Systemic Lupus Erythematosus (SLE) in Adults

Background

• Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder of connective tissue characterized by autoantibodies that target nuclear antigens, remissions and flares, and a highly variable clinical presentation, disease course, and prognosis.
• Multiple organs and systems may be involved in SLE, including the kidneys, skin, musculoskeletal system, cardiovascular system, central and peripheral nervous systems, and blood.
• SLE is more common in women and people of African descent, American Indians, Alaska Natives, and persons of Arab origin
• Etiology of SLE is unknown, but it likely involves the loss of self-tolerance and resulting autoimmunity in individuals with a genetic predisposition after exposure to environmental triggers in the setting of various immunologic and hormonal factors.
• Certain medications are associated with lupus-like syndrome. The cardiac drugs procainamide and hydralazine have the highest reported risk (though they are not commonly used today), but more commonly used isoniazid, quinidine, and sulfadiazine have been associated with a moderate risk (see Drug-induced Lupus for additional information).

Evaluation

• Most patients present with constitutional symptoms (such as, fatigue, fever, or weight loss) with cutaneous, musculoskeletal, and mild hematologic involvement but presentation with an organ-specific disease, including nervous system manifestations or kidney involvement, is not uncommon.
• Inflammatory arthritis, malar rash, fever, and photosensitivity are reported to be the most frequent manifestations.
• The diagnosis of SLE can be difficult and may be delayed because the presentation varies widely among patients, the symptoms evolve over time, and it may not be considered in the differential diagnosis.
• The diagnosis is clinical and is often based on European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) 2019 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria (originally established for research purposes):
  • For EULAR/ACR 2019 classification, a confirmed diagnosis requires the presence of entry criterion (a history of antinuclear antibodies [ANA] at titer ≥ 1:80 on human epithelial type 2 [HEp-2] cells or equivalent positive test), ≥ 1 clinical criterion, and a total score ≥ 10 points.
  • For SLICC 2012 classification, a diagnosis occurs in patients with either ≥ 4 of 17 criteria (including ≥ 1 clinical and 1 immunologic criteria) OR biopsy-proven lupus nephritis in the presence of ANA or anti-double‐stranded DNA (anti-dsDNA) antibodies.
• Tests used to establish a diagnosis include certain autoantibody titers, as well as specific testing to determine the extent of organ involvement.
  • Approach to testing for neuropsychiatric disease is similar to that in patients without SLE and may include neuropsychological and cognitive tests, cerebrospinal fluid analysis, electroencephalogram (EEG), and central nervous system imaging.
  • Joint imaging may be used to detect musculoskeletal involvement.
  • Lupus nephritis is diagnosed based on a urinalysis and a kidney biopsy (see also Kidney Disease in Systemic Lupus Erythematosus).
  • Skin biopsy may be useful for a diagnosis of cutaneous involvement.

Management

• The treatment goals include minimizing organ damage, preventing flares during periods of stability, and optimizing health-related quality of life.
• Treat all patients with active disease with an antimalarial, usually hydroxychloroquine 300-400 mg/day orally (maximum daily dose 5 mg/kg/day based on real body weight), unless not tolerated or contraindicated (Strong recommendation).
• Consider glucocorticoids, with the dose and route of administration based on the type and severity of the organ involvement (Weak recommendation).
  • Oral glucocorticoid use should be avoided if possible.
  • If glucocorticoid use is required, treatment should be minimized and tapered as soon as possible. Initiation of immunomodulatory agents may aid in tapering.
  • High-dose or pulsed glucocorticoids may be considered in patients with life- or organ-threatening manifestations (for example, lupus nephritis, vasculitis, or central nervous system involvement).
• In patients who are not responding to hydroxychloroquine (alone or in combination with glucocorticoids) or patients who are unable to reduce oral prednisone dose (or equivalent) ≤ 7.5 mg/day:
  • Consider the addition of immunomodulating/immunosuppressive agents, such as, methotrexate, azathioprine, or mycophenolate mofetil (Weak recommendation).
  • Cyclophosphamide may be considered in patients with severe organ- or life-threatening disease or in patients who are not responding to other immunosuppressive agents (Weak recommendation).
• Consider the use of biologics in patients with an inadequate response to first-line immunosuppressive agents.
• Treatment for specific organ involvement:
  • For patients with major neuropsychiatric manifestations of an inflammatory origin, give combination glucocorticoids and immunosuppressive therapy (Strong recommendation).
  • See Kidney Disease in Systemic Lupus Erythematosus for management of lupus nephritis.
  • For cutaneous lupus, advise patients to use precautions against ultraviolet light exposure and consider first-line therapeutic options including antimalarials, topical therapies (including glucocorticoids and calcineurin inhibitors), and systemic glucocorticoids.
• Hematopoietic or mesenchymal stem cell transplant may be considered for patients with SLE refractory to standard therapy.
• For the management of SLE during pregnancy, monitor the disease activity and the effects on pregnancy with more frequent prenatal visits and fetal assessments, and treat SLE flares during pregnancy with glucocorticoids (see Lupus in Pregnancy for details).
• For patients with SLE and antiphospholipid antibody syndrome, consider low-dose aspirin 75-100 mg/day orally for primary prevention of thrombosis and pregnancy loss (see Antiphospholipid Antibody Syndrome (APS) for details).