SYSTEMIC LUPUS ERYTHEMATOSUS ( SLE) د.عقبة
SLE: Is a multisystemic C.T dis. characterized by numerous auto antibodies, circulating immune complex & widespread immunologically determined tissue damage.Epidemiology:
*young women* 15-40 ys.
* F/ M 9:1 but equal in childhood & elderly
Aetiology & pathogenesis:
Although the cause is obscure but there is a multifactorial disorder ;Defect of T-lymphocyte function with polyclonal B-lymphocyte activation .
Uncontrolled production of auto antibodies & immune complexes .
Mechanism of Immunologically mediated tissue damage ;
*Direct type II AB mediated cytotoxicity causing brain damage & abortion due to
cytotoxic effect of cold AB on the neural & trophoblastic tissue.
*Immune complex mediated hypersensitivity type III affect renal & vascular T. lesion.
Evidences of genetic factor ;
*Monozygotic twin pairs 25% - 50%
*Strong familial aggregation
*Among 1st degree relative
*Inherited deficiency of isolated complement component C2
*HLA-B8 & DR3 increase prevalence
V. Evidence of environmental factor ;
*Sunlight provocate SLE
*Drug induce SLE
*Pregnancy , puerperium , fertile women using contraceptives &
men with klinefelter dis. exacerbate SLE
Evidence of viral infection (( in animal model ))
CLINICAL FEATURES:
mild & incomplete cases frequently occur
Skin & mucocutaneous manifestations :
*2/3 of patient
*Alopecia patchy or diffuse in 50% of cases
*Photosensevity erythematosus (Butterfly malar rash )20-30%
*Discoid lupus
*Livedoreticularis
*Raynaud s phenomena ; common
*Oral , nasopharyngeal & vaginal ulcer ; painful
*Lupus profundus ; bullous eruption & panniculitis (rare)
*Chilblain like lesion or digital infarct or periungual erythema
*Subcutaneous nodule ; occasionally
Musculoskeletal manifestations:
*Most common presenting symptoms*Arthritis: Migratory , transient , persistent (chronic) , symmetric,
Non erosive non destructive but deforming & reversible
( unlike R.A)
*Tenosynovitis, sublaxation & contracture causing Jaccoud s
Arthritis (reversible deformity)
*Septic arthritis & osteonecrosis
Cardiopulmonary manifestations :
*Pericarditis , myocarditis & endocarditis
*Pleurisy , fibrosing aleveolitis & acute lupus pneumonitis
*Shrinking lung syndrome
*Impaired lung function test
*Echo-cardiography show verrucous endocarditis (libmann-sack)
Renal manifestations :
*Worst prognosis*Nephrotic syndrome & renal failure
*Sometime limited to ; protein urea or RBC or cast in urine
CNS manifestations:
50% of pat.
Depression , dementia & organic psychosis
Cranial N. lesion , hemiplesia & transverse myelitis
Chorea , cerebellar ataxia & peripheral neuropathy
GIT manifestations:
Frequent but not specific
Peritonitis , perisplenitis , pancereatitis due to vasculitis (abd.pain)
Gasteric or duodenal perforation ( steroid or dis.)
Colonic or gall bladder perforation due to necrotizing arteritis
Eye manifestations:
Keratoconjuctivitis sicca
Episcleritis
Retinal vasculitis (soft exudates)
Lymphatic system:
Lymphadenopathy 50%
Splenomegaly 20-30%
DRUGS INDUCE SLE:
syndrome resembling SLE:Procainamine
Hydralazine
Anticonvulsants
Oral contraceptives
Phenothiazine
Clinical features:
Fever, Polyarthritis, Skin lesion, Lymphadenopathy, Serositis & Pulmonary infiltrate.But: NO renal involvement
NO CNS involvement
NO anti- double stranded DNA (anti-ds-DNA)
NO complement activation
Serology:
* ANA +ve
* Anti- Histon AB +ve 90%
Patient at risk are :
* Slow acetylators taking certain drugs (hydralazin)
* HLA-DR4
Treatment :
* Drug withdrawal get remission
* Short course of CS
Chronic discoid lupus erythematosus :
* It s skin limited .
* More common than SLE.
* Characterized by erythema , scaly follicular plugging & telangectasia.
* ANA+ve but complement are normal .
* SLE occasionally supervene .
AMERICAN DIAGNOSTIC CRITERIA OF SLE (American Rheumatism Association)
Malar rash
Discoid skin rash
Photosensitivity
Mucous membrane ulceration
Arthritis 2 joints or more
Serositis
Renal abnormalities (protein urea , cast)
CNS ( Seizures , psychosis )
Blood count ( WBC↓, RBC↓, platlate ↓)
Auto antibodies (comb s test +ve , VDRL test +ve ……)
ANA +ve
*11 criteria were established ; 4 or more of these the diagnosis is strongly suggested .
INVESTIGATIONS:
Hematological
* Anemia
* Leukopenia
*Lymphocytopenia
*Thrombocytopenia
ESR , plasma viscosity & acute phase reactant ( CRP , S.amyloid are hepatic synthesis in response to active inflammation ).
Serology:
* ANA 90% *Other autoAB : anti RNP (SLE ,MCTD)
* RF anti- SM
* Anti-ds-DNA (most specific) anti-Histon
anti-phospholipids * LE cell test
* VDRL test false +ve anti-RO ,anti-LA
4. Immune complex & complement activation ; measurement of total hemolytic complement (CH50 & C3,C4 component)
5. Synovial fluid analysis
6. Synovial tissue biopsy
7. Arthroscopy
8. Renal biopsy
9. Image studies : X-ray , CT- scan , U.S , MRI , Skeletal scintigraphy & Renal or celiac angiography (sp. In vasculitis).
MANAGEMENT OF SLE:
*Prophylactic measure:-Avoid exposure to sun light ; long sleeved clothes , large brimmed hats & going outdoor in morning hours .
-Avoid photosensitive drugs like antibiotics .
-Immunization for influenza & early treatment of any infection .
-Birth control in SLE pregnant women specially those with nephritis & pregnancy is contraindication with cytotoxic drugs .
-Patient education & psychological support.
*Drug treatment:
1. NSAID2. Corticosteroid:
-Acute life threatening complications(vasculitis , renal dis.).
-As a bridge therapy .
-Initial dose 40-80 mg , tapering the dose gradually to reach the maintenance
Dose.
3. Disease modifying anti-rheumatic drugs (DMARD) ;
It s used in most of C.T dis. as a slow acting & INDICATED IN ;
1/ Persistent sign & symptoms of inflam. arthritis .
2/ Evidence of progressive articular radiological damage sp. In R.A.
3/ Extra-articular manifestation .
4/ Palindromic rheumatism ; a recurring acute arthritis & periarthritis , with symptom
free intervals of days to months between the attacks . It may evolves to typical R.A.
in 30-40%.
DMARD:
Antimalarial drugs:Hydroxychloroquin 200-400mg , 6.5mg/Kg
Chloroquin 250mg
Quenacrin 100mg
*Used in caution with liver dis. & G6PD deficiency .
*S.E ;
- Retinal toxicity .
-Ototoxicity .
-Hemolytic anemia.
-Neuromyopathy .
*C.I in pregnancy, causing:
-Cleft palate.
-Sensory neural deafness.
-Post. Column defect.
*Baseline slit lamb every 6 ms. & CBP , liver function test .
II. Immunosuppressive drugs :
Methotraxate (MTX) ,
Azothioprine (IMMURAN) ,
Cyclophosphomide (INDOXAN) ,
Cyclosporin A (SANDIMMUNE).
Sulfasalazine(SSZ)
Indications:
1/Sever focal or diffuse G.N.
2/Instead high dose of steroid causing sever S.E.MTX:
*Folate antagonist .
*Dose 7.5 -15 mg /week
*Effect after 4-6weeks
*S.E ; GIT , Hepatotoxicity , Nephrotoxicity.
*C.I ; Pregnancy , Alcoholics , Sulphonamide & D.M .
*Regular twice monthly monitoring ; CBP , LFT , Urine analysis .
* Stop the drug - after 2-3 years
- if persistent liver enz. elevation & liver fibrosis
- hypoalbuminemia
AZOTHIPRINE:
*It is asteroid sparing agent
*Used in lupus nephritis & protein urea
*S.E ; mucocutaneous ,hematological , GIT ,hepatic ,malignancy (leukemia , non
Hodgkin lymphoma)
*Regular twice monthly monitoring ; CBP , liver enz .
CYCLOPHOSPHAMIDE:
*Alkalating agent
*Low dose 1-4mg/kg orally , high dose 0.5-1mg I.V
*It secreted by kidney so should reduce the dose in renal impairment *S.E;GIT , Alopecia , hemorrhagic cystitis , ,Scaring of the kidney & it is a carcinogenic to the bladder. gonadal & ovarian T. damage & azospermia.
CYCLOSPORIN:
*Cytokine inhibiter
*CBP & RFT checking regularly
*S.E ; GIT , Renal , Hematological & Hypertension
III. OTHER BIOLOGIC & NON-BIOLOGIC DMARD :
Abatacept (ABA)
Leflunomide (LEF)
Minocycline (MIN)
Rituximab (RIT)
Anti-tumor necrosis factor-
DIAMINODIPHENYLSULPHON (DAPSON):
*Effective in cutaneous discoid lupus & lupus profundus*Dose 50-150mg
*C.I in G6PD deficiency
* S.E ; Hemolytic anemia ,GIT , Tachycardia & abdominal pain
RETIN A :
*Used for skin lesion*Tretinoin (vit. A used in acne vulgaris )
*S.E ; Myalgia , Arthralgia & hyperostosis bone.
MYCOPHENOLATE MOFETIL (Cellcept) :
Used in renal involvement
IV. PLASMAPHERESIS :
To remove immune complex & auto antibodies sp. Cryoglobulines that cause vasculitis . But it is a transient procedure .V. DIALYSIS RENAL TRANSPLANTATION :
Useful in end stage renal damage .
VI. Treatment in pregnancy:
ANTIPHOSPHOLIPID SYNDROMEIs a disorder of recurrent vascular thrombosis , pregnancy wastage & thrombocytopenia associated with persistently +ve lupus anticoagulant &/or +ve anticardiolpin test.
*Salicylate is permitted till 7-10 days before delivery
*Prednisolone less than 60mg not affect the fetus because it metabolize by placenta.
* immunosuppressive are C.I since Azothioprine is probably safe *Breast feeding is not C.I .
Ideal Group
A.H.Yahia
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