1
Q
What is SLE?
A
Chronic multi systemic autoimmune disease
2
Q
Who does Lupus commonly affect?
A
Predominantly young women in their reproductive years
3
Q
How should SLE be conceptualized in terms of disease manifestations?
A
Spectrum of disease
Ranges from mild, clinically stable disease to severe systemic disease
4
Q
Which comorbidities have the greatest impact on morbidity & mortality in SLE?
A
- CVD & Infections
5
Q
What are examples of mild vs severe disease manifestations in SLE?
A
Mild: Predominant skin &/or join involvement
Severe: Severe disease with potentially life threatening end organ damage
6
Q
What major comorbidities are patients with SLE at increased risk for?
A
Cardiovascular (CVD)
Infections
Osteoporosis
7
Q
What are the Goals of Therapy?
A
- Improve long term survival & QoL
- Treat SLE symptoms & prevent damage & complications
- Induce & maintain remission or low disease activity by controlling inflammation & autoimmune activation
- Reduce corticosteroid doses (e.g., prednisone < 5 mg/day) to prevent medication related organ damage
8
Q
Is the etiology for SLE known or unknown?
A
Unknown
9
Q
What are the key features of SLE?
A
Loss of immunologic tolerance to nuclear antigens
Development of antibodies directed against self
10
Q
What role do autoantibodies play in SLE?
A
- Autoantibodies, produced by B cells and other immune cells, play a major role in disease pathogenesis
- Responsible for the wide variability of clinical manifestations
11
Q
Which autoantibody is highly specific but has low sensitivity for SLE?
A
Anti-Smith (anti-Sm)
12
Q
Which autoantibodies are associated with neonatal lupus erythematosus?
A
- Anti- SSA (Ro) & Anti-SSB (La)
13
Q
What clinical features are associated with anti-SSA (Ro) & anti-SSB (La) antibodies?
A
- Dry eyes
- Photosensitive rashes
- Neonatal complications (including congenital heart block for anti-SSA)
14
Q
Which autoantibody may be associated with antiphospholipid syndrome?
A
Antiphospholipid (cardiolipin, lupus anticoagulant and anti-beta-
2 glycoprotein)
15
Q
How is antiphospholipid syndrome diagnosed?
A
≥3 pregnancy losses before 10 weeks gestation
≥1 pregnancy loss at ≥10 weeks gestation
Preterm delivery before 34 weeks
+ lupus anticoagulant & cardiolipin on 2 separate occasions 12 weeks apart
*Anti-beta-2 glycoprotein is an alternate test to cardiolipin but is not tested in all regions
16
Q
What is the sensitivity & specificity of ANA?
A
- Highly sensitive & low specificity
17
Q
What other conditions can cause a positive ANA besides SLE?
A
Sjögren syndrome
Systemic sclerosis
Diabetes mellitus
Infectious mononucleosis
18
Q
What is the typical clinical course of SLE?
A
Fluctuating course with relapses & remissions
19
Q
Why can diagnosing SLE be challenging?
A
Variable presentation
Involves multiple organ systems
20
Q
Are there diagnostic criteria for SLE?
A
No formal diagnostic criteria
Classification criteria are often used as a guide
21
Q
Is there a single test or symptom that can diagnose SLE?
A
No - diagnosis requires a combination of findings
22
Q
What factors are used together to diagnose SLE?
A
Typical clinical symptoms
Abnormal laboratory tests
Biopsy results (if applicable)
Presence of autoantibodies
23
Q
Which autoantibody in SLE correlates with disease activity & kidney involvement?
A
Anti-double stranded DNA (anti-dsDNA)
- Highly specific for SLE
- Associated with lupus nephritis, serositis, & hematologic manifestations
24
Q
What aspects of history are important when evaluating a patient for SLE?
A
Overall health status & QoL
Pregnancy Hx
Drug Review
Vaccination record
25
What skin and oral mucosa findings may be seen in SLE?
Acute cutaneous lupus
- Malar rash (butterfly appearance) & a generalized maculopapular rash
Subacute cutaneous lupus
- Annular or psoriasiform eruptions
Nonscarring alopecia
Oral ulcers
26
What MSK findings suggest SLE?
Synovitis in ≥ 2 joints
Morning stiffness ≥ 30 minutes in ≥ 2 joints
27
When is imaging indicated in SLE?
Chest x-ray
CT scan
ECG
if pleural effusion, pericardial effusion or acute pericarditis suspected
28
Which labs are important to evaluate cytopenias & kidney involvement in SLE?
CBC: anemia, leukopenia, thrombocytopenia
Creatinine, albumin, urinalysis to evaluate kidney involvement
*If indicated*
- Quantification of albumin/protein in urine, kidney biopsy
29
Which autoantibodies & complement levels are useful in SLE diagnosis & monitoring?
Anti-dsDNA antibodies: specific, high in active disease
C3 and C4 complement: low in active disease
Anti-SSA/Ro and Anti-SSB/La: important if pregnancy considered
Antiphospholipid antibodies: if unexpected clots or pregnancy complications
30
What are the recommended non-pharmacologic measures for SLE?
- Patient education (key component)
- Sun avoidance
- Sun protection
- Protective hat & clothing & Sunscreen (SPF ≥ 30)
- Important for all patients since sun-induced skin changes can trigger rashes & disease flares
- Heart healthy diet & adequate exercise
- Smoking cessation
- Smoking adds to the already increased vascular risk associated with SLE & decreases the effectiveness of antimalarial drugs
- Maintain patient's immunization including annual influenza vaccination (avoid live vaccines)
31
What is the first line pharmacologic therapy for SLE if not contraindicated?
Hydroxychloroquine (HCQ)
Recommended for all SLE patients unless contraindicated
May add NSAIDS and/or corticosteroids PRN for symptom control
32
What is the management if SLE symptoms are controlled on therapy?
Continue HCQ (hydroxychloroquine)
Regular ophthalmologic examinations
33
What is the next step if SLE symptoms are not controlled on HCQ?
Assess disease severity
- Mild/moderate
- Severe (organ or life threatening)
34
What clinical features define mild to moderate SLE?
Skin rashes
Arthritis
Fatigue
Fever
Pleuritis or pericarditis
35
What treatments can be added for mild to moderate SLE?
Add to HCQ
- Methotrexate
- Azathioprine
- Topical agents
- NSAIDs PRN
- Corticosteroids PRN
36
What clinical features define severe SLE?
Life or organ threatening disease, including
- Lupus nephritis
- Vasculitis
- Nervous system involvement
- Hematologic manifestations
37
What is the initial management of severe SLE?
Continue HCQ & add systemic corticosteroids (most patients)
38
What are the options for induction therapy in severe SLE?
Induction (3-6 months)
Cyclophosphamide IV
- Monthly x 6 or Q2Weeks x 6 doses
Mycophenolate mofetil (divided doses)
39
What is the maintenance therapy for severe SLE after induction?
Maintenance (up to 2 years or longer)
-Mycophenolate mofetil (divided doses)
- Azathioprine (preferred in pregnancy)
40
How are SLE associated rashes (seen in ~70% of patients) initially treated?
Topical corticosteroids
41
What topical agents can be used as steroid sparing therapy for SLE skin rashes?
Topical calcineurin inhibitors
- Tacrolimus
- Pimecrolimus
42
What is the treatment for more refractory cutaneous SLE?
Systemic therapy
Most commonly antimalarial drugs (HCQ)
43
What are the main indications for NSAID use in patients with SLE?
Joint pain (arthritis) & Pleuritic chest pain (pericarditis or pleuritis)
44
What serious neurologic adverse effect have high dose NSAIDs (e.g., ibuprofen and sulindac) been associated with in SLE?
Aseptic meningitis
45
What cardiovascular risks are associated with NSAID use?
- Increased risk of Stroke & MI
- Applies to all NSAIDS
46
Which patients require careful monitoring when using NSAIDS?
Patients with CVD & Renal disease
47
When is the risk of MI highest with NSAID use?
- High doses
- During the initial treatment phase i.e., first month of treatment
48
Why may low dose ASA be used in patients with SLE?
- Reduce the risk of MI & Stroke
49
What is the role of low dose ASA in pregnant patients with SLE?
- Reduce the risk of pregnancy complications related to the presence of antiphospholipid antibodies
50
What is the role of HCQ in the management of SLE?
Baseline therapy for the majority of SLE patients
51
Which SLE manifestations are most responsive to HCQ?
Arthritis
Fatigue
52
With which medications is HCQ commonly combined in SLE?
Corticosteroids
Immunosuppresants
53
What long term disease modifying benefit is associated with early HCQ use in SLE?
Reduced accrual of organ damage over time
54
What additional benefits are associated with antimalarial therapy in SLE?
- Lipid & glucose lowering effects
- Reduced risk of blood clots
55
How long should HCQ be continued in patients with stable SLE?
Long term/indefinite therapy
Discontinuation is associated with disease flares
56
What is the major serious toxicity of HCQ?
Irreversible retinopathy
57
What are the risk factors for ophthalmologic toxicity?
High dose therapy
Liver or kidney disease
Advanced age
Obesity
Pre-existing ophthalmologic disease
Treatment for greater than 5-7 years
58
What ophthalmologic screening is required for low risk patients on HCQ?
Baseline eye exam
Annual screening after 5 years of therapy
59
What ophthalmologic screening is required for high risk patients on HCQ?
Annual ophthalmologic assessment
No 5 year delay
60
When are low dose corticosteroids (<15 mg/day) used in SLE, and how are they managed?
Used for debilitating constitutional symptoms refractory to other agents:
- Arthralgias/arthritis
- Myalgias
- Fatigue
- Low grade fever
Almost always combined with antimalarials
Weaned to the lowest effective dose
61
When are moderate dose corticosteroids (0.5-1 mg/kg/day) used in SLE?
Used for pleuritis or pericarditis
Sometimes higher doses are required depending on severity
62
When are high dose corticosteroids (≥1 mg/kg/day) indicated in SLE?
Life or organ threatening disease
- Renal involvement
- Hematologic involvement
- Nervous system involvement
- Vasculitis
- Myositis
63
What is IV "pulse" corticosteroid therapy in SLE, and when is it used?
500-1000 mg daily for 3 doses
Used in urgent situations for severe organ or life threatening diseases
64
How are corticosteroid associated adverse effects minimized in SLE treatment?
Corticosteroids are combined with corticosteroid sparing agents such as:
-Immunosuppresants
-Immunomodulators
-Biologic agents
65
When is Azathioprine used in SLE?
- Moderate to severe lupus
- Maintenance therapy
66
What is the role of cyclophosphamide in SLE treatment?
Induction therapy for severe SLE
Goal: minimize organ damage & induce remission
67
How is cyclophosphamide used in severe SLE?
Combined with corticosteroids
Used for severe SLE involving
- Kidneys
- Nervous system
- Vasculitis
68
For which patients is the low dose cyclophosphamide regimen recommended in SLE?
Caucasian patients with Western or Southern European backgrounds or for patients with mild cases
Regimen showed fewer adverse effects & equivalent efficacy compared to high dose
69
What is a major risk of high dose cyclophosphamide in SLE?
Permanent infertility
Associated with higher adverse effects compared to low dose
70
When is leflunomide used in SLE?
For refractory arthritis - evidence limited
71
What is the role of methotrexate in SLE?
Steroid-sparing; effective for refractory arthritis, skin disease, myositis, pleuritis, pericarditis
72
When do we use mycophenolate in SLE?
Induction therapy in proliferative lupus nephritis
- as effective as cyclophosphamide
- fertility sparing
Maintenance therapy in patients with nephritis
- more effective than azathioprine; safe
73
What is the role of calcineurin inhibitors (CNIs) in SLE?
Not well studied for extra renal SLE
Used for refectory proliferative lupus nephritis
Used for maintenance therapy
Helpful in severe lupus nephritis with proteinuria
74
How does cyclosporine compare to azathioprine in lupus nephritis?
Comparable to azathioprine for maintenance of remission after induction
74
What is the role of tacrolimus in lupus nephritis?
Used for maintenance therapy
Can be part of multi target therapy (steroids + mycophenolate + tacrolimus)
Evidence mainly from Asian populations
75
Why is tacrolimus often preferred over cyclosporine?
Fewer adverse effects:
Less hypertension
Less hyperlipidemia
Less gingival hyperplasia
Less hirsutism
*Limited long-term data and multi-ethnic studies lacking
76
What class of biologic is belimumab?
B-lymphocyte stimulator (BLyS)-specific inhibitors
77
When is belimumab used in SLE?
Mild to moderate active autoantibody-positive SLE
78
What benefits has belimumab shown in SLE?
- Reduces disease severity
- Improves HRQOL
- Reduces corticosteroid use
79
What renal benefits does belimumab provide in lupus nephritis when added to standard therapy?
- Improves renal efficacy
- Decreases renal-related mortality compared to standard care alone
80
Are biologic response modifiers other than belimumab approved for SLE?
No - other biologics are still under study
81
When may Rituximab be used in SLE?
- Severe refractory hematologic involvement
- Refractory lupus nephritis
82
What is anifrolumab & how does it work in SLE?
- Second biologic approved for SLE
- Monoclonal antibody blocks type I interferon-alpha receptor on immune cells
- Decreases interferon pathway activation
83
What benefits does anifrolumab provide in SLE?
Improves skin rashes & inflammatory arthritis
Reduces lupus flares & steroid burden
84
What vaccination should be given before starting anifrolumab & why?
Herpes zoster vaccination due to increase risk of viral infections
85
What is drug induced lupus & when does it occur?
- Lupus like syndrome caused by medications
- Develops weeks to months after drug initiation
- Resolves after discontinuation
- Autoantibodies may take up to 1 year to normalize
86
Which drugs are commonly associated with drug induced lupus?
- Procainamide
- Hydralazine
- Quinidine
- Isoniazid
- Chlorpromazine
- Minocycline
- Terabinafine
- TNF-alpha inhibitors
87
Who is most commonly affected by DIL & how does it present?
More frequent in older Caucasians
Symptoms include:
- Weakness
- Malaise
- Arthralgia
- Myalgia
- Serositis
88
What autoantibodies are typically seen in DIL?
ANA: universally positive
Anti-histone antibodies in ≥75% of cases
89
How doe autoantibodies differ between DIL & idiopathic SLE?
Idiopathic SLE: anti-dsDNA & multiple autoantibodies
DIL: usually no anti-dsDNA
90
Which drugs are seen in subacute cutaneous lupus?
- CCBs
- ACEIs
- Hydrochlorothiazide
- Leflunomide
- Interferons
- Terbinafine
91
How does pregnancy affect disease activity in SLE?
- Effect is variable
- Some patients may have increased disease activity
- Overall flare risk is not higher than in nonpregnant patients
92
What type of SLE flare is particularly concerning during pregnancy?
Flares of renal disease activity (renal lupus nephritis)
93
Why may SLE disease activity increase during the postpartum period?
- Due to hormonal fluctuations
- Increased prolactin
- Changes in estrogen & progesterone levels
94
What pre-pregnancy assessments are recommended for patients with SLE?
- Assess disease activity especially renal function at baseline & at least once per trimester
94
How long should patients be in remission prior to conception?
6 months
95
What are the risks of active SLE prior to pregnancy?
- Associated with high activity lupus during pregnancy & negative outcomes:
- Increased rates of
Renal disease
Preeclampsia
Preterm delivery
Cesarean section
Low birth weight
Pregnancy loss
96
What severe organ damage may preclude pregnancy in SLE patients?
Cardiomyopathy
Cardiac valve disease
Renal insufficiency
97
What is the recommendation for methotrexate & mycophenolate in patients planning pregnancy?
- Avoid pregnancy while on these medications
Methotrexate should be stopped 3 months prior to attempting conception
Mycophenolate should be stopped 6 weeks prior to attempting conception
98
What medications are preferred when switching from teratogenic agents prior to pregnancy in SLE?
Azathioprine
Hydroxychloroquine
Observe disease activity for 6 months before conception
99
What is the recommendation regarding leflunomide & pregnancy?
Generally avoided if future pregnancy is possible
If pregnancy desired:
- Wait 2 years
OR
- Perform a wash out regimen
100
What wash out regimens are used after stopping leflunomide?
- Cholestyramine 8 g TID
OR
- Activated charcoal 50 g QID
Duration: 11 days (not necessarily on consecutive days)
101
What is required after leflunomide wash out before pregnancy?
Verification of plasma levels
*2 tests 14 days apart
* Target plasma concentration: < 0.02 mg/L
102
What fertility risk is associated with cyclophosphamide?
- May cause permanent fertility
- Risk depends on cumulative dose & age of the patient
103
What fertility preservation options can be offered to SLE patients receiving cyclophosphamide?
GnRH analogs
Oocyte cryopreservation
Embryo cryopreservation
104
How should high risk pregnancies in patients with SLE be managed?
Multidisciplinary approach
Managed by a high risk pregnancy team
105
What pregnancy risks are associated with antiphospholipid antibodies in SLE?
Increased risk of:
- Thrombosis
- Pregnancy loss
- Preeclampsia
106
What fetal complications are associated with maternal SSA/Ro and SSB/La antibodies?
Neonatal lupus
May progress to congenital complete heart block
Occurs in ~1–2% of cases
107
What is the role of low dose ASA in pregnant patients with SLE?
Given empirically for preeclampsia prevention
Safe in pregnancy
Start at ~ 12 weeks gestation & continue to term
108
How are pregnant SLE patients with antiphospholipid antibodies but no overt antiphospholipid antibody syndrome managed?
ASA & low dose heparin (LMWH or unfractionated)
109
How is pregnancy managed in patients with antiphospholipid syndrome?
Prophylactic full dose heparin + low dose ASA
Improves live birth rate & reduces preeclampsia
110
When can NSAIDS be used during pregnancy in SLE?
Restricted to 1st or 2nd trimester only
111
Why are NSAIDS contraindicated after 32 weeks gestation?
Increased risk of premature closure of the ductus arteriosus
Not recommended even for short term use
112
What fetal complication is associated with NSAID use between 20-30 weeks gestation?
Oligohydramnios due to fetal kidney effects
Use lowest effective dose for shortest duration
Use beyond 48 hours may require ultrasound monitoring of amniotic fluid
Discontinue if fetal oligohydramnios detected
113
Is HCQ safe in pregnancy, and what are its benefits?
Yes - reduces flares & the need for more aggressive (and toxic) therapies
114
What are the risks and recommendations for prednisone use during pregnancy?
Generally safe - associated with a small increase in the risk of cleft palate
Higher doses associated with complications such as
- HTN
- Preeclampsia
- Prematurity
115
How should prednisone dosing be managed during & after pregnancy?
Use lowest effective dose
Do not taper until 3 months postpartum
116
Why are dexamethasone and other fluorinated glucocorticoids generally avoided in pregnancy?
They cross the placenta
117
When may dexamethasone be appropriate in pregnancy?
Maternal SSA/Ro or SSB/La antibodies
Fetal congenital heart block due to neonatal lupus
118
Is Azathioprine safe in pregnancy?
Yes - at doses ≤ 2mg/kg
119
Are cyclosporine & tacrolimus safe in pregnancy?
Yes - reserved for refractory cases
120
Which SLE medications are teratogenic?
Methotrexate
Mycophenolate
Cyclophosphamide
121
What is common practice for patients on mycophenolate considering pregnancy?
Switch to azathioprine
Early data suggest azathioprine is safe in pregnancy
