Inflammatory Autoimmune Connective Tissue Disease

Question 1

Outline the epidemiology of systemic lupus erythematosus (SLE).

Answer 1

• The highest reported incidence of SLE is in North America and the lowest reported incidences are in Africa and Ukraine.
• Incidence is higher in women than in men; reported sex ratios range from 2:1 to 15:1
• Peak age of onset ranges from 30 to 70 years in women and between 50 and 70 years in men.

Question 2

What are the risk factors of systemic lupus erythematosus (SLE) (4)?

Answer 2

• Female sex
• Age > 30 years
• African descent in Europe and US
• Drugs (some medication)

Question 3

Outline the pathogenesis of systemic lupus erythematosus (SLE).

Answer 3

• The aetiology of SLE is not known but the interaction of an environmental agent in a genetically susceptible host is thought to be fundamental
  
  • The association may be non-infectious or infectious

Question 4

Outline the pathophysiology of systemic lupus erythematosus (SLE).

Answer 4

• SLE is primarily an antigen-driven immune-mediated disease characterised by high-affinity immunoglobulin G antibodies to double-stranded DNA, as well as nuclear proteins (Genes implicated in SLE may contribute to pathology by breaching immune tolerance and promoting auto-antibody production)
  
  • Rapid clearance of cells through apoptosis typically prevents exposure of nuclear antigens to the immune system. However, failure of this process, and that of other mechanisms that confer immune tolerance to nuclear antigens, may provoke an immune response. Loss of immune tolerance in this manner is evidenced by the presence of antinuclear antibodies.
• Several mechanisms have been proposed, by which T-cell dysregulation of B cells may arise, resulting in autoimmunity

Question 5

How would a patient with systemic lupus erythematosus (SLE) present (17)?

Answer 5

• Malar (butterfly) rash
• Photosensitive rash
• Discoid rash
• Fatigue
• Weight loss
• Fever
• Oral ulcers
• Alopecia (hair loss)
• Arthralgia / arthritis
• Fibromyalgia
• Raynaud’s phenomenon
• Chest pain and shortness of breath
• Venous or arterial thrombosis
• Hypertension
• Signs of nephrosis (e.g., oedema)
• Lymphadenopathy
• GI symptoms: abdominal pain, vomiting, or diarrhoea

Question 6

What investigations are suggested in a suspected systemic lupus erythematosus (SLE) (8)?

Answer 6

• Full blood count and differential
• Activated partial thromboplastin time (PTT)
• U&E
• Erythrocyte sedimentation rate and C-reactive protein (ESR & CRP)
• Antinuclear antibodies (ANA), double-stranded (ds)DNA, Smith antigen
• Urinalysis
• CXR
• ECG

Question 7

What would a full blood count and differential show in a patient with systemic lupus erythematosus (SLE) (3)?

Answer 7

• Anaemia
• Leukopenia
• Thrombocytopenia

Question 8

What would an activated partial thromboplastin time (PTT) test show in a patient with systemic lupus erythematosus (SLE)?

Answer 8

• May be prolonged in patients with antiphospholipid antibodies

Question 9

What would a U&E test show in a patient with systemic lupus erythematosus (SLE)?

Answer 9

• Elevated

Question 10

What would an erythrocyte sedimentation rate and C-reactive protein (ESR & CRP) test show in a patient with systemic lupus erythematosus (SLE)?

Answer 10

• Elevated

Non-specific

Question 11

What would an antinuclear antibodies (ANA), double-stranded (ds)DNA, Smith antigen test show in a patient with systemic lupus erythematosus (SLE)?

Answer 11

• Positive

Question 12

What would a urinalysis show in a patient with systemic lupus erythematosus (SLE)?

Answer 12

• Haematuria, casts (red cell, granular, tubular, or mixed) or proteinuria

Question 13

What would a CXR show in a patient with systemic lupus erythematosus (SLE)?

Answer 13

• Pleural effusion
• Infiltrates
• Cardiomegaly

Question 14

What would an ECG show in a patient with systemic lupus erythematosus (SLE)?

Answer 14

• Clear, may exclude other causes of chest pain

Question 15

What is involved in the management of systemic lupus erythematosus (SLE) (4)?

Answer 15

• Treatment in SLE aims at remission or low disease activity and prevention of flares
• Patients with SLE should be assessed for their antiphospholipid antibody status
• Patients with SLE should be assessed for their infectious and cardiovascular diseases risk profile
• Pregnancy planning

Hydroxychloroquine is recommended in all patients with lupus
Maintenance treatment glucocorticoids should be minimised and, when possible, withdrawn.
Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of glucocorticoids
In persistently active or severe disease we use cyclophosphamide and B cell targeted therapies (rituximab and belimumab)

Question 16

What is involved in the treatment of systemic lupus erythematosus (SLE) (4)?

• Treatment in SLE aims at remission or low disease activity and prevention of flares

Answer 16

• Hydroxychloroquine is recommended in all patients with lupus
• Maintenance treatment glucocorticoids should be minimised and, when possible, withdrawn.
• Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of glucocorticoids
• In persistently active or severe disease we use cyclophosphamide and B cell targeted therapies (rituximab and belimumab)