MON-047 - When Wheezing Is Not Asthma: Pulmonary Manifestations of AIRE-Related Autoimmune Polyendocrine Syndrome

Background
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene, resulting in defective central immune tolerance and multisystem autoimmunity. While classically defined by autoimmune endocrinopathies and chronic mucocutaneous candidiasis, APECED is increasingly recognized as a systemic immune disorder with impaired mucosal host defense. Pulmonary manifestations remain underrecognized and are frequently misattributed to common respiratory conditions. Reports of structural lung disease such as bronchiectasis in APECED are limited, contributing to delayed diagnosis.

Case Presentation
A 30-year-old woman with a longstanding diagnosis of APECED presented with progressive dyspnea, wheezing, and chronic cough refractory to standard asthma therapy. She denied fever or infectious symptoms. Laboratory evaluation revealed no leukocytosis, and chest radiography showed no acute abnormalities. She was treated for presumed asthma exacerbation without improvement. Given persistent symptoms and her underlying endocrine-immune disorder, further evaluation was pursued. Chest computed tomography demonstrated lower-lobe–predominant bronchiectasis. Bronchoscopy with bronchoalveolar lavage grew Staphylococcus aureus. Targeted therapy with intravenous linezolid led to rapid clinical improvement. She was discharged on inhaled corticosteroid–long-acting beta-agonist therapy. At follow-up, she remained clinically stable without recurrent exacerbations.

Discussion
APECED results from impaired thymic negative selection, allowing autoreactive T cells and pathogenic autoantibodies to persist. Autoantibodies against IL-17 and IL-22 disrupt mucosal immunity, predisposing patients to chronic airway infection, inflammation, and structural lung remodeling. This case highlights the risk of anchoring bias when respiratory symptoms in APECED are attributed solely to asthma, delaying appropriate investigation.

Conclusion
Pulmonary disease represents an underrecognized manifestation of AIRE-mediated immune dysregulation in APECED. Persistent wheezing or dyspnea in patients with autoimmune polyendocrine syndromes should prompt evaluation for structural lung disease and infection. Long-term pulmonary surveillance may be warranted in symptomatic patients to prevent irreversible lung damage.

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