Blau Syndrome Complicated by Atypical Type IIa Takayasu Arteritis

Abstract

Blau syndrome (BS) is a rare, autosomal dominant monogenic autoinflammatory disease, usually presenting as a triad of symptoms (granulomatous dermatitis, uveitis, and nonerosive arthritis) and caused by gain-of-function mutations in the nucleotide oligomerization domain 2 (NOD2) gene. However, very few reports in children of copresence of BS with large vessel vasculitis exist. We hereby describe a case of BS associated with clinical features of Takayasu arteritis. An 8.5-year-old boy presented with hypertension, cardiac insufficiency, arthritis, and ocular disease. Among other investigations, he underwent cervical and chest computed tomography and computed tomography angiography scans that revealed the presence of type IIa Takayasu arteritis lesions. Genetic analysis revealed a heterozygous mutation of NOD2 gene leading to the amino acid exchange Arg-587-Cys in the NACHT domain of the NOD2 protein (R587C) as pathogenic cause of BS. He received treatment with prednisolone, methotrexate, and infliximab (antitumor necrosis factor-α) in addition to antihypertensive medication with a favorable clinical response. Cases of BS should be investigated for the coexistence of Takayasu arteritis. However, further research is required to delineate a possible common pathogenic mechanism between the two clinical entities.

Blau syndrome with hypertension and hepatic granulomas: a case report and literature review

“…Among the 33 English language articles we found of patients with BS, there were 24 cases with hypertension ( 4 – 19 ) and 38 cases with digestive system involvement ( 5 – 7 , 11 – 13 , 18 – 36 ) ( Supplementary Tables S1 , S2 ). The 24 patients with hypertension included 10 men, nine women, and five with unknown gender, with a median age at baseline evaluation of 17.1 years (range: 4–57).…”

“…The 38 patients with digestive system involvement comprised 15 men, 18 women, and five with unknown gender, with a median age at baseline evaluation of 20.3 years (range: 1.4–57). Of the 38 patients with digestive system involvement, 14 had hepatic granulomas proven by liver biopsy ( 5 , 7 , 11 , 16 , 20 – 27 ); five patients with hepatic granulomas had liver cirrhosis ( 21 , 23 , 24 , 26 , 27 ); 24 had enlarged liver and/or spleen ( 5 , 11 , 12 , 15 , 16 , 18 , 22 , 26 , 27 , 29 – 35 ); six had elevated liver enzymes including transaminase and cholestatic liver enzyme ( 21 – 24 , 26 , 27 ); five had gastrointestinal diseases including gastric ulcer, diverticulitis, Barrett's esophagus and small and large intestine granulomas ( 6 , 13 , 36 ); one had multiple splenic and hepatic lesions ( 28 ); and one had fatty liver ( 13 ) ( Supplementary Table S2 ).…”

“…In our study, seven patients presented with large-vessel vasculitis resembling Takayasu arteritis, just like our patient. Of the seven cases, one had only renal artery stenosis ( 14 ), five had aortic stenosis other than renal artery stenosis ( 9 , 10 , 15 , 17 , 18 ), and in one, other artery involvement was not specified, except renal artery stenosis ( 11 ). Ten patients were reported to have other forms of renal diseases, such as chronic renal failure, granulomatous nephritis, tubulointerstitial nephritis, renal tubular dysfunction, and nephrocalcinosis ( 4 – 8 , 11 , 12 , 16 , 19 ).…”