Childhood Polyarthritis As Early Manifestation of Autoimmune Polyendocrinopathy with Candidiasis and Ectodermal Dystrophy Syndrome

Abstract

Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED) is a rare disorder of immune dysregulation caused by mutations in the autoimmune regulator (AIRE) gene. Individuals affected with APECED develop a clinical syndrome characterized by ectodermal abnormalities, autoantibody production, and organ-specific autoimmune manifestations. Inflammatory arthritis is usually not described as a part of the syndrome, and only sporadic cases are reported. We describe the case of a preschool-age girl who presented with hypoparathyroidism, hepatitis, interstitial pneumonitis, and chronic polyarthritis at 4 years of age and was found to have two compound heterozygous disease-associated mutations in the AIRE gene. We also conducted a literature review of the main characteristics of inflammatory arthritis in APECED patients. Our case and review demonstrate that (1) inflammatory arthritis, although rare, can be an early manifestation of APECED; (2) the diagnosis of APECED should be considered if mucocutaneous candidiasis, multiple organ-specific autoimmune manifestations, polyendocrinopathy, especially hypoparathyroidism or adrenal failure, or ectodermal dystrophy accompany joint symptoms; and (3) genotyping interpretation should take into account that mutations are found in the 14 exons of the gene, compound heterozygosity is common, and in some cases, only one or no mutated alleles are found.

Keywords: arthtritis; autoimmune polyendocrinopathy syndrome I; autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy; autoimmune regulator; chronic mucocutaneous candidiasis; hypoparathyroidism.

Figure 1

Right wrist radiograph. Radiographic changes consistent with damage secondary to inflammatory arthritis were observed. The patient had approximately a 6-month history of a decreased range of motion of right wrist. Widening of the scapholunate interval is noted on the AP view. Volar displacement of the capitate from the axis of the radius and lunate and volar rotation of the lunate are seen on the lateral view. Periarticular osteopenia and soft tissue swelling are seen on both views.

Figure 2

(A) Chest X-ray images during initial pneumonitis episode demonstrated interstitial infiltrates with ground-glass opacities of both lungs. (B) Chest CT scan demonstrating diffuse ground-glass opacities throughout both lungs without focal consolidation.

Figure 3

Genotyping. (A) Initial sequence analysis of exons 2, 3, 6, 7, 8, and 10 identified a non-sense heterozygous c.769C>T (R257X) mutation in exon 6 of the AIRE gene. This mutation is known to be disease causing and is the most common mutation found in European autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED) patients. (B) Subsequent sequencing of the remaining exons yielded a c.132 + 1_132 + 3delGTGinsCT splice site mutation in AIRE. The confirmation of AIRE compound heterozygosity in this patient was consistent with the clinical diagnosis of APECED.