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Autoimmune polyglandular syndrome-3C in a child

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Autoimmune polyglandular syndrome-3C in a child
Zafer Turkoglu1, Mukaddes Kavala1, Ozlem Kolcak2, Ilkin Zindanci1, Burce Can1
Dermatology Online Journal 16 (3): 8

1. Department of Dermatology, Göztepe Training and Research Hospital, Istanbul, Turkey.
2. Department of Radiology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.


Vitiligo is a chronic disorder that causes hypopigmentation in patches of skin. It occurs when the melanocytes, which are derived from neural crest, die or are unable to function. The precise pathogenesis is not yet fully understood but there is evidence suggesting it is caused by a combination of autoimmune, genetic, and neurohumoral factors. Autoimmune polyglandular syndrome (APS) is one of these diseases. APS has a rare incidence; its four subtypes are accompanied by multiple endocrine deficiencies. Autoimmune polyglandular syndrome-3C appears with autoimmune thyroid disease along with one of autoimmune pathologies of skin, neuromuscular system, and nervous system. We report a case of APS-3C in 12-year-old boy with generalized vitiligo, alopecia universalis, and Hashimoto thyroiditis that is the youngest of previous reported cases.


Autoimmune polyglandular syndrome (APS) has been defined as a wide spectrum of associations between various individual autoimmune endocrinopathies and exhibits overlap with other endocrine or non-endocrine autoimmune diseases. Autoimmune polyglandular syndrome is classified into four groups. These include a very rare juvenile type (APS-1), a relatively common adult type with adrenal failure (APS-2), a relatively common adult type without adrenal failure (APS-3), and combinations not included in the previous groups (APS-4) [1, 2]. Patients with APS-3 have autoimmune thyroid disease (AITD) without Addison disease, but with at least one associated organ specific autoimmune disease, such as type 1 diabetes mellitus, pernicious anemia, or alopecia. The subgroups (3A, 3B, 3C, 3D) indicate the form of the associated disease (Table 1) [1]. Here we report an extraordinary case of APS-3C with vitiligo, alopecia, and Hashimoto thyroiditis that is the youngest of previous reported cases.

Case report

Figure 1Figure 2
Figure 1. Diffuse alopecia on his head, eyebrows, and eyelashes with white hypopigmented multiple macules

Figure 2. Vitiligo patches located to his lower limbs

A 12-year-old boy was referred to our clinic because of milky-white patches on his face for three years and the loss of his hair and eyebrows for one year. The patient had no family history of such a disorder. Physical examination revealed multiple whitish, hypopigmented macules located around both eyes, around his mouth, and on his left forehead. In addition, hypopigmentation involved bilateral finger tips of the hands and feet, knees, ankles and the right areola. There was complete loss of hair on his head, trunk, axillary region, and genital region; there was loss of eyebrows and eyelashes (Figures 1 and 2). He was considered to have a generalized form of vitiligo with alopecia universalis.

Laboratory findings were within normal limits except raised thyroid-stimulating hormone: 7.25 µ IU/ml (normal range: 0.27-4.2) and thyroperoxidase antibody: 83.61 IU/ml (normal range: 0-34) levels. Antinuclear antibody (ANA), anticardiolipin antibody, anti-smooth muscle antibody (ASMA), anti-mitochondrial antibody (AMA), and anti-gastric parietal cell antibody (AGPCA) were negative. There was no evidence of type 1 diabetes mellitus after testing hemoglobin A1c and insulin. The patient had neither adrenal disease nor hypoparathyroidism. An ultrasonographic study of the thyroid gland showed that the parenchymal apperance of the gland was heterogeneous and diffusely hypoechoic; that these structural changes are radiologically common for AITD. Based on the findings our patient was diagnosed with hypothyroidism of Hashimoto thyroiditis. As a result of clinical and laboratory evaluation a diagnosis of APS-3C was considered.


Vitiligo is an acquired pigmentary disorder characterized by amelanotic patches surrounded by healthy skin. Vitiligo lesions may be localized or generalized and range from millimeters to centimeters in size. The lesions are often initially found on hands, forearms, feet and face. There are localized, segmental and universal forms of vitiligo with focal, dermatomal, linear, and whole body loss of pigment, respectively [3]. Our patient had generalized vitiligo with face and distal extremity involvement.

Autoimmune and neurohumoral mechanisms are involved in the development of vitiligo. A variety of autoimmune disorders such as AITD, adrenal insufficiency, pernicious anemia, and type 1 diabetes mellitus have been reported to be associated with vitiligo [3, 4, 5]. Autoimmune thyroid disease includes Hashimoto thyroiditis, primary myxoedema, symptomless autoimmune thyroiditis, Grave disease, pretibial myxoedema, and endocrine ophthalmopathy; it usually follows the onset of vitiligo in both adult and pediatric populations [1, 5]. In children, there have been conflicting studies regarding the association of vitiligo and AITD, predominantly producing hypothyroidism, as in our patient [6].

Autoimmune polyglandular syndrome-3 is an important condition among the other autoimmune diseases that occur with vitiligo. It is a rare syndrome that is characterized by the association of endocrine and non-endocrine organ specific autoimmune disorders in which T cell infiltration results in target cell dysfunction [7]. It has four subtypes according to its clinical course [1]. They are inherited autosomal recessively or in a polygenic pattern, triggered by enviromental factors [7, 8]. Autoimmune polyglandular syndrome-3C includes AITD, with one of the autoimmune diseases related to skin (vitiligo, alopecia areata) or the neuromuscular and nervous system (myasthenia gravis, multiple sclerosis) (Table 1) [1].

Alopecia areata is an organ specific autoimmune disease in which hair is lost in various patterns. Its most extreme form, alopecia universalis, is the total loss of all scalp and body hair. The association of autoimmune diseases such as alopecia areata and thyroiditis with vitiligo lend strength to the theory of an autoimmune basis [1, 2, 3, 9]. Alopecia areata involves predominantly a Th1 lymphocytic infiltrate just like the immunopathological pathway of Hashimoto thyroiditis. As an autoimmune disease, Hashimoto thyroiditis can also be associated with alopecia areata; more extensive alopecia was reported to show a higher percentage of thyroid disease [9, 10, 11, 12]. Our patient had the extensive form of alopecia areata, alopecia universalis.

There have been several theories that attempt to explain the polyglandular sydrome [2, 13, 14]. The most accepted and supported is the autoimmune genetic hypothesis. Autoimmune polyglandular syndrome-3 is often observed in individuals in the same family, suggesting that its inheritance could be an autosomal dominant trait with incomplete penetrance [13, 14]. Our patient’s family history did not reveal APS or AITD. HLA-DQB1*03 is the HLA haplotype frequently associated with AITD and the HLA-DRB1*04 haplotype of AITD is usually associated with vitiligo [15, 16]. Besides, alopecia areata is strongly associated with DQB1*03 and DRB1*1104. The frequency of HLA-DRB1*0401 and DQB1*0301 is remarkably increased among patients with alopecia totalis and those with alopecia universalis [17]. These results support the role of the HLA-DRB1*04 haplotype as a possible genetic locus that might be present in our patient with alopecia areata, Hashimoto thyroiditis, and vitiligo. However, we couldn’tdo this histocompatibility antigen study in our patient. Many studies have reported the association of anti-smooth muscle antibodies (ASMA), anti-mitochondrial antibodies (AMA), gastric parietal cell antibodies (GPCA), and anticardiolipin positivity with Hashimoto thyroiditis [1, 7, 18]. We did not determine any other autoantibodies with thyroperoxidase antibody in our patient. The patient had neither adrenal disease nor hypoparathyroidism. Therefore, we concluded that this patient has APS-3C that involved the coexistence of Hashimoto thyroiditis, vitiligo, and alopecia universialis [1]. This is an interesting case, because we could not find any previous report that has this combination in a patient as young as ours.

Vitiligo has classically been associated with thyroid diseases but the occurrence of vitiligo with thyroid disease and alopecia is observed uncommonly, especially in children. According to our knowledge this is the youngest case of APS-3C in the literature.


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