Systemic lupus

Erythromatosus
SLE
 Introduction

▪ Systemic lupus erythematosus (SLE) is a

multiorgan autoimmune disease which is
characterised by the presence of auto-antibodies
and immune complexes.
 Introduction

▪SLE usually presents as a multi-systemic

disease and frequently manifests as
musculoskeletal and cutaneous presentations,
such as arthritis, myalgia and malar rash.
Prevalence rates in lupus are estimated to be as
high as 51 per 100 000 people in the USA. The
incidence of lupus has nearly tripled in the last
40 years.
▪Women are affected nine times more frequently
than men (female: male = 9:1).

▪ The disease appears to be more common in

urban than rural areas.

▪ 65% of patients with SLE have disease onset

between the ages of 16 and 55 years, 20% present
before age 16, and 15% after the age of 55.
▪ SLE is a chronic disease of variable severity
with a waxing and waning course, with
significant morbidity that can be fatal if not
treated early in some patients.
Several factors acting
on the immune
system, resulting in
the generation of
autoantibodies,
immune complexes,
inflammatory T cells,
and inflammatory
cytokines that may
initiate inflammation
and damage to
various organs.
 Criterion Definition
Malar Rash Rash over the cheeks

Discoid Rash Red raised patches

Photosensitivity Reaction to sunlight, resulting in the development of or increase in skin

rash

Oral Ulcers Ulcers in the nose or mouth, usually painless

Arthritis Nonerosive arthritis involving two or more peripheral joints (arthritis in

which the bones around the joints do not become destroyed)

Serositis Pleuritis or pericarditis (inflammation of the lining of the lung or heart)

Renal Disorder Excessive protein in the urine (greater than 0.5 gm/day or 3+ on test
sticks) and/or cellular casts (abnormal elements the urine, derived from
red and/or white cells and/or kidney tubule cells)
 Criterion Definition
Neurologic Seizures (convulsions) and/or psychosis in the
Disorder absence of drugs or metabolic disturbances
which are known to cause such effects
Hematologic Hemolytic anemia , leukopenia , lymphopenia
Disorder or thrombocytopenia. The leukopenia and
lymphopenia must be detected on two or
more occasions. The thrombocytopenia must
be detected in the absence of drugs known to
induce it.
Antinuclear Positive test for antinuclear antibodies (ANA)
Antibody in the absence of drugs known to induce it.
Immunologic Positive anti-double stranded anti-DNA test,
Disorder positive anti-Sm test, positive antiphospholipid
antibody such as anticardiolipin, or false
positive syphilis test (VDRL).

Definite SLE 4 or more positive criteria

❖ ≥ 4 criteria (1 immunological, 1 cilnical at least), or

❖Biopsy-proven lupus nephritis with positive ANA or

anti-dsDNA antibodies.
•Acute cutaneous lupus erythematosus
Abrupt in onset.
Frequently appear after sun exposure.
Characterised by erythema and oedema.

Malar rash Generalized erythema &

30-60% Bullous lesions
•Subacute cutaneous lupus lesions:

Symmetric, widespread.

Superficial, and non-scarring lesions.

In the neck, shoulders, upper chest, upper back,

and extensor surface of the arms.

Begin as small photosensitive, erythematous,

scaly papules or plaques that evolve into a
papulosquamous (psoriasiform) or annular
polycyclic form
•Chronic cutaneous lupus lesions:
•Other rashes
Livedo reticularis.
Periungal erythema.
Vasculitic lesions.
 Alopecia.
Exaggerated hair
Loss.
Occurs in most SLE
patients.

 Photosensitivity.
Rash after exposure
to ultraviolet (UV) B
radiation.
Occurs in 60–100% of
SLE patients.
•Oral and nasal ulcers:

The most common SLE

manifestation.

Usually painless.

No temporal association
with disease activity.

Involvement of the upper

airway mucosa can also
occur and cause hoarseness.
•Arthralgia:
The most common presenting
symptom in SLE (76-100%).

•Arthritis/arthropathy:
Non-erosive, non-deforming
arthralgias/ arthritis.
Primarily affecting the small joints
of the hands, wrists, and knees.

Jaccoud arthropathy (10%)

•Myositis:
Generalised myalgia and muscle tenderness are
common during disease exacerbations.

Inflammatory myositis involving the proximal

muscles has been reported in 5–11%.

Drug-induced (glucocorticoids or antimalarial).

•Avascular bone necrosis:

Acute joint pain presenting late in the course of
SLE and localised to a very few areas, especially
shoulders, hips, and knees, may indicate AVN.
✓Renal involvement occurs in 40–70% of all SLE
patients and is a major cause of morbidity and
hospital admissions.

✓LN is defined as clinical and laboratory

manifestations that meet ACR criteria
(persistent proteinuria 0.5 gm per day or
greater than 3+ by dipstick, and/or cellular
casts including red blood cells [RBCs],
hemoglobin, granular, tubular, or
mixed).
 Abbreviated International Society of Nephrology/
Renal Pathology Society (ISN/RPS) 2003 Classification of
Lupus NephritiS

Class I: Minimal mesangial lupus nephritis

Class II: Mesangial proliferative lupus nephritis

Class III: Focal lupus nephritis

Class IV: Diffuse segmental (IV-S) or global (IV-G) lupus nephritis

Class V: Membranous lupus nephritis

Class VI: Advanced sclerosing lupus nephritis

 4- Nervous system features
•Central nervous system: •Peripheral nervous
▪Aseptic meningitis system:
▪Cerebrovascular disease ▪Acute inflammatory
▪Demyelinating syndrome demyelinating
▪Headache (including polyradiculoneuropathy
migraine and benign (Guillain-Barré
intracranial hypertension) syndrome)
▪Movement disorder (chorea) ▪Autonomic disorder
▪Myelopathy ▪Mononeuropathy,
▪Seizure disorders single/multiplex
▪Acute confusional state ▪Myasthenia gravis
▪Anxiety disorder ▪Neuropathy, cranial
▪Cognitive dysfunction ▪Plexopathy
▪Mood disorder ▪Polyneuropathy
▪Psychosis
▪ Pericarditis (25%).

▪ Pericardial effusions (asymptomatic and are

usually mild to moderate).

▪ Myocardial involvement (rare).

▪ Accelerated, premature atherosclerosis and

valvular heart disease.

▪ An increased risk for myocardial infarction or

stroke.
▪ Pleuritic chest pain or pleurisy
▪ Pleural effusion
▪ Acute pneumonitis
▪ Interstitial lung disease
▪ Pulmonary capillaritis or diffuse alveolar
haemorrhage
▪ Shrinking lung syndrome
▪ Pulmonary embolism or infarction
▪ Pulmonary hypertension
Major clinical manifestations include anaemia,
leucopenia, thrombocytopenia, and the
antiphospholipid syndrome.

The immunosuppressive drugs used in the

treatment of SLE may cause pancytopenia.
▪ Lymphadenopathy (40%), is a benign finding in
SLE, commonly seen in young patients with
cutaneous involvement and constitutional
symptoms, with good response to
corticosteroids.

▪ Splenomegaly (10–45%), particularly during

active disease, and is not necessarily associated
with cytopenias.
Abdominal Pain (30%)
Serositis/ Peritonitis
Pancreatitis
Mesenteric Ischemia
Dyspepsia
Protein-losing enteropathy

Hepatomegaly (12–25%).
Abnormal Liver Enzymes.
Autoimmune hepatitis.
▪Retinal vasculitis may present as ‘cotton
wool’ spots in the retina visible on
ophthalmoscopy or fluorescein
angiography.

▪ Corneal and conjunctiva involvement is

usually part of Sjogren’s syndrome.

▪ Uveitis and scleritis (rare).

▪ Optic neuritis (rare).

❑Hematological Manifestations

❑Urine analysis

❑Imaging Studies

❑Renal biopsy
 Hematological Manifestations

•Anemia: Hemolytic with coomb’s positive and

reticulocytosis, may also be secondary to chronic
disease, CRF, blood loss, drugs.

•Leukopenia / Lymphopenia: in active disease.

•Thrombocytopenia.

•ESR is frequently elevated.

•A rise in CRP is an indicator of infection.

 Autoantibodies

❖ANA assay is an ideal screening test because

of its sensitivity (95%) and simplicity.

❖Patient with a negative ANA test has less than

a 3% chance of having SLE; thus, a test is useful
for excluding the diagnosis of SLE. However, in
the presence of typical features of lupus, a
negative ANA test does not exclude the
diagnosis.
Anti-dsDNA have been correlated with LN and
increased disease severity, damage or poor
survival.

Antiphospholipid antibodies are strongly

associated with features of the antiphospholipid
syndrome (APS), CNS involvement, severe LN,
and death.

Anti-Ro (SS-A) and anti-La (SS-B) antibodies have

been associated with neonatal lupus, and
congenital heart block in the children of
seropositive mothers.
Autoantibodies to single stranded DNA (ssDNA)
and individual histones are common in SLE as
well as in drug-induced lupus.

Anti-Sm (Smith) antibodies are detected in 10–

30% and their presence is pathognomonic for
SLE.

Anti-ribosomal P antibodies clinical association

with diffuse CNS involvement, psychosis, and
major depression.

Rheumatoid factor found in 18% of the patients.

 Urine analysis

•Proteinuria over 0.5g/day or +3 dipstick if

quantitation not performed.

•Hematuria or pyuria.

•Cellular casts: may be red cell,

haemoglobin, granular, tubular, or mixed.
 Imaging Studies

•Joint radiography often provides little

evidence of SLE given the absence of
erosions. The most common radiographic
changes include periarticular osteopenia and
soft tissue swelling.

•Chest radiography and high-resolution CT

scans can be used to monitor interstitial lung
disease
 Renal biopsy

•Identify the specific type of glomerulonephritis.

•Aid in prognosis, and to guide treatment.
•Distinguish renal lupus from renal thrombosis,
which may complicate antiphospholipid antibody
syndrome and require anticoagulation rather
than immunomodulatory therapy.
SLE treatment is highly individualized
and depends on symptom
manifestations, organ involvement,
and disease severity.

Duration of therapy is also highly

individualized and is based on the
patient's response.
 General
considerations

 Avoidance of UV lights.

 Using sunscreens.

 Termination of the use of provoking

drugs.

 Avoidance of contraceptive pills.

 Adequate antibiotics therapy for

infections.
 Steroid and non-steroidal anti-
inflammatory drugs

• NSAIDs:
Used for musculoskeletal complaints, pleurisy,
pericarditis, and headache.

• Steroids:
Dose according to organ involvement up to full
dose and pulse intravenous steroid in major
organ involvement as renal, cerebral affection.
 Disease-Modifying Antirheumatic
Drugs (DMARDs)

•Antimalarial drugs
Hydroxychlorquine or chloroquin in the cases
of arthralgia, arthritis, skin symptoms, and
serositis.

•Methotrexate
Dose: 7.5-25 mg/week for treatment of
polyarthritis, vasculitis
Azathiorpine
May be used as alternative to
cyclophoshamide in lupus nephritis, or as
steroid sparing agent.

Cyclophosphamide
It remains the main stay in the cases of lupus
nephritis, alveolitis, vasculitis, CNS
involvement
Dose: 500-1000 mg/m2/month for 6 months, then
same amount/3 months for 1.5 years.
•Cyclosporine
In the cases of hematology involvement,
membranous lupus nephritis
Dose: 3 mg/kg/day
Side effect: hypertension, increased serum
creatinin, gingival hyperplasia, hypertrichosis.

•Mycophenolate Mofetil
In adults, mycophenolate is typically taken twice
daily for a total dose of 2 - 3 grams (2000 - 3000mg)
per day.
 B-cell targets

T-cell target and

costimulatory blockers

Cytokine inhibition
 B-cell T-cell target Cytokine
&costimulato
targets ry blockers inhibition

Anti-CD20 antibody: Abatacept Anti-TNF-α:

Rituximab IDEC-131 Infliximab
Ocrelizumab

Anti-IL-1:
Anakinra
BLyS blockers:
Belimumab Anti-IL-6:
Atacicept
Tocilizumab
Take Home Message
SLE is a clinically and immunologically heterogeneous
disease.

Over the last 50 years, the prognosis of SLE has

improved considerably.

Advanced knowledge of the pathogenesis of SLE

has led to new therapeutic approaches targeting
specific Molecules.

Targeted therapies will hopefully allow for

individualized treatment regimens tailored to each
patient’s immune system. And thus the toxicities
associated with current broad-based
immunosuppression may some day be avoidable.