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1. Systemic Lupus Erythematosus
Done by: BaraaMohammed Karajah
(200010)
Supervised by: DR. Sofian Zawahreh

2. Definition:
•Systemic Lupus Erythematosus: an autoimmune disorder leading to inflammation and tissue
damage in multiple organ systems.
•Epidemiology:
oSex:>(10:1)
oPeakincidenceandprevalence
oAge of onset
oWomen:15–44 years
oMen: no particular age
oRace:highest in populations of African descent

3. Etiology:
•Systemic lupus erythematosus (SLE) is an idiopathic chronic inflammatory
disease with genetic, environmental, and hormonal factors.
•Genetic predisposition:
•HLA-DR2andHLA-DR3are commonly present in individuals with SLE.
•Genetic deficiency ofclassical pathwaycomplement proteins(C1q, C2,
C4)inapprox. 10%of affected individuals
•Hormonal factors:
•Hyperestrogenicstates(e.g., due tooral
contraceptiveuse,postmenopausalhormonal therapy,endometriosis) are
associated with an increased risk of SLE.
•Environmental factors
•Cigarette smokingand silica exposure increase the risk of developing SLE.
•UV light andEBV infectionmay trigger disease flares, but there is insufficient
evidence on whether they cause SLE.
•Drugs such asprocainamideorhydralazine.

4. Pathophysiology
•The exact pathomechanismof SLE is not fully understood, but the following two
processes are the most widely accepted hypotheses:
•Autoantibodydevelopment:deficiency of classicalcomplement proteins(C1q, C4,C2)
→failure ofmacrophagestophagocytoseimmune complexesandapoptoticcell material
(i.e., plasma and nuclearantigens) →dysregulated, intolerantlymphocytestargeting
normally hidden intracellularantigens→autoantibodyproduction (e.g.,ANA,anti-
dsDNA)
•Autoimmune reactions
•Type III hypersensitivity(most common inSLE) →antibody-antigen
complexformationinmicrovasculature→complementactivation andinflammation
→damage toskin,kidneys,joints, small vessels
•Type II hypersensitivity→IgGandIgMantibodiesdirected againstantigenson cells (e.g.,red
blood cells)→cytopenia

5. Types
a. Spontaneous SLE
b. Cutaneous lupus erythematosus (skin lesions without systemic disease)
c. Drug-induced lupus
d. ANA-negative lupus—associated findings
•Arthritis, Raynaud phenomenon, subacute cutaneous lupus.
•Serology: Ro (anti-SS-A) or antiphospholipid antibody positive, ANA negative.
•Risk of neonatal lupus in infants of affected women.
•ANA negativity can be influenced by laboratory testing methods, disease duration, and
treatment.

6. Clinical Features
•ThediagnosisofSLEisbasedonthepresenceofatleast4of11known
manifestationsofthedisease:
A.Constitutionalsymptoms:Fatigue,malaise,fever,weightloss.
B.Skin:FourofthemanifestationsofSLEareoftheskin:
oMalarrash.
oPhotosensitivity:flarewithexposuretoUV-Blight(thusareconsideredphotosensitive)andresolve
withnoscarringoftheskin.
oDiscoidrash.
oOralulcers.
C.Joint:
oArthritisispresentin90%ofthosewithSLEandisoftenthefirstsymptomthatbringspatientstoseek
medicalattention.
oSLEgivesjointpainwithoutdeformationorerosion.Thatiswhythex-rayisnormal

7. D. Serositis: Inflammation of the pleura and pericardium gives chest pain potentially with both pericardial
and pleural effusion.
E. Renal:
o Any degree of abnormality can occur, from mild proteinuria to end-stage renal disease requiring dialysis.
o The most common glomerulonephritis is membranous.
o Red cell casts and hematuria occur.
F. Neurologic: Symptoms include psychosis, seizures, headache, or stroke from vasculitis.
G. Hematologic:
o Hemolytic anemia is part of the diagnostic criteria, but the anemia of chronic disease is more
commonly found.
o Lymphopenia, leukopenia, and thrombocytopenia are also seen.
o Any blood involvement counts as 1 criterion.
H. Immunologic (laboratory) abnormalities:
o Positive ANA.
o Anti-double-stranded DNA.
o Anti-Sm.
o False positive test for syphilis.
o Each of the serologic abnormalities counts as 1 criterion.

8. -Additional findings:
•Mesenteric vasculitis.
•Raynaud phenomenon.
•Antiphospholipid syndromes.
•Alopecia is common in SLE but is not one of the “official” diagnostic criteria.
•Pneumonia, alveolar hemorrhage, and restrictive lung disease happen in SLE
but are not criteria for the diagnosis of the disease.
•Ocular findings are not part of formal diagnostic criteria (Photophobia, Retinal
lesions, Blindness)

10. Diagnosis
•Diagnostic Tests:
-Antinuclear antibodies (ANA):
o Found in 95% to 99% of cases.
o A negative ANA is extremely sensitive for lupus, but a positive ANA has little specificity.
o Many rheumatologic diseases are associated with a positive ANA. Do not treat an
asymptomatic ANA.
-Antinuclear antibody is a very sensitive but nonspecific marker for systemic lupus
erythematosus. If antinuclear antibody is elevated, more specific autoantibodies (anti-double-
stranded DNA) can confirm the diagnosis.
-Anti-double-stranded (DS) DNA (60%) and anti-Sm (30%): These are found only in SLE. They
are extremely specific for SLE.

11. -Anti-SSA (10%) and anti-SSB (20%): They add little to the diagnosis if the DNA is positive.
These tests are most often found in Sjogrensyndrome (65% of cases).
-The SSA, SSB, and anti-Sm tests are most useful when the ANA is positive and DS-DNA
test is negative.
-Decreased complement levels: They can correlate with disease activity. They can drop
further with acute disease exacerbations.
-In an acute lupus flare, complement levels drop and anti-DS DNA levels rise.
-MRI of the brain is most often normal in lupus cerebritisunless there has been a stroke.

12. Treatment
1. Preventive treatment: avoid sun exposure, smoking cessation, vaccines, diet and exercise.
2. All patients with any active disease should receive hydroxychloroquine—for constitutional,
cutaneous, and articular manifestations. Hydroxychloroquineis continued as a preventative
measure even after resolution of symptoms. Baseline and subsequent annual eye examinations are
needed because of retinal toxicity.
3. Mild active disease: NSAIDs or low-dose steroids.
4. Moderate or severe disease typically requires a steroid-sparing immunosuppressive agent.
5. Severe organ-or life-threatening flares should be treated with high-dose steroids and other
immunosuppressive agents (azathioprine,mycophenolate, cyclophosphamide, etc.).
6. Many other treatment options are specific to the organ and manifestation of disease. For
example, cutaneous lupus is treated very differently than lupus nephritis.

13. Drug induced lupus:
The most common causes of drug-induced lupus are hydralazine, isoniazid, and
procainamide.
Keep the following in mind:
-Drug-induced lupus gives anti-histone antibodies and always a positive ANA.
-Complement level and anti-DS DNA are normal.
-It never gives renal or CNS involvement.

14. Antiphospholipid Syndrome
•APL syndrome is an idiopathic disorder with IgG or IgM antibodies made against negatively
charged phospholipids.
•The biggest risk factor for APS is SLE; APS occurs in up to 40% of these patients.
•The 3 main types are:
o Lupus anticoagulant.
o Anticardiolipinantibodies.
o Anti-beta2-glycoprotein-I antibody

15. Presentation/Diagnostic Tests:
-Antiphospholipid syndrome (APS) presents with a thrombotic event (deep venous
thrombus or arterial thrombus) or pregnancy morbidity (fetal loss, severe
preeclampsia, placental insufficiency) plus a positive serology for 1 of 3
antiphospholipid antibodies: anticardiolipinantibody, anti-beta2-glycoprotein-I
antibody, or lupus anticoagulant.

16. -Unlike the other causes of thrombophilia, APL syndrome is often associated with an elevation of
the aPTTwith a normal prothrombin time (PT) and normal INR.
-False positive VDRL or RPR with a normal FTA occurs because the antibody reacts with the reagent
in the lab which is a cardiolipin.
-Anticardiolipinantibodies more often give spontaneous abortion, and the lupus anticoagulant is
more often associated with an elevated aPTT.
APL = clotting + elevated aPTTand normal PT

17. -The best initial test is the mixing study, in which the patient’s plasma is mixed with an
equal amount of normal plasma:
o If the elevation in aPTTis from a clotting factor deficiency, the aPTTwill come down to normal.
o If the APL syndrome antibody is present in plasma, the aPTTwill remain elevated.
-The most specific test for the lupus anticoagulant is the Russell viper venom test (RVVT).
The RVVT is prolonged with APL antibodies and does not correct on mixing with normal
plasma.

18. Treatment
-Clots in APL are initially treated with a NOAC or warfarin.
-An asymptomatic APL antibody does not need to be treated.
-Thromboses (DVT or PE) are treated with a NOAC or heparin and warfarin as would be done with
any other form of thrombosis. The duration of treatment is controversial. It is not clear if lifelong
therapy,
instead of the usual 6 months of treatment, is indicated after a single thrombotic episode.
Recurrent thrombotic episodes are treated lifelong.