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
Femalemale1.4-5.81 (children) 8-131 (adult) 21 (older)
Onset age65 between 16-55 y/o 20 lt 16 y/o 15 gt 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-nDNA uncommon
Anti-Ro in two thirds patients
HLA-DR3 present in the majority of patients
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Table 61-1. FREQUENCY OF CLINICAL SYMPTOMS IN SLE
AT ANY TIME
Symptoms Percentage
Fatigue 80-100
Fever gt80
Weight loss gt60
Arthritis, arthralgia 95
Skin Butterfly rash Photosensitivity Mucous membrane lesion Alopecia Raynauds phenomenon Purpura Urticaria gt80 gt50 lt58 27-41 lt71 17-30 15 8
Renal Nephrosis 50 18
Castrointestinal 38
Pulmonary Pleruisy Effusion Pneumonia 0.9-98 45 24 29
Cardiac Pericarditis Murmurs ECG changes 46 8-48 23 34-70
Lymphadenopathy 50
Splenomegaly 10-20
Hepatomegaly 25
Central nervous system Functional Psychosis Convulsions 25-75 most 5-52 15-20
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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 proteins Anti-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 Components Anti-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 (tRNAhistidyl synthetase) 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 gt 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
Lymphoma Leukemia Melanoma Solid tumors (ovary, breast, lung, kidney)
8. Hematologic disorders
Idiopathic thrombocytopenic purpura Autoimmune hemolytic anemia
9. Miscellaneous
Endocrine disorders (type I diabetes mellitus, Graves disease) Neurologic diseases (multiple sclerosis) End-stage renal failure After organ transplantation
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Serological Tests to Aid Diagnosis of SLE
Test 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

• HomogenousAnti-histone
• PeripheralAnti-dsDNA, Anti-lamine
• Speckled A large family of nonhiston antigens
• -CoarseAnti-Sm, Anti-U1-nRNP
• -FineAnti-Ro, Anti-La
• -Distinct speckles varying in number(PBC)
• Anti-p80-coilin, Anti-p95
• Nucleolar Scleroderma or overlap syndrome
• DNA topoisomerasenucleolar speckles
• PM-Sclhomogenous decorating nucleoli
• Fibrillarin (U3-RNP)clummy nucleolar
• NOR-90nucleolar speckles
• Centromere CREST syndrome, and PBC
• Cytoplasmic ANCA,

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Tabel 1. CUTANEOUS CHANGES IN LUPUS ERYTHEMATOSUS
Speclfic Discold Subacute cutaneous Papulosquamous Annular/polycyclic Neonatal lupus erythematosus Malar dermatitis
Nonspeclfic Lesions Bullous Lupus panniculitis Alopecia Vasculitis Urticaria-like vasculitis Livedo reticularis Raynauds 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 gt MCP gt wrist gt knee MCp gt wrist gt 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 Uncommon
Osteoporosis 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. MCP, Metacarpophalangeal joint PIP, proximal interphalangeal joint. 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 AN APPROACH TO THE MANAGEMENT OF LUPUS THROMBOCYTOPENIA
Confirm diagnosis by examining peripheral smear and bone marrow examination, and determine severity
Rule out drug effects and discontinue all but absolutely essential drugs
Rule out thrombotic throbocytopenic purpura (may be indicated by anemia with pronounced reticulocytosis and fragmented erythrocytes in the peripheral smear)
Rule out infection viralHIV, HBV, CMV bacterialsubacute 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 lt 50.000/mm3 (unless otherwise indicated for other manifestations of lupus) taper after 3-4 weeks The goal is a stable platelet count gt 50.000/mm3
If prednisone fails or unable to tape, consider danazol (400-800mg/day),?-globulin or splenectomy
In patients refractory to these modalities or patients with major organ involvement, use monthly pulses of cyclophosphamide for at least 6 months
Fig. 7.14 An approach to the management of lupus thrombocytopenia. 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 lupus lymphadenitis, the hematoxylin body, was described by Ginzler and Fox in 1940, which stain with periodic acid-Schiff and Feulgen methods, are coalescent amorphic aggregates of deeply basophilic material found within areas of lymph node necrosis.
The hematoxylin bodies are highly specific for SLE, are also found in glomeruli, endocardium and spleen
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Lupus lymphadeenitis (II)
Other lymph node features include paracortical focl of necrosis marked infiltration by histiocytes, lymphocytes and plasma cells and the preesence of imunoblasts. Neutrophils, eosinophils and granulomata are conspiculously absent.
Both lupus lymphadenitis and KFD are characterized by of histiocytic and immunoblastic infiltrates. A prominent plasma cell component strongly suggests lupus lymphadenitis. When present, hematoxylin bodies are virtually diagnostic of SLE.
The clinical feature, building on these pathologic resemblances, supports a link between KFD and SLE. Perhaps KFD and SLE share a common inclting event, such as 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 balance
Nocturia, decreased urinary concentrating capacity, hyperkalemia, renal tubular acidosis
Nephritic syndrome
Hematuria, cellular casts variable bypertension, edema, proteinuria, azotemia
Nephrotic syndrome
Frothy urine, edema, proteinuria gt3.5g per day, lipiduria (fatty casts, oval fat bodies, doubly refractile fat bodies), hypoalbuminemia, hyperlipidemia Secondary complications of nephrotic syndrome include volume 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 proteinuria Pathologysegmental proliferation, necrosis, crescents compromising capillary loops in lt50 of glomeruli mesangial and subendothelial immune complex deposits
Diffuse proliferative lupus nephritis
Clinical nephritic urine sediment, nephrotic syndrome, hypertension, variable renal insufficiency Pathologyglobal proliferation, necrosis in gt50 of glomeruli variable sclerosis, atrophy, and fibrosis 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 alteration
III Focal proliferative glomerulonephritis
IV Diffuse proliferative glomerulonephritis
V Menbranous glomerulopathy
VI 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 inflammation
Chronicity index (Range 0 to 12)
Glomerular lesions
Glomerular sclerosis Fibrous crescents
Tubulointerstitial lesions
Tubular 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 gt1g/day
The threshold is conventionally 1-2g/day Less proteinuria does not preclude biopsy if it occurs in the context of major serologic abnormalities, especially hypocomplementemia At the other extreme, the presence of full-bolwn nephrotic and nephritic syndromes may make renal biopsy unnecessary
Progressive azotemia
Decreasing renal function in associtaion with active urinary sediment is an indication for biopsy in order to assess the extent of crescents and necrosis which would warrant very aggressive therapy
Ambiguity or inconsistency of data
Lupus nephritis of indeterminate duration, severity and potential responsiveness warrants the establishment of a fresh baseline database including determination of class,activity and chronicity indices
Overlapping clinical features
Situations where clinical and laboratory data are compatible with different classes of lupus nephritis, for which different approaches to management are warranted
Redirection of therapy
Partially treated or incompletely responsive lupus nephritis for which a change in therapeutic plan 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
  all ESRD
• 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 itself
• 4.Nature end point in SLE
• Survival of lupus patients on dialysis versus
  non-SLE dialysis patientsno significant

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SLE and ESRD (2)

• Renal transplant graft survival of lupus versus
  non-lupus patientsno difference
• Lupus patients have slightly better outcome with
  LR rather than CAD grafts
• The transplantation time following dialysis need
  at least 3 months
• Recurrence of transplanted allograft is often
  similar to histologic or immunofluorescent type
  as in the origin kidney, but it is a rare event.

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NEUROPSYCHIATRIC MANIFESTATIONS IN SYSTEMIC LUPUS
ERYTHEMATOSUS
Central Nervous System 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 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 mediated Antineuronal 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 Infection Hypertension Uremia Electrolyte imbalances Hypoxia Fever Thyroid disease Thrombotic thrombocytopenic purpura Atherosclerotic 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 events
Infection (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
Special
Antineuronal 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 (vascular hyalinization, 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 patient
  nonadherence
• 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 fogbiofeedback for
  Raynauds phenomenon
• Counseling and stress management
• Physical and occupational therapy, ergonomic work
  station 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.
  Smoking cessation.
• Yearly bone densitometry and osteoporosis
  prevention measures.
• Annual electrocardiogram and chest x-ray
• Prompt evaluation of all fevers
• Periodic screening with carotid duplex scanning,
  treadmill, or stress testing screening for, and
  prophylactic management of, antiphospholipid
  antibodies.

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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 topical
  nitrogen 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 with extremely low
  platelet counts (e.g.lt30000/mm3)
• Autoimmune hemolytic anemia
• Acute pneumonitis caused by SLE.
• Others severe vasculitis with visceral organ
  involvement, serious complications from serositis
  (pleuritis, pericarditis, or peritonitis)

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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 to
  glucocorticoids
• Thrombosisincludes strokes
• Glomerulonephritisscarred end-stage renal
  disease, pure membranous glomerulonephritis
• Resistant thrombocytopenia or hemolytic
  anemiaoccurs in a minority of patients consider
  splenectomy, cytotoxics, danazol, or
  cyclosporine/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 with high
  dose prednisone
• Responded to corticosteroids but require an
  unacceptably high dose to maintain a response.
• Unacceptable side effects from corticosteroids.
• Chronic damage on a renal biopsy and other
  indicators 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)
• Advantageprobably reduces flares, reduces renal
  
  
  
  
  scarring, 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 dose1-3 mg/kg/day orally or 820
  
  mg/kg intravenously once a month
  
  plus mesna
• Maintenance dose0.52 mg/kg/day orally or
  820mg/kg intravenously every 412 wks plus
  mesna
• Adverse effectsprobably reduces flares, reduces
  renal 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-weight
  heparin with or without aspirin
• -If heparin ineffective or not tolerated,
  use low-dose aspirin alone
• -Glucocorticoids plus aspirin in moderate to
  high dose 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 other
  serious 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-sulfa
  antibiotics, sun, high estrogen-containing birth
  control pills,alfalfa sprouts
• Prevent atherosclerosis
• Prevent osteoporosis
• Prevent infection
• Prevent progression of renal disease
• Prevent clots in patients with antiphospholipid
  antibodies
• Treat fatigue.