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Systemic Lupus Erythematosus

Definition – The diagnostic criteria are – (Ref. Hari. 18th ed., Pg-2728, table 319.3)
  1. Malar rash – Fixed erythema, flat or raised over the molar eminences. 
  2. Discoid rash – Erythematous raised patches with adherent keratotic scaling and follicular plugging
  3. Photosensitivity – Exposure to UV light causes rash.
  4. Oral ulcers. - Pain less
  5. Arthritis (Non erosive)
  6. Poly Serositis – Pleuritis, pericarditis, ascites
  7. Renal disorder – Proteinuria > 0.5 g/d or cellular cast, Renal failure. 
  8. Neurologic disorder – Seizure or psychosis, stroke, neuropathy, Aseptic meningitis
  9. Hematologic disorder
    1. Hemolytic anemia or
    2. Leukopenia (< 4000/ul) or
    3. Lymphopenia (<1500/ul) or
    4. Thrombocytopenia (<100,000/ul)
  10. Antinuclear antibody – 
    1. Anti ds DNA
    2. Anti – Sm Ab and/or
    3. anti phospholipid ab
To diagnosis SLE the criteria is ≥ 4 features of the above.


Important Points

Uveitis, Lung cavitation & Joint deformity are not the features of SLE.

Differential Diagnosis of Rash over face (Malar)
  1. Non erythematous-
    1. Chloasma
  2. Erythematous-
    1. SLE
    2. Photosensitivity reaction
    3. Contact dermatitis
Raynaud phenomena is not a feature of SLE.


Important Points:

Cutaneous manifestation in SLE

  1. Systemic rash
  2. Discoid rash
  3. Subacute cutaneous lupus erythematosus (LE) Rash is a photosensitive.
  4. Urticaria
  5. Lichen planus-like dermatitis
  6. Bullae.
  7. Small painful ulcerations on the oral or nasal mucosa are common in SLE.
  8. Tin-tack sign,
    1. Also known as carpet tack sign (LQ 2012), is a useful clinical feature in diagnosing discoid lupus erythematosus.
    2. Hyperkeratotic scale extending into the follicular infundibulum creates keratotic spikes when viewed from the scale’s undersurface, resembling a carpet tack.


Note: Patients with these manifestations are exquisitely photosensitive; most have antibodies to Ro (SS-A).


Drugs associated with SLE are:
  1. Antiarrhythmics → (Procainamide, disopyramide, propafenone)
  2. Antihypertensives → (Hydralazine,. ACE inhibitors, and Beta blockers)
  3. Antithyroid → (Propylthiouracil)
  4. Antipsychotics → (Chlorpromazine and lithium)
  5. Anticonvulsant → (Carbamazepine and phenytoin) 
  6. Antibiotics → (Minocycline and Macrolides, INH)
  7. Antihyperlipidemic  → (Lovastatin, Simvastatin)
In drug induced SLE
  1. Anti histone antibodies are positive
  2. Anti dsDNA is usually absent
  3. Renal involvement is not a feature or very uncommon
  4. Polyserositis is a feature
  5. Rash is very common
  6. Features disappear on discontinuation of drugs.
Systemic features of SLE
  1. Renal
Table: Classification for Lupus Nephritis (Ref. Hari. 18th ed., Pg-2727, table 319.2)
Class I Minimal mesangial Normal histology with mesangial deposits
Class II Mesangial proliferation Mesangial hypercellularity with expansion of the mesangial matrix
Class III Focal nephritis Focal endocapillary ± extracapillary proliferation with focal subendothelial immune deposits and mild mesangial expansion
Class IV Diffuse nephritis Diffuse endocapillary ± extracapillary proliferation with diffuse subendothelial immune deposits and mesangial alterations (Diffuse wire loop deposits)
Class V Membranous nephritis Thickened basement membranes with diffuse subepithelial immune deposits; may occur with Class III or IV lesions and is sometimes called mixed membranous and proliferative nephritis
Class VI Sclerotic nephritis Global sclerosis of nearly all glomerular capillaries
(Note: In SLE, wire loop deposits is seen in diffuse nephritis)
Factors associated with Adverse Prognosis and High Risk of Renal Progression in Lupus Nephritis
  1. Hypertension
  2. Hypocomplementemia
  3. High Anti Ds DNA antibody titres
  4. Pregnancy
  5. Nephritic urinary sediment
  6. Azotemia  
  7. Thrombocytopenia
  8. Proteinuria
  9. Decreased GFR
Note: Presence of anti LA (SSB) indicate lower involvement of kidney in SLE


Extra Edge Most common cause of death in SLE is renal failure followed by infection.

  1. Lungs involvement in SLE
    1. Pleuritis and pleural effusions (the most common pulmonary manifestations). 
    2. Alveolar injury (edema and hemorrhage)
    3. Chronic interstitial fibrosis.
    4. The chest radiograph reveals elevated diaphragms, and pulmonary function tests shows reduced lung volumes
Important Points
  1. Cavitatory lesion in lungs are not a feature of SLE.
  2. Shrinking lung in SLE is caused by diaphragmatic myopathy).
  1. Hematologic
    1. Coombs positive hemolytic anemia
    2. Lymphopenia
    3. Thrombo cytopenia
    4. Anti phospholipid syndrome – lupus anti coagulant and anti cardiolipin are present. It consists of thrombocytopenia, recurrent fetal loss, recurrent venous or arterial clotting. (AIIMS Nov 2010)

Extra Edge autoimmune destruction of RBC, WBC and platelet due to warm antibodies so Pancytopenia can occur. Treatment is high dose of cortico steroid. (Ref. Hari. 18th ed., Pg-2733)

  1. Cardiac Manifestations in SLE
    1. Pericarditis is the most frequent cardiac manifestation;
    2. Endocarditis of Libman-sacks. (LQ 2012)
    3. AR, MR
    4. Risk for myocardial infarction
    5. Myocarditis
    6. Endocarditis
Important Points

Systemic Hypertension is not a feature

  1. Antiphospholipid antibody syndrome
    1. This syndrome occurs in 5% of the general population, but is associated with 50% cases of SLE. 
    2. Patients have anti phospholipid antibodies such as lupus anticoagulant, anticardiolipin antibody or anti beta 2 glycoprotein (AIPG 2011) (Ref. Hari. 18th ed., Pg- 2736)
    3. Because phospholipids are integral parts of the control of coagulation, these antibodies can lead to a hypercoagulable state, i.e., anti phospholipid antibody syndrome.
Clinical manifestations of antiphospholipid antibody syndrome:
  1. Asymptomatic.
  2. Arterial and venous thromboembolism (LQ 2012), avascular osteonecrosis. 
  3. Hematologic
    1. Cytopenia: Thrombocytopenia, autoimmune hemolytic anemia, leukopenia. Pancytopenia can occur. (AIIMS May 2011)
    2. Coagulopathy: Platelet dysfunction, prothrombin deficiency.
  4. Neurologic
    1. Acute ischemia (CVA, TIA, encephalopathy); 
  5. Dermatologic
    1. Livedo reticularis, acrocyanosis, wide spread cutaneous necro¬sis, 
  6. Cardiopulmonary
    1. Marantic endocarditis, myocardial infarction, peripheral arterial disease. pulmonary hypertension.
  7. Obstetric
    1. Recurrent spontaneous abortion predominantly second trimester, IUGR, preeclampsia, 
  8. Catastrophic antiphospholipid syndromes
Important Points

In lupus anticoagulant thrombosis occurs (there is no increase in thrombocytes).


Coagulation tests in lupus anticoagulant


PTT  → Prolonged


PT  → Normal


Fibrinogen → Normal


  1. Antiphospholipid antibodies bind to cardiolipin antigen, used in serologic tests for syphilis, and therefore lupus patients may have a false-positive test result for syphilis.
  2. Thrombocytopenia occurs.
  3. Sterility is not a featureImportant Points


  1. An additional autoantibody test with predictive value (not used for diagnosis) detects anti-Ro, which indicates increased risk for neonatal lupus, sicca syndrome, and Sub acute cutaneous lupus erythematosus (SCLE).
  2. Women with child-bearing potential and SLE should be screened for aPL and anti-Ro.
Table - Classification and Nomenclature of Antiphospholipid Antibodies (Ref. Hari. 18th ed., Pg-2736, table 320.1)
  1. Anti cardiolipin antibody (aCL), detected by (ELISA)
  2. Anti beta 2 glycoprotein, (anti-β2GPI) detected by ELISA.
  3. Lupus anti coagulant (LA) detected by clotting assays. LA antibodies induce Prolongation in vitro of the following clotting times:
    1. PTT,
    2. Kaolin clotting time (KCT),
    3. Dilute Russel viper venom test (dRVVT)
      Note: PTT is increased but PT is normal.
  4. False positive VDRL for syphilis
Sapporo Criteria
Classification with APS requires one clinical and one laboratory manifestation:
  1. A documented episode of arterial, venous, or small vessel thrombosis — other than superficial venous thrombosis — in any tissue or organ by objective validated criteria
  2. 1 or more unexplained deaths of a morphologically normal fetus (documented by ultrasound or direct examination of the fetus) at or beyond the 10th week of gestation and/or 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation.
  1. Anti-cardiolipin IgG and/or IgM
  2. Anti-β2 glycoprotein I IgG and/or IgM
  3. Lupus anticoagulant.
Types of APS:
Patients with antiphospholipid antibody syndrome fall into two categories.
  1. Primary: In these cases there is no evidence of other autoimmune disease, the patient exhibit only the manifestations of antiphospholipid antibody syndrome.
  2. Secondary (when there is a pre-existing autoimmune condition, most frequently, SLE) 
Special Conditions in SLE that May Require Additional or Different Therapies
Pregnancy and Lupus
  1. Fertility rates for men and women with SLE are normal. 
  2. Rate of fetal loss is increased (approximately two- to threefold) in women with SLE. 
  3. Fetal demise is higher in mothers with high disease activity, antiphospholipid antibodies, and/or nephritis. Suppression of disease activity can be achieved by administration of systemic glucocorticoids. 
  4. A placental enzyme, 11--dehydrogenase 2, deactivates glucocorticoids; it is more effective in deactivating prednisone and prednisolone than the fluorinated glucocorticoids dexamethasone and betamethasone. 
  5. Therefore, maternal SLE should be controlled with prednisone/prednisolone at the lowest effective doses for the shortest time required. 
  6. In SLE patients with aPL (on at least two occasions) and prior fetal losses, treatment with heparin (standard or low-molecular-weight) plus low-dose aspirin has been shown in prospective controlled trials to increase significantly the proportion of live births. 
  7. An additional potential problem for the fetus is the presence of antibodies to Ro, sometimes associated with neonatal lupus consisting of rash and congenital heart block. 
  8. The latter can be life-threatening; therefore the presence of anti-Ro requires vigilant monitoring of fetal heart rates with prompt intervention (delivery if possible) if distress occurs.
Autoantibodies in SLE
Table - Autoantibodies in Systemic Lupus Erythematosus (SLE) (Ref. Hari. 18th ed., Pg-2726, table 319.1)
Antibody Prevalence, % Clinical Utility
Antinuclear antibodies 98 Best screening test; repeated negative tests make SLE unlikely
Anti-dsDNA 70 High titers are SLE-specific and in some patients correlate with disease activity, nephritis, vasculitis
Anti-Sm 25 Specific for SLE; no definite clinical correlations; most patients also have anti-RNP
Anti-RNP 40 Not specific for SLE; high titers associated with syndromes that have overlap features of several rheumatic syndromes including SLE;
Anti-Ro (SS-A) 30 Not specific for SLE; associated with sicca syndrome, subacute cutaneous lupus, and neonatal lupus with congenital heart block; associated with decreased risk for nephritis
Anti-La (SS-B) 10 Usually associated with anti-Ro; associated with decreased risk for nephritis
Antihistone 70 More frequent in drug-induced lupus than in SLE
Antiphospholipid 50 Three tests available— ELISA s for cardiolipin and 2G1, sensitive prothrombin time (DRVVT); predisposes to clotting, fetal loss, thrombocytopenia
Antierythrocyte 60 Measured as direct Coombs' test; a small proportion develops overt hemolysis
Antiplatelet 30 Associated with thrombocytopenia but sensitivity and specificity are not good; this is not a useful clinical test


Extra Edge
  1. Antinuclear antibodies – Most sensitive test. 
  2. Anti – DNA – Anti ds DNA is most specific
  3. Complement level are reduce in SLE.
Immune complex diseases associated with hypocomplementemia (AIIMS Nov 10)
  1. SLE
  2. Vasculitis
    1. Hypocomplementemic urticarial vasculitis
    2. Polyarteritis nodosa (especially hepatitis B-associated) (necrotizing vasculitis) 
  3. Glomerulonephritis
    1. Post-streptococcal
    2. Membranoproliferative
    3. Cryoglobulinemia (types II and III)
  4. Bacterial endocarditis
  5. Serum sickness
Treatment of SLE
Cutaneous lupus
  1. Avoidance of sun exposure and use of sun blocks
  2. Hydroxychloroquine is used to treat photosensitive rashes.
  3. Corticosteroids can be used for the period till the response of hydroxychloroquine develops
  4. Several immunosuppressive drugs such as methotrexate, cyclophosphamide, mycophenolate can be used. 
  5. Anticoagulation - for anti phospholipid syndrome. Low dose aspirin, oral anticoagulant. 
Low dose aspirin (St Joseph aspirin) therapy is used in
  1. Pre-eclampsia
  2. Coronary artery disease.
  3. Anti phospholipid syndrome
  4. IUGR
Important Points

Low dose aspirin is used in APLS but it is not used in SLE without APLS.

Indication steroid therapy in SLE (Ref. Hari. 18th ed., Pg-2733)
  1. Nephritis
  2. Thrombocytopenic purpura
  3. Hemolytic anemia
  4. Pericarditis
  5. Convulsion
Important Points

It has not been proven that glucocorticoid or other immunosuppressive therapies lead to improvement of lupus myocarditis or endocarditis, but it is usual practice to administer a trial of high-dose steroids along with appropriate supportive therapy for heart failure, arrhythmia or embolic events. (Ref. Hari. 18th ed., Pg-2733)


Manifestations of SLE which don't improve to immunosuppression are
  1. Clotting disorders
  2. Behavior abnormalities
  3. End stage GN
Table 319-5 Medications for the Management of SLE (Ref. Hari. 18th ed., Pg - 2732)
  1. NSAIDs, salicylates (St. Joseph's aspirin (low dose aspirin)
  2. Topical glucocorticoids
  3. Topical sunscreens
  4. Hydroxychloroquine (quinacrine can be added or substituted)
  5. DHEA (dehydroepiandrosterone)
  6. Methotrexate (for dermatitis, arthritis)
  7. Glucocorticoids, oral
  8. Methylprednisolone sodium succinate, IV
  9. Cyclophosphamide IV
  10. Mycophenolate mofetil or mycophenolic acid
  11. Azathioprine
  12. Belimumab
  13. Rituximab
Recent Advances
Belimumab & Rituximab are new drugs being used for SLE. (Ref. Hari. 18th ed., Pg- 2732)
Newer Diagnostic criteria of SLE:
  1. Cell bound compliment activation product (CB – CAP) is a newer technique for the diagnosed of SLE based on bound form of compliment activated in the disease. 
  2. Such compliment has got a higher half life and hence is used in diagnosis. It is used in the form of erythrocytes, leucocytes, platelet bound product. 
  3. Platelet bound compliment product (P-C4d) has got highest diagnostic specificity.
  4. Diagnostic marker in Urine.
    1. Endothelin 1
    2. Lipocalcin 2
    3. U-MCP-1
    4. Hepcidin
Newer Treatment:
B-cell depletion in SLE is done with following method.
  1. Monoclonal antibodies –
    1. Rituximab
    2. Ocrelizumab – Humanized anti CD 20 Ab
    3. Ofatuzumab – Fully human anti CD 20 Ab.
  2. Induction of negative signaling in B cells – Epratuzumab which is a anti CD 22 Ab.
  3. Blocking B cell survival and activation factor (anti – BAFF) – Belimumab
  4. Inhibition of co-stimulatory B and T cell (CTLA-4 → Ig) – Abatacept

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