A Systematic Analysis of Treatment and Outcomes of NOD2-Associated Autoinflammatory Disease

Abstract

As a systemic disease, Yao syndrome uncommonly affects the solid internal organs, but it can be complicated with chronic pain syndrome and even disability. Glucocorticoids or sulfasalazine may be considered as the first-line treatment option, and interleukin (IL)-1/IL-6 inhibitors may be tried for refractory cases. The potential associations between certain comorbidities and Yao syndrome deserve further study.

Alterations in nucleotide-binding oligomerization domain-2 expression, pathway activation, and cytokine production in Yao syndrome

“…More recently, specific NOD2 variants have been linked to Yao syndrome (YAOS, OMIM#617321), a systemic autoinflammatory disease (SAID) characterized by recurrent episodes of fever, dermatitis, and inflammatory arthritis ( Figure 1 ) (4–6). All YAOS patients carry NOD2 variants (6), and nearly all patients are heterozygous for a C>T single nucleotide polymorphism (SNP) in intron 8 of NOD2 (rs5743289, IVS8 +158 ) (6, 7).…”

“…All YAOS patients carry NOD2 variants (6), and nearly all patients are heterozygous for a C>T single nucleotide polymorphism (SNP) in intron 8 of NOD2 (rs5743289, IVS8 +158 ) (6, 7). Approximately 20% of patients carry both IVS8 +158 and a nonsynonymous C>T SNP that results in an arginine to tryptophan substitution at amino acid 702 (rs2066844, R702W; haplotype IVS8 +158 /R702W) (4, 6, 8). Other rarer NOD2 variants have also been identified at a low frequency in the disease (6).…”

“…YAOS patients are predominantly white adults with a female to male ratio of 2:1 at an estimated disease prevalence of 1–10/100,000(6). YAOS was initially identified in the United States (4, 12) and reports are now appearing in Europe (13). Disease occurrence is primarily sporadic, although a minority of patients can have a positive family history (4, 14).…”

“…YAOS was initially identified in the United States (4, 12) and reports are now appearing in Europe (13). Disease occurrence is primarily sporadic, although a minority of patients can have a positive family history (4, 14). Apart from the characteristic clinical phenotype described above, patients can also have distal lower extremity swelling, gastrointestinal, and sicca-like symptoms (10, 15).…”

“…Approximately 50% of YAOS patients experience frequent and severe flares despite treatment with glucocorticoids and sulfasalazine, which are more effective compared with other disease modifying anti-rheumatic drugs (4). To meet the outstanding therapeutic challenge, a search for more effective, targeted therapies is warranted.…”