FAMILY CASE OF BLAU SYNDROME IN 3 CHILDREN, INITIALLY DIAGNOSED AS JUVENILE IDIOPATHIC ARTHRITIS

Background: Juvenile Idiopathic Arthritis (JIA) is heterogeneous group of diseases which may include genetically determined conditions. Extremely rare monogenic hereditary autoinflammatory disease, such as Blau syndrome (BS) is usually difficult to recognize and JIA is initially established. BS is caused by a mutation in the NOD2/CARD5 gene and phenotypically characterized by triad of granulomatosis polyarthritis, uveitis and skin rash. Objectives: To present the family case of genetically confirmed BS in 2 siblings, initially diagnosed as patients with JIA. Methods: Two brothers of 15 and 3 years old were examined in our clinic. Additional genetic assay was performed because of unusual clinical picture. Results: Case report. Older brother, 15 y.o. developed arthritis of both wrist joints at the age of two. There was erythematous maculo-micropapular scaly rash on the trunk and extremities before the onset of arthritis. By 2009 (5 y.o.), the knees, ankles, and three PIP joints of the left hand were involved. Polyarthritis was characterized by severe effusion and periarticular tissues swallowing. He was treated in regional hospital by NSAID, methotrexate, cyclosporine A without significant positive effect. Since 2012 etanercept was added for treatment with variable result. Inactive status of the disease is never reached. Repeated intra-articular GC injections were needed from 4 to 10 times per year. The patient was admitted to our clinic in November 2019. He was suffering from severe polyarthritis and uveitis de novo (granulomatous chorioretinitis) was detected. At the same time his younger 3 y. o. brother with recently started disease was hospitalized in our clinic. He had polyarthritis with typical features of “boggy” synovitis and tenosynovitis of wrists, ankles and knees, anterior uveitis was determined. The onset of arthritis was preceded by a small-spotted rash with desquamation. This classical clinical features in younger brother let us suggest the BS. There was no increasing of ESR and CRP in both sibs throughout the course of the disease. A molecular genetic study of the NOD2/CARD15 gene in both brothers revealed the same mutation of c.1001G\u003eA (p. Arg334Gln). Because of the absence of specific treatment for this disease and due to insufficient effect of etanercept with uveitis de novo therapy was changed to golimumab and good initial effect is reached. The youngest brother has started his therapy by methotrexate. It should be noted that the family has the eldest brother (20 y.o.), who has been suffering from arthritis since an early childhood with similar clinical picture. We are going to perform genetic analysis of the NOD2/CARD15 gene for the eldest brother. Conclusion: Our clinical case shows that extremely rare BS may be misdiagnosed as JIA. Lack of efficacy of the etanercept therapy and uveitis de novo developing may be caused by genetic (non-idiopathic) nature of disease. Classic triad of boggy-arthritis, granulomatous uveitis and/or skin lesions without acute phase markers is required to perform genetic assay for the detection of a pathogenic mutation of the NOD2/CARD15 gene. This case is remarkable by the presence of BS in two (or 3) children of the family. References: [1]Wouters C.H, Maes A, Foley K, et al. Blau Syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatric Rheumatology. 2014; 12: 33. Disclosure of Interests: None declared