A 67-year-old man presented with a 15-year history of chronic urticaria. It was distributed symmetrically on the limb trunk (Fig. 1A and B) without pruritus. No fever or joint pain or headache is observed. He showed no signs of angioedema. He was referred to our hospital for treatment of chronic urticaria. An antihistamine was ineffective. He was diagnosed with mild sensorineural hearing loss. He had no family history of autoinflammatory diseases. White blood cell counts and C-reactive protein (CRP) levels were 8000/μL and 10 mg/dL, respectively. Creatinine, amyloid A, and urine protein levels were 1.2 mg/dL(eGFR 47.3 mL/min/1.73m2), 8.3 μg/mL, and 2.7 g/day, respectively. Complement C3 and C4 levels were normal. Monoclinal protein of immunoglobulin was negative. Pathological findings in the skin lesion showed remarkable infiltration of neutrophils at the interstitial lesion (Fig. 1C and D), but no vasculitis. What is the diagnosis? A NOD-like receptor protein 3 (NLRP3) mutation was detected, and Muckle–Wells syndrome (MWS) was diagnosed. After canakinumab treatment, the rashes disappeared, and CRP and urine protein levels normalized. MWS, characterized by intermittent fever, urticaria, progressive sensorineural deafness, and renal amyloidosis, is an inherited autoinflammatory disease caused by the CIAS1/NLRP3 mutation. This causes an inflammatory reaction resulting in elevated CRP and amyloid A levels, thus leading to renal failure due to amyloidosis [[1]Kuemmerle-Deschner J.B. Dembi Samba S. Tyrrell P.N. Koné-Paut I. Marie I. Deschner N. et al.Challenges in diagnosing Muckle–Wells syndrome: identifying two distinct phenotypes.Arthritis Care Res. 2014; 66: 765-772https://doi.org/10.1002/acr.22206Crossref Scopus (12) Google Scholar]. Interleukin-1 antagonists prevent organ damage progression and improves the quality of life (QOL) of patients diagnosed with MWS [[2]Tran T.A. Muckle–Wells syndrome: clinical perspectives.Open Access Rheumatol. 2017; 9 (10.2147%2FOARRR.S114447): 123-129Crossref PubMed Scopus (21) Google Scholar]. However, the average time to diagnosis is 18.5 years [[1]Kuemmerle-Deschner J.B. Dembi Samba S. Tyrrell P.N. Koné-Paut I. Marie I. Deschner N. et al.Challenges in diagnosing Muckle–Wells syndrome: identifying two distinct phenotypes.Arthritis Care Res. 2014; 66: 765-772https://doi.org/10.1002/acr.22206Crossref Scopus (12) Google Scholar]. While most autoinflammatory diseases occur in children, MWS is often diagnosed in adults. Adult cases have less fever and more hearing loss than pediatric cases; the absence of severe symptoms such as periodic fever causes diagnostic delay [[1]Kuemmerle-Deschner J.B. Dembi Samba S. Tyrrell P.N. Koné-Paut I. Marie I. Deschner N. et al.Challenges in diagnosing Muckle–Wells syndrome: identifying two distinct phenotypes.Arthritis Care Res. 2014; 66: 765-772https://doi.org/10.1002/acr.22206Crossref Scopus (12) Google Scholar]. For early diagnosis, MWS should be considered for recurrent and persistent urticarial rashes in which antihistamines are ineffective, pruritus is absent, urticarial rashes are symmetrical, and CRP levels are high [[3]Davis M.D.P. van der Hilst J.C.H. Mimickers of urticaria: urticarial vasculitis and autoinflammatory diseases.J Allergy Clin Immunol Pract. 2018; 6: 1162-1170https://doi.org/10.1016/j.jaip.2018.05.006Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]. The most characteristic finding in MWS is the high CRP level. Pathological neutrophil infiltration encompasses blood vessels and interstitial lesions [[2]Tran T.A. Muckle–Wells syndrome: clinical perspectives.Open Access Rheumatol. 2017; 9 (10.2147%2FOARRR.S114447): 123-129Crossref PubMed Scopus (21) Google Scholar]. When patients with chronic urticaria have these characteristics, M protein, urinalysis, and pathological and genetic tests are recommended to distinguish cryopyrin-associated periodic syndrome, Schnitzler syndrome, and urticaria-like vasculitis. Early MWS diagnosis improves patients’ QOL.