Abstract Introduction Intermediate sweat chloride values are typically seen in individuals with Cystic Fibrosis Related Disorder, however with negative Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) genetic testing, alternative diagnoses should be considered. We present a case of Autoimmune Polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) that resulted in abnormal sweat chloride testing. Case Report A 14 year old male with a history of recurrent pneumonia, bronchiectasis, enamel hypoplasia, mucocutaneous candidiasis, and chronic otitis media was admitted for persistent cough, poor growth, and chronic diarrhea. On examination, he had oral thrush, diffuse inspiratory crackles, and weight below 1st percentile. Sweat chloride testing revealed intermediate values of 50 mmol/L and 42 mmol/L; comprehensive CFTR sequencing was negative. Bronchoscopy demonstrated copious purulent secretions, with cultures positive for Pseudomonas aeruginosa and Candida Albicans. Fecal pancreatic elastase was low (142 µg/g), consistent with pancreatic insufficiency. Additional testing was significant for low serum sodium. Immunologic evaluation revealed impaired lymphocyte proliferation to Candida and Tetanus, as well as markedly elevated CXCL9 (1, 925 pg/mL). Genetic testing identified a homozygous pathogenic AIRE variant (c. 967₉79del; p. Leu323Serfs*51), confirming the diagnosis of APECED. He is being managed with an intensive airway clearance regimen- inhaled bronchodilators, hypertonic saline, chest vest and every other month inhaled tobramycin. Ruxolitinib was initiated for the immune dysregulation. Demonstrable improvements were noted in cough, bowel movements, and growth. A repeat CT chest and pulmonary function test showed improvement. Discussion APECED results from AIRE mutations that impair central tolerance, leading to exaggerated type-1 immune responses characterized by excess interferon-γ (IFN-γ). It commonly presents with the classic triad of mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency with pneumonitis and bronchiectasis increasingly encountered as complications. Abnormal sweat chloride values have been reported in several dermatologic and autoimmune conditions. In these disorders, local epithelial inflammation, barrier disruption, and sweat duct injury are thought to impair normal chloride reabsorption. We postulate that immune-mediated epithelial and glandular inflammation might have disrupted sweat duct function and accounted for the elevated sweat chloride values. The mechanisms underlying abnormal sweat chloride in APECED are poorly understood, particularly the interplay between autoimmunity, glandular dysfunction, malnutrition, and adrenal insufficiency. It is therefore important to consider alternative diagnoses, initiate genetic workup to facilitate timely recognition, and guide tailored management in patients with an unclear clinical picture, particularly when sweat chloride values are in the intermediate range and CFTR genetic testing is negative. This abstract is funded by: none
Shehata et al. (Fri,) studied this question.