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7/27/2019 Guideline for SLE Management
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Guideline for SLE
management
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Epidemiology of SLE
Prevalence of SLE
In U.S18-24/100000
black female7.9-10.5/100000
white female4/100000
More common in urban than in rural areas
Femalemale=1.4-5.81 (children)8-131 (adult)
21 (older)
Onset age=65% between 16-55 y/o
20% < 16 y/o
15% > 55 y/o
Identical twin30%
first degre relative5%
Annual incidence of new case6/100000 (low-risk group)
35/100000 (high risk group)
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Subacute Cutaneous Lupus
Erythematosus Widespread, non-scarring but often
photosensitive rash
Annular or papulosquamous morphology Mild systemic disease common but renal
involvement rare
Positive ANA in most patients, but anti-nDNAuncommon Anti-Ro in two thirds patients
HLA-DR3 present in the majority of patients
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Symptoms Percentage
Fatigue 80-100
Fever >80
Weight loss >60
Arthritis, arthralgia 95
SkinButterfly rashPhotosensitivityMucous membrane lesion
AlopeciaRaynauds phenomenonPurpuraUrticaria
>80>50
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Table 9-3. THE SPECTRUM OF ANAs
Chromatin
Anti-native DNA
Anti-single-stranded DNA
Anti-Z DNA
Anti-centromere
Anti-Ku
Anti-HMG proteinsAnti-topoisomerase I (Scl-70 antigen)
Anti-topoisomerase II
Anti-PBC 95K
Anti-lamins
Nucleolar Components
Anti-RNA polymerase I
Anti-Th
Anti-Us (fibrillarin)
Anti-Pm/Scl
Anti-NOR-90
Other Cellular ComponentsAnti-unclear pore complexes
Anti-centrosomes
Anti-midbody
Anti-spindle
Anti-Mi
Anti-Su
Nuclear Ribonucleoproteins
Anti-U1 RNP
Anti-Sm
Anti-Ro
Anti-La
Anti-U2 RNP
Anti-U4 U6 RNP
Anti-U5 RNP
Anti-5S rRNAprotein
Cytoplasmic Components
Anti-Jo-1 (tRNAhistidylsynthetase)
Anti-tRNAalanyl synthetase
Anti-tRNAthreonyl synthetase
Anti-tRNAglycyl synthetase
Anti-signal recognition particle (SRP)Anti-ribosomes
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Fig 1 Four steps in the indirect immunofluorescence assay (cross-sectional view).
Monolayer cells grown on a glass slide (A) are fixed and permeabilized (B) with chemicals
such as acetone, methanol, ethanol, or formaldehyde. After a first incubation with patients
serum containing autoantibodies , cells are washed to get rid of unbound antibodies, and
the second incubation takes place with fluorescent-labeled anti-buman antibody (D). The
slides are again washed, mounted with coverslips, and read on a fluorescence microscope.
Nu, nucleoplasm; Cy, cytoplasm.
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CAUSES OF POSITIVE ANTINUCLEAR ANTIBODIES
1. Rheumatic diseases
Systemic lupus erythematosus
Polymyositis
Sjogrens syndrome
Scleroderma
Vasculitis
Rheumatoid arthritis
2. Normal, healthy individuals
Females > males, prevalence increases with age
Relatives of patients with rheumatic diseases
? Pregnant females
3. Drug-induced
4. Hepatic diseases
Chronic active hepatitis
Primary biliary cirrhosis
Alcoholic liver disease
5. Pulmonary diseases
Idiopathic pulmonary fibrosis
Asbestos-induced fibrosis
Primary pulmonary hypertension
6. Chronic infections
7. Maliganncies
LymphomaLeukemiaMelanomaSolid tumors (ovary, breast, lung, kidney)
8. Hematologic disorders
Idiopathic thrombocytopenic purpuraAutoimmune hemolytic anemia
9. Miscellaneous
Endocrine disorders (type I diabetes mellitus, Graves disease)Neurologic diseases (multiple sclerosis)End-stage renal failureAfter organ transplantation
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Serological Tests to Aid
Diagnosis of SLETest % positive in SLE
ANA 95%
Anti-nDNA 60%
Anti-nRNP 80%
Anti-Sm 20%
Anti-Ro 30%
Anti-La 10%
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Main patterns of autoantibody
1. HomogenousAnti-histone
2. PeripheralAnti-dsDNA, Anti-lamine
3. SpeckledA large family of nonhiston antigens
-Coarse:Anti-Sm, Anti-U1-nRNP
-Fine:Anti-Ro, Anti-La
-Distinct speckles varying in number(PBC)
Anti-p80-coilin, Anti-p95
4. Nucleolar Scleroderma or overlap syndrome
DNA topoisomerase:nucleolar speckles
PM-Scl:homogenous decorating nucleoliFibrillarin (U3-RNP):clummy nucleolar
NOR-90:nucleolar speckles
5. CentromereCREST syndrome, and PBC
6. Cytoplasmic
ANCA,
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Positive
ANA
Nucleoli
Raynauds
phenomenon
Scleroderma
Diffuse (honogeneous)
Anti-nucleoprotein
SLERADrug LE
Histone
SLERADrug LE
Centromere
CRESTSdleroderma
Peripheral (rim)
Anti-dsDNA
SLE
Negative
No disease
Lab errorTreatmentRemissionAntigen XSNephrotic syndrome
No specificityUCTDSLERALiver diseaseMono
Any chronicinflammatory disease
RNP
SLEMCTDRASclerodermaUCTD
Sm
SLE
RO (SS-A)
SLE
Sogrenssyndrome
PcNA
SLE
Scl-70
Scleroderma
PM/Jo/Ku/Mi
PM/DM
La
SLE
Sogrenssyndrome
Speckled
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Tabel 1. CUTANEOUS CHANGES IN LUPUS ERYTHEMATOSUS
Speclfic
Discold
Subacute cutaneousPapulosquamous
Annular/polycyclic
Neonatal lupus erythematosus
Malar dermatitis
Nonspeclfic Lesions
Bullous
Lupus panniculitis
Alopecia
Vasculitis
Urticaria-like vasculitis
Livedo reticularisRaynauds phenomenon
Photosensitivity
Oral ulcerations
Nail changes
Cutaneous mucinosis
Rheumatoid nodules
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Table 61-2. MUSCULOSKELETAL MANIFESTATIONS IN SLE
SLE RA
Arthralgia Common Common
Arthritis Common Deforming
Symmetry Yes Yes
Joints involved PIP > MCP > wrist > knee MCp > wrist > knee
Synovial hypertrophy Rare Common
Synovial membrane abnormality Minimal Proliferative
Synovial fluid Transudate Exudate
Subcutaneous nodules Rare 35%
Erosions Very rare Common
Morning stiffness Minutes Hours
Myalgia Common Common
Myositis Rare UncommonOsteoporosis Variable Common
Avascular necrosis 5-50% Uncommon
Deforming arthritis
Swan neck
Ulnar deviation
Uncommon
10%
5%
Common
Common
Common
MCP, Metacarpophalangeal joint; PIP, proximal interphalangeal joint.
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Possible causes of leukopenia in SLE
Immune destruction
Marrow suppression
Hypersplenism
Drugs
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Possible causes of anemia in SLE
Anemia of chronic disease
Auto-immune hemolytic anemia
Hypoplastic anemia Blood loss due to thrombocytopenia or NSAID use
Hypersplenism
Anemia of renal failure
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AN APPROACH TO THE MANAGEMENT OF LUPUS THROMBOCYTOPENIA
Confirm diagnosis by examining peripheral smear and bone marrow examination, and determineseverity
Rule out drug effects and discontinue all but absolutely essential drugs
Rule out thrombotic throbocytopenic purpura (may be indicated by anemia with pronouncedreticulocytosis and fragmented erythrocytes in the peripheral smear)
Rule out infectionviral
HIV, HBV, CMVbacterialsubacute bacterial endocarditis, gram-negative sepsis
Look for evidence of lupus activity in other organs; beware of major organ involvement
Use prednisone 0.25-1.0mg/kg/day for 3-4 weeks if platelets < 50.000/mm3 (unless otherwiseindicated for other manifestations of lupus); taper after 3-4 weeks
The goal is a stable platelet count > 50.000/mm3
If prednisone fails or unable to tape, consider danazol (400-800mg/day),-globulin orsplenectomy
In patients refractory to these modalities or patients with major organ involvement, use monthlypulses of cyclophosphamide for at least 6 months
Fig. 7.14 An approach to the management of lupus thrombocytopenia.
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Lupus lymphadeenitis (I)
The prevalence of lymphadenopathy range from 12-59% of lupus patients The most common sites are cervical (43%), mesenteric
(21%), axillary (18%) and inguinal (17%). Unusual sites
such as hilar, mediastinal and retroperitoneal were also
reported
The pathognomonic pathologic feature of lupuslymphadenitis, the hematoxylin body, was described by
Ginzler and Fox in 1940, which stain with periodic acid-
Schiff and Feulgen methods, are coalescent amorphicaggregates of deeply basophilic material found within
areas of lymph node necrosis.
The hematoxylin bodies are highly specific for SLE, arealso found in glomeruli, endocardium and spleen
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Lupus lymphadeenitis (II)
Other lymph node features include paracortical focl ofnecrosis marked infiltration by histiocytes, lymphocytes andplasma cells and the preesence of imunoblasts. Neutrophils,
eosinophils and granulomata are conspiculously absent.
Both lupus lymphadenitis and KFD are characterized by ofhistiocytic and immunoblastic infiltrates. A prominent plasmacell component strongly suggests lupus lymphadenitis. When
present, hematoxylin bodies are virtually diagnostic of SLE.
The clinical feature, building on these pathologicresemblances, supports a link between KFD and SLE.
Perhaps KFD and SLE share a common inclting event, suchas exposure to an enviromental or infectious agent, that can
produce either disorder. Alternatively, KFD may be an
antoimmune-midiated necrotizing lymphadenitis that can
remain self-limited or develop into SLE
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Primary Respiratory System Involvement in Systemic Lupus Erythematosus
Upper airway disease
Epiglottitis
Subglottic stenosis
Vocal cord paralysis
Laryngeal edema or ulceration
Inflammatory mass lesions or nodules
Cricoarytenoid arthritis
Necrotizing vasculitis
Parenchymal disease
Acute lupus pneumonitis
Alveolar hemorrhage syndrome
Chronic lupus pneumonitis or interstitial lung disease
Lymphocytic interstitial pneumonia or pseudolymphoma
Bronchiolitis obliterans with or without organizing pneumonia
Respiratory muscle disease
Shrinking lung syndrome
Pleural disease
Pleuritis with or without effusion
Vascular diaease
Pulmonary hypertension
Pulmonary embolism
Acute reversible hypoxemia
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Pulmonary Involvement In SLE
Pleural disease
Acute lupus pneumonitis
Chronic interstitial lung disease
Pulmonary hemorrhage
Pulmonary embolism
Pulmonary vascular disease
Diaphragmatic dysfunction
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Cardic manifestation of SLE
Pericardium Pericarditis with or without
effusion
Cardiac tamponade (rare)
Constrictive perlcarditis
Myocardium Myocarditis
Endocardium Libman-Sacks endocarditis
Coronary artery Accelerated atherosclerosis
vasculitis
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Common Clinical and Laboratory Findings in Lupus Nephritis
Disordered fluid and electrolyte balanceNocturia, decreased urinary concentrating capacity, hyperkalemia,
renal tubular acidosis
Nephritic syndromeHematuria, cellular casts; variable bypertension, edema, proteinuria,
azotemia
Nephrotic syndromeFrothy urine, edema, proteinuria >3.5g per day, lipiduria (fatty casts,
oval fat bodies, doubly refractile fat bodies), hypoalbuminemia,
hyperlipidemia
Secondary complications of nephrotic syndrome includevolume depletion, prerenal azotemia, venous thrombosis, pulmonary embolism,
atherosclerosis, hypogammaglobulinemia
Renal insufficiency
Acute, rapidly progressive or chronic renal failure
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Characteristic Clinicopathologic Correlations in the Major Classes of Lupus Nephritis
Normal or minimal disease
Mesangial lupus nephritis
Clinicallow-grade hematuria, proteinuria, normal renal function
Pathologyincreased mesangial cells, matrix, and immune complexes; patent glomerular
capillary loops
Focal proliferative lupus nephritis
Clinicalnephritic urine sediment, variable but usually nonnephrotic proteinuriaPathologysegmental proliferation, necrosis, crescents compromising capillary loops in 50% of glomeruli; variable sclerosis, atrophy, andfibrosis; mesangial, subendothelial, and subepithelial immune complex deposits
Membranous nephropathy
Clinicalnephrotic syndrome
Pathologydiffuse capillary loop thickening; subepithelial immune deposits
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Morphological Classification of Lupus Nephritis
(modified WHO Classification)
Class Biopsy finding
I Normal glomerule
II Pure messngial alterationIII Focal proliferative glomerulonephritis
IV Diffuse proliferative glomerulonephritis
V Menbranous glomerulopathyVI Advanced glomerulosclerosis
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INDICES OF ACTIVITY AND CHRONICITY IN LUPUS NEPHRITIS*
Activity Index (Range 0 to 24)
Glomerular hypercillularity
Leukocyte exudation
Karyorrhexis/fibrinoid necrosis
Cellular crescents
Hyaline thrombi
Tubulointerstitial inflammationChronicity index (Range 0 to 12)
Glomerular lesions
Glomerular sclerosis
Fibrous crescents
Tubulointerstitial lesionsTubular atrophy
Interstitial fibrosis
*Individual lesions are scored 0 to 3+ (absent, mild, moderate, severe). Indices are composite scores for
individual lesions in each category of activity or chronicity. Necrosis/karyorrhexis and cellular crescents
are weighted by a factor of 2.
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INDICATIONS FOR RENAL BIOPSY IN LUPUS NEPHRITIS
Proteinuria of >1g/day
The threshold is conventionally 1-2g/dayLess proteinuria does not preclude biopsy if it occurs in the context of major serologicabnormalities, especially hypocomplementemiaAt the other extreme, the presence of full-bolwn nephrotic and nephritic syndromes may makerenal biopsy unnecessary
Progressive azotemia
Decreasing renal function in associtaion with active urinary sediment is an indication for biopsyin order to assess the extent of crescents and necrosis which would warrant very aggressivetherapy
Ambiguity or inconsistency of data
Lupus nephritis of indeterminate duration, severity and potential responsiveness warrants theestablishment of a fresh baseline database including determination of class,activity andchronicity indices
Overlapping clinical features
Situations where clinical and laboratory data are compatible with different classes of lupusnephritis, for which different approaches to management are warranted
Redirection of therapy
Partially treated or incompletely responsive lupus nephritis for which a change in therapeuticplan is deemed appropriate
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SLE and ESRD (1)
5-22% of SLE patients progress to ESRD requiring H/D
In USA, Iupus nephropathy accounting for 1.4% off allESRD
Decreased clinical and serological lupus activity
following ESRD. Some theories had
1.Depressed cellular and humoral immunity
2.Lack of mediators produced by the kidney
3.Removal of lupus factors by dialysis itself4.Nature end point in SLE
Survival of lupus patients on dialysis versus non-SLEdialysis patientsno significant
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SLE and ESRD (2)
Renal transplant graft survival of lupus versus non-lupuspatientsno difference
Lupus patients have slightly better outcome with LRrather than CAD grafts
The transplantation time following dialysis need at least3 months
Recurrence of transplanted allograft is often similar to
histologic or immunofluorescent type as in the originkidney, but it is a rare event.
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NEUROPSYCHIATRIC MANIFESTATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Central Nervous System
Diffuse manifestations (35%-60%) Seizures (15%-35%)
Organic brain syndromes
Organic amnestic/cognitive dysfunction
Dementia
Altered consciousness
Grand mal
Focal
Temporal lobe
Petit mal
Psychiatric
Psychosis
Organic mood/anxiety syndromes
Other
Headaches
Aseptic meningitis
Pseudotumor cerebri
Normal pressure hydrocephalus
Focal manifestations (10%-35%)
Cranial neuropathies
Cerebrovascular accidents/strokes
Transverse myelltis
Movement disorders
Peripheral Nervous System
Peripheral Neuropathies (10%-20%) Other
Sensory polyneuropathy
Mononeruitis multiplex
Chronic, relapsing polyneruopathy
Guillien-Barre syndrome
Autonomic noruopathy
Myasthenial gravis
Eaton-Lambert syndrome
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PATHOGENETIC MECHANISMS CAUSING NEUROPSYCHIATRIC
SYMPTOMS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Primary Secondary
Autoantibody mediatedAntineuronal antibodies
Vascular occlusion
Immune complex-mediated vasculitis
Immune complex-mediated anaphylatoxin
release causing leukoagglutination
Antiphospholipid antibody-associated
hypercoagulability
Thrombosis
Emboli from cardiac source
Cytokine effects
Combination of mechanisms
InfectionHypertensionUremia
Electrolyte imbalances
Hypoxia
Fever
Thyroid disease
Thrombotic thrombocytopenic purpuraAtherosclerotic strokes
Emboli from valvular vegetations
Subdural hematoma
Cerebral lymphoma
Medications
Drug overdose
Corticosteroids
NSAIDs
Hydroxychloroquine
Azathioprine
Fibromyalgia
Reactive depression
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Pathogenesis of Neuropsychiatric Events in Patients with SLE
Primary events
Vascular occlusion from immune-complex-mediated or antibody (for example,antiphospholipid)mediated vasculopathy, vasculitis, leukoagglutination, or
thrombosis.
Cerebral dysfunction from antibodies to brain tissue (antineruonal,
antiribosomal P protein) or cytokines (interleukin-6, interferon-).
Secondary eventsInfection (meningitis, abscess, discitis)
Cerebrovascular accidents due to accelerated atherosclerosis
Hypertensive encephalopathy
Metabolic encephalopathy (uremia, electrolyte imbalance, fever, hypoxia)
Hypercoagulable state due to the nephrotic syndrome
Drugs (glucocorticoids, nonsteroidal anti-inflammatory agents, trimethoprim and
sulfamethoxazole, hydroxychloroquine, azathioprine).
Intrathecal production or entrance through a blood-brain barrier disturbed by
vascular injury.
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FREQUENCY OF ABNORMAL LABORATORY TESTS COMMONLY USED IN THE
EVALUATION OF NEUROPSYCHIATRIC LUPUS ERYTHEMATOSUS
Test Frequency of
Abnormal Test Result
Range (%)
Comment
Serologic
Antimeuronal antibodies
Antineurofilament antibodies
Antiribosomal-P antibodies
Antiphospholipid antibodies
30-92
58
45-90
45-80
Diffuse manifestations
Diffuse manifestations
Psychosis/depression
Focal manifestations, strokes
Cerebrospinal fluid
Routine
Pleocytosis
Increased protein]
Low glucose
6-34
22-50
3-8
Rule out infection and NSAID meningitis
Nonspecific
Rule out infection, transerse myelitis
SpecialAntineuronal antibodies (lgG)
Elevated Q albumin
Elevated lgG/lgM index
Oligoclonal bands (2 bands)
90
8-33
25-66
20-82
Diffuse manifestations, present in 40%
with focal manifestations
Break in blood-brain barrier
Diffuse manifestations
Diffuse manifestations
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Pathologic studies in NPLE
Several autopsy series agree on several important points
There is no pathognomonic lesion that NPLE causes in
the brain that is diagnostically specific like the wire loop
lesion observed in lupus nephritis.
Active vasculitis is rare, bland vasculopathy (vascularhyalinization, perivascular imflammation, and endothelial
proliferation associated with microinfarcts and
hemorrhage is the most common pathologic abnormalities
seen.)
Clinical manifestations may not be readily explained by
pathologic findings, some NPLE patients, particularly
those with diffuse neuropsychiatric manifestations may
have normal or unremarkable brain pathology.
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Proactive and preventive strategies in
addition to lupus therapies(1)
Patients education programs, eliminate patientnonadherence
Monitor vital signs, update physical examination, and
have laboratory work done Adhere to a general conditioning exercise program to
minimize osteoporosis and muscle atrophy
Cognitive therapy for lupus fog;biofeedback forRaynauds phenomenon
Counseling and stress management
Physical and occupational therapy, ergonomic workstation evaluation
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Proactive and preventive strategies in
addition to lupus therapies(2)
Aggressive proactive management of blood pressure,blood sugars, serum lipids, and weight. Smokingcessation.
Yearly bone densitometry and osteoporosisprevention measures.
Annual electrocardiogram and chest x-ray
Prompt evaluation of all fevers
Periodic screening with carotid duplex scanning,treadmill, or stress testing; screening for, andprophylactic management of, antiphospholipidantibodies.
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Therapies for lupus patients with
skin lesions(1)
General
Avoid sun: clothing, sunscreens, avoid hot part of
day with most UV-B light, camouflage cosmetics
Stop smoking (so antimalarials works better)
Thiazides and sulfonylureals may exacerbate skin
disease
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Therapies for lupus patients with
skin lesions(2)
Routine therapy
Topical steroids, intralesional steroids
Hydroxychloroquine
Oral corticosteroids
Dapsone for bullous lesions
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Therapies for lupus patients with
skin lesions(3)
Advanced therapy for resistant causes
Subacute cutaneous lupus: mycophenylate
mofetil, retinoids, or cyclosporine Discoid lesions: chloroquine, clofazimine,thalidomide, or cyclosporine
Lupus profundus: dapsone
Chronic lesions over 50% of body: topicalnitrogen mustard, BCNU, or tacrolimus
Vasculitis: may need immunosuppressives
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Therapy for lupus patients with arthritis
(no internal organ involvement)
First line: NSAIDs
Cyclooxygenase-2 specific inhibitors
(but may induce thrombotic risk in
patients with antiphospholipid antibodies)
Low dose hydroxychloroquine(200mg
twice a day)
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Indications of high dose corticosteroid
therapy in lupus patients
Severe lupus nephritis
CNS lupus with severe manifestations
Autoimmune thrombocytopenia withextremely low platelet counts(e.g.
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Life-Threatening Manifestations of SLE:
Responses to glucocorticoids(1)
Manifestations often responsive to glucocorticoids
Vasculitis
Severe dermatitis of subacute cutaneous lupus
erythematosus or SLE
Polyarthritis
Polyserositispericarditis, pleurisy, peritonitis
Myocarditis Lupus pneumonitis
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Life-Threatening Manifestations of SLE:
Responses to glucocorticoids(2)
~(continue)
Glomerulonephritisproliferative forms
Hemolytic anemia
Thrombocytopenia Diffuse CNS syndromeacute confusional state,
demyelinating syndromes, intractable headache
Serious cognitive defects
Myelopathies Peripheral neuropathies
Lupus crisishigh fever and prostration
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Life-Threatening Manifestations of SLE:
Responses to glucocorticoids(3)
Manifestations not often responsive toglucocorticoids Thrombosisincludes strokes
Glomerulonephritisscarred end-stage renaldisease, pure membranous glomerulonephritis
Resistant thrombocytopenia or hemolyticanemiaoccurs in a minority of patients; considersplenectomy, cytotoxics, danazol, orcyclosporine/neoral therapies
Psychosis related to conditions other than SLE,such as glucocorticoid therapy
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Therapy for patients with lupus nephritis
Previously untreated patients with active
lupus nephritis or severe manifestations
( decreased renal function and /or high-grade proteinuria)
First line: high doses of corticosteroids
(about 1mg/kg/day) Cytotoxic drugs or other
immunosuppressive drugs
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The indications of cytotoxic drugs use in
the treatment of lupus nephritis
Active and severe GN despite treatment withhigh dose prednisone
Responded to corticosteroids but require anunacceptably high dose to maintain aresponse.
Unacceptable side effects fromcorticosteroids.
Chronic damage on a renal biopsy and otherindicators of a poor prognosis.
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Systemic therapies for nonorgan-
threatening lupus
Nonsteroidal anti-inflammatory drugs
Antimalarials
Thalidomide Hormonal interventions:
dehydroepiandrosterone, testosterone
patches, bromocriptine, prolactin Immunosuppressive therapies:
azathioprine, methotrexate, leflunomide
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The management of organ-threatening lupus
Existing immunosuppressive therapies:
cyclophosphamide, mycophenolate mofetil,
cyclosporine A, fludarabine, cladribine (2-CDA)
Apheresis
Intravenous immunoglobulin
Various biologic agents: BlyS inhibitor, CTLA-4Ig,
LL2IgG
Stem cell transplantation
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Use of Cytotoxic Drugs in SLE :
Azathioprine
requires 612 months to work well
13 mg/kg/day(initial dose)
12 mg/kg/day(maintenance dose) Advantage:probably reduces flares, reduces
renalscarring, reduces glucocorticoid dose
requirement Side effects: Bone marrow suppression,
leukopenia, infection(herpes zoster), infertility,malignancy, early menopause, hepatic
damage, nausea
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Use of Cytotoxic Drugs in SLE:
Cyclophosphamide
requires 216 weeks to work well
Initial dose:1-3 mg/kg/day orally or 820mg/kg intravenously once a monthplus mesna
Maintenance dose:0.52 mg/kg/day orally or 820mg/kg intravenously every 412 wks plus mesna
Adverse effects:probably reduces flares, reducesrenal scarring, reduces glucocorticoid dose
requirement Adverse effects: marrow suppression, leukopenia,
infection, infertility, malignancy,menopause,cystitis,nausea
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The treatment in lupus patients with
autoimmune thrombocytopenia
Splenectomy
Danazol
Immunosuppressive or cytotoxic drugs:azathioprine, cyclophosphamide
Intravenous immunoglobulin(IVIG)
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Other management principles in the
treatment of lupus patients(1)
Thrombosis-Anticoagulation
Recurrent fetal loss with antiphospholipid
-Heparin in low dose or low-molecular-weightheparin with or without aspirin
-If heparin ineffective or not tolerated, use low-doseaspirin alone
-Glucocorticoids plus aspirin in moderate to highdose may be used but is controversial
Thrombocytopenia or hemolytic anemia
-Intravenous gamma globulin, splenectomy, danazol,
cyclosporine, cytotoxic drugs
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Other management principles in the
treatment of lupus patients(2)
Seizures without other serious manifestations
-Anticonvulsants
Behavior disorders or psychosis without otherserious manifestations:
-Psychoactive drugs, neuroleptics
Pure membranous glomerulonephritis:
-Limited trials of immunosuppressives or no specific
treatment
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Other management principles in the
treatment of lupus patients(3)
Avoid possible disease triggers-sulfaantibiotics, sun, high estrogen-containingbirth control pills,alfalfa sprouts
Prevent atherosclerosis Prevent osteoporosis
Prevent infection
Prevent progression of renal disease
Prevent clots in patients with antiphospholipidantibodies
Treat fatigue.