12.2 Systemic Lupus Erythematosus (SLE)

Question 1

What is SLE, in a nutshell?

Answer 1

• Chronic autoimmune disease, where the body develops both innate and adaptive autoimmunity to self antigens of nucleic acids
• This results in autoantibody-mediated tissue damage

Question 2

What are some epidemiological risk factors for SLE?

Answer 2

• Young women of childbearing age (usually 20s and 30s)
• Non-white populations (such as southeast asia)

(Data depends on country/strength of data collection though)

Question 3

Which joints are most commonly affected in Lupus?

Answer 3

• Small joints of the hands and feet
• Can also affect elbows, knees, and large joints like shoulders etc.

Question 4

List some sites of tissue damage/systemic dysfunction in SLE

Answer 4

• Cutaneous complications (photosensitive rash, Raynaud’s, hair loss)
• Serositis (pulmonary effusion, pericardial effusion)
• MSK: Arthritis, serositis
• Systemic: fatigue, malaise
• Haem: anaemia, thrombocytopaenia, haemolysis
• Neuro: psychiatric, cognitive problems

Question 5

Which end organs can be damaged in lupus?

Answer 5

• Kidneys (lupus nephritis 2° to antibody deposition)
• Heart (effusion)
• Lungs (effusion)
• Brain (neuroinflammation)

Question 6

Lupus nephritis pathogenesis

Answer 6

• Lupus autoantibodies are present in the bloodstream
• Immune complexes deposit in the glomerulus, causing localised inflammation and activation of the complement system

Question 7

Typical presentation of lupus nephritis?

Answer 7

• Extra-renal lupus symptoms (fever, hair loss, malar rash, joint pain etc.); renal complications may be asymptomatic
• Requires bloods (high creatinine, CRP, GFR etc.) and urine (majority nephrotic, can be nephritic) to confirm renal involvement

(“Silent killer”; like CKD)

Question 8

What diagnostic tests do we use for SLE nephritis?

Answer 8

• Bloods: creatinine, eGFR, CBC (anaemia, thrombocytopaenia), serology (first Anti-nuclear antibodies, then anti-DS-DNA, then Extracatable nuclear antigen test)
• Urine: ACR, microscopy (?casts and RBCs)

Question 9

What does lupus nephritis look like on biopsy?

Answer 9

Every part of the glomerulus and surrounding tissue is inflamed. We can see immune deposits, fibrosis, and thickening of:

• Mesangium
• Glomerulus endothelium
• Podocytes
• GBM

Question 10

Recall the 6 histopathological classes of lupus nephritis

Answer 10

1. Minimal mesangial: mesangial deposits invisible on light microscopy
2. Mesangial hypercellularity of any degree, seen on light microscopy
3. Focal. Less than 50% of glomeruli affected on light microscopy
4. (Most common) More than 50% of glomeruli are affected
5. Diffuse thickening of glomerular capillary walls + subendotrhelial immune depo’s
6. Global sclerosis >90% of glomeruli

Question 11

Describe the three phases of SLE treatment

Answer 11

1. Induction: high dose immunosuppression
2. Maintenance: Lower-level immunosuppression for years
3. Monitoring: for relapse/treatment side effects

Question 12

Outline the broad classes of drugs that can be used to treat SLE

Answer 12

• Anti-inflammatory: pred etc.
• Drugs to reduce immune cell proliferation
• Block autoantibodies - biologic mAbs (e.g. rituximab)

Question 13

What is cyclophosphamide, and how can it treat SLE?

Answer 13

• Alkylating agent
• Acts on DNA to stop immune cell replication

Question 14

What is azathioprine? How can it be used to treat SLE?

Answer 14

• Antimetabolite
• Inhibits DNA synthesis of immune cells

Question 15

How can rituximabn treat SLE?

Answer 15

• Targets B cells (CD 20 surface marker)
• This helps to reduce autoantibody production