Alopecia Areata Universalis in the Onset of Autoimmune Polyendocrine Syndrome Type III C.

Alopecia areata (AA) is an organ-specific autoimmune disease which affects hair follicles. It usually presents as a transient patchy hair loss, but it can sometimes progress into more severe forms such as AA totalis or AA universalis (AAU). Different autoimmune diseases, as well as autoimmune polyglandular syndromes (APS), have been associated with AA, especially with Type I and Type II APS. Herein, we describe the case of a 16-year-old boy with a severe form of AAU and early onset of adult APS, Type III C. As far as we are aware, this combination of AAU, Hashimoto thyroiditis, and Type I diabetes in a teenager has not been previously described in the literature. Furthermore, the early onset of AAU followed by a premature debut of adult APS Type III is again unique, which is why we report this case. Copyright:

INTRODUCTION

Alopecia areata (AA) is an organ-specific autoimmune disease mediated by CD8 + T cells which affect hair follicles.[1] Different autoimmune diseases, as well as autoimmune polyglandular syndromes (APS), have been associated with AA.[2] AA universalis (AAU), the most severe form of AA, has rarely been reported in association with APS.[2345] In addition, the association with cutaneous autoimmune diseases such as vitiligo and alopecia appears to occur more often in APS Type I patients rather than in the adult type.[6] Herein, we describe the case of a 16-year-old boy with a 10-year long history of AAU and early onset of adult APS, Type III C.

CASE REPORT

We present the case of a 16-year-old boy with a 10-year history of AAU. It first started as patchy AA and then gradually progressed to total hair loss. The grandfather also had universal alopecia. Five years ago, the boy was diagnosed with Hashimoto thyroiditis, and substitutive levothyroxine 150 μg daily treatment was initiated. He tested positive for thyroid peroxidase autoantibodies with a value of 314.7 UI/mL (normal range [NR] 0–34) and had elevated levels of thyroid-stimulating hormone (80.57 μUI/mL; NR: 0.51–4.30) with normal free thyroxine. One year ago, he presented with polyuria, polydipsia and blood tests revealed hyperglycemia (314.4 mg/dL; NR 50–80), a glycosylated hemoglobin value of 10.4% (NR 4.8–5.9), borderline normal C-peptide values (1.10 ng/mL; NR: 1.1–4.4), and negative anti-insulin antibodies. He was diagnosed with Type I diabetes and substitutive insulin treatment was started. The association of AAT with Hashimoto thyroiditis and Type I diabetes, in the absence of other endocrinopathies, is specific for Type III C autoimmune polyglandular syndrome.

Clinical examination revealed a complete absence of scalp and body hair. In addition, nail changes in the form of trachyonychia and longitudinal ridges involving three fingers were observed [Figure 1]. Trichoscopy of the scalp and eyebrow area was performed to assess the integrity of the follicular units. Typical features of AA were found: multiple yellow dots, few vellus hairs, and areas devoid of any follicular units.

Figure 1

(a) Profile image: absence of scalp, eyebrow, and eyelash hair. (b) Nail involvement: trachyonychia and longitudinal ridges (affecting 3 out of 10 fingers)

DISCUSSION

AA is a frequent nonscarring type of alopecia with an autoimmune etiopathogenesis. It has no sex predilection and can present at any age.[2] Our study presents an early onset of AAU at the age of 6 years old in an infant with positive family history.

Poor prognosis of hair regrowth in AA has been associated with factors such as extensive hair loss, long duration of hair loss, nail involvement, a history of atopy, concomitant autoimmune diseases, and young age of first onset.[2] The particular presentation of universal alopecia in our case with an age of onset at 6 years old associated with long duration of hair loss (10 years), family history of AAU, nail involvement, autoimmune thyroiditis, and Type I diabetes has most of the criteria linked to poor prognosis.

Trichoscopy is a useful tool in assessing disease activity. Characteristic trichoscopic features of AA are black dots, exclamation mark hairs, broken hairs, yellow dots, and clustered short vellus hairs. In a study by Hamidreza et al., yellow dots and vellus hairs were the most common features in patients with universalis subtype of AA. Regarding scalp severity, yellow dots related positively, while vellus hairs, broken hairs, and exclamation mark hairs related negatively.[7] Our findings are in consistency with this study. Trichoscopic examination revealed multiple, heterogeneous yellow dots, and few vellus hairs in a patient with a long history of AAU [Figure 2].

Figure 2

Trichoscopic images of scalp hair. (a) Area with minimal hair regrowth after local caffeine treatment: one and two thin hairs per follicular unit, multiple yellow dots, and few vellus hairs. (b) Area with no hair regrowth: multiple, heterogeneous yellow dots, and the absence of follicular units

Sergio et al. described previous or concomitant autoimmune diseases which were detected in 23% of the patients with AAT and AAU in their study. Thyroid disease was the most prevalent (20%), followed by vitiligo (3%) and diabetes mellitus Type I (2%). %). Other comorbidities were atopic dermatitis (20%), dislipidemia (9%), high blood pressure (5%), psoriasis (3%), and previous cancer in two patients. Clinically, nail involvement was observed in 20% of the patients.[2] In AA nail changes have been described in the form of trachyonychia, pitted nail, or longitudinal ridges. The frequency of nail changes increases with disease severity.[1] In our case too, nail changes have been observed by the patient to appear a few months ago, after almost 10 years of AA progression and after Hashimoto thyroiditis and Type I diabetes diagnosis only recently, after a long disease progression.

AAU has rarely been reported in association with APS. The classification of APS[58] is presented in Table 1. With a monogenetic inheritance, the prevalence of APS I is estimated at 1:100,000 and it is usually diagnosed during infancy. In contrast, the adult form of APS is determined by multiple genes, has a higher prevalence of 1:20,000 and is recognized beyond the age of 20 years with a manifestation peak in the fourth and fifth decades.[6] However, in our case, APS Type III has an unusually early onset. We have not found cases with a similar debut in the literature.

Table 1

Classification of autoimmune polyglandular syndromes

PAS type	Characteristics
Juvenile
Type I	Chronic candidiasis, chronic hypoparathyroidism, and Addison’s disease (at least two present)
Adult
Type II	Addison’s disease (always present), autoimmune thyroid disease and/or diabetes mellitus Type I
Type III	Autoimmune thyroid disease associated with another autoimmune disease (excluding Addison’s disease and/or hypoparathyroidism)
IIIA	APS Type III + endocrine diseases
IIIB	APS Type III + gastrointestinal or hepatic autoimmune diseases
IIIC	APS Type III + skin or neuromuscular or nervous system autoimmune diseases
IIID	APS Type III + collagen diseases, vasculitis, or hematologic autoimmune diseases
Type IV	Combinations of glandular autoimmune diseases that are not included in the previous groups

Although the exact pathogenesis remains uncertain, it is assumed that AA is an organ-specific autoimmune disease mediated by autoreactive CD8 + T cells targeted at hair follicles. There are variable reports on serologic findings in patients with AA and the tendency for them to show higher levels of autoantibodies than the general population. Therefore, the association between AA and other autoimmune diseases is well established.[1] The decision to treat AAU should take into account the risk of adverse effects as well as the duration of the response. Unfortunately, no therapy has been shown to have a significant long-term effect compared to placebo.[2] This is a severe form of AAU with many poor prognosis criteria, including concomitant autoimmune diseases and a particularly early onset of adult APS, which make it highly unlikely to respond to treatment. There is no current evidence to support the fact that systemic treatment for concomitant autoimmune diseases would influence the evolution of AAU.

To our knowledge, AAU in association with APS Type II has been reported in two instances and only once with APS Type I.[345] Sheehan et al. also described an unusual case of silent thyroiditis, isolated corticotropin deficiency, and alopecia universalis in a patient with ulcerative colitis and elevated levels of plasma factor VIII in a 43-year-old man, which would qualify as a case of adult Type III APS.[9] The only other case of AAU with APS Type III described in the literature is a 33-year-old male who underwent chemotherapy for Hodgkin lymphoma.[10] However, the effects of ABVD chemotherapy should be considered in generalized hair loss.

This might be the first case report of AAU in association with early-onset APS Type III. As far as we are aware, this combination of AAU, Hashimoto thyroiditis, and Type I diabetes has not been previously described in a teenager. We consider that screening for autoimmune diseases, especially for thyroid disease in pediatric patients with AA, is extremely important and should be regulated. In addition, we postulate that the poor prognosis of AA might predict an early onset of other autoimmune diseases or even syndromes.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

The authors received no financial support and/or sponsorship.

Conflicts of interest

The authors declare no conflicts of interest.