Clinical Characteristics Analysis Of Different Disease Patterns In Adult-onset Still’s Disease

BackgroundAdult-onset Still’s disease(AOSD)is a systemic autoimmune inflammatory disease with relatively low morbility,which is hard to diagnose.It mainly presents various clinical manifestations characterized by refactory high spiking fevers,arthralgia or arthritis and an evanescent congenstve red or pink skin rash.Laboratory findings include leukocyte counts and ferritin typically elevated.AOSD complicated with macrophage activation syndrome is a rather severe and urgent clinical situation.Treatment options include non-steriods anti-inflammatory drugs(NSAIDs),glucocorticoids,disease mordifying anti-rheumatological drugs,biological agents and immnoglobins.Recently,according to the clinical studies of AOSD,the evolution of AOSD is divided into three distinct models:namely(1)self-limiting or single-cycle type(the clinical manifestations characterized by fever,rash,joint affectation,organ enlargement and so on,with long-term remission and good prognosis after treatment);(2)intermittent systemic or multi-cycle type(with episodes or recurrent outbreaks,with or without joint symptoms,symptoms disappear during the intercritical periods,most of the symptoms are tender than initial symptoms and gradually achieve complete remission);(3)chronic arthritis type(with usually destructive progressive polyarticular,which ultimately results in increased disability).Different patterns present different clinical manifestations.Thus,it is very important for the early diagnosis and effective treatment of AOSD to study the disease patterns.However,there’s still a blank in China.ObjectiveTo compare the clinical characters between different patterns of AOSD,and to find out suitable indicators and cut-off points for different patterns,and to explore the possible risk factors of the comorbility of AOSD and MAS.MethodsWe conducted a retrospective research of AOSD patients from Changhai Hospital of the Second Military Medical University,including 10cases complicated by macrophage activation syndrome(MAS)were enrolled in this study from January 2001 to December2016.The diagnosis of AOSD is based on the Yamaguchi et al(1992).The clinical manifestations,serological parameters,therapies and the therapeutic response of these hospitalized patients were collected.The data collected included patient age,sex,age at diagnosis,delayed diagnosis time,typical rash,arthralgia,arthritis,myalgia,sore throat,lymphadenopathy,hepatomegaly,splenomegaly large,pleurisy,pericarditis and other rare discoveries.The patient’s laboratory results were also recorded.The initiation of the drug after diagnosis and remission with the first treatment were analyzed.The disease patterns and related factors were also investigated.Monovariate and multivariate analysis was performed to assess the factors associated with mitigation.ROC curve and logistics analysis was made to find out suitable indicators and risk factors respectively.ResultsThis retrospective study included 162 AOSD patients.Among them,98 cases were single circulation type,57 cases were multiple circulation type,7 cases were chronic arthritis type.The male/female ratio was 1:2.24,average age was(40.3+14.9)years old,the median time of diagnosis was 4(2,8)weeks,the highest median temperature was39.7(39,40)℃,fever duration was 4(3,8)weeks,the median WBC counts was14.4×10~9/L(11×10~9/L,19.7×10~9/L),the median percentage of neutrophils was 83.2%(78.5%,89.4%),ALT,AST,ALP,LDH,globulin and fibrinogen medians were 44.5(20.0,100.3)U/L,43(23.8,85.5)U/L,91(68.8134.8)U/L,32.3(29,37)g/L,410(266.8531.3)U/L and 5.7(4.6,6.5)g/L respectively.The median IgG and CRP were 14(12.2,17.0)g/L and 83.6(31.9,128.0)mg/L.mean ESR,C3 and C4 were(74.1+33.4)mm/H,(1.3±0.4)g/L and(0.3±0.1)g/L.The proportion of ferritin over 2000 ug/L was 64.8%,the proportion of RF positive was 6.8%,and the proportion of ANA positive was 9.9%(g/L).Monovariate analysis showed that diagnosis duration,the highest temperature,fever durations,weight loss,joint pain incidence,alanine aminotransferase elevation and rheumatoid factor positivity of three disease patterns had significant differences.Multivariate analysis found that three kinds of disease patterns have significant differences in the distribution of the diagnosis time,fever length,myalgia and rash.P values were less than 0.05.The proportion of antibiotic use in patients with single cycle and multi cycle AOSD was significantly higher than that of chronic arthritis,and there was no significant difference in the proportion of different treatment drugs among the three disease patterns.Using receiver operating characteristic(ROC)curve and area under the curve(AUC),we found that ALT/IgM,ferritin×ESR and IgG might be helpful to classify three disease patterns of AOSD.When ALT/IgM is greater than 81.25U/g,the pattern of single cycle AOSD is more possible;when ferritin×ESR is greater than x 1.05×10~5,the pattern of multi cycle AOSD is more possible.Using binary logistics regression analysis,we found that multiple cycle AOSD,hepatomegaly and fibrinogen reduction may be the risk factors of AOSD combined with MAS.ConclusionThree disease patterns of AOSD,Single-cycle,multi-cycle and chronic arthritis type are significantly different at diagnosis time,fever length.ALT/IgM and ferritin×ESR may help to distinguish between disease patterns of AOSD.Multi-cycle AOSD,enlargement of the liver and fibrinogen reduction might be risk factors of AOSD complicated with MAS.