Systemic Lupus Erythematosus

Definition:

  • Multi-system autoimmune disorder
  • Drug-induced lupus: Hydralazine, Procainamide, Isoniazid, Methyldopa, Quinidine, and Chlorpomazine
    • Sx reslove when drug is discontiniued (ANA may persist for years)
    • Primarily in older pts
    • No CNS or renal involvement
    • (+) antihistone, (-) anti-ds DNA

 

Epidemiology and risk factors:

  • Women of child bearing age (90%). Female-to-male ratio is 8:1
  • Ethincity: african-american, asians, hispanics. African-american:Caucasian ratio is 4:1
  • Appears in late childhood or adolescence
  • Mild in elderly, severe in children

Genetics:

  • HLA DR2 and DR3
  • Congenital deficiency of complement components: C1, C2, and C4

SLE 1

 

Pathogenesis:

  • A combination of type II and III hypersensitivity
  • Production of auto-Ab against nuclear, cytoplasmic, and cell-surface Ag
  • Defective clearing of apoptotic cells + blebs containg surface protiens (act as auto-Ag)

Tissue injury involves:

  • Immune complex deposition: MC Id is anti-dsDNA -> form in circulation then deposit in kidney, or form in-situ
  • Cell specific Ab: don’t destroy cells directly, but mark cells for premature destruction by reticuloendothelial system -> hemolytic anemia, leukopenia, and thrombocytopenia

SLE 2

 

Presentation:

1. Constitutional symptoms: fatigue, malaise, fever, wt loss

2. Skin:

  • Malar rash: butterfly rash over cheeks and bridge of nose, sparing the nasolabial folds, nonscarring
  • Discoid lesions: typically occur over exposed areas (face and scalp) -> deeper, often scarring
  • Subacute cutaneous lupus: erythematous, annular, polycyclic lesions, slightly scaling border with central clearing
  • Most rashes are photosensitivite (esp if + anti-Ro)
  • Oral or nasopharyngeal ulcers
  • Alopecia
  •  

3. Raynaud’s phenomenon:

  • Vasospasm of small vessels when exposed to cold (usually in fingers)
  • Needs to be differentiated from primary Raynaud’s -> common in health young women

SLE 6

4. Lungs:

  • Pneumonitis and pleural effusion
  • Pneumonia, atelectasis, pulmn fibrosis, alveolar hemorrhage, restrictive lung ds -> common in SLE but not diagnostic
  • Shrinking lung syndrome: smaller lung volumes due to diaphragm weakness

5. Cardiovascular:

  • Pericarditis, endocarditis, myocarditis
  • Libman-Sacks endocarditis is a serious complication: a form of non-bacterial endocarditis, that causes vegetations on the valves (mitral mainly) which can embolize

6. Joints and muscles:

SLE 7

  • Arthralgia w morning stiffness: episodic, migratory, non-erosive, symmetrical distribution (similar to RA; peripheral joints)
  • Jaccoud’s arthropathy: joint deformity bc tendon damage (wout joint erosion)
  • Mayalgia (50%), myositis (<5%)

7. Kidneys:

  • Hematuria, proteinuria, high BUN and Cr, and urinary casts
  • The most common and severe: diffuse proliferative GN -> rapidly prog renal failure

SLE 8

8. CNS:

  • Psychosis, seizures, headache, depression, TIA, stroke (from vasculitis)
  • Commonest finding in MRI: increased white matter signal

9. Hematologic:

  • Hemolytic anemia
  • Anemia of chronic ds (normocytic, normochromic)
  • Lymphopenia, leukopenia, thrombocytopenia

10. GI:

  • NV, dyspepsia, dysphagia, peptic ulcer disease

11. Ocular:

  • Photophobia, conjunctivitis, retinal lesions (cotton wool spots), blindness

12. Other:

  • Antiphospholipid syndromes
  • Sjögren syndrome AKA Sicca syndrome
  • Mesenteric vasculitis: can present w abdominal pain, bowel infarction, perforation

13. Immunologic:

  • ANA (90%): to multiple nuclear Ags. Sensitive, not specific. Screening test. Not diagnostic w out clinical features. “Don’t treat asymptomatic (+) ANA”
  • Anti-DNA (60%): to native ds DNA, Poor prog (renal ds). Highly specific
  • Anti-Smith (Sm) (30%): to smith nuclear ribonuclearprotein. Most specific
  • Antihistone: to DNAprotein complex. Sensitive for drug-induced lupus
  • Anti-RNP: to ribonuclearprotein. Overlap SLE, scleroderma, and myositis
  • Anti-Ro (SS-A)La (SS-B): in SjogrenSLE overlap and neonatal lupus
  • Decreased C3, C4, and CH50 bc immune complex formation. Drop further with acute exacerbations!
  • Anti-phospholipid Abs (anti-cardiolipin and SLE anti-coagulant): ↑ risk of clotting and aPTT
  • False-positive test for syphilis
  • Positive LE preparations: ANAs bind to nuclei of damaged cells -> LE bodies

SLE 9

Diagnosis:

2012: “SOAP BRAIN MD” 4 out of 11; at least 1 clinical and 1 immunologic

SLE 10

Indications for renal biopsy:

  • Increasing serum creatinine in the absence of strong evidence for another etiology (eg, sepsis, hypovolemia, medication)
  • Proteinuria of more than 1 g24 hr
  • Proteinuria of ≥0.5 g24 hr, along with either (1) hematuria (≥5 RBCs/hpf) or (2) cellular casts

Treatment:

  • Treat the ds, not the serologic activity
  • Avoid sun exposure
  • For mild sx: NSAIDs (ibuprofen 400-800 mg 3-4 txd)
  • For acute exacerbation: corticosteroids (either systemic or local)
  • For mild nephritis: 1st line: Mycophenolate mofetil 2-3 gd. 2nd line: Azathioprine (AZA) – steroid sparing
  • For severe nephritisserious SLE: cytotoxic agentsimmunosuppressive agents (cyclophosphamide IV pulse 500-750 mgM2 x 6 mo, followed by maintenance w Mycophenolate mofetil or AZA) added to steroids. SE: Myelosuppression, hemorrhagic cystitis, bladder Ca, teratogen.
  • For long-termpreventive (for cutaneous, constitutional and articular manifestations): antimalarial agents (Hydroxychloroquine; 400 mgd). Requires annual eye exam for possible retinal toxicity. Other SE is Stevens-Johnson synd

 

SLE 11

 

Complications and Prognosis:

  • Bimodal mortality pattern:
  • Early (win 2 yrs): infections (50% are opportunistic; PCP and candida), or active ds (renal or CNS)
  • Late (>10 yrs): atherosclerosis and accelerated coronary artery ds (MI)
  • Prognosis: 10-yr survival is > 85%

 

Pregnancy and SLE:

  • Normal fertility rates, but they have increased spontaneous abortions and stillbirths compared with normal pts
  • Why? Anti-phospholipid Abs -> placental infarcts
  • How to treat? Low-molecular weight heparin (LMWH) during pregnancy
  • In case of a lupus flare during pregnancy -> safely use steroids
  • All preg ladies should be screened for Anti-Ro (SS-A)
  • Why? These Abs cross placenta -> passively transferred to fetus -> neonatal lupus + heart block

 


Download the PDF version: here


References:

  • Pocket medicine
  • Toronto notes
  • Step up to medicine 
  • Master the boards
  • The Johns Hopkins Internal Medicine Board Review
  • Davidson’s Principles and Practice of Medicine

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