Clinical And Genetic Features Of Patients With Three Kinds Of Difficult Systemic Autoinflammatory Diseases

Objectives:Systemic autoinflammatory diseases(SAIDs)is a group of inflammatory diseases associated with innate immune disorders.We aimed to characterize the clinical and genetic features of patients with three kinds of difficult SAIDs.Methods:Patients were diagnosed and followed up as tumour necrosis factor receptor-associated periodic fever syndrome(TRAPS),chronic non-bacterial osteomyelitis(CNO)and adult onset Still’s disease(AOSD)with neurological system involved during April 2015 to August 2019,at the Department of Rheumatology,Peking Union Medical College Hospital(PUMCH).Clinical and genetic features of these patients were evaluated.Results:1.Totally,nine adult patients were diagnosed as TRAPS.Adult-onset was observed in 2(22.2%)patients.The median time of diagnosis delay was 16.5(1.5-50)years.The common manifestations included fever(9,100%),rash(7,77.8%),arthralgia/arthritis(5,55.6%),and abdominal pain(5,55.6%).Nine TNFRSF1A gene variants were identified,including 2 novel variants.2.There were 9 patients diagnosed as CNO and 6 of them were adult-onset.The frequent symptoms were bone pain(9,100%)and fever(7,77.8%).Mandible was the most common location involved with an incidence of 13.3%.The radiology mainly presented as bone destruction with marginal sclerosis.Bone biopsy manifested as chronic osteomyelitis.Gene variants with uncertain significance were detected in PSTPIP1 and CLCN7.3.Fourteen of the hospitalized AOSD patients presented with neurological symptoms,and the incidence was 7.5%.Central nervous system involved ranked to the first.Macrophage activation syndrome was more common in AOSD patients with neurological system involvement than in those without.Conclusion:SAIDs is a group of rare diseases with various clinical manifestations and difficult to be diagnosed.The difference of clinical phenotype of SAIDs between Chinese adults and foreign patients might be related to different genotypes.The recognition of these rare diseases by physicians helps to make early diagnosis and proper treatments.