Background: Yao syndrome (YAOS, OMIM 617321), formerly termed nucleotide-binding oligomerization domain 2( NOD2 )-associated autoinflammatory disease, is characterized by periodic fever, dermatitis, arthritis, and swelling of the distal extremities, as well as gastrointestinal and sicca-like symptoms. This disorder shares similar clinical phenotypes with hereditary periodic fever syndromes (HPFS) and thus can mimic one another.

Objectives: This study aimed to exemplify by a comparison of YAOS vs familial Mediterranean fever (FMF).

Methods: In this retrospective study, electronic medical records of a series of patients with YAOS were analyzed. All patients underwent genetic testing for periodic fever syndrome 6-gene panel (MEFV, TNFRSF1A, NLRP3, MVK, NLRP12 and NOD2).

Results: All patients were Caucasian and had recurrent fever, patchy erythema, arthralgia, and gastrointestinal symptoms (Table 1). With negative DNA sequencing for MEFV, these patients were treated with colchicine for presumed FMF, with a good response in patient 2 and minimal or transient response in other two patients. Further genetic testing identified the NOD2 variants. Unlike HPFS, YAOS is generally sporadic and is mostly reported in adults; spongiotic dermatitis is common; YAOS is associated with the NOD2 variants, IVS8 + 158 in nearly all patients, IVS8 + 158/R702W in up to 30%, and IVS8 + 158/1007fs, G908R or other rarer NOD2 variants in some patients.

Conclusion: YAOS can masquerade HPFS like FMF. Molecular analysis should cover NOD2 whole gene sequencing to help distinguish these diseases.

REFERENCES:

[1]Yao Q, et al. Dermatitis as a characteristic phenotype of a new autoinflammatory disease associated with NOD2 mutations. J Am Acad Dermatol. 2013;68(4):624-31.

Trueb B, et al. Coincidence of NOD2-Associated Autoinflammatory Disease (Yao Syndrome) and HCV Infection With Fatal Consequences: Interaction Between Genes and Environment. J Clin Rheumatol. 2018 Dec 28. doi: 10.1097/RHU.0000000000000963. [Epub ahead of print].

China

[2]Yao Q. Research letter: Effectiveness of canakinumab for the treatment of Yao syndrome patients. J Am Acad Dermatol. 2019.

[3]Yao Q, Shen M, McDonald C, Lacbawan F, Moran R, Shen B. NOD2-associated autoinflammatory disease: a large cohort study. Rheumatology (Oxford). 2015;54(10):1904-12.

[4]Yao Q, Shen B. A Systematic Analysis of Treatment and Outcomes of NOD2-Associated Autoinflammatory Disease. Am J Med. 2017;130(3):365 e13- e18.

[5]McDonald C, et al. Alterations in nucleotide-binding oligomerization domain-2 expression, pathway activation, and cytokine production in Yao syndrome. Autoimmunity. 2018;51(2):53-61.

Acknowledgments: The author is thankful to the statistician, Ms. Erin Taub for her help with making the table.

Disclosure of Interests: None declared