Review Article DOI: http://doi.org/10.4038/jmj.v31i2.

73
Systemic Lupus Erythematosus (SLE) - A Review of clinical approach for diagnosis
and current treatment strategies
Narani A1
1
Teaching Hospital Jaffna

Abstract of the disease. Predisposition to SLE is influenced

by genetic factors. The female predominance in
Systemic lupus erythematosus (SLE) is a chronic, SLE may be explained, in part, by the contribution
complicated and challenging disease to diagnose
of certain hormones. Environmental factors,
and treat. The etiology of SLE is unknown
such as smoking, exposure to ultraviolet light,
and various criteria were created to aide in the
diagnosis, focusing on clinical manifestations viral infections, and specific medications (e.g.
and antibody profiles specific to SLE. Treatment sulfonamide antibiotics) are known to trigger
options are limited to a few medications to control SLE. The pathogenesis of SLE is complex with
the inflammation and decrease organ damage. contribution from many components of the immune
Treatment strategies vary according to the specific system. With the underlying genetic predisposition
organ complication. and in response to various triggers the balance of
the immune system shifts towards reacting against
Keywords: Systemic Lupus Erythematosus, Auto
itself, rather than self-tolerance. T and B cells
immunity, Immune complex, Lupus nephritis
become activated, leading to antibody production
SLE Introduction and eventual immune complex formation. These
complexes circulate and deposit in critical tissues
Systemic lupus erythematosus (SLE) is a chronic causing organ injury.
autoimmune disease that can affect almost any
organ system such as the skin, joints, kidneys, SLE Diagnosis
nervous system, heart, lungs and the serous
membranes. Its presentation and course are highly Classification criteria have been derived for
variable, ranging from indolent to fulminant. (1) SLE, mainly for research purposes, to achieve
population homogeneity among research studies.
SLE Epidemiology
The American College of Rheumatology (ACR)
The frequency of SLE varies by sex, age, race and published criteria in 1982, which were revised in
ethnicity. More than 90% of cases of SLE occur 1997. The Systemic Lupus Collaborating Clinics
in women, frequently starting at childbearing age. (SLICC) international group undertook the
The risk of SLE development in men is similar to evaluation and further revision of the above criteria
that of pre pubertal or postmenopausal women. resulting in a new classification system that is based
The female to male ratio peaks at 11:1 during the on clinical and immunologic manifestations. In an
childbearing years. Onset of SLE is usually after actual clinical practice setting, both criteria were
puberty, typically in20s and 30s. analyzed; it was determined that the SLICC 2012
criteria were more sensitive and may allow patients
SLE Pathogenesis
to be classified with SLE earlier in the disease
The etiology of SLE is unknown. Certain course. In the clinical setting, these criteria can be
risk factors have been identified and shown to used as an aid in diagnosis, but formal diagnostic
contribute to disease susceptibility or activate criteria for SLE are lacking.
the immune system causing an inflammatory The SLICC criteria have also been criticized
response, ultimately leading to the development because they were derived comparing the expert’s

Corresponding author: Narani A, email: naraniaravinthan@gmail.com, https://orcid.org/0000-0002-8294-7788, Submitted 16th

October 2019 Accepted 25th November 2019
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted
use, distribution and reproduction in any medium provided the original author and source are credited

Vol.31, No.2, December 2019 -9-

decision (“gold standard”) with a standardized group of manifestations. Moreover, as SLICC criteria
emphasize immunological and hematological events, it might be possible that subjects classified through
SLICC criteria may exhibit less clinically significant multisystem involvement compared with subjects
classified through ACR criteria. (2) 

In 2017, the EULAR and ACR joined in a four-phase project to develop more sensitive (especially for
initial classification) and more specific SLE classification criteria. (3)

New ACR and EULAR criteria for classification of SLE

All patients classified as having systemic lupus erythematous must have a serum titer of antinuclear
antibody of at least 1:80 on human epithelial-2-positive cells or an equivalent positive test .In addition,
a patient must tally at least 10 points from these criteria. A criterion is not counted if it has a more likely
explanation than SLE. Occurrence of the criterion only once is sufficient to tally the relevant points, and
the time when a patient is positive for other criteria.SLE classification requires points from at least one
clinical domain, and if a patient is positive for more than one criterion in a domain only the criterion
with the highest point value counts:

Clinical domains Points Immunological domains Points

Constitutional domain Antiphospholipid antibody
2
Fever domain
Cutaneous domain Anticardiolipin 1gG>40 GPL or 2
Non scarring alopecia 2 anti ß2GP1 IgG>40units or
Oral Ulcers 2 lupus anticoagulant
Subacute cutaneous or discoid lupus 4 Complement proteins domain
Acute cutaneous lupus 6 Low C3 or low C4 3
Arthritis domain Low C3 and low C4 4
Synovitis in at least two joints 6 Highly specific antibodies domain
or tenderness in at least two Anti- ds DNA antibody 6
joints, and at least 30 min of Anti-Smith antibody 6
morning stiffness
Neurologic domain
Derillium 2
Psychosis 3
Seizure 5
Sirositis domain
Pleural or pericardial effusion 5
Acute Pericarditis 6
Hematologic domain
Leukopenia 3
Thrombocytopenia 4
Autoimmune hemolysis 4
Renal domain
Proteinuria>0.5g/24hr 4
Class 11 or V lupus nephritis 8
Class 111 or V lupus nephritis 10

Source: Dr.Johnson

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Treatment of SLE duration, often more than 12 and until 24 months.
Overarching principles In monitoring renal response, reduction of UPr
(to less than 0.8 g/day) following treatment is
SLE represents a challenge for the treating more important than residual haematuria. Patients
physician in terms of diagnosis and treatment. with more severe proteinuria and longer-standing
Its protean manifestations, often multisystem disease are less likely to respond or show more
but occasionally limited to a few or single organ, delayed responses.
have led some physicians to focus exclusively on
evidence of serological autoimmunity (antinuclear Prevention of disease flares is an additional
and more specific auto antibodies), for a disease milestone of SLE treatment. Flares are common
where diagnosis is clinical after excluding in the disease course and contribute significantly
competing diagnoses. Monitoring of SLE through to organ damage accrual and worse outcome.
validated disease activity and chronicity indices, Consistently reported risk factors for a higher
including physician global assessment (PGA), is disease flare rate include younger age at disease
recommended. For patients with severe disease, onset, no use of anti malarial drugs, persistent
multidisciplinary care in dedicated lupus centers generalized disease activity and serological activity
is desirable. Immunosuppressive (IS) therapy (anti-dsDNA, low complement). Assessment of
(for induction and maintenance of remission) is adherence to drug treatment, close monitoring and
indicated in organ-threatening lupus. (4) optimization of disease control in these patients
may reduce the risk for a flare. (7)
Recommendations
Goals of treatment DRUGS USED IN SLE
Hydroxychloroquine
To improve long-term patient outcomes,
management should aim at remission of disease Hydroxychloroquine (HCQ) is recommended
symptoms and signs, prevention of damage accrual for all patients with SLE. There is evidence for
and minimization of drug side-effects, as well as multiple beneficial effects of HCQ in SLE, yet poor
improvement of quality of life. adherence to treatment is not uncommon.
Complete remission (absence of clinical activity Concerns for retinal toxicity with long-term
with no use of GC and IS drugs) is infrequent. (5) To
HCQ therapy led to the use of more sensitive
this end, newly defined low disease activity statesscreening techniques, with a prevalence of retinal
(based on a SLEDAI score ≤3 on anti malarial, or abnormalities exceeding 10% after 20 years
alternatively SLEDAI ≤4, PGA≤1 with GC ≤7.5 of continuous use. (8) Major risk factors for
mg of prednisone and well tolerated IS agents) haveretinopathy include duration of treatment (OR
shown comparable rates with remission, regarding 4.71 for every 5 years of use), dose (OR 3.34 for
halting of damage accrual (OR 0.5–0.7 for increase every 100 mg daily dose), chronic kidney disease
in damage index) and prevention of flares. (adjusted OR 8.56) and pre-existing retinal or
macular disease. Based on existing evidence
Accordingly, treatment in SLE should aim at
suggesting that the risk of toxicity is very low for
remission or, if this state cannot be achieved,
doses below 5 mg/kg real body weight, the daily
at low disease activity in all organ systems.
dose should not exceed this threshold.
(6) In LN, therapy should aim at least partial
remission  (defined as ≥50% reduction in Patients in long-standing remission may have their
proteinuria [UPr] to subnephrotic levels and serum dose lowered, although no studies have formally
creatinine within 10% from baseline) by 6–12 addressed this strategy. The choice of quinacrine,
months; complete renal remission (proteinuria an alternative anti malarial, can be considered in
<500 mg/24 hours and SCr within 10% from patients with cutaneous manifestations and HCQ-
baseline), however, may require longer treatment induced retinal toxicity. (9)

Vol.31, No.2, December 2019 - 11 -

Glucocorticoids higher cost compared with AZA or MTX, and poses
a limitation towards universal recommendation
GC can provide rapid symptom relief, but the in women of reproductive age with non-renal
medium to long-term aim should be to minimize manifestations. Cyclophosphamide (CYC) can be
daily dose to ≤7.5 mg/day prednisone equivalent considered in organ-threatening disease (especially
or to discontinue them, because long-term GC renal, cardiopulmonary or neuropsychiatric) and
therapy can have various detrimental effects only as rescue therapy in refractory non-major
including irreversible organ damage. (10) Risks organ manifestations; due to its gonado-toxic
are substantially increased at continuous GC doses effects, it should be used with caution in women
above 7.5 mg/day, with some studies suggesting and men of fertile age. (13)
that also lower doses might be harmful.
Biological agents
To this end, two approaches can be considered: (1)
use of pulses of intravenous methylprednisolone There is evidence to support beneficial effects
(MP) of various doses (depending on severity of B-cell targeting agents in SL. Belimumab
and body weight), which take advantage of the should be considered in extra renal disease with
rapid non-genomic effects of GC and may allow inadequate control (ongoing disease activity or
for a lower starting dose and faster tapering of PO frequent flares) to first-line treatments (typically
GC, and early initiation of IS agents, to facilitate including combination of HCQ and prednisone
tapering and eventual discontinuation of oral GC. with or without IS agents), and inability to taper
High-dose intravenous MP (usually 250–1000 GC daily dose to acceptable levels (ie, maximum
mg/day for 3 days) is often used in acute, organ- 7.5 mg/day). (14)
threatening disease (renal, neuropsychiatric) after
excluding infections. (11) Patients with persistent disease may benefit from
belimumab; more likely to respond are patients
Immunosuppressive (IS) drugs with high disease activity (eg, SLEDAI >10),
prednisone dose >7.5 mg/day and serological
Consequent initiation of IS drugs facilitates a more activity (low C3/C4, high anti-dsDNA titres),
rapid GC tapering and may prevent disease flares. with cutaneous, musculoskeletal and serological
The choice of agent depends on prevailing disease manifestations responding the most. (15)
manifestation(s), patient age and childbearing
potential, safety concerns and cost. (12) Due to the negative results of randomized controlled
trials (RCTs), RTX is currently only used off-label,
Methotrexate (MTX) and azathioprine (AZA) in patients with severe renal or extra renal (mainly
should be considered in patients with poor symptom haematological and neuropsychiatric) disease
control after a trial with GC and HCQ or when HCQ refractory to other IS agents and/or belimumab, or
alone is unlikely to be sufficient, due to the large in patients with contraindications to these drugs.
experience gained with their use and their relatively
CONCLUSION
safe profile. (12) Mycophenolate mofetil (MMF)
is a potent immunosuppressant with efficacy
SLE remains a challenging disorder that requires
in renal and non-renal lupus (although not in
an interdisciplinary approach with a team of health-
neuropsychiatric disease). 
care providers to diagnose, manage and tailor
In a recent randomized, open-label trial in extra treatment to individual patient needs.
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