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ORIGINAL ARTICLE
Year : 2017  |  Volume : 62  |  Issue : 4  |  Page : 407-410
Vitamin D level in alopecia areata


1 Department of Dermatology, STD and Leprosy, Government Medical College, University of Kashmir, Srinagar, Jammu and Kashmir, India
2 Department of Biochemistry, Government Medical College, University of Kashmir, Srinagar, Jammu and Kashmir, India
3 Department of Preventive and Social Medicine, Government Medical College, University of Kashmir, Srinagar, Jammu and Kashmir, India

Date of Web Publication10-Jul-2017

Correspondence Address:
Yasmeen Jabeen Bhat
Department of Dermatology, STD and Leprosy, Government Medical College, University of Kashmir, Srinagar - 190 010, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_677_16

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   Abstract 

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.


Keywords: 25-hydroxyvitamin D, alopecia areata, severity of alopecia tool score, Vitamin D receptors


How to cite this article:
Bhat YJ, Latif I, Malik R, Hassan I, Sheikh G, Lone KS, Majeed S, Sajad P. Vitamin D level in alopecia areata. Indian J Dermatol 2017;62:407-10

How to cite this URL:
Bhat YJ, Latif I, Malik R, Hassan I, Sheikh G, Lone KS, Majeed S, Sajad P. Vitamin D level in alopecia areata. Indian J Dermatol [serial online] 2017 [cited 2019 Jan 19];62:407-10. Available from: http://www.e-ijd.org/text.asp?2017/62/4/407/210092

What was known?
Alopecia areata is an immune.mediated disorder of hair that responds to immunosuppressant drugs.



   Introduction Top


Alopecia areata (AA) is a common form of nonscarring alopecia characterized by hair loss with no clinical signs of inflammation and can affect scalp and/or any hair-bearing area of the body.[1] It is a common dermatological disorder and accounts for 25% of all alopecia cases.[2] It can occur at any age and there is no sex predilection although some studies show male preponderance.[3] Scalp is the most common site (90%). AA is classified on the basis of extent and pattern of hair loss.[4] It can be patchy AA, alopecia totalis in which entire scalp and body hair such as eyebrows, eyelashes, beard, axillary hair, and pubic hair is affected, and alopecia universalis if the total body hair is involved. Various patterns of AA include reticular, ophiasis, and sisaipho, acute diffuse and total alopecia. The unusual variants include perinaevoid and linear forms.[5]

AA is an autoimmune disease mediated by T-lymphocytes in which autoantigens play an important part in activating T-cells and is associated with other autoimmune diseases.[6],[7] Hair follicle is an immune-privileged site where major histocompatibility complex (MHC) Class I and II molecules are not expressed.[8] This immune privilege is collapsed in AA by the presence of increased MHC I and II complexes, decreased immunosuppressive molecules, and higher expression of adhesion molecules (ICAM-2 and ELAM-1) in the perivascular and peribulbar hair follicular epithelium, leading to perifollicular inflammation which causes thin dystrophic hair with miniaturization.[9]

Vitamin D functions such as a hormone and its main sources are through endogenous synthesis in the skin and diet.[10] It has a role in control and regulation of immune mechanisms.[11] It has been demonstrated that Vitamin D receptors (VDRs) are strongly expressed in hair follicles, and lack of VDRs reduces epidermal differentiation and growth of hair follicles.[12],[13]

In view of these points, we designed this study to find the association between Vitamin D level and AA.


   Materials and Methods Top


This was a hospital-based cross-sectional study involving 50 patients of AA, attending our outpatient department (OPD) from May to October 2015. The diagnosis was made on the basis of clinical features and trichoscopy. The control group consisted of 35 age- and sex-matched individuals selected randomly from our OPD with no history of AA.

Exclusion criteria

(1) Patients suffering from any other dermatological condition or any systemic or autoimmune illness. (2) Other causes of alopecia including scarring alopecia, androgenic alopecia, telogen effluvium, and female pattern hair loss. (3) Patients who had received oral or topical medications during the past 4 weeks (topical, intralesional, or oral steroids, immunosuppressants, Vitamin D supplements, and topical vitamin D analogs). (4) Pregnant and lactating females. (5) Patients with body mass index (BMI) more than 25 (since there is a relationship between obesity and Vitamin D deficiency [14]) were excluded from the study.

An informed consent was obtained from all patients after explaining to them the nature of the study and the procedures. The study was approved by the ethical committee of the hospital.

History regarding the onset, progression, duration of disease, presence of any other systemic or autoimmune disease, history of any significant drug intake, family history, and approximate number of hours of daily sun exposure was noted.

Demographic, clinical, and laboratory data were recorded in both the groups. Anthropometric measurements including height, weight, and BMI were also recorded. Laboratory tests performed included complete blood count, liver and renal function tests, thyroid function test, and calcium and Vitamin D level.

The trichoscopic findings (DermLite DL3N, California, USA, ×10) for diagnosing AA included black dots, exclamation mark hairs, coudability hairs, and yellow dots. The severity of AA was scored by severity of alopecia tool score (SALT score), and patients were further subgrouped into following SALT subclasses: S0 = no hair loss; S1= <25; S2 = 26–50; S3 = 51–75; S4 = 76–99; and S5 = 100.

Serum 25-hydroxyvitamin D level analysis

Blood samples were taken from both cases as well as controls after an overnight fast, and samples were immediately processed by centrifugation of 4000rpm at room temperature. Plasma 25-hydroxyvitamin D (25(OH)D) was analyzed by Chemiluminescence method/kit method (Siemens USA) as per manufacturers protocol, using Siemens ADVIA Centaur Analyzer. The coefficient of variation for interassay analyses was 18.4% at a 25(OH)D level of 16 ng/ml and 11.7% at 48.4 ng/mL. A deficiency in Vitamin D was defined as serum 25(OH)D concentrations <30 ng/ml.

Statistical analysis

Statistical analysis was done using student's t-test. For comparison of categorical data such as sex and residence, Chi-square test was used. P value < 0.05 was considered statistically significant.


   Results Top


The mean age of cases and controls was 22.4 ± 8.6 and 29.2 ± 7.6, respectively. Among patients, 33 were from urban areas and 17 were from rural areas, whereas in control group, 22 were from urban areas and 13 were from rural areas (P = 0.765). The mean duration of the disease was 4.80 ± 4.58 months. The mean BMI in cases was 20.96 ± 1.91, whereas in controls, it was 21.37 ± 1.70 (P = 0.31) [Table 1]. Both the cases and controls were normocalcemic, and the difference between the groups was statistically insignificant [Table 1]. Among patients of AA, 29 patients had a single patch and 21 patients had multiple patches. All the lesions were on the scalp. Thirty-eight patients had S1, 12 had S2, whereas there were no patients with S3 to S5 SALT score.
Table 1: Comparison of Vitamin D level in cases and controls

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The mean serum 25(OH)D concentration of patients with AA was 16.6 ± 5.9ng/ml, whereas in control group, the mean concentration was 25.49 ± 1.02. The difference in Vitamin D (serum 25(OH)) levels between two groups was statistically significant (P < 0.001).

Among the patients of AA, mean concentration of 25(OH)D in S1 group was 19.02 ± 4.4 ng/ml whereas the mean concentration in S2 group was 9.00 ± 2.80 ng/ml (P < 0.001). A significant negative correlation was found between SALT score and Vitamin D level (P < 0.001; r = −0.730) [Table 2]. The patients with single patch alopecia had mean concentration of 25(OH)D of 19.9 ± 4.45 ng/ml whereas those with multiple patches had mean value of 12.0 ± 4.45 ng/ml and the difference was statistically significant (P < 0.001) [Table 3]. A significant negative correlation was found between number of patches and Vitamin D level (P < 0.001, r = −0.670).
Table 2: Correlation of Vitamin D level with severity of alopecia areata

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Table 3: Correlation of Vitamin D level with number of alopecia patches

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Among patients of AA, there was no significant difference in Vitamin D level between men and women (P > 0.05). There was no significant correlation between Vitamin D level and duration of the disease (P > 0.05).


   Discussion Top


Our study was designed to determine the relation between Vitamin D level and AA. In our study, we found that the levels of 25(OH)D were low in patients of AA when compared with the healthy controls and the difference was statistically significant (P < 0.001). Furthermore, we found that the levels were much lower in patients with higher SALT score or multiple patches, i.e., a negative correlation was found between the levels of Vitamin D and the severity of AA (determined by SALT score and number of patches).

The mechanism by which Vitamin D deficiency and AA are related is still not clear. Vitamin D has a role in innate and acquired immune systems, and the expression of VDRs and its activating enzyme 1α-hydroxylase on various cells of immune system, for example, macrophages, dendritic cells, and T-cells suggests its role.[14] VDR is a member of nuclear hormone receptor family and acts as a ligand-inducible transcription factor that regulates Vitamin D responsive genes.[15] Although studies have suggested an important role of VDR in the pathogenesis of AA, we did not evaluate the levels of VDR because of the lack of facility and expertise for the same in our hospital.

Various studies have shown that 1,25(OH)2D3 modulates the activity of dendritic cells.[14] It inhibits the differentiation and maturation of dendritic cells; reduces the expression of MHC Class II, CD40, CD80, and CD86; and inhibits the secretion of proinflammatory cytokines such as interleukin (IL)-1, IL-2, IL-6, IL-12, interferon-c, and tumor necrosis factor-α. IL-12 which is an immunostimulatory cytokine involved in shifting the immune system toward the T-helper (Th) 1 phenotype is inhibited by 1,25(OH)2D3, thereby shifting the immune response toward the Th2 phenotype.[16],[17] The inhibition of the Th1 phenotype and potentiation of the Th2 phenotype has been suggested to be one of the mechanisms, by which 1,25(OH)2D3 suppresses Th1-mediated autoimmune diseases.[14],[17] In addition, 1,25(OH)2D3 enhances the production and function of T-regulatory cells, which may also help in suppressing autoimmune disorders.

In the present study, the assessment of T-cell function was not feasible because of the nonavailability of the requisite infrastructure.

Our study shows a significant relationship between levels of Vitamin D and AA. Similar results were seen in many other studies as well. In a study by Yilmaz et al. ,[18] low serum 25(OH)D and 1,25(OH)2D3 levels were seen in patients with AA compared with healthy controls. Another study by d'Ovidio et al. , involving 156 patients with AA and 148 controls, revealed that an insufficiency or deficiency of 25(OH)D was not significantly different between patients with AA and the controls.[19] However, a deficiency in 25(OH)D was present in 42.4% of patients, which was significantly higher than the 29.5% observed in the healthy controls. Furthermore, the correlation was not obtained between the levels and the extent of hair loss. Another study by Cerman et al. found deficient serum 25(OH)D levels in patients with AA and inverse correlation with disease severity.[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. Furthermore, the dietary intake of Vitamin D in patients was not assessed and no therapeutic trial of Vitamin D was given.

Our study was the first of its kind from a temperate area with a high altitude. The levels of exposure to the ultraviolet, seasonal changes and altitude, level of activity, and BMI should be considered to justify the level of Vitamin D in patients in further studies.

Systemic Vitamin D supplementation had been shown to be therapeutically effective in different autoimmune diseases, such as inflammatory bowel disease, Behcet's disease, rheumatoid arthritis, and systemic lupus erythematosus. Therefore, as we do not know at present whether Vitamin D supplementation would be effective in the therapy of AA or not, further clinical trials are needed to evaluate its efficacy in treating this common dermatosis.


   Conclusion Top


In our study, we found that the levels of 25(OH)D were low in patients of AA when compared to healthy controls. Furthermore, there was a negative correlation between the levels and severity of AA assessed by SALT score. Thus, the study suggests the role of Vitamin D in pathogenesis of AA and hence a possible role of Vitamin D supplementation in the treatment of same.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: Part II. Treatment. J Am Acad Dermatol 2010;62:191-202.  Back to cited text no. 1
[PUBMED]    
2.
McMichael AJ, Pearce DJ, Wasserman D, Camacho FT, Fleischer AB Jr., Feldman SR, et al. Alopecia in the United States: Outpatient utilization and common prescribing patterns. J Am Acad Dermatol 2007;57 (suppl 2):S49-51.  Back to cited text no. 2
    
3.
Tan E, Tay YK, Goh CL, Chin Giam Y. The pattern and profile of alopecia areata in Singapore – A study of 219 Asians. Int J Dermatol 2002;41:748-53.  Back to cited text no. 3
[PUBMED]    
4.
Madani S, Shapiro J. Alopecia areata update. J Am Acad Dermatol 2000;42:549-66.  Back to cited text no. 4
    
5.
Sato-Kawamura M, Aiba S, Tagami H. Acute diffuse and total alopecia of the female scalp. A new subtype of diffuse alopecia areata that has a favorable prognosis. Dermatology 2002;205:367-73.  Back to cited text no. 5
    
6.
Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC. CNS immune privilege: Hiding in plain sight. Immunol Rev 2006;213:48-65.  Back to cited text no. 6
    
7.
Barahmani N, Schabath MB, Duvic M; National Alopecia Areata Registry. History of atopy or autoimmunity increases risk of alopecia areata. J Am Acad Dermatol 2009;61:581-91.  Back to cited text no. 7
    
8.
Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: Part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol 2010;62:177-88.  Back to cited text no. 8
    
9.
Wang E, McElwee KJ. Etiopathogenesis of alopecia areata: Why do our patients get it? Dermatol Ther 2011;24:337-47.  Back to cited text no. 9
    
10.
LoPiccolo MC, Lim HW. Vitamin D in health and disease. Photodermatol Photoimmunol Photomed 2010;26:224-9.  Back to cited text no. 10
    
11.
Van Etten E, Decallonne B, Verlinden L, Verstuyf A, Bouillon R, Mathieu C. Analogs of 1alpha, 25-dihydroxyvitamin D3 as pluripotent immunomodulators. J Cell Biochem 2003;88:223-6.  Back to cited text no. 11
    
12.
Bikle DD. Vitamin D metabolism and function in the skin. Mol Cell Endocrinol 2011;347:80-9.  Back to cited text no. 12
    
13.
Malloy PJ, Feldman D. The role of Vitamin D receptor mutations in the development of alopecia. Mol Cell Endocrinol 2011;347:90-6.  Back to cited text no. 13
    
14.
Di Rosa M, Malaguarnera M, Nicoletti F, Malaguarnera L. Vitamin D3: A helpful immuno-modulator. Immunology 2011;134:123-39.  Back to cited text no. 14
    
15.
Chen CH, Sakai Y, Demay MB. Targeting expression of the human Vitamin D receptor to the keratinocytes of Vitamin D receptor null mice prevents alopecia. Endocrinology 2001;142:5386-9.  Back to cited text no. 15
    
16.
Hewison M. An update on Vitamin D and human immunity. Clin Endocrinol (Oxf) 2012;76:315-25.  Back to cited text no. 16
    
17.
Ersoy-Evans S. Commentary: Vitamin D and autoimmunity: Is there an association? J Am Acad Dermatol 2010;62:942-4.  Back to cited text no. 17
    
18.
Yilmaz N, Serarslan G, Gokce C. Vitamin D concentrations are decreased in patients with alopecia areata. Vitam Trace Elem 2012;1:105-9.  Back to cited text no. 18
    
19.
d'Ovidio R, Vessio M, d'Ovidio FD. Reduced level of 25-hydroxyvitamin D in chronic/relapsing alopecia areata. Dermatoendocrinol 2013;5:271-3.  Back to cited text no. 19
    
20.
Aksu Cerman A, Sarikaya Solak S, Kivanc Altunay I. Vitamin D deficiency in alopecia areata. Br J Dermatol 2014;170:1299-304.  Back to cited text no. 20
    
21.
Mahamid M, Abu-Elhija O, Samamra M, Mahamid A, Nseir W. Association between Vitamin D levels and alopecia areata. Isr Med Assoc J 2014;16:367-70.  Back to cited text no. 21
    

What is new?
Vitamin D deficiency may be an important factor in the etiopathogenesis of alopecia areata, and oral Vitamin D supplementation and topical Vitamin D analogs may be used to treat alopecia areata.



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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