Children with systemic autoinflammatory diseases have multiple, mixed ethnicities that reflect regional ethnic diversity.

OBJECTIVES: To evaluate the ethnic diversity of children with a systemic autoinflammatory disease (SAID) in a multi-ethnic Canadian province. METHODS: Self-reported ethnicity of 149 children and adolescents with a SAID in British Columbia, Canada, was analysed for ethnic representation among individual patients, across the cohort, within particular SAIDs, and compared to provincial census data on ethnic diversity. RESULTS: Half of reported cases had a diagnosis of either PFAPA (23.5%) or an unclassifiable autoinflammatory syndrome (31.5%), with a monogenic SAID diagnosed in only 12.8% of cases. The majority of participants (73.1%) were mixed ethnicity with European and Asian heritage reported most frequently (57.0% and 23.0% of all responses, respectively). Ethnic diversity reflected regional diversity except for West Asian, Arabic, Jewish, and Eastern European heritage, which were over-represented in SAID patients, and Chinese descent, which was under-represented in our cohort compared to the general population of British Columbia. CONCLUSIONS: Results from this study show extensive multi-ethnic diversity in individual patients and across the various SAIDs inclusive of monogenic SAIDs that are frequently associated with particular ethnicities. Although not disproportionately represented, this is the first report of systemic autoinflammatory disease in Canadian children of Indigenous heritage.

The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus.

OBJECTIVES: Clinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life. METHODS AND RESULTS: By harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain-of-function p.G13C KRAS mutation, in a boy with the seemingly unrelated immune dysregulatory conditions of Rosai-Dorfman and systemic lupus erythematosus (SLE). CONCLUSIONS: This case expands our understanding of the clinical phenotypes associated with the extremely rare condition of RALD, and emphasizes the importance of always considering the possibility of a monogenic cause for autoimmunity, particularly when the disease manifestations begin early in life and do not follow a typical clinical course.