SLE

Infections in SLE :

- Patients with SLE may be functionally asplenic and at risk from encapsulated bacterial infections like meningococcemia.
- Immunosuppred patients are at increased risk of sepsis
- Infection can mimic a lupus flare
- ESR and CRP may be raised. CRP changes more acutely, and the ESR lags behind disease changes.
- Measurement of complement may be useful as C3 and C4 levels are reduced in patients with active SLE due to consumption by immune complex–induced inflammation.

Raynaud's phenomenon

- Diagnostic criteria for primary Raynaud phenomenon :

1. Attacks triggered by exposure to cold and/or stress
2. Symmetric bilateral involvement
3. Absence of necrosis
4. No detectable underlying cause
5. Normal inflammatory markers and negative antinuclear factors.

Raynaud's phenomenon

Raynaud phenomenon:

- Recurrent vasospasm of the fingers and toes usually in response to stress or cold exposure.

- Characterised by 3 phases of change:

1. White (vasoconstriction), followed by
2. Blue (cyanosis), and then
3. Red (rapid blood reflow)

- Raynaud disease (primary Raynaud phenomenon) is characterised by the occurrence of the vasospasm alone, with no association with another illness

- Secondary Raynaud phenomenon is vasospasm associated with another illness, usually an autoimmune disease – typically systemic sclerosis, SLE and mixed connective tissue disease

- Diagnostic criteria for primary Raynaud phenomenon :

1. Attacks triggered by exposure to cold and/or stress
2. Symmetric bilateral involvement
3. Absence of necrosis
4. No detectable underlying cause
5. Normal inflammatory markers and negative antinuclear factors.

- Young women with Raynaud phenomenon alone for more than 2 years and no additional manifestations are at low risk for developing an autoimmune disease.

SLE - Challenges in management in pregnancy

1. Differentiating signs and symptoms of normal pregnancy from those of exacerbations SLE
2. Differentiate malar rash from chloasma
3. Differentiate proteinuria secondary to preeclampsia from proteinuria due to lupus nephritis. Lupus nephritis is often associated with proteinuria and cellular casts whereas only proteinuria is seen in patients with preeclampsia.
4. Differentiating renal disease secondary to an exacerbation of SLE from preeclampsia.
5. Differentiating thrombocytopenia in pregnancy from thrombocytopenia of SLE exacerbation

SLE

Pulmonary features of SLE

• Pleurisy with pleuritic chest pain +/- pleural effusions is the commonest feature
• Pulmonary embolism, lupus pneumonitis, chronic lupus interstitial lung disease, pulmonary hypertension, alveolar hemorrhage and infection are other complications

GI features

• Abdominal pain in active SLE may be due to peritonitis, pancreatitis, mesenteric vasculitis or bowel infarction

Cardiac features

• Pericarditis is the most common cardiac feature, presenting with positional chest pain that is relieved on leaning forward.
• Myocarditis and pulmonary hypertension can present with breathlessness and chest pain
• Coronary artery disease presents with angina

SLE - Rx & effects

Maternal effects :
- Treatment with cyclophosphamide may lead to premature ovarian failure and infertility

- Increased risk of hypertensive disorders: Pre-eclampsia occurs in ~15% of women and may be difficult to distinguish from lupus nephritis

- Increased risk of UTI

- Increased risk of gestational diabetes

- VTE – risk especially increased in women with anti-phospholipid antibodies. 

1. Women already on warfarin should be switched to therapeutic LMWH as soon as the pregnancy is recognized. 
2. Women with antiphospholipid syndrome but no previous VTE should be treated with prophylactic LMWH and low-dose aspirin during subsequent pregnancies. 
3. Women with SLE + antiphospholipid antibodies but no past morbidity can be managed with low-dose aspirin +/- hydroxychloroquine.

SLE - preconceptional counselling

Preconception management :

1. Assess disease activity from history, examinations and investigations

2. Risk assessment by checking for antiphospholipid antibodies (for a risk of fetal loss) and for anti-Ro and anti-La antibodies (for a risk of neonatal lupus) should be performed before pregnancy.

3. If active disease, advise to defer pregnancy and continue effective contraception

4. Discuss effect of SLE on pregnancy management and outcome. 

5. Women with anti-phospholipid antibody syndrome will require more frequent monitoring than those with SLE alone

6. Discuss effect of pregnancy on SLE

7. Discuss terratogenic effects of drugs such as methotrexate, cyclophosphamide and mycophenolate. 
Due to long half-lives, these drugs should be stopped at least 3 months before the planned conception.

8. Women should use contraception while on immunosuppressive disease-modifying drugs such as mycophenolate and cyclophosphamide. 
 Cyclophosphamide is absolutely contraindicated during pregnancy.

9. Discuss drugs that need to be stopped as soon as pregnancy is detected, such as warfarin.

10. Discuss general measures including folic acid supplementation, screening for rubella immunity

Immune diseases & pregnancy

• Rheumatoid arthritis typically improves in pregnancy
• Sarcoidosis is unaffected or may improve during pregnancy
• Asthma may improve, worsen (typically severe disease) or remain unchanged

• Eczema often, but not invariably improves in pregnancy

SLE - Diagnosis

Diagnosis of SLE :

SLE is diagnosed if the patient has biopsy-proven lupus nephritis with anti-nuclear antibodies or anti-dsDNA antibodies, or the patient has four of the criteria below, including at least one clinical and one immunologic criterion.

Clinical criteria :

•     Serositis – pleurisy or pericarditis

•     Oral or nasopharyngeal ulcers

•     Arthritis - two or more peripheral joints with tenderness or swelling

•     Photosensitivity

•     Blood disorders - Leukopenia, lymphopenia, thrombocytopenia, hemolytic anemia

•     Renal involvement - Proteinuria (>0.5 g/24h) or cellular casts

•     Neurologic disorder - seizures or psychosis in the absence of other causes

•     Malar rash

•     Discoid rash

Systemic Lupus Erythematosus

- Chronic systemic inflammatory disease with a relapsing and remitting course. 
- Can affect any organ system, but mainly involves the skin, joints, kidneys, blood cells, and nervous system.
- Serum antinuclear antibodies (ANAs) are found in nearly all individuals with active SLE.
- Antibodies to double-stranded DNA (dsDNA) are relatively specific for SLE.

Prevalence

Highest in Afro-Caribbean population in the UK.  However, SLE is rare among blacks in Africa, suggesting that there may be an environmental trigger as well as a genetic basis for their disease. Presents typically in women of childbearing age.
Use of exogenous hormones has been associated with onset and flares of SLE. The risk of SLE development in men is similar to that in prepubertal or postmenopausal women.

Rheumatoid arthritis

• Auto-immune disease affecting mainly small joints and characterised by exacerbations and remissions
• Extra-articular manifestations include pleurisy, pericarditis, sub-cutaneous nodules, pulmonary fibrosis

• Characteristically improves during pregnancy with relapse in the puerparium

• Impact of disease on risk of miscarriage and IUD is controversial
• No effect on risk of pre-eclampsia, IUGR or pre-term delivery