Risk Factors Of Infection And Relapse In ANCA-associated Vasculitis

ObjectiveTo analyze the clinical and infectional characteristics in newly diagnosed patients with antineutrophil cytoplasmic antibody(ANCA)associated vasculitis(AAV).The risk factors of AAV co-infection and recurrence were explored to provide clinical basis for disease diagnosis and treatment and delay disease progression.MethodsPart one:The clinical data of 308 patients with AAV who were newly diagnosed in the Affiliated Hospital of Qingdao University from January 1,2015 to December 31,2021 were retrospectively collected.According to whether infection occurred during the follow-up,the patients were divided into infected group and non-infected group.The clinical characteristics,infection frequency,location,and type of pathogenic bacteria of the two groups were analyzed.Kaplan-Meier survival curve with no cumulative infection was drawn,and Cox regression model was used to explore the influencing factors of co-infection.Part two:A total of 132 patients with AAV who were newly admitted to our hospital from January 1,2015 to December 31,2021 and underwent at least 3 consecutive ANCA tests(each time approximately 1 month apart)were included.Clinical data were retrospectively collected,and the patients were divided into continuous positive group,negative turning group and positive recovery group according to ANCA test.The clinical characteristics,treatment plan and prognosis of the three ANCA models were compared.According to whether relapse occurred during follow-up,the patients were divided into relapse group(44 cases)and non-recurrence group(88 cases),and the clinical data of the two groups were compared.Univariate and multivariate regression models were used to analyze the risk factors for clinical recurrence in the general population,MPO subgroup and renal involved subgroup,respectively.Kaplan-Meier survival curve was used to evaluate the recurrence of the three ANCA models.ResultsPart one:1.Among the 308 patients,162(52.5%)were males and 146(47.4%)were females.The mean age of onset was 66.5(59.8,71.2)years,with 256(83.1%)MPO-ANCA positive and 52(16.9%)PR3-ANCA positive.There were 107 cases(34.7%)in the infected group and 201 cases(65.3%)in the non-infected group.2.The proportion of of hypertension,basic pulmonary diseases,and receiving hormone shock therapy and plasma exchange,the involvement rates of lung,kidney,heart and gastrointestinal tract,and serum creatinine and FFS at initial diagnosis were significantly higher in infection group,while e GFR,albumin and hemoglobin were significantly lower than those in non-infection group,with statistical significance(all P <0.05).There was significant difference in the proportion of pulmonary underlying diseases between the two groups(P=0.001).3.A total of 152 infections occurred in the infected group,and Kaplan-Meier survival curve showed that 72 infections(47.4%)occurred within 6 months after initial diagnosis.Lung(74.3%)was the main infection site of AAV patients,and the most common pathogenic microorganisms were bacteria(62.7%),mainly Pseudomonas aeruginosa and Staphylococcus aureus.This was followed by fungi(35.6%,mainly Candida albicans).4.Multivariate Cox regression analysis showed that pulmonary involvement(HR=1.931,95%CI 1.26～2.958,P=0.002)and gastrointestinal involvement(HR=2.402,95%CI 1.05～5.495,P=0.038)were independent influencing factors for infection in AAV patients.Part two:1.Of the 132 patients,67 were males and 65 were females,107 were MPO-ANCA positive(81.1%)and 25 were PR3-ANCA positive(18.9%).There were 43 cases(32.5%)of ANCA positive group,65 cases(49.2%)of ANCA negative group,and 24 cases(18.2%)of ANCA re-positive group.44 patients(33.3%)had at least one clinical recurrence.There were significant differences in ANCA pattern and infection events between relapsed and non-relapsed groups(P<0.001).2.Multivariate Cox regression model showed that in the general population,the ANCA model(P<0.001;persistent positive pattern: HR=3.352,95%CI 1.463～7.678,P=0.004;positive conversion pattern: HR=4.760,95%CI 2.094～10.820,P<0.001)and infection(HR= 4.684,95%CI 1.980～11.079,P<0.001)were significantly correlated with clinical recurrence.In MPO-AAV patients,ANCA pattern(P=0.001;persistent positive pattern: HR=4.495,95%CI 1.508～13.396,P=0.007;positive conversion pattern:HR=7.404,95%CI 2.652～20.671,P<0.001)and infection(HR=3.594,95%CI1.511～8.547,P=0.004)were significantly correlated with clinical recurrence.In patients with renal involvement,ANCA pattern(P=0.004;persistent positive pattern: HR=3.618,95%CI 1.364～9.592,P=0.01;positive conversion pattern: HR=4.492,95%CI1.778～11.352,P<0.001)and infection(HR=7.791,95%CI 2.511～24.174,P<0.001)were significantly associated with clinical recurrence,but not in patients without renal involvement.3.Kaplan-Meier survival curve showed significant differences in clinical recurrence rates among ANCA models in the general population,MPO-AAV and renal involved subgroups,and the recurrence rate in the rehabilitation group was significantly higher than that in the other two groups(P<0.001).ConclusionsPart one:1.Infection in AAV patients is mostly concentrated within 6 months after diagnosis.2.AAV patients are often complicated with basic pulmonary diseases,and the most common site of infection is the lung.Common pathogenic microorganisms are Pseudomonas aeruginosa,Staphylococcus aureus and Candida albicans.3.Lung involvement and gastrointestinal involvement are independent risk factors for infection in patients with AAV.Part two:1.ANCA continuous detection of predictable clinical recurrence of AAV.Patients with re-positive ANCA had the highest risk of relapse.2.For MPO-AAV and AAV with kidney involvement,more strengthen ANCA monitoring should be paid attention to.