Systemic lupus erythematous

Question 1

Systemic lupus erythematosus : Definition

Answer 1

1. (SLE) is an inflammatory autoimmune connective tissue disorder.

2 . It is “systemic” because it affects multiple organs and systems.

3 .“Erythematosus” refers to the typical red malar rash across the face

Question 2

Systemic lupus erythematosus : Incidence

Answer 2

SLE can affect anyone but occurs more commonly in:
* Women of reproductive age
* Asian, African, Caribbean and Hispanic ethnicity

Question 3

Systemic lupus erythematosus : Risk factors

Answer 3

1. Environmental factors
   * UV radiation
   * Smoking
2. Viral/ bacterial infections
3. Genetic factors
   * HLA B8, DR2, DR3

Question 4

Systemic lupus erythematosus : Pathophysiology

Answer 4

1. Trigger causes DNA damage
   * Environmental triggers damage DNA within cells
   * Cell apoptosis - releasing nuclear bodies with their nuclear antigens in the bloodstream
2. Abnormal immune system response due to genetic deflect
   * Immune system is more likely to identify nuclear bodies antigens as ‘foreign’
   * Less effective clearance resulting in increased amount of nuclear antigens in the blood steam
3. Anti-bodies against nuclear antigens
   * B cells produce antibodies called ‘ Anti-nuclear antibodies’ against the antigens of the nucleus and form immune complexes
4. Type III hypersensitivity reaction : antigen - antibody complex
   * Deposit in tissues and lead to local inflammation

Question 5

Systemic lupus erythematosus : Clinical features

Answer 5

1 . Systemic features :
Fever, weightloss
mouth ulcers, lymphadenopathy

2 . Skin : Increase hypersensitivity of the skin
* Malar ‘butterfly rash’ over the cheeks which spares the nasolabial folds after sun exposure
* Discoid plaque-like rash following sun exposure
* Raynauds syndrome

3 . Heart : Pericarditis of the heart, Libman-sacks endocarditis

4 . Lungs : pleuritic of the lungs, fibrosing alveoli’s

5 . Joints : arthritis, arthralgia

6 . Kidneys : Lupus nephritis

7 . Neurological sx :
* Optic neuritis, Transverse myelitis or Psychosis

8 . Blood disorder - antibodies against blood can cause thrombocytopenia or leukopenia, lymphadenopathy
* Anaemia of chronic disease

Question 6

SLE : Investigations : Antibody serology

Answer 6

Antibody serology
1 . Anti-nuclear antibodies (ANA) :
* Sensitive for autoimmune conditions but not specific to SLE

2 . Anti-dsDNA : highly specific, positive result suggests SLE rather than other causes.
* Can be used to monitor disease activity

3 . Anti-Smith antibody : highly specific to SLE but not very sensitive

4 . Antiphospholipid antibodies
* Antiphospholipid syndrome can occur secondary to SLE
* Associated with an increased risk of venous thromboembolism.

Question 7

SLE : Investigations

Answer 7

1. Full blood count may show ;
   * anaemia of chronic disease,
   * low white cell count
   * low platelets
2. Inflammatory markers : CRP and ESR may be raised with active inflammation
3. Urinalysis and urine protein:creatinine ratio shows proteinuria in lupus nephritis

Question 8

SLE : Management

Answer 8

First line :
1. Hydroxychloroquinine
2. NSAIDs
3. Steroids*(e.g., prednisolone)

Severe disease;
* DMARDs : methotrexate, cyclophosphamide

Question 9

Drug-induced lupus erythematosus : Definition

Answer 9

1. (DILE) is a condition that mimics systemic lupus erythematosus (SLE) but is caused by exposure to certain medications.
2. drug-induced lupus typically resolves after discontinuation of the offending medication

Question 10

Drug-induced lupus erythematosus : Pathophysiology

Answer 10

Pathophysiology
1. Metabolites of drug trigger abnormal immune response
2. Lead to production of antibodies similar to that of Lupus
3. Target Tissues and Clinical Manifestations:
* The immune response and formation of immune complexes can target various tissues and organs,
* leading to clinical manifestations that resemble systemic lupus erythematosus.

Question 11

Drug-induced lupus erythematosus : Clinical features

Answer 11

• arthralgia
• myalgia
• skin (e.g. malar rash) and pulmonary involvement (e.g. pleurisy) are common

Question 12

Drug-induced lupus erythematosus : Common drug causes

Answer 12

• procainamide
• hydralazine

Question 13

Drug-induced lupus erythematosus : Investigations

Answer 13

• ANA positive in 100%, dsDNA negative
• anti-histone antibodies are found in 80-90%

Question 14

Antiphospholipid syndrome : Definition

Answer 14

1. autoimmune disorder caused by antiphospholipid antibodies.
2. These antibodies target the proteins that bind to the phospholipids on the cell surface,
3. inflammation and increasing the risk of thrombosis(blood clots).
4. associated with systemic lupus erythematosus

Question 15

Antiphospholipid syndrome : Pathophysiology

Answer 15

1 . Autoimmune dysregulation
2 . Antibodies target phospholipid molecules in cell membrane of cell
* Cardiolipin etc

3 . Endothelial injury
aPL bind to endothelial cells

4 . Platelet activation
aPL directly activate platelets

5 . Microvascular thrombosis and tissue ischamia

Question 16

Antiphospholipid syndrome : Common presentation

Answer 16

1. Venous thromboembolism
   deep vein thrombosis and pulmonary embolism
2. Arterial thrombosis
   stroke, myocardial infarction and renal thrombosis
3. Pregnancy-related complications recurrent miscarriage, stillbirth and *pre-eclampsia

Question 17

Antiphospholipid syndrome : Clinical signs

Answer 17

1 . Livedo reticularis is a purple lace-like (reticular) rash that gives a mottled appearance to the skin.
* A more permanent version of this rash, called livedo racemosa, is associated with antiphospholipid syndrome.

2 . Libmann-Sacks endocarditis is a non-bacterial endocarditis with growths (vegetations) on the heart valves (most often the mitral and aortic valves).
* It is associated with SLE and antiphospholipid syndrome

3 . Thrombocytopenia (low platelets) is common in antiphospholipid syndrome.

Question 18

Antiphospholipid syndrome : Ix

Answer 18

1 . The specific antiphospholipid antibodies are:

• **Lupus anticoagulant
• Anticardiolipin antibodies
• Anti-beta-2 glycoprotein I antibodies**

2 . Thrombocytopenia (low platelets) is common in antiphospholipid syndrome.

Question 19

Antiphospholipid syndrome : Diagnosis

Answer 19

1. Diagnosis is based on clinical features and persistent antiphospholipid antibodies.

Question 20

Antiphospholipid syndrome : Management

Answer 20

1. Long-term warfarin with a target INR of 2-3 is used to prevent thrombosis.
2. Pregnancy : Low molecular weight heparin (e.g., enoxaparin) and aspirin are used in pregnancy to reduce the risks.
   * Warfarin is contraindicated in pregnancy.