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Systemic Lupus Erythematosus (SLE)

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Mais Ayoub

on 8 February 2014

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Transcript of Systemic Lupus Erythematosus (SLE)

Systemic Lupus Erythematosus (SLE)
Pathophysiology
Clinical features
Diagnosis
Definition
Normal
During apoptosis, the cell's cytoskeleton breaks up and causes the membrane to bulge outward (Blebs). These bulges -or blebs- may separate from the cell taking a portion of cytoplasm with them to become known as apoptotic bodies. Phagocytic cells eventually consume these fragments .. so self-Ag are normally hidden from the immune system .
SLE
In patients with SLE , removal of these blebs by phagocytes is inefficient so that they are transferred to lymphoid tissues where they can be taken up by antigen presenting cells . The self-antigens from these blebs can then be presented to T-cells which in turn stimulate B-cells to produce autoantibodies directed against self-antigens.
--> the combination of availability of self-antigen and failure of the immune system to inactivate B-cells and T-cells which recognize these self-antigens leads to :-
-Development of autoantibodies that either form circulating complexes (type 3 hypersensitivity reactions), or deposits by binding directly to tissues (type 2 hypersensitivity reactions).
-This leads to activation of complement and influx of neutrophils causing inflammation in those tissues
-abnormal cytokine production ; increased blood levels of IL-10 and alpha-interferon.
Most common connective tissue disease.
Chronic, inflammatory, multisystem disorder with arthralgia and rashes as the most common clinical features, and
cerebral
and
renal
disease as the most serious problems
SLE occurs world-wide but the prevalence varies from country to country, with the most common prevalence of 1:250 being in African American women. In other populations the prevalence varies between 1:1000 and 1:10000.
It is about nine times as common in
women
as in men, with a peak age of onset between 20 and 40 years.

Epidemiology :-
Genetics
Hormonal
Drugs
Aetiology
Environmental factor
immunologic
There is a higher concordance rate in monozygotic twins (up to 25%) compared to dizygotic twins (3%).
First-degree relatives have a 3% chance of developing the disease, but approximately 20% have autoantibodies
Eight different chromosomal areas have been identified containing genes linked to development of SLE. These include some HLA genes, especially A1, B8 and DR3. Homozygous deficiencies of the complement genes C1q, C2 or C4 convey a high risk of developing SLE.

Premenopausal women are most frequently affected. In addition, SLE has been seen in males with Klinefelter's syndrome (XXY)

hydralazine, isoniazid, procainamide and penicillamine can induce a form of SLE which is usually mild in that kidneys and the CNS are not affected.

-Ultraviolet light can trigger flares of SLE, especially in the skin.


Nervous system
Involvement of it occurs in up to 60% of cases and symptoms often fluctuate.

Fatigue
,
headache
and
poor concentration
are common, and often occur without laboratory evidence of active disease.
Epilepsy, migraines, cerebellar ataxia, aseptic meningitis, cranial nerve lesions, cerebrovascular disease or a polyneuropathy may be seen
Lesions may be due to
vasculitis
or
immune-complex deposition
,
thrombosis
or
non-inflammatory microvasculopathy
.
The commonest finding on MRI scan is of
increased white matter signal abnormality
Eyes
Retinal vasculitis
can cause
infarcts
(cytoid bodies) which appear as hard exudates, and
haemorrhages
.
There may be
episcleritis
,
conjunctivitis
or
optic neuritis
, but
blindness is uncommon
.
Secondary Sjögren's syndrome is seen in about 15% of cases.

Gastrointestinal
Mouth ulcers
may occur, which may or may
not be painful
.

Mesenteric vasculitis
is a serious complication which can present with abdominal pain, bowel infarction or perforation.

Lungs
Up to 50% of patients will have lung involvement sometime during the course of the disease.
Recurrent
pleurisy
and
pleural effusions
(exudates) are the most common manifestations and are
often bilateral
.
Pneumonitis and atelectasis may be seen; eventually a restrictive lung defect develops with loss of lung volumes and raised hemidiaphragms.
Rarely, pulmonary fibrosis occurs, more commonly in overlap syndromes.
Intrapulmonary haemorrhage associated with vasculitis is a rare but potentially life-threatening complication.
The risk of thromboembolism is increased
, especially in patients with antiphospholipid antibodies.

CVS
The heart is involved in 25% of cases.
Pericarditis
, with small
pericardial effusions
detected by echocardiography, is common.
mild
myocarditis
also occurs, giving rise to
arrhythmias
.
Aortic valve lesions and a cardiomyopathy can rarely be present.
A non-infective
endocarditis
involving the mitral valve (Libman-Sacks syndrome) is very rare

There is an increased frequency of ischaemic heart disease and stroke in patients with SLE
.

Kidney
This is one of the main determinants of
prognosis
.
The typical renal lesion is a
proliferative glomerulonephritis
, characterised by heavy haematuria, proteinuria and casts on urine microscopy.
asymptomatic patient with proteinuria may be in the early stages of lupus nephritis, and treatment may prevent progression to renal impairment.

regular monitoring of urinalysis and blood pressure is essential
.
Renal vein thrombosis
can occur in nephrotic syndrome or associated with antiphospholipid antibodies.

Skin of the face
Erythema, in a 'butterfly' distribution on the cheeks of the face and across the bridge of the nose, is characteristic. (
malar rash
)
Discoid lupus
is a benign variant of lupus in which only the skin is involved (SLE <5%). The rash is characteristic and appears on the face as well-
defined
erythematous plaques that progress to
scarring
and pigmentation

Arthritis and arthralgia
> 90%
A variety of joint problems occur, including migratory arthralgia and early morning stiffness, tenosynovitis and small joint synovitis that can
mimic rheumatoid
.
However,
joint deformities and erosion are rare
and synovitis is seldom obvious clinically. When joint deformities do occur, they result more from
tendon inflammation
and damage than from bone destruction (Jaccoud's arthropathy).

-
Raynaud's
:is common and may antedate other symptoms by months or years.

-
Vasculitic lesions
on the finger tips and around the nail folds, purpura and urticaria occur.


- In 40-50% of cases there is
photosensitivity
(diffuse and maculopapular) .
- palmar and plantar rashes, pigmentation , alopecia and Livedo reticularis(
Pink-blue mottling caused by capillary obstruction and swelling in skin venules
)
Hematology
A variety of abnormalities may occur, including neutropenia, lymphopenia, thrombocytopenia or haemolytic anaemia, due to antibody-mediated destruction of peripheral blood cells. The degree of lymphopenia is a good guide to disease activity.

Vary greatly between patients.
Remitting and relapsing illness, typically present with non-specific constitutional symptoms .
fever ,fatigue, arthralgia, myalgia, malaise and/or skin problems.

The American College of Rheumatology (ACR), has developed and refined a set of classification criteria. if at least 4 of the 11 criteria develop at one time or individually over any period of observation, then the patient is likely to have SLE.

DOPAMINE RASH
D=Discoud lupus / O=oral ulcers/ P=photosensitivity A=arthritis (hands,wrists,knees)/M=malar rash/I=immunologic criteria =anti-Smith, anti-ds-DNA, anti-Ro, anti-La/N=neurologic changes/E=incr. ESR(not criteria)
R=renal disease/A=ANA+/S-serositis (pleurisy, pericarditis)
Hematologic disease=hemolytic anemia, thrombocytopenia, leukopenia

Investigations
-A
full blood count
may show a leukopenia, lymphopenia and/or -thrombocytopenia.
-Anemia of chronic disease or autoimmune haemolytic anaemia also occurs.
-The
ESR
is
raised
in proportion to the disease activity. In contrast, the
CRP
is usually
normal
but may be high when the patient has lupus pleuritis or arthritis or a coexistent infection.
-
Urea
and
creatinine
only
rise
when
renal disease
is advanced. --Low serum albumin or high urine protein/creatinine ratio are earlier indicators of lupus nephritis.

-
Autoantibodies
- many different autoantibodies may be present in SLE but the most significant are
ANA
(>95%+ve but not specific) ,
anti-dsDNA
(highly specific, only >60%), anti-Ro, anti-Sm and anti-La . 40% are +ve RhF ,
Antiphospholipid
antibodies are present in 25-40% of cases but not all of these patients develop antiphospholipid syndrome, anticardiolipin antibodies cause false +ve syphilis serology.
drug induced: antihistones
-Serum complement
C3
and
C4
levels are often
reduced
during active disease. The
combination of high ESR, high anti-dsDNA and low C3 may herald a flare of disease
. All these markers tend to return towards normal as the flare
improves
but in some patients anti-dsDNA levels
remain
high even during clinical remission.

-
Histology
, Characteristic histological and immunofluorescent abnormalities are seen in biopsies from the
kidney
and skin.
-
Diagnostic imaging
,
CT
scans of the brain sometimes show
infarcts
or
haemorrhage
with evidence of cerebral atrophy. MRI can detect lesions in white matter which are not seen on CT. However, it can be very difficult to distinguish true vasculitis from small thrombi.

Management
There is NO cure for SLE, and complete sustained remissions are rare.
* we use drugs :-
-To control acute, severe flares.
-To develop maintenance strategies that suppress symptoms to an acceptable level.
-To prevent organ damage
Should be through specialist SLE and lupus nephritis clinics .
Conservative ttt:
-prevent rashes with high-factor sunblock creams, sunglasses.
reduce Cardiovascular risk factors

Many patients do not need ttt with corticosteroids or immunosuppressive tablets only needing NSAIDs for symptoms




topical corticosteroids--> cutaneous symptoms

Antimalarial (chloroquine and hydroxychloroquine)->mild skin disease fatigue and arthralgia that cannot be controlled by NSAIDs [retinal toxicity side effect]

Severe flares(pericarditis,pleuritis),renal or cerebral involvement reflect severe disease activity must be treated with high doses corticosteroids.

Renal and cerebral involvement require immunosupressants
as well,
cyclophosphamide
was the drug of choice but due to side effects it is now replaced with
mycophenolate mofeitil.
Azathioprine used to maintain remission.
Rutiximab->
antiCD20 in
refractory cases
(antiCD20 B lymphocytes-->reduce autoantibodies)

Prognosis
episodic
course is characteristic, with exacerbations and complete remissions that may last for long periods.
SLE
can also be a chronic persistent condition.
The mortality rate in SLE has fallen dramatically over the last 50 years; the
10-year survival rate is about 90%
, but this is lower if major organ-based complications are present.

Deaths early in the course of disease are mainly due to renal or cerebral disease or infection.
Later coronary artery disease and stroke become more prevalent.
Chronic progressive destruction of joints as seen in RA and OA occurs rarely, but a few patients develop deformities such as ulnar deviation.
Patients with SLE have an
increased long-term risk of
developing some cancers, especially
lymphoma

Mais Ayoub
Rawan Ghishan

A 35-year-old
woman
is brought for the evaluation of confusion lasting 1 day. her friends and family inform you that "she did not know how to come home from work" and that lately "she has not been herself"

you found that the patient has :
elevated BP,
Decreased air entry on the right lung base with dullness to percussion
symmetrical MCP and wrist joint swelling

chemistry profile:
Creatinine elevated
Proteinurea


classification of lupus nephritis :-
class 1-Minimal mesangial lupus nephritis
class 2-Mesangial proliferative lupus nephritis
class 3-Focal lupus nephritis <50% of glomeruli
class 4-Diffuse lupus nephritis >50% of glomeruli
class 5-Membranous lupus nephritis
class 6-Advanced sclerosing lupus nephritis >90% of glomeruli
Full transcript