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A. Epidemiologynavigator

  1. Disease primarily affects women (90%) with onset in their early 20s-40s
  2. Incidence is 5.5 - 7.5 per 100,000 persons per year
  3. Prevalance is ~124 per 100,000 persons in USA [2]
    1. White: 4000 males, 41,000 females
    2. Black: 31,000 males, 163,000 females
    3. Asians also at higher risk than whites
  4. Prognosis
    1. >70% alive over 10 years overall
    2. Treatment with cytotoxic agents has improved overall survival in severe SLE
    3. Nephritis and CNS disease (seizures) increased risk of death in SLE ~2 fold
  5. Drug Induced Lupus Erythematosus

B. Common Presenting Symptoms [18]navigator

  1. Systemic Symptoms [12]
    1. Fatigue and Malaise (~100%)
    2. Fevers (~80%); up to 40% will have fevers >102°F
  2. Skin Disease [4,12]
    1. Photosensitivity
    2. Erythematous, confluent, butterfly-like eruption on cheeks with face scaling (25%)
    3. Raynaud's Disease - seen in many patients with SLE; more common in overlap syndrome
    4. Subacute cutaneous lupus erythematosus (SCLE)
    5. Consider erythema multiforme or urticarial vasculitis [21]
  3. SCLE [20]
    1. Cutaneous form of SLE with minimal systemic involvement (<20% of cases)
    2. Intense photosensitivity is primary
    3. Polyarthritis in ~35%; polyarthralgias common
    4. Most cases ANA+ with ~65% anti-Ro+
    5. Discoid lupus is one variant of SCLE
  4. Arthritis/Arthralgias (~50%)
    1. Oligoarticular, often migratory
    2. Periarthritis may be present
    3. Jaccoud Arthropathy - swan neck deformities without joint erosions; may become fixed
  5. Cardiovascular Disease
    1. Pericardial Disease - pleuritic chest pain [21]
    2. Valve insufficiency (Libman-Sachs Endocarditis)
    3. Thromboembolic events - usually with antiphospholipid (APL) antibodies (Abs)
    4. Accelerated coronary calcification, hypertriglyceridemia, systemic inflammation [11]
    5. Increased risk of premature atherosclerosis [1,11,13]
  6. Renal Dysfunction
    1. Initial presentation in <30% of patients overall
    2. Very common in patients with severe SLE
  7. Rheumatoid nodules ~10% of SLE, usually with rheumatoid factor (RF)
  8. Lymph Nodes [5,6]
    1. Lymphadenopathy not uncommon
    2. Necrotizing lymphadenitis can occur
  9. Serositis - Pleurisy
    1. Pleural effusion, pleuritic chest pain: ~30%
    2. Pericarditis and Pericardial Effusion: less common, but may lead to tamponade
  10. Central Nervous System Disease - variable (see below)
  11. Overlap with vasculitis [4]

C. Summary of SLE Diagnostic Criteria [3]navigator

  1. Two SLE Diagnostic Lab Tests and Four Organ Systems Involved required
  2. Laboratory Tests
    1. Antinuclear Antibody (ANA) Positive: most sensitive but less specific serological test
    2. One or more positive tests: Anti-dsDNA or Anti-Sm, positive APL Abs
    3. APL Abs: lupus anticoagulant, anticardiolipin Abs (IgG or IgM), False Positive RPR
  3. Hematologic Abnormalities
    1. Hemolytic Anemia
    2. Thrombocytopenia (platelets <100K/µL) - autoimmune type
    3. Leukopenia: leukocytes <4K/µL, often with lymphopenia most pronounced
  4. Hemolytic Anemia [7]
    1. Coombs' positive test with antiglobins (must be hemolytic for criterion)
    2. Occurs in ~10% of cases of SLE
    3. Hemolytic anemia is associated with renal involvement and thrombocytopenia
    4. Also associated with IgG anticardiolipin Abs in SLE patients
    5. Following treatment initiation, recurrence of hemolytic anemia is rare
  5. Musculoskeletal
    1. Polyarthralgias* (~90% overall)
    2. Non-erosive polyarthritis
    3. Myositis* (may be overlap syndrome)
  6. Skin Lesions
    1. Butterfly erythematous rash (~75%)
    2. Discoid rash
    3. Photosensitivity - sunlight triggers flare
    4. Oral (aphthous) ulcers
    5. Raynaud's Phenomenon*
  7. Renal
    1. Proteinuria (>500mg/day)
    2. Cellular casts (any type)
  8. Pleuropulmonary
    1. Pleuritic pain ± Pleural effusion
    2. Pulmonary Hypertension (usually in patients with Raynaud's Disease)
    3. Atelectasizing (acute) pneumonitis and chronic intersitial pneumonitis
    4. Alveolar Hemorrhage - uncommon, life threatening
  9. Cardiac Disease (~50% overall)
    1. Pericarditis (may include pericardial effusion)
    2. Myocarditis [28]
    3. Pleurisy
    4. Endocarditis*
    5. Pulmonary Hypertension / Right Heart Dysfunction
    6. Conduction Anomalies
    7. Thromboembolic Events (including myocardial infarction)
    8. Valvular Abnormalities - including vegetations (Libman-Sacks), regurgitations
  10. Systemic* (95%): fever, fatigue, anorexia, weight loss, malaise, lymphadenopathy
  11. Neurological (35%)
    1. Psychosis, Seizures
    2. Transverse myelitis (especially with Antiphospholipid Ab)
    3. Stroke, TIAs
    4. Neurobehavioral abnormalities* / Organic Brain Syndrome
  12. Gastrointestinal* (~30%)
    1. Abdominal pain - particularly in active disease and patients on glucocorticoids
    2. Hepatomegaly
    3. Odynophagia [12]
  13. * Frequently observed but not considered a criterion for diagnosis of SLE

D. Etiology [44]navigator

  1. Systemic inflammatory disease characterized by autoantibody (autoAb) production
  2. Genetic Contribution
    1. Increased risk in HLA Class II DRB1*0301 and DRB1*1501 alleles
    2. Polymorphism in STAT4 signaling molecule (signaling for IL17, IL23, IL12, type 1 interferons) associated with 2X increased risk of SLE [32]
    3. Mutations in interferon regulatory factor 5 (IRF5)
    4. Deficiency (mutations) in complement C1 proteins very common in SLE [35]
    5. B lymphoid tyrosine kinase (BLK) transcription initiation site mutations associated with SLE [43]
    6. Mutations in integrin alpha M or X (ITGAM, ITGAX) associated with SLE [43]
  3. Role of Lymphocytes
    1. T helper and B cells clearly play a role in disease
    2. B cells are required for Ab production against self antigens (called autoAb)
    3. Formation of autoAbs requires T cell help
    4. CD40L (CD154, helper T cells) overexpression in SLE, interaction with B cell CD40 [2]
    5. Overactivation of X-chromosome genes including CD40L [2]
    6. CD28-B7 interactions increased; CTLA4-B7 interactions decreased [44]
    7. Abnormal cellular immunity with T cells driving process
  4. Role of Cytokines [29]
    1. Underexpression of tumor necrosis factor alpha (TNFa)
    2. Underexpression of transforming growth factor ß (TGFß) and its receptor
    3. Polymorphisms in STAT4 (see above) controlling cytokine production
    4. Elevated levels of interleukin 10 (IL10), which stimulates polyclonal B cell activation
    5. IL10 is a Th2 produced cytokine
    6. Elevation of B lymphocyte stimulator protein (BLS), which activates B cells
  5. Role of AutoAbs
    1. Microbial overstimulation of immune system may stimulate autoAbs [2]
    2. Apoptosis of normal cells leads to release of nuclear contents and many targets of autoAbs
    3. Direct binding of autoAbs to cell targets may induce damage
    4. Antinuclear Abs (ANA) cross-react with membrane structures including alpha-actinin
    5. Anti-dsDNA and Anti-Ribosomal P Abs are directly toxic to many cell types
    6. Direct toxicity due to binding to heparans and other polyanionic structures
  6. Role of Complement (C') [35]
    1. Activation of C' by bound Abs leads to vessel and organ destruction
    2. C' deficiency is a risk factor for SLE
    3. C' may normally play a role in "disposal" of damaged self antigens
    4. Abnormal disposal of self antigens (even after apoptosis) reported [1]
    5. Increased frequency of SLE in persons with C4 null C' alleles
    6. 60-90% of people with C1 deficiencies have SLE
    7. About 10% of people with C2 deficiencies have SLE
    8. Thus, activation of C' up to cleavage of C4 appears to protect against developing SLE
  7. Premature Atherosclerosis
    1. Immune complex (IC) deposition in vasculature may play a role
    2. Homocysteine eelvations may contribute
    3. Systemic (vascular) inflammation likely major contributor
  8. Role of Estrogen
    1. High female predominance with SLE
    2. Disease modifying activity of some androgenic hormones
    3. Small (2X) Increased risk of SLE development with estrogen replacement therapy (ERT)
    4. Pregnancy can cause SLE exacerbation, including nephritis, hypertension [14]
    5. ERT causes small increase in mild-moderate but not severe flares [31]
    6. Oral contraceptive pills (OCP) are safe in patients with stable SLE [9,10]
  9. No association or increased risk with breast implants, including silicone types [15]

E. Laboratorynavigator

  1. ANA titres 1:320 or higher are usually seen in true SLE
    1. Lower ANA titers are usually false positive in absence of other AutoAbs
    2. ANA- SLE occurs in <5% of cases in most series and may be lab error
    3. Of the ANA- cases, some will be Anti-Ro+
    4. Anti-Ro should usually be assessed (ANA+ or ANA- cases with clinical suspicion)
    5. Lupus (LE) cell preparations - no longer performed
  2. Other AutoAbs
    1. About 70% of SLE patients have anti-dsDNA Abs
    2. Anti-dsDNA Abs often cross react with alpha-actinin and these can cause kidney disease
    3. Anti-dsDNA Abs are associated with kidney, CNS, and skin disease
    4. Parvovirus B19 infection can present with transient elevation of anti-dsDNA Abs [22]
    5. About 20% of SLE patients have Anti-Sm Abs; these are associtaed with kidney disease
    6. Sm is a nuclear particle consisting of several distinct polypeptides
    7. Anti-nucleosome (>75% of cases) autoAbs are found; more common in skin and kidney SLE
    8. Anti-Ro (ribonucleoprotein complex) Abs associated with skin, kidney, fetal heart disease
    9. Anti-La (RNA binding protein) Abs associated with fetal heart problems
    10. Anti-NMDA receptor Abs (>40% of SLE) associated with CNS disease
    11. Anti-C1q Abs (>45%) associated with kidney disease
    12. Antiphospholipid Abs (>25%) associated with antiphospholipid syndrome (APLS, see below)
  3. Timing of AutoAbs [1,26]
    1. In 88% of SLE patients, at least 1 autoantibody present prior to diagnosis (mean 3.3 years)
    2. Present prior to diagnosis: ANA 78%, anti-dsDNA 55%, anti-Ro 47%, anti-La 34%
    3. Present prior to diagnosis: anti-Sm 32%, anti-RNP 26%, anti-phospholipid (APL) 18%
    4. ANA, APL, anti-Ro, anti-La present before anti-Sm or anti-RNP
    5. Anti-dsDNA Abs present mean 2.2 years before diagnosis
    6. One or more AutoAbs found in 3.8% of age and sex matched controls
  4. Cytopenias
    1. Common in patients with SLE, particularly moderate and severe disease
    2. Thrombocytopenia (30%) - best correlated with APL Abs
    3. Leukopenia (WBC 2.5-4.5K/µl) - autoimmune etiology
    4. Hemolytic Anemia - Coombs' positive, Ab mediated
    5. Aplastic Anemia - occurs but uncommon
  5. Coagulopathy
    1. Three APL Ab patterns
    2. Prolonged PTT: "Lupus Anticoagulant" in ~15% (prolonged russel viper venom time)
    3. Anti-cardiolipin Abs - IgG and IgM types, mainly platelet anti-ß2glycoprotein-1 (ß2-GP-1)
    4. Abs to ß2-GP-1 correlate well with coagulopathy
    5. Acquired factor inhibitors - especially factor VIII Abs
    6. Homozygous variant alleles of mannose binding lectin (MBL2) associated with 7X increased risk for arterial (but not venous) thrombosis in SLE [17]
  6. Raynaud's Disease
    1. Patients with SLE and Raynaud's have increased titers of anti-endothelial cell Abs
    2. These patients are at increased risk for pulmonary hypertension
  7. Lupus Hepatitis
    1. Overall rare occurrance in lupus, with <5% of patients affected
    2. Transaminase elevations most common, sometimes with pain, jaundice
    3. Low indicence of anti-smooth muscle Abs
    4. 100% incidence of anti-ribosomal P Abs in lupus hepatitis versus 10% overall SLE
    5. Anti-ribosomal P Ab titers also correlate with renal disease
  8. Active Disease
    1. Increased ESR and normal or increased C-reactive protein (CRP) [1]
    2. Decreased serum complement levels (especially in renal disease)
    3. Anti-dsDNA and anti-Ribosomal P Ab levels correlate with disease activity

F. Diagnosis Summary [3]navigator

  1. In patient with disease manifestations of 2 or more organ systems:
    1. ANA titer at least 1:40: full SLE evaluation (consider referral to rheumatologist)
    2. Titer <1:40 - unlikely that SLE is diagnosis; consider other explanations
  2. SLE Evaluation
    1. ACR Diagnostic criteria (as above)
    2. Full battery of SLE biased lab testing
  3. SLE Biased Laboratory Testing
    1. Complete blood and differential counts
    2. Urinalysis including spot urine and creatinine
    3. Chemistry panel including renal and liver tests
    4. Coagulation parameters
    5. APL Ab titer
    6. Anti-dsDNA and anti-Sm Abs
  4. Four or more ACR criteria confirm the diagnosis
  5. Rheumatology referralIf no other explanation for clinical situation is found and ANA <1:40

G. Treatment [1] navigator

  1. Based primarily on symptoms
    1. NSAIDs for arthalgias and arthritis
    2. Hydrochloroquine - skin and joint disease, alopecia, oral ulcers
    3. Glucocorticoids - serositis, renal disease, CNS disease, arthritis, cytopenias
    4. Cytotoxic Agents - renal disease, CNS disease
  2. Glucocorticoids
    1. Oral prednisone or prednisolone is the mainstay of therapy for most symptoms
    2. Effective for myocarditis, pleuritis and other organ inflammation [28]
    3. Patients usually begun on moderate (0.4-0.6mg/kd) to high doses (1-2mg/kg) po qd
    4. In general, dose should be tapered over weeks to months
    5. Increase in prednisone by 30mg/day up to maximum 60mg po qd (with rapid taper) when dsDNA antibody titers increased reduced flares by ~75%
    6. "Safe" (reduced/mild side effect) dose for adults is <10-15mg/day
    7. Alternating day therapy is very desirable with increased safety
  3. Hydroxychloroquine (Plaquenil®)
    1. Best for skin lesions and arthritis
    2. Begin 400mg po qd x 1-2 weeks, then 200mg po qd
    3. Usually equires 4-12 weeks for efficacy
    4. Side effects include uncommon cataracts (q6-12 month ophthalmological exams), myositis
    5. Mepacrine 100mg po qod may be added (available in UK) if symptoms persist
    6. Thalidomide 50-100mg po qd may be used for severe resistant disease
  4. Mycophenolate Mofetil (CelCept®) [24,38]
    1. Developed for renal transplantation
    2. Mainly reduces B cell proliferation and antibody production
    3. Excellent glucocorticoid sparing agent and induction / maintenance for lupus nephritis
    4. increasing use for lupus, well tolerated with diarrhea main side effect
  5. Azathioprine (Imuran®)
    1. Used as "steroid sparing" agent; reduces level of steroid required for control
    2. Usual dose is 2-3mg/kg qd
    3. Effective for leukopenia, skin symptoms
    4. Inferior to mycophenolate with poorer tolerability
    5. Monitor blood counts, liver function tests and amylase
    6. Main side effects are leukopenia, anemia, pancreatitis and hepatitis
    7. Usually requires 2-4 months for effect
  6. Androgens [23,25]
    1. Danazol may be useful for thrombocytopenia (possibly for hemolytic anemia also)
    2. Dehydroepiandrosterone (DHEA) appears is minimally effective in mild disease [25]
    3. DHEA given 200mg / day po reduced prednisone dosage and disease flare
    4. Side effects of DHEA mainly frequent but mild acne and hirsutism common
  7. Cyclophosphamide (CYC, Cytoxan®; see below)
    1. Oral is usually used for vasculitis
    2. Pulse intravenous (IV) was most commonly used in lupus nephritis / cerebritis
    3. CYC is used increasingly less frequently
  8. Lupus Anticoagulant / APL Ab [1]
    1. Warfarin with INR 2-3 for patients with previous thrombotic episodes
    2. No benefit to INR >3 for any patients with APL Ab
    3. Aspirin + subcutaneous heparin for APL Ab in pregnancy
    4. Acquired free Protein S deficiency and increased thrombin may be involved
  9. Thrombocytopenia
    1. Treat as idiopathic (autoimmune) thrombocytopenia
    2. Danazol 400-800mg po qd (up to 1200mg per day)
    3. May require 4-8wks for efficacy
    4. Prednisone with taper or high dose dexamethasone
    5. Intravenous Immunoglobulin (IVIg) for resistant cases
  10. Rituximab (Rituxan®) [1]
    1. Anti-CD20 monoclonal Ab, depletes B cells (not plasma cells)
    2. Infusions q2 weeks x 2-4 reported to induce remission
    3. Generally well tolerated
    4. May reduce B cells, but also alters CD4+ T cell populations
    5. Epratuzumab (anti-CD22) also reported to have activity
  11. Stem Cell Transplantation (SCT) [1,27]
    1. Reserved for severe disease where CYC has failed
    2. Stem cells harvested after CYC and G-CSF therapy
    3. Enriched for CD34+ cells and reinfused after bone marrow ablation
    4. All of 7 evaluable patients were free from signs of active lupus 12-40 months after SCT
    5. Non-myeloablative SCT improved outcomes in 50 patient non-randomized trial [19]

H. Lupus Nephritis [24,30] navigator

  1. Risk Factors for Development [33]
    1. Anti-dsDNA Abs in high titer associated with diffuse proliferative glomerulonephritis
    2. Presence of antihistone Abs gives high odds for proliferative glomerulonephritis
    3. Low C' levels (C' deficiency) [35]
  2. Nearly all patients with lupus have deposition of immune complexes in their glomeruli
    1. Anti-ds DNA Abs often found on basement membrane (subepithelial; formed in situ)
    2. IgA and Complement deposition also found membrane
    3. Subendothelial immune complexes very common as well (typically in Classes III, IV)
    4. Distinguish from renal failure due to APL Ab syndrome (which may catastrophic) [36]
  3. World Health Organization Classification of Lupus Nephritis
    1. Class I: normal glomeruli (~8% of biopsies)
    2. Class II: pure mesangial alterations (~40% of biopsies)
    3. Class IIIA: focal segmental glomerulonephritis (~12% of biopsies)
    4. Class IIIB: focal proliferative glomerulonephritis
    5. Class IV: diffuse glomerulonephritis (~25% of biopsies)
    6. Class V: diffuse membranous glomerulonephritis (~8% of biopsies)
    7. Class VI: advanced sclerosing glomerulonephritis
  4. Usually asymptomatic at presentation unless nephrotic syndrome develops [5]
    1. Most renal lupus lesions lead to nephrosis (little or no azotemia) - Class II / V
    2. However, most renal biopsies are Class III or IV (with poorer prognosis)
    3. A small subset have glomerular sclerosis, prominent azotemia, little protein loss
  5. Renal Biopsy
    1. Most patients with any active sediment should undergo early renal biopsy
    2. Consider biopsy for: proteinuria >500-1000mg/day or azotemia (creatinine > ~1.1mg/dL)
    3. Also used for restaging, prognosis, and adjustment of therapy
    4. Should be considered after relapse on stable therapy
  6. Treatment Overview
    1. Mycophenolate mofetil is superior to IV CYC for induction therapy Classes III, IV, V [38]
    2. Induction with CYC + glucocorticoids for Class III and IV was previous standard [39]
    3. Complete remission at 24 weeks: mycophenolate 22%, IV CYC 6% [38]
    4. Glucocorticoids: prednisone 0.5-1.0mg/kg/day initially with taper after 3-6 months
    5. Maintenance therapy with azathioprine or mycophenolate after induction
    6. All patients on glucocorticoids should be on calcium + Vitamin D supplementation
    7. All patients should be immunized aggressively, preferably prior to immunosuppresion
  7. Mycophenolate Mofetil (CellCept®) [1,24,40,41]
    1. More effective than CYC in induction therapy for lupus nephritis [24,38]
    2. Induction dose 500mg po bid increased to 1000mg po tid for at least 24 weeks [38]
    3. May be used effectively and safely as maintenance after CYC [41]
    4. Mycophenolate has less toxicity than CYC, particularly on fertility, neoplasms [24]
  8. CYC [30,39]
    1. Mycophenolate is superior to CYC, with fewer side effects [24,38]
    2. CYC induces neutropenia, increased infection risk, hemorrhagic cystitis
    3. Over long term, ovarian failure, malignancy can occur
    4. Mesna 400mg po qd can be added during therapy to reduce bladder irritation
    5. CYC should be used only as last line therapy
  9. Azathioprine (Imuran®) [1]
    1. Dose is 2-4 mg/kg/day po for maintenance after 6-7 months of induction therapy [41]
    2. Azathioprine is less toxic than CTX but moreso than mycophenolate
    3. Decreasing role for azathioprine in lupus nephritis
  10. Immunoablative CYC Dosing is generally reserved for refractory, severe SLE

I. Neurological Involvement [1]navigator

  1. CNS Disease is quite common, especially in severe SLE
    1. Over 19 distinct CNS lupus syndromes have been identified
    2. Diffuse Disease - organic brain syndrome, coma, generalized seizures, psychiatric
    3. Focal Presentation - stroke, focal seizures, transverse myelitis, chorea, migraines
    4. Complex Presentation - combinations of above
    5. APLS also associated with CNS symptoms
  2. Organic Brain Syndrome (~20%)
    1. Deliurium
    2. Dementia
    3. Neuropsychiatric Symptoms and Major Affective Disorder (<1%)
    4. Presence of neuropsychiatric symptoms increases risk of poor outcomes [37]
  3. Psychosis (10%)
    1. Aggressive treatment can stabilize and improve condition
    2. Glucocorticoids + oral cyclophosphamide induction with azathioprine maintenance [8]
  4. Stroke Syndromes (5%)
    1. Thrombotic - often with anti-phospholipid (APL) antibodies (Abs)
    2. Embolic - possibly secondary to Libman-Sachs Endocarditis Lesion
    3. Atheroembolic lesions
    4. Presence of anti-phospholipid antibodies is a poor overall prognostic feature [37]
  5. CNS Inflammation
    1. Meningoencephalitis
    2. Abnormally high IgG production
    3. White Matter Disease - may be difficult to distinguish from multiple sclerosis
    4. Vasculitis
    5. Seizures (15%)
  6. Other
    1. Transverse Myelitis (~1%)
    2. Peripheral Neuropathy - mononeuritis multiplex, sensorimotor neuropathy (~10%)
    3. Inflammatory Demyelinating Polyneuropathy
    4. Movement Disorders (~3%)
  7. Differential Diagnosis
    1. Separate Disease process
    2. Infection - important to rule out prior to therapy
    3. Incorrect initial diagnosis
    4. Consider generalized versus focal presentation
  8. Evaluation
    1. Spinal fluid analysis is essential, especially if therapy is to be instituted
    2. CSF anti-neuronal antibodies and IgG levels should be obtained
    3. Serum Anti-ribosomal P antibodies correlate with neurospychiatric symptoms
    4. CSF Culture for atypical (viral, fungal, mycobacterial, bacterial) organisms critical
    5. Magnetic Resonance Imaging ± Angiography - type of disease, follow progression
    6. APL Abs are usually seen in focal disease
    7. APL Abs are correlated with any CNS disease in SLE patients [37]
    8. 55% of SLE patients with CNS disease had APL Ab versus 20% without CNS symptoms
    9. Abs to dsDNA, Ro, RNP, and Sm did not correlate with CNS disease [38]
  9. Treatment Overview
    1. Usually divide into definite inflammatory versus non-inflammatory lesions
    2. CNS inflammation may be treated with glucocorticoids ± immunosuppression
    3. Patients with psychiatric symptoms are treated with psychiatric medications
    4. Some neurobehavioral symptoms respond to glucocorticoids, but most patients have other symptoms of SLE being treated with these agents
    5. Seizures should be treated acutely with anti-seizure agents
    6. If inflammation is present (with seizures), treat aggressively (see below)
    7. Coagulopathies, strokes, should be treated with anti-coagulation therapy, usually alone
  10. Glucocorticoids and Immunosuppressive Agents
    1. Glucocorticoids may be effective in some patinets
    2. Intravenous Pulse CYC IV 500-1000mg/sq meter may be used
    3. Azathioprine usually of limited benefit
    4. It is critical to rule out infection prior to starting highly immunosuppressive therapy
    5. Plasmapheresis may add some benefit to CYC in severe patients
    6. Aggressive immunosuppressive therapy is most effective in patients with inflammation
    7. Little benefit in patients with pure organic brain syndromes
    8. One approach is treat patients aggressively who have abnormal lumbar punctures or MRI
    9. Reasonable that patients with high CSF WBC due to SLE would respond

J. Morbidity Associated with SLE and its Therapynavigator

  1. Infection - especially herpes zoster, bacterial infections. Usually related to therapy
  2. Osteonecrosis - combination of SLE itself and glucocorticoids
  3. Atherosclerosis - increased risk due to SLE itself [1]
  4. Malignancy - increased risk of non-Hodgkin's Lymphoma, ~40X over normal persons
  5. Glucocorticoid Side Effects
    1. Osteoporosis, diabetes, hypertension
    2. Weight gain, thin skin (easy bruising), buffalo hump
    3. Myopathy, cardiomyopathy
    4. Many other side effects
  6. Other organ dysfunction due to SLE
  7. Side effects of other therapies
  8. Prognosis
    1. Highly dependent on degree of major organ involvement and medications
    2. Early deaths (within 5 years) usually due to active SLE
    3. Late deaths (after 5 years) usually related to therapy
    4. 93% 5 year survival, 85% 10 years, 79% 15 years, and 68% at 20 years
    5. Nephritis and seizures each increased risk of death ~2 fold

K. Neonatal Lupus Syndrome navigator

  1. Manifestations
    1. Round to oval, erythematous scaling plaques (telangiectasia, scarring), photosensitivity
    2. Organ involvement: hepatosplenomegaly, pulmonary disease, heart block
    3. Hematologic: anemia, neutropenia, thrombocytopenia
  2. Congenital Heart Block [6]
    1. Most lethal manifestation
    2. Associated with maternal anti-Ro/SS-A (± anti-La/SS-B) Abs
    3. Mother's are either asymptomatic, have Sjogren's Syndrome or SLE or undefined CVD
    4. Asymptomatic mothers (~50% overall) go on to develop some type of CVD
    5. Myocardial specific microchimerism with maternal cells in fetal hearts could provide a target for neonatal lupus congenital heart block [42]
    6. Overall neonatal mortality ~30% (anti-La/SS-B may be a risk for neonatal death)
    7. ~67% receive pacemakers, usually within three months of birth
  3. Treatment
    1. Counselling parents along with screening for antibodies in high risk populations
    2. Pacemaker where indicated
    3. Other manifestations usu resolve over 2-6 months as maternal Abs are lost in newborn

References navigator

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