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.

Keywords

autoinflammatory disease - Blau syndrome - Takayasu - NOD2 - anti-TNF-α

Publication History

Received: 29 May 2021

Accepted: 26 September 2021

Article published online:
13 December 2021

• References

• 1 Jindal AK, Pilania RK, Suri D. et al. A young female with early onset arthritis, uveitis, hepatic, and renal granulomas: a clinical tryst with Blau syndrome over 20 years and case-based review. Rheumatol Int 2021; 41 (01) 173-181
• 2 Wouters CH, Maes A, Foley KP, Bertin J, Rose CD. Blau syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatr Rheumatol Online J 2014; 12: 33
• 3 Velickovic J, Silan F, Bir FD, Silan C, Albuz B, Ozdemir O. Blau syndrome with a rare mutation in exon 9 of NOD2 gene. Autoimmunity 2019; 52 (7-8): 256-263
• 4 Li C, Zhang J, Li S. et al. Gene mutations and clinical phenotypes in Chinese children with Blau syndrome. Sci China Life Sci 2017; 60 (07) 758-762
• 5 PaÇ Kisaarslan A, SÖzerİ B, Şahİn N. et al. Blau syndrome and early-onset sarcoidosis: a six case series and review of the literature. Arch Rheumatol 2019; 35 (01) 117-127
• 6 Iwasaki T, Kaneko N, Ito Y. et al. Nod2-nodosome in a cell-free system: implications in pathogenesis and drug discovery for Blau syndrome and early-onset sarcoidosis. ScientificWorldJournal 2016; 2016: 2597376
• 7 Imayoshi M, Ogata Y, Yamamoto S. A case of sporadic Blau syndrome with an uncommon clinical course. Case Rep Rheumatol 2018; 2018: 6292308
• 8 Kim W, Park E, Ahn YH. et al. A familial case of Blau syndrome caused by a novel NOD2 genetic mutation. Korean J Pediatr 2016; 59 (Suppl. 01) S5-S9
• 9 Inoue Y, Kawaguchi Y, Shimojo N. et al. A case of infantile Takayasu arteritis with a p.D382E NOD2 mutation: an unusual phenotype of Blau syndrome/early-onset sarcoidosis?. Mod Rheumatol 2013; 23 (04) 837-839
• 10 Khubchandani RP, Hasija R, Touitou I, Khemani C, Wouters CH, Rose CD. Blau arteritis resembling Takayasu disease with a novel NOD2 mutation. J Rheumatol 2012; 39 (09) 1888-1892
• 11 Rosé CD, Aróstegui JI, Martin TM. et al. NOD2-associated pediatric granulomatous arthritis, an expanding phenotype: study of an international registry and a national cohort in Spain. Arthritis Rheum 2009; 60 (06) 1797-1803
• 12 Aróstegui JI, Arnal C, Merino R. et al. NOD2 gene-associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a Spanish cohort. Arthritis Rheum 2007; 56 (11) 3805-3813
• 13 Gross KR, Malleson PN, Culham G, Lirenman DS, McCormick AQ, Petty RE. Vasculopathy with renal artery stenosis in a child with sarcoidosis. J Pediatr 1986; 108 (5 Pt 1): 724-726
• 14 Caso F, Galozzi P, Costa L, Sfriso P, Cantarini L, Punzi L. Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease. RMD Open 2015; 1 (01) e000097
• 15 Matsuda T, Kambe N, Ueki Y. et al; PIDJ members in the JSIAD, PIDJ (Primary Immunodeficiency and Autoinflammatory Diseases Database Project) members in the JSIAD (Japanese Society for Immunodeficiency and Autoinflammatory Diseases). Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by genetic analysis of the NOD2 mutation. Ann Rheum Dis 2020; 79 (11) 1492-1499
• 16 Wang X, Kuivaniemi H, Bonavita G. et al. CARD15 mutations in familial granulomatosis syndromes: a study of the original Blau syndrome kindred and other families with large-vessel arteritis and cranial neuropathy. Arthritis Rheum 2002; 46 (11) 3041-3045
• 17 Seyahi E. Takayasu arteritis: an update. Curr Opin Rheumatol 2017; 29 (01) 51-56
• 18 Takada S, Saito MK, Kambe N. Blau syndrome: NOD2-related systemic autoinflammatory granulomatosis. G Ital Dermatol Venereol 2020; 155 (05) 537-541
• 19 Rose CD, Martin TM, Wouters CH. Blau syndrome revisited. Curr Opin Rheumatol 2011; 23 (05) 411-418
• 20 Chen J, Luo Y, Zhao M. et al. Effective treatment of TNFα inhibitors in Chinese patients with Blau syndrome. Arthritis Res Ther 2019; 21 (01) 236
• 21 Serra R, Butrico L, Fugetto F. et al. Updates in pathophysiology, diagnosis and management of Takayasu arteritis. Ann Vasc Surg 2016; 35: 210-225
• 22 Murdaca G, Spanò F, Cagnati P, Puppo F. Free radicals and endothelial dysfunction: potential positive effects of TNF-α inhibitors. Redox Rep 2013; 18 (03) 95-99