A Chinese case series of Yao syndrome and literature review

Abstract

Yao syndrome (YAOS), formerly named NOD2-associated autoinflammatory disease, is a periodic disease characterized by fever, dermatitis, polyarthritis, distal extremity swelling, and gastrointestinal and sicca-like symptoms associated with specific NOD2 sequence variants. All patients in the literature were Caucasians. Herein, we report the first case series of YAOS in China to further expand the clinical and genetic characteristics of this disorder. A retrospective review of patients who were diagnosed with YAOS at our tertiary medical center was conducted. Three Han Chinese women with YAOS were included. Recurrent fever occurred in all patients and each febrile episode lasted several days to several weeks, and asymptomatic intervals ranged from several weeks to several months. Two patients experienced intermittent arthritis/arthralgia and abdominal pain, and one had sicca-like symptoms. None had dermatitis. Three variants in NOD2 were identified, including Q902K, R541P, and Y514H. The patients' symptoms significantly improved after treatment with glucocorticoids and/or sulfasalazine. YAOS exists in the Chinese population, and it may be a global disorder. Our patients appear to exhibit somewhat distinct clinical phenotypes from those in the Caucasian population, and three novel NOD2 variants have been identified in the disease.

New insights on multigenic autoinflammatory diseases

“…Also, the cells of the patients had high basal IL-6 levels which were increased by muramyl dipeptide stimulation, indicating that NOD2 expression and pathway activation are aberrant in YAOS. 242 In a case series, 241 genetic testing in three YAOs patients detected presence of the following heterozygous NOD2 variants:…”

“…The molecular mechanisms and underlying pathogenesis of YAOS are unclear, but there is a genetic association with certain NOD2 variants. 239 , 241 A study that examined NOD2 expression and activation of signaling pathway reported that NOD2 transcript level and basal p38 mitogen-activated protein kinase activity was elevated in peripheral blood mononuclear cells from IVS8 + 158 YAOS patients. Also, the cells of the patients had high basal IL-6 levels which were increased by muramyl dipeptide stimulation, indicating that NOD2 expression and pathway activation are aberrant in YAOS.…”

“…Erythematous patches or plaques can be seen in patients with YAOS, and recurrent mild to moderate abdominal pain, bloating, cramping, and diarrhea may also be present. 80,240,241 YAOS is a systemic inflammatory disease which can lead to chronic pain syndrome and disability, but it rarely affects the solid internal organs. 79 The diagnosis of YAOS is mainly dependent on the phenotype and genotype characteristic of the disease.…”

Cutaneous manifestations of autoinflammatory diseases

“…YAOS, formerly termed NOD2 -associated autoinflammatory disease (NAID), is a polygenic AID characterized by recurrent fever, dermatitis, arthritis, swelling of the distal extremities, gastrointestinal and sicca-like symptoms with eyelid swelling. [ 44 ] The disorder has a genetic association with certain NOD2 variants. [ 45 ] Intermittent dermatitis develops in 90% of YAOS patients, which often manifested as erythematous patches, flushing, and plaques ( Figure 1I ).…”

Expansion of Phenotypic and Genotypic Spectrum in Yao Syndrome

“…14 The disease is reported in North America, 15 Europe, 16,17 and Asia. 18 With the disease being increasingly recognized among the medical community, we have gained first-hand experience and advanced knowledge on the disease. Herein, we report new clinical and molecular data to expand the spectrum of YAOS.…”