**2.4. Discusion**

304 Thyroid Hormone

Type of

types of alopecia areata

(P=0.047472) (Table 4.)

12

1

value115 IU/ml)

0

5

10

15

20

25

30

35

(Table 5).

anti-Tg

Total 54 16 70

30

7

(threshold value115 IU/ml) Types of alopecia areata (P)

alopecia areata Negative n Positive n Total Multiloculares Totalis Universalis Unilocularis 12 1 13 0.662246 0.160248 0.047472\* Multiloculares 30 7 37 N/A 0.426673 0.085080 Totalis 8 4 12 N/A N/A 0.647916 Universalis 4 4 8 N/A N/A N/A

**Table 4.** The frequencies of positive detectable thyroid autoantibody (anti-Tg) and differences between

A Fisher's exact indicated significant association between higher values of anti-Tg (values more than 115 IU/ml) and some types of alopecia areata, Universalis vs Unilocularis

> **Types of alopecia areata and frequencies positive/negative values of anti-Tg (threshold value115 IU/ml)**

**Scheme 3.** Types of alopecia areata and frequencies positive/negative values of anti-Tg (threshold

Unilocularis Multiloculares Totalis Universalis

8

4

Negative Positive

4 4

A Fisher's exact indicated significant association between higher values of anti-TPO (values more than 34 IU/ml) and some types of alopecia areata: Unilocularis vs Totalis (P=0.005217), Unilocularis vs Universalis (P=0.000069) and Multiloculares vs Universalis (P=0.000925) Alopecia areata is an ancient disease that was known to Egyptians even in the pre-Christian time [33]. Despite its long history, our knowledge is actually limited. Today, AA is hypothezed to be an autoimmune, organ specific T-cell mediated reaction directed against an unknown autoantigen of the hair follicle. T lymphocytes that have been shown to be oligoclonal and autoreactive are predominantly present in the peribulbous inflammatory infiltrate [34]. Although the skin is the primary location of the clinical phenotype, the determination of disease expression involves a complex interplay between different

inflammatory cell subsets in the skin, skin draining lymphonodes, and spleen of the affected individuals [35].

Thyroid Autoimmunity in Patients with Skin Disorders 307

association with alopecia areata. Although their etiology is still unclear, the autoimmune

The nature of the relationship between anti-thyroid autoimmunity and the pathogenesis of autoimmune diseases is presently unknown. Some authors have shown that anti-Tg antibodies can form immune complexes [46], and anti-microsomal antibodies not only bind to thyroid peroxidase but also modulate natural killer cell activity in autoimmune thyroiditis [47]. Possible explanations for the relationship of these autoimmune diseases include: (1) immunomodulatory effects of antithyroid antibodies, (2) molecular mimicry between thyroid and disease-specific epitopes, and (3) genetic link between anti-thyroid autoimmunity and the susceptibility to autoimmune disease [48]. It is a multidisciplinary problem requiring cooperation of specialists in different fields of medicine. Both dermatologists and endocrinologists have to inquire their patients about the family history

This chapter is an attempt to update the current knowledge about the relationship between the thyroid and the skin diseases. Although cutaneous manifestations of autoimmune thyroid diseases are well described and thyroid hormone is known to regulate the development and function of skin, a better understanding of these processes is needed.

[1] Mullin GE, Eastern JS (1986) Cutaneous signs of thyroid disease. Am Fam Physican. 34:

[2] Mullin GE, Eastern JS (1986) Cutaneous consequences of accelerated thyroid function.

[3] Safer JD, Crawford TM, Fraser LM, Hoa M, Ray S, Chen TC at al. (2003) Thyroid hormone action on skin: Diverging effects of topical varsus intraperitoneal

[4] Holt PJA (1978) In vivo responses of the epidermis to triiodthyronine. J Invest Derm. 71:

[5] Leonhardt JM, Heyman WR (2002) Thyroid disease and the skin. Dermatol Clin. 20:473-

of autoimmune diseases and to look for associated autoimmune disorders.

*Department of Dermatovenerology, Sarajevo University Clinical Center, Sarajevo,* 

*Department of Clinical Pharmacology, Sarajevo University Clinical Center, Sarajevo,* 

hypothesis is most commonly accepted.

**Author details** 

Emina Kasumagic-Halilovic\*

*Bosnia and Herzegovina* 

*Bosnia and Herzegovina* 

Cutis. 37: 109-114.

administration. Thyroid. 13: 159-165.

Begler Begovic

**4. References** 

93-98.

202-204.

Corresponding Author

481.

 \*

Clinical association with AA has known for many years. AA frequently occurs in association with other autoimmune disorders such as vitiligo, lupus erythematosus, pernicious anemia and others [34, 36-38]. Among endocrine disorders, thyroid diseases are the commonest that has been described as associated with AA, but the issued values were different. In the greatest study reported till now, Muller and Winkelmann have found the evidences of different types of thyroid disease in 8% of 736 patients in compare to less than 2% of the control population in North America [39]. Broniarczyk-Dyla *et al.* observed abnormalities of thyroid structure and function in even 78% of AA patients [40]. Conversely, Puavilai *et al.* estimated that the prevalence of thyroid disease is relatively low (7.2%) and was not statistically different from the control group [41].

In accordance to previous studies, current study reported a high frequency of thyroid diseases in AA patients. We detected elevated anti-Tg in 16 (23%) and elevated anti-TPO in 21 (30%) of patients with AA. Compared with the control group, the frequency of the both anti-Tg and anti-TPO antibodies was significantly higher in those with AA. Statistically significant difference was also found in values of anti-Tg and anti-TPO between patients with different clinical type of the disease. The highest anti-Tg concentrations were observed in patients with alopecia universalis. Patients with thyroid diseases were on an average older and reported longer duration, but the results were not statistically significant. These results are consistent with a clinical study performed by Seyrafi *et al.* [32]. They analyzed serum TgAb level in 123 Iranian patients with AA and found it to be elevated in 29.3% of study patients. Grandolfo *et al.* observed the presence of thyroid autoantibodies in even 44% of AA patients [42]. Goh *et al.* also confirmed the frequent coexistence of AA and thyroid abnormalities [43]. They found 19% of probands with thyroid disease including simple goitre, Grave´s disease and Hashomoto´s thyroiditis. Our findings showed that the frequency of anti-TPO was more significant than anti-Tg. This antibody, historically referred to as the antimicrosomal antibody, is established as a sensitive tool for the detection of early subclinical autoimmune thyroid diseases and identification of at-risk cases for autoimmune thyroid diseases [44]. Nordyke *et al.* reported that anti-TPO antibody tends to have more correlation than does the anti-Tg antibody [45].

Alopecia areata offers many benefits as a model for the study of autoimmunity, in that it can be used to identify the contributing roles of immunogenetics and neuroendocrine factors in the initiation and propagation of autoimmune disease [24].

The study revealed a significant association between AA and thyroid disease and showed the tests used to detected thyroid autoantibodies to be relevant in patients with AA. Further exploration of this relationship in clinical setting and at a molecular level may help in the understanding of the pathogenesis of both diseases.
