Which one is better for diagnosing SLE?

*It is only for medical professionals to read and reference.
Only when you get started, then there will be the next thing! Systemic lupus erythematosus (SLE) is an autoimmune disease with high heterogeneity and complex disease
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Therefore, for every doctor, it is of great significance to diagnose SLE accurately, which is related to correct treatment and improvement of prognosis
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The diagnostic classification guidelines for SLE have also gone through decades of vicissitudes.
The 1997 SLE diagnostic classification standard of the American College of Rheumatology (ACR) was once the most widely used diagnostic standard in the world, and then the Systemic Lupus Erythematosus International Clinical Assistance Group (SLICC) in 2012 A new classification standard was promulgated in the year
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Both of these standards have limited the diagnosis and treatment practice of SLE due to insufficient sensitivity and specificity.
Therefore, the European Union Against Rheumatism (EULAR) and ACR released the latest diagnostic classification standards for SLE in 2019
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Now, the new classification standard has been released for 2 years.
Looking back at the EULAR/ACR SLE classification standard 2 years later, what experience do you have? Professor Martin Aringer from Germany shared his thoughts at the APLAR annual meeting in the recent past
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How to improve the diagnosis accuracy in 2019? ANA titer ≥ 1:80 is the key.
In the past SLE diagnosis and treatment practice and research, it was found that the sensitivity of the 1997 ACR classification standard was 83% and the specificity was 93%, which is likely to cause missed diagnosis
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The 2012 SLICC classification standard emphasizes the combination of clinical manifestations and immunological indicators, and pays more attention to the significance of system involvement.
The diagnostic sensitivity is increased to 97%, but the specificity is reduced to 84%
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In 2019, EULAR and ACR can increase the sensitivity and specificity of SLE classification diagnosis to 96% and 93%
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Why the 2019 EULAR/ACR classification standard performs so well? In addition to the rigorous methodology in the standard formulation process, the secret is that it uses antinuclear antibody (ANA) titer ≥ 1:80 (Hep-2 cell method) as the entry standard! If a patient suspected of SLE meets the entry criteria, he may be further classified and diagnosed and used as a reference for treatment
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Figure 1: EULAR/ACR 2019 standard for SLE classification and diagnosis requires Master ANA to lead the door.
SLE classification diagnosis is based on personal research and found that ANA titer ≥ 1:80 is more sensitive than 1:160 and 1:320 , And has a higher specificity than 1:40
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The entry standard of "ANA titer ≥1:80" is not based on paper talk, but a threshold set after testing 13,080 SLE patients (Figure 2)
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Figure 2: The source of the entry standard.
The tests related to the entry standard are not stable in all cases.
Different reagent testing methods may also cause negative results [1].
Some scholars are beginning to worry about the sensitivity of the ANA test
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Fortunately, in the worldwide SLE study studied by Professor Aringer, the average sensitivity of ANA test reached 97.
4%, and that of pediatric SLE also reached 97.
1%[2]
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It shows that in the 2019 EULAR/ACR SLE classification diagnostic criteria, the entry criteria are reliable enough! This is also the basis for further targeted treatment based on the SLE classification criteria
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Who will kill you: Which one is the best diagnostic criterion for classification of SLE? The sensitivity of the entry criteria is trustworthy, so what is the overall performance of the 2019 EULAR/ACR SLE classification diagnostic criteria? Is this standard the best diagnostic standard for SLE classification so far? A set of data shows that the classification standard performs very well in sensitivity in all races (Figure 3)
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Figure 3: The 2019 EULAR/ACR classification of SLE has excellent sensitivity.
Of course, this classification also has flaws
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Observation of a small sample confirmed that when SLE patients themselves have uncommon skin lesions, the 2019 EULAR/ACR classification standard may cause more missed diagnoses than the SLICC 2012 standard [3]
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The flaws are not concealed, the sensitivity of the 2019 EULAR/ACR classification criteria in patients with early SLE (ie, undifferentiated connective tissue disease) remains stable, reaching 89%-97%
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However, it is worth noting that some studies have found that although both 2019 EULAR/ACR and SLICC 2012 can improve the efficiency of diagnosis and classification of SLE patients, the former may not be as good as the latter in the recognition of renal involvement [4]
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In the comparison of sensitivity, SLICC 2012 and 2019 EULAR/ACR are almost the same, so which one is more specific? How can it be just that "every grass and trees are all soldiers"? SLE classification and diagnosis still need to be targeted! Sensitivity is a standard alarm, and the state of being "all soldiers" is less prone to missed diagnosis
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The specificity is more like a standard weapon, which can make the standard classification more accurate, and it is not easy to kill the innocent by mistake
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2019 EULAR/ACR is a diagnostic classification standard for SLE with good sensitivity and specificity.
After the patient reaches the short-listing standard, doctors need to score and classify the patient based on the patient's clinical manifestations and other data.
In practice, the following principles should be followed: ①If the classification standard item can be explained by other diseases that are more in line with SLE, the item will not be scored; ②The performance in the classification item can be scored once; ③The classification standard requires at least one clinical classification standard and a total score of ≥10 Divided can be diagnosed; ④The items in the classification standard do not have to occur at the same time; ⑤In the classification standard, only the highest score is recorded in different dimensions
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However, in clinical practice, classification diagnosis often encounters difficult problems: clinical manifestations may be caused by other diseases, this problem is the biggest obstacle to classification diagnosis of SLE
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In the face of this situation, Professor Aringer recommended three methods: a.
List the exclusion diagnostic criteria for each diagnostic item, but the workload is very huge; b.
Exclude patients with other clear disease diagnoses from the criteria Exclude, but this may accidentally injure patients with overlap syndrome or multiple diseases; c.
Directly classified as SLE of unknown classification, but this will impair the accuracy of diagnosis
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The 2019 EULAR/ACR classification and diagnosis principle① can indeed circumvent this situation, but it may exaggerate the effect of other causes on certain symptoms, and it is very dependent on the experience of the evaluation doctor
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In a test of 1074 non-SLE patients, the specificity of complying with the classification diagnosis principle was significantly higher than that of the group that did not comply with the classification principle, which shows that the classification principle of 2019 EUALR/ACR is very important in the practice of SLE classification diagnosis
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For SLE patients, the specificity of 2019 EUALR/ACR is still excellent (85%-98%), and the specificity performance in various races is better than that of ACR 1997 and SLICC 2012 (Figure 4)
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Figure 4: The specific performance of the three classification diagnostic criteria in different races distinguishes "class" and treatment.
When applying 2019 EULAR/ACR, what important points should be paid attention to? After reviewing the sensitivity and specificity of different standards, Professor Aringer pointed out that 2019 EULAR/ACR is the best diagnostic classification standard for SLE so far.
Skin involvement, central nervous system involvement, blood system involvement, complement system abnormalities and other causes can be classified, so that "types" can be distinguished and treated
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Figure 5: 2019 EULAR/ACR classification criteria So, in addition to reliable sensitivity and specificity, whether 2019 EULAR/ACR can aggregate the performance of SLE with different characteristics, so as to ensure complete independence between each item
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Studies have explored the independence between different SLE performances, and have proved the independent existence of each dimension of the 2019 EULAR/ACR classification standard [5] (Figure 6)
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Figure 6: Significant degree of difference between the clinical manifestations of SLE (red: four-point correlation coefficient> 0.
3; purple: four-point correlation coefficient> 0.
2; green: four-point correlation coefficient> 0.
15, note: four-point correlation coefficient <0.
3 can be It is considered that the items are independent of each other; the positional relationship of the circles represents the significant degree of mutual connection) In addition, the anti-double-stranded DNA antibody test in the 2019 EULAR/ACR classification standard is often not accurate enough, especially the ELISA method, which is The 90% specificity in the 2019 standard is compared with other diseases.
Care should be taken when testing and scoring this item
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Clinically, among the manifestations required for the diagnosis of SLE, symptoms such as fatigue, rash, and discoid erythema may not originate from SLE, while the differential diagnosis of clinical manifestations such as fever, weight loss, rash, photosensitivity, oral ulcers, and hair loss is relatively significant Bigger
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Therefore, the unexplained fever is listed as a separate classification standard for SLE, which depends on the specificity of the symptoms themselves
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The focus of 2019 EULAR/ACR will also be an important basis for treatment decisions for SLE patients
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Summary: Professor Aringer believes that two years after its launch, 2019 EULAR/ACR still exhibits a wide range of high sensitivity and specificity
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Moreover, if accurate methods are used to test indicators such as anti-double-stranded DNA antibodies on the premise of complying with the principles of the use of classification standards, the conclusions of classification diagnosis will be very meaningful for reference
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Geng Yan commented that the classification standards of rheumatic immune diseases have gradually changed with the advancement of inspection methods and deepening understanding of the disease.
SLE is no exception.
It has gone through 1997 ACR to 2012 SLICC, and then to 2019 EULAR/ACR classification standards, diagnostic sensitivity And specificity has been further improved
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The ANA titer ≥ 1:80 (Hep-2 cell method) as the entry standard has played an important role.
Only when this standard is met, can it enter the scoring system for classification diagnosis
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In addition, the ANA titer is set at ≥1:80, which is not hand-crafted, but verified through large-scale data comparison
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In terms of autoantibody detection, whether it is ANA or anti-dsDNA antibody, the accuracy of the detection is very important, and it is related to whether it can truly reflect the value of the classification standard
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ANA false negatives will directly lead to misleading exclusion diagnosis and increase the missed diagnosis rate
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Professor Aringer's research shows that the detection method of ANA is relatively stable, and ANA is sufficiently reliable as an entry standard in the 2019 EULAR/ACR SLE classification and diagnostic criteria
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The accuracy of anti-dsDNA antibody detection and its impact on the new classification standards need to be further studied
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Comparing the sensitivity of the 2012 SLICC and 2019 EULAR/ACR classification criteria in different races, some studies have found that the sensitivity of the 2019 EULAR/ACR classification criteria in patients with early SLE (ie, undifferentiated connective tissue disease) is relatively higher than in 2012 SLICC standard
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In terms of the specificity of different races, 2019 EULAR/ACR performed better than ACR 1997 and SLICC 2012
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A very innovative study explored the independence between different SLE performances, proving that each dimension of the 2019 EULAR/ACR classification standard exists independently, and the clinical performance in each dimension cannot be independently scored, but the highest score is taken.
Avoid repeating the accumulation of related items, leading to over-diagnosis
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Two years after the publication of the 2019 EULAR/ACR classification standard, its high sensitivity and specificity have been widely recognized, providing a key basis for early and accurate diagnosis and timely and precise treatment of SLE
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 Expert Profile Associate Professor Geng Yan, Associate Chief Physician and Associate Professor of the Department of Rheumatology and Immunology, Peking University First Hospital Member and Secretary EULAR Certified International Musculoskeletal Ultrasound Trainer Reference: [1] Pisetsky DS, Spencer DM, Lipsky PE, et al.
Assay variation in the detection of antinuclear antibodies in the sera of patients with established SLE[J].
Annals of the rheumatic diseases,2018,77(6):911-913.
[2]Aringer M,Johnson S R.
Systemic Lupus Erythematosus Classification and Diagnosis[J].
Rheumatic Disease Clinics,2021.
[3]Zapata L,Chong B F.
Exclusion of cutaneous lupus erythematosus subtypes from the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus:comment on the article by Aringer M et al[J].
Arthritis&Rheumatology(Hoboken,NJ),2020.
[4] Drehmel KR, Erickson AR, England BR, et al.
Applying SLICC and ACR/EULAR systemic lupus erythematosus classification criteria in a cohort of patients with undifferentiated connective tissue disease[J].
Lupus,2021,30(2):280-284.
[5]Touma Z,Cervera R,Brinks R, et al.
Associations between classification criteria items in systemic lupus erythematosus[J].
Arthritis care&research,2020,72(12):1820-1826.