Introduction

Alopecia areata (AA) is a common autoimmune disease affecting hair follicles and nails. This disease causes hair loss in all age groups and the round patches of hair loss appeared in different body parts mainly scalp and face [1, 2]. Globally, the incidence rate of alopecia areata reached to about 20.2/100,000 population/year with life time risk of about 2%, while the AA prevalence is ranging between 0.1-0.2% in regard to location and ethnicity [3]. However, the AA prevalence could reach up to 8.6% in adults with positive family history [4]. It was shown that AA incidence increased with advancing age with high incidence in age group of 25-35 years old. However, more severe cases recorded in paediatric age group 4. No sex differences are reported in regard to AAincidence [5].

The Alopecia Areata is highly related to other autoimmune diseases such as vitiligo, lupus erythematosus, atopic dermatitis, and thyroid disorders. Alopecia areata has been shown to be associated with atopic dermatitis in 39% of cases [5, 6]. The complex pathophysiology of AA involves an autoimmune basis, and its association with other autoimmune diseases supports this etiology. For instance, the presence of lymphocytes around hair follicles and the good response of patients to immunosuppressive treatment also indicate an autoimmune pathogenesis [7]. Moreover, AA diagnosis has been associated with an increased risk of other autoimmune diseases, including systemic autoimmune disorders like ulcerative colitis, type 1 diabetes, thyroid diseases, coeliac disease, and rheumatoid arthritis, as well as dermatological autoimmune conditions such as vitiligo, lupus erythematosus, and scleroderma [8]. The exact etiology of alopecia areata is not fully understood till now, however,

The AA is thought to be an autoimmune disease resulted from combination of genetic factor that play a major role in AA development with predisposition of positive family history and effect of environmental factors that exacerbate the disease. The environmental factors like stress, infection, hormonal changes, diet, and vitamins insufficiency were involved as risk factors. Normally, the hair follicle has immune privilege zone caused by immuosupression mechanisms and lowering antigens activity [9, 10]. The immune privilege zone is an immunosuppressive area around the hair bulb, which protects the hair follicle from immunopathogenic injury [11]. This unique feature of hair follicles demonstrates the ability to regenerate itself during each anagen (growth) phase [12]. Several mechanisms collaborate in providing immune protection, including passive and active mechanisms [13]. However, the collapse of this immune privilege zone can be triggered by genetic and environmental factors, leading to autoimmune reactions against hair follicle autoantigens [11]. This collapse results in increased levels of interferons and interleukins, causing infiltration by inflammatory cells and inflammation of the hair follicle, ultimately leading to hair loss [12, 14].

Clinically, the alopecia areata is presented by smooth, sharply lined, round patches of hair loss without atrophy shown at peripheral parts of patches. The disease is either presented as total body hair loss (alopecia universalis) or total scalp hair loss (alopecia totalis). The alopecia areata may also be presented as band-like hair loss in the temporal and occipital scalp (alopecia ophiasis). Other presentations of alopecia areata included some diffuse variants by sporadic or diffuse thinning of hair in the scalp or reticular sites with frequent hair loss and re-growth of hair in the same area [15]. In some cases, hair loss in frontoparietotemporal parts is presented in the ophiasis inversus pattern. Nail abnormalities are reported in 7-66% of AA patients commonly trachyonychia, onychorrhexis, nail thinning, thickening, red spot lunulae, etc [16]. The alopecia areata cases could be clinically presented with thyroid dysfunction features in about 8 to 28% of cases [17], or presented with vitiligo clinical features in about 1.8 to 16% of cases or with atopy clinical features in about 1 to 52% of cases [17, 18].

Thyroid gland dysfunction disorders affected all body organs and thyroid diseases are also presented clinically by some dermatological manifestations like hair loss [19]. The thyroid hormones have a direct effect on the skin by protein synthesis stimulation, and oxygen consumption of epidermis, and also play a major role in epidermis thickness and mitosis in addition to significant organization of epidermal homeostasis [20]. The relationship between hair loss and autoimmune thyroid diseases was reported by different literature in regard to the autoimmune etiology of alopecia areata [21]. Both thyroid hormones (Triiodothyronine [T3] and Thyroxin [T4]) are essential in the development of epidermal keratinocytes and dermal fibroblasts, maintenance and stimulation of hair growth in addition to help in secreting sebum [22, 23]. Overt hypothyroidism which is characterized by high thyroid stimulating hormone (TSH) and thyroid anti-bodies is highly related to cases of alopecia areata [24, 25].

The alopecia areata cases in Iraq are common with different etiological and clinical patterns [26]. In Iraq, various studies have been conducted to understand the etiology and clinical patterns of alopecia areata. Some studies have found associations between viral infections, such as cytomegalovirus (CMV), and alopecia areata [27, 28]. Other research has focused on the role of immune cells, such as CD4+, CD39+, and FOXP3+ T regulatory cells, in Iraqi patients with alopecia areata [29]. Dermatoscopic assessments have additionally been carried out to evaluate the features of alopecia areata and their connections with different clinical variations, alterations in the nails, and the extent of the condition [30]. Also, autoimmune disorders are detected in 12.8% of Iraqi patients with alopecia areata [31]. These studies provide insights into the different etiological and clinical patterns of alopecia areata in Iraq.

In Erbil City, the alopecia areata is a common dermatological disease with a family history background and it is related to autoimmune diseases in 11% of cases [32]. However, there is a national scarcity of literature discussing the effect of thyroid hormones on the development of hair loss. This study aims to investigate the levels of thyroid biomarkers in patients with alopecia areata (AA) compared to healthy individuals. By exploring this association, the research seeks to address a knowledge gap in understanding the potential role of thyroid hormones in the AA development. This information could contribute to improved diagnosis and treatment strategies for AA patients, particularly those with thyroid disorders. 

Materials and Methods

The present study was a cross-sectional study carried out in Erbil Dermatology Teaching center in Erbil City, Kurdistan region-Iraq during six months from the 1^st of January to the 30^th of June, 2022. The studied population was patients with alopecia areata. Patients with different age and sex groups in all hairy areas of the body, while the control group was apparently healthy individuals without alopecia areata and hair fall were included. The study ethics were implemented by documented approval of Kurdistan Board and Hospital authority, agreement of patients, in addition to the confidentiality of data and management of complications accordingly.

Inclusion criteria for the evaluation of thyroid biomarkers in patients with alopecia areata included participants of any age and sex with a confirmed diagnosis of alopecia areata. Likewise, patients should not have a history of thyroid disease, use of thyroid drugs, and autoimmune diseases. The exit criteria comprised patients who withdrew their consent to take part in the study, experienced any thyroid disorder throughout the study, underwent any treatment for alopecia areata during the study, and failed to adhere to the study protocol.  One hundred patients diagnosed with Alopecia Areata (AA) were carefully chosen based on predefined criteria, while another group of one hundred healthy individuals was also selected to serve as controls. The selection process involved assessing eligibility for inclusion and exclusion criteria to ensure a representative sample for the study.

Information on patients with alopecia areata was collected directly and filled in a prepared questionnaire designed by researchers. The questionnaire included general characteristics of alopecia areata patients (age, sex, marital status, residence, occupation, body mass index, disease duration, and age of patients at disease onset), clinical characteristics of alopecia areata patients (previous illness, symptoms, associated diseases, previous attack, family history, and treatment), Alopecia areata characteristics (number of patches, erythema, size, the area involved, patterns of involvement, nail involvement and Alopecia areata severity index (AASI) score)) and thyroid profile of alopecia areata patients (Thyroid Stimulating Hormone (TSH), T3, T4, Anti-TPO, and Anti-TGT).

The Alopecia Areata Severity Index (AASI) is a scoring system that evaluates the severity of alopecia areata on the face and scalp. Unlike traditional systems that only consider scalp involvement, the AASI includes an assessment of beard hair, eyebrows, and eyelashes. Each area is individually evaluated and assigned a score from 0 to 100 (0-50 for the upper face). The total AASI score is obtained by adding the scores for the scalp, upper face, and beard. This comprehensive scoring system provides an objective measure for evaluating treatment response and disease progression in alopecia areata [33]. To validate the AASI score, a pilot study was conducted to assess the reliability of scoring system. The study found that the AASI score is a reliable scoring system used to assess the AA severity in research studies [33].

The diagnosis of alopecia areata was made by a dermatologist and hair specialist based on clinical examination and medical history. In addition, dermoscopy and scalp biopsy were used to confirm the diagnosis. The samples were collected by obtaining five milliliters of venous blood from each participant with alopecia areata using plastic disposable syringes. The blood samples were then centrifuged to separate the serum, which contained the target biomarkers. The serum samples were frozen and stored at -20 °C or lower until they were transported to the laboratory for analysis. Thawed samples were subjected to specific laboratory techniques, such as immunoassays, to quantify the levels of thyroid biomarkers (T3, T4, TSH, antithyroglobulin, and anti thyroperoxidase antibodies). Quality control measures were implemented throughout the process to ensure accurate and reliable results.

The patient’s data were inputted into the SPSS program-26 and analysed statistically. Appropriate tables were created to present the results. Statistical tests such as chi-square and Fisher’s exact tests were utilized to examine relationships between variables, while independent sample t-tests and One-way Analysis of Variance (ANOVA) were employed for continuous variables. A significance level of p ≤ 0.05 was considered statistically significant.

Results and Discussion

In this study, 100 alopecia areata (AA) patients participated with mean age (23.2 years old); 18% of them were in the age of less than 10 years old, 26% of them were in the age group 10-19 years old, 26% of them were in the age group 20-29 years old, 16% of them were in the age group 30-39 years, and 14% of them were in the age of 40 years old and over 40. Male AA patients were more than females (69% vs. 31%). About two-thirds of AA patients were singles, while 34% of them were married. The residents inside Erbil city were represented by 75% of AA patients and outside city in 25% of them. The occupation of AA patients was distributed as followings; child (12%), student (29%), governmental employee (20%), private employee (21%), retired (1%), housewife (8%), and jobless (9%). The mean body mass index of AA patients was (24.3 Kg/m2); 8% of patients were underweight, 33% of patients were overweight and 10% of them were obese. The mean disease duration of AA patients was (5.8 months); 34% of patients had disease duration of less than one month, 58% of them had disease duration of 1-12 months and 8% of them had disease duration of more than 12 months. 40% of patients experienced the onset of AA disease during childhood, while 57% experienced it during adulthood, and the remaining 3% had a late onset of the disease (Table 1).

History of previous illness within the last 3 months was absent in 89% of AA patients, while chronic psychological stress was reported in 8% of AA patients, febrile illness in one patient, and others in two patients.

Most (90%) of patients had no symptoms, while the main reported AA symptoms were itching (8%) and pain (2%). In 72% of AA patients, there were no associated diseases detected, whereas atopy was observed in 15% of patients, thyroid diseases in 8%, and vitiligo in 5%. Previous AA attack was shown by 34% of studied patients. The family history of AA patients was negative in 46% of patients, while positive family history of diabetes mellitus was shown in (19%) of patients, positive family history of thyroid diseases was indicated in (13%) of patients, positive family history of AA was demonstrated in (6%) of patients, positive family history of thyroid diseases, DM was illustrated in (5%) of patients, etc. Out of the AA patients, treatment information was unavailable for 76% of them, while 24% of the patients underwent treatment. The most commonly administered treatments were topical steroids (15%), a combination of topical steroids and salicylic acid (7%), and systemic therapy (2%) (Table 2).

The mean number of AA patches was (3.5); 39% of them had one patch and 28% of them had five patches and more.

Erythema was indicated by 3 AA patients and scale was shown by 2 AA patients. The mean size of the patch was (3.7 mm); 7% of them had a patch size of 10mm and more. The common areas involved by AA were beard area (29%), occipital (22%), vertex (10%), different areas (10%), frontal (6%), temporal (6%), etc. The common pattern of involvement was patchy (87%), followed by; patchy and sapho (5%), patchy, ophiasis & sapho (3%), patchy, ophiasis, totalis & beard area (2%), etc. Nail involvement was absent in 87% of AA patients, while 13% of them had nail involvement; 9% pitting, 3% biting and 1% ridging. AASI score was 0 in one AA patient, less than 25% in 73% of AA patients, 25-49% in 8% of AA patients, 50-74% in 9% of AA patients, 75-99% in 5% of AA patients and 100% in 4% of them (Table 3).

The mean TSH of AA patients was 8.23 mIU/L, while the mean T3 of them was 2.8 ng/dl, and the mean T4 of AA patients was 126.5 ng/dl. The mean of anti-TPO for AA patients was (26.35 IU/L) and the anti-TGT mean (53.35 IU/L) (Table 4).

No significant differences were observed between AA patients and controls regarding age (p=0.96) and sex (p=0.65). There was a significant association between single-status and AA patients (p=0.002). A significant association was observed between inside city residences and AA patients (p=0.01). A significant association was observed between alopecia areata (AA) disease and employment status, particularly among individuals working in both private and governmental sectors (p=0.03). There was a highly significant association between underweight and AA disease (p<0.001) (Table 5 and Figure 1).

The mean TSH was significantly higher among AA patients as compared to controls (p=0.02). Mean T3 was not statistically different between the two study groups. Mean T4 was significantly higher among AA patients as compared to controls. There was a significant association between positive anti-TPO and alopecia areata (p=0.05). A significant association was observed between positive anti-TGT and alopecia areata (p=0.004) (Table 6 and Figure 2).

No significant relationship between the AA severity and thyroid profile measures of AA patients was observed (p>0.05) (Table 7).

Although the long history of alopecia areata and its publicity all over the world, the etiology and mechanisms of this disease are limited. In general, the pathogenesis and clinical spectrum of alopecia areata are variations between different communities [16].

Mesinkovska et al. (2020) conducted a cross-sectional study in the USA. They proved that psychosocial burden is high in patients with alopecia areata and there is a significant relationship between single status and AA disease, which is similar to our study [34].

Harries et al. [35] conducted a population-based cohort study in the UK. They found that there is a significant relationship between the high incidence rate of alopecia areata and urban residence. Gorrell et al. [36], and Falkai et al. [37], also found that urbanization is associated with unhealthy diet, high stress, and other environmental factors that exacerbate alopecia areata. This result is consistent with the present study.

Kim et al. [38], did a study in South Korea, and reported that longer work duration is related to high probability of developing alopecia areata in men. This result is consistent with the present study.

Our study also found a highly significant association between underweight and AA disease. This finding parallels the results of study conducted by Almohanna et al. (2019), in Saudi Arabia. They showed that underweight along with vitamin and mineral deficiencies were associated with the risk of developing alopecia areata [39].  

The interesting finding in the present study was the significant increase in mean TSH among alopecia areata patients, as compared to controls. This finding is consistent with the results of Bakry et al. [40], who did a case-control study in Egypt on 50 patients with AA and 50 healthy controls; they found a significant increase in TSH level as compared to controls. Another study was conducted by Thomas and Kadyan [41], in India, that significantly prevalent hypothyroidism in patients with alopecia areata, as compared to controls. However, our study found no significant difference in T3 level between AA cases and controls. This finding coincides with the results of Odum et al (2018) [42], retrospective study in Nigeria which reported no significant difference in T3 level between AA cases and controls, but they showed an obvious relationship between thyroid dysfunction and alopecia areata. Our study found that mean T4 was significantly higher among AA patients as compared to controls. This finding is parallel to reports of Grymowicz et al. [43], a study in Poland which stated that hormonal disturbances especially in TSH and T4 lead to hair loss. Our study findings regarding TSH and T4 hormones effects on developing alopecia areata are consistent with the results of Almohanna et al, [40], case-control study in Iraq which found a significant differences in TSH and T4 hormones levels between AA cases and controls.

Rahnama et al. (2014), conducted a study in Iran; they observed a high level of positive Anti-TPO in patients with alopecia areata, which is consistent with the results of the present study [22]. On the other hand, according to the study conducted by Park et al. (2019), in South Korea, there is a significant relationship between positive anti-thyroglobulin antibodies and alopecia areata, which is in line with the present study [44]. Autoimmunity significantly contributes to the AA occurrence, and in instances where alopecia areata is accompanied by autoimmune thyroid diseases, both immune mechanisms play a substantial part in the onset of hair loss. T-cell-mediated immunity, similar to other autoimmune disorders, assumes a crucial function in this process [45, 46].

Conclusion

In conclusion, the thyroid dysfunctions play a major role in development of alopecia areata. The alopecia areata is highly related to thyroid autoimmunity disorders. The alopecia areata is more likely to be related to social deprivation, urbanization, occupation, and underweight. This study recommended the screening of thyroid hormones during the assessment of cases with alopecia areata.

Acknowledgements

The authors would like to present their gratitude and thank for the staff of Erbil Dermatology Teaching Centre.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' Contributions

All authors contributed to data analysis, drafting, and revising of the paper and agreed to be responsible for all the aspects of this work.

Orcid

Chiman Yousif Younis

https://orcid.org/0000-0001-5175-8653

Dindar Sharif Qurtas

https://orcid.org/0000-0002-2537-520X

Raza Hassan Muhammed

https://orcid.org/0000-0003-3276-4729

HOW TO CITE THIS ARTICLE

Chiman Yousif Younis, Dindar Sharif Qurtas, Araz Hassan Muhammed. Evaluation of Thyroid Biomarkers in Patients with Alopecia Areata. J. Med. Chem. Sci., 2023, 6(10) 2480-2493

DOI: https://doi.org/10.26655/JMCHEMSCI.2023.10.22

URL: https://www.jmchemsci.com/article_172159.html