Basics
Description
- Chronic autoimmune disease; peak onset between ages 15 and 40 yr; characterized by flares and remissions
- Multisystem disease with diverse clinical manifestations:
- Mucocutaneous:
- Most commonly involved system
- 4 specific skin rashes
- Arthritis
- Cardiac:
- Endocarditis
- Myocarditis
- CHF
- Conduction abnormalities
- Atherosclerosis
- MI
- Renal:
- Glomerulonephritis
- Renal failure
- Pulmonary:
- Pleural effusion (usually exudative)
- Pneumonitis/pleuritis
- Pulmonary hemorrhage
- Pulmonary embolism
- Pneumonia
- Pulmonary edema
- Pulmonary hypertension
- Neurologic:
- Vascular:
- Vasculitis
- Thrombosis
- Atherosclerosis
- GI:
- Peritonitis
- Mesenteric vasculitis and ischemia
- Pancreatitis
- Neonatal lupus may occur when maternal autoantibodies cross the placenta:
- Associated with transient anemia and thrombocytopenia
- Congenital heart block is the most serious complication
- 10 times greater risk of MI due to atherosclerosis
- High incidence of osteoporosis related to chronic steroid use
Risk Factors
Genetics
- More common in females than males (9:1 ratio)
- More common in women of childbearing age
- More common in African Americans
- Higher frequency of systemic lupus erythematosus (SLE) and other autoimmune diseases among 1st-degree relatives
Etiology
- Autoantibody production against cell nucleus and cytoplasmic structures, leading to inflammatory changes, vasculitis, and immune complex deposition in multiple organ systems
- A significant percentage of patients have an associated antiphospholipid syndrome:
- Characterized by antibodies against cellular phospholipid components
- Tendency toward recurrent vascular thrombosis
- Lupus is a chronic disease with several exacerbating factors:
- Infection
- Sun exposure
- Fatigue
- Trauma
- Medications (sulfonamides)
- Stress
- Diet
- Drug-induced lupus is a milder disease that eventually resolves once the drug is discontinued. Usually presents with skin and joint manifestations while renal and neurologic involvement is rare.
- Common medications include:
- Chlorpromazine, methyldopa, procainamide, hydralazine, isoniazid, quinidine, minocycline
Diagnosis
- 4 of the 11 criteria in the following list are needed to make the diagnosis:
- Malar rash
- Discoid rash
- Photosensitivity rash
- Oral ulcers
- Arthritis
- Serositis
- Neurologic disorders
- Hematologic disorders
- Immunologic disorders
- Renal disorders
- Antinuclear antibodies
Signs and Symptoms
- Systemic:
- Fatigue
- Fever
- Weight loss
- Dyspnea
- Skin:
- Malar rash (butterfly maculopapular facial)
- Discoid rash (raised red patches)
- Photosensitivity rash (subacute cutaneous lupus)
- Bullous rash (large blisters)
- Musculoskeletal:
- Myalgias
- Joint pain
- Arthritis:
- Defined as 2 or more peripheral joints
- Polyarthritis, symmetric, or migratory
- Heart:
- Chest pain
- Pericardial rub
- Murmur
- Vascular:
- Vasculitis
- Thrombosis
- Atherosclerosis
- Peripheral vascular disease
- Lungs:
- Dyspnea
- Tachypnea
- Pleural rub
- Rales
- Nervous system:
- Psychosis/depression
- Headache
- Seizures
- Peripheral neuropathies
- Stroke/cranial nerve deficits
- Cerebritis
- GI:
- Painless oral ulcers
- Abdominal pain
- Positive stool guaiac suggests mesenteric ischemia
History
- Symptoms commonly accumulate and exacerbate over years, with flares and remissions. A history of fatigue, rashes, and joint pain may point to the diagnosis.
- Patients describe arthralgias out of proportion to physical findings
Physical Exam
- Check for fever
- Carefully evaluate skin for rashes and vasculitis
Essential Workup
- Thorough history and physical exam needed to distinguish between major and minor flare-ups
- Major flare-ups:
- CBC
- Electrolytes, BUN, creatinine, glucose
- UA
- ESR
- Chest radiograph, ECG, and pulse oximetry for cardiorespiratory symptoms
Diagnosis Tests & Interpretation
Lab
- CBC:
- Leukopenia, thrombocytopenia, normochromic normocytic anemia
- Degree of hematologic disorders suggests degree of disease activity
- ESR:
- May be elevated during acute exacerbations
- Not a good indicator of active disease
- CRP may also be elevated; marked elevation may be a sign of infection
- PTT:
- May be elevated in patients with lupus anticoagulant
- UA:
- Protein (persistent proteinuria > 0.5 g/day or 3+ persistently)
- Casts (red blood cell)
- Hematuria
- WBCs
- Amylase is elevated in mesenteric ischemia and pancreatitis
- Send antinuclear antibody, rheumatoid factor (RF), antistreptolysin O (ASO) titer if diagnosis unclear
- Anti-Sm and anti-dsDNA are diagnostic
- A false-positive Venereal Disease Research Laboratory (VDRL) test is supportive of the diagnosis
- Joint aspirate typically shows fluid with fewer than 3,000 WBCs
- LP if suspicion for meningitis or encephalitis
Imaging
- CXR:
- Pneumonitis
- Pneumonias
- Pleural effusion
- Cardiomegaly
- ECG/echocardiogram
- CT chest:
- Pulmonary embolus
- Pulmonary hemorrhage
- Diffuse alveolar hemorrhage
- CT head for change in mental status or neurologic findings (lupus cerebritis is a diagnosis of exclusion)
- Pregnancy is not recommended during active disease owing to the high risk of spontaneous abortion
- The effect of pregnancy on disease activity is variable
Differential Diagnosis
- Hypotension in the known lupus patient may be due to shock from a major flare-up, secondary to acute steroid withdrawal, or the result of sepsis
- Other autoimmune diseases:
- Rheumatic fever
- Rheumatoid arthritis
- Dermatomyositis
- Overlap syndromes
- Skin changes:
- Urticaria
- Erythema multiforme
- Idiopathic thrombocytopenic purpura
- Multiple sclerosis
- Epilepsy
Treatment
Initial Stabilization/Therapy
ABCs ‚
Ed Treatment/Procedures
- Mainstays include NSAIDs, corticosteroids, antimalarials, and immunosuppressive drugs
- Special attention must be given to CNS and renal involvement as well as infections; these are the main determinants of morbidity
- Mild flare-ups " ”arthralgias, myalgias, fatigue, and rash:
- NSAIDs (careful with lupus nephritis), acetyl salicylic acid (ASA), topical steroids for rash, sunscreen
- Topical steroids for most cutaneous manifestations
- If not sufficient, begin low-dose prednisone
- Major flare-ups " ”life- or organ-threatening:
- Methylprednisolone
- Anticoagulation for thrombosis; give blood products early if needed
- Psychotropics for neuropsychiatric symptoms
- Anticonvulsants for seizures
- If poor response, consult rheumatology before starting cytotoxic medications
- Chronically:
- Prednisone taper
- NSAIDs
- Rheumatologist initiated:
- Antimalarials: Quinacrine, chloroquine:
- Side effect is irreversible retinopathy
- Cyclophosphamide
- Azathioprine
- Methotrexate
- Belimumab (FDA approved for active, autoantibody positive disease in patients under active treatment)
- Hormonal therapy, mycophenolate mofetil, rituximab, and autologous marrow stem cell transplant are under investigation
Medication
- Methylprednisolone: 15 mg/kg/d IV up to 1 g; consult rheumatologist for peds dosing
- Prednisone: 5 " “30 mg (peds: <0.5 mg/kg) PO daily for minor flare
- Prednisone: 1 " “2 mg/kg/d PO for major flares in adults
- Ibuprofen: 800 mg (peds: 5 " “10 mg/kg) PO TID
Follow-Up
Disposition
Admission Criteria
- Patients who have end-organ disease such as renal, cardiac, or CNS involvement
- Thrombocytopenia with hemorrhage, arterial or venous thrombosis
- Consider admission with pericarditis, myocarditis, pleural effusion or infiltrates, and evidence of vasculitis
- Those with severe end-organ or life-threatening manifestations should be admitted to the ICU
- Patients with lupus should be treated as immunocompromised and suspected or diagnosed infections should be treated aggressively
Discharge Criteria
- Patients may be discharged home with mild flare-ups if afebrile, well hydrated, and not ill appearing
- ESR should not be used as disposition criterion as it may be elevated long after a flare-up has subsided
Issues for Referral
Because lupus is a chronic disease, a rheumatologist or knowledgeable primary care physician (PCP) must follow the patient adequately ‚
Followup Recommendations
PCPs must educate patients regarding sun protection, immunizations, and lowering risks of atherosclerosis ‚
Pearls and Pitfalls
- The diagnosis of SLE is complicated and requires a thorough history and physical exam supported by appropriate lab testing
- Chronic steroid therapy leads to immunosuppression
- Renal involvement confers a poor prognosis
- Serum creatinine may be elevated, but is a poor indicator of the disease (urinalysis is more sensitive with proteinuria and/or red blood cell casts)
- All patients with SLE should be offered annual, seasonal influenza vaccinations and be sure that pneumococcal vaccination is up to date
- VDRL may be falsely positive
Additional Reading
- Buyon ‚ JP. Systemic lupus erythematosus: Clinical and laboratory features. In: Klippel ‚ JH, ed. Primer on the Rheumatic Diseases. 13th ed. Atlanta: Arthritis Foundation; 2008:303 " “318.
- Coca ‚ A, Sanz ‚ I. Updates on B-cell immunotherapies for systemic lupus erythematosus and Sjogrens syndrome. Curr Opin Rheumatol. 2012;24:451 " “456.
- Lehrmann ‚ J, Sercombe ‚ CT. Systemic lupus erythematosus and the vasculitides. Rosen's Emergency Medicine. 7th ed. Philadelphia, PA: Mosby Elsevier; 2010.
- Schur ‚ PH, Wallace ‚ DJ. Overview of the therapy and prognosis of systemic lupus erythematosus in adults. UptoDate.com. Available at http://utdol.com/.
Codes
ICD9
- 420.0 Acute pericarditis in diseases classified elsewhere
- 583.81 Nephritis and nephropathy, not specified as acute or chronic, in diseases classified elsewhere
- 710.0 Systemic lupus erythematosus
- 517.8 Lung involvement in other diseases classified elsewhere
- 424.91 Endocarditis in diseases classified elsewhere
ICD10
- M32.9 Systemic lupus erythematosus, unspecified
- M32.12 Pericarditis in systemic lupus erythematosus
- M32.14 Glomerular disease in systemic lupus erythematosus
- M32.13 Lung involvement in systemic lupus erythematosus
- M32.10 Systemic lupus erythematosus, organ or system involv unsp
- M32.11 Endocarditis in systemic lupus erythematosus
- M32.15 Tubulo-interstitial neuropath in sys lupus erythematosus
- M32.19 Oth organ or system involv in systemic lupus erythematosus
- M32.1 Systemic lupus erythematosus w organ or system involvement
- M32.8 Other forms of systemic lupus erythematosus
SNOMED
- 55464009 Systemic lupus erythematosus (disorder)
- 309762007 Systemic lupus erythematosus with pericarditis
- 68815009 Systemic lupus erythematosus glomerulonephritis syndrome (disorder)
- 196138005 Lung disease with systemic lupus erythematosus (disorder)
- 95408003 Systemic lupus erythematosus arthritis (disorder)
- 95644001 Systemic lupus erythematosus encephalitis