Yao Syndrome: An Overview of Genotypic Associations, Clinical Manifestations, Diagnosis, and Treatment.

Abstract

Background: Yao syndrome (YAOS) is a rare systemic autoinflammatory disorder (AID) of the innate immune system. It was recently categorized as genetically transitional disease (GTD) and is associated with NOD2 variants located at multiple NOD2 gene loci. Unlike most other periodic fever syndromes, the estimated disease prevalence is 1-10/100,000 with a predominance for females and white adult population. In this review, we aimed to provide a detailed analysis of different aspects of this syndrome to help better understand the underlying pathogenesis and incorporate the current evidence-based medicine published to diagnose and manage these patients.

Summary: We conducted literature search on YAOS from 2011 to 2024 using PubMed, Embase, and Scopus databases. Thirty-two studies were included in our narrative review. A descriptive analysis was performed of both Yao and non-Yao authored records to embrace the syndrome reported from all investigators and assess differences and similarities. The most reported gene variant is the homozygous IVS8+158 followed by compound heterozygous IVS8+158 and R702W. Mean age of disease onset is between 36 and 42 years. The mean age of disease diagnosis is between 40 and 45 years with a variable disease duration. Fever is the most commonly reported symptom followed by musculoskeletal, gastrointestinal symptoms and dermatitis. On laboratory workup, patients have elevated levels of erythrocyte sedimentation rate, C-reactive protein, and serum ferritin with negative autoantibody workup. Arthritic symptoms in YAOS patients have a positive response to sulfasalazine and glucocorticoids, while nonsteroidal anti-inflammatory drugs and colchicine produce minimal response. Anti-IL1 and anti-IL6 agents (canakinumab, anakinra, and tocilizumab) are effective treatment modalities.

Key messages: The evolving concept and acceptance of GTD will hopefully further our understanding about this SAID and similar disorders. We suggest developing a registry of patients with YAOS to keep track of expanding data on this subject. It is important to understand various aspects of YAOS including genetic and environmental factors, differential diagnosis, clinical manifestations, laboratory findings, and treatment options available to diagnose and manage these patients appropriately and timely.