The Treatments And Prognosis Of 82 Cases Of Chronic Granulomatous Disease Patients In Single Center Of China And Two Missed Diagnosed Patients With STING-associated Vasculopathy With Onset In Infancy

PART I THE TREATMENTS AND PROGNOSIS OF 82 CASES OF CHRONIC GRANULOMATOUS DISEASE PATIENTS IN SINGLE CENTER OF CHINABackground: To summarize the treatments and outcomes of patients with CGD in single center in Chongqing,China,so as to improve the managements of the disease and improve the quality of life of the patients.Methods: Clinical data of 82 CGD patients born between 1999 and 2016 were collected.Patients were divided into the survival group and the dead group.The general information,infectious and inflammatory events,as well as anti-infectious therapies and inflammatory complications were collected.Kaplan–Meier methods and survival curves were used to assess overall survival.Results: A total of 82 CGD patients(80 males and 2 females)were analyzed.The mean age of onset was 3.7(0.1-24.0)months;the mean age of diagnosis was 26.3(0.6-165.3)months,and the median follow-up time was 25.9(0.1-164.0)months.The overall survival rate was 67.1%.27(32.9%)patients died at a mean age of 37.6(2.0-190.3)months.49(59.8%)cases developed manifestations in neonatal period,which were more in death group,and the diagnostic time of these children was earlier.58(70.7%)patients began to receive SMZ since diagnosis with an average duration of 36.8 months.52(63.4%)received voriconazole or itraconazole to prevent fungal infection with an average duration of 34.3 months.The most frequent bacteria were Klebsiella pneumoniae,Staphylococcus aureus,Burkholderia onion and Escherichia coli,while Klebsiella pneumoniae and Escherichia coli were all resistant bacteria.The use of advanced-antibiotics(eg.,the fourth-generation cephalosporins,?-lactam antibiotics,carbapenems,vancomycin)in the death group was higher(70.7%)than that in the survival group(40.0%)(p<0.05).17(20.7%)patients developed inflammatory complications.32(39.0%)children received hematopoietic stem cell transplantation(HSCT)and 25 in our center with a success rate of 96%.The Kaplan–Meier survival curves showed a worse prognosis in those who manifested in neonates,more dependent on advanced-antibiotics,and those who did not receive transplantations.Conclusion: The earlier the clinical manifestations appear,and the higher utilization rate of advanced-antibiotics,the more serious the condition is.It reflected that there is still insufficiency of conservative drug treatment,and the emergence of drug-resistant bacteria increases the difficulty of treatment.Inflammatory complications are noteworthy that the diagnosis and treatments needs more explorations.HSCT is so far the curative therapy for CGD in China.Future work should focus more on the efficient treatments of infections and inflammation in order to improve the outcomes of them.PART II TWO MISSED DIAGNOSED PATIENTS WITH STING–ASSOCIATED VASCULOPATHY WITH ONSET IN INFANCYObjective: Stimulator of interferon genes(STING)–associated vasculopathy with onset in infancy(SAVI)was first described in 2014 as a type I interferonopathy resulting from heterozygous mutations in the TMEM173 gene.SAVI is characterized by the neonatal onset of systemic inflammation,severe cutaneous vasculopathy and interstitial lung disease.JAK inhibitors are considered effective therapeutics.We sought to describe two patients that were diagnosed with SAVI only at postmortem to increase awareness of this disorder.Methods: Clinical data were collected,and Sanger sequencing of the TMEM173 gene was performed in two patients suspected of SAVI.This paper reviews details of these cases and lessons learned from clinical review and postmortem studies.Results: Two male children shared similar manifestations,including recurrent skin abscesses in winter,skin lesions and recurrent respiratory tract infections since birth.Computed tomography of the chest revealed pulmonary fibrosis,but no mutations in relevant genes(including ABCA3 and SFTPC)were discovered in patient 1(P1).Joint pain was significant in P2,and he was diagnosed with arthritis.Antibiotic treatment yielded little improvement and did not prevent progression.Finally,P1 and P2 died of respiratory and circulatory failure in 2016 and 2012,respectively.In 2018,mutations(P1: c.463G>A,p.V155M;and P2: c.461A>G,p.N154S)in exon 5 of the TMEM173 gene were discovered,confirmingthe diagnosis of SAVI.Conclusion: The experience with these two patients suggests that SAVI should be considered in children with systemic inflammation,chilblain skin lesions and pulmonary fibrosis,and TMEM173 gene analysis can be beneficial in the diagnosis of SAVI.