Monogenic Autoinflammatory Disease Due to Blau Syndrome with Nucleotide Oligomerization Domain 2 Gene Mutation in an Indian Family

Abstract

Background: Blau syndrome is a monogenic disease resulting from mutations in nucleotide oligomerization domain 2 (NOD2) and is phenotypically characterized by a triad of dermatitis, arthritis, and uveitis. We report Blau syndrome in a child who had been symptomatic for years, without the typical clinical triad. Clinical Description: A 7-year-old girl child presented with bilateral knee, wrist, and ankle joint swelling since the age of 2 years. She had recently developed a rash on the body. Her mother, mother’s identical twin sister, and the latter’s 5-year-old daughter had similar joint pain and swellings since childhood. In view of the strong positive family history of polyarthritis, monogenic cause of arthritis was suspected. Management and Outcome: Complete blood count was unremarkable. Erythrocyte sedimentation rate was 20 mm at C-reactive protein was 36 mg/L, antinuclear antibody and rheumatoid arthritis factor were negative. X-ray of the knee joints and wrist joints showed soft-tissue swellings around the knee and lumbar scoliosis. A heterozygous pathogenic variant in NOD2 gene confirmed the diagnosis of Blau syndrome. After receiving the genetic report, the girl was started on prednisolone and weekly methotrexate. Conclusion: Early-onset arthritis, with recurrent episodes of fever, is not to be ignored if autoimmune markers are negative. Knowledge about the clinical features of autoinflammatory diseases and the spectrum of NOD2 variants will enable physicians to carry out specific investigations, especially genetic analysis for confirmation of the diagnosis and hence administer the right treatment.