Background/Purpose: Yao syndrome (YAOS, OMIM 617321) is formerly named Nucleotide-binding oligomerization domain containing protein 2 (NOD2)-associated autoinflammatory disease affecting multiorgan systems characterized by recurrent fever, dermatitis, arthralgias, gastrointestinal, sicca symptoms, eyelid swelling, and distal leg swelling. Sicca symptoms are common in YAOS, which can be confused with Sjögren’s syndrome. This study aimed to compare the clinical and laboratory characteristics between YAOS and primary Sjögren’s Syndrome (pSS).  

Methods: A retrospective study of 27 adult patients with YAOS seen in the Center of Autoinflammatory Disease at Stony Brook University Hospital between 2015 and 2025 was conducted. YAOS was diagnosed based on our prior published criteria in the American Journal of Medicine in 2017. Since the presence of certain NOD2 gene mutations is required for the diagnosis of YAOS, a periodic fever syndrome gene panel was performed for all these patients. To compare patients with pSS, we also performed a chart review of 29 adult patients with pSS diagnosed in the same Institution during the same period. Patients with pSS were diagnosed based on the 2016 ACR/EULAR diagnostic criteria. Categorical variables were compared between the YAOS and pSS groups using either Fisher’s exact test or the Chi-squared test. Continuous variables were compared using two-sample t-tests.

Results: In both YAOS and pSS groups, females were predominant, and an overwhelming majority of patients were Caucasian. Disease onset occurred at an earlier age in YAOS than pSS (27.7 ± 13.9 vs. 42.7 ± 15.2 years, p = 0.002). Although Sicca symptoms were common in both diseases, compared with pSS, several presentations were significantly more frequent in YAOS, including fever (66.7% vs. 10.3%, P=0.00002), rash (100% vs. 24.1%, p < 0.000001), eyelid swelling (52% vs. 0%, p = 4.1 × 10⁻⁵), abdominal pain (70.4% vs. 20.7%, p = 5.2 × 10-4), and non-bloody diarrhea (51.9% vs. 14.3%, p = 0.007) (Table to be presented). In addition, oral ulcers, chest pain, arthralgia, and asthma were more common in YAOS. All patients with pSS had positive autoantibodies, SSA in particular, whereas patients with YAOS did not have elevated autoantibodies in general.

Conclusion: While both YAOS and pSS share sicca symptoms, YAOS possesses a characteristic manifestation and distinctive clinical constellation from pSS. Since therapeutic approaches and outcomes differ between these two conditions, this study will further increase awareness of YAOS, an underdiagnosed disease, to avoid diagnostic confusion. References: Yao Q et al. A Systematic Analysis of Treatment and Outcomes of NOD2-Associated Autoinflammatory Disease. Am J Med. 2017 Mar;130(3):365.e13-365.e18. Nomani H et al. Comprehensive clinical phenotype, genotype and therapy in Yao syndrome. Front Immunol. 2024 Sep 20;15:1458118.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-comparative-study-of-yao-syndrome-and-primary-sjogrens-syndrome/