Updated: 11/23/25
Considerations for Treatment & Management
Treatment in patients with mild disease may be achieved with short courses of oral glucocorticoids for flares and daily hydroxychloroquine and/or sulfasalazine.
First Line Treatment - DMARDs
Hydroxychloroquine (Plaquenil)
Hydroxychloroquine (HCQ) blocks IL-1, IL-6, and IFN-γ production. HCQ also has an effect on the arachidonic acid cascade caused by downregulation of phospholipases. Other Benefits: HCQ inhibits platelet adhesion and aggregation, leading to an anti-thrombotic effect. HCQ favorably alter the lipid profile, with reductions in total cholesterol, triglycerides, VLDL, and LDL, particularly in patients on concomitant corticosteroid therapy.
Sulfasalazine (Azulfidine)
Sulfasalazine (SSZ) is commonly used in ulcerative colitis and Crohn's Disease. SSZ has both anti-microbial and anti-inflammatory properties. It weakly inhibits the pro-inflammatory effects of the arachidonic acid cascade.
Note: Combination Therapy, whether step-up or initial therapy, has been shown in multiple trials to be superior than monotherapy without increase in toxicity.
Second Line - IL-1 Inhibitors
Canakinumab (Ilaris)
Canakinumab is a monoclonal antibody of the IgG1κ isotype. It binds to IL-1β and neutralizes its activity by blocking interaction with IL-1 receptors. It does NOT bind with IL-1α or IL-1Ra. Bioavailability is 66% and reaches maximum concentration in 7 days. Route of administration is subcutaneous, maintenance dosing is 150 mg every 4 weeks.
Anakinra (Kineret)
Anakinra is an IL-1 receptor antagonist. It blocks the activity of IL-1α and IL-1β by competitively inhibiting IL-1 binding to the IL-1 type 1 receptor (IL-1R1). Bioavailability is 95% and reaches maximum plasma concentrations 3 to 7 hours after administration. Route of administration is subcutaneous, maintenance dosing is 100 mg daily.
Rilonacept (Arcalyst)
Rilonacept is a fusion protein previously known as IL-1 Trap. It has a very high binding affinity for IL-1 and is specific for IL-1α and IL-1β. Rilonacept blocks IL-1β signaling by acting as a soluble decoy receptor that binds IL-1β and prevents interaction with surface receptors. It also binds IL-1α and IL-1Ra. Bioavailability is 50% and reaches maximum plasma concentrations 48 to 72 hours after administration. Route of administration is subcutaneous, maintenance dosing is 160 mg weekly following a loading dose of 320 mg.
Refractory Cases - IL-6 & JAK Inhibitors
There is limited information on general efficacy in Yao Syndrome but there have been Case Reports.
Tocilizumab (Actemra)
Tocilizumab is a monoclonal antibody of the IgG1κ isotype. It inhibits IL-6 mediated interactions. It is commonly used for RA, aJIA, JIA, SSC-ILD, and Giant Cell Arteritis. Route of administration is intravenous. In the United States the starting dose is 4mg/kg followed by an increase to 8mg/kg based on clinical response.
Upadacitinib (Rinvoq)
Upadacitinib is a JAK inhibitor that is selective for JAK1. It is commonly used for atopic dermatitis, RA, PsA, Ulcerative Colitis, Ankylosing Spondylitis, axSpA, and Crohn's Disease. It is rapidly absorbed with Tmax of 2 to 3 hours. Route of administration is a once daily pill.
Lifestyle Changes
Lifestyle changes can be a great compliment to traditional treatment plans!
Dietary
Anti-Inflammatory Diets:
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Mediterranean Diet
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Japanese Diet
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Traditional Korean Diet
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Other diets that follow the same premise
Low FODMAP Diet:
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Low Carb
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Low Dairy
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Low Gluten
These two diets work to help reduce inflammation and assist digestion respectively.
Other Recommendations
Exercise
The recommendation is for proper physical exercise as tolerated.
Recommendations:
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Pilates
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Tai Chi and Qigong
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Yoga
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Walking or light hiking
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Low Impact Exercises
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Cycling, Swimming, etc
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Resistance Training
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Dancing
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Elliptical Training
The aim is to build strength, balance, and bone health without causing additional pain or harm.
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Minimize Stress
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Promote Sleep and Good Sleep Hygiene
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Probiotics
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Consider Gingers
References
Medication Use in Yao Syndrome
Nomani H, Wu S, Saif A, Hwang F, Metzger J, Navetta-Modrov B, Gorevic PD, Aksentijevich I and Yao Q (2024)
Comprehensive clinical phenotype, genotype and therapy in Yao syndrome.
Frontiers in Immunology, 15:1458118.
doi: 10.3389/fimmu.2024.1458118
Brailsford, Caroline & Khamdan, Fatema & Elston, Dirk. (2022).
Successful Treatment of Refractory Yao Syndrome with Canakinumab.
JAAD Case Reports. 29. doi: 10.1016/j.jdcr.2022.08.035.
Yao, Q., & Shen, B. (2017).
A systematic analysis of treatment and outcomes of NOD2-associated autoinflammatory disease.
The American Journal of Medicine, 130(3), 365.e13–365.e18.
doi: 10.1016/j.amjmed.2016.09.028
Williamson KA, Samec MJ, Patel JA, Orandi AB, Wang B, Crowson CS, Loftus EV Jr., Alavi A, Moyer AM and Davis JM III (2024)
Clinical phenotype, NOD2 genotypes, and treatment observations in Yao syndrome: a retrospective case series.
Front. Immunol. 15:1304792.
doi: 10.3389/fimmu.2024.1304792
Karamanakos A, Vougiouka O, Sapountzi E, Venetsanopoulou AI, Tektonidou MG, Germenis AE, Sfikakis PP and Laskari K (2024)
The expanding clinical spectrum of autoinflammatory diseases with NOD2 variants: a case series and literature review.
Front. Immunol. 15:1342668.
doi: 10.3389/fimmu.2024.1342668
Zhang J, Huang X and Shen M (2024)
Expanding clinical characteristics and genotypic profiling of Yao syndrome in Chinese patients.
Front. Immunol. 15:1444542.
doi: 10.3389/fimmu.2024.1444542
Yao, Q. (2023).
Effectiveness of canakinumab for the treatment of patients with Yao syndrome.
Journal of the American Academy of Dermatology, S0190-9622(19)32757-4.
doi: 10.1016/j.jaad.2019.32757
Esse, I., Kincaid, C., Horton, L., Arnold, J. D., Mesinkovska, N. A. (2023).
Yao syndrome: Cyclical folliculitis, fevers, and abdominal pain.
JAAD Case Reports, 35, 71–73.
doi: 10.1016/j.jaadcasereports.2023.00082
Rheumatology Advisor. (2022, November 13). Autoinflammatory disease. Rheumatology Advisor. https://www.rheumatologyadvisor.com/ddi/autoinflammatory-disease/
Khalid A, Kaell A.
Yao Syndrome: An Overview of Genotypic Associations, Clinical Manifestations, Diagnosis, and Treatment.
Int Arch Allergy Immunol. 2025;186(2):189-202. doi: 10.1159/000540188.
Hasbani GE, Davis JM 3rd.
Managing Yao Syndrome: A Case of Beneficial Treatment with Upadacitinib and Leflunomide.
Mediterr J Rheumatol. 2025 Jul 15;36(3):502-504.
doi: 10.31138/mjr.261224.erh.
Lee J., Bizzocchi L., Jain R., Tagoe C.E.,
An autoinflammatory syndrome with compound heterozygous MEFV and NOD2/CARD15 gene mutations successfully treated with tocilizumab, Rheumatology Advances in Practice, Volume 6, Issue 2, 2022.
doi: 10.1093/rap/rkac035
Medication Information
Urien, S., et al. (2013). Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoinflammatory syndromes. BMC Pharmacology & Toxicology, 14:40.
Swedish Orphan Biovitrum AB. (2015). Kineret [Package insert]. Stockholm, Sweden.
Janssen, C. A., et al. (2019). Anakinra for the treatment of acute gout flares: A randomized, double-blind, placebo-controlled, active-comparator, non-inferiority trial. Rheumatology (Oxford).
Autmizguine, J., et al. (2015). Rilonacept pharmacokinetics in children with systemic juvenile idiopathic arthritis. Journal of Clinical Pharmacology, 55(1), 39–44.
Regeneron Pharmaceuticals, Inc. (2016). Arcalyst [Package insert]. Tarrytown, NY.
McDermott, M. F. (2009). Rilonacept in the treatment of chronic inflammatory disorders. Drugs of Today, 45(6), 423–430.
Church, L. D., McDermott, M. F. (2010). Canakinumab: A human anti-IL-1β monoclonal antibody for the treatment of cryopyrin-associated periodic syndromes. Expert Review of Clinical Immunology, 6(6), 831–841.
Church, L. D., Savic, S., & McDermott, M. F. (2008). Long-term management of patients with cryopyrin-associated periodic syndromes (CAPS): Focus on rilonacept (IL-1 Trap). Biologics, 2(4), 733–742.
Hoffman, H. M. (2009). Rilonacept for the treatment of cryopyrin-associated periodic syndromes (CAPS). Expert Opinion on Biological Therapy, 9(4), 519–531.
Hoffman, H. M., et al. (2008). Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: Results from two sequential placebo-controlled studies. Arthritis & Rheumatism, 58(8), 2443–2452.
Ilowite, N. T., et al. (2014). Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in systemic juvenile idiopathic arthritis. Arthritis & Rheumatology, 66(9), 2570–2579.
Sun, H., et al. (2016). Pharmacokinetics and pharmacodynamics of canakinumab in patients with systemic juvenile idiopathic arthritis. Journal of Clinical Pharmacology, 56(12), 1516–1527.
Novartis Pharmaceuticals Corporation. (2016). Ilaris [Package insert]. East Hanover, NJ.
Bresnihan, B., et al. (1998). Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis & Rheumatism, 41(12), 2196–2204.
Jiang, Y., et al. (2000). A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human IL-1 receptor antagonist in rheumatoid arthritis: Radiologic progression and correlation of Genant and Larsen scores. Arthritis & Rheumatism, 43(5), 1001–1009.
Firestein, G. S., McInnes, I. B., Koretzky, G., Mikuls, T., Neogi, T., & O’Dell, J. R. (Eds.). (2024). Firestein & Kelley’s Textbook of Rheumatology (12th ed., 2-volume set). Elsevier.
Bondeson, J., & Sundler, R. (1998). Antimalarial drugs inhibit phospholipase A₂ activation and induction of interleukin-1β and tumor necrosis factor in macrophages: Implications for their mode of action in rheumatoid arthritis. General Pharmacology, 30, 357–366.
Chen, X., Gresham, A., Morrison, A., et al. (1996). Oxidative stress mediates synthesis of cytosolic phospholipase A₂ after UVB injury. Journal of Biological Chemistry, 111, 693–695.
Ruzicka, T., & Printz, M. (1982). Arachidonic acid metabolism in guinea pig skin: Effects of chloroquine. Agents and Actions, 12, 527–529.
Ramakrishnan, N., Kalinich, J., & McClain, D. (1996). Ebselen inhibition of apoptosis by reduction of peroxides. Biochemical Pharmacology, 51, 1443–1451.
Yamazaki, T., Miyai, E., Shibata, H., et al. (1991). Pharmacological studies of salazosulfapyridine (SASP): Evaluation of anti-rheumatic action. Pharmacometrics, 41, 563–574.
Tornhamre, S., Edenius, C., Smedegard, G., et al. (1989). Effects of sulfasalazine and sulfasalazine analogue on the formation of lipoxygenase and cyclo-oxygenase products. European Journal of Pharmacology, 169, 225–234.
Gronberg, A., Isaksson, P., & Smedegard, G. (1994). Inhibitory effect of sulfasalazine on production of IL-1β, IL-6 and TNF-α. Arthritis & Rheumatism, 37(Suppl), S383.
Other References
Willcox DC, Scapagnini G, Willcox BJ. Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet. Mech Ageing Dev. 2014 Mar-Apr;136-137:148-62.
doi: 10.1016/j.mad.2014.01.002
Calder PC. Omega-3 fatty acids and inflammatory processes. Nutrients. 2010 Mar;2(3):355-374.
doi: 10.3390/nu2030355
Shin D, Lee KW, Brann L, Shivappa N, Hébert JR. Dietary inflammatory index is positively associated with serum high-sensitivity C-reactive protein in a Korean adult population. Nutrition. 2019 Jul-Aug;63-64:155-161.
doi: 10.1016/j.nut.2018.11.016
Almajano MP, Carbo R, Jimenez JAL, Gordon MH, 2008. Antioxidant and antimicrobial activities of tea infusions. Food Chem. 108 (1), 55–63.
Arai H, Ouchi Y, Toba K, Endo T, Shimokado K, Tsubota K, Matsuo S, Mori H, Yumura W, Yokode M, Rakugi H, Ohshima S. Japan as the front-runner of super-aged societies: Perspectives from medicine and medical care in Japan. Geriatr Gerontol Int. 2015 Jun;15(6):673-87.
doi: 10.1111/ggi.12450
Shin PK, Park SJ, Kim MS, Kwon DY, Kim MJ, Kim K, Chun S, Lee HJ, Choi SW. A Traditional Korean Diet with a Low Dietary Inflammatory Index Increases Anti-Inflammatory IL-10 and Decreases Pro-Inflammatory NF-κB in a Small Dietary Intervention Study. Nutrients. 2020 Aug 16;12(8):2468.
doi: 10.3390/nu12082468
Lange KW, Nakamura Y. Japanese cuisine and its health benefits: food bioactives, dietary features, and public health. Journal of Food Bioactives, 2025, 31: 1-7. doi: 10.26599/JFB.2025.95031417
Ghosh-Jerath S, Singh A, Suresh M, P P A, Price S, Khan S, Ali K, Bakshi N, Hebert JR, Roy A. Development of an Indian-adapted anti-inflammatory Mediterranean diet for coronary artery disease patients. BMC Nutr. 2025 Jul 4;11(1):129. doi: 10.1186/s40795-025-01102-5
Subin P, Sabuhom P, Naladta A, Luecha P, Nualkaew S, Nualkaew N. An Evaluation of the Anti-Inflammatory Effects of a Thai Traditional Polyherbal Recipe TPDM6315 in LPS-Induced RAW264.7 Macrophages and TNF-α-Induced 3T3-L1 Adipocytes. Curr Issues Mol Biol. 2023 Jun 5;45(6):4891-4907. doi: 10.3390/cimb45060311
Thaochalee, C., Sarikaputi, A., Bumrungpech, A., Chalermchai, T., & Nararatwanchai, T. (2021). Anti-inflammatory effects of plant-based Thai diets in overweight and obese individuals. Songklanakarin Journal of Science & Technology, 43(3), 840–846. doi: 10.14456/sjst-psu.2021.111