1 guideline for sle management 高雄長庚醫院風濕過敏免疫科. 2 epidemiology of sle...

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Guideline for SLE management

高雄長庚醫院風濕過敏免疫科高雄長庚醫院風濕過敏免疫科

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Epidemiology of SLE

Prevalence of SLE：　 In U.S： 18-24/100000

　 black female： 7.9-10.5/100000

　 white female： 4/100000

More common in urban than in rural areas

Female：male=1.4-5.8： 1 (children)

8-13： 1 (adult)

2： 1 (older)

Onset age=65% between 16-55 y/o

20% < 16 y/o

15% > 55 y/o

Identical twin ： 30%

first degre relative ： 5%

Annual incidence of new case： 6/100000 (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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Symptoms Percentage

Fatigue 80-100

Fever >80

Weight loss >60

Arthritis, arthralgia 95

Skin　 Butterfly rash　 Photosensitivity　 Mucous membrane lesion　 Alopecia　 Raynaud’s phenomenon　 Purpura　 Urticaria

>80>50<58

27-41<71

17-30158

Renal　 Nephrosis

5018

Castrointestinal 38

Pulmonary　 Pleruisy　 Effusion　 Pneumonia

0.9-98452429

Cardiac　 Pericarditis　 Murmurs　 ECG changes

468-4823

34-70Lymphadenopathy 50

Splenomegaly 10-20

Hepatomegaly 25

Central nervous system　 Functional　 Psychosis　 Convulsions

25-75most5-52

15-20

Table 61-1. FREQUENCY OF CLINICAL SYMPTOMS IN SLE AT ANY TIME

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Table 9-3. THE SPECTRUM OF ANAsChromatinAnti-native DNAAnti-single-stranded DNAAnti-Z DNAAnti-centromereAnti-KuAnti-HMG proteinsAnti-topoisomerase I (Scl-70 antigen)Anti-topoisomerase IIAnti-PBC 95KAnti-laminsNucleolar ComponentsAnti-RNA polymerase IAnti-ThAnti-Us (fibrillarin)Anti-Pm/SclAnti-NOR-90Other Cellular ComponentsAnti-unclear pore complexesAnti-centrosomesAnti-midbodyAnti-spindleAnti-MiAnti-SuNuclear RibonucleoproteinsAnti-U1 RNPAnti-SmAnti-RoAnti-LaAnti-U2 RNPAnti-U4 U6 RNPAnti-U5 RNPAnti-5S rRNAprotein

Cytoplasmic ComponentsAnti-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 patient’s 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　 Sjogren’s 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

　 Lymphoma　 Leukemia　Melanoma　 Solid tumors (ovary, breast, lung, kidney)

8. Hematologic disorders

　 Idiopathic thrombocytopenic purpura　 Autoimmune hemolytic anemia9. 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 autoantibody1. Homogenous ： Anti-histone

2. Peripheral ： Anti-dsDNA, Anti-lamine

3. Speckled ： A 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 nucleoli

Fibrillarin (U3-RNP):clummy nucleolar

NOR-90:nucleolar speckles

5. Centromere ： CREST syndrome, and PBC

6. Cytoplasmic ： ANCA,

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Positive

ANA

Nucleoli

Raynaud’s phenomenon Scleroderma

Diffuse (honogeneous)

Anti-nucleoprotein

SLERADrug LE

Histone

SLERADrug LE

Centromere

CRESTSdleroderma

Peripheral (rim)

Anti-dsDNA

SLE

Negative

No diseaseLab error Treatment RemissionAntigen XSNephrotic syndrome

No specificityUCTDSLERALiver diseaseMonoAny chronic inflammatory disease

RNP

SLEMCTDRASclerodermaUCTD

Sm

SLE

RO (SS-A)

SLESogren’s syndrome

PcNA

SLE

Scl-70

Scleroderma

PM/Jo/Ku/Mi

PM/DM

La

SLESogren’s syndrome

Speckled

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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

　 Raynaud’s 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 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.

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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 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 ：　 viral ： HIV, HBV, CMV　 bacterial ： subacute 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 otherwise indicated for other manifestations of lupus); taper after 3-4 weeksThe goal is a stable platelet count > 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.

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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 >3.5g 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

　 Clinical ： low-grade hematuria, proteinuria, normal renal function

　 Pathology ： increased mesangial cells, matrix, and immune complexes; patent glomerular 　　　 capillary loops

Focal proliferative lupus nephritis

　 Clinical ： nephritic urine sediment, variable but usually nonnephrotic proteinuria

　 Pathology ： segmental proliferation, necrosis, crescents compromising capillary loops in <50% 　　　　　　　 of glomeruli; mesangial and subendothelial immune complex deposits

Diffuse proliferative lupus nephritis

　 Clinical ： nephritic urine sediment, nephrotic syndrome, hypertension, variable renal insufficiency

　 Pathology ： global proliferation, necrosis in >50% of glomeruli; variable sclerosis, atrophy, and 　　　　　　　　 fibrosis; mesangial, subendothelial, and subepithelial immune complex deposits

Membranous nephropathy

　 Clinical ： nephrotic syndrome

　 Pathology ： diffuse 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 >1g/day

The threshold is conventionally 1-2g/dayLess proteinuria does not preclude biopsy if it occurs in the context of major serologic 　　　　 abnormalities, especially hypocomplementemiaAt 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 patients ： no significant

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SLE and ESRD (2)

• Renal transplant graft survival of lupus versus non-lupus patients ： no 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

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 SecondaryAutoantibody 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

InfectionHypertensionUremia

Electrolyte imbalances

Hypoxia

Fever

Thyroid disease

Thrombotic thrombocytopenic purpura

Atherosclerotic strokes

Emboli from valvular vegetations

Subdural hematomaCerebral lymphomaMedications　 Drug overdose　 Corticosteroids　 NSAIDs　 Hydroxychloroquine　 AzathioprineFibromyalgiaReactive 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


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



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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 “fog”;biofeedback for Raynaud’s phenomenon

• Counseling and stress management• Physical and occupational therapy, ergonomic work s

tation 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, trea

dmill, 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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• Routine therapy– Topical steroids, intralesional steroids– Hydroxychloroquine– Oral corticosteroids– Dapsone for bullous lesions

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• Advanced therapy for resistant causes– Subacute cutaneous lupus: mycophenylate

mofetil, retinoids, or cyclosporine– Discoid lesions: chloroquine, clofazimine, t

halidomide, or cyclosporine– Lupus profundus: dapsone– Chronic lesions over 50% of body: topical n

itrogen 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 extremel

y low platelet counts (e.g.<30000/mm3)• Autoimmune hemolytic anemia• Acute pneumonitis caused by SLE.• Others: severe vasculitis with visceral organ i

nvolvement, 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 erythem

atosus or SLE– Polyarthritis– Polyserositis—pericarditis, pleurisy, peritonitis– Myocarditis– Lupus pneumonitis

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~(continue)– Glomerulonephritis—proliferative forms– Hemolytic anemia– Thrombocytopenia– Diffuse CNS syndrome—acute confusional state,

demyelinating syndromes, intractable headache– Serious cognitive defects– Myelopathies– Peripheral neuropathies– Lupus crisis—high fever and prostration

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• Manifestations not often responsive to glucocorticoids– Thrombosis—includes strokes– Glomerulonephritis—scarred end-stage renal dise

ase, pure membranous glomerulonephritis– Resistant thrombocytopenia or hemolytic anemia

—occurs 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 (ab

out 1mg/kg/day)– Cytotoxic drugs or other immunosuppressi

ve 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.

46

Systemic therapies for nonorgan-threatening lupus

• Nonsteroidal anti-inflammatory drugs• Antimalarials• Thalidomide• Hormonal interventions: dehydroepiandr

osterone, testosterone patches, bromocriptine, prolactin

• Immunosuppressive therapies: azathioprine, methotrexate, leflunomide

47

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, LL2

IgG• Stem cell transplantation

48

Use of Cytotoxic Drugs in SLE : Azathioprine

• requires 6–12 months to work well• 1–3 mg/kg/day(initial dose)• 1–2 mg/kg/day(maintenance dose)• Advantage:probably 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

49

Use of Cytotoxic Drugs in SLE: Cyclophosphamide

• requires 2–16 weeks to work well• Initial dose:1-3 mg/kg/day orally or 8–20

mg/kg intravenously once a month plus mesna

• Maintenance dose:0.5–2 mg/kg/day orally or 8–20mg/kg intravenously every 4–12 wks plus mesna

• Adverse effects:probably reduces flares, reduces renal scarring, reduces glucocorticoid dose requirement

• Adverse effects: marrow suppression, leukopenia, infection, infertility, malignancy, menopause,cystitis,nausea

50

The treatment in lupus patients with autoimmune thrombocytopenia

• Splenectomy

• Danazol

• Immunosuppressive or cytotoxic drugs: azathioprine, cyclophosphamide

• Intravenous immunoglobulin(IVIG)

51

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 wit

h or without aspirin -If heparin ineffective or not tolerated, use low-dose aspiri

n alone -Glucocorticoids plus aspirin in moderate to high dose ma

y be used but is controversial

• Thrombocytopenia or hemolytic anemia -Intravenous gamma globulin, splenectomy, danazol, cycl

osporine, cytotoxic drugs

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• 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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• 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.

1 guideline for sle management 高雄長庚醫院風濕過敏免疫科. 2 epidemiology of sle...

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