II. Background
- Named in 1851 for wolf (lupus) bite-like facial rash
- First described by Moritz Kaposi
III. Epidemiology
-
Prevalence
- England: 200 per 100,000 women aged 18 to 65 years
- U.S
- Adults: 40 to 50 per 100,000 persons (up to 1 in 1000)
- Children 3.3 to 8.8 per 100,000 persons
- Over-diagnosed in United States
- Of 2 million U.S. cases, only 25% have true disease
- As of 2008, estimated true Prevalence in U.S.: 300,000
- Age distribution
- Young adult onset is most typical (but onset may be at ages 15-64 years)
- Children comprise 10 to 20% of cases (median onset 11 to 12 years, uncommon before age 8)
- Gender
- More common in women (especially child-bearing age) by ratio of 9:1 (women 90%, men 10%)
- Ratio 4-5:1 male to female in children
- Ethnic and racial predisposition
- Native American
- African American (twice as prevalent than in white patients)
- Hispanic
- Chinese
- Filipino
- References
IV. Causes
- Idiopathic
- Drug Induced lupus
- More than 80 drugs associated, esp. Hydralazine, Procainamide, Beta Blockers
V. Pathophysiology
- Tissue damage by Antibody and immune complex deposition
- Autoantibodies form to cell nucleus components
VI. Findings: Presentations
- Consider SLE when multiple organ systems are involved
- Most common presenting symptoms (90% of cases)
- Women of child-bearing age (age 15 to 50 years old)
- Fever
- Malar Rash
- Arthralgias (or myalgias)
- Men
- Less skin and joint involvement in men than women and children
- Hematologic disorder
- Renal disorder
- Neurologic disorder (esp. CNS)
- Children
- Fever
- Malar Rash
- Arthralgias
- Alopecia
- Hematologic disorder (Anemia, Leukocytopenia)
- Renal involvement
-
Drug-induced Lupus (occurs equally in men and women, typically closer to age 50 years old)
- Fever
- Rash
- Arthralgias and myalgias
- Pleuritic Chest Pain
- Rare renal involvement and rare CNS involvement
- Resolves in most cases after offending drug is stopped (see list of drug causes above)
VII. Symptoms
- Arthralgias and myalgias (95% at presentation)
- Fatigue (Prevalence overall: 90%)
- Fever
- Malaise
- Weight loss
- Malar Rash (31% at presentation)
- Photosensitivity (23% at presentation)
- Pleuritic Chest Pain (16% at presentation)
- Raynaud Phenomenon (16% at presentation)
- Oral Lesions such as Oral Ulcers or mucositis (12% at presentation)
VIII. Signs: General
- Dermatologic
- Discoid Rash (LR +18)
- Malar "butterfly" rash (50% of cases, 31% at presentation, LR+ 14)
- Photosensitivity (23% at presentation, LR+ 11)
- Vasculitis
- Alopecia
- Oral Ulcers or mucositis (often painless Oral Ulcers on Palate)
- Sicca Syndrome
- Rheumatologic or musculoskeletal symptoms (95% of cases)
- Arthralgias or Arthritis with symmetric Polyarthritis (esp. small joints)
- Myalgias or Myositis
- Raynaud Phenomenon (16% at presentation)
- Fibromyalgia (often comorbid in SLE patients)
- Abdominal
- Lymphadenopathy
- Splenomegaly
- Nephritis
- Mesenteric Vasculitis
- Neuropsychiatric
- Organic brain syndrome
- Seizures (LR+ 13)
- Psychosis (LR+ 13)
- Thrombotic Cerebrovascular Accident
- Transverse Myelitis
- Cognitive dysfunction (spectrum from mild cognitive deficits to Dementia)
- Migraine Headaches
- Peripheral Neuropathy
- Cardiovascular
- Pericarditis
- Myocarditis
- Acute Coronary Syndrome
- Venous thrombosis (DVT)
- Suggests Antiphospholipid Antibody Syndrome
- Pulmonary
- Pleuritis
- Pneumonitis or Pneumonia
- Interstitial Lung Disease
- Pulmonary Arterial Hypertension
- Pulmonary Embolism
- Ocular changes (20% of SLE cases)
- Anterior eye disorders
- Keratoconjunctivitis Sicca (25% of patients)
- Uveitis
- Episcleritis and Scleritis
- Keratitis
- Blepharitis-like Discoid Lupus eyebrow involvement
- Retinal Disorders
- Cotton wool spots
- Retinal Hemorrhages
- Proliferative Retinopathy
- Neurologic conditions
- Anterior eye disorders
IX. Diagnosis: EULAR/ACR Criteria 2019
- Background
- New 2019 EULAR/ACR guidelines included many of the SLICC Criteria (2012), which replaced original ACR Criteria (1997)
- Test Sensitivity: 96%
- Test Specificity: 93%
-
Antinuclear Antibody (ANA) positive is required for all SLE Diagnoses
- Titer >1:80 on HEp-2 Cells or equivalent positive at any time in patient's past history
- Titer over 1:320 is very suggestive
- Prior discriminatory value was 1:40 dilution
- Adjunctive Criteria Background
- SLE diagnosis requires at least one clinical criterion and at least 10 total points
- Criteria may have occurred previously and need not occur simultaneously with other criteria
- Only count criteria that can be attributed to SLE, and not to another more likely diagnosis
- Only count the highest weighted criterion from each domain, when a domain has more than one positive feature
- Adjunctive Clinical: Constitutional
- Weight 2: Fever (>38.3 C or 101 F)
- Adjunctive Clinical: Hematologic
- Weight 3: Leukopenia (<4000/uL)
- Weight 4: Thrombocytopenia (<100,000/mm3)
- Weight 4: Autoimmune Hemolysis or Hemolytic Anemia
- Findings include Reticulocytosis, low Haptoglobin, increased Indirect Bilirubin, increased LDH, positive Direct Coombs test
- Adjunctive Clinical: Neuropsychiatric
- Weight 2: Delirium
- Altered consciousness for <2 days, fluctuating throughout the day, affecting cognition or behavior, mood or affect
- Weight 3: Psychosis
- Findings include Delusions and/or Hallucinations without insight, and without comorbid Delirium
- Weight 5: Seizure Disorder (generalized or partial/focal)
- Findings
- Neurologic changes or Lupus Cerebritis is ultimately present in 75% of SLE cases
- Other neurologic criteria per SLICC (not part of EULAR/ACR Criteria)
- Thrombotic Cerebrovascular Accident
- Transverse Myelitis
- Cognitive dysfunction (spectrum from mild cognitive deficits to Dementia)
- More subtle, less specific or dramatic changes (Migraine Headache, Peripheral Neuropathy)
- Weight 2: Delirium
- Adjunctive Clinical: Mucocutaneous (findings must be observed by clinician)
- Weight 2: Non-scarring Alopecia
- Weight 2: Oral Ulcers
- Typically painless, oral or nasopharyngeal lesions
- Weight 4: Subacute cutaneous or Discoid Lupus
- Annular or papulosquamous (psoriaform) skin eruption typically in sun exposed regions (and phoosensitivity)
- Raised erythematous patches with adherent keratotic Scaling
- Follicular plugging
- Atrophic scarring in older patients
- Weight 6: Acute Cutaneous Lupus
- Generalized maculopapular rash
- Malar Rash (present in 30-50% of SLE cases)
- Erythema (may be raised) over the cheeks and sparing the nasolabial folds
- Photosensitivity
- Atypical sunlight skin reactions
- Biopsy findings
- Perivascular lymphohistiocytic infiltrate
- Adjunctive Clinical: Serosal (Lupus Serositis)
- See cardiac complications and pulmonary complications described below
- Weight 5: Pleural or Pericardial Effusion
- Weight 6: Acute Pericarditis
- Findings
- Pleuritic Chest Pain, friction rub or Pleural Effusion
- Positional Chest Pain worse supine
- Improved sitting or leaning forward
- Pericardial Effusion or friction rub
- EKG changes with diffuse ST Elevation, PR Depression and no reciprocal changes
- Adjunctive Clinical: Musculoskeletal
- Weight 6: Joint involvement (SLE Polyarthritis)
- Synovitis (swelling or effusion) involving 2 or more joints OR
- Joint tenderness and >=30 minutes morning stiffness affecting 2 or more joints
- Findings
- Polyarthritis is present in 90% of SLE cases
- SLE Polyarthritis is non-erosive and involves 2 or more joints
- Weight 6: Joint involvement (SLE Polyarthritis)
- Adjunctive Clinical: Renal
- Weight 4: Proteinuria >0.5g/24 hours (or equivalent Urine Protein to Creatinine Ratio)
- Weight 8: Renal biopsy class 2 or 5 Lupus Nephritis
- Weight 10: Renal biopsy class 3 or 4 Lupus Nephritis
- Findings
- Renal disease or Lupus Nephritis is ultimately present in 60% of SLE cases
- Persistent Proteinuria >500 mg/day (>3+ Urine Protein)
- RBC Cellular Casts (or mixed casts) may also be present
- Adjunctive Immunologic: Antiphospholipid Antibodies
- Weight 2: Anti-cardiolipin antibodies (medium or high titer) OR anti-B2GP1 Antibodies OR Lupus Anticoagulant
- Adjunctive Immunologic: Complement Proteins
- Weight 3: Low C3 OR low C4
- Weight 4: Low C3 AND Low C4
- Adjunctive Immunologic: SLE Specific Antibodies
- Weight 6: Anti-dsDNA Antibody OR Anti-Smith Antibody
- References
X. Labs: Protocol
- Lab interpretation described specifically below
- Indications for ANA titer
- Unexplained involvement of Two or more organ systems
- ANA positivity at low titers <1:320 is very prevalent in normal population (esp. children)
- Initial Screening
- ANA titer positive if 1:80 dilution (prior cut-off was 1:40)
- Secondary testing if ANA titer positive
- Complete Blood Count
- Comprehensive metabolic panel including Serum Creatinine
- Urinalysis
- Antiphospholipid Antibody
- Anticardiolipin Antibody
- Double Stranded DNA Antibody (Anti-dsDNA)
- Smith Antibody (Anti-Smith or Anti-Sm)
- Anti-ribonucleoprotein (Anti-RNP)
- Anti-Beta2-Glycoprotein1
- C-Reactive Protein
- Direct Coombs
- Alternative diagnosis labs to consider
- Thyroid Stimulating Hormone (Hypothyroidism)
- Blood Cultures (endocarditis)
- HIV Test
- Rheumatoid Factor and anticyclic citrullinated Antibody (Rheumatoid Arthritis)
XI. Labs: Interpretation
-
Complete Blood Count
- Anemia
- Lymphopenia
- Thrombocytopenia
-
Urinalysis
- Consider 24 Hour Urine Protein
- Consider 24 hour Creatinine Clearance
- Lupus Nephritis findings
- Persistent Proteinuria > 500 mg/day (>3+ Urine Protein) or
- RBC Cellular Casts (or mixed casts)
-
Coagulation Factors
- Prothrombin Time
- Partial Thromboplastin Time (PTT)
- Increased (prolonged) in Antiphospholipid Antibody Syndrome
- Other initial basic labs
- Comprehensive metabolic panel
- Direct Coombs test
- Primary Antinuclear Antibodies (and other autoantibodies)
- Antinuclear Antigen (ANA)
- Positive in 94-98% of true SLE cases
- Typically positive in Drug-induced Lupus
- Only 5% of ANA positive patients have SLE
- Smith Antibody (Anti-Smith or Anti-Sm)
- Positive in 20-30% of SLE cases
- Highly specific for SLE (nearly pathognomonic)
- Does not correlate with disease activity (unlike Anti-dsDNA)
- Double Stranded DNA Antibody (Anti-dsDNA)
- Positive in 50-70% of SLE cases
- Specific for Systemic Lupus Erythematosus
- Associated with Lupus Nephritis
- Associated with Lupus CNS Involvement
- Also positive in Syphilis and Bacterial Endocarditis
- Antinuclear Antigen (ANA)
- Antiphospholipid Antibody Syndrome related labs
- Other Autoantibodies
- Anti-ribonucleoprotein (Anti-RNP)
- Beta-2 GlycoproteinAntibody
- Anti-ribosomal P (Lupus sensitivity: 20-30%)
- Highly specific for lupus erythematosus
- Associated with Lupus Psychosis
- Anti-Ro (Anti-SSA)
- Positive in 40% of SLE cases
- Anti-La (Anti-SSB)
- Positive in 10-15% of SLE cases
- Histone Antibody (Anti-histone)
- Positive in 50-70% of SLE cases (especially drug induced lupus)
- Other labs used historically in Lupus evaluation
- Complement Levels
- Complement C3, Complement C4, Complement CH50
- Typically unreliable in predicting acute lupus flare
- Low complement levels are more consistent with SLE
- Syphilis Serology (VDRL or RPR)
- Erythrocyte Sedimentation Rate >100 mm (LR+ 5.3)
- C-Reactive Protein
- May be used to gauge lupus activity
- Complement Levels
XII. Diagnostics
- Electrocardiogram
-
Lumbar Puncture
- Evaluate differential diagnosis of Lupus Cerebritis (e.g. Meningitis or encephilitis, Multiple Sclerosis)
- Findings suggestive of increased CNS Lupus activity
- CSF White Blood Cells increased
- CSF Protein increased
- Immunoglobulin synthesis or Immunoglobulin G increased
XIII. Differential Diagnosis
- Children
- Cancer (e.g. Leukemia, Lymphoma)
- Juvenile Rheumatoid Arthritis (Juvenile RA)
- Immune Thrombocytopenic Purpura (ITP)
- Infections
- Thyroid disorders
- Adults
- Behcet Syndrome
- Chronic Fatigue Syndrome
- Dermatomyositis
- Endocarditis
- Fibromyalgia
- HIV Infection
- Hypothyroidism
- Fibromyalgia
- Inflammatory Bowel Disease
- Lyme Disease
- Malignancy
- Mixed Connective Tissue Disease
- Psoriatic Arthritis
- Reactive Arthritis
- Rheumatoid Arthritis or adult onset Still's Disease
- Sarcoidosis
- Systemic Sclerosis
- Sjogren's Syndrome
- Thrombotic Thrombocytopenic Purpura (TTP)
- Vasculitis
XIV. Imaging
-
Brain MRI
- Indicated in suspected Lupus Cerebritis or other neuropsychiatric findings
- Findings are typically non-specific
-
Echocardiogram (or Bedside Ultrasound)
- Indicated for suspected Myocarditis or Pericarditis
- Evaluate for overall Left Ventricular Dysfunction and Pericardial Effusion
XV. Complications
-
Immunocompromised state
- Hyposplenism
- Immunosuppressants used to treat systemic lupus
- Lupus Nephritis (50% lifetime Prevalence)
- Lupus Nephritis is a Glomerulonephritis of several different types (worst is diffuse proliferative nephritis)
- Lupus Nephritis is a predictor of increased mortality risk
- Renal biopsy is typically required for diagnosis of specific Glomerulonephritis type, which in turn drives management
- Lupus Cerebritis
- Various presentations (see above under diagnosis) of CNS disease are seen in 75% of Lupus patients
- Consider MRI and Lumbar Puncture (see above under imaging and diagnostics)
- Cardiovascular disease (28 to 40% lifetime Prevalence)
- Coronary events
- Coronary atherosclerosis
- Autoantibody related Vasculitis
- Lupus medication adverse effects
- Coronary Vasculitis with secondary ST Segment elevation Myocardial Infarction (STEMI)
- Spontaneous Coronary Artery Dissection
- Coronary atherosclerosis
- Pericarditis (most common)
- Risk of Cardiac Tamponade (has even occurred in children)
- Myocarditis
- Presents with conduction abnormalities, Arrhythmias
- Associated with Cardiomyopathy or Heart Failure
- Coronary events
- Pulmonary disease
- Lung disease affects 50% of Lupus patients and is a presenting symptom in up to 5% of cases
- Pleuritis and pulmonary infections are most common presentations
- Interstitial Lung Disease, pneumonitis, Pulmonary Arterial Hypertension, Pulmonary Embolism may also occur
-
Venous Thromboembolism (VTE)
- Higher risk by a factor of 100 in SLE (and at a younger age)
- Occurs in up to 26% of lupus patients (contrast with 0.2% in the general population)
- Increased risk with Antiphospholipid Antibody positive status
- D-Dimer has less less utility in SLE due to a high False Positive Rate in this population (less specific)
- However, a negative D-Dimer in SLE suggests a very low likelihood of VTE
- Wu (2008) Clin J Am Soc Nephrol 3(6): 1628-36 [PubMed]
- Higher risk by a factor of 100 in SLE (and at a younger age)
-
Antiphospholipid Antibody Syndrome (Hughes Syndrome, Anticardiolipin Syndrome)
- Affects 15% of Lupus patients
- Risk of thromboembolic complications (despite prolonged PTT)
- Venous Thromboembolism
- Acute Coronary Syndrome
- Acute thrombotic stroke
- Acute Limb Ischemia
- Mesenteric Ischemia
- Renal artery thrombosis
- Raynaud's Phenomenon (with risk of digital ischemia)
- Hematologic (most SLE patients)
- Malignancy
- Non-Hodgkin Lymphoma (risk increases 3-4 fold over general population)
- Lung Cancer
- Cervical Cancer
- Pregnancy-related complications
- Preeclampsia
- Preterm Labor
- Miscarriage or Stillbirth
- Pregnancy may trigger increased SLE acitivity and flares
- Risk Factors for increased pregnancy complications
- Active disease 6 months before pregnancy
- Lupus Nephritis
- Discontinuation of Hydroxychloroquine
XVI. Management: General Principles
- Reevaluate every 3-6 months
- Employ measures to relieve Fatigue
- Sunscreen and other protection due to photosensitivity
- Reduce risk of infection (e.g. Immunizations)
- Birth Control is critical during exacerbations
- Monitor Disease Activity: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
- https://www.mdcalc.com/calc/10099/systemic-lupus-erythematosus-disease-activity-index-2000-sledai-2k
- Mild Disease: Score <=6 on SLEDAI-2K
- Moderate Disease: Score 7 to 12 on SLEDAI-2K
- Severe Disease: Score >12 on SLEDAI-2K
XVII. Management: Hospitalization Indications
- Acute lupus presentation
- Female aged 15 to 50 years old with fever, Arthralgias and Malar Rash and associated findings (esp. nephritis)
- May benefit from admission for diagnosis and acute management
- Significant febrile illness
- Lower threshold for hospital admission given underlying Immunocompromised state and potential Hyposplenism
- Acute lupus flare with severe pain
- Consider IV cytotoxic agents and Corticosteroids
- Lupus Nephritis (acute onset or worsening)
- See below
- Heralded by abnormal Urinalysis (Hematuria, 3+ Proteinuria, RBC Cellular Casts) or increased Serum Creatinine
- Renal biopsy is typically required for diagnosis of specific Glomerulonephritis type, which in turn drives management
- Nephritis is a predictor of increased mortality and morbidity, including progression to Renal Failure
- Acute Induction Management
- Lupus Cerebritis (e.g. Seizures, Psychosis, Dementia)
- Initial evaluation typically with MRI Brain and Lumbar Puncture
- Hospitalization for further evaluation and acute management
- Acute cardiovascular conditions
- Acute Coronary Syndrome
- Pericarditis
- Myocarditis (may cause life threatening, Acute Heart Failure)
-
Venous Thromboembolism
- Suggests Antiphospholipid Antibody Syndrome (higher risk of thrombotic complications)
-
Acute Abdominal Pain
- Hospitalization indicated where diagnosis is unclear or for associated Lactic Acidosis
- Normal Complete Blood Count or non-diagnostic CT Abdomen does not exclude serious cause in SLE
- Acute Abdominal Pain in SLE presenting to the emergency department is associated with 57% morbidity and 11% mortality
XVIII. Management: System Based
- See complications and hospital indications above
- Musculoskeletal (Arthralgias, myalgias in 95% of cases)
- First-Line Medications
- Medications in Refractory cases
- Methotrexate
- Mycophenylate
- Skin Involvement (70-80% of cases)
- Use sun screen (minimum SPF 15)
- Avoid Photosensitizer medications
- First-Line Medications
- Topical Corticosteroids (and consider Systemic Corticosteroids)
- Topical Calcineurin Inhibitors
- Hydroxychloroquine
- Medications in Refractory cases
- Methotrexate
- Retinoids
- Dapsone
- Mycophenylate
- Hematologic effects (e.g. Leukopenia, Anemia, Thrombocytopenia)
- Thrombocytopenia
- Monitor Platelet Count weekly if Platelets <50,000 cells/mm3
- Glucocorticoids AND Immunosuppressants (e.g. Azathioprine, mycophenylate, Cyclosporine)
- Consider Rituximab in refractory cases
- Automimmune Hemolytic Anemia
- Monitor Hematocrit, Hemoglobin And Reticulocyte Count weekly in severe Hemolytic Anemia
- Glucocorticoids AND Immunosuppressants
- Leukopenia
- Reduce infection risk
- Thrombocytopenia
- Lupus Nephritis
- Lifetime Prevalence 50%
- Screen Urinalysis and Serum Creatinine every 3-6 months (reflex to Urine Protein to Creatinine Ratio)
- Renal biopsy indications
- Proteinuria >=1 g per 24 hours OR
- Hematuria > 0.5 g per 24 hours OR
- Cellular Casts
- Acute Induction Management
- Chronic Maintenance Management
-
Cardiovascular Risk
- Acute Coronary Syndrome risk increased in women 35-44 years old by factor of 52
- Reduce Cardiovascular Risk Factors (Tobacco Cessation; Hyperlipidemia, Hypertension, Diabetes Mellitus management)
- Neuropsychiatric symptoms
- Consider MRI Brain for Headache or Seizure
- Risk of Cerebrovascular Accident
XIX. Management: Pregnancy
-
General measures
- Aspirin 81 mg orally daily started after 12 weeks (due to risk of Preeclampsia)
- Consider Anticoagulant (e.g. LMWH) during pregnancy and Postpartum Period in Antiphospholipid Antibody Syndrome
- Consult Maternal-Fetal Medicine and Rheumatology for co-management during pregnancy
- SLE Control Medications
- Continue Hydroxychloroquine during pregnancy
- Decreases pregnancy complications and controls SLE
- Other medications that may be used in pregnancy
- Contraindicated Medications in Pregnancy (transition to safe medications at least 3 months before conception)
- Continue Hydroxychloroquine during pregnancy
- Monitor for Fetal Cardiac Complications (cardiac neonatal lupus)
- Risk of congenital Heart Block in 1 to 3% of seropositive SLE
- Hydroxychloroquine during pregnancy reduces risk of cardiac neonatal lupus
- Risk Factors: Cardiotoxic Antibodies
- Antiphospholipid Antibodies positive
- Anti-Ro or SS-A Antibody Positive
- Anti-La or SS-B Antibody Positive
- Obtain serial fetal echo between 12 and 26 weeks gestation if Anti-Ro or Anti-La Antibody Positive
- Incomplete Heart Block (treated with Dexamethasone)
- Complete Heart Block (no known treatment as of 2023)
XX. Management: Severity Based for Non-Renal SLE
- Background
- Severity based on Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
- Goals of therapy
- Remission (SLEDAI-2K of 0, on Hydroxychloroquine and no Corticosteroids) OR
- Low disease activity (SLEDAI-2K of <=4, on Hydroxychloroquine and Prednisone <=7.5 mg/day)
- Mild Disease: Score <=6 on SLEDAI-2K
- First-Line
- Hydroxychloroquine AND
- Systemic Corticosteroids (as needed)
- Refractory
- Add Methotrexate
- First-Line
- Moderate Disease: Score 7 to 12 on SLEDAI-2K
- First-Line
- Hydroxychloroquine AND
- Systemic Corticosteroids (as needed) AND
- Other agents (choose one to add)
- Refractory
- Add Belimumab (Benlysta)
- First-Line
- Severe Disease: Score >12 on SLEDAI-2K
- First-Line
- Hydroxychloroquine AND
- Systemic Corticosteroids (as needed) AND
- Other agents (choose one to add)
- Refractory
- First-Line
- References
XXI. Management: Medications
-
Corticosteroids
- Longterm goal (once controlled) is to minimize the use of Glucocorticoids
- Indicated as a mainstay of acute flare management at lowest effective dose (then taper off or to dose <=7.5 mg/day)
- Low dose: Indicated for most patients
- Prednisone 7.5 to 10 mg orally daily or less
- High dose: Indicated in Lupus Cerebritis, nephritis, Thrombocytopenia
- Prednisone 40-60 mg orally daily
- Acute organ-threatening disease may require IV doses 250 to 1000 mg/day for up to 3 days
- Low dose: Indicated for most patients
- Systemic Corticosteroids in moderate to severe exacerbations
- Prednisone 0.5 to 1 mg/kg/day up to 4 weeks or
- Solu-Medrol 15 mg/kg IV for 3 days
- Skin lesions (no significant evidence to support use)
- Topical Corticosteroids
- Intralesional Corticosteroids
- Monitoring
- Serum Glucose every 3 months
- DEXA Scan every 1 to 2 years
- Monitor for symptoms of avascular necrosis (e.g. Hip Pain)
- Use every visit to attempt to taper Corticosteroids, and employ steroid-sparing agents instead
-
Salicylates and NSAIDs
- Indicated for mild to moderate pain from Arthralgias, Headache or other lupus-related conditions
- Contraindicated in renal disease
- Preparations
- Enteric Coated ASA 650 mg PO every 4-6 hours prn
- Ibuprofen 400-800 mg PO tid-qid prn
- Monitoring
- Obtain Serum Creatinine and Complete Blood Count annually
- Cytotoxic agents (and other Immunosuppressants): First-Line
- Hydroxychloroquine (Plaquenil)
- First-line agent in Systemic Lupus management (prevents flares, organ injury, thrombosis and decreases mortality)
- Also indicated for Lupus Nephritis, Arthritis and lupus-related skin lesions
- Dosing: 200-400 mg/day (limit to <5 mg/kg/day to reduce Macular complication risk)
- Effects are delayed for 2 to 8 weeks
- Monitoring
- Annual dilated Eye Exam and Visual Field testing (including baseline exam)
- Low risk patient dilated Eye Exams may be spaced to every 5 years
- Hydroxychloroquine (Plaquenil)
- Cytotoxic agents (and other Immunosuppressants): Second-Line
- Azathioprine (Imuran)
- Indicated in Lupus Nephritis and severe SLE
- Dosing 1.5 to 2.5 mg/kg/day
- Therapeutic response and toxicity monitored with thiopurine metabolites (6-MMP, 6-TGN)
- Monitoring
- Complete Blood Count, comprehensive metabolic panel every 3 months
- Observe for hepatotoxicity, lymphoproliferative disorders, myelosuppression
- Methotrexate
- Indicated in Arthritis, Cutaneous Lupus, serositis and severe SLE
- Dosing: 7.5 to 15 mg per week
- Monitoring
- Complete Blood Count, comprehensive metabolic panel every 3 months
- Observe for hepatotoxicity, myelosuppression
- Azathioprine (Imuran)
- Cytotoxic agents (and other Immunosuppressants): Third-Line
- Cyclophosphamide
- Indicated in Lupus Nephritis or severe SLE
- Daily dosing: 1.5-2.5 mg/kg/day or
- Monthly dosing: 10-15 mg/kg OR 500 to 1000 mg/m2 IV every 4 weeks
- Monitoring
- Complete Blood Count, comprehensive metabolic panel, Urinalysis every 3 months
- Risk of hemorrhagic cystitis, myelo and Immunosuppression, malignancy
- Mycophenolate Mofetil (Cellcept)
- Therapeutic response and toxicity monitored with Mycophenolic acid (MPA)
- Indicated in Lupus Nephritis and refractory SLE
- Typical doses: 2-3 grams/day
- Monitoring
- Complete Blood Count and comprehensive metabolic panel every 3 months
- Observe for signs infection, myelosuppression
- Voclosporin (Lupkynis)
- Oral Calcineurin Inhibitor
- Indicated in Lupus Nephritis (in combination with Mycophenolate and steroids)
- Dose 23.7 mg orally every 12 hours
- Monitor GFR at baseline, then every 2 weeks for first month, then every 4 weeks
- Monitor Blood Pressure every 2 weeks
- Cyclophosphamide
- Monoclonal antibodies (indicated as third-line agent for severe SLE)
- Anifrolumab (Saphnelo)
- IgG 1 Kappa Monoclonal Antibody against Interferon (type 1)
- Dose: 300 mg every 4 weeks via IV infusion
- Risk of respiratory infection, Hypersensitivity
- Belimumab (Benlysta)
- B Lymphocyte Stimulating Factor
- Dose: 10 mg/kg IV OR 200 mg SQ once weekly
- Risk of serious infections, malignancy
- Rituximab (Rituxan)
- Dose: 1 g IV repeated in 2 weeks (one time delivery of 2 doses)
- Anifrolumab (Saphnelo)
-
Anticoagulation
- Indicated in Antiphospholipid Antibody Syndrome (to prevent thrombotic complications)
- Warfarin (Coumadin) with goal INR of 2.5 to 3.0
- Additional measures
- Ophthalmology Consultation for dilated Eye Exam
- Initial exam on starting steroids or Plaquenil
- Repeat exam yearly in high risk patients
- Ophthalmology Consultation for dilated Eye Exam
XXII. Prevention
- See Adult Health Maintenance Screening
- Co-management with rheumatology
- Clinic follow-up every 3 to 6 months in stable disease (more often in moderate to severe disease)
- Symptom screen
- Physical exam
- Cardiopulmonary exam
- Musculoskeletal Exam
- Skin exam
- Lymph Node exam
- Mental health and Neurologic Exam
- Screen for signs and symptoms of malignancy
- Medication monitoring
- Each medication has specific monitoring recommendations (see above)
- Labs every 3 months (or at each clinic visit)
- Complete Blood Count
- Urinalysis
- Obtain Urine Protein to Creatinine Ratio (or 24 Hour Urine Protein) if Lupus Nephritis suspected
- See Lupus Nephritis management above
- Specific metabolic tests (comprehensive metabolic panel is needed if on indicated medications as above)
- Lupus activity markers
- Anti-dsDNA
- Serum complement levels
-
Immunizations
- See Adult Immunization
- Prevnar 20 (PCV20) if Lupus Nephritis or on Immunosuppressants longterm
- Pneumovax (PPSV23) is also needed if PCV15 is used
- Avoid Live Vaccine (e.g. MMR) if on Immunosuppressants
- Do not give Live Vaccine within 1 month of Immunosuppressant
- Other diagnostics as indicated
- Dilated Eye Exam yearly (if on Hydroxychloroquine)
- DEXA Scan yearly (if on Corticosteroids)
-
Cardiovascular Risk Reduction
- See Cardiac Risk Management
- Tobacco Cessation
- Manage Hyperlipidemia and Hypertension
- Screen for and optimize control of Diabetes Mellitus
- Encourage Exercise and Healthy Diet
- Obesity Management
-
Contraception
- Intrauterine Device
- Avoid Oral Contraceptives (due to Hypercoagulable state, esp. in Antiphospholipid Antibody Syndrome)
XXIII. Prognosis
- Drug-induced Lupus typically resolves spontaneously after stopping the offending agent
- Overall five year survival: 91-97%
- Worse prognosis for childhood onset
- Lupus Nephritis occurs in 40% of children with SLE (half of these will have CKD 4)
- Neuropsychiatric manifestations in one third of children
- Increased risk of infection, cardiovascular disease
- Much higher mortality in children (10 fold higher than adults)
- Untreated mortality approaches 90% at 5 years
- Other worse prognostic factors
- Seizure Disorder
- Lupus Nephritis
- Azotemia
- References
XXIV. Resources
- Lupus Foundation of America
XXV. References
- Edworthy in Ruddy (2001) Kelly's Rheumatology, 1105-19
- Green (2014) Crit Dec Emerg Med 28(10): 2-9
- Orandi (2024) Mayo Clinic Pediatric Days, lecture attended 1/18/2024
- Sercombe in Marx (2002) Rosen's Emergency, p. 1607-13
- Ali (2018) Am Fam Physician 98(3): 164-70 [PubMed]
- Gill (2003) Am Fam Physician 68:2179-86 [PubMed]
- Lam (2016) Am Fam Physician 94(4): 284-94 [PubMed]
- Lam (2023) Am Fam Physician 107(4): 383-95 [PubMed]