Systemic Lupus
Erythematosus
SLE
Let’s start with the questions
QUESTIONS?
1. What is SLE?
2. How does SLE occur in the patient?
3. How can we know this patient has SLE or not?
4. How can I diagnose / classify SLE? ***
5. Can SLE be fatal?
6. Can SLE be cured?
7. How can I manage SLE patient in hospital?
8. How can I manage SLE patient at GP clinic?
9. When will we refer SLE patient to rheumatologist?
10. What are important points in SLE with pregnancy?
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1. What is SLE?
SLE
● Systemic lupus erythematosus (SLE) is a chronic, relapsing, multisystemic autoimmune
disorder with protean manifestations in which almost any organ system can be affected.
● The absence of a unique presentation makes its diagnosis difficult, even for qualified
clinicians.
● The explanation of the term is as follows:
Ø Systemic: means affecting many body systems.
Ø Lupus: derived from lupinus ‘wolf’ because doctors in the past considered that the
skin flare on the face had a wolf-like or werewolf-like appearance.
Ø Erythematosus: means inflamed and red.
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History of SLE
● Classic period - The first time the term lupus was used in the English literature was in the tenth
century by Hebernus of Tours.
● Neoclassic period - The first description of the systemic nature of lupus was reported by Kaposi in
1872.
● Modern period - The description of LE cells by Hargraves (1948).
● The studies of familial aggregation by Leonhardt (1964) and Morteo (1961) were the first steps towards
understanding the pathogenesis of lupus.
● Classification criteria for lupus were first proposed in 1971 by the American College of Rheumatology
(then the American Rheumatism Association).
● Glucocorticoids, the cornerstone in the treatment of lupus, were first used and reported by Hench in
1951.
● Now Contemporary period: SLE in the twenty-first century
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LE Cell
● LE cell is polymorphonuclear leukocytes, contains purple, smoky
homogenous mass of material which is so large that it pushes the nucleas to
one side of the cell
● LE cell phenomenon - Serum from subjects with SLE when incubated with
leucocytes causes cell damage followed by ingestion of resulting cellular
debris by neutrophils, to produce a neutrophil distended by a large,
homogenous, round body which appears pale purple with Romanovsky
staining.
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2. How does SLE occur
in the patient?
Aetiopathogenesis of SLE
● Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the
presence of autoreactive B and T cells and the production of a broad, heterogeneous
group of autoantibodies (autoAb).
● The pathogenesis of lupus can be divided into three stages:
1. genetic predisposition and environmental exposures,
2. loss of tolerance, and
3. immune activation.
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Aetiopathogenesis of SLE
● In stage one, there is a long period of predisposition to autoimmunity with genetic
susceptibility and environmental exposures each contributing to disease development.
○ More than fifty genes have been associated with SLE.
○ Environmental factors, such as ultraviolet light exposure, and exposure to infection, such as that
of Epstein–Barr virus, have been suspected as inducers or enhancers of SLE.
● Stage two develops when there is a loss of tolerance to self-antigens, and autoAb are
generated.
● The third and final stage is inadequate regulation of autoAb production with T and B
cells hyperactivated, and innate immune systems also programmed toward inflammation
eventually leading to tissue damage and clinical manifestations of disease.
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Precipitating factors of Lupus
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Anti-phospholipids { Anticardiolipin (IgG,IgM), lupus anticoagulant } – antiphospholipid syndrome
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Does ANA-negative SLE exist?
● The human epithelial type 2 (HEp-2) cells assay captures the vast majority of SLE;
● However, ANA-negative disease can rarely occur. This has been described in patients
who have antibodies only against SS-A/Ro or ribosomal P, which are cytoplasmic (not
nuclear) antigens.
● ANA-negative disease has also been described in the following scenarios:
1. severe proteinuria (no Igs in the serum to bind with HEp-2 cells) ; usually ANA
turns positive after treatment
2. after cytotoxic therapy
3. in disease remission
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3. How can we know this
patient has SLE or not?
Who is the typical patient with SLE?
● The prevalence is three to four times higher in non-Caucasian
individuals (African-American, Asian)
Demographic of SLE by age of onset
Age of onset < 16 year 16 – 55 year > 55 year
SLE patient % 20 65 15
Female : Male ratio 8:1 10 – 15 : 1 3:1
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• Lung involvement is common and most
frequently manifests as pleuritic pain
(serositis) or pleural effusion.
• Other features include pneumonitis,
atelectasis, reduced lung volume and
pulmonary fibrosis.
• The risk of thromboembolism is increased,
especially in patients with antiphospholipid
antibodies.
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• Raynaud’s phenomenon (RP) is
characterised by vasoconstriction of the
small vessels of the hand and feet in
response to cold, leading to pallor followed
by cyanosis of the affected digits followed
by vasodilatation causing the affected digits
to turn red.
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• 90 % of patients
• Offen associated with early morning
stiffness
• Tenosynovitis
• Joint deformites may arise (Jaccoud’s
arthropathy) as result of tenson damage
(not main complication of SLE)
• Joint erosions are not a feature
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• More specific features of cerebral SLE include visual
hallucinations, chorea, organic psychosis, transverse
myelitis and lymphocytic meningitis.
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• The most common manifestation is pericarditis.
• Myocarditis and Libman–Sacks endocarditis can
also occur.
• The endocarditis is due to accumulation on the
heart valves of sterile fibrin-containing vegetations,
which is thought to be a manifestation of
hypercoagulability associated with antiphospholipid
antibodies.
• The risk of atherosclerosis is greatly increased, as
is the risk of stroke and myocardial infarction. This
is thought to be multifactorial due to the adverse
effects of inflammation on the endothelium, chronic
glucocorticoid therapy and the procoagulant effects
of antiphospholipid antibodies.
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• Medication (such as peptic ulceration or
infection)
• Peritoneal serositis can cause acute pain.
• Mesenteric vasculitis is a serious
complication, which can present with
abdominal pain, bowel infarction or
perforation.
• Lupus enteritis is an important and
potentially life-threatening cause of acute
abdomen
• Thrombotic disease (mesenteric, renal,
and hepatic thrombosis)
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When to suspect SLE?
1. Suspected clinical features from classification
criteria OR
2. Atypical features in one system (eg., young stroke)
OR
3. Involvement of more than one system
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What to do when SLE is suspected?
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4. How can I diagnose
SLE?
4. How can I diagnose SLE?
● Either
○ Revised ACR (American College of Rheumatology) 1987 criteria (1997
update) or
○ SLICC (Systemic Lupus International Collaborating Clinics) 2012 or
○ ACR-EULAR (EUropean League Against Rheumatism) 2017 criteria
Ø can be used to classify SLE.
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How do the criteria for the classification of SLE
relate to making a diagnosis of SLE?
● Although these criteria are extremely helpful when considering the diagnosis
of SLE for an individual patient, it should be emphasized that these criteria
were designed for research purposes and not diagnosis. Especially for mild
cases and patients with early disease, the classification criteria may not be
sensitive enough to make the diagnosis.
● The term incomplete lupus erythematosus (ILE) has recently been used to
describe patients who do not fully meet the criteria for lupus. ILE patients
typically have a positive ANA, arthritis, hematologic involvement, and/or
immunologic abnormalities.
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ACR 1987 criteria (1997)
update (4 out of 11
criteria)
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Mnemonic
for SLE
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SLICC criteria (2012)
● The SLICC criteria for SLE classification requires:
1. Fulfillment of at least four criteria, with at least one clinical
criterion AND one immunologic criterion OR
2. Lupus nephritis as the sole clinical criterion in the presence
of ANA or anti-dsDNA antibodies.
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New
EULAR/ACR
criteria for
classification
of SLE (2017)
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5. Can SLE be fatal?
Prognosis
● The overall 5-year survival rate has improved in the last 20 years to 95% and
● 10-year survival to 90% likely due to earlier diagnosis and aggressive management of
comorbidities.
● Bimodal pattern of mortality in SLE.
Ø Death early in the disease is generally a reflection of active lupus or its treatment
(infection), whereas
Ø Death late in disease is due to active disease, atherosclerosis, and malignancy.
● The most common causes of death are:
1. Infection
2. Active SLE
3. Cardiovascular disease
4. Malignancy
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Four most common causes of death
in SLE patients
● Infection:
○ accounts for 20% to 25% of all deaths and increased five times compared with the general
population.
○ All infections (bacterial, fungal, tuberculous, nontuberculous mycobacterial, viral) are increased
mostly related to the complications of immunosuppressive therapy, especially due to prolonged
use of high-dose corticosteroids.
○ For each increase of prednisone by 10 mg/day, the risk of serious infection increases 11-fold.
● Active SLE:
○ accounts for 35% of deaths especially during first 5 years of disease.
○ Lupus nephritis with renal failure, CNS lupus, vasculitis, and pneumonitis are most lethal.
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Four most common causes of death
in SLE patients
● Cardiovascular disease:
○ accounts for 30% to 40% of deaths particularly after 10 years of disease.
○ The risk of coronary artery disease (2.5 times), stroke (2.5 times), and peripheral
artery disease (9 times) is increased in SLE patients compared with age-matched
general population.
○ Factors playing a role in the development of premature atherosclerosis in SLE
patients include corticosteroid therapy, hyperlipidemia from renal disease,
proinflammatory high-density lipoprotein, HTN, smoking, coagulation abnormalities,
elevation of inflammatory mediators such as type I IFNs, obesity, and vasculopathy
from immune injury.
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Four most common causes of death
in SLE patients
● Malignancy: accounts for 5%–10% of deaths.
○ HPV-associated cervical cancer.
○ Hematologic malignancies and non-Hodgkin’s lymphoma
○ Lung cancer risk increased n smokers
○ Squamous cell skin cancers can arise in discoid lesions.
○ The most common morbidities (SLE damage index) seen in SLE patients are renal
failure, AVN, neuropsychiatric deficits, cardiovascular disease, disfiguring skin
lesions, and osteoporosis.
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Other common morbidities
1. Avascular necrosis of hip
2. Neuropsychiatric deficits
3. Disfiguring skin lesions and
4. Osteoporosis.
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6. Can SLE be cured?
Explain to the patient
● Lupus is a chronic autoimmune disease for which there is no cure.
● Available treatments can relieve symptoms and prevent further damage.
● Research has uncovered new, effective treatments for lupus, and more may
be on the way.
● Regular follow up and good drug compliance are important.
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7. How can I manage
SLE patient in hospital?
7. How can I manage SLE patient in
hospital?
● According to severity / complications of SLE
● According to activity of SLE
1. Non-organ threatening lupus i.e. mild to moderate
disease acitivity
2. Organ threatening lupus – severe disease activity
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Disease activity (extra-renal) has been broadly categorized as mild, moderate or severe
Mild activity Moderate activity Severe activity
SLEDAI <6 6-12 >12
General fatigue fever
lupus-related rash up to 2/9 body Rash involving > 2/9 body surface area,
malar rash, diffuse
Mucocutaneous surface area, cutaneous vasculitis, severe digital vasculitis with impending
alopecia, mouth ulcers,
alopecia with scalp inflammation gangrene
Musculoskeletal arthralgia, myalgia arthritis severe symptomatic myositis
Haematology Platelets 50-149 x 109/l platelets 25-49 x109/l platelets <25x109/l
severe pleurisy and/or pericarditis with
Serositis pleurisy, pericarditis
effusion,ascites
CVS Myocarditis , endocarditis
GI hepatitis enteritis
myelopathy, psychosis, Acute confusion,
CNS
optic neuritis 60
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ESR, CRP, and WBC count Vs Disease activity Vs infection
● ESR – may remain elevated even when the disease is controlled (due to a persistent
polyclonal gammopathy)
● CRP - < 6 times of the upper limit of normal - during a disease flare
● CRP - > 6 times of the upper limit of normal - systemic vasculitis, significant
serositis, or co-existing infection (SLE + fever + elevated CRP – infection needs to be sought out )
● Leucopenia – SLE activity (more common) or infection
● Normal WBC – SLE + infection (low baseline WBC due to SLE)
● WBC differential showing a “left shift” – Infection
● Complement levels – rise in infection and drop with a SLE flare
● An elevated procalcitonin level or lactate may be suggestive of a bacterial infection in a
febrile SLE patient
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Mild disease activity of Lupus
● Prednisolone - 20mg/day for 1-2 weeks and taper gradually AND
● Hydroxychloroquine
○ ± Methotrexate-7.5-15mg/week OR
○ ± leflunomide 20 mg per day
● NSAID should be given as necessary
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Moderate disease activity of Lupus
● Prednisolone 0.5 mg/kg/day for 2-4 weeks and taper gradually (If necessary Pulse IVI
Methylprednisolone 250 mg for 1-2days can be given) AND
● HCQ 6.5 mg/kg/day (200 mg per day should work) AND
○ Azathioprine 1.5 -2.0mg/kg/day or
○ MTX 10- 20 mg/week or
○ MMF 1-2g/day or
○ leflunomide 20 mg/ day or
○ ciclosporin 2.0mg/kg/day or
○ tacrolimus 1-4mg per day in 2 divided doses
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Severe disease activity of Lupus
● Indications for intensive therapy
I. Renal indications – lupus nephritis
II. Extra-renal indications
1. Neuropsychiatric SLE (NPSLE) - cerebritis, myelopathy, optic neuritis,
mononeuritis multiplex, severe peripheral neuropathy
2. Organ-threatening vasculitis – retinal vasculits, mesenteric vasculitis, coronary
vasculitis, severe digital vasculitis with impending gangrene
3. Myocarditis, severe pericarditis with impending cardiac temponade
4. Severe interstitial lung disease
5. Severe symptomatic myositis
6. Lupus gut - Enteropathy
7. Haematological involvement - Severe autoimmune haemolytic anaemia
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Severe disease activity of Lupus
● Intensive therapy 2 phases –
1. Induction therapy (month 1-6)
Ø 2 options – monthly CYC regime or daily MMF regime
2. Maintenance therapy (after 6 month of induction therapy up to at
least 3 – 5 years)
Ø 4 options – MMF , Azathioprine , Leflunomide , 3 monthly CYC
regime
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8. How can I manage
SLE patient at GP clinic?
8. How can I manage SLE patient at
GP clinic?
● CR, ESR, ALT, Creatinine, Urine RE should be monitored at
follow up.
● Adjunctive treatments.
● Management of minor infection.
● Refer back to rheumatogist when indicated.
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Adjunctive treatments
● Advise to avoid sun and ultraviolet light exposure and to employ sun blocks (sun
protection factor 25–50).
● Give Calcium and vit D supplement at start of treatment.
● SLE + ACLA (+) antiphospholipid antibody syndrome
○ Add aspirin to all patients who are ACLA positive unless it is contraindicated.
○ Patients who have had previous thrombosis, require life-long warfarin therapy.
● Cardiovascular risk factors such as obesity, hypertension and hyperlipidaemia, should be
controlled and patients should be advised to stop smoking and reduce excess alcohol
intake.
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Management of minor infection
● Patients can be managed at primary health care for following minor infections
1. Non severe GE without features of sepsis
2. Upper respiratory tract infection
3. Lower UTI (eg, cystitis)
4. Minor skin infection
● For above infections, treat infection appropriately, correct fluid and electrolyte
imbalance and advice adequate and balanced nutrition.
● Continue current dose of steroid (Steroid should not be stopped abruptly)
● Withold DMARDS (eg, methotreaxate, leflunomide, azathioprine,
mycophenolate mofetil, cyclosporine, tacrolimus) until infection is resolved. 70
9. When will we refer
SLE patient to
rheumatologist?
9. When will we refer SLE patient to
rheumatologist?
● At the first time of diagnosed / classified as SLE
● Refer back to rheumatogist when indicated
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What to do when SLE is suspected?
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Refer back to rheumatologist - A
1. CP- cytopenia except mild degree of anaemia OR
2. ESR > 50 OR
3. ALT ≥ 2 times upper limit of normal OR
4. Creatinine > upper limit OR
5. Urine RE- active urinary sediments or hematuria or pyuria or proteinuria ≥ 1+
Ø If the results are acceptable but current steroid dose is prednisolone ≥ 7.5
mg/day or methyl prednisolone ≥ 6 mg/day, refer back to rheumatologist to
adjust steroid dose.
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Refer back to rheumatologist - B
● Red flag signs in SLE
1. Cough ≥ 3 weeks
2. Fever ≥ 2 weeks
3. Vasculitic rash on palms and tip of toes
4. New onset edema
Ø If the results are acceptable and current steroid dose is prednisolone < 7.5
mg/day or methyl prednisolone < 6 mg/day, continue current treatment and
repeat CP, ESR, ALT, creatinine and urine RE after 3 months and review the
patient 75
10. What are important
points in SLE with
pregnancy?
10. What are important points in SLE
with pregnancy?
● Pregnancy may be planned in stable patients with inactive lupus and UPCR
<50 mg/ mmol or 24 hr Urinary proteinuria <0.5G/day, for the preceding 6
months, with GFR that should preferably be >50 ml/min.
● The following medications must be stopped before planning the pregnancy.
○ Leflunomide – 2 years
○ MTX (methotrexate) – 3-6 months
○ CYC (cyclophosphamide) – 3-6 months
○ MMF (mycophenolate mofetil) – 3-6 months
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10. What are important points in SLE
with pregnancy?
● Acceptable medications include hydroxychloroquine, and where needed, low
dose prednisone, azathioprine and/or calcineurin inhibitors (cyclosporin,
tacrolimus).
● The intensity of treatment should not be reduced in anticipation of pregnancy.
● During pregnancy, acetylsalicylic acid should be considered to reduce the risk
of pre-eclampsia.
● Patients should be assessed at least every 4 weeks, preferably by a
specialist physician and obstetrician.
● Flare of LN during pregnancy can be treated with acceptable medications
stated above depending on severity of flare. 78
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