Type I Polyglandular Autoimmune Syndrome Clinical Presentation

Updated: Nov 11, 2021
  • Author: Saleh A Aldasouqi, MD, FACE, ECNU; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Presentation

History and Physical Examination

Overview of clinical features

The 3 major components of polyglandular autoimmune (PGA) syndrome, type I, are (1) chronic mucocutaneous candidiasis, (2) hypoparathyroidism, and (3) autoimmune adrenal insufficiency.

The presence of all 3 components is not required to make a diagnosis; at least 2 components have to be present in an individual. Additional manifestations, including, among others, type 1A diabetes (documented autoimmune etiology), primary hypogonadism, pernicious anemia, malabsorption, autoimmune hepatitis, ovarian failure, pure red cell aplasia, alopecia, and vitiligo, may be present as well.

The first manifestation usually occurs in childhood, and the complete evolution of the 3 main diseases takes place within the first 20 years of life. Accompanying diseases continue to appear at least until the fifth decade of life.

Candidiasis usually is the first clinical manifestation, most often presenting in people younger than 5 years. Hypoparathyroidism occurs next, usually in people younger than 10 years. Lastly, Addison disease occurs in people younger than 15 years.

Overall, the 3 components occur in fairly precise chronological order, and they are present in roughly 40% of cases. As mentioned earlier, however, careful follow-up is mandatory to watch for the more dreadful manifestations, eg, adrenal insufficiency, regardless of the reportedly expected pattern of appearance.

The probability that multiple components of the disease will occur depends on how early the symptoms appear.

In a case of PGA-I reported by Bhansali and colleagues, no candidiasis was noted in an East Indian boy aged 16 years. [5]

Mucocutaneous candidiasis

This condition usually occurs earliest and is the most common of the 3 main diseases of PGA-I.

Assess any young person with moniliasis for a possible state of T-cell deficiency and PGA-I.

Between 50% and 100% of patients with PGA-I develop a recurrent monilial infection. Most of the lesions are limited to the skin (usually < 5% of surface area), nails, and oral and anal mucosa. [16]  Esophageal involvement may be complicated by strictures and stenosis.

Even though the presence of candidiasis is consistent with a T-cell defect, no increased frequency of other opportunistic infections exists.

Because these patients have a normal B-cell response to candidal antigens, they are spared from developing disseminated candidiasis.

Hypoparathyroidism

Hypoparathyroidism is the first endocrine disease to occur during the course of PGA-I, usually developing after candidiasis and before Addison disease. [4]  In the case of a 50-year-old man with PGA-I reported by Lima Ferreira et al, the first and only manifestation for decades was hypoparathyroidism. [13]

Antiparathyroid antibodies have been reported in 10-40% of patients with hypoparathyroidism; however, whether these are being confused with mitochondrial autoantibodies is still under debate. The pathologic significance of these antibodies is not clear.

Other disease states presenting with neonatal hypocalcemia (DiGeorge syndrome or congenital absence or malformation of the parathyroid) must be differentiated from PGA-I. DiGeorge syndrome results from a congenital defective disorder of the branchial clefts. It manifests as hypoparathyroidism and cutaneous candidiasis; unlike PGA-I, DiGeorge syndrome does not involve the adrenal glands.

More than 75% of patients develop hypoparathyroidism, which usually presents in persons younger than 10 years.

Clinical features may include, among others, (1) tetanic clinical symptoms, such as carpopedal spasm and paresthesias of the lips, fingers, and feet; (2) seizures; (3) laryngospasm; (4) leg cramps; (5) diffuse mild encephalopathy; (6) cataracts; and (7) papilledema. Electrocardiography may show a prolonged QT interval.

Adrenocortical failure (Addison disease)

Addison disease typically occurs in people aged 10-30 years (mean, 12-13 y); it usually is the third disease to appear in PGA-I.

Mineralocorticoid and glucocorticoid deficiencies usually arise simultaneously, but their onset can be dissociated by up to 3 years.

CYP21 appears to be the major autoantigen in isolated Addison disease and Addison disease associated with PGA-II. Autoantibodies to CYP17 and a side-chain cleavage enzyme (CYP11A1) have been associated with Addison disease in PGA-I.

Early symptoms include weakness, fatigue, and orthostatic hypotension.

Pigmentation usually is increased and may serve as a differentiating point from secondary hypoadrenalism (primary pituitary failure).

Anorexia, nausea, vomiting, diarrhea, and cold intolerance often occur.

Late symptoms include weight loss, dehydration, hypotension, and a small-sized heart.

Less common clinical manifestations

Less common clinical manifestations include the following:

  • Hypergonadotropic hypogonadism (primary hypogonadism)

  • Type 1 diabetes mellitus

  • Autoimmune thyroid disease (not including Graves disease)

  • Pernicious anemia

  • Chronic atrophic gastritis

  • Chronic active hepatitis

  • Enamel hypoplasia, which occasionally precedes the onset of hypoparathyroidism

  • Asplenia

  • Keratoconjunctivitis

  • Cholelithiasis

  • Malabsorption

  • Alopecia

  • Vitiligo

  • Interstitial nephritis

  • Pure red cell aplasia

Physical examination

Physical findings in polyglandular autoimmune (PGA) syndrome, type I, are dependent on the components of the syndrome that are clinically manifested at the time of examination.