Article

Association between Vitamin D Levels and Alopecia Areata

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Abstract

Background: Alopecia areata (AA) is an autoimmune disease, based on the response to local and/or systemic corticosteroid treatment. The role of vitamin D in the pathogenesis of immune/autoimmune mediated diseases has been widely studied. Objectives: To investigate a possible association between serum 25-hydroxyvitamin D levels and alopecia areata. Methods: The study included 23 patients diagnosed with AA followed at our outpatient clinic during the period March 2010 to May 2011, as well as a control group matched for age and gender. All subjects underwent a complete work-up and medical examination, anthropometric measurements and laboratory tests. Laboratory tests included complete blood count, C-reactive protein (CRP), and vitamin D levels. Results: Mean CRP values were significantly higher in the AA group than the control group (1.1 +/- 0.7 mg/dl vs. 0.4 +/- 0.8 mg/ dl, P < 0.05). Vitamin D levels were significantly decreased in the AA group (11.32 +/- 10.18 ng/ml vs. 21.55 +/- 13.62 ng/ml in the control group, P < 0.05). Multivariate analysis showed that CRP (odds ratio 3.1, 95% confidence interval 2.6-4.2, P = 0.04) and serum vitamin D levels < 30 ng/ml (OR 2.3, 95% CI 2.2-3.1, P = 0.02) were associated with AA. Conclusions: We found a significant correlation between AA and vitamin D deficiency. Vitamin D deficiency can be a significant risk factor for AA occurrence.

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... It was established that decrease VDR expression is associated with impaired growth of hair follicle and reduction of epidermal differentiation [8]. It was found that patients with AA have a deficiency of serum vitamin D 3 levels and a decrease VDR expression in affected hair follicles [9][10][11]. ...
... NB-UVB has been included as a treatment option in some AA treatment guidelines and it is known that NB-UVB has a positive effect on vitamin D synthesis by skin [10,21]. The biological actions of vitamin D 3 derivatives include regulation of epidermal cell proliferation and differentiation and modulation of cytokine production [13,22]. ...
... This finding is in a congruence with D'Ovidio et al. who found non-significant difference in deficiency or insufficiency of vitamin D 3 between patients with AA and controls [23]. On the other hand, there are some reports detected lower levels of vitamin D 3 in patients with AA, and a negative correlation between serum vitamin D 3 levels and AA severity was found [8][9][10]. The non-significant correlation between serum vitamin D 3 levels and SALT score in the present study may be due to small sample size which can affect the level of significance. ...
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Alopecia areata is a chronic relapsing autoimmune inflammatory hair disorder with no novel therapy. The objectives of this study are to compare the efficacy of topical calcipotriol vs narrow band ultraviolet B phototherapy (NB-UVB) in the treatment of alopecia areata and its correlation with serum vitamin D 3 levels. A randomized-controlled trial has been conducted on 60 patients with scalp alopecia areata randomized into four groups; topical calcipotriol, NB-UVB, both and placebo. All patients were evaluated by assessment of severity of alopecia areata by severity of alopecia tool (SALT) score at baseline and 3 months after treatment and vitamin D 3 levels at baseline and after 3 months. SALT score and vitamin D 3 levels were significantly improved in all groups except placebo after treatment with (P = 0.026, P = 0.005, P = 0.004, P = 0.140) and (P = 0.028, P = 0.011, P = 0.003, P = 0.725), respectively. Combined therapy showed non-significant improvement in SALT score (P = 0.530, P = 0.643), respectively, and significant improvement in serum vitamin D 3 levels than each line alone with (P = 0.021, P = 0.044), respectively. Both topical calcipotriol and NB-UVB are effective therapies in the treatment of AA and associated with improvement of SALT score and vitamin D 3 levels.
... This is in line with the study done by Mahamid et al on 23 patients of AA where the mean age noted was 24.2 years. 7 In a study by Bakry et al mean age of presentation was 20.70 years among 60 patients of AA included in their study. 15 In the current study slight male preponderance was seen (M: F=1.10: 1). ...
... 15 In the current study slight male preponderance was seen (M: F=1.10: 1). These findings are consistent with studies by Cerman et al, Mahamid et al and Bakry et al. 4,7,15 The lowest SALT score recorded in our study was 5% while the highest SALT score was seventy-four per cent. Twenty-eight (70.0%) patients were in S1 subgroup while only 3 (7.5%) ...
... 4 Similarly, Mahamid et al in a prospective study with 23 consecutive patients diagnosed with AA found a significant correlation between AA and vitamin D deficiency (p<0.05) and they were of the opinion that vitamin D deficiency can be a risk factor for AA occurrence. 7 Bakry et al did a study on serum vitamin D levels in patients with AA (N=60) and documented that serum 25(OH)D levels were significantly lower (p<0.001) when compared with healthy controls. ...
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p class="abstract"> Background: Alopecia areata (AA) is a T cell-mediated autoimmune disorder of anagen hair follicle leading to distressing and relapsing non-scarring hair loss. Vitamin D an immunomodulator plays important role in regulating normal hair cycle. Recent evidence suggests inconsistent association between vitamin D deficiency and alopecia areata. Methods: Hospital-based cross-sectional observational study of forty untreated cases of alopecia areata and forty age and sex-matched healthy controls in 18-45 years of age group recruited from out-patient department. Each patient will undergo a detailed history, clinical examination and SALT (Severity of alopecia tool) scoring. Enhanced chemiluminesence method (Eci) will be used to estimate serum 25-hydroxy vitamin D [25(OH)D]. Results: The mean 25(OH)D level in patients of AA was 12.45±4.80 ng/ml (deficient), while that of controls was 33.73±10.02ng/ml (normal). The difference between the levels of 25(OH)D in patients of AA and controls came out to be statistically significant (p≤0.0001). A strong negative correlation was seen between SALT score and 25(OH)D level (-0.32), which was found to be statistically significant (p=0.0462). Conclusions: The present study established that vitamin D levels are either insufficient/deficient in alopecia areata and it correlates negatively with severity of SALT (severity of alopecia tool) score.</p
... Since the immunomodulatory effect of vitamin D was demonstrated, its potential role has been studied in many areas of medicine. A growing body of evidence shows that vitamin D and its receptor may be involved in skin homeostasis [1,4,[12][13][14][15][16]. ...
... Literature data suggest that vitamin D, due to its immunomodulatory effect, may be involved in the pathogenesis of AA [12,16,33]. ...
... Decreased serum 25(OH)D levels in AA in comparison to healthy subjects were reported in many studies [12,13,16,[33][34][35][36][37] (Table 1). ...
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Non-scarring hair loss is a common problem that affects both male and female patients. Since any disturbances in the hair follicle cycle may lead to hair shedding, or alopecia, it is not surprising that the possible role of vitamin D in alopecia was investigated in many studies. Vitamin D has been shown to have many important functions. A growing body of evidence shows that vitamin D and its receptor are responsible for maintaining not only calcium homeostasis but also skin homeostasis. Moreover, vitamin D could also regulate cutaneous innate and adaptive immunity. This paper presents a review of current literature considering the role of vitamin D in alopecia areata, telogen effluvium, and female pattern hair loss. The majority of studies revealed decreased serum 25-hydroxyvitamin D levels in patients with different types of non-scarring alopecia, which could suggest its potential role in the pathogenesis of hair loss. According to the authors, vitamin D supplementation could be a therapeutic option for patients with alopecia areata, female pattern hair loss, or telogen effluvium. However, further studies on a larger group of patients are required.
... It was reported only in a seven year-old patient with AA treated with topical calcipotriol [17]. There are also a few studies regarding the relationship between serum 25(OH)D levels and AA [14][15][16]18]. ...
... This finding was not surprising for us because the prevalence of vitamin D deficiency was found 93% in spring and 71% in autumn in healthy school-children in our previous study [19]. Studies investigating the association between hypovitaminosis D and AA have yielded conflicting results [14,15,18]. In a cross-sectional study from Turkey, 42 adults with AA and healthy controls were analyzed in terms of 25(OH)D levels and found that 25(OH)D levels were significantly lower in patients than that of controls [14]. ...
... They also reported that decreased level of 25(OH)D was not correlated with extent of hair loss. In a recent study from Israel, 25(OH)D levels were evaluated in 23 adult patients with AA and controls (n=20) [18]. The authors reported that vitamin D levels were significantly lower in patients than those controls and suggested vitamin D deficiency could be a risk factor for AA occurrence. ...
Article
Objectives: Little is known about the association of vitamin D and alopecia areata (AA). Our objectives were to search a relation between 25-hydroxyvitamin D [25(OH)D] levels and the development of AA and the efficacy of oral vitamin D treatment in children with AA and vitamin D deficiency.Methods: Thirty newly diagnosed AA patients and 30 sex- and age-matched controls were included in the study. Levels of 25(OH)D, parathormone, calcium, inorganic phosphate, alkaline phosphatase were measured at baseline and sixth month. Both patients and controls who diagnosed vitamin D deficiency were treated with oral vitamin D for six months.Results: Serum 25(OH) D levels of the patients and controls were 25.3 ± 19.4 ng/ml and 21.3 ± 12.5 ng/ml, respectively (p>0.05). The frequency of vitamin D deficiency was similar in patients and controls. Serum levels of 25(OH)D and calcium were increased significantly after six months of the treatment in both patients and controls with vitamin D deficiency (p<0.05). A higher frequency (47%) of complete improvement was observed in patients with AA and vitamin D deficiency during oral vitamin D treatment.Conclusions: There was no statistically significant difference in 25(OH)D levels between the patients with AA and controls. However, we observed a higher frequency of complete improvement in these patients with an improved vitamin D status. Thus, oral vitamin D treatment can be given only to selected AA patients who are also deficient in vitamin D.
... It was established that decrease VDR expression is associated with impaired growth of hair follicle and reduction of epidermal differentiation [8]. It was found that patients with AA have a deficiency of serum vitamin D 3 levels and a decrease VDR expression in affected hair follicles [9][10][11]. ...
... NB-UVB has been included as a treatment option in some AA treatment guidelines and it is known that NB-UVB has a positive effect on vitamin D synthesis by skin [10,21]. The biological actions of vitamin D 3 derivatives include regulation of epidermal cell proliferation and differentiation and modulation of cytokine production [13,22]. ...
... This finding is in a congruence with D'Ovidio et al. who found non-significant difference in deficiency or insufficiency of vitamin D 3 between patients with AA and controls [23]. On the other hand, there are some reports detected lower levels of vitamin D 3 in patients with AA, and a negative correlation between serum vitamin D 3 levels and AA severity was found [8][9][10]. The non-significant correlation between serum vitamin D 3 levels and SALT score in the present study may be due to small sample size which can affect the level of significance. ...
Article
Abstract Alopecia areata is a chronic relapsing autoimmune inflammatory hair disorder with no novel therapy. The objectives of this study are to compare the efficacy of topical calcipotriol vs narrow band ultraviolet B phototherapy (NB-UVB) in the treatment of alopecia areata and its correlation with serum vitamin D3 levels. A randomized-controlled trial has been conducted on 60 patients with scalp alopecia areata randomized into four groups; topical calcipotriol, NB-UVB, both and placebo. All patients were evaluated by assessment of severity of alopecia areata by severity of alopecia tool (SALT) score at baseline and 3 months after treatment and vitamin D3 levels at baseline and after 3 months. SALT score and vitamin D3 levels were significantly improved in all groups except placebo after treatment with (P = 0.026, P = 0.005, P = 0.004, P = 0.140) and (P = 0.028, P = 0.011, P = 0.003, P = 0.725), respectively. Combined therapy showed non-significant improvement in SALT score (P = 0.530, P = 0.643), respectively, and significant improvement in serum vitamin D3 levels than each line alone with (P = 0.021, P = 0.044), respectively. Both topical calcipotriol and NB-UVB are effective therapies in the treatment of AA and associated with improvement of SALT score and vitamin D3 levels.
... There are also studies evaluating the effect of vitamin D on hair diseases. 4,[16][17][18][19][20][21][22][23][24] To our knowledge there are limited number of studies investigating the relationship between TE and vitamin D and results of these studies were contradictory. 4,[21][22][23][24] We planned this study to evaluate the vitamin D levels in TE patients and to investigate whether there is a relationship between vitamin D status and TE. ...
... 10,15 After the immunomodulatory effect of vitamin D was demonstrated, its potential role has been studied in many areas of medicine including skin and hair diseases. 10,[12][13][14][15][16][17][18][19][20][21][22][23][24] It was demonstrated that keratinocytes are capable of metabolizing vitamin D to the active form. 25 Other cells including macrophages and dendritic cells are also capable of synthesizing the active form of vitamin D, and this process is predominantly regulated by immune signals. ...
... There were studies investigating the relationship between alopesi areata and vitamin D. [16][17][18][19] In most of these studies, patients with alopecia areata had lower levels of vitamin D than the control group. 16,17,19 Only in one study vitamin D level was found to be similar in patient and control group. ...
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Objective: Telogen effluvium (TE) is most commonly seen type of hair loss and multiple factors play role in ethiopathogenesis of this disease. Vitamin D is closely related to hair and skin diseases due to its immunomodulatory and anti-inflammatory effects. In this study we aimed to determine the effect of Vitamin D on TE by evaluating the levels of Vitamin D in these patients. Material and Methods: The medical records of the patients who were admitted to our hospital dermatology polyclinic between January 2015 and March 2018 were evaluated retrospectively. The control group was created retrospectively from medical records of the individuals who visited other outpatient clinics and whose Vitamin D levels were measured. In the both groups, individuals with history of other systemic and dermatologic disease were excluded. The demographic characteristics and the levels of serum Vitamin D levels were recorded. Statistical analysis was performed using SPSS 17 (Chicago, IL) pack program. Results: There were 155 patients in the study group, 168 age- And sex- matched healthy individual in the control group. Mean 25- hydroxy Vitamin D (25OHD3) levels of the patient and control group were 13.42±6.28 ng/ml and 14.62±6.56 ng/ml, respectively. The difference was not statistically significant (p=0.09). Conclusion: Vitamin D levels were found to be lower in our patient group but the difference statistically insignificant. Our results indicate that there is no correlation between TE and Vitamin D levels. However, more scrutinized and prospective studies are warranted to address the issue of Vitamin D deficiency in TE. © 2018 Ortadog Reklam Tanitim Yayincilik Turizm Egitim Insaat Sanayi ve Ticaret A.S. All rights reserved.
... [12] Recent study demonstrated that the decreased expression of Vitamin D receptor in alopecia areata lesions is related to decreased expression of the Wnt signaling pathway, which inhibits proliferation and differentiation of hair follicles and epidermal cells. [13] Studies by Aksu Cerman et al., [4] Yilmaz et al., [12] Mahamid et al., [14] Attawa et al., [15] El-Mongy et al., [16] and Bhat et al. [17] found decreased serum Vitamin D levels in alopecia areata. However, all these studies included adult population. ...
... This was significantly less than the controls, 25.03 ± 13.84 ng/ml, and it was statistically significant (P < 0.05). Even Yilmaz et al., [12] Aksu Cerman et al., [4] Mahamid et al., [14] Attawa et al., [15] El-Mongy et al., [16] and Bhat et al. [17] found similar significant lower levels of serum Vitamin D in cases when compared to controls. ...
... An analysis of the distribution of serum Vitamin D deficiency among cases and controls showed a significantly increased percentage of Vitamin D deficiency among cases than in controls (73% vs. 46%; P < 0.05). Similarly, Mahamid et al., [14] Aksu Cerman et al., [4] and Yilmaz et al. [12] found that the percentage of Vitamin D deficiency was significantly more among cases when compared to controls. ...
Article
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Background: Alopecia areata is a common form of autoimmune, non-scarring alopecia and about one-third of cases affect people aged below 18 years. Alopecia in pediatric age group can cause psychological stress to parents and patients. Vitamin D plays a role in immune regulation and maintenance of hair cycle. Aims and Objectives: To evaluate serum vitamin D levels in pediatric alopecia areata cases. Methods: A comparative case-control study with 30 cases of pediatric alopecia areata and 30 age and sex matched healthy controls was conducted between Feb 2015 to July 2015. All subjects underwent complete evaluation and laboratory investigations including serum vitamin D was done. Results: Mean serum vitamin D level of pediatric alopecia areata cases (17.21±6.57 ng/ml) was significantly lower when compared to controls (25.03±13.84 ng/ml) (P < 0.05). Distribution of vitamin D deficiency was significantly higher in cases (73%) when compared to controls (46%) (P < 0.05). There was a significant inverse correlation between SALT scores of cases and their serum vitamin D levels (P < 0.05). Conclusions: There was decreased vitamin D levels observed in cases suggesting a possible role of vitamin D in alopecia areata and treating the deficiency may prevent the chronicity of the disease in children.
... Studies investigating serum levels of vitamin D in patients with AA have reported that serum vitamin D levels were significantly lower in AA patients compared to healthy controls (36,37) Similar to other studies in the literature, in our study, vitamin D levels of AA cases were found to be significantly lower than controls. Vitamin D levels were found to be less than 15 µg/L in 25 of 106 patients with AA (25/106). ...
... In the control group, none of the study participants had vitamin D values below 15 µg/L (0/106). Most studies reported low levels of vitamin D in both summer and winter periods (36,37) . In our study, summer values of vitamin D were taken into account and relatively lower levels were noted. ...
Article
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Objective: Alopecia areata (AA); is a sudden onset, non-scaring hair loss. Twenty percent of cases are children.Although it is thought to be related to genetic predisposition, inflammation, immunological processes or psychological triggers, its pathophysiology is still not fully understood. This study was planned to investigate the levels of serum 25-hydroxy vitamin D, vitamin B12, thyroid-stimulating hormone (TSH) and free T4 FT4) in children with AA and compare the results with age-matched healthy individuals. Methods: A retrospective medical record review was carried out in an outpatient dermatology clinic in a tertiary medical center between January 1,2013 and December 31, 2017. The study included 520 patients (ages 0-18 years) who received a clinical diagnosis of AA.106 patients with AA met the inclusion criteria.Patients in the control group (n=106) were selected among children aged 0-18 years without any medical and/or psychiatric diagnosis. Both past medical and family medical history were also noted. Results of laboratory tests including vitamin D, vitamin B12, TSH, FT4, and thyroid auto-antibodies were noted. Results: There was no significant difference between the patient and control groups in terms of mean age.Mean age of onset was 8.0 years. The number of boys and girls in both the patient and control groups were 55 and 51. Serum levels of FT4 and TSH in patients with AA were significantly higher than the control group. Both vitamin D and vitamin B12 levels of the patients with AA were significantly lower than the control group. Conclusion: Although its role in etiopathogenesis is not understood, the importance of monitoring both vitamins and thyroid functions in childhood AA cases is obvious.
... Currently, there is evidence that the levels of vitamin D are lower in AA patients than in healthy controls. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] It should also be noted that there are a few studies that did not demonstrate significantly lower levels of vitamin D in AA patients. [25][26][27][28] The increased prevalence of vitamin D deficiency, defined as \20 ng/mL or \30 ng/mL, depending on the study, was also seen among AA patients. ...
... [25][26][27][28] The increased prevalence of vitamin D deficiency, defined as \20 ng/mL or \30 ng/mL, depending on the study, was also seen among AA patients. 12,13,15,19,[21][22][23]25,28 A major limitation of applying these findings is that vitamin D levels are mainly affected by sun exposure combined with other factors, such as age, sex, weight, lifestyle, and diet, all of which vary widely in different regions of the world. [29][30][31][32][33] Hence, the need for local data on vitamin D levels in AA patients. ...
Article
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Background Alopecia areata (AA) has been postulated to be an autoimmune disease affecting the hair follicles. Because vitamin D receptors are present in the immune system and hair follicles, vitamin D has been hypothesized to affect the disease. Objective The aim of this study was to determine serum 25-hydroxyvitamin D levels and the percentage of vitamin D deficiency in AA patients and compare them with those in healthy controls in a Philippine tertiary hospital. Methods This cross-sectional study included 29 AA patients and 29 healthy controls. The serum 25-hydroxyvitamin D levels were determined using the chemiluminescent immunoassay method. Results There was no significant difference in the mean vitamin D levels between AA patients (24.41 ± 6.87 ng/mL) and healthy controls (24.68 ± 6.68 ng/mL) (P = .88). The percentage of patients with vitamin D deficiency, defined as <20 ng/mL, trended to higher among AA patients (34.4%) than among healthy controls (17.2%), with an odds ratio of 2.53 (95% CI 0.73-8.65), though this was not statsitically significant. Limitations This study involved a limited number of patients in an urbanized area in the Philippines, and majority of the AA cases seen had mild AA. Conclusion The trend toward the increased percentage of vitamin D-deficient individuals among AA patients seen in this study may provide insight into the association of vitamin D with AA.
... A number of studies demonstrated significantly lower levels of vitamin D in the patients with AA than the control group [11][12][13][14][15][16][17]. Several studies showed significantly higher prevalence of vitamin D insufficiency in patients with AA than the control group [12,13,18,19]. ...
... A number of studies demonstrated significantly lower levels of vitamin D in the patients with AA than the control group [11][12][13][14][15][16][17]. Several studies showed significantly higher prevalence of vitamin D insufficiency in patients with AA than the control group [12,13,18,19]. But there were two reports of inconsistent results. ...
Article
Alopecia areata is characterized by the loss of hair on the scalp and elsewhere on the body. It affects approximately 2% of the general population. It is believed to be an autoimmune disease. However, its pathogenesis remains incompletely understood. Recent studies have revealed a substantial link between vitamin D and alopecia areata. But the underlying mechanism still yet to be deciphered. This article reviews the current literature and discusses the possible roles of vitamin D in the pathogenesis of alopecia areata in the context of (1) loss of immune privilege in hair follicle, (2) autoreactive effector T cells and mast cells, (3) nature killer group 2 member d-positive cytotoxic T cells, (4) Janus kinase/signal transducers and activators of transcriptional signaling pathway, (5) regulatory T cells, (6) immune checkpoints, and (7) oxidative stress, which are believed to play important roles in autoimmunity in AA. This paper provides new insights into research directions to elucidate the exact mechanisms of vitamin D in the pathogenesis. Calcipotriol, a vitamin D analog, has been reported to be topically used in treating alopecia areata with promising results. Combination therapy of vitamin D analogs with corticosteroids might also be used in treating alopecia areata.
... Dermatolojik hasta grubunda yapılan çalışmalarda bu vitaminin eksikliği yaygın olarak görülmektedir. D vitamininin, Behçet hastalığı, atopik dermatit, allerjik kontak dermatit, psoriasis, vitiligo, alopesi areata, pemfigus vulgaris ve rozasea gibi deri hastalıkları üzerindeki antienflamatuar ve immünmodülatör etkisinden bahseden pek çok çalışma bulunmaktadır (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). ...
... [9] Serum and tissue levels of Vitamin D receptors are found to be decreased in patients of alopecia areata, suggesting a role in the pathogenesis. [10] Vitamin D deficiency is said to be a risk factor for the occurrence of alopecia areata, [11,12] and nutritional supplementation of Vitamin D has been proposed as a treatment modality. [13] Kim et al. reported a case of alopecia areata in a 7-year-old boy with decreased Vitamin D receptor expression, and the topical application of Vitamin D analog calcipotriol resulted in complete recovery in that child. ...
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Background: Alopecia areata is one of the common causes of nonscarring hair loss with autoimmune etiology. This study was designed to evaluate any added benefit of topical calcipotriol when combined with topical mometasone in the treatment of alopecia areata. To the best of our knowledge, no such study has been conducted in the past. Materials and methods: It was a comparative analytical study done over 100 patients of clinically diagnosed alopecia areata. Group A patients (n = 50) were advised to apply topical mometasone 0.1% cream along with topical calcipotriol 0.005% ointment each once daily, whereas patients of Group B (n = 50) were advised to apply only topical mometasone 0.1% cream in the same amount, once a day. Follow-up of all patients was done at 6, 12, and 24 weeks, and the outcome was assessed according to the Severity of Alopecia Tool (SALT) score at every visit. Results: Both the groups were statistically comparable in terms of age (P = 0.694) and sex (P = 0.683) distribution. Baseline mean SALT score of Group A and Group B patients was 7.22 and 6.05, respectively (P = 0.145). At the end of 24 weeks, mean SALT score of Group A and Group B patients decreased by 4.24 and 3.39, respectively (P < 0.001). We also found that there was a significant decrease (P < 0.001) in mean SALT score at 24 weeks in patients of both groups when compared with baseline values. Conclusion: We found that adding topical calcipotriol 0.005% ointment with topical mometasone 0.1% cream has higher efficacy than topical mometasone alone, in the treatment of alopecia areata.
... Literature data suggest that vitamin D, due to its immunomodulatory effect, may be involved in the pathogenesis of AA. Decreased serum 25(OH)D levels in AA in comparison to healthy subjects were reported in many studies [11,12]. Since the majority of studies were conducted on adult patients, the study by Unal et al. is of special interest. ...
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Introduction Vitamin D deficiency is a global health problem. With all the medical advances of the century, vitamin D deficiency is still epidemic. Over a billion people worldwide are vitamin D deficient or insufficient [1]. The prevalence of vitamin D deficiency is rising up in Saudi Arabia, according to a study done in 2014 in three regions in Saudi Arabia among students (n = 4,035) and employee (n = 2,104), the results showed that 49% of students and 44% of employee were vitamin D deficient [2]. There are many studies that discussed vitamin D deficiency in Saudi Arabia, a cross-sectional study conducted in Riyadh among first-trimester pregnant ladies in 2010, it showed that 50% of all the sample (n = 160) were vitamin D deficient [3]. In another cross-sectional study conducted among King Faisal University Medical Students in 2009, the result was 96% of the total (95 male and 103 female) students had vitamin D deficiency [4]. Vitamin D is an essential fat-soluble vitamin that is required for regulation of calcium metabolism and to maintain good health. It is obtained through either dietary sources or synthesis in the human skin by exposure to ultraviolet B (UVB) radiation [3]. In recent years, the ABSTRACT Background: Vitamin D deficiency is still epidemic and it represents a global health concern. Vitamin D deficiency is associated with several diseases, including bone diseases, multiple sclerosis, Alzheimer's disease, alo-pecia, and obesity. The deficiency of vitamin D is rising in Saudi Arabia. The presence of sufficient knowledge about this problem may lead to a decrease in its prevalence. The aim of the current study was to assess the knowledge and practice of adult population regarding vitamin D deficiency and risk of hair loss.
... We found that serum 25(OH)D levels were significantly lower in the case group in comparison with the control group. This goes with a study by Mahamid et al. [8]. ...
... A significant lower serum 25 (OH) D level (below 20 ng/ml) were observed in patients with alopecia areata compared with a healthy control group [49,[58][59][60]. ...
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Alopecia is a common dermatological complaint. Affected patients are often distressed and attempt to arrest the hair loss by taking various over the counter nutritional supplements containing vitamins and minerals. The evidence supporting their efficacy however is limited. Moreover, there are toxicity reports. We reviewed the literature about the normal levels and the daily dietary needs of the most common micronutrients, their role in the hair follicle cycle as well as their use in the hair loss treatment. 4 independent researchers reviewed a total of 119 papers, and 92 articles published in the English language within the last 30 years were included. Telogen effluvium and alopecia areata have been associated with lower iron, zinc and vitamin D levels. Androgenetic alopecia has been associated with lower iron and vitamin D levels. Both lower and increased vitamin A levels can result in telogen effluvium, but lower levels are associated also with hair breakage. Vitamin C insufficiency results in hair shaft abnormality (cork screw hairs). No data exist about hair loss associated with abnormal biotin levels. The role of micronutrients for the hair follicle function is not completely understood. Empiric treatments of hair loss with micronutrients without confirmed deficiencies have not shown utility.
... protein deficiency or compromised immune status, as shown in other studies. [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] The SC agreed that the clinical implications of hypophenylalaninemia are not clear and therefore recommended that extended periods of hypophenylalaninemia should be avoided. Although intake of intact protein should be increased as tolerated until ≥DRI is reached, the SC suggests that this alone may be insufficient to increase blood Phe concentrations in patients with hypophenylalaninemia and pegvaliase dose reduction may also be required. ...
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Purpose: Phenylketonuria (PKU) is a rare metabolic disorder that requires life-long management to reduce phenylalanine (Phe) concentrations within the recommended range. The availability of pegvaliase (PALYNZIQ™, an enzyme that can metabolize Phe) as a new therapy necessitates the provision of guidance for its use. Methods: A Steering Committee comprising 17 health-care professionals with experience in using pegvaliase through the clinical development program drafted guidance statements during a series of face-to-face meetings. A modified Delphi methodology was used to demonstrate consensus among a wider group of health-care professionals with experience in using pegvaliase. Results: Guidance statements were developed for four categories: (1) treatment goals and considerations prior to initiating therapy, (2) dosing considerations, (3) considerations for dietary management, and (4) best approaches to optimize medical management. A total of 34 guidance statements were included in the modified Delphi voting and consensus was reached on all after two rounds of voting. Conclusion: Here we describe evidence- and consensus-based recommendations for the use of pegvaliase in adults with PKU. The manuscript was evaluated against the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument and is intended for use by health-care professionals who will prescribe pegvaliase and those who will treat patients receiving pegvaliase.
... Published data on AA suggest that vitamin D, due to its immunomodulatory effect, may be involved in AA [66,67]. Lee et al. conducted a systematic review and meta-analysis of observational studies on the prevalence of vitamin D deficiency and/or serum vitamin D levels and AA [68]. ...
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People commonly inquire about vitamin and mineral supplementation and diet as a means to prevent or manage dermatological diseases and, in particular, hair loss. Answering these queries is frequently challenging, given the enormous and conflicting evidence that exists on this subject. There are several reasons to suspect a role for micronutrients in non-scarring alopecia. Micronutrients are major elements in the normal hair follicle cycle, playing a role in cellular turnover, a frequent occurrence in the matrix cells in the follicle bulb that are rapidly dividing. Management of alopecia is an essential aspect of clinical dermatology given the prevalence of hair loss and its significant impact on patients’ quality of life. The role of nutrition and diet in treating hair loss represents a dynamic and growing area of inquiry. In this review we summarize the role of vitamins and minerals, such as vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, iron, selenium, and zinc, in non-scarring alopecia. A broad literature search of PubMed and Google Scholar was performed in July 2018 to compile published articles that study the relationship between vitamins and minerals, and hair loss. Micronutrients such as vitamins and minerals play an important, but not entirely clear role in normal hair follicle development and immune cell function. Deficiency of such micronutrients may represent a modifiable risk factor associated with the development, prevention, and treatment of alopecia. Given the role of vitamins and minerals in the hair cycle and immune defense mechanism, large double-blind placebo-controlled trials are required to determine the effect of specific micronutrient supplementation on hair growth in those with both micronutrient deficiency and non-scarring alopecia to establish any association between hair loss and such micronutrient deficiency. Plain Language Summary: Plain language summary available for this article.
... In a study conducted on by Mahamid M et al., low vitamin-D level was detected in alopecia areata patients [26]. In another study conducted by Fawzi et al, it was found that vitamin-D receptor levels in serum and tissue were relatively low in patients with AA and alopecia areata in pathogenesis of which vitamin-D receptors are of vital importance [27]. ...
Article
INTRODUCTION: Androgenic Alopecia (AA) is defined as progressive miniaturization of scarless hair follicle prevailing among both male and female. Telogen effluvium (TE) is the most common hair loss form accompanying sistemic diseases. It is aimed to determine the role of vitamine D, the significance of which has been increasing in recent years, in hair loss problem within the scope of this study. METHODS: The patients who applied to Dermatology clinic with the complaint of hair loss and diagnosed AA and TE by clinic examination between the years 2015-2016 were included into this study. The age, gender and 25’OHvitamin-D level of the patients were recorded retrospectively. RESULTS: One-hundred eighty seven (N=187) participants (140 female / 47 male) were included in this study. Fifty-eight (N=58) patients (28 female / 30 male) with AA diagnosis formed the first group; 71 patients (65 female / 6 male) with TE were formed the second group and 58 healthy volunteers (47 female / 11male) were included in the control group. When Vitamin-D level of first group (AA) was compared with that of the second group (TE) and the control group, there was a statistically significant difference observed (p=0.01/p=0.01 respectively). However, there was no statistically significant difference between the vitamin-D level of second group (TE) and that of the healthy control group (p=0.61). CONCLUSION: The level of 25'(OH) vit D was found high in AA group than TE and controls. Revealing the relationship between vitamin-D level and hair loss might give us the opportunity to come up with new treatmant options considering refractory patients.
... Vitamin D deficiency and its relationship with alopecia has been studied for years. A deficiency of vitamin D has been reported as associated with AA (Aksu Cerman et al., 2014;Mahamid et al., 2014;Miller et al., 2015). In our literature review, there was no published association between vitamin D deficiency and LPP and to a magnitude whereby 50% of our patients with LPP were deficient (p = .014). ...
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Background Lichen planopilaris (LPP) is a rare, cicatricial, lymphocyte-mediated alopecia that is thought to have an autoimmune pathogenesis and possibly related to other autoimmune diseases. However, data are limited and studies that examine comorbid conditions are lacking. Objectives We sought to determine the prevalence of systemic comorbid conditions, nutritional deficiencies, psychological problems, and skin cancers in patients with LPP. Methods We identified 334 patients with LPP who were seen in the Department of Dermatology at the Cleveland Clinic Foundation between 2000 and 2016. Patients with LPP were compared with 78 control patients with a diagnosis of seborrheic dermatitis. Results There were more female patients with LPP compared with the controls (93.1% vs. 79.5%; p < .001) but the average age did not differ (54.77 ± 12.83 vs. 52.19 ± 15.37; p = .12). Conditions positively associated with LPP were Hashimoto’s thyroiditis (6.3% vs. 0%; p = .023), hypothyroidism (24.3% vs. 12.8%; p = .028), and hirsutism (11.4% vs. 1.3%; p = .006). Negatively associated conditions were allergic rhinitis (15% vs. 24.4%; p = .046), diabetes mellitus type II (11.7% vs. 21.8%; p = .019), hyperlipidemia (38.6% vs. 52.6%; p = .024), vitamin D deficiency (50% vs. 65.4%; p = .014), depression (15.6% vs. 28.9%; p = .018), and sleep problems (7.5% vs. 29.5%; p < .001). Conclusions Our study further emphasizes that dermatologists should screen patients with LPP for autoimmune disorders that are associated with LPP and complete a full metabolic workup to avoid missing other abnormalities. The importance of atopy, autoimmune disorders, endocrine disorders, nutritional deficiencies, psychological problems, and skin cancers in patients with scarring alopecia should be better understood.
... Inspired by Dr Yao's analysis, we performed another metaregression analysis with a different approach that included more studies. In this analysis, 10 studies were included: Mahamid et al, 4 in which patients were classified into extensive and patchy AA groups; Bakry et al, 5 in which patients were grouped into mild, moderate, and severe AA; and the rest of the studies from our original report 3,[6][7][8][9][10][11][12] in which the authors evaluated the severity of their patients using their SALT scores. We redefined a new group called severe AA, which included patients with extensive AA, severe AA (as defined in Bakry et al), 5 and a SALT score $3. ...
... This study showed that mean vitamin D levels were lower in patients of AA as compared to healthy controls; this difference was statistically significant (p-value <0.05). More severe deficiency of vitamin D was seen in more severe AA. [8][9][10] The seasonal variation in vitamin D levels is well established. 8 All the patients and controls were taken from same timeframe, i.e. from October to March. ...
Article
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Objective: To compare the mean Vitamin D level in patients with alopecia areata (AA) with age and gender controlled matched healthy controls. Study design: Case-control study. Place and duration of study: Dermatology OPD, JPMC, from October 2014 to March 2015. Methodology: All the patients diagnosed of alopecia areata by a trained dermatologist were selected. Controls were age and gender matched healthy volunteers. Venous blood was drawn and sent to hospital laboratory for 25 (OH) vitamin D by enzyme immunoassay method on chemical analyser. Data was recorded on SPSS version 16. Mann-Whitney test was applied to compare vitamin D levels of cases and controls. P-value <0.05 was taken as significant. Results: There are 30 cases of AA, and 30 age and gender matched controls. The mean age of our study group was 23.77 ±8.86 ng/dL in patients and 24.03 ±8.62 ng/dL in the control group. Fifteen (50%) patients presented between 3-12 months of onset of AA. Median (IQR) vitamin D level of cases was 13.5 (18.6) ng/dL and healthy controls was 22.5 (16.25) (p=0.001). Conclusion: Serum Vitamin D levels were significantly lower in patients with alopecia areata compared to healthy controls.
... Studies performed initially by Aksu Cerman et al., 11 Mahamid et al., 12 Yilmaz et al., 13 Similarly we found that serum Vit.D level of AA patients was significantly lower than controls, showing that Vit.D deficiency could be related to the disease pathogenesis or disease course. One hypothesis may be that people deficient in Vit.D are more prone to develop autoimmunity thus secondarily predisposed to develop AA and are psychologically distressed, and avoid exposure in public and in open air, which may further lead to decreased sun exposure and reduced Vit.D synthesis. ...
Article
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Background: Vitamin D (Vit.D) deficiency has been reported in alopecia areata (AA). Downregulation of Vitamin D receptor (VDR) on hair follicles is associated with reduced hair growth. Objective: To correlate serum Vit.D levels with severity, pattern, and duration of AA, and density of VDR expression over hair follicles in AA patients. Methods: Prospective study including 30 AA patients and 30 healthy controls. Clinical details and serum Vit.D measurement and scalp biopsy for histopathology and VDR expression was performed in patients and controls at baseline and after 6 months of treatment of AA. Results: Mean age of patients and controls was 28.9 ± 9.96 and 31.17 ± 9.43 years, respectively. Mean SALT score in patients was 35.8 ± 27.5 with a median disease duration of 48 weeks. Mean serum Vit.D levels was 7.65 ± 4.50 ng/ml and 15.8 ± 11.47 ng/ml in patients and controls, respectively. Twenty-nine (96.7%) patients were Vit.D deficient (<20 ng/ml), compared to 22 (73.3%) controls (P = 0.001). Serum Vit.D levels inversely correlated with severity of the disease (r = -256), P = 0.17, and duration of disease but did not correlate with pattern of AA and VDR expression in tissue samples. VDR expression was reduced in all patients and was normal in controls. Inverse correlation of VDR was noted with presence of inflammation on histology (P = 0.02). VDR upregulation post treatment was seen only in 13% of patients and demonstrated no correlation with response to treatment. Conclusion: Vit.D deficiency in AA correlates inversely with disease severity and duration. VDR expression is reduced in AA and inversely correlate with inflammation histologically but does not correlates with serum Vit.D levels, severity, pattern, or duration of illness.
... The mean value of vitamin D among the cases came out to be significantly lower than the controls (P value =0.018). This was similar to a study on AA where the patients with AA had significantly lower values of vitamin D than controls (P value > 0.001) (35,36) . In our study, the mean value of vitamin D among the females was significantly lower for the cases as comparison to the controls (P value =0.018) which is in agreement with another study, in which the vitamin D levels in females with CTE came out to be significantly lower among cases as compared to the controls (P > 0.001) (37) . ...
Article
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Back ground : Diffuse hair loss is a very common complaint usually occurs without inflammation or scarring .The loss affects hairs throughout the scalp in a more or less uniform pattern. That is characterized by the ingress of a large number of hairs prematurely into telogen phase resulting in diffuse hair shedding at one time often with an acute onset so named acute telogen effluvium .A chronic form with a more insidious onset and a longer duration also exists called chronic telogen effluvium which primarily affects women between the ages of 30 and 60 years and is a diagnosis of exclusion and can cause a great psychological impact on the life of the affected person. Objective: Measurement the level of serum ferritin and the level of serum vitamin D In adult females with chronic telogen effluvium in order to validate their role in the process of hair loss. Patients& Methods : This cross-sectional study was conducted at the outpatient Department of Dermatology and Venereology in Al-kindy Teaching Hospital between March and November 2017.Sixty adult Female at age (12 to 52 years) with hair loss in the form of CTE otherwise they are healthy and sixty adult healthy with same age-matched female with no hair loss were included in the study. Diagnosis was based upon clinical examination as well as hair pull test. Serum ferritin and vitamin D levels and Hemoglobin were determined for each participant. Results : Hair loss can have an emotional impact on patients leading to anxiety and frustration. Therefore, diagnosing the underlying etiology is necessary for the better management of the disorder The results of this study suggest that the reduced hair density seen in CTE may possibly be associated with low serum levels of ferritin and vitamin D. It is recommended that hemoglobin level measurement should not be solely relied on in the assessment of hair loss, as it was not significantly different between patients with CTE and controls as seen in our study. Conclusions: The female cases in this study had significantly low levels of serum ferritin and vitamin D than controls .Our study highlights the importance of serum ferritin and vitamin D evaluation in case of diffuse hair fall.
... [20] In yet another study by Mahamid et al., a significant correlation was found between Vitamin D deficiency and AA. [21] However, our study has certain limitations. The number of AA cases was less, and our study did not include positive controls as was done in few previous studies. ...
Article
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Background Alopecia areata (AA) is an immune-mediated disease in which autoantigens play an important part in activating T-lymphocytes. Vitamin D has been associated with various autoimmune diseases, and Vitamin D receptors are strongly expressed in hair follicles and their expression in keratinocytes is necessary for the maintenance of the normal hair cycle. Aim The aim of this study was to find the association between Vitamin D level and AA. Materials and Methods This was a hospital-based cross-sectional study in which 50 patients with clinically and trichoscopically diagnosed AA cases, and 35 healthy age- and sex-matched controls were studied in summer months. Blood samples were taken from both cases as well as controls and samples were immediately processed by centrifugation (4000 rpm) at room temperature. Plasma 25-hydroxyvitamin D (25(OH)D) was analyzed by chemiluminescence method. A deficiency in Vitamin D was defined as serum 25(OH)D concentrations <30 ng/ml. Results The mean body mass index in cases was 20.96 ± 1.91, whereas in controls, it was 21.37 ± 1.70 (P = 0.31). The mean serum 25(OH)D levels of AA patients was 16.6 ± 5.9 ng/ml, whereas in control group, the mean level was 40.5 ± 5.7, the difference being statistically significant (P < 0.001). A significant negative correlation was found between severity of alopecia tool score and Vitamin D level (P < 0.001; r = −0.730) and also between the number of patches and Vitamin D level (P < 0.001, r = −0.670). Conclusion In our study, we found that the levels of 25(OH)D were low in AA patients when compared to healthy controls. Furthermore, there was a significant negative correlation between the levels of serum Vitamin D and severity of AA. Thus, the study suggests the role of Vitamin D in pathogenesis of AA and hence a possible role of Vitamin D supplementation in treatment of same. Limitations Our study was limited by the lesser number of patients and lack of therapeutic trial of Vitamin D for these patients.
... This difference was observed to be statistically significant. Various other authors (Mahamid et al., Aksu Cerman et al. and Attawa et al. [19][20][21] had conducted studies with similar objectives. Findings of Nassiri et al. 22 are a bit different from ours. ...
... Our study showed a significant correlation between vitamin D [5] deficiency and the severity of androgenetic alopecia . This suggests that vitamin D may play a role in the premature onset [4] of androgenetic alopecia . However, further studies on a larger population and the effect of vitamin D supplementation on the progression of androgenetic alopecia are required to validate the above findings. ...
Article
Androgenetic alopecia is common dermatological problem among the young to middle aged population.Androgenetic alopecia is labeled as 'premature' or 'Early' androgenetic alopecia when the onset of disease is before 30 years of age. There is very little data available regarding the role of vitamin D in the Premature androgenetic alopecia. Vitamin D deficiency is diagnosed when the levels of vitamin D in the serum is <30 ng/ml. This study focuses on establishing association between serum vitamin D levels and severity of premature androgenetic alopecia. Conclusion:Vitamin D plays a major role in premature onset of androgenetic alopecia.
... Anders lassen sich den Artikeln von Bhat et al.[14], Cerman et al.[4], Fattah et al.[1], Gade et al.[33] und Unal et al.[85] die Ergebnisse in Form eines Korrelationskoeffizienten und eines p-Wertes entnehmen. Des Weiteren gibt Mahamid et al.[56] seine Untersuchungsergebnisse als Odds Ratio mit p-Wert an. In den Studien von Darwish et al.[23], El-Mongy et al.[29], Erpolat et al.[30] und Nassiri et al.[68] ist hingegen nur der p-Wert aufgeführt. ...
... 3 Vitamin D is an important secosteroid hormone which is vital Although many studies have been done to evaluate the role of vitamin D in different hair disorders, they have failed to establish a clear association between the two. Some studies have shown an association between low serum levels of vitamin D in women with chronic telogen effluvium, female pattern hair loss, and alopecia areata, 3,4 while other studies showed no correlation between the severity of male androgenetic alopecia with serum vitamin D3 levels. 5 In view of the conflicting results seen above, we undertook this study to evaluate the levels of vitamin D in patients with androgenetic alopecia, to determine its possible role in the etiopathogenesis of male androgenetic alopecia. ...
Article
Background Vitamin D deficiency had been associated with various hair loss disorders, such as telogen effluvium, alopecia areata, and female pattern hair loss. However, previous studies have not found a correlation between serum vitamin D levels and the severity of androgenetic alopecia. Methods A case‐control study was conducted for a period of one year in a public tertiary care hospital. Fifty males clinically diagnosed with androgenetic alopecia and 50 age‐matched healthy controls were recruited. Serum vitamin D levels in both cases and controls were measured by radioimmunoassay technique, and the results were compared. Results A total of 50 cases and 50 controls were recruited and analyzed. The mean age of the cases was 23 years and that of controls was 24.2 years. The mean levels of serum vitamin D significantly decreased in cases, compared to controls (20.10 vs. 29.34 ng/mL; P ≤ 0.001). Eighty‐six percent of the cases had deficiency of vitamin D (<30 nmol/L), while 14% had insufficient vitamin D levels (31–50 nmol/L). There was a positive correlation between vitamin D deficiency and severity of androgenetic alopecia (AGA), which was statistically significant (P ≤ 0.5). However, there was no correlation between the duration of sun exposure and serum vitamin D levels (2.36 ± 1.2 in cases and 3.23 ± 1.6 in controls, P value = 0.98). Conclusion Our study showed a significant correlation between vitamin D deficiency and the severity of androgenetic alopecia. This suggests that vitamin D may play a role in the premature onset of androgenetic alopecia. However, further studies on a larger population and the effect of vitamin D supplementation on the progression of androgenetic alopecia are required to validate the above findings.
... [197,198] The interested reader can find more information elsewhere. [199][200][201][202][203][204][205][206] ...
Article
The skin as a neuroendocrine organ and the role of neuroendocrine signaling in the development of disorders affecting the skin and its appendages has received increasing attention in the last years. Different neuroendocrine systems have been described in the barrier organ skin, including the thyroid system, the hypothalamic‐pituitary‐adrenal axis, the opioid, the endocannabinoid, the cholinergic, the secosteroidogenic and the serotonergic systems. All of these systems have been implicated in the development of skin diseases, which often have an inflammatory origin. These discoveries have led to an increase in the development of new drugs targeting components of neuroendocrine signaling pathways. Additionally, attempts have been made to repurpose already approved drugs targeting neuroendocrine signaling pathways in other organs for the treatment of skin diseases. Recently published results from preclinical and clinical studies look promising and may offer improved therapies to patients suffering from skin diseases in the near future. In this review, from a pharmaceutical point of view, we focus on recent progress in synthetic drug development of compounds targeting neuroendocrine signaling in the skin and its appendages to treat skin diseases such as atopic dermatitis, psoriasis, acne, alopecia areata and hyperhidrosis.
... The flowchart of the study selection process is shown in Fig. 1 [20][21][22][23][24][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. The sample size of the included studies ranged from 43 to 756, and publication date from 2012 to 2019. ...
Article
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IntroductionTo investigate the associations of alopecia areata (AA) with serum vitamin D and calcium levels.MethodsA systematic review of all relevant articles published up to February 2020 in PubMed, Embase, and Cochrane Library databases was conducted. Primary endpoints were serum 25-hydroxyvitamin D [25(OH)D] levels and vitamin D deficiency, and the secondary endpoint was serum calcium level. Odds ratio (OR) and standardized mean difference (SMD) with 95% CI across studies were analyzed.ResultsData on 1585 patients with AA and 1114 controls from 16 case–control studies and three cross-sectional studies were included in this meta-analysis. A pooled meta-analysis was conducted using the random-effects model because of inter-study heterogeneity (vitamin D level, I2 = 87.90%; vitamin D deficiency, I2 = 81.10%; serum calcium level, I2 = 83.80%). A combined analysis revealed that patients with AA had significantly lower mean serum 25(OH)D level compared with control (WMD − 9.08, 95% CI − 11.65, − 6.50, p < 0.001), and were more likely to have vitamin D deficiency (OR 4.14, 95% CI 2.34, 7.35, p < 0.001). However, the pooled analysis revealed that patients with AA did not have significantly lower serum calcium levels compared with control (WMD − 0.17, 95% CI − 0.40, 0.06, p = 0.143). Subgroup analysis suggested that matched control, mean age, and country might contribute to the heterogeneity of serum vitamin D level, while study design, matched control, and country might contribute to the heterogeneity of vitamin D deficiency.Conclusion Deficiency of serum 25(OH)D level, rather than calcium level, was present in patients with AA. Screening for vitamin D deficiency and vitamin D supplementation may be beneficial in the treatment of patients with AA.
... Studies performed initially by Aksu Cerman et al., 11 Mahamid et al., 12 Yilmaz et al., 13 Uniquely we observed a positive correlation between VDR expression and absence of inflammation, a finding not highlighted in literature to the best of our knowledge. VDR positivity correlated inversely with severity of inflammation seen on histology. ...
Article
Introduction There is scarcity of prospective studies assessing the correlation between vitamin D deficiency and atopic dermatitis (AD). Materials and methods We conducted a prospective study where in serum 25-hydroxy-vitamin D levels were measured in 35 AD patients and 35 age and sex-matched controls. AD patients deficient in vitamin D were supplemented with 1000 IU of vitamin D per day for three months. Serum vitamin D levels and SCORAD were again measured at the end of three months in all AD patients. Results The baseline vitamin D levels in patients and controls did not have any statistically significant difference (p = .97). There was a statistically significant (p = .02) inverse relationship between the AD severity and serum vitamin D levels at baseline (r = −0.52). Maximum reduction in SCORAD (41.4 ± 12.7) after 3 months of vitamin D supplementation was seen in severe AD and the minimum (2.4 ± 13.2) in mild AD (p = .0003). Conclusions We found no difference in the mean serum vitamin D levels between AD patients and controls. An inverse correlation was seen between serum vitamin D levels at baseline and severity of AD. Beneficial effect of vitamin D supplementation was observed maximally in severe AD as observed by a reduction in SCORAD.
Chapter
People commonly inquire about vitamin and mineral supplementation and diet as a means to prevent or manage dermatological diseases and, in particular, hair loss. Answering these queries is frequently challenging, given the enormous and conflicting evidence that exists on this subject. There are several reasons to suspect a role for micronutrients in non-scarring alopecia. Micronutrients are major elements in the normal hair follicle cycle, playing a role in cellular turnover. The role of nutrition and diet in treating hair loss represents a dynamic and growing area of inquiry. This chapter summarizes the role of vitamins and minerals in non-scarring alopecia. Micronutrients such as vitamins and minerals play an important, but not entirely clear role in normal hair follicle development and immune cell function. Deficiency of such micronutrients may represent a modifiable risk factor associated with development, prevention, and treatment of alopecia.
Article
Background Although the etiopathogenesis of alopecia areata (AA) is still unclear, inflammation, oxidative stress, and subsequent DNA damage might be considered role players in disease development. Aim We aimed at exploring the potential link between oxidative DNA damage and inflammation in AA patients through measuring 8‐hydroxy deoxyguanosine (8‐OHdG), high mobility group box 1 protein (HMGB1), and one of the inflammatory mediators, C‐reactive protein (CRP). Methods A total of 79 subjects (49 AA patients in addition to 30 apparently healthy control subjects) were tested for serum levels of 8‐OHdG, HMBG1, and CRP. Results Compared with the control group, serum 8‐OHdG, HMBG1, and CRP levels were significantly elevated in the studied patients group (0.031, <0.001, and <0.001, respectively). Moreover, logistic regression analysis revealed that disease course, serum levels of 8‐OHdG, and HMBG1 were considered independent predictors for AA severity in both uni‐ and multivariable analyses. Conclusion Our results suggest a possible role of oxidative stress together with proinflammatory biomarkers in development of AA and their benefit in predicting a severe form of the disease.
Article
delete Edited by K O'Connor, L J Golderg Healthy hair results from a combination of good generalized health and mindful health care practices. Many nutritional deficiencies lead to poor hair health and include changes to hair structure, texture, and viability. Although the mechanisms by which individual nutrients contribute to hair growth and maintenance have yet to be fully resolved, there are a variety of risk factors that predispose an individual to a nutritional deficiency; age, malnutrition, malabsorption, and medication use are among the most common. A thorough history should be taken in a patient with a hair disturbance to identify risk factors for a nutritional deficiency, which will then guide directed laboratory testing and treatment.
Article
Objectives To determine the relation between serum vitamin D levels and alopecia areata. Materials and Methods This cross-sectional study included patients with AA who were above 12 years of age and age- and sex-matched controls who attended the dermatology department of a tertiary care center during a period of 1 year. Serum Vitamin D level was determined in each participant. Serum Vitamin D levels documented in both groups were compared. Results Thirty patients and 30 age- and sex-matched controls constituted the study population. The male-to-female ratio was 1.7:1. Most of the patients (9/30, 30%) were in the age group of 31–40 years. We observed patchy AA in 17 patients (56.7%). Nail involvement was seen in 9 patients (30%). Serum vitamin D levels were insufficient/deficient in 16 patients (53.3%), while in the age- and sex-matched comparison group, vitamin D was insufficient / deficient in 7 cases (23.3%). The difference was statistically significant ( P = 0.03). No significant relation was noted either between serum vitamin D levels and number of alopecia lesions or between serum vitamin D levels and the clinical pattern of AA. No significant difference was noted in the vitamin D levels between patients who had involvement of only scalp and those who showed involvement of other body sites. Limitations Small sample size was the major limitation of the study. Conclusion Low serum vitamin D levels were more frequent in patients with AA in comparison to healthy controls.
Article
Background Alopecia areata (AA) is a hair follicle‐specific autoimmune disorder. Vitamin D deficiency has been associated with various autoimmune disorders for its immunomodulatory effects. However, in previous studies, there had been inconsistent association found between AA and vitamin D deficiency. Objective To demonstrate the differences of the mean serum 25‐hydroxyvitamin D level and prevalence of vitamin D deficiency between AA subjects and non‐AA controls. Methods A systematic review and meta‐analysis of observational studies on AA and serum vitamin D levels and/or prevalence of vitamin D deficiency was performed searching MEDLINE, Cochrane, Web of Science, and Google Scholar databases. Results In all, 14 studies including a total of 1,255 AA subjects and 784 non‐AA control were analyzed. The mean serum 25‐hydroxyvitamin D level was significantly lower in AA subjects (‐8.52 ng/dL; 95% confidential interval; ‐5.50 to ‐11.53). The subjects with AA had higher odds of vitamin D deficiency of vitamin D deficiency (odds of 3.55; 2.03 to 6.20, mean prevalence of 75.5%; 60.8 to 86.0%). However, it was difficult to find clear correlation between serum 25‐hydroxyvtamin D level and extent of hair loss in AA. Conclusion The AA subjects had lower serum 25‐hydroxyvitamin D level and vitamin D deficiency was highly prevalent compared to non‐AA controls. Hence, Vitamin D deficiency should be assessed in AA patients. Furthermore, nutritional supplementation of vitamin D or topical vitamin D analogues can be considered for AA patients with vitamin D deficiency. The limitation of this study is the highly heterogeneity of the included studies. This article is protected by copyright. All rights reserved.
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The development of androgenetic alopecia is associated with a risk of developing cardiovascular diseases, but the association of alopecia areata with cardiovascular diseases in humans is largely unexplored. We measured the plasma level of two common cardiovascular disease markers, cardiac troponin I and C-reactive protein, in alopecia areata and androgenetic alopecia affected subjects. Also, we investigated the possible presence of pro-apoptotic factors in the plasma of hair loss subjects. The mean plasma cardiac troponin I level was highest in alopecia areata subjects, moderately higher in androgenetic alopecia subjects, and lowest in subjects without hair loss (p < 0.05). Alopecia areata subjects not receiving treatments had highest levels of cTnI (p < 0.05). Alopecia areata plasma samples with high cardiac troponin I levels also induced significantly higher rates of cardiomyocyte apoptosis in cell culture assays. The results suggest the potential for increased heart remodelling. Close monitoring of cardiovascular health in alopecia areata subjects, as well as subsets of androgenetic alopecia patients, may be appropriate.
Article
Abstract Background: Although the etiopathogenesis of alopecia areata (AA) is still unclear, inflammation, oxidative stress, and subsequent DNA damage might be considered role players in disease development. Aim: We aimed at exploring the potential link between oxidative DNA damage and inflammation in AA patients through measuring 8-hydroxy deoxyguanosine (8-OHdG), high mobility group box 1 protein (HMGB1), and one of the inflammatory mediators, C-reactive protein (CRP). Methods: A total of 79 subjects (49 AA patients in addition to 30 apparently healthy control subjects) were tested for serum levels of 8-OHdG, HMBG1, and CRP. Results: Compared with the control group, serum 8-OHdG, HMBG1, and CRP levels were significantly elevated in the studied patients group (0.031, <0.001, and <0.001, respectively). Moreover, logistic regression analysis revealed that disease course, serum levels of 8-OHdG, and HMBG1 were considered independent predictors for AA severity in both uni- and multivariable analyses. Conclusion: Our results suggest a possible role of oxidative stress together with proinflammatory biomarkers in development of AA and their benefit in predicting a severe form of the disease.
Chapter
The quantity and quality of hair are closely related to the nutritional state of an individual. In instances of protein and calorie malnutrition, deficiency of essential amino acids, of trace elements, and of vitamins, hair growth and pigmentation may be perturbed. The effects of nutrition on hair growth and pigmentation have been recognized from observations in rare inborn errors of metabolism of copper (Menkes kinky hair syndrome), zinc (acrodermatitis enteropathica), biotin (biotinidase and holocarboxylase synthetase deficiency), and amino acids (homocystinuria, Hartnup disease, phenylketonuria, and methionine malabsorption syndrome), in specific acquired deficiency disorders, and from the respective supplementation studies. All vitamins were identified by 1948, ushering in a half century of discovery focused on single-nutrient-deficiency diseases. The first half of the twentieth century witnessed the identification and synthesis of many of the known essential vitamins and minerals and their use to prevent and treat nutritional deficiency-related diseases, specifically protein-calorie malnutrition, deficiencies of biotin, vitamin C, vitamin B12, niacin, essential fatty acids, iron, zinc, copper, selenium, and vitamin D. Accelerating economic development and modernization of agricultural, food processing, and food formulation techniques continued to reduce single-nutrient-deficiency diseases globally. In response, nutrition science shifted to the research on the role of nutrition in more complex conditions, such as gluten sensitivity, obesity, bariatric surgery, anorexia and bulimia, alcoholism, aging, and the oncologic patient. Additional complexity may arise in nutritional recommendations for general well-being versus treatment of specific conditions. Recognition of complexity is a key lesson of the past. Initial observations lead to reasonable, simplified theories that achieve certain practical benefits, which are then inevitably advanced by new knowledge and recognition of ever-increasing complexity.
Article
Background: Alopecia areata is a common autoimmune disorder which is characterized by non-scarring hair loss. Vitamin D plays an important role in immune regulation, cell growth, differentiation, and maintenance of hair cycle. Aims and objectives: (1) To evaluate serum vitamin D levels in alopecia areata. (2) To compare serum vitamin D levels in new versus old cases and with respect to severity of alopecia areata. Materials and methods: A retrospective case-control study with 100 cases of alopecia areata and 100 age- and sex-matched healthy controls was conducted from December 2014 to November 2015. All subjects underwent complete clinical evaluation and serum vitamin D levels. Results: The mean serum vitamin D level was significantly lower in patients with alopecia areata (18.90 ± 8.32 ng/mL) (64%) as compared to healthy controls (28.21 ± 18.32 ng/mL) (38%) (P < 0.001). The mean serum vitamin D levels was significantly lower in old cases (15.11 ± 4.75 ng/mL) as compared to new cases (20.85 ± 9.09 ng/mL) (P < 0.001). The proportion of subects with vitamin D deficiency was significantly higher among old cases (84.3%) as compared to new cases (53.1%) (P < 0.05). There was a significant inverse correlation between Severity of Alopecia Tool scores and serum vitamin D levels (r = -0.298, P < 0.05). Conclusion: Decreased vitamin D levels were observed in patients with alopecia areata and significant inverse correlation exists between vitamin D levels and duration/severity of the disease. These findings may suggest a causal role of vitamin D deficiency in the pathogenesis and therapeutic role of vitamin D supplementation in the management of alopecia areata.
Article
Background: Alopecia areata (AA) may be associated with various systemic diseases according to several studies. Objective: To identify prevalent and incident diseases in AA patients and quantify their prevalence and odds and hazard ratio compared with those in non-AA controls. Methods: A systematic review of the studies published before February 28, 2018 was performed using MEDLINE, Embase, Web of Science and Cochrane Library databases. Observational studies on prevalent or incident diseases in AA patients were included, whereas studies limited to pediatrics or providing only laboratory results or continuous data were excluded. Inverse variance method with random-effects model was used for meta-analyses. Results: Eighty-seven studies were analyzed. Atopic diseases, metabolic syndrome, Helicobacter pylori infection, lupus erythematosus, iron deficiency anemia, thyroid diseases, psychiatric diseases, vitamin D deficiency, and audiologic and ophthalmic abnormalities were more prevalent in AA patients. AA patients had a higher risk of developing autoimmune diseases. Limitations: Some diseases were investigated by an insufficient number of studies to be meta-analyzed. Meta-analysis on incident diseases was not performed owing to the limited availability on cohort studies. Conclusion: AA is associated with various systemic and psychiatric diseases. Physicians are encouraged to evaluate and manage potential comorbid conditions to achieve better outcomes.
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Background: Alopecia areata is an autoimmune disorder of anagen hair follicle leading to distressing and relapsing non-scarring hair loss. Vitamin D is an immunomodulator and plays a role in regulating normal hair cycle. Recent evidence suggests inconsistent association between vitamin D deficiency and alopecia areata.Methods: This case control study included 70 newly diagnosed cases of alopecia areata and 70 healthy controls. Competitive chemiluminescence immunoassay was used to determine and compare the serum vitamin D (25‑hydroxyvitamin D) levels between these groups. Also, the serum vitamin D levels correlation with severity of the disease was studied. ANOVA test and student t test were used for the statistical analysis.Results: Serum Vitamin D levels were significantly decreased in alopecia areata patients than in controls (p<0.05). There was no stastically significant relationship between serum 25-OH Vitamin D levels and severity of the disease (p=0.06).Conclusions: Prevalence of serum 25 (OH) deficiency was significantly higher in alopecia areata group. However no significant relation was found with disease severity.
Chapter
Alopecia areata is a complex immune-mediated disease that targets anagen hair follicles. Therapeutic strategies must be directed as either immunosuppressive or immunomodulating and may consist of monotherapy or combination therapy and should be different depending on patient’s age, extent, and chronicity of the disease. The physician must discuss mild and aggressive options, as well as the possibility of no treatment, camouflage options, and social/psychological support. Topical, intralesional, and systemic steroids, as well as corticosteroid-sparing agents and disease-modifying antirheumatic drugs are useful as local or systemic immunosuppressors. Topical immunotherapy, anthralin, and phototherapy have proved useful as immunomodulators. Target therapy with JAK inhibitors is useful in alopecia areata totalis or universalis. Treatment in special areas such as eyelashes, eyebrows, or beard benefit from treatment with steroids, minoxidil, prostaglandin F2a analogs, and topical tofacitinib. Vitamin D3, ezetimibe/simvastatin, platelet-rich plasma, antihistamines, and aromatherapy may be used as adjuvant therapies. We discuss a practical but evidence-based approach for treatment in different cases of alopecia areata with detailed information about doses, administration, and possible side effects.
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Background: Alopecia areata is the commonest cause of non-scarring alopecia. Few previous studies have found correlation between AA and vitamin D deficiency, suggesting that vitamin D deficiency can be a risk factor for Alopecia areata. To compare serum vitamin D level between Alopecia areata patients and healthy controls; and to assess the relation between serum vitamin D levels and AA disease severity. Methods: This case control study included 30 newly diagnosed Alopecia areata patients. Thorough history was taken, detail examination was done and relevant findings were recorded in the standardized pro-forma. Their serum vitamin D (25-hydroxyvitamin D) levels were determined by competitive chemiluminescence methods; and were compared with that of age and sex matched healthy controls. Chi square test and Spearman’s rho correlation test were used for the inferential statistics using SPSS version 11.5. Results: There were 30 AA patients with mean age 28.37+10.07 years. Mean Severity of Alopecia Tool score was 3.56+3.50. Prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency was significantly higher in AA group (83.3%) compared to the control group (53.3%) (P=0.01). Similarly, serum 25(OH)D level was reduced more in Alopecia areata group (12.84, IQR=8.87-20.47) than the control group (29.5, IQR=19.85-41.27) (P=0.06). There was inverse co-relation between serum 25(OH)D level and SALT score. Conclusions: Prevalence of serum 25(OH)D deficiency was significantly higher in Alopecia areata group compared to the control, with inverse co-relation between its level and Alopecia areata disease severity. Keywords: Alopecia areata; Nepal; SALT Score; Vitamin D.
Article
Background It has been suggested that low vitamin D levels may affect the development of hair loss. Aims Our aim was to evaluate the serum 25‐hydroxy vitamin D [25(OH)D] status in Chinese patients with alopecia areata (AA), female pattern hair loss (FPHL), and male androgenetic alopecia (MAGA) compared with healthy individuals. Methods We performed a case‐control study including 443 AA patients, 657 FPHL patients, 777 MAGA patients, and 2070 normal controls (1064 male and 1006 female healthy individuals) from 2015 to 2017 to analyze the correlation of serum 25(OH)D levels and hair loss in a Chinese population. Results Serum 25(OH)D levels stratified by age, sex, and season were compared between patients and healthy individuals. AA patients' serum 25(OH)D levels were statistically lower than that of controls (P < .0001, α = .05). Serum 25(OH)D levels of FPHL patients (P < .0001, α = .05) and MAGA patients (P = .0005, α = .05) were also significantly lower than counterpart control subjects. Conclusion Our findings suggest an association between serum 25(OH)D levels and alopecia areata, female pattern hair loss, or male androgenetic alopecia in a Chinese population.
Article
Resumen El papel de la vitamina D en enfermedades cutáneas ha cobrado interés en los últimos años. La relación entre esta vitamina y algunas dermatosis ha supuesto la publicación de múltiples trabajos al respecto. Como dermatólogos, conocer sus principales fuentes, síntesis, niveles plasmáticos y algunos de los factores modificadores son varios de los aspectos a recordar. Asimismo, es preciso resaltar los últimos descubrimientos sobre el papel de la vitamina D en las diferentes enfermedades dermatológicas, como el lupus eritematoso, la ictiosis, la dermatitis atópica, la hidrosadenitis supurativa, el acné, la alopecia areata y androgenética, el melanoma y el cáncer cutáneo no melanoma, así como la relevancia como terapia adyuvante en pacientes en tratamiento crónico con corticoides. Acercamos al lector la información más relevante y reciente de la relación entre la vitamina D y las enfermedades de la piel, así como la importancia de conocer los niveles de esta vitamina.
Article
Background Alopecia areata (AA) is an autoimmune disease which is characterized by hair loss and affects any hair-bearing area. Low levels of Vitamin D have been implicated in a variety of autoimmune diseases. This study was conducted to assess the levels of Vitamin D in patients with AA and its correlation with severity, pattern, and extent of the disease. Materials and Methods This hospital-based study included 135 cases with AA and 135 age- and sex-matched controls. AA cases were grouped according to the severity, pattern, and extent of the disease. The levels of Vitamin D were assessed and compared between cases and controls and among different groups of cases. The data were analyzed, and the correlation was derived. Results The more number of patients from the case group had deficient and insufficient levels of Vitamin D as compared to controls, the difference being statistically significant (P = 0.01). A highly significant difference was found in mean Vitamin D levels between cases and controls (P = 0.0004). A negative correlation was found between Vitamin D levels and severity of AA as accessed by SALT score. A negative correlation was also found between Vitamin D levels with pattern and extent of the disease. Conclusion Vitamin D deficiency may be one of the factors having a role either in etiopathogenesis or exacerbation of AA. Supplementation of Vitamin D as a treatment modality may improve the clinical outcome of AA.
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In recent years, the growing interest in the role played by vitamin D in skin disease has given rise to the publication of many studies of the relationship between this vitamin and certain skin conditions. As dermatologists, we need to understand, among other aspects, how vitamin D is synthesized and the main sources in humans, as well as plasma levels and the factors that can modify them. Of particular interest are the latest discoveries about the role of vitamin D in skin diseases such as lupus erythematosus, ichthyosis, atopic dermatitis, hidradenitis suppurativa, acne, alopecia areata, androgenetic alopecia, melanoma, and nonmelanoma skin cancer. Also of interest is the importance of vitamin D as adjuvant therapy in patients on long-term treatment with corticosteroids. In this review, we provide an overview of the most important and most recent information regarding the relationship between vitamin D and skin disease and discuss the importance of assessing individual vitamin D status and correcting deficiencies.
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Background: Alopecia areata is the commonest cause of non-scarring alopecia. Few previous studies have found correlation between AA and vitamin D deficiency, suggesting that vitamin D deficiency can be a risk factor for Alopecia areata. To compare serum vitamin D level between Alopecia areata patients and healthy controls; and to assess the relation between serum vitamin D levels and AA disease severity. Methods: This case control study included 30 newly diagnosed Alopecia areata patients. Thorough history was taken, detail examination was done and relevant findings were recorded in the standardized pro-forma. Their serum vitamin D (25-hydroxyvitamin D) levels were determined by competitive chemiluminescence methods; and were compared with that of age and sex matched healthy controls. Chi square test and Spearman's rho correlation test were used for the inferential statistics using SPSS version 11.5. Results: There were 30 AA patients with mean age 28.37+10.07 years. Mean Severity of Alopecia Tool score was 3.56+3.50. Prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency was significantly higher in AA group (83.3%) compared to the control group (53.3%) (P=0.01). Similarly, serum 25(OH)D level was reduced more in Alopecia areata group (12.84, IQR=8.87-20.47) than the control group (29.5, IQR=19.85-41.27) (P=0.06). There was inverse co-relation between serum 25(OH)D level and SALT score. Conclusions: Prevalence of serum 25(OH)D deficiency was significantly higher in Alopecia areata group compared to the control, with inverse co-relation between its level and Alopecia areata disease severity.
Article
The article presents an analysis of modern domestic and foreign publications on the research of the etiology and pathogenesis of the alopecia areata in children. The article brings up the information on the incidence of this type of alopecia in the population, its relationship with heredity, immune and environmental factors. According to generalized literary data, the authors focus on the importance of the role of violations in the lipid peroxidation system and antioxidant protection in the development of the nest alopecia. According to the authors, these processes lead to violations of the function of organs and systems which is reflected in the state of local blood flow and the functional parameters of the skin. The article indicates the literature data on the role of microcirculation violations in the development of the alopecia areata, as well as the pathophysiological mechanisms of its development in children with vitamin D deficiencies The results of a study on the mechanisms for the development of the alopecia areata in children indicate that when conducting children with this pathology, it is necessary to envisage individual approach taking into account the local blood flow, functional parameters of the skin, concomitant pathology, level of vitamin D in the blood and violations in the antioxidant protection system.
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Vitamin D status is not evaluated routinely in cancer patients with bone metastasis who are treated with bisphosphonates. To assess the effect of vitamin D status on risk of hypocalcemia and quality of life in these patients. We performed laboratory tests for routine serum biochemistry, 25(OH)D, plasma parathyroid hormone (PTH) and bone turnover markers (CTX, P1NP) in 54 patients aged 57.5 +/- 13 years treated with intravenous bisphosphonates. Most of the patients (n = 44, 77.8%) did not receive calcium and vitamin D supplementation. Their mean serum 25(OH)D levels (12.83 +/- 6.86 ng/ml) correlated with vitamin D daily intake (P = 0.002). In 53 patients (98.1%) 25(OH) D levels were suboptimal (< 30 ng/ml). Albumin-corrected calcium levels correlated with plasma PTH (P = 0.001). No correlation was observed between daily calcium intake and serum calcium (P = 0.45). Hypocalcemia was observed in one patient. Mean plasma PTH was 88.5 - 65 ng/L. Plasma PTH correlated negatively with 25(OH)D serum levels (P = 0.003) and positively with P1NP (P = 0.004). Albumin-corrected calcium correlated negatively with P1NP (mean 126.9 +/- 191 ng/ml) but not with CTX levels (mean 0.265 +/- 0.1 ng/ml) (P < 0.001). There was no correlation among quality of life parameters, yearly sun exposure and 25(OH)D levels (P = 0.99). Vitamin D deficiency is frequent in oncology patients with bone metastasis treated with bisphosphonates and might increase bone damage. Our results indicate a minor risk for the development of severe hypocalcemia in vitamin D-deficient patients receiving bisphosphonate therapy. Although vitamin D deficiency might have some effect on the quality of life in these patients, it was not proven significant.
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Excessive activity of dendritic cells (DCs) is postulated as a central disease mechanism in Systemic Lupus Erythematosus (SLE). Vitamin D is known to reduce responsiveness of healthy donor DCs to the stimulatory effects of Type I IFN. As vitamin D deficiency is reportedly common in SLE, we hypothesized that vitamin D might play a regulatory role in the IFNalpha amplification loop in SLE. Our goals were to investigate the relationship between vitamin D levels and disease activity in SLE patients and to investigate the effects of vitamin D on DC activation and expression of IFNalpha-regulated genes in vitro. In this study, 25-OH vitamin D (25-D) levels were measured in 198 consecutively recruited SLE patients. Respectively, 29.3% and 11.8% of African American and Hispanic SLE patient had 25-D levels <10 ng/ml. The degree of vitamin D deficiency correlated inversely with disease activity; R = -.234, p = .002. In 19 SLE patients stratified by 25-D levels, there were no differences between circulating DC number and phenotype. Monocyte-derived DCs (MDDCs) of SLE patients were normally responsive to the regulatory effects of vitamin D in vitro as evidenced by decreased activation in response to LPS stimulation in the presence of 1,25-D. Additionally, vitamin D conditioning reduced expression of IFNalpha-regulated genes by healthy donor and SLE MDDCs in response to factors in activating SLE plasma. We report on severe 25-D deficiency in a substantial percentage of SLE patients tested and demonstrate an inverse correlation with disease activity. Our results suggest that vitamin D supplementation will contribute to restoring immune homeostasis in SLE patients through its inhibitory effects on DC maturation and activation. We are encouraged to support the importance of adequate vitamin D supplementation and the need for a clinical trial to assess whether vitamin D supplementation affects IFNalpha activity in vivo and, most importantly, improves clinical outcome.
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Unlabelled: Various therapeutic agents have been described for the treatment of alopecia areata (AA), but none are curative or preventive. The aim of AA treatment is to suppress the activity of the disease. The high rate of spontaneous remission and the paucity of randomized, double-blind, placebo-controlled studies make the evidence-based assessment of these therapies difficult. The second part of this two-part series on AA discusses treatment options in detail and suggests treatment plans according to specific disease presentation. It also reviews recently reported experimental treatment options and potential directions for future disease management. Learning objectives: After completing this learning activity, participants should be able to compare the efficacy and safety of various treatment options, formulate a treatment plan tailored to individual patients, and recognize recently described treatments and potential therapeutic approaches.
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The vitamin D endocrine system is involved in a wide variety of biological processes including bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation. Variations in this endocrine system have, thus, been linked to several common diseases, including osteoarthritis (OA), diabetes, cancer, cardiovascular disease, and tuberculosis. Evidence to support this pleiotropic character of vitamin D has included epidemiological studies on circulating vitamin D hormone levels, but also genetic epidemiological studies. Genetic studies provide excellent opportunities to link molecular insights with epidemiological data and have therefore gained much interest. DNA sequence variations, which occur frequently in the population, are referred to as "polymorphisms" and can have modest and subtle but true biological effects. Their abundance in the human genome as well as their high frequencies in the human population have made them targets to explain variation in risk of common diseases. Recent studies have indicated many polymorphisms to exist in the vitamin D receptor (VDR) gene, but the influence of VDR gene polymorphisms on VDR protein function and signaling is largely unknown. So far, three adjacent restriction fragment length polymorphisms for BsmI, ApaI, and TaqI, respectively, at the 3' end of the VDR gene have been the most frequently studied. Because these polymorphisms are probably nonfunctional, linkage disequilibrium with one or more truly functional polymorphisms elsewhere in the VDR gene is assumed to explain the associations observed. Research is therefore focussed on documenting additional polymorphisms across the VDR gene to verify this hypothesis and on trying to understand the functional consequences of the variations. Substantial progress has been made that will deepen our understanding of variability in the vitamin D endocrine system and might find applications in risk assessment of disease and in predicting response-to-treatment.
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The rising number of children and adults with allergic disorders worldwide has prompted interest in strategies to prevent or reduce the risk of allergy. This article discusses the role of early nutritional strategies in the prenatal/ postnatal periods that potentially may modify disease risk. Exclusive breastfeeding may help to prevent allergic disease by decreasing exposure to exogenous antigens, protecting against infections, promoting gastrointestinal mucosal maturation and the development of gut microbiota, and conferring immunomodulatory and anti-inflammatory benefits. However, the results of the studies are inconsistent, showing a protective effect, no effect, or even a predisposing effect. Still, breastfeeding should be promoted for its nutritional, immunological and psychological benefits. For infants with a documented hereditary risk of allergy (i.e., an affected parent and/or sibling) who cannot be breastfed exclusively, dietary products with confirmed reduced allergenicity are recommended. Previously, for complementary feeding, early exposure to solid foods during infancy was associated with the development of allergic diseases, particularly eczema. Currently, the guidelines downplaythe role of solid foods in the development of allergies, stating that there is no convincing scientific evidence that the avoidance or delayed introduction of potentially allergenic foods beyond 4-6 months reduces allergies in infants considered to be at increased risk for the development of allergic diseases or in those not considered to be at increased risk. Evidence from some trials with probiotics or prebiotic oligosaccharides suggests some benefits, but at present there is insufficient evidence to support their routine use. Neither can specific recommendations be made for the use of long-chain polyunsaturated fatty acids, antioxidants, folate, and vitamin D.
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Information is accumulating which implicates airway inflammation resulting from respiratory viral infections, acting against a background of atopy, in both the cause and pathogenesis of atopic asthma. This review brings together the most recent publications relevant to this rapidly evolving area, particularly those focusing on underlying pathogenic mechanisms. Salient findings from the recent literature include increased respiratory infection-associated symptom severity/duration and loss of asthma control in atopic relative to nonatopic children; up-regulation of FcεR1 expression on circulating monocytes/dendritic cells occurs during virus-associated atopic asthma exacerbations, providing a mechanism for transient amplification of underlying allergic airways inflammation; high potency of hRV-type C in induction of infection-associated wheeze; Th2-polarized immunity to mucosal dwelling bacteria and protection against asthma; a role for IL-15 in viral-associated airways inflammation; vitamin D and protection against infection-associated asthma exacerbations; strategies for reduction of infection-associated wheezing severity by boosting mucosal Treg cell activity via immunostimulation of the gut mucosa. Research in this area is pointing towards new rationales for development of early intervention strategies for prevention of asthma initiation and progression in childhood, based on control of respiratory infections and/or sensitization to aeroallergens.
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Vitamin D supplements are often recommended to restore sufficiency, although the adherence to treatment is low. This study assessed vitamin D status at different time intervals following the cessation of treatment. The database of Clalit-Health-Services (CHS), a not-for-profit HMO covering more than half of the Israeli population, was retrospectively searched for all members with available serum 25OHD test results in 2009 (245,493). We then identified those who filled any cholecalciferol prescription in 2008-2009 (121,817). Subjects were included in the final analysis only if they started treatment in 2009, had serum 25OHD < 50 nmol/l before the first prescription in 2009, and had at least one additional test result after the last dated prescription in 2009 (5,461). Serum 25OHD increased from 32 ± 11 nmol/l at baseline to 58.6 ± 22.3 nmol/l after treatment (P < 0.001). The proportion of subjects with sufficient vitamin D after treatment increased with increasing cholecalciferol daily dose and treatment duration (P < 0.001) and decreased with increasing time from cessation of treatment (P < 0.001). The effect of time from treatment cessation persisted after controlling for baseline serum 25OHD, daily cholecalciferol dose, treatment duration, seasonality, gender, age, ethnicity, and BMI; the ORs for sufficient vitamin D were 2.02 (95% CI 1.66-2.45), 1.67 (1.39-2.01), and 1.23 (1.04-1.47) for >30-60, 61-99, and 100-155 days compared to >155 days, respectively. Long-term vitamin D treatment is needed to maintain sufficient levels in those with baseline serum 25OHD below 50 nmol/l.
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Rickets, osteomalacia, osteoporosis and myopathy are among the better known consequences of a low to very low vitamin D status. Over the past several years various predominantly epidemiological and prospective cohort studies have found associations between low vitamin D levels and various extraskeletal conditions. These findings may particularly become important over the next years since large proportions of the population have low vitamin D levels. Increasing incidence rates of obesity, adverse life-style factors and active avoidance of sunlight seem to decrease average population mean vitamin D levels further. This article gives a brief overview of known and also less well-established potential detrimental effects of a low vitamin D status.
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Alopecia areata (AA) is a nonscarring hair loss disorder with a 2% lifetime risk. Most patients are below 30 years old. Clinical types include patchy AA, AA reticularis, diffuse AA, AA ophiasis, AA sisiapho, and perinevoid AA. Besides scalp and body hair, the eyebrows, eyelashes, and nails can be affected. The disorder may be circumscribed, total (scalp hair loss), and universal (loss of all hairs). Atopy, autoimmune thyroid disease, and vitiligo are more commonly associated. The course of the disease is unpredictable. However, early, long-lasting, and severe cases have a less favorable prognosis. The clinical diagnosis is made by the aspect of hairless patches with a normal skin and preserved follicular ostia. Exclamations mark hairs and a positive pull test signal activity. Dermoscopy may reveal yellow dots. White hairs may be spared; initial regrowth may also be nonpigmented. The differential diagnosis includes trichotillomania, scarring alopecia, and other nonscarring hair loss disorders such as tinea capitis and syphilis.
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Although diphenylcyclopropenone (DCP) is frequently used for the treatment of alopecia areata (AA), large studies with more than 100 patients are still scarce. To determine the efficacy of DCP immunotherapy in a large cohort of patients with AA who had been treated in our institute from January 2000 to December 2006. A total of 142 patients with AA undergoing topical DCP therapy in a self-controlled design were evaluated retrospectively. Seven patients (4.9%) were anergic to DCP. Two of 135 patients (1.5%) discontinued DCP therapy because of adverse effects. Fifty-one patients (37.8%) had a complete response (CR: >90% re-growth of hair), 20 patients (14.8%) exhibited a partial response (PR: >50-90% re-growth), 26 patients (19.3%) experienced a minimal response (MR: 10-50% re-growth) and 38 patients (28.1%) had no response after DCP therapy (NR: <10% re-growth). Bivariate logistic analysis revealed that severity of hair loss at the beginning of DCP (P=0.001) is the only significant prognostic factor for therapeutic outcome. Twenty-three patients (45.1%) with CR had relapses upon discontinuation of the treatment or even during prolonged DCP therapy. Topical immunotherapy with DCP of patients with AA is rather effective and mostly well tolerated. The extent of hair loss before therapy is the main predictor for the therapeutic success of DCP. However, DCP therapy is associated with a high degree of relapse of which patients should be well informed.
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1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the active form of vitamin D, is known to regulate calcium and phosphorus metabolism, thus being a key-player in bone-formation. However 1,25(OH)(2)D(3) also has a physiological role beyond its well-known role in skeletal homeostasis. Here, we describe 1,25(OH)(2)D(3) as an immunomodulator targeting various immune cells, including monocytes, macrophages, dendritic cells (DCs), as well as T-lymphocytes and B-lymphocytes, hence modulating both innate and adaptive immune responses. Besides being targets, immune cells express vitamin D-activating enzymes, allowing local conversion of inactive vitamin D into 1,25(OH)(2)D(3) within the immune system. Taken together, these data indicate that 1,25(OH)(2)D(3) plays a role in maintenance of immune homeostasis. Several epidemiological studies have linked inadequate vitamin D levels to a higher susceptibility of immune-mediated disorders, including chronic infections and autoimmune diseases. This review will discuss the complex immune-regulatory effects of 1,25(OH)(2)D(3) on immune cells as well as its role in infectious and autoimmune diseases, more in particular in tuberculosis and type 1 diabetes (T1D).
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To the Editor.— No estimates of the incidence or prevalence of alopecia areata (AA) have been published. The First National Health and Nutrition Examination Survey (NHANES-I), conducted from 1971 through 1974, contained a dermatologic examination of 20 749 individuals in a probability sample of the US population. This communication presents the prevalence of AA as estimated from the findings of NHANES-I. Materials and Methods.— The survey design and methods of NHANES-I have been well described by the National Center for Health Statistics (NCHS).1,2 The examiner's diagnosis of AA could be recorded in four places on the survey form as follows: (1) "significant dermatological diagnosis" (limit of three); (2) a finding on the scalp; (3) a finding on the face; or (4) a finding on the nail.Using a published table of upper- and lower-bound factors based on the Poisson distribution,3 95% confidence intervals (CIs) for total prevalence and
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Since 1986, 10 men and one woman were ambulatory while supported with mechanical assist devices as a bridge to heart transplantation. Four patients received a subclavian intraaortic balloon pump, two were supported with a Novacor left ventricular assist system, three patients received Pierce-Donachy ventricular assist devices, and one patient received a Jarvik 7 total artificial heart. One patient with an intraaortic balloon pump later received a left ventricular assist system because of hemodynamic deterioration despite the intraaortic balloon pump. Before device insertion all 11 patients were in cardiogenic shock despite inotropic and vasodilator support. The time of support ranged from 8 to 440 days (median, 24 days). In-house coverage by the circulatory support team was necessary only during the first 24 to 72 hours of support. When the patient's condition was stabilized, nursing staff monitored the devices with "on-call" availability of the circulatory support team. After implant of the device, all patients were able to perform activities of daily living. Once patients were able to walk in their hospital rooms, ambulation began in the hallways; frequency and distance were gradually increased. Four of the patients walked outside the hospital while tethered to the drive console. Daily physical therapy contributed to increased exercise tolerance. Protective isolation was used before and after transplantation to minimize the risk of infection. Sterile dressing changes (gown, gloves, mask) were applied to drive lines, cannula sites, and incisions. All invasive lines and catheters were removed as soon as the patient's clinical condition warranted, and noninvasive monitoring was used to decrease the chance of infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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A modified double blind crossover study was performed to assess the effect of 1% topical minoxidil as compared with placebo in 30 patients with alopecia areata and alopecia totalis. The active preparation produced a highly significant incidence of hair regrowth. A cosmetically acceptable response was noted in 16 patients. No side effects were seen. The study confirmed that topical minoxidil will induce new hair growth in alopecia areata but that it is less likely to do so in more severe and extensive disease. Furthermore, patients with alopecia universalis and totalis may not respond at all. Nevertheless, as compared with other drugs minoxidil applied topically is relatively non-toxic, is easy to use, and has no systemic or local side effects.
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Because the hair follicle is a highly hormone-sensitive miniorgan, the role of hormones produced locally in the skin in the control of hair growth deserves systematic analysis. It has been shown previously that the potent steroid hormone 1,25-dihydroxyvitamin D3 (1,25-D3) modulates growth and differentiation of keratinocytes via binding to a high-affinity nuclear vitamin D receptor (VDR). In this study, we have examined the in situ expression of VDR during the murine hair cycle. VDR expression was detected immunohistochemically. To obtain defined stages of the murine hair cycle, hair growth was induced by depilation in C57 BL-6 mice. In addition to the recognized VDR expression of outer root sheath keratinocytes, we detected VDR immunoreactive cells in the dermal papilla, the mesenchymal key structure of the hair follicle. Furthermore, VDR immunoreactivity in the nuclei of outer root sheath keratinocytes and in dermal papilla cells was stronger during anagen IV-VI and catagen than during telogen and anagen I-III. This suggests hair cycle-associated changes in the expression of VDR, and points to a potential role for 1,25-D3 in hair follicle biology. Selected follicular cell populations may display hair cycle-dependent sensitivity to 1,25-D3 stimulation.
Article
The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), used for control of weeds in agriculture, forestry, and rights of way, can accumulate as a residual chemical in soil. The objective was to determine percutaneous absorption of 2,4-D from soil, with emphasis on soil load and skin contact time. With control acetone vehicle, in vivo absorption of 2,4-D in the rhesus monkey was 8.6 +/- 2.1% of the dose, which compared closely to published human absorption of 6.0 +/- 2.4%. Percutaneous absorption from soil loads of 1 and 40 mg/cm2 were 9.8 +/- 4.0 and 15.9 +/- 4.7%, respectively, values similar to acetone vehicle. In vitro absorption in human skin calculated from skin contact accumulation over 24 h was 1.8 +/- 1.7, 1.7 +/- 1.3, and 1.4 +/- 1.2% for soil loads of 5, 10, and 40 mg/cm2, respectively. Thus, soil load did not affect 24-h percutaneous absorption. Current Environmental Protection Agency (EPA) recommended calculated reductions due to soil load are not supported by these results with 2,4-D. Percutaneous absorption of 2,4-D from acetone vehicle for 8 h dosing period was 3.2 +/- 1.0%, one-third the value of 8.6 +/- 2.1% over 24 h. With soil vehicle, absorption for 8 h was only 0.03 +/- 0.02% for 40 mg/cm2 soil load and 0.05 +/- 0/.004% for 1 mg/cm2 soil load. Absorption for 16 h was 2.2 +/- 1.2%. Absorption over time was linear for acetone vehicle, where total dose is deposited on skin, but not linear for soil vehicle, which had an 8-h delay (lag time). This equates with a normal 8-h work day where most of the contaminated soil can be washed off the skin. The apparent partition coefficient of 2,4-D between soil and water changed over time. This suggests there is a "mobility" phase for 2,4-D in soil that will change with time. For soil vehicle, percutaneous absorption of 2,4-D was not linear in respect to soil load or to skin contact time. Calculation based on assumed linearity can falsely estimate potential human health hazard. Clearly, the dermatokinetics with soil and skin represent complex interactive forces that require detailed evaluation before overgeneralizing rules for interpretation in terms of risk assessment.
Article
Vitamin D receptor (VDR) null mice develop hypocalcemia, hyperparathyroidism, rickets, osteomalacia and alopecia. Normalization of mineral ion homeostasis prevents all of these abnormalities except alopecia. Hair reconstitution assays, performed in athymic nude mice, demonstrate that the lack of VDR in keratinocytes leads to a defect in anagen initiation, similar to that observed in VDR null mice. Although these studies demonstrate that expression of the VDR in keratinocytes is necessary, they do not prove that it is sufficient for maintenance of the normal hair cycle. To address this hypothesis, we generated transgenic mice expressing the human VDR under the control of the keratin 14 (K14) promoter. Two highly expressing transgenic lines were mated with VDR null mice to obtain VDR null mice expressing the human VDR transgene (hVDR+/mVDR-). Expression of the transgene in the VDR null mice prevented alopecia. Furthermore, when subjected to anagen initiation, the hair follicle keratinocytes of the hVDR+/mVDR- mice demonstrated an enhanced proliferative response compared to those of control littermates. Restoration of VDR expression in the keratinocytes of VDR null mice, prevents the hair cycle defect that leads to the development of alopecia.
Article
We examined polymorphisms of vitamin D receptor (VDR) gene in Japanese patients with psoriasis vulgaris (PsV). We also studied the association between VDR gene polymorphisms and the response to vitamin D (VD) topical treatment in psoriatic patients. FokI, BsmI, ApaI and TaqI genotypes were determined by restriction fragment patterns in patients (n = 115) and controls (n = 69). In addition, 54 psoriatic patients were divided into two groups in terms of their response to VD (tacalcitol) topical treatment: non-responsive (n = 30) and responsive (n = 24) patients. The frequencies of B allele and t allele were lower in patients than in controls (9 vs. 19%: p < 0.01, 7 vs. 14%: p < 0.05, respectively). In regard to response to VD treatment, F allele was lower in non-responsive patients than in controls (47 vs. 64%, p < 0.05). We show that polymorphisms of VDR gene are associated with Japanese patients with PsV. Allelic variance in the VDR gene or other genes in linkage disequilibrium with this gene might predispose to the development of PsV.
Article
Alopecia areata (AA) is an autoimmune disease that targets actively growing (anagen) hair follicles in humans and other mammals. C3H/HeJ, but not C57BL/6J, mice spontaneously develop an adult-onset form of AA. A segregating population of C3HB6F2 female mice (n=1096), generated from crossing these two strains, was used for genome-wide linkage analysis to identify AA genetic susceptibility. Previous analysis identified susceptibility intervals on chromosomes 17 (Alaa1) and 9 (Alaa2). Using additional markers in these intervals and saturation mapping purported intervals on chromosomes 8 and 15, two additional regions were identified (Alaa3 and Alaa4, respectively). Human gene association studies identified specific human leukocyte antigen intervals comparable with those (major histocompatibility complex) found in Alaa1 in the mouse. Other human studies identified genes not found in this linkage study, but these human transcription factors are directly regulated by genes within Alaa1. These results indicate the necessity of integrating both gene association and genome-wide linkage studies in both mice and humans to understand the complex nature of these and other polygenic diseases.
Article
Central nervous system (CNS) immune privilege is an experimentally defined phenomenon. Tissues that are rapidly rejected by the immune system when grafted in sites, such as the skin, show prolonged survival when grafted into the CNS. Initially, CNS immune privilege was construed as CNS isolation from the immune system by the blood-brain barrier (BBB), the lack of draining lymphatics, and the apparent immunoincompetence of microglia, the resident CNS macrophage. CNS autoimmunity and neurodegeneration were presumed automatic consequences of immune cell encounter with CNS antigens. Recent data have dramatically altered this viewpoint by revealing that the CNS is neither isolated nor passive in its interactions with the immune system. Peripheral immune cells can cross the intact BBB, CNS neurons and glia actively regulate macrophage and lymphocyte responses, and microglia are immunocompetent but differ from other macrophage/dendritic cells in their ability to direct neuroprotective lymphocyte responses. This newer view of CNS immune privilege is opening the door for therapies designed to harness autoreactive lymphocyte responses and also implies (i) that CNS autoimmune diseases (i.e. multiple sclerosis) may result as much from neuronal and/or glial dysfunction as from immune system dysfunctions and (ii) that the severe neuronal and glial dysfunction associated with neurodegenerative disorders (i.e. Alzheimer's disease) likely alters CNS-specific regulation of lymphocyte responses affecting the utility of immune-based therapies (i.e. vaccines).
Article
Several lines of evidence support a genetic component to alopecia areata (AA), including differences in patients based on severity of AA, associated diseases and family history. We aimed to examine clinical and genetic features of patients with AA with a focus on associated diseases, especially atopy, and family history of AA in the USA. From 1998 to 2001, 513 patients with AA completed interviews consisting of demographic information, patient's medical history, and family history of AA. Forty per cent of respondents had alopecia totalis and/or universalis (AT/AU). These patients were younger at the age of onset than those with patchy AA (P < 0.001), were more likely to have associated autoimmune or atopic disease (P = 0.047), most notably atopic dermatitis (P = 0.021) and thyroid disease (P = 0.012). They also had a greater number of relatives affected by AA (P < 0.05). Our findings show marked associations between severity of AA, atopic dermatitis, thyroid disease and other autoimmune diseases, and extensive family history of AA, suggesting two clinically distinct subtypes of AA with the severe subtype possibly associated with greater familial autoimmunity. Further research exploring the possibility of a genetic basis to explain these clinical findings will be helpful in clarifying our understanding of AA, leading to improvements in diagnosis and treatment.
Article
Alopecia areata (AA) is an autoimmune disorder of the hair follicle characterized by inflammatory cell infiltrates around actively growing (anagen) hair follicles. Substance P (SP) plays a critical role in the cutaneous neuroimmune network and influences immune cell functions through the neurokinin-1 receptor (NK-1R). To better understand the role of SP as an immunomodulatory neuropeptide in AA, we studied its expression and effects on immune cells in a C3H/HeJ mouse model for AA. During early stages of AA development, the number of SP-immunoreactive nerve fibers in skin is increased, compared to non-affected mice. However, during advanced stages of AA, the number of SP-immunoreactive nerves and SP protein levels in skin are decreased, whereas the expression of the SP-degrading enzyme neutral endopeptidase (NEP) is increased, compared to control skin. In AA, NK-1R is expressed on CD8+ lymphocytes and macrophages accumulating around affected hair follicles. Additional SP supply to the skin of AA-affected mice leads to a significant increase of mast cell degranulation and to accelerated hair follicle regression (catagen), accompanied by an increase of CD8+ cells-expressing granzyme B. These data suggest that SP, NEP, and NK-1R serve as important regulators in the molecular signaling network modulating inflammatory response in autoimmune hair loss.
Article
It has been demonstrated that the vitamin D receptor (VDR) is strongly expressed in key structures of hair follicles, and a lack of VDR leads to alopecia. We investigated whether there was any association between VDR gene polymorphisms (BsmI, ApaI, and TaqI) and alopecia areata (AA). Thirty-two patients with AA and 27 healthy control subjects were genotyped using polymerase chain reaction and restriction fragment length polymorphism analysis. In the patient group, the B and b allele frequencies were 53.1% and 46.9%, A and a allele frequencies were 70.3% and 29.7%, and T and t allele frequencies were 62.5% and 37.5%, respectively. In the control group, the corresponding values were 51.9% and 48.1%, 63.0% and 37.0%, and 77.8% and 22.2%, respectively. In the patient group, the BB, Bb, and bb genotype frequencies were 25.0%, 56.2%, and 18.8%, AA, Aa, and aa genotype frequencies were 43.8%, 53.1%, and 3.1%, and TT, Tt, and tt genotype frequencies were 37.5%, 50.0%, and 12.5%, respectively. In the control group, the corresponding values were 11.1%, 81.5%, and 7.4%, 29.6%, 66.7%, and 3.7%, and 63.0%, 29.6%, and 7.4%, respectively. None of the allele or genotype frequencies showed statistically significant differences between the patient and control groups. These findings suggest that there is no relationship between VDR gene polymorphisms and AA.