19. Systemic lupus erythematosus (SLE)

Question 1

What is SLE?

Answer 1

• It is an autoimmune disorder that leads to tissue damage and inflammation
• The pathogenesis is not completely understood
• It is an idiopathic chronic inflammatory disease with genetic, environmental and hormonal factors
• Exacerbation and remission are very common

Question 2

What is the epidemiology of SLE?

Answer 2

• It affects mostly women of child-breaing age (90%)
• African-American patients are more frequently affect that caucasian patients
• Usually appears in late childhood or adolescence

Question 3

What is the pathophysiology of SLE?

Answer 3

Autoantibodies production

Deposition of immune complexes

Complement activation

Accompanying tissue destruction/vasculitis

Question 4

What are the types of SLE?

Answer 4

• Spontaneous SLE
• Discoid lupus: skin lesions without systemic disease
• Drug-induced lupus (> 50 drugs) isoniazid, hydralazine, chlorpromazine
• ANA-negative lupus:
  
  • Has the following associated findings
    
    • Arthritis, Raynaud’s phenomenon, subacute cutaneous lupus
    • Serology: Anti-Ro (Anti-SSA) antibody positive, ANA negative
    • Risk of neonatal lupus in infants of affected women

Question 5

What are the clinical features of SLE?

Answer 5

• Constitutional symptoms:
  
  • _​_Fatigue, fever, weight loss
• Cutaneous:
  
  • Butterfly (malar) rash (33%), oral or naopharyngeal ulcers, Raynaud’s (20%), discoid rash
• Musculoskeletal:
  
  • ​Joint paint (usually 1st symptom), arthritis (inflammatory and asymmetric, not as erosive as RA), arthralgia, myalgia
• Cardiac:
  
  • Pericarditis, myocarditis, endocardidits (Liebman-Sacks)
• Pulmonary:
  
  • Pleuritis
• Hematologic:
  
  • Hemolytic anemia with/without reticulocytosis of chronic disease, leukopenia, thrombocytopenia
• Renal:
  
  • Proteinuria (possible nephrotic syndrome), cellular casts, glomerulonephritis (may be hematuria), azotemia, pyuria, uremia, HTN
• Immunologic:
  
  • Impaired immune response due to many factors including autoantibodies to lymphocytes, abnormal T cell function and immunosuppressive medications
• GI:
  
  • Nausea, vomiting, peptic ulcer
• CNS:
  
  • Seizures, headache, TIA, cerebrovascular accidents
• Others:
  
  • ​Conjunctivits and increased incidence of Raynauds and Sjögren’s syndrome

Question 6

How do we diagnose SLE?

Answer 6

• Positive ANA antibodies screening
  
  • Sensitive but not specific
  • Almost all SLE patients have serum ANA
• Anti-dsDNA (in 40%) and anti-SM antibodies (in 30%)
  
  • The presence of either of these is diagnostic of SLE
  • Very specific but obviously not sensitive
• Anti-histone antibodies (in 70%) are present in 100% of cases of drug-induced lupus
  
  • If negative, drug-induced lupus is ruled out
• Anti-Ro (SSA) and anti-La (SSB) are found in 30% and are associated with:
  
  • Sjögren’s syndrome
  • Subacute cutaneous SLE
  • Neonatal lupus
• Anti-phospholipid antibodies (anticardiolipin or lupus anticoagulant) may also be positive
• Decreased complement levels
• Genetic testing: HLA-DR2/3
• Clinical presentation

Question 7

What is the treatment of SLE?

Answer 7

• Avoid sun exposure (exacerbates cutaneous rashes) protect hands against cold
• Less severe symptoms
  
  • NSAIDs
• Exacerbation of joint pain
  
  • Methotrexate
• Severe flares:
  
  • ​Cyclophosphamide + high dose prednisolone
• Maintenance:
  
  • NSAIDs and hydroxycholoroquine (antimalaria) for joints and skin
  • Low dose steroids is good for chronic disease and increase the dose in exacerbation
  • Methotrexate is used as a steroid-sparing agent

Question 8

What else does the doctor need to do to treat the patient?

Answer 8

Detect flare by monitoring activity of:

• Anti-dsDNA antibodies titers
• Complement decrease
• Increase of ESR and normal CRP