systemic%20lupus%20erythematosus
SYSTEMIC LUPUS ERYTHEMATOSUS
Systemic lupus erythematosus is a chronic, multisystem, inflammatory, autoimmune disorder characterized by formation of autoantibodies directed against self-antigens and immune-complex formation.
It can be suspected when ≥2 organ systems are involved.
It is predominantly diagnosed in females of childbearing age, rarely diagnosed before 8 years old.
Clinical presentation varies in different patients and the disease activity varies over time in a single patient. Majority of patients have arthralgia of the hand.

Principles of Therapy

  • Patients require individualized therapy depending on disease manifestations, activity & severity
  • Control disease manifestations
  • Allow the patient to have a good quality of life w/o major exacerbations
  • Prevent serious organ damage that adversely affect function or life span
  • Prevent adverse effects of the drugs used

Pharmacotherapy

Corticosteroids
Oral corticosteroids
  • Patients w/ mild systemic lupus erythematosus (SLE) do not normally require use of systemic corticosteroids but there are patients who has low quality of life if not given low-dose corticosteroids
  • Actions: Decreases inflammation by suppression of the immune system
    • Decreases lymphocyte volume & activity, PMN migration, capillary permeability
    • High doses over periods of >2-3 weeks, suppress adrenal function
  • Used as initial therapy for severe discoid lupus erythematosus or lupus vasculitis
  • Low-dose corticosteroids may be added to Hydroxychloroquine for fatigue & fever
  • High-dose corticosteroids are necessary for refractory manifestations of SLE & for severe organ involvement especially CNS, renal & hematologic manifestations
    • Patients w/ milder forms of renal manifestations (eg mesangial glomerulonephritis & focal proliferative glomerulonephritis) may respond to corticosteroids monotherapy
    • Show improved survival in patients w/ severe forms of SLE nephritis
    • May also be useful in severe, life-threatening thrombocytopenia & hemolytic anemia
    • May also be useful in pleuritis or pericarditis
  • Corticosteroid use should be tapered as soon as desired response is observed (control of inflammatory manifestations) to avoid toxicity
Topical corticosteroids
  • Helpful for discoid lesions especially on the scalp
  • Use a less potent steroid on the face because it is more prone to atrophy
Parenteral Corticosteroids
  • Pulse therapy w/ IV corticosteroids in combination w/ immunosuppressive therapy is recommended for Class III/IV SLE patients w/ confirmed glomerulonephritis
Hydroxychloroquine
  • Inhibits chemotaxis of eosinophils & locomotion of neutrophils & impairs complement-dependent antigen-Ab reactions
  • Used for skin & joint manifestations
    • Useful for patients w/ skin disease that are unresponsive to topical corticosteroids & in patients w/ arthritis that does not respond to NSAID
  • Recommended as background treatment for Class III/IV SLE patients w/ nephritis
    • Patients w/ continuing treatment w/ Hydroxychloroquine showed less renal damage as compared to those on placebo
  • Also used for preventing flares, reducing CV risk & recurrent infection, & other constitutional symptoms
Immunosuppressants
Choice of immunosuppressant will depend on nature & severity of disease manifestation
  • These agents act as immunosuppressive, cytotoxic & anti-inflammatory agents
    • In the treatment of severe CNS & severe glomerulonephritis, thrombocytopenia & hemolytic anemia, high-dose glucocorticoids & immunosuppressants are used
    • Concomitant use w/ corticosteroids allows lower doses of immunosuppressants
Azathioprine
  • Antagonizes purine metabolism & inhibits synthesis of DNA, RNA & proteins
  • May be used as the initial immunosuppressant for SLE nephritis
  • A steroid-sparing agent in SLE-related organ involvements (ie renal, neurological, hematological)
  • May decrease proliferation of immune cells, resulting in lower autoimmune activity
Belimumab
  • The first US FDA-approved biologic therapy for the treatment of SLE
  • A human monoclonal antibody that binds to soluble B-lymphocyte stimulator (BLyS/BAFF) to reduce disease activity
  • Used for active, autoantibody-positive SLE patients currently on standard therapy
  • Not recommended for patients w/ severe active lupus nephritis or severe active CNS disease
  • Studies have shown that patients on Belimumab therapy experienced reduced risk of severe flares, improved health-related quality of life & reduced steroid use as compared to those on placebo
Cyclophosphamide
  • As an alkylating agent, may involve cross-linking of DNA, which may interfere w/ growth of normal & neoplastic cells
  • Used as the initial immunosuppressant for SLE nephritis
    • Concomitant use w/ Prednisone is the standard treatment for lupus nephritis as it helps preserve renal function
  • Useful for severe SLE w/ involvement of different organ systems (eg severe CNS involvement, vasculitis or lupus nephritis)
Mycophenolic acid
  • A reversible inhibitor of inosine monophosphate dehydrogenase which is the rate-limiting step in de novo purine synthesis
  • An alternative treatment, both in initial and maintenance therapy of lupus nephritis
  • Recommended as induction & maintenance therapy for patients w/ lupus nephritis & has shown better results (less adverse effects & infections) as compared to intravenous Cyclophosphamide
Intravenous Immune Globulin (IV Ig)
  • Neutralizes circulating myelin antibodies through anti-idiotypic Abs
    • Down-regulates proinflammatory cytokines, including interferon-gamma
    • Blocks receptors on macrophages, suppresses inducer T & B cells, & augments suppressor T cells
    • Blocks complement cascade, promotes remyelination & may increase colony stimulating factor lgG
  • Used as immunosuppressant in serious SLE flares
Methotrexate
  • Blocks purine synthesis, increases anti-inflammatory adenosine concentration at sites of inflammation
  • May be used as the initial immunosuppressant for severe arthritis
Rituximab
  • A chimeric anti-human CD20 antibody w/c regulates B-cells
  • Used as rescue therapy for SLE patients unresponsive to standard therapy
  • Further studies are needed to determine the efficacy of Rituximab & other anti-CD20 antibodies (ie Ocrelizumab) in patients w/ SLE
Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Inhibit inflammatory reactions & pain by decreasing prostaglandin synthesis
  • These drugs provide symptomatic relief of fever, arthritis & mild serositis
  • SLE patients have a high incidence of NSAID-induced hepatotoxicity
Sunscreen
  • Patients w/ SLE should apply sunscreen w/ at least an SPF of 30 to prevent dermal or systemic disease flares upon exposure to ultraviolet light

Non-Pharmacological Therapy

Sunscreen

  • Patients w/ systemic lupus erythematosus (SLE)  should apply sunscreen w/ at least an sun protection factor (SPF) of 30 to prevent dermal or systemic disease flares upon exposure to ultraviolet light
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