, a full pelage of hair covered the treated side in all the mice and was maintained during the study, whereas the vehicle-treated sides showed either no change or continued hair loss. Immunohistochemistry revealed that infiltrated CD4+ and CD8+ lymphocytes were eliminated from the treated side. In vitro cell viability assay showed that lymphocytes were much more sensitive to the cytotoxic effects of mechlorethamine than skin and hair follicular cells. RNase protection assay and real-time reverse transcription polymerase chain reaction showed that tumor necrosis factor alpha/beta, interleukin-12, and interferon-gamma were inhibited by mechlorethamine upon successful treatment. Our findings support that mechlorethamine restores follicular activity by selectively targeting infiltrated lymphocytes in vivo in alopecia-areata-affected mice.

Alkylating Agents↗
PubMed1999

Hair grafting in postburn alopecia.

BACKGROUND: Hair micrografting has been widely used in male and female androgenetic alopecia but there is little experience with cicatricial or burn alopecia. OBJECTIVE: To evaluate the clinical outcome of a case of postburn alopecia with marked inelastic affected areas but with good elasticity and hair density over occipital donor site, treated with multiple sessions of hair micrografting. METHODS: Single-hair micrografts were employed to reconstruct the hair line but 2- and 3-hair micrografts were implanted over other alopecic areas. Grafts were placed into oblique slits made with N degrees 15 scalpel blade bevelled due to reduced dermis in the recipient area. Donor site was closed with vertical mattress and running suture with 3-0 silk. RESULTS: In 4 sessions 6500 micrografts were implanted into the affected areas, achieving a natural appearing hair line and a good cosmetic result. CONCLUSION: Hair micrografting is a promising restorative technique for inelastic plaques of postburn alopecia.

Adult↗