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PubMed2002

The pattern and profile of alopecia areata in Singapore--a study of 219 Asians.

BACKGROUND: Alopecia areata is believed to be an autoimmune condition with a worldwide occurrence. It usually presents as patchy, nonscarring hair loss. There is a paucity of clinical data in Asians. OBJECTIVE: To study the epidemiology, clinical aspects, associations, and treatment of alopecia areata in an Asian population over a 1-year period. METHODS: Records of all newly diagnosed alopecia areata cases seen from May 1998 to April 1999 at the National Skin Center were collated with regard to the epidemiology, pattern of alopecia, and associations according to the investigational guidelines published by Oslen et al. The treatment and psychologic impact of alopecia areata were also assessed. RESULTS: Two hundred and nineteen new case referrals of alopecia areata were seen from May 1998 to April 1999. The incidence of alopecia areata was 3.8%. There were 173 Chinese (79%), 35 Indians (16%), and 11 Malays (5.0%). The male to female ratio was 1 : 1.3. The median age at presentation was 25.2 years. The majority of patients (85.5%) had their first episode of alopecia areata before the age of 40 years. Of the patients with onset of alopecia areata before the age of 40 years, 36.5% presented with extensive alopecia, compared with 5.5% above the age of 40 years (P < 0.05). Nail changes, consisting of pitting, trachyonychia, and longitudinal ridging, were reported in 23 patients (10.5%). A significant percentage of patients had an associated personal and family history of atopy (60.7%). There was no significant association between a personal history of atopy and the extent of alopecia areata. The frequencies reported for the following associated diseases were: thyroid disease, 2.3%; vitiligo, 4.1%; diabetes mellitus, 3.2%; Down's syndrome, 1.4%; and rheumatic arthritis, 0.9%. A family history of alopecia areata was reported in 4.6%. Intralesional triamcinolone acetonide was the first-line treatment for limited alopecia areata, while squaric acid dibutyl ester was used for extensive involvement. The majority of patients with limited alopecia areata (82.1%) had more than 50% improvement with intralesional triamcinolone acetonide after 3 months. The majority of patients who received squaric acid dibutyl ester (87.5%) achieved more than 50% regrowth at the end of 6 months. Poor prognostic factors for alopecia areata were extensive involvement, early age of onset, and Down's syndrome. Thirteen out of 132 respondents (9.8%) recalled stressful events preceding hair loss. Patients with extensive alopecia areata experienced more psychologic adverse effects than those with limited alopecia areata (P < 0.05). Males with extensive alopecia areata experienced more severe psychologic ill-effects, such as depression and feelings of inability to improve hair loss. CONCLUSIONS: Our findings are similar to those reported in the Western literature where alopecia areata is predominantly a disease of the young. A holistic approach is important in the management of alopecia areata as the disease can have a severe psychologic impact on an individual's well-being.

Adjuvants, Immunologic↗
PubMed2002

Resistance to alopecia areata in C3H/HeJ mice is associated with increased expression of regulatory cytokines and a failure to recruit CD4+ and CD8+ cells.

Grafting alopecia areata affected C3H/HeJ mouse skin to littermates induces alopecia areata, but high dietary soy oil reduces alopecia areata susceptibility. Alopecia areata affected and resistant mice were characterized to evaluate possible mechanisms involved in alopecia areata resistance. Of 44 mice that received alopecia areata affected skin grafts but failed to develop alopecia areata, only two of 22 receiving further alopecia areata affected skin grafts developed alopecia areata, whereas 39 of 44 controls developed alopecia areata. Alopecia areata affected skin contained increased numbers of CD4+ and CD8+ cells, increases in pro inflammatory T helper 1 and T helper 2 type cytokines, and upregulation of CD28, CD40L, and their ligands. In draining lymph nodes, a relatively high number of antigen-presenting cells was recovered, whereas several CD44v variants were downregulated. In contrast, alopecia areata resistant mouse skin did not display increased numbers of CD4+ and CD8+ cells, whereas counter-regulatory cytokines interleukins 4 and 10 were upregulated. High expression of CD28, CD80, CD86, CD40, CTLA4, CD44v variants, and FasL occurred in alopecia areata resistant mouse spleens. In vitro, lymph node cells of susceptible and resistant mice responded equally to a mitogenic stimulus, but only lymph node cells from alopecia areata affected mice displayed an increased response with T cell receptor stimulation via anti-CD3 cross-linking. These results suggest alopecia areata is a cell-mediated autoimmune disease, but alopecia areata affected skin graft hosts may resist alopecia areata onset through active counter-regulatory mechanisms. Because alopecia areata resistant mice showed unimpaired responsiveness and a transient inflammatory response towards the graft, it is suggested that alopecia areata develops as a consequence of an inappropriate immune response regulation.

Alopecia Areata↗
PubMed2005

Frontal fibrosing alopecia: a survey in 16 patients.

BACKGROUND: Postmenopausal frontal fibrosing alopecia (PFFA) was described by Kossard et al. as a progressive recession of the frontal hairline affecting particularly postmenopausal women. Further cases of PFFA have been reported to date, all of them considering it as a variant of lichen planopilaris on the basis of its clinical, histological and immunohistochemical features. OBJECTIVE: To describe clinical features, and response to treatment of 16 cases of frontal fibrosing alopecia diagnosed at our department in the last 6 years. METHODS: In addition to clinical data, biopsies and laboratory tests (antinuclear antibodies, sex hormones, thyroid hormones) were performed in order to rule out other causes of scarring alopecia. Patients were treated with intralesional corticosteroids, finasteride, and minoxidil, depending on the stage of the disease and association to androgenetic alopecia. RESULTS: All patients presented progressive alopecia localized to the frontal and temporal hairlines. Eight patients (50%) had loss of eyebrows, and six patients (37.5%) had axillar alopecia. Ages ranged from 45 to 79. Three of these women were premenopausal. Androgenetic alopecia was evident in seven patients (43.8%). All patients biopsied showed perifollicular lymphocitic infiltrate with lamelar fibrosis limited to the upper portions of the follicle. The progression of the condition stopped in most patients after a variable period on treatment. When treatment was abandoned the alopecia progressed to 'clown alopecia' appearance. DISCUSSION: Cases of Kossard's type scarring alopecia affecting premenopausal women made us consider that this condition is not exclusive of postmenopausal women. Differential diagnosis should take into account conditions like female androgenetic alopecia, fibrosing alopecia in a pattern distribution, alopecia areata, and chronic lupus erythematosus. Except for the pattern of alopecia, lichen planopilaris and frontal fibrosing alopecia are indistinguishable, thus the latter is included as a variant of lichen planopilaris. Although the disease tends to spontaneous stabilization, intralesional and topical corticosteroids, and anti-androgens may stop the progression of the disease and improve the female androgenetic alopecia that usually is associated to FFA.

Aged↗
PubMed2002

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.

Adoptive Transfer↗
PubMed2002

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).

Alleles↗
PubMed2004

Primary cicatricial alopecias: clinicopathology of 112 cases.

BACKGROUND: Cicatricial alopecias represent a diverse group of diseases characterized by a lack of follicular ostia and irreversible alopecia. There is limited literature on the epidemiology and therapeutics of cicatricial alopecias. OBJECTIVE: The aim of this study was to review the epidemiology, clinical characteristics, and treatment of inflammatory cicatricial alopecias in a mixed ethnic population referred to a university hair clinic. METHODS: The study population consisted of 112 patients seen during a 5-year period with acquired primary cicatricial alopecias. This represented 3.2% of the total number of trichologic consultations seen at the University of British Columbia Hair Clinic, Vancouver, British Columbia, Canada. RESULTS: The ratio of lymphocytic to neutrophilic cicatricial alopecias was 4:1. Lymphocytic cicatricial alopecias had a tendency to affect middle-aged women, whereas neutrophilic cicatricial alopecias had a predilection for middle-aged men. CONCLUSIONS: An accurate diagnosis of cicatricial alopecia is achieved through careful clinicopathologic evaluation. We suggest that a scalp biopsy is mandatory in all cases. Multiple biopsies may be necessary for some affected individuals to achieve a definitive diagnosis as a result of a highly variable clinical course. An aggressive multiple modality therapeutic approach is often necessary to prevent further irreversible follicular destruction, implying cicatrical alopecia should be considered a trichologic emergency. Current therapeutic options for lymphocytic cicatricial alopecia include corticosteroids, antimalarials, and isotretinoin versus antibiotics, corticosteroids, and isotretinoin for neutrophilic cicatricial alopecias.

Adolescent↗
PubMed2003

Decreased serum ferritin is associated with alopecia in women.

Alopecia in women is a common problem, and conflicting observational data have failed to determine whether an association exists between alopecia and iron deficiency in women. We therefore utilized an analytical cross-sectional methodology to evaluate whether common types of alopecia in women are associated with decreased tissue iron stores, as measured by serum ferritin. We studied patients with telogen effluvium (n = 30), androgenetic alopecia (n = 52), alopecia areata (n = 17), and alopecia areata totalis/universalis (n = 7). The normal group consisted of 11 subjects without hair loss from the same referral base and source population as those patients with alopecia. We analyzed the data utilizing the unpaired Student's t test assuming unequal variances with an alpha adjustment for multiple comparisons to assess whether the mean ages, ferritin levels, and hemoglobin levels of women without hair loss differed from the means in each alopecia group. The mean age of patients and normals did not differ significantly. We found that the mean ferritin level (ng per ml [95% confidence intervals]) in patients with androgenetic alopecia (37.3 128.4, 46.1]) and alopecia areata (24.9 [17.2, 32.6]) were statistically significantly lower than in normals without hair loss (59.5 [40.8, 78.1]). The mean ferritin levels in patients with telogen effluvium (50.1 [33.9, 66.33]) and alopecia areata totalis/universalis (52.3 [23.1, 81.5]) were not significantly lower than in normals. Our findings have implications regarding therapeutics, clinical trial design, and understanding the triggers for alopecia.

Adolescent↗
PubMed2003

[Intravenous pulse methylprednisolone therapy for severe alopecia areata: an open study of 66 patients].

INTRODUCTION: Treatment of alopecia areata is a difficult challenge. Some European publications have shown encouraging results with high dose pulse corticosteroid therapy in extensive plurifocal alopecia areata. We undertook a prospective open study between January 2000 and December 2001 using repeated pulse each month, with the aim of identifying the effects of this repetition and underlining the best indications. PATIENTS AND METHODS: Sixty-six patients aged 9 to 60 years old presenting an extensive alopecia areata exceeding 30% of the scalp surface (n=47), alopecia totalis (n=8), alopecia universalis (n=8), ophiasic alopecia (n=3), for less than 12 months entered this study. The administered treatment was methylprednisolone 500 mg/d during 3 days or 5 mg/kg twice per day during 3 days in children. These pulses were repeated after 4 and 8 weeks, then a second series was carried out or not according to cases. The main evaluation criterion was the percentage of new terminal hair appearing on the bald areas, appreciated by clinical and photographic evaluation at 3 and 6 months. RESULTS: Ophiasic alopecia areata did not respond to treatment. A quarter of patients presenting universal alopecia had a good response (higher than 80 p. 100) followed by a relapse in half the cases. Half of the patients presenting alopecia totalis had a good response, which was maintained three times out of four. Multifocal alopecia areata seems the best indication since the patients under study presented a good response in 63.8 p. 100 of cases (78 p. 100 when it was a first episode and 90.5 p. 100 if the treatment had been started in less than 3 months before). The repetition of the pulses did not appear to increase the number of responders. CONCLUSION: This study provides the best indication of pulse methylprednisolone therapy: first recent episode of extensive plurifocal alopecia areata. These results are less convincing in long term history or other forms of alopecia areata.

Adolescent↗
PubMed1994

Alterations in androgen conjugate levels in women and men with alopecia.

OBJECTIVE: To assess levels of androgen metabolites thought to reflect, at least in part, peripheral androgen activity in women with androgenic alopecia and men with premature balding in an effort to determine if a common abnormality exists. DESIGN: Prospective study in various groups of women and men. SETTING: Reproductive Endocrine Clinic at our university medical center. PATIENTS: Ten normal ovulatory female controls and 50 hyperandrogenic women divided on the basis of hirsutism and alopecia as follows: [1] 8 hirsute women with androgenic alopecia; [2] 12 nonhirsute women with androgenic alopecia; [3] 18 hirsute women without androgenic alopecia; and [4] 12 nonhirsute women without androgenic alopecia. Ten normal men and 10 young premature balding men matched for age and weight also were compared. INTERVENTION: Blood was obtained from all subjects. MAIN OUTCOME MEASURE: Comparison of blood hormone levels in the various groups. RESULTS: Serum T, androstenedione, and DHEAS were similarly elevated in hyperandrogenic women with and without alopecia, compared with controls. The female groups were then divided on the basis of hirsutism. Hirsute groups with and without alopecia had similarly elevated levels of unconjugated 3 alpha-androstanediol, 3 alpha-androstanediol glucuronide, 3 alpha-androstanediol sulfate, androsterone glucuronide, and androsterone sulfate compared with controls. In the nonhirsute groups, androgenic alopecia patients were compared with hyperandrogenic females and cycling controls. The androgenic alopecia patients had elevated levels of 3 alpha androstanediol (0.75 +/- 0.12 versus 0.46 +/- 0.1 and 0.41 +/- 0.1 nmol/L), 3 alpha-androstanediol sulfate (200 +/- 31 versus 79.6 +/- 6 and 67.0 +/- 4.0 nmol/L), elevated ratios of 3 alpha-androstanediol sulfate:3 alpha-androstanediol (267 +/- 49 versus 170 +/- 20 and 164 +/- 49 nmol/L), elevated ratios of 3 alpha-androstanediol sulfate:3 alpha-androstanediol glucuronide (32.2 +/- 6 versus 10.8 +/- 1 and 10.0 +/- 1) and lower ratios of 3 alpha-androstanediol glucuronide:3 alpha-androstanediol glucuronide (8.3 +/- 1.8 versus 17 +/- 1.7 and 15.2 +/- 1.6 nmol/L). In men the premature balding group had lower levels of 3 alpha-androstanediol glucuronide compared with the male controls (29.8 +/- 4.4 versus 15.2 +/- 1.6 nmol/L). Also, the ratio of 3 alpha-androstanediol glucuronide:3 alpha-androstanediol was significantly decreased, whereas the ratio of 3 alpha-androstanediol sulfate:3 alpha-androstanediol glucuronide was elevated. CONCLUSIONS: These data provided evidence confirming that enhanced 5 alpha-reductase activity occurs in androgenic alopecia but also suggests that a disorder of androgen conjugation, favoring sulfurylation over glucuronidation, may be a characteristic feature of scalp hair loss.

Adolescent↗
PubMed1999

Successful treatment of alopecia areata-like hair loss with the contact sensitizer squaric acid dibutylester (SADBE) in C3H/HeJ mice.

A type of hair loss closely resembling human alopecia areata has been described in C3H/HeJ mice. In order to test the assumed analogy with human alopecia areata, we investigated the efficacy of treatment with the contact allergen squaric acid dibutylester. In 12 C3H/HeJ mice with alopecia areata an allergic contact dermatitis was induced and elicited weekly on one side of the back by topical applications of squaric acid dibutylester. Overt hair regrowth was observed only on the treated side of the back in nine of 12 mice. Histopathologic examination revealed a change in the distribution of the inflammatory infiltrate from a dense perifollicular lymphocytic infiltrate around the mid and lower regions of hair follicles in untreated skin to a uniform presence in the upper dermis in treated skin. Immunohistomorphometric studies revealed that treatment with squaric acid dibutylester increased the CD4+/CD8+ ratio from approximately 1:2 in untreated alopecia areata to 1:1 in treated alopecia areata. Additional immunohistochemical investigations showed an aberrant expression of major histocompatibility complex class I, major histocompatibility complex class II and intercellular adhesion molecule 1 on keratinocytes of the mid and lower parts of hair follicles in untreated alopecia areata. In successfully treated skin ectopic major histocompatibility complex class I and II expression was clearly reduced, whereas intercellular adhesion molecule 1 expression showed only minor changes. In conclusion, alopecia areata-like hair loss in C3H/HeJ mice responded to treatment with the contact sensitizer squaric acid dibutylester analogous to human alopecia areata. Moreover, successful treatment changes the aberrant expression of major histocompatibility complex class I and II in a way similar to that observed in human alopecia areata. These observations support the concept that alopecia areata-like hair loss in C3H/HeJ mice can be utilized as an appropriate model for the study of human alopecia areata.

Allergens↗
PubMed2002

Transient CD44 variant isoform expression and reduction in CD4(+)/CD25(+) regulatory T cells in C3H/HeJ mice with alopecia areata.

Alopecia areata, an autoimmune disease affecting anagen stage hair follicles, can be induced by grafting spontaneous alopecia areata affected skin to normal-haired C3H/HeJ mice. As the onset of alopecia areata can be significantly retarded by anti-CD44 variant isoform 10 treatment, it was interesting to explore the underlying disease mechanism. Two weeks after transplanting alopecia areata affected skin, expression of CD44 variant isoforms 3, 6, 7, and 10 was strikingly upregulated as compared with sham-grafted mice. By 6 wk after grafting, CD44 variant isoform levels had returned to normal, whereas in draining lymph nodes, CD44 variant isoform expression was slightly decreased. Leukocytes in the skin of mice with chronic alopecia areata expressed a hematopoietic isoform of CD44 and CD44 variant isoform 6 at an elevated level, but CD44 variant isoform 3 expression was reduced. Cytokine expression in leukocytes of chronic alopecia areata affected skin was higher than in normal-haired controls. Cytokine expression also increased postsurgery in sham and alopecia areata grafted mice, but remained elevated only in mice receiving alopecia areata affected skin. Finally, from the skin of mice with chronic alopecia areata and of mice transplanted with alopecia areata affected skin, an increased number of CD4(+) and CD8(+) cells, but a strongly decreased number of CD4(+)/CD25(+) regulatory T cells was recovered. Thus, expression of CD44 variant isoforms is important for the migration of leukocytes during the initial period of alopecia areata. CD44, however, is apparently not involved in the maintenance of the disease state, which is characterized by high cytokine expression levels, an increased number of CD4(+) and CD8+ cells, but a low level of CD4(+)/CD25(+) suppressor cells.

Alopecia Areata↗
PubMed1996

Profile of alopecia areata in Northern India.

BACKGROUND: Epidemiologic studies of alopecia areata (AA) are available from USA, Japan and European countries, but there is a paucity of literature on AA from Asian countries, especially from the Indian subcontinent. METHODS: In a prospective, hospital-based study lasting for a decade (1983-1992), the epidemiology of AA was studied, including associated diseases and risk factors for development of severe AA. Simultaneously a similar study was carried out in age- and sex-matched controls. RESULTS: Eight hundred and eight patients (532 men, 276 women) and 572 age- and sex-matched controls (370 men, 202 women) were studied. The incidence of AA was 0.7% of new dermatology outpatients. The majority of patients (712, 88%) were below 40 years of age, including 196 children < 16 years of age (24%). Almost half (46%) of the women patients had onset of AA in childhood, compared to only 19% in men (P < 0.001). Alopecia was total, universal, or extensive in 154 patients (19%). An onset in the first two decades was more often associated with severe alopecia (P < 0.001), especially in men (P < 0.01). Alopecia areata was recorded in family members of 70 patients (9%), being more frequent in the severe forms of AA (16%). Evidence of atopy was recorded in a total of 146 instances (18%). The frequency of atopy was the same in circumscribed alopecia (18.1%) and severe alopecia (18.2%). Nail changes were found in 162 patients (20%) and were more frequent in 76 (47%) with the severe form of AA (P < 0.001). On 39 occasions (5%), autoimmune-related diseases were detected: vitiligo in 15 (1.8%), thyroid disorders in 8 (1%), lichen planus in 6 (0.7%), collagen vascular diseases in 5 (0.6%), diabetes mellitus in 4 patients (0.4%), and pemphigus foliaceus in 1 (0.1%) patient. Patients with family members having vitiligo (recorded in 5.9% of patients), were more frequently affected with severe alopecia (P < 0.001). CONCLUSIONS: Alopecia areata in North Indians showed a preponderance in men (M:F = 2:1) and the majority of persons with disease (88%) were below 40 years of age. Onset in childhood was more frequent in girls or women, but the incidence of severe alopecia was higher in boys or men with onset at an earlier age. Diseases associated with autoimmunity were seen in only 5% of patients. Atopy was found to be associated in 18% of patients, but its reported association with younger age of onset and severe alopecia was not confirmed. Presence of vitiligo in family members and onset before 20 years of age, especially in boys or men, were found to be risk factors for severe alopecia.

Adolescent↗