EULAR 2018

What did we learn: Written by Jennifer Nelson R.N.

I am reporting on the Presentation of the new SLE classification criteria given by Sindhu
Johnson, MD PhD of the University of Toronto. On behalf of Martin Aringer, EULAR Co-
Chair, SLE Classification Steering Committee and Investigators.

Of note, the work shown in Dr. Johnson’s presentation was supported by EULAR and
ACR but has not been reviewed for endorsement.

The 1982 ACR classification criteria for SLE includes 11 criteria, of which at least 4
needed to be met to diagnose or classify a patient with lupus. The criteria included:
Malar rash, Discoid rash, Photosensitivity, Oral ulcers, Arthritis, Serositis, Renal disorder,
Neurologic disorder, Hematologic disorder, Immunologic disorder (LE cell preparation,
Anti-DNA, Anti-Sm, Lues serology false positive), and Antinuclear antibodies.

In 1997, the ACR criteria were revised to reflect changes in thinking. LE cell preparation
was removed and Anti-Phospholipid antibodies were added. These criteria were in
play for quite a while with very good sensitivity and specificity. However, as
Rheumatologists moved toward a notion of identifying earlier disease, they found that
the ACR criteria don’t perform as well in the first 5 years of early disease.

In 2012, the SLICC group proposed a new set of classification criteria. The 2012 SLICC
criteria says that to classify a patient as having SLE, he or she must satisfy 4 of the clinical
and immunologic criteria used in the SLICC classification criteria, including at least one
clinical criterion and one immunologic criterion, OR if he or she has biopsy-proven
nephritis compatible with SLE in the presence of Antinuclear antibodies or Anti-dsDNA
antibodies. SLICC also add more criteria to the old ACR criteria. In doing so, they
improved the validity of the SLE Classification. These changes had improved sensitivity
but had decreased specificity relative to the old ACR criteria.

The goal of the combined EULAR/ACR supported project was to see if they could
develop one set of criteria where they could have worldwide consensus. They wanted
the new criteria to be more sensitive than, but equally specific to the ACR criteria. They
wanted it to reflect updates in the understanding of SLE. And they wanted it to be
useful for early classification of disease.

They used a 4-phase methodologic approach to develop the new classification criteria.
Phase I: Criteria Generation. They wanted to capture all the potential criteria that
should be considered in the development of new lupus criteria. This required four
studies. 1. Systemic review and Meta regression ANA Entry Criterion. They found that an
ANA of > 1:80 has an excellent sensitivity, but it is not enough to classify a patient. 2.
Delphi Exercise of international SLE experts. The international lupus community was
asked to nominate criteria that can distinguish SLE from non SLE. 145 criteria were
nominated and ultimately reduced to 40 criteria. 3. International Early SLE cohort.
Fever, Arthralgia and Fatigue appear to distinguish early SLE from closely mimicking
conditions. 4. SLE patient survey. Phase II: Criteria Reduction to a more manageable
number. The criteria were again reduced from 40 to 21. ANA was considered Entry
criteria. Phase III: Item reduction, weighting, and threshold score determination. The
criteria were clustered into categories of lupus manifestations. Phase IV: Refinement
and Validation leading to the new SLE Classification criteria. In order to validate the
findings 21 international lupus centers were each asked to contribute 100 cases and
100 controls. They also focused on obtaining a sample of early cases. They chose
controls that could mimic SLE. The data was reviewed by 3 independent reviewers.
There were >2200 subjects entered and of those 501 cases and 500 controls were
randomly selected to form the Derivation cohort. The remainder comprised the
validation cohort.

The newly proposed Classification criteria is as follows:

Entry criteria: Antinuclear antibodies (ANA) at a titer of >1:80 on Hep-2 or an equivalent

positive test. The first step will be to test the ANA. If the ANA is positive at >1:80, we
move on to the next criteria.

Additive criteria: Do not count a criterion if there is a more likely explanation than SLE.
Occurrence of a criterion on a least one occasion is sufficient. SLE classification requires
at least one clinical criterion. Criteria need not occur simultaneously. Within each
domain, only the highest weighted criterion is counted toward the total score.

Clinical Domains and criteria, including weight:

Constitutional domain

Fever (2)

Cutaneous domain

Non-scarring alopecia (2)

Oral ulcers (2)

Subacute cutaneous or discoid lupus (4)

Acute Cutaneous lupus (6)

Arthritis domain

Synovitis in >2 joints or tenderness >2 joints and >30 minutes of morning stiffness (6)
Neurologic domain

Delirium (2)

Psychosis (3)

Seizure (5)

Serositis domain

Pleural or pericardial effusion (5)

Acute Pericarditis (6)

Hematologic domain

Leukopenia (3)

Thrombocytopenia (4)

Autoimmune hemolysis (4)

Renal domain

Proteinuria >0.5g/24h (4)

Class II or V Lupus Nephritis (8)

Class III or IV Lupus Nephritis (10)

Immunologic domains and criteria, including weight:

Antiphospholipid antibodies domain

Anticardiolipin IgG >40 GPL or anti B2GP1 IgG >40 units or Lupus anticoagulant (2)

Complement proteins domain

Low C3 or low C4 (3)

Low C3 and low C4 (4)

Highly specific antibodies domain

Anti-dsDNA antibody (6)

Anti-Smith antibody (6)

Classify SLE > 10 points

If a patient has a positive ANA and scores 10 points, they can be classified with SLE.
In conclusion, the Derivation cohort has higher sensitivity and specificity than previous
criteria sets. They have defined a system of criteria, which produces a measure of the
relative probability that a particular case (combination of clinical features) has SLE.
This system has defined the 10 most important criteria in defining that probability and
defined them carefully to improve reliability of application. The system has been
validated against a large number of cases including many cases which are not clear
cut SLE. This provides a new foundation for SLE research.