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Related Subjects: |Systemic Lupus Erythematosus (SLE) |Drug induced Lupus Erythematosus |Discoid lupus erythematosus (DLE) |Neonatal Lupus Erythematosus |Rheumatology Autoantibodies

Multisystem disease mainly affecting females. The most concerning feature is in those who develop Lupus nephritis

About

• Autoimmune Rheumatic Diseases
• Common chronic multisystem connective tissue disorder
• More common in Afro-Caribbeans and Asian communities
• Drugs can cause a lupus-like syndrome (see Drug-Induced lupus)

Aetiology

• Affects young females age 20-40 (F:M 9:1)
• Associated with HLA B8, DR2, DR3 and A1
• Associated with deficiencies of complement genes C1q, C2 or C4.
• Genetic: Identical twins show a 25% concordance
• Autoantibodies are found to intracellular and nuclear components
• Hormones: Females, Klinefelter's syndrome.
• Drugs: Hydralazine, isoniazid, procainamide and penicillamine
• UV light can trigger flares of SLE, especially in the skin.
• Identical twins 25%, Siblings 3%

Pathology

• Immune complex deposition with damage
• Apoptosis: Studies suggest a defect in the apoptosis gene
• Haematoxylin bodies seen. If ingested by neutrophils form LE cells
• Fibrinoid necrosis is found in vessel walls
• Onion skin lesions of splenic arteries
• High levels of IL-10 and α-interferon

American College of Rheumatology Criteria: = 4/11 criteria needed to make the diagnosis

• 1. Malar rash - spares nasolabial folds
• 2. Discoid rash - scaling, follicular plugging
• 3. Photosensitivity
• 4. Oral ulcers or nasal
• 5. Arthritis - non-erosive usual tenderness, swelling, effusion
• 6. Serositis - pleuritis or pericarditis
• 7. Renal disorder - 3+ proteinuria or > 0.5 g /24 hrs
• 8. CNS involvement - seizures or psychosis
• 9. Haematological ( Thrombocytopenia < 100 x 10⁹/l, Haemolytic anaemia, Leucopenia < 4.0 x 10⁹/l on 2+ or more occasions, Lymphopenia < 1.5 x 10 ⁹/l on 2+ or more occasions, )
• 10. Immunological - Raised anti native DNA antibody binding or Anti-Sm antibody or positive Anticardiolipin
• 11. An antinuclear antibody is raised titre seen in 95%

Clinical

• Systemic
  • Fatigue, Tiredness, Malaise
  • Weight loss, Depression, Fever
  • Raised ESR
• Dermatology
  • Butterfly rash which is redness over the cheeks and bridge of the nose.
  • Photosensitive skin rashes may be seen.
  • Urticaria and purpura
  • Discoid lupus with follicular plugging and hyperkeratosis.
  • Scarring alopecia can be disfiguring.
  • Livedo reticularis.
• Neurological disease
  • Antiphospholipid syndrome and strokes
  • Acute psychotic episodes
  • Focal epilepsy
  • Migrainous attacks
  • Cerebellar signs and ataxia
  • Aseptic meningitis
  • Cranial nerve palsies
  • Polyneuropathy
• Renal: Lupus nephritis
  • Glomerulonephritis
  • Nephrotic syndrome
  • Nephritic syndrome
  • Interstitial nephritis
  • Rapidly progressive glomerulonephritis
  • End stage renal failure: Dialysis and renal transplantation
• Haematology
  • Normochromic and normocytic anaemia
  • Low platelets
  • Low WCC and High WCC
• Cardiac/Vascular
  • Pericarditis and effusions may be seen
  • Myocarditis
  • Aortic valve involvement
  • APL: Arterial. Venous thrombosis
  • Vasculitis
  • Premature atherosclerosis
  • Libman sacks endocarditis
  • Secondary Raynaud's syndrome
• Pulmonary
  • Pleurisy and pleural exudative effusions
  • Restrictive lung defect 'shrinking lung syndrome'
  • Pneumonitis, pulmonary vasculitis
  • Secondary pulmonary hypertension
• Joints
  • Symmetrical arthritis and arthralgia
  • Generalized aches and morning stiffness
  • Jaccoud's arthropathy
  • Generalized joint deformity with SLE rare
  • Polyarthritis.
• Gastrointestinal
  • Oral ulcers (common)
  • Mesenteric vasculitis and ischaemia
• Pregnancy
  • Neonates at increased risk of neonatal lupus
  • Neonatal heart block if mother positive SSA/SSB

Lupus Rash

Investigations

• FBC
  • Anaemia of chronic disease
  • Haemolytic anaemia possible
  • Iron deficiency anaemia from NSAIDS
  • A low platelet count is seen
  • A low or high WCC is seen
• Renal
  • Raised creatinine with AKI or CKD
  • Proteinuria
  • Renal biopsy in severe disease of lupus nephritis
• Inflammatory markers
  • ESR is raised normally with SLE
  • CRP is normal unless other cause e.g. infection
• Autoantibodies
  • Anti ANA: Antinuclear antibodies positive in 99%. Absence makes SLE unlikely. However a positive ANA does not confirm SLE diagnosis.
  • Anti dsDNA (double-strand DNA) : Seen in approximately 50% and more specific
  • Rheumatoid factor 25%
  • Antiphospholipid antibody: check in those with a history of fetal loss or thrombotic events
  • Anti-smith
  • Anti-Ro (SSA) antibody.
• Low complement C3 and C4 levels in active disease
• Elevated APTT suggests the antiphospholipid syndrome
• Echo: if concerns of Libman-Sacks endocarditis which is sterile verrucous endocarditis. It tends to involve the mitral valve, most commonly with vegetations seen on the forward flow side of the valve. May also have Pericarditis with fibrinous exudate is common
• Lymph nodes: Lymphadenopathy with follicular hyperplasia with giant cells, plasma cells infiltration of the interfollicular zones, and necrosis of the paracortical T-cell zones

Renal disease

• I: Minimal mesangial lupus nephritis
• II: Mesangial proliferative lupus nephritis
• III: Focal lupus nephritis
• IV: Diffuse segmental or global lupus nephritis
• V: Membranous lupus nephritis
• VI Advanced sclerosing lupus nephritis

Management

• Simple analgesia and NSAIDs for arthralgia and mild disease
• Photosensitive: Avoid UV light and minimize exposure to the sun.
• Low Dose steroid creams for skin complications. Avoid smoking.
• Mild disease involving skin and joints: Chloroquine or Hydroxychloroquine
• Moderate/Severe disease: Steroids e.g. Prednisolone 30 mg/day for 4 weeks before gradually reducing the dose. Consider steroid-sparing agents such as azathioprine or mycophenolate mofetil.
• Immunosuppressive: Methotrexate or leflunomide can be considered.
• Biologicals: Rituximab (anti CD20) for refractory cases
• Serositis: Try NSAIDs or oral steroids.
• Warfarin: prevent thrombosis with Antiphospholipid syndrome (APS)
• Pregnancies: High risk. Watch for neonatal heart block. Hydroxychloroquine, azathioprine and steroids may be used. Anticoagulant therapy may be necessary APS.

References

• Systemic Lupus Erythematosus (SLE)
• SLE and pregnancy