Diffuse
Systemic Lupus Erythematosus
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Systemic Lupus Erythematosus
, Lupus, SLE, Lupus Serositis, Lupus Nephritis, Lupus Cerebritis
See Also
Cutaneous Lupus Erythematosus
Drug-induced Lupus
Background
Named in 1851 for wolf (lupus) bite-like facial rash
First described by Moritz Kaposi
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
Duarte-García (2022) Ann Rheum Dis +PMID: 35577385 [PubMed]
Kamphuis (2010) Nat Rev Rheumatol 6(9):538-46 +PMID: 20683438 [PubMed]
Causes
Idiopathic
Drug Induced lupus
More than 80 drugs associated, esp.
Hydralazine
,
Procainamide
,
Beta Blocker
s
Pathophysiology
Tissue damage by
Antibody
and immune complex deposition
Autoantibodies form to cell nucleus components
Findings
Presentations
Consider SLE when multiple organ systems are involved
Most common presenting symptoms (90% of cases)
Fatigue
Weight loss
Fever
without focal infection
Women of child-bearing age (age 15 to 50 years old)
Fever
Malar Rash
Arthralgia
s (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
Arthralgia
s
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
Arthralgia
s 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)
Symptoms
Arthralgia
s 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 Lesion
s such as
Oral Ulcer
s or mucositis (12% at presentation)
Signs
Gene
ral
Dermatologic
Discoid Rash (LR +18)
See
Cutaneous Lupus Erythematosus
Malar "butterfly" rash (50% of cases, 31% at presentation, LR+ 14)
Photosensitivity (23% at presentation, LR+ 11)
Vasculitis
Alopecia
Oral Ulcer
s or mucositis (often painless
Oral Ulcer
s on
Palate
)
Sicca Syndrome
Rheumatologic or musculoskeletal symptoms (95% of cases)
Arthralgia
s 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
Seizure
s (LR+ 13)
Psychosis
(LR+ 13)
Thrombotic
Cerebrovascular Accident
Transverse Myelitis
Cognitive dysfunction (spectrum from mild cognitive deficits to
Dementia
)
Migraine Headache
s
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 Disorder
s
Cotton wool spots
Retina
l
Hemorrhage
s
Proliferative
Retinopathy
Neurologic conditions
Optic Neuritis
Ischemic Optic Neuropathy
Amaurosis Fugax
Diagnosis
EULAR/ACR Criteria 2019
Background
New 2019 EULAR/ACR guidelines included many of the
SLIC
C 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
Delusion
s and/or
Hallucination
s 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
SLIC
C (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
)
Adjunctive Clinical: Mucocutaneous (findings must be observed by clinician)
Weight 2: Non-scarring
Alopecia
Weight 2:
Oral Ulcer
s
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
Gene
ralized 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
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 Cast
s (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
Protein
s
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
Aringer (2019) Arthritis Rheumatol 71(9):1400-12 +PMID: 31385462 [PubMed]
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-
Glycoprotein
1
C-Reactive Protein
Direct Coombs
Alternative diagnosis labs to consider
Thyroid Stimulating Hormone
(
Hypothyroidism
)
Blood Culture
s (endocarditis)
HIV Test
Rheumatoid Factor
and anticyclic citrullinated
Antibody
(
Rheumatoid Arthritis
)
Labs
Interpretation
Complete Blood Count
Anemia
Lymph
openia
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 Cast
s (or mixed casts)
Coagulation Factor
s
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
Antiphospholipid Antibody Syndrome
related labs
Antiphospholipid Antibody
Anticardiolipin Antibody
Partial Thromboplastin Time
(PTT)
Prolonged in
Antiphospholipid Antibody Syndrome
Other Autoantibodies
Anti-ribonucleoprotein (
Anti-RNP
)
Beta-2
Glycoprotein
Antibody
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
Diagnostics
Electrocardiogram
Pericarditis
See
EKG in Pericarditis
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 Cell
s increased
CSF Protein
increased
Immunoglobulin
synthesis or
Immunoglobulin G
increased
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
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
Complications
Immunocompromised
state
Hyposplenism
Immunosuppressant
s 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
Pericarditis
(most common)
Risk of
Cardiac Tamponade
(has even occurred in children)
Myocarditis
Presents with conduction abnormalities,
Arrhythmia
s
Associated with
Cardiomyopathy
or
Heart Failure
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]
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)
Thrombocytopenia
Autoimmune Hemolytic Anemia
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
Management
Gene
ral Principles
Reevaluate every 3-6 months
Employ measures to relieve
Fatigue
Sunscreen
and other protection due to photosensitivity
Reduce risk of infection (e.g.
Immunization
s)
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
Management
Hospitalization Indications
Acute lupus presentation
Female aged 15 to 50 years old with fever,
Arthralgia
s 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
Corticosteroid
s
Lupus Nephritis (acute onset or worsening)
See below
Heralded by abnormal
Urinalysis
(
Hematuria
, 3+
Proteinuria
, RBC
Cellular Cast
s) 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
Systemic Corticosteroid
s AND
Mycophenolate
or
Cyclophosphamide
Lupus Cerebritis (e.g.
Seizure
s,
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
Vergara-Fernandez (2009) J Gastrointest Surg 13(7): 1351-7 [PubMed]
Management
System Based
See complications and hospital indications above
Musculoskeletal (
Arthralgia
s, myalgias in 95% of cases)
First-Line Medications
NSAID
s
Corticosteroid
s
Hydroxychloroquine
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 Corticosteroid
s (and consider
Systemic Corticosteroid
s)
Topical
Calcineurin Inhibitor
s
Hydroxychloroquine
Medications in Refractory cases
Methotrexate
Retinoid
s
Dapsone
Mycophenylate
Hematologic effects (e.g.
Leukopenia
,
Anemia
,
Thrombocytopenia
)
Thrombocytopenia
Monitor
Platelet Count
weekly if
Platelet
s <50,000 cells/mm3
Glucocorticoid
s AND
Immunosuppressant
s (e.g.
Azathioprine
, mycophenylate,
Cyclosporine
)
Consider
Rituximab
in refractory cases
Automimmune
Hemolytic Anemia
Monitor
Hematocrit
,
Hemoglobin A
nd
Reticulocyte Count
weekly in severe
Hemolytic Anemia
Glucocorticoid
s AND
Immunosuppressant
s
Leukopenia
Reduce infection risk
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 Cast
s
Acute Induction Management
Systemic Corticosteroid
s AND
Mycophenolate
or
Cyclophosphamide
Chronic Maintenance Management
Mycophenolate
or
Azathioprine
Cardiovascular Risk
Acute Coronary Syndrome
risk increased in women 35-44 years old by factor of 52
Reduce
Cardiovascular Risk Factor
s (
Tobacco Cessation
;
Hyperlipidemia
,
Hypertension
,
Diabetes Mellitus
management)
Neuropsychiatric symptoms
Consider
MRI Brain
for
Headache
or
Seizure
Risk of
Cerebrovascular Accident
Management
Pregnancy
Gene
ral 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
Prednisone
Azathioprine
Tacrolimus
Contraindicated
Medications in Pregnancy
(transition to safe medications at least 3 months before conception)
Methotrexate
Mycophenolate
Cyclophosphamide
Leflunomide
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)
Management
Severity Based for Non-Renal SLE
Background
Severity based on Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
https://www.mdcalc.com/calc/10099/systemic-lupus-erythematosus-disease-activity-index-2000-sledai-2k
Goals of therapy
Remission (SLEDAI-2K of 0, on
Hydroxychloroquine
and no
Corticosteroid
s) 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 Corticosteroid
s (as needed)
Refractory
Add
Methotrexate
Moderate Disease: Score 7 to 12 on SLEDAI-2K
First-Line
Hydroxychloroquine
AND
Systemic Corticosteroid
s (as needed) AND
Other agents (choose one to add)
Methotrexate
Azathioprine
Calcineurin Inhibitor
s
Mycophenolate
Refractory
Add Belimumab (Benlysta)
Severe Disease: Score >12 on SLEDAI-2K
First-Line
Hydroxychloroquine
AND
Systemic Corticosteroid
s (as needed) AND
Other agents (choose one to add)
Mycophenolate
Cyclophosphamide
Refractory
Add
Rituximab
(
Rituxan
)
References
Fanouriakis (2019) Ann Rheum Dis 78(6):736-45 +PMID: 30926722 [PubMed]
Management
Medications
Corticosteroid
s
Longterm goal (once controlled) is to minimize the use of
Glucocorticoid
s
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
Systemic Corticosteroid
s 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 Corticosteroid
s
Intralesional
Corticosteroid
s
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
Corticosteroid
s, and employ steroid-sparing agents instead
Salicylate
s and
NSAID
s
Indicated for mild to moderate pain from
Arthralgia
s,
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
Immunosuppressant
s): 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
Macula
r 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 Exam
s may be spaced to every 5 years
Cytotoxic agents (and other
Immunosuppressant
s): 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
Cytotoxic agents (and other
Immunosuppressant
s): 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
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)
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
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
Hematologic Malignancy
Non-Hodgkin Lymphoma
Lung Cancer
Cervical Cancer
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)
Serum Creatinine
Serum Glucose
(if on
Corticosteroid
s)
Lupus activity markers
Anti-dsDNA
Serum complement levels
Immunization
s
See
Adult Immunization
Prevnar 20
(
PCV20
) if Lupus Nephritis or on
Immunosuppressant
s longterm
Pneumovax
(PPSV23) is also needed if PCV15 is used
Avoid
Live Vaccine
(e.g. MMR) if on
Immunosuppressant
s
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
Corticosteroid
s)
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 Contraceptive
s (due to
Hypercoagulable
state, esp. in
Antiphospholipid Antibody Syndrome
)
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
Ambrose (2016) Lupus 25(14):1542-50 +PMID: 27147622 [PubMed]
Cimaz (2016) Nat Rev Rheumatol 12(7):382-3 +PMID: 27305850 [PubMed]
Resources
Lupus Foundation of America
http://www.lupus.org
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]
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