1. Systemic Lupus Erythematosus
Yi Zhao, MD & PhD, vice-director, associate professor
Department of Rheumatology & Immunology

2. AIMS To establish a definition of SLE
To introduce some background epidemiology
To recognise the clinical features of SLE
To develop an awareness of the drug therapy related to SLE

3. AIMS
By the end of this session you will be able to describe the presenting clinical features of SLE
Outline the investigations required to confirm the diagnosis
Describe the drug therapy used in the management of SLE

4. a damage variety of of multiple autoantibodies organs
Definition Of SLE
SLE is a systemic autoimmune disease in which the body loses tolerance to self: a
variety of
autoantibodies
damage of
multiple
organs

5. Epidemiology: Race, Gender and Age
More prevalent in African Americans, Caribbean populations, Hispanics and Asians
Female > Male
Most commonly seen in women of childbearing age

6. SLE Onset By Sex And Age

7. What Causes Lupus? Genetics Environment Hormones
Lupus is an extremely complex disease, and although scientists are making progress in understanding the causes of lupus, there is still no single known cause. It is thought that a combination of genetics, environment, and possibly hormones act together to trigger the disease.
Genetics: There is considerable evidence indicating that genes play a major role in the disease process. Researchers believe that there may be as many as 100 genes, which contribute to the genetic predisposition and development of SLE, and they have recently discovered a single gene that causes a lupus-like illness in mice.
Hormones: The effect of hormones in humans with lupus is not clear. However, because the majority of lupus patients are women in their childbearing years, it seemed a logical aspect to study. Female hormones tend to stimulate the immune system or promote an immune response, (remember that having lupus means having an overactive immune system), whereas male hormones have the opposite effect and are more immunosuppressive. There does not seem to be any evidence that men or women with lupus produce abnormal levels of hormones, however, there may be differences in the way people with lupus process these hormones.
Environment: Although it has not yet been fully proven, there may be certain environmental factors that play a role in initiating or triggering lupus in a genetically predisposed person.

8. Environmental Factors
— UVA and UVB light can stimulate/ up-regulate autoimmunity
stimulating keratinocytes to produce cytokines -> activate B cells to produce ab
—Viruses/Bacteria: molecular mimicry
SLE patients have higher titers of antibodies to
Epstein-Barr virus (EBV), increased circulating EBV
viral loads; SSA ab has a sequence similar to EBV
nuclear ag 1 Parvovirus B19
—Drugs
—Silica exposure, tobacco smoke, emotional stress

9. Genetics of Lupus —High concordance in monozygotic twins
—5-12% or relatives with lupus have the disease
—No single lupus gene
—Disease is polygenic
—At least 30 susceptiblility genes identified
—HLADR2, HLADR3, HLADR4, HLADR8 (present in 75%)

10. Immunological Mechanisms
Two Stage Disease
Loss of self-tolerance
/Auto-Abs generation
Immune complex formation,
causes inflammation/disease

11. Immunological Mechanisms
Stage One:
Loss of Self-tolerance
Involves self-antigen
presentation by DCs
Role of Apoptosis
Impaired clearance of apoptotic cells
Results from defective complement system
C2, C4, C1q defects
Reduced CR1 receptors
Cells serve as immunogens
Induce auto-reactive T/B cells

12. Immunological Mechanisms
Aberrant DC activity
—DC’s present self antigens from apoptotic cells
Mostly nucleosomes, apoptotic blebs
— DCs present to CD4 cells
Aberrant Lymphocyte Activity
—Unregulated T-cell dependent B-cell activation
Aberrant Germinal Center Activity
— Ligation between certain CD pairings
—Somatic Hypermutation
Autoantibody Production
—95% are antinuclear Abs (anti-Sm, Anti-DNA)

13. Immunological Mechanisms
Stage Two:
Immune Complex Formation
Auto-Abs bind to: Pieces of DNA
Nucleosomes
Proteoglycans
Immune complex formation
Accumulate in organ basement membranes
Results of Immune Complexes
Local inflammation
Local complement activation
Local apoptosis
Positive feedback loop

14. Pathologic Change inflammatory response vascular abnormalities
The inflammation
and necrosis
of the blood
vessel walls
cause secondary
thrombosis
the deposition of
immune complexes
ischemia
and
dysfunction of
local tissue
Direct invasion
of antibodies

15. The Characteristic Changes
lupus cells
Onion skin change in Arteriole
fluorescence：Immunoglobulin and complement deposition

16. lupus cells
The LE cell is a neutrophil that has engulfed the antibody-coated nucleus of another neutrophil.
LE cells may appear in rosettes where there are several neutrophils vying for an individual complement covered protein.

17. Onion skin change
there are significantly centripetal fiber hyperplasia around the small artery，especially in the spleen central artery，this results from vasculitis.

18. Immunoglobulin and complement deposition

19. LUPUS IS… Different for each person. Myriad of symptoms
Symptoms are often non-specific
A disease that ranges from mild to life threatening.
Characterized by flares and remissions.
Since lupus can attack any organ or organ system in the body, it affects everyone differently and there are no two cases that are alike. It can range from mild to life threatening and anywhere in between. People with lupus generally go through periods of flares, which are sudden increases in disease activity or development of new symptoms, and remissions, which are periods of disease-free activity.

20. What are the initial symptoms
The initial manifestations of SLE are: fatigue, fever, malaise, weight loss, musculoskeletal manifestations similar to arthritis.
SLE can affect multiple systems. Let’s take a look at each of those systems.

21. Clinical Manifestations

22. What Are The Dermatological Signs?
The client may have Cutaneous Lupus Erythematosus
Malar "butterfly" rash
Photosensitivity
Vasculitis
Alopecia
Oral Ulcers

23. Malar Rash Fixed erythema, flat or raised, over the malar eminences
Tending to spare the nasolabial folds
30-60 %

24. Photosensitivity Rash over the sun exposed areas.
Face,neck and V shaped area of chest.
See rash varies in severity depending on exposure.
Less under the orbit protected areas.

25. Discoid lupus Erythematous hyper pigmented margins
flat scarred hypo pigmented centers
This can be seen in SLE and pure cutaneous lupus

26. Discoid Rash
Erythematous raised patches with adherent keratotic scaling and follicular plugging
Atrophic scarring may occur in older lesions
Atrophic scarring 萎缩性瘢痕

27. Subacute Cutaneous Lupus32

28. 33

29. Alopecia 36

30. SLE — Vasculopathy Small vessel vasculitis Raynaud’s phenomenon
Antiphospholipid antibody syndrome

31. Oral Lesions
Erythema of hard and soft palate, papules ,vesicles and petechiae
Erythematous rash of the tongue

32. Oral Ulcers Oral or nasopharyngeal ulceration
usually painless observed by physician

33. Neurological Symptoms
A client may have the following symptoms:
Neuropathies (peripheral and central)
Seizures
Depression
Psychosis
A client may have the following complications from an exacerbation of SLE:
CVA
Organic Brain Syndrome
Intellectual impairment
Memory Loss
Personality Changes
Disorientation

34. Neuropsychiatric Systemic Lupus Erythematosus (NPSLE)
CNS (diffuse & central)
PNS
Acute confusional state
Psychosis
Anxiety
Depressive disorders
Cognitive dysfunction
Seizures
CVA
Chorea
Myelopathy
Demyelinating syndrome
Headaches
Neuropathies
Acute inflammatory demyelination

35. Ocular Changes Conjunctivitis Photophobia
Retinal vasculitis with transient blindness
Cotton-wool spots on retina
Cotton wool spots are small areas of yellowish white coloration in the retina. They occur because of swelling of the surface layer of the retina, which consists of nerve fibers. This swelling almost always occurs because the blood supply to that area has been impaired and in the absence of normal blood flow through the retinal vessels the nerve fibers are injured in a particular location resulting in swelling and the appearance of a "cotton wool spot. "

36. Musculoskeletal Changes
Synovitis-90% patients, often the earliest sign
Osteoporosis
From SLE itself and therapy (usually steroids)
Osteonecrosis (avascular necrosis)
Can occur with & without history of steroid therapy

37. 45

38. SLE Arthropathy Non erosive arthritis
Hand may show diffuse soft tissue swelling,ulnar deviation,swan neck deformity,MCP subluxation.

39. 努力要趁早

40. How Can SLE Effect The Renal System
Proteinuria
Cellular casts
Potential complications resulting from SLE are:
Nephrotic syndrome
Renal failure
50% of all lupus patients will have kidney involvement during their life
of these, 50 % will have serious kidney disease

41. Persistent proteinuria greater than 0
Persistent proteinuria greater than 0.5 grams per day or greater than 3+
Cellular casts--may be red cell, hemoglobin, granular, tubular, or mixed
Impaired kidney function
Lupus nephritis predict out come (prognosis)
Major cause of mortality

42. How Does Lupus Damage The Kidneys
Autoantibodies are formed against antigens in the glomerulus basement membrane
Circulating immune complexes bind to the basement membrane of the glomeruli
These result in inflammation of the glomeruli (glomerulonephritis) 49

43. How Does Lupus Damage The Kidneys
The basement membrane is damaged by the inflammation
Appearance of protein, white and red blood cells and ‘casts’ in the urine
Low albumin levels in the blood resulting in leakage of fluid from the vessels into the tissues (edema)
Accumulation of waste proteins (uremia)
Hypertension 49

44. How can SLE effect the GI system?
Uncommon
Severe abdominal pain often indicate mesenteric vasculitis, resembling medium vessel vasculitis (PAN)
Hepatic abnormalities more often due to therapy than to SLE itself
Less common manifestations of lupus involving the gastrointestinal tract include mesenteric ischemia from mesenteric vasculitis and pancreatitis

45. How can SLE effect the Cardiovascular system?
Pericarditis
Myocarditis
Endocarditis
Vasculitis
Venous or arterial thrombosis (anywhere in the body)
Pericarditis: most common cardiac manifestation and usually responds to NSAIDs.
Myocarditis (rare) and fibrinous endocarditis (Libman-Sacks) may occur. Steroids plus treatment for CHF/arrhythmia or embolic events.
MI due to atherosclerosis can occur in <35 y/o

46. hematologic system Anemia Leukopenia Thrombocytopenia Splenomegaly
Anemia: usually Normochromic, normocytic
Leukopenia: almost always consists of lymphopenia, not granulocytopenia
Thrombocytopenia

47. Antiphospholipid Syndrome（APS）
thrombocytopenia
APS
Arteriovenous
thrombosis
recurrent
spontaneous
abortions
Antiphospholipid Syndrome (APS)
Hypercoagulability with recurrent thrombosis of either venous or arterial circulation
Thrombocytopenia-common
Pregnancy complication-miscarriage in first trimester
Lifelong anticoagulation warfarin is currently recommended for patients with serious complications due to common recurrence of thrombosis
Antiphospholipid Antibodies
Primary when present without other SLE feature.
Secondary when usual SLE features present

48. Respiratory System Pleuritis with or without effusion
Life-threatening manifestations: interstitial inflammation which can lead to fibrosis and intra-alveolar hemorrhage
Also pneumothorax and pulmonary HTN can occur

49. What Lab Assessments help in the diagnosis
general
inspection
autoantibody
complement
lupus band test
renal biopsy
imaging tests
blood routine
urinalysis
ESR
APL
antibody
ANA profile
AOCA C3 C4
CH50
SLE50%-70%（+）
Means disease
activity
diagnosis
treatment
prognosis
MRI CT
antinuclear
antibody
抗组织细胞抗体 AOCA 抗磷脂抗体 antiphospholipid（APL）antibody
RNP
Antinuclear
antibody profile Sm
SSA
Anti-dsDNA
antibody
rRNP
SSB
Anti-ENA
antibody

50. Laboratory Findings in SLE
97% positive ANA
61% low complement levels (C3, C4)
50% dsDNA ab
46% leukopenia
42% anemia
40% proteinuria, nephritis
35% anticardiolipin antibodies
25% sjogren’s syndrome with positive SSA, SSB
12% pleural effusion
Others: thrombocytopenia, anti SM, antiRNP, elevated LFTs, splenomegaly, thrombophilia, miscarriages

51. ANA in Lupus Sensitivity 93-99% in SLE
Sensitivity % in drug induced Lupus
Specificity is not great
Higher the titer, higher the specificity
1:40- 30% normal population
1:160- seen in 5% of the population

52. How is a diagnosis of SLE made?
SLE often a diagnostic challenge
Multisystem (cutaneous, renal, respiratory, CV, CNS, GI)
Manifestations may characterize numerous other conditions
Use ACR classification criteria as a guide
Patients need to fulfil 4 of the 11 criteria to reach a diagnosis of SLE
Sensitivity 96% Specificity 96%

53. Diagnostic Criteria Of SLE
狼疮的诊断标准

54. Diagnostic criteria of SLE（MD+SOAP＋BRAIN）
Malar rash
Discoid lesions MD
Serositis
Oral ulcer
Arthritis
Photosensitivity
SOAP
Blood disorder
disorderRenal disorder
Antinuclear antibody
Immunological disorder
Neurological disorder
BRAIN

55. 2012 SLICC Classification Criteria
Need at least 4 criteria (1 clinical and 1 lab)
Or biopsy proven Lupus Nephritis with Pos ANA or pos dsDNA

56. Differential Diagnosis
Rheumatic: RA, Sjogren’s syndrome, systemic sclerosis, dermatomyositis
Nonrheumatic: HIV, endocarditis, viral infections, hematologic malignancies, vasculitis, ITP, other causes of nephritis 69

57. Treatment Individualized Evaluate their risks for organ involvement
dsDNA ab: renal and neurologic
SSA/SSB ab: rashes, pregnancy risks
APL ab: clotting
RNP ab: may develop overlap diseases

58. Treatment: Patient Education
1. Avoidance sun
2. Use of SPF > 35 sunblocks UVA and UVB
3. Sun-protective clothing
4. Promote exercise
5. Healthy diet (low chol, low sugar, low salt)
6. Smoking cessation
7. Avoidance of stress (animal models)
8. Good sleep hygiene
Good patient care is just as important, if not more important than medications
Emotional stress flares autoimmune disease in animal models 74

59. What medications are used to treat lupus?
Glucocorticoids
First-line agents for most manifestations
Dosage and duration based on clinical experience
don’t forget side effects, osteoporosis, atherosclerosis
Antimalarials
Hydroxychloroquine: cornerstone of SLE treatment
To prevent disease flares
Clinicians use a broad range of medications to treat lupus, including glucocorticoids, antimalarials, and nonsteroidal anti-inflammatory drugs (NSAIDs) (Table 2). Hydroxychloroquine prevents disease flares and is considered the cornerstone of SLE treatment. Glucocorticoids are first-line agents for most SLE manifestations, with dosage and treatment duration based on clinical experience and consensus. Immunosuppressive treatment in lupus nephritis is based on histopathologic classifications. Treatment of other lupus manifestations is based on sparse evidence from clinical trials and clinical experience and often requires immunosuppressive therapy and a multidisciplinary approach. 67

60. What medications are used to treat lupus?
NSAIDs
Immunosuppressive treatment （eg.cyclophosphamide/azathioprine/
cyclosporine ）
In lupus nephritis: based on histopathologic classifications
Other manifestations: treatment often includes immunosuppressives and a multidisciplinary approach
Biological agents
Clinicians use a broad range of medications to treat lupus, including glucocorticoids, antimalarials, and nonsteroidal anti-inflammatory drugs (NSAIDs) (Table 2). Hydroxychloroquine prevents disease flares and is considered the cornerstone of SLE treatment. Glucocorticoids are first-line agents for most SLE manifestations, with dosage and treatment duration based on clinical experience and consensus. Immunosuppressive treatment in lupus nephritis is based on histopathologic classifications. Treatment of other lupus manifestations is based on sparse evidence from clinical trials and clinical experience and often requires immunosuppressive therapy and a multidisciplinary approach. 68

61. How should clinicians initiate therapy in a stable patient who is not having a flare?

62. Hydroxychloroquine and other antimalarials
Used to treat inflammatory arthritides
for >50 years
Prevents relapses
Reduces risk for congenital heart block in neonatal SLE
Well-tolerated with rare side effects (retinopathy; skin hyperpigmentation; neuromuscular or cardiac toxicity)
Need eye examination every 6 months
Hydroxychloroquine and other antimalarial agents have been used to treat inflammatory arthritides for at least 50 years (20). In addition to preventing lupus relapses and reducing the risk for congenital heart block in neonatal SLE, hydroxychloroquine has antithrombotic effects that are particularly important to SLE patients with antiphospholipid antibody-related prothrombotic diathesis (21). Hydroxychloroquine is generally well-tolerated and the rare risk for retinopathy is directly related to the years of exposure to the drug and the age of the patient.
In a study of 29 cases of antimalarial retinal toxicity over a period of 30 years, all patients were older than 40 years and had had exposure to the agents over 5 years. (22).
Skin hyperpigmentation and rare cases of neuromuscular or cardiac toxicity have also been reported. 70

63. How should clinicians choose therapy for a patient who is having a flare?

64. IV glucocorticoids + immunosuppressive medications
For severe manifestations (lupus nephritis, alveolar hemorrhage, CNS vasculitis)
Withdraw glucocorticoids once remission achieved
Oral prednisone or methlyprednisolone
Severe SLE manifestations, such as lupus nephritis, alveolar hemorrhage, or CNS vasculitis, should be treated with glucocorticoids administered intravenously (IV) in conjunction with immunosuppressive medications. Glucocorticoids can be gradually withdrawn once remission is achieved. Oral prednisone or methlyprednisolone is used for arthritis, pleuropericarditis, cutaneous vasculitis, and uveitis.
Early studies demonstrated that glucocorticoids could ameliorate SLE, although subsequent controlled trials showed that the therapeutic effect was not sustained (23). Early studies also linked glucocorticoids to improved survival in severe SLE (24), but similar studies have not been done for mild or moderate disease. Current decisions about glucocorticoid dosage and the duration of treatment for specific manifestations rely largely on clinical experience, because too few clinical trials have been done.
An early study comparing 100 mg versus 1000 mg IV methylprednisolone, suggested that 3 daily doses of 1000 mg did not have significant advantage over 3 daily doses of 100 mg (25). A more recent randomized study showed that a dose of 1000 mg to 1500 mg over 3 days is as effective as doses ranging from 2000 mg to 5000 mg over 3 days and is associated with a decreased risk for infections (26).
Significant overlap exists between lupus manifestations and some glucocorticoid complications, including osteoporosis, avascular bone necrosis, myopathy, and psychosis. Furthermore, despite the abundance of observational data on glucocorticoid toxicity, evidence from randomized controlled clinical trials (RCTs) is limited. Table 2 summarizes the 2002 European League Against Rheumatism recommendations on glucocorticoid treatment (27). These recommendations define a low daily dose of prednisone (or equivalent) as ≤7 mg. Low doses are associated with relatively low risk for toxicity, although monitoring for cushingoid symptoms, osteoporosis, cataracts, glaucoma, hyperglycemia, and hypertension is probably justified. Prolonged treatment with medium to high dose carries higher risk of complications, including myopathy, psychosis, hyperlipidemia, and atherosclerosis. However, the prevalence and incidence of these complications in different corticosteroid regimens are still unclear (28).

65. Overlap: lupus manifestations, glucocorticoid complications
Osteoporosis, avascular bone necrosis, myopathy, psychosis
Glucocorticoid dosage, duration: rely on clinical experience
Prolonged medium-to-high dosing increases complications

66. How should clinicians choose and dose drug therapy for lupus nephritis?

67. Class I or II: no immunosuppressive therapy
Class III or IV: treat aggressively
Standard therapy: cyclophosphamide + IV glucocorticoids
Dose cyclophosphamide by total body surface area, adjusted for decreased creatinine clearance
Dose glucocorticoids using ACR recommendations
Newer regimen: mycophenolate mofetil + glucocorticoids
GI and hematologic toxicity common
Contraindicated in pregnancy (possibly teratogenic)

68. For patients who don’t respond to either
Maintenance therapy
Mycophenolate mofetil
Azathioprine
Both superior to cyclophosphamide
For patients who don’t respond to either
Calcineurin inhibitors (cyclosporine, tacrolimus)
Rituximab (monoclonal antibody against CD20)
Either in combination with glucocorticoids
Maintenance therapy
Current guidelines recommend either mycophenolate mofetil or azathioprine for maintenance therapy in lupus nephritis. Both are superior to cyclophosphamide for this purpose (39). Evidence from 2 studies of comparative efficacy of mycophenolate mofetil vs. azathioprine is conflicting (40,41). Treatment duration is guided by clinical experience.
In a study of 227 patients with lupus nephritis class III, IV or V, who showed a clinical response to a 24-week induction with either cyclophosphamide or mycophenolate mofetil patients were randomly assigned to treatment with mycophenolate mofetil (2 gm/d) or azathioprine (2 mg/kg/d). After 3 years of follow up, mycophenolate mofetil was significantly superior to azathioprine with respect to time to treatment failure (primary end point), time to renal flare, and time to rescue therapy (40).
In contrast, an open-label study demonstrated no significant difference in patients treated with mycophenolate mofetil vs. azathioprine for maintenance treatment of lupus nephritis over a period of 4 years. All patients in this study were initially treated with low-dose cyclophosphamide for induction therapy (41).
Calcineurin inhibitors such as cyclosporine are also used for maintenance therapy.
A multicenter, randomized, open pilot trial compared the efficacy of cyclosporine vs. azathioprine for maintenance therapy of lupus nephritis. Seventy five patients with lupus nephritis IV, Vc or Vd, initially treated with IV glucocorticoids (1 mg/kg/3 d) followed by oral cyclophosphamide and prednisone for a median of 90 days, were randomized to treatment with azathioprine or cyclosporine for 2 (core study) and 4 years. Azathioprine and cyclosporine were equally effective in preventing disease flares, the primary outcome of the study. Proteinuria, a secondary end point, decreased significantly with both treatments. Blood pressure and creatinine clearance did not change significantly with either treatment; extrarenal manifestations and clinical activity decreased with both treatments (42). Data from this study indicate that cyclosporine and azathioprine are equally effective for maintenance treatment of lupus nephritis and have similar effects on blood pressure and renal function.
Tacrolimus, also a calcineurin inhibitor, may be used to treat diffuse proliferative or membranous lupus nephritis. Meta analysis of data from open-label trials, case-control studies, and RCTs showed that tacrolimus may be effective as induction and maintenance therapy for lupus nephritis or in treatment of refractory lupus nephritis with persistent proteinuria (43).
Rituximab is a monoclonal antibody directed against CD20, a membrane protein expressed on B-cells. Rituximab depletes B cells from the peripheral blood. Open-label trials indicated improvement of lupus nephritis after B-cell depletion; however RCTs did not show statistically significant response compared with placebo (44-46).
Current ACR guidelines propose mycophenolate mofetil or azathioprine as preferred maintenance therapy for proliferative lupus nephritis. Calcineurin inhibitors or rituximab combined with glucocorticoids may be used for patients with inadequate response to cyclophosphamide or mycophenolate mofetil (38). To date, no RCT has directly compared calcineurin inhibitors to mycophenolate mofetil for maintenance treatment of class III or IV lupus nephritis. 76

69. How should clinicians choose therapy for neuropsychiatric lupus?
Treatment relatively empirical
IV glucocorticoids, immunoglobulin, cyclophosphamide
Relapse may be more common in glucocorticoid vs cyclophosphamide treatment
Rituximab may be beneficial, but relapse rate seems high
Treatment of serious neuropsychiatric SLE manifestations is relatively empirical and includes IV glucocorticoids, immunoglobulin and cyclophosphamide.
An RCT comparing cyclophosphamide to glucocorticoids after 3 days of IV immunoglobulin for treatment of transverse myelitis in lupus showed that relapse was more common in the steroid group. (51).
Case reports and small, uncontrolled studies suggest beneficial effect of rituximab in treatment of neuropsychiatric lupus; however, the relapse rate seems to be high. 79

70. How should clinicians modify treatment for pregnant patients?

71. Higher flare rate in pregnancy + immediate post-partum
Initial presentation with hematologic or renal manifestations during pregnancy not uncommon
Consider pregnancy-related abnormalities that mimic SLE (eclampsia, HELLP syndrome)
Treat active lupus manifestations
Use hydroxychloroquine and prednisone
Discontinuation associated with increased flare risk
If severe, consider IV glucocorticoids + azathioprine
Contraindicated: mycophenolate mofetil, methotrexate, cyclophosphamide
Fertility is not significantly affected in SLE; however, SLE flares at a higher rate during pregnancy and the immediate post-partum period. The presence of anti-SSA antibodies may predict adverse pregnancy outcomes, as may other factors, including antiphopsholipid antibodies, renal disease, thrombocytopenia, hypertension, and the use of prednisone. Becoming pregnant during clinical remission correlates with lower frequency and severity of lupus exacerbations.
The initial presentation of SLE with hematologic or renal manifestations during pregnancy is not uncommon. Clinicians should also consider pregnancy-related hematologic, vascular and renal abnormalities that mimic SLE manifestations, including eclampsia and the HELLP syndrome (a group of symptoms that occur in pregnant women with hemolysis, elevated liver enzymes, and low platelet count). Antimalarials can be used safely in pregnant SLE patients (63). Active lupus manifestations in pregnancy are usually treated with hydroxychloroquine and prednisone. It is advisable to continue hydroxychloroquine in pregnancy because discontinuation is associated with increased risk for flares and pregnancy is associated with risk for increased disease activity. Hydroxychloroquine may also offer protection against cardiac manifestations of neonatal lupus (65).
For severe manifestions, IV glucocorticoids and azathioprine may be considered because azathioprine has not been identified as a human teratogen (64). Mycophenolate mofetil, cyclophosphamide or methotrexate are contraindicated due to potential teratogenicity. 85

73. Prognosis Poor prognosis if the clients have： high serum creatinine
hypertension
Myocardial damage associated with cardiac insufficiency
Severe NP lupus
pneumovax  
肺炎疫苗 78

74. Prognosis
Most SLE patients die from infection, probably related to therapy which suppresses immune system
Recommend smoking cessation, yearly flu shots, pneumovax q 5years
Most SLE patients die from infection, probably related to therapy which suppresses immune system
85%
70%
1year
10 years
Survival
rate
5 years
20 years
96%
80%

75. Thank You for Your Attention