Systemic Lupus Erythematosus

Introduction

Chronic inflammatory disease of unknown cause can affect -

• Skin
• Joints
• Kidneys
• Lungs
• Nervous system
• Serous membranes
• Other organs of the body

Lupus
Lupus is an auto-immune disease in which
body creates antigens that attack different
body tissues.

Common Symptoms of Lupus

• Painful or swollen joints and muscle pain

• Unexplained fever
• Red rashes, most commonly on the face
• Chest pain upon deep breathing
• Unusual loss of hair
• Pale or purple fingers or toes from cold or stress (Raynaud's phenomenon)
• Sensitivity to the sun
• Swelling (edema) in legs or around eyes
• Mouth ulcers
• Swollen glands
• Extreme fatigue

There are three types of Lupus: Discoid,

Systemic and Drug-induced.

Types of Lupus

Systemic Lupus: This type of lupus is the most common,it affects major organs, and can
be fatal.

Discoid Lupus: This type of Lupus affects only the skin.

It is not fatal, but can cause severe scarring, and maydevelop into Systemic Lupus if not
treated.
Drug-induced Lupus: This form of Lupus is Systemic Lupus caused by certain
medications. When the
medicine is stopped, the disease goes away.

The History of Lupus

It is not known when Lupus first
appeared, yet there are
mentions of similar diseases
made by Hippocrates in Ancient
Greece.

It was originally known as

simply “Lupus.” This name
came from a rash that most
patients get on their face that
resembles the markings of a
wolf.

A French-man named Pierre

Cazenave made the first clinical
records of Lupus, giving it the
clinical name “Lupus
Erythematosus” in 1851

Who Gets SLE?

80-90% are women of child

bearing age

People of African, Native

American, Hispanic, and
Asian descent are more
likely to get Lupus.
Prevalence of SLE in US is
15 to 50 per 100,000.

24-year-old African-American woman presents to you

for a routine health examination. Your examination
reveals a fine macular rash across the nasal bridge, as
well as painless oral ulcers. Heart, lung, abdominal,
and joint examinations are normal. Antinuclear
antibody (ANA) assay shows a titer of 1:640. Double
stranded (ds)-DNA testing is negative. The CBC is
normal.
Which statement regarding the epidemiology of systemic
lupus erythematosus (SLE) is true?
It most commonly occurs in whites
Overall survival is worse in African Americans
There is a male predominance
The incidence is increased in persons with HLA-B27

Pathophysiology
Hyperreactivity and Hypersensitivity of
immune system
Predisposing genes
HLA II DR- (DR2, DR3) and DQ
HLA III C’2 and C’4
HLA-B8

Genetic + Genetic +
Enviironment factors

î Pathogenic Auto antiibodiies

-DNA/protein, RNA/protein
complexes

IImmune compllexes

Complement activation
Destruction of
Chemotaxins
IL-10 cells
IL-4, IL-6
leukocytes factors
mononuclear cells Inflammatory
What are the symptoms of SLE?

Lupus can present itself in very different ways from person to person. About 80% of
people develop joint and muscle pain, skin rashes, fatigue and a general feeling of being
unwell.

During a lupus flare-up the most common complaints are of flu-like symptoms (with or
without fever), fatigue, muscle and joint pains. Often symptoms are reported to be worse
before a menstrual period and they are often thought to be just pre-menstrual tension.
The following signs and symptoms are the most common:
Arthritis - The pain and inflammation of the joints occurring in SLE differs from that in
rheumatoid arthritis. Although the arthritis can be very troublesome, the joints are rarely
damaged, making SLE a less severe disease in this respect than rheumatoid arthritis. The
pain and discomfort can seem to flit from one joint to another.
The joints most commonly affected are the hands, feet and knees but it can occur
anywhere. Inflammation of the tendons and muscles can also occur.

Fatigue - People often report this as being the most disabling feature of SLE. Fatigue is
not visible and people can have great difficulty in explaining to others how exhausted
they can feel.
At first, most people find it difficult to accept the need for extra rest. However, this is an
essential part of managing the disease and there is no need to feel guilty about it. Have
realistic expectations about how much you can do and avoid 'overdoing' it even if you
feel energetic.

Skin rashes - Skin rashes are common and almost any form can occur. People with SLE
often develop facial rashes; these can vary from a mild redness on both cheeks to a more
pronounced scaly rash. The famous butterfly rash over the bridge of the nose and cheeks
is seen only rarely.
The skin rashes can occur on any part of the body, often on the areas exposed to sunlight.
They usually clear up spontaneously but in some people the rashes can be very
troublesome. Sometimes ulcers occur in the mouth and nose. Mild facial rashes can make
you appear in excellent health although your skin is sore.
Having an invisible illness can be very deceptive.
Sun sensitivity - Many people with lupus are sensitive to sunlight and ultraviolet
radiation. If you are affected in this way, you may find that the prolonged exposure to
sunlight makes your arthritis worse or gives you rashes.
You should avoid sunbathing during the times when the sun is at its most intense, ie
between lOam and 3pm. Use a high factor sunscreen at all times even in winter as
ultraviolet rays penetrate through cloud.
Fluorescent lighting emits more ultra-violet light than normal light bulbs. Ifyou are light-
sensitive a simple, inexpensive plastic filter that can be wrapped round the tube and
secured with a piece of tape is readily available. These can be very important in the
workplace. An employer should be able to get these paid for by the Placement,
Assessment and Counselling Team (PACT) which is part of the Employment Service.

Hair loss - Some people experience varying degrees of hair loss. Although this can be
very distressing it is almost always temporary. Only in rare instances when hair follicles
are scarred is the hair loss permanent.

Kidneys - Kidney involvement was thought to occur in 20-40 per cent of people with
lupus and often caused them much anxiety. However, now that mild lupus is recognised,
doctors realise this figure is overestimated and that kidney involvement is rare in mild
disease. Your urine may be tested at each visit to the clinic as a matter of routine to check
your kidneys. With early detection, kidney involvement can be monitored and treated
successfully if the need arises. The old anxiety that with every flare-up the kidneys will
be further damaged is not well founded. See our separate information on Lupus and the
kidneys.

Depression - People with lupus may experience occasional periods of depression. Some
experience depression as a reaction to long-term illness. For others it can be a result of
the disease attacking the nervous system. Depression often strikes during a flare-up.
However, in either case, these periods can pass without requiring special treatment.

Other symptoms - People with lupus can also have a variety of other symptoms
including high temperature, blood disorders, miscarriage, headaches, weight loss, chest
pain and abdominal pain. However, it is important to remember that the symptoms can
vary greatly from person to person.

Musculoskeletal

90 percent of patients at some time

The earliest manifestation

Polyarticular- knees, carpal joints, and

joints of the fingers, PIIP joint.

Intermittent and migratory.

Morning stiffness last minutes

The arthritis is moderately painful, and

rarely deforming

Myositis

Tenosynovitis

Ischemic necrosis of bone

Cutaneous

Discoid rash
Discrete, erythematous, slightly
infiltrated plaques covered by a
well-formed adherent scale that
extends into dilated hair follicles
(follicular plugging).

Face, neck, and scalp

Slowly expand with active

inflammation at the periphery, and
then to heal, leaving depressed
central scars, atrophy,
telangiectasias, and
hyperpigmentation/depigmentation

Cutaneous
• Oral ulcers
• Alopecia
• Vasculitis rash
• Bullous lessions
• Photosensivity

Cutaneous

Subacute cutaneous
lupus
50 % of affected
patients have SLE
10 % patients with
SLE have this type of
skin lesion
HLA-DR3
Ab to Ro/SSA
Renal involvement
WHO Clasification

• Class I - Minimal mesangial lupus nephritis

• Class II - Mesangial proliferative lupus
• nephritis
• Class III - Focal lupus nephritis
• Class IV - Diffuse lupus nephritis
• Class V - Membranous lupus nephritis
• Class VI -Advanced sclerosing lupus
• Nephritis

Membranoproliferativ Membranoproliferative

• Areas of cellular proliferation

• Thickening of the glomerular
• capillary wall
• “Wiire-lloop”
• Although proliferative
• changes can be focal
• (affecting less than 50% of
• glomeruli), disease of this
• severity is usually diffuse.

Renal

• Tubulointerstitial nephritis

• Vascular disease

• Renal disease infrequently associated with drug-induced lupus

• Pericarditis

• Myocarditis

• Fibrinousendocarditis Libman Sachs

• Atherosclerosis
 •
• MI

Pulmonary Pulmonary involvement

• Pleuritis
• Pulmonary infiltrates
• Interstitial inflammation
• Alveolar hemorrhage

Neurologic
• Cognitive disorders
• Headache
• Mood disorder
• Stroke/TIA
• Seizure
• Neuropathy
• Psychosis
• Aseptic meningitis
• Myelopathy

Hematologic
• Anemia

• Hemolysis
•
• Leukopenia - lymphopenia
•
• Thrombocytopenia

Gastrointestinal
Peritonitis

Vasculitis

Pancreatitis

Dysphagia

Diagnosis
LE cell
ANA titer
Anti-DNA
Complement fixation
ESR

The 11 criteria used for diagnosing systemic lupus erythematosus

1.malar (over the cheeks of the face) "butterfly" rash
2.discoid skin rash: patchy redness that can cause scarring
3.photosensitivity: skin rash in reaction to sunlight exposure
4.mucus membrane ulcers: ulcers of the lining of the mouth, nose or throat
5.arthritis: two or more swollen, tender joints of the extremities
6.pleuritis/pericarditis: inflammation of the lining tissue around the heart or lungs,
usually associated with chest pain with breathing

7.kidney abnormalities: abnormal amounts of urine protein or clumps of cellular

elements called casts

8.brain irritation: manifested by seizures (convulsions) and/or psychosis

9.blood count abnormalities: low counts of white or red blood cells, or platelets
10.immunologic disorder: abnormal immune tests include anti-DNA or anti-Sm (Smith)
antibodies, falsely positive blood test for syphilis, anticardiolipin antibodies, lupus
anticoagulant, or positive LE prep test
11.antinuclear antibody: positive ANA antibody testing

Lupus criteria
M-Mallar rash
D- Diiscoiid rash
S- Serosiitiis
O- Orall ullcers
A-Arthriitiis
P-Photosensiiviity
B-Bllood abnormalliitiies
R- Renall
A- ANA antiibodiies
I- Immune abnormalliitiies
N-Neurollogiic

Blood Abnormalities

.Leukocytopenia (< 4000 on 2 + occasions)

• Lymphopenia (< 1500 on 2 + occasions)

• Hemolytic anemia

• Thrombocytopenia (<100, 000)

Auto antibodies
The ANA test is the best screening test for SLE and
should be performed whenever SLE is suspected

The ANA is positive in significant titer (usually 1:160 or

higher) in virtually all patients with SLE

Immune Abnormalities
Smith antibody
• Anti-ds DNA antibody

• Anti-phospholipid antibody (1997 modification)

• Anti-cardiolipin antibody (IgG or IgM)
• Biologic false positive VDRL (> 6 months)
• Lupus anticoagulant

Disease activity
• Anti-double-stranded DNA titers
• Complement levels (CH50, C3, C4)
• ESR
• CRP
• Complement split products
• Î Erythrocyte-bound C4d
• Complement C1q
• Investigational markers —levels of Ig subclasses,
Ab to C1q and nucleosomes,
Complement activation products,
Soluble T cell activation markers,
Serum levels of various cytokines,
Angiogenic factors, adhesion molecules,
Cell surface makers of immunologic activation

Treatment
NSAIDs
• Antimalarials
(Hydroxychloroquine)

• Corticosteroids

• Immunosuppressive agents
(Cyclophoshamide, Methotrexate,
Azathioprene, Mycophenolate)

• Hematopoietic stem cell transplantation

• Immunoablation alone
• Rituximab
• + cyclophosphamide+ glucocorticoids
• DHEA
• IV Immunoglobulin