Blau Syndrome Complicated by Atypical Type IIa Takayasu Arteritis

Efstathia Danai C Bikouli,Dimitrios Delis,Despoina N Maritsi,Andriani Vazeou,Maria Xatzipsalti,Georgios Servos

doi:10.1055/s-0041-1740463

Abstract

AbstractBlau 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.

Highlights

Blau’s syndrome (BS) is a rare, monogenic autoinflammatory disease with an autosomal dominant inheritance pattern,[1,2] sporadic cases caused by de novo mutations have been described
nucleotide oligomerization domain 2 (NOD2) protein known as caspase recruitment domain-containing protein 15 or inflammatory bowel disease protein 1 is an intracellular pattern recognition receptor implicated in the innate immune responses through the activation of nuclear factor kappa B pathway and autophagy.[6]
The patient reported recurrent episodes of fever since the age of 1 year. He was diagnosed with juvenile idiopathic arthritis at the age of 2.5 years based on the findings of oligoarthritis and severe uveitis and was treated with nonsteroidal anti-inflammatory drugs, corticosteroids and hydroxychloroquine

Summary

Introduction

Blau’s syndrome (BS) is a rare, monogenic autoinflammatory disease with an autosomal dominant inheritance pattern,[1,2] sporadic cases caused by de novo mutations have been described. The patient reported recurrent episodes of fever since the age of 1 year He was diagnosed with juvenile idiopathic arthritis at the age of 2.5 years based on the findings of oligoarthritis and severe uveitis and was treated with nonsteroidal anti-inflammatory drugs, corticosteroids and hydroxychloroquine. He underwent lens replacement due to cataract of his right eye at the age of 5 years. In view of the presence of the vascular lesions, he was commenced on infliximab (a chimeric anti–tumor necrosis factor [TNF]-α antibody given IV) at a dose of 6 mg/kg every 4 to 6 weeks His clinical course was favorable over a period of 15 months of follow-up regarding elimination of disease flares and blood pressure control. The clinical course of his ocular disease has shown marked improvement

Discussion

Conclusion