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Systemic Lupus Erythematosus, Emergency Medicine

Basics

Description

- 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

- Systemic: - Fatigue - Fever - Weight loss - Dyspnea

- Musculoskeletal: - Myalgias - Joint pain - Arthritis: - Defined as 2 or more peripheral joints - Polyarthritis, symmetric, or migratory

- Heart: - Chest pain - Pericardial rub - Murmur

- Lungs: - Dyspnea - Tachypnea - Pleural rub - Rales

- GI: - Painless oral ulcers - Abdominal pain - Positive stool guaiac suggests mesenteric ischemia

- 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

- CXR: - Pneumonitis - Pneumonias - Pleural effusion - Cardiomegaly

- ECG/echocardiogram - CT chest: - Pulmonary embolus - Pulmonary hemorrhage - Diffuse alveolar hemorrhage

- Skin changes: - Urticaria - Erythema multiforme

- 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)

  • 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 system4 specific skin rashesArthritisCardiac:EndocarditisMyocarditisCHFConduction abnormalitiesAtherosclerosisMIRenal:GlomerulonephritisRenal failurePulmonary:Pleural effusion (usually exudative)Pneumonitis/pleuritisPulmonary hemorrhagePulmonary embolismPneumoniaPulmonary edemaPulmonary hypertensionNeurologic:Vascular:VasculitisThrombosisAtherosclerosisGI:PeritonitisMesenteric vasculitis and ischemiaPancreatitis
  • 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 componentsTendency toward recurrent vascular thrombosis
  • Lupus is a chronic disease with several exacerbating factors:InfectionSun exposureFatigueTraumaMedications (sulfonamides)StressDiet
  • 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 rashDiscoid rashPhotosensitivity rashOral ulcersArthritisSerositisNeurologic disordersHematologic disordersImmunologic disordersRenal disordersAntinuclear antibodies

Signs and Symptoms

  • Systemic:FatigueFeverWeight lossDyspnea
  • Skin:Malar rash (butterfly maculopapular facial)Discoid rash (raised red patches)Photosensitivity rash (subacute cutaneous lupus)Bullous rash (large blisters)
  • Musculoskeletal:MyalgiasJoint painArthritis:Defined as 2 or more peripheral jointsPolyarthritis, symmetric, or migratory
  • Heart:Chest painPericardial rubMurmur
  • Vascular:VasculitisThrombosisAtherosclerosisPeripheral vascular disease
  • Lungs:DyspneaTachypneaPleural rubRales
  • Nervous system:Psychosis/depressionHeadacheSeizuresPeripheral neuropathiesStroke/cranial nerve deficitsCerebritis
  • GI:Painless oral ulcersAbdominal painPositive 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:CBCElectrolytes, BUN, creatinine, glucoseUAESRChest radiograph, ECG, and pulse oximetry for cardiorespiratory symptoms

Diagnosis Tests & Interpretation

Lab

  • CBC:Leukopenia, thrombocytopenia, normochromic normocytic anemiaDegree of hematologic disorders suggests degree of disease activity
  • ESR:May be elevated during acute exacerbationsNot 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)HematuriaWBCs
  • 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:PneumonitisPneumoniasPleural effusionCardiomegaly
  • ECG/echocardiogram
  • CT chest:Pulmonary embolusPulmonary hemorrhageDiffuse 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 feverRheumatoid arthritisDermatomyositisOverlap syndromes
  • Skin changes:UrticariaErythema 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, sunscreenTopical steroids for most cutaneous manifestationsIf not sufficient, begin low-dose prednisone
  • Major flare-ups " ”life- or organ-threatening:MethylprednisoloneAnticoagulation for thrombosis; give blood products early if neededPsychotropics for neuropsychiatric symptomsAnticonvulsants for seizuresIf poor response, consult rheumatology before starting cytotoxic medications
  • Chronically:Prednisone taperNSAIDsRheumatologist initiated:Antimalarials: Quinacrine, chloroquine:Side effect is irreversible retinopathyCyclophosphamideAzathioprineMethotrexateBelimumab (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