Genetic:
v High association with HAL-DR2 & HLA-B8
v More common in females (possible association with chromosome X).
v An increase in relative risk in monozygotic twins & in relatives of patients with SLE
Infection: High association with hepatitis B virus infection
Immunological:
v Decreased clearance of circulating antigens due to defect in early complement
components
v Defective immuntolerance
v Exposure of antigens on apoptotic cells after oxidant stress e.g.UV rays, may activate
lymphocytes.
v Dysfunction of T-suppressor lymphocytes with overactivity of B-lymphocytes producing
antibodies against exogenous and endogenous antigens:
o Anti-Cell antibodies: against RBCs, WBCs, and platelets
o Antinuclear antibodies: The speckled pattern is more specific than the diffuse one
o Anti- DNA antibodies: anti- double strand antibodies are more specific than
single strand. Theses antibodies form immune complexes and consume C3. The
main reaction is in the kidney resulting glomerulonephrittis.
o Lupus cells: The WBCs destroyed by anti-WBCs→ nucleaproteins that reacts
with ANA→ formation of immune complex. The surviving WBCs will engulf this
immune complex. The resulting cells will contain an esinophilic inclusion body
with peripheral displacement of the nucleus
o Anti-VII, anti, thyroid antibodies,
o Anti Sm antibodies
o Anti Ro & anti La antibodies.
o Rheumatoid factor, false +ve Coomb's and test for syphilis
4- Endocrinal: SLE exacerbates by contraceptive drugs, pregnancy, and ovulation inhibitors
(estrogen binds to the receptors of T & B lymphocytes increasing activation and
survival of these cells)
5- Drugs: Hydralazine, INH, procainamide, D-pencillamine& interferon alpha.
6- Physical agents: Sunlight and ultraviolet rays.
Clinical picture:
· Female:male 9:1
· Onset around the 2nd or 3rd decade
· Prevalence: 30/100000 in Caucasians, 200/100000 in africans
1-Cutaneouse: presents the second most common presentation
§ Alopecia: is seen in 50% of cases
§ Purpura: due to thrombocytopenia or vasculitis.
§ Photosensitivity
§ Butterfly lupus: area of eryhrema in butterfly area that becomes scaly with hyper or
hypopigmentation. It spares the naso-labial fold.
§ Raynaud's phenomenon and skin ulcers
§ Vitiligo
§ Discoid rash: erytmatous raised patches with keratotic scaling and scarring
2-CNS:
§ Cerebral: ataxia, aseptic meningitis, cranial nerves palsy, convulsions, stroke
§ Chorea
§ Transverse myelitis
§ Psychological: psychosis or depression (it should be diffrentiated from steroid
induced psychosis that occurs in the 1st few weeks of steroid treatment by > 40 mg
prednisone, and resolves by decreasing or disontinuation of the tretment).
§ Peripheral neuropathy
3-Eye:
§ Sjogren syndrome
§ Episcleritis, conjunctivitis
§ Optic neuritis
§ Retinal vasculitis can lead to infarcts(cystoid bodies).
4-CVS:
§ Pericarditis +pericardial effusion + constrictive pericarditis
§ Myocarditis & cardiomyopathy
§ Sterile endocarditis (Verrrucous endocarditis or Libman- Sacs endocarditis): it may
lead to AR or MR
§ Vascular: arterial(coronary arteries)and venous thrombosis(DVT & pulmonary
embolism) + Raynaud's phenomenon.
§ Hypertension may occur with renal affection.
5-Pulmonary:
§ Pleurisy ± pleural effusion
§ Acute lupus pneumonitis & fibrosing alveolitis
§ Interstitial lung fibrosis
§ Shrinking lung syndrome : caused by recurrent pulmonary infarction
§ Pulmonary hypertension & cor-pulmonale (especially with antiphospholipid
syndrome).
§ Intra-alveaolar hemrrhage wirh ARDs
6-GIT:
§ Mouth: ulcers up to cancrun oris. Associated fungal infection may be seen.
§ Esophagus: esohagitis & dysphagia
§ Intestine: nausea, vomiting, diarrhea & bleeding
7-Renal:
§ Pathological changes (WHO classification):
I- No renal affection
II- Mesengial nephritis
III- Focal proliferative nephritis
IV- Diffuse proliferative nephritis
V- Membranous nephritis
VI- Sclerosing nephropathy
§ Clinical presentation: Hematuria, proteinuria, nephritic syndrome, and nephrotic
syndrome, acute or chronic renal failure.
8-RES: Hepatosplenomegaly & generalized lymphadenopathy
9-Muscles: Myalgia & myositis
10-Skeletal system:
§ Joints: arthralgia & picture of RA may be present in 30 % of cases
§ Bone: Osteonecrosis (Avascular necrosis) that affects mainly hip joint
§ Osteoporosis.
11-Hematological:
§ Pancytopenia
§ Increased incidence of thrombosis (antiphospholipid) and infection (leucopenia,
deficiency of complemnt & immunosuppressive therapy).
§ Lymphopenia(guide for disease activity).
Variants of SLE:
I- Discoid lupus:
· Skin lesion is the main presentations
· SLE may supervene.
· ANA positive(30% of cases) but anti-DNA is negative
II- Antiphospholipid syndrome:
Etiology: Antibodies directed against glycoprotein (Apolipoprotein H) in platelets and
endothelium
Types:
· Type I: No other associated disorders
· Type II: associated with SLE or other connective tissue disorders.
Clinical picture:
· Recurrent arterial and venous thrombosis
· Recurrent abortions
· Cutanoeus vasculitis
· Verrucous endocarditis
Investigations:
1. Thrombocytopenia
2. Prolongation of PTT which fails to be corrected by addition of plasma
3. Three types of antibodies
§ Lupus anticoagulant
§ Anticardiolipin antibodies
§ Antibodies responsible for false positive test of syphilis.
III- Drug induced lupus:
§ Cause: Hydralazine, procainamide phenytoin.
§ C/P: mainly cutanouse manifestations, arthritis, fever and skin eash but without
systemic affection(No nephritis or cerebral diseases).
§ Resolves when drug stopped
§ Invstigations: anti-DNA antibodies are negative
.
III- Others:
· Overlap syndrome
· Subacute cutaneous lupus: +ve ANA, +ve anti Ro and anti La antibodies.
· Late onset; after the age of 50 years
· Neaonatal lupus: with +ve anti Ro and anti La antibodies.
Investigations:
I- Serological:
1. Increased ESR(parallel disease activity), normal CRP (unless there is infection).
2. Positive antibodies:
· Anti-Cell antibodies: against RBCs, WBCs, and platelets
· Antinuclear antibodies
· Anti- DNA antibodies
· Lupus cells
· Anti-VII, anti, thyroid antibodies,
· Rheumatoid factor
· Anti Ro and anti La antibodies: done if ANA is –ve
· Anti Sm antibodies: specific for lupus
3. Low serum level C3 & C4 especially in case of active nephritis
II- Investigations according to organ affection e.g.
1- Renal function tests or renal biopsy & urine analysis
2- CBC: pancytopenia
3- Echocardiography: verrocus endocarditis
Crteria for disease activity;
C/P: seizures, hair loss, fever, mouth sores, oliguria, hematuria, rashes and anemia
Lab.: -↓C3, C4 -+ve anti DNA antibodies(high titre)
Criteria for the diagnosis of SLE according to the American Coullege of
rheumatology:
1- Malar rash
2- Discoid rash
3- Photosensitivity
4- Oral ulcers
5- Arthritis in 2 or more peripheral joints with tenderness, swelling or effusion(noneosive)
6- Serositis
7- Renal disorder: presistant proteinuria of > 0.5 gm/24hrs or cellular acsts.
8- Neurological disorder: sizures or pschosis in the absence of drugs or known metabolic
derrangments
9- Hematological disorders:
· Hemolytic naemia
· Leucopenia: < 4000/mm on two or more occasions
· Lymphopenia: <1500/mm on two or more occasions
· Thrombocytopenia: < 100,000/mm on two or more occasions
10- Immunological disorders
· Anti native DNA in abnormal titre
· Anti SM
· Positive antiphospholipid antibodies
11- Antinuclear antibodies: by immunofluorescence in the absence of any drugs known to
induce ANAs
To diagnsoe SLE, 4 or more of these criteria should be present..
Treatment
1. Avoidance of:
· Exposure to sun light and to drugs that exacerbate lupus (e.g. penicillin,
sulfonamides, contraceptive pills).
· Unnecessary surgery or immunization
2. NSAID: used in articular symptoms and mild inflammatory manifestations
3. Antimalarial drugs: Hydroxychloroquine (4-7 mg/Kg/day orally), used in skin disease,
arthritis(not responding to NSAID), antiphospholipid syndrome
4. Corticosteroids: is used with severe systemic manifestations as cerebral, renal or
hematological manifestations:
· In cases with severe lupus nephritis or cerebritis, steroids is used in pulse therapy
starting by large dose ( lgm prednisone)/ IV/ day for 3-5 days followed by
maintainace therapy
· Maintenance dose is 1 mg/kg/day prednisone till manifestations of disease activity
disapper(resolution of symptoms and signs, normal C3 &C4, -ve anti DNA) then
reduce to small maintanince dose (10-15 mg/day) to prevent relapse and end organ
damage.
· Intra-articular triamcinolone:in severe joint affection
5. Immunosuppressive drugs: Used in steroid resistant cases or as steroid sparing drugs.
· Azathioprine(Immuran): 2mg/Kg/day oral. Side effects: pancytopenia and prolonged
use may lead to increased risk of hematological malignancy
· Cyclophosphamide(Endoxan): reserved for severe manifestations as it's extremely toxic
, it may lead to BM depression or infertility. Dose: 1-3 mg/Kg/ day orally.(Pulse therapy
0.5- 1 gm IV in combination with pulse steroid is more effective)
· Cyclosporin(Sandoimmun)
6. Plasmapharesis: Used in severe cases with systemic affection e.g. nephrititis to remove
circulating immuncomplexes.
7. Immunoglobulin therapy: for thrombocytopenia
