Pathophysiology

Autoimmune Igs are produced for an unknown reason and form immune complexes and activate the inflammatory response throughout the body. This immune activation and autoreactive Its lead to tissue damage, and immune complex deposition can lead to lupus nephritis.

SSx

Many variable SSx, both constitutional and organ-specific

Organ System	SSx
Systemic	Fatigue Fever Wt Loss
Dermatological	Photosensitivity Malar (butterfly) rash Oral Ulcers Alopecia Raynaud’s Phenomenon Discoid Rash (Circular, red, and scaly)
Renal	Lupus Nephritis Hematuria / Proteinuria Casts Nephrotic Syndromes
GI	N / V Anorexia Abd Pain
Psych / Neuro	Psychosis Szs Depression Anxiety
CV	Pericarditis / Myocarditis Valve Disease CAD HTN
Pulm	Cough Dyspnea Pneumonitis Pleurisy
Heme	Hemolytic Anemia Thrombocytopenia Leukopenia Anti-Phospholipid Igs
Immunologic	Anti-dsDNA or ANA Ig production

Dx Criteria

ACR (1997)

DOPAMINE RASH (does not involve dopamine)

≥ 4/11 is diagnostic

• Discoid Rash
• Oral Ulcers
• Photosensitivity
• Arthritis
• Malar Rash
• Immune Involvment
• Neuro Involvment
• Renal Involvment
• ANA (+)
• Serositis
• Hematologic Involvment

SLICC (Systemic Lupus International Collaborating Clinics) (2012)

• ≥ 4/17 including at least 1 immunologic and 1 clinical criteria
• OR
• Biopsy proven nephritis with (+) ANA or (+) Anti-dsDNA
• Clinical Criteria
  • Acute Cutaneous Lupus
  • Chronic Cutaneous Lupus
  • Non-Scarring Alopecia
  • Oral / Nasal Ulcers
  • Joint Disease
  • Seorsitis
  • Renal Involvment
  • Neuro Involvment
  • Hemolytic Anemia
  • Leukopenia
  • Thrombocytopenia
• Immunologic Criteria
  • Elevated ANA
  • Elevated Anti-dsDNA
  • Anti-Sm Antigen
  • Antiphospholipi Igs
  • Low Complement Levels
  • (+) Direct Coombs Test

Treatment

• Non-Pharm
  • Limit sun exposure w/ sunblock and avoiding direct sunlight
  • Balanced diet
  • No live vaccinations if immunocompromised, and be cautious during flares
  • Smoking cessation
  • Regular exercise
• NSAIDs
  • First line for pain and fever associated with flairs
  • Ibuprofen 400-800mg PO Q6-8H
  • Naproxen 440-500mg PO BID
  • Increase risk of aseptic meningitis
  • Monitoring
    • Baseline: SCr, UA, CBC, LFTs, BP
    • Annual: SCr, CBC, LFTs, BP
• Antimalarials
  • Chronic use if NSAIDs not managing SSx
  • Can take up to 6-12mo to take effect
  • Hydroxychloroquine (Plaquenil) 200-400mg PO QD divided (Preferred)
  • Chloroquine (Aralen) 250-500mg PO QD
  • SEs
    • Corneal deposits (Reversible if caught early, causes halos around light sources, chloroquine has higher risk)
    • Rash
    • Pigment changes in hair / skin
    • HA
    • Anxiety
    • Insomnia
    • GI Upset
  • Monitoring
    • Baseline: Ophthalmologic Screening, CBC, LFTs, SCr
    • Periodic: Ophthalmologic test q3mo w/ chloroquine, q12mo w/ hydroxychloroquine
• Topical GCs
  • Second-Line for cutaneous SSx
  • Low-Potency for Face
    • Fluocinolone Acetonide 0.01%
    • Hydrocortisone Butyrate 1%
  • Mid-Potency for Trunk and Extremities
    • Triamcinolone Acetonide
    • Betamethasone valerate
  • High-Potency for Scalp, Soles, and Palms
    • Clobetasol
  • Can also consider topical calcineurin inhibitors
    • Pimecrolimus
    • Tacrolimus
  • SEs
    • Skin atrophy
    • Rosacea
    • Telangiectasia
• Systemic GCs
  • Mild disease not controlled on antimalarials / NSAIDs or severe disease
  • Maintenance
    • Mild: Prednisone 10-20mg PO QD
    • Severe: 1-2 mg/kg PO QD (can divide dose)
  • Pulse
    • Methylprednisolone 500-1000mg IV QD x3-6d THEN
    • Prednisone 1-1.5 mg/kg PO QD w/ taper following
  • See steroids page for SEs
  • Monitoring
    • Baseline: BP, Bone Mineral Density, BMP, FLP
    • Routing: BMP and FLP q6mo, Bone mineral density q12mo
• Cytotoxic Agents
  • Use in severe disease threatening organ function
  • Cyclophosphamide (Cytoxan)
    • Used for life-threatening disease or nephritis
    • 1-3 mg/kg PO QD OR
    • 0.5-1 g/m^2 q1mo x6-7mo then q3mo x2yrs or x1yr after nephritis remission
    • SEs
      • Myelosuppression
      • Infection
      • Hemorrhagic cysts (more common w/ PO)
      • Bladder cancer
      • Infertility
    • Monitoring
      • Baseline: CBC w/ diff, UA, SCr, LFTs
      • Routine: CBC and UA q1mo, Urine cytology and PAP q12mo, SCr and LFTs as well
  • Azathioprine (Imuran)
    • Long-term therapy for renal flairs or decrease dose of GCs
    • 1-3 mg/kg PO QD
    • Commonly used w/ GCs
    • SEs
      • Myelosuppresion
      • Infection
      • Hepatotoxicity
      • Ovarian failure
      • Thrombocytopenia
    • Monitoring
      • TPMT Activity Assay
      • CBC
      • Plts
      • SCr
      • LFTs
      • Chem7
      • Albumin
      • PAP
  • Mycophenolate mofetil (Cellcept)
    • Lupus nephritis, derm SSx, arthritis, and hematologic SSx (not first line)
    • 1-3g PO QD
    • Commonly used w/ GCs
    • SEs
      • Myelosupression
      • N / V / D
      • BP Changes
      • CNS effects
      • Electrolyte disturbances
      • Renal / Hepatic problems
      • Pulmonary problems
    • Take on an empty stomach 1hr before or 2hr after meal
    • Monitoring
      • Baseline: CBC, LFTs, SCr / BUN, CXR, Chem7
      • Routine: CBC weekly x1mo, then biweekly x2mo, then monthly
• Biologic Agents
  • Belimumab (Benlysta)
    • Apoptosis of B cells
    • Add-on to standard treatment in presence fo (+) auto-Igs
    • 10 mg/kg q2wks x3 doses then 10 mg/kg q4wks
  • Rituximab (Rituxan)
    • Kills B cells
    • Used in lupus nephritis, may be more effective w/ cyclophosphamide
    • 375 mg/m^2 IV weekly x4 doses OR 500-1000mg on day 1 and 15
• Additional Therapies
  • MTX 7.5mg PO weekly (Max 20mg QD) w/ 1mg folate QD
  • TNF-α inhibitors (Adalimumab, etanercept, and infliximab)
  • Tacrolimus

Pregnancy and SLE

• Avoid pregnancy w/ active disease
• 6mo exacerbation free 6mo before conception
• Anti-Phospholipid syndrome should avoid estrogen-containing contraceptives
• NSAIDs are safe, just D/C last week before delivery
• GCs are safe, use < 10 mg QD prednisone equivalent
• Hydroxychloroquine is safe, drug of choice
• Azathioprine is safe NTE 2 mg/kg QD
• Cyclophosphamide, mycophenalate, and MTC are contraindicated

SLE and Coagulation

• Anti-Phospholipid Igs increases risk of thrombosis and spontaneous abortion
• ASA 81mg PO QD if not prior fetal loss
• ASA 81mg PO QD +/- low-dose heparin or LMWH w/ recurrent fetal loss
• Therapeutic heparin or LMWH w/ Hx of thrombosis or acute thrombotic events

Drug-Induced Lupus

• Procainamide
• Hydralazine
• Isoniazid
• Chlorpromazine
• Methyldopa
• Minocycline
• Quinidine
• TNG-α Inhibitors

Treat by D/C-ing agent and adding GCs or NSAIDs as necessary