APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy), also known as APS-1, is a rare monogenic autoimmune disease caused by loss-of-function mutations in the AIRE gene. This impairs central immune tolerance, leading to autoreactive T lymphocytes and autoantibodies against various organs. It typically presents with chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency, plus other diverse manifestations. Novel therapeutic strategies, such as Janus kinase (JAK) inhibitors, are crucial for improving clinical management.
We present the case of a 37-year-old female patient with a molecularly confirmed diagnosis of APECED. Her comprehensive clinical history includes severe recurrent hypocalcemia due to hypoparathyroidism, adrenal insufficiency, universal alopecia areata, chronic mucocutaneous candidiasis (onicomycosis, oral candidiasis), multiple verrucae, chronic diarrhea, hypogonadism, dry eye with corneal erosions, dyslipidemia, renal lithiasis, bilateral cataracts, and an epileptic syndrome. Parental consanguinity was identified; her older brother, also diagnosed with APECED, passed away in his third decade of life from complications of his disease. Genetic analysis revealed a pathogenic variant, c.232T>C (p.W78R) in homozygosity in the AIRE gene, consistent with autosomal recessive inheritance. This variant is classified as pathogenic in ClinVar (ID. 189060) and Human Genome Mutation Database (CM012586) and has a population frequency (minor allele frequency: 0.000007970, gnomAD). Current treatment includes symptomatic and hormone replacement therapies. Ruxolitinib was initiated in May 2024. By April 2025, (approximately 11 months of treatment), the patient demonstrated significant improvement, including hair regrowth, resolution of plantar verruca, and partial improvement of onychodystrophy. This case is notable due to the patient's adult age, contrasting with the predominantly adolescent or young adult cases typically reported.
This case highlights APECED's marked complexity and multisystemic nature. The favorable clinical response to ruxolitinib in multiple manifestations underscores the significant potential of targeted immunomodulatory therapies. These findings suggest JAK/STAT pathways are involved in APECED pathogenesis and that JAK inhibitors can improve patient quality of life.
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