Lupus

PRIMER
Box 4 | 1997 update of the 1982 ACR revised criteria for classification of SLE
Although in clinical trials, four or more parameters are required to classify SLE, many
patients — especially in early disease stages — have fewer parameters. In addition,
the complete range of systemic lupus erythematosus (SLE) phenotypes is not taken
into account, which limits the use of these classification criteria for diagnostic
purposes in routine clinical care.
Malar rash
• Fixed, flat or raised erythema (superficial reddening of the skin) over the malar
eminences, but tends to spare the nasolabial folds
Discoid rash
• Erythematous raised patches with adherent keratotic scaling and follicular
plugging
• Atrophic scarring may occur in older lesions
Photosensitivity
• Skin rash as a result of unusual reaction to sunlight
• Diagnosis is based on patient history or physician observation
Oral ulcers
• Oral or nasopharyngeal ulceration, usually painless and based on physician
examination
Non-erosive arthritis
• Tenderness, swelling or effusion in two or more peripheral joints
Pleuritis or pericarditis
• Pleuritis is defined by a convincing history of pleuritic pain, rubbing heard by
a physician or evidence of pleural effusion
• Pericarditis is documented by an electrocardiogram, rubbing heard by a physician
or evidence of pericardial effusion
Renal disorder*
• Persistent proteinuria of >0.5 g daily or >3 on urine dipstick if quantification
is not performed
• Cellular casts in urine, including red blood cells or haemoglobin, and can be
granular, tubular or mixed
Neurological disorder
• Seizures or psychosis in the absence of offending drugs or known metabolic
derangements, such as uraemia, ketoacidosis or electrolyte imbalance
Haematological disorder*
• Haemolytic anaemia with reticulocytosis
• Leukocytopaenia: <4,000 per mm 3 on two or more occasions
• Lymphocytopaenia: <1,500 per mm 3 on two or more occasions
• Thrombocytopaenia: <100,000 per mm 3 in the absence of causative drugs
Immunological disorders*
• Anti-DNA autoantibody
• Anti‐Sm autoantibody
• Antiphospholipid autoantibodies (including an abnormal serum level of IgG or IgM
anticardiolipin autoantibodies, a positive test result for lupus anticoagulants using
a standard method, or a false-positive test result for >6 months confirmed by
Treponema pallidum immobilization or fluorescent treponemal antibody
absorption test)
Positive antinuclear autoantibody
• An abnormal titre of antinuclear autoantibody by immunofluorescence or an
equivalent assay at any point in time and in the absence of drugs
For the 1982 American College of Rheumatology (ACR) revised classification criteria see
REF. 95. For the 1997 update of the 1982 ACR revised classification criteria see REF. 96.
*Only one parameter needs to be present. Adapted with permission from REF. 96,
John Wiley and Sons.
SLICC classifi cation criteria for SLE in 2012 (REF. 98).
With the current SLICC classification criteria, it is possible
to meet the classification criteria with 4 of the 17
criteria (including at least one clinical and one immunological
criterion) or biopsy-proven lupus nephritis in
the presence of ANAs or anti-dsDNA autoantibodies.
Unfortunately, with the wide range of SLE manifestations
covered by the SLICC classification criteria and
despite the increase in the sensitivity to 97% (compared
with 86% for ACR classification criteria), the specificity
has dropped to 84% (compared with 94% for the ACR
classifi cation criteria) 97,98 . One study showed that, of
2,055 patients with SLE from 17 centres in the Portuguese
and Spanish national registries, 296 patients did not
fulfil the ACR 1997 criteria; however, 63% of those did
meet the SLICC classification criteria 102 . The increased
sensitivity gives the SLICC classification criteria greater
validity, but the loss in specificity compromises them as
classification criteria 99 . However, the SLICC classification
criteria clearly have not made considerable improvement
compared with the existing ACR classification criteria in
identifying patients with early disease other than for renal
disease as an isolated clinical manifest ation. The use of
one of these sets of criteria over the other remains to be
tested in future trials and research studies 103 .
Assessment of disease activity
The assessment of disease activity is challenging because
of the multifaceted complexity of the clinical presentations
and their variation over time. Thus, at least in clinical
trials and research settings, the use of instruments
is essential for a standardized assessment of the disease
activity to enable comparison between different centres
and to monitor patients reliably. For this purpose, several
instruments have been developed and validated 104 (BOX 5).
The ability to measure disease activity also facilitates
the management of the disease in patients. It is also known
that severe disease activity at presentation (a SLEDAI‐2K
score of ≥20) is a prognostic factor associated with mortality
105 . Standardized definitions of clinically meaningful
change in disease activity (that is, remission, worsening
or flare, improvement and persistent active disease) have
been developed and validated 104 . Prolonged remission
(inactive disease) is an infrequent outcome and only
occurs in ~2.4% of patients with SLE without treatment
106 . Patients who manifest a prolonged serologically
active (high anti-dsDNA antibodies or low complement
values) and clinically quiescent (SACQ) period require
no specific treatment during this period and accrue less
damage over a decade than matched controls. However,
close surveillance is warranted for this group 107 . More
recently, a consensus definition of lupus low disease activity
(LLDAS) has been developed, but this requires further
external validation 108 .
In 1996, the SLICC group, in collaboration with the
ACR, developed the SLICC ACR Damage Index (SDI) 109 ,
which measures the accumulation of organ damage
that has occurred since the onset of SLE. The SDI has
been shown to be valid and reliable 110 and is accepted
as an independent outcome measure 111 . Damage in SLE
predicts future damage accrual and mortality 112 .
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