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Systemic Lupus Erythematosus, ANA’s, etc. Hermine Brunner, MD MSc Assistant Professor of Pediatrics Division of Rheumatology Cincinnati Children’s Hospital Medical Center. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)- DEFINITION/DIAGNOSIS. Prototype of auto-immune, multi-system disease

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Systemic lupus erythematosus ana s etc

Systemic Lupus Erythematosus, ANA’s, etc.

Hermine Brunner, MD MSc

Assistant Professor of Pediatrics

Division of Rheumatology

Cincinnati Children’s Hospital Medical Center


Systemic lupus erythematosus sle definition diagnosis
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)- DEFINITION/DIAGNOSIS

  • Prototype of auto-immune, multi-system disease

  • Onset maybe acute, episodic, or insidious

  • “Anything” can happen to “any organ system”

  • Antinuclear antibodies are almost always present

  • Serositis & Immune complexes


Sle epidemiology
SLE - EPIDEMIOLOGY

  • 20% of all SLE is pediatric age group

  • Incidence 0.6/100,000

  • Prevalence 5-10/100,000

  • Overall 5-10,000 children in U.S.A.

  • Approximately 5% of new diagnoses in Pediatric Rheumatology clinics

  • SLE : JRA/1:10 ratio


Pediatric sle versus adult onset sle
Pediatric SLE versus Adult Onset SLE

  • More severe symptoms at onset

  • More aggressive clinical course than adults

  • Increased need for corticosteroid; 77% vs 16%

  • Children tend to die during acute SLE phase

    Adults tend to die secondary to complications

  • African American and Hispanic children have a higher incidence of disease

  • African American patients have

    • higher prevalence and severity of renal

    • higher prevalence neuropsychiatric SLE

    • higher titers of anti-DNA and anti-SSA antibodies in association with cardiac disease


Genetics in sle
Genetics in SLE

  • Eight of the best supported SLE susceptibility loci are the following

    • 1q23

    • 1q25-31

    • 1q41-42

    • 2q35-37

    • 4p16-15.2

    • 6p11-21

    • 12p24

    • 16q12

Tsao, BP, Curr Opinion Rheum, 2004; 16: 513-521


The 1982 revised criteria for classification of sle
THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

Malar rash Serositis

Discoid rash Renal disorder

Photosensitivity Neurologic disorder

Oral ulcers Hematologic disorder

Arthritis Immunologic disorder

Antinuclear antibody

Revised 1997


The 1982 revised criteria for classification of sle1
THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

  • For the purpose of identifying patients in clinical studies, a person shall be said to have SLE if any 4 or more of the 11 criteria are present, serially or simultaneously, during any interval of observation.

    • Sensitivity 96%

    • Specificity 96% in adults

    • Similar percentages in pediatric group.


Malar rash
MALAR RASH

  • Fixed erythema, flat or raised, over the malar eminences

  • tending to spare the nasolabial folds


Discoid rash
DISCOID RASH

  • Erythematous raised patches with adherent keratotic scaling and follicular plugging;

  • Atrophic scarring may occur in older lesions


Photosensitivity
PHOTOSENSITIVITY

  • Skin rash as a result of unusual reaction to sunlight

  • by patient history or physician observation


Oral ulcers
ORAL ULCERS

  • Oral or nasopharyngeal ulceration

  • Usually painless, observed by a physician


Arthritis
ARTHRITIS

  • Nonerosive arthritis involving 2 or more peripheral joints

  • Characterized by tenderness, swelling, or joint effusion.


Serositis
SEROSITIS

A) Pleuritis - convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion

OR

B) Pericarditis - documented by ECG or rub or evidence of pericardial effusion


Renal disorder
RENAL DISORDER

A) Persistent proteinuria greater than 0.5 grams per day or greater than 3+ if quantitation not performed

OR

B) Cellular casts - may be red cell,hemoglobin, granular, tubular, or mixed


Neurologic disorder
NEUROLOGIC DISORDER

A) Seizures - in the absence of offending drugs or known metabolic derangements, e.g., uremia, ketoacidosis, or electrolyte imbalance

OR

B) Psychosis - in the absence of offending drugs or known metabolic derangements, e.g. uremia, ketoacidosis, or electrolyte imbalance


Hematologic disorder
HEMATOLOGIC DISORDER

A) Hemolytic anemia - with reticulocytosis

OR

B) Leukopenia - less than 4,000/mm3 total on 2 or more occasions

OR

C) Lymphopenia - less than 1,500/mm3 on 2 or more occasions

OR

D) Thrombocytopenia - less than 100,000/mm3 in the absence of offending drugs


Immunologic disorder
IMMUNOLOGICDISORDER

A) Anti-dsDNA: antibody to native DNA in abnormal titer

OR

B) Anti-Sm: presence of antibody to Sm nuclear antigen

OR

C) Antiphospholipid antibodies by positive IgG or IgM anticardiolipin antibodies or positive test for lupus anticoagulant


Antinuclear antibody
ANTINUCLEAR ANTIBODY

  • An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay

    • at any point in time

    • and in the absence of drugs known to be associated with

  • “drug-induced lupus” syndrome


Drug induced lupus
Drug-Induced Lupus

  • Minocycline (Minocin)

  • Phenytoin (Dilantin)

  • Carbamazepine (Tegretol)

  • Ethosuximide (Zarontin)


Antinuclear antibody1
ANTINUCLEAR ANTIBODY

  • 1:20 - 1:40 Screening titer

    • 1: x titer

  • Pattern

    • speckled - + ENA’s

    • rim - ds DNA

    • homogeneous - DNA (LE prep)

    • nucleolar - Scl - 70


SLE

Tissue Specific Nuclear

Antibodies Antibodies

ATA Ro/SSA

Anti ASMA La/SSB

Anti-MITO RNP

Anti-LKM Sm

Anti-PC ds DNA

Hep-2 ss DNA


Arthralgia and positive ana or rf
Arthralgia and Positive ANA or RF

  • Remember that objective signs of joint inflammation substantiate diagnosis of arthritis

  • Comprehensive review of systems may uncover clues

  • Perform a critical, complete physical examination

  • Serial re-evaluations may be necessary

  • Most children do not progress to a C.T.D.

  • Positive serologies may be seen in:

    • Normal children - approximately 3-12%

    • Response to infection


Persistent ana
Persistent ANA

  • 24/108 children with musculoskeletal problems had positive ANA

  • 21/24 had persistent ANA, mean duration 38 mo

  • No patient developed an overt autoimmune or inflammatory disease, mean F/U 61 mo (13-138)

  • Conclusion: a child with positive ANA and musculoskeletal problems , but with no evidence at presentation of AID or inflammatory disease is at low risk of developing such a disease.

Cabral, DA, et al Pediatrics 1992, 89(3):441-444


Outcome of children referred to pediatric rheumatology clinic with a positive ana but without aid
Outcome of Children referred to Pediatric Rheumatology Clinic with a positive ANA but without AID

  • 500 new patients reviewed, 113 had positive ANA

  • 72 (64%) had an autoimmune disease AID,

    10 (9%) were lost to F/U, 31 (27%) had no AID,

  • Mean ANA titer 1:160, varied pattern

  • Mean clinical F/U 37 mos

  • 25 (81%) cleared their symptoms, 5 (16%) had improvement, 1 developed autoimmune hepatitis

  • Prognosis with +ANA is excellent in absence of AID at presentation

Deane, PMG, et al, Pediatrics 1995, 95:892-895


Clinical utility of antinuclear ana tests in children mcghee jl et al bmc pediatrics 2004 4 13
Clinical Utility of Antinuclear ANA Tests in Children Clinic with a positive ANA but without AIDMcGhee JL et al, BMC Pediatrics 2004, 4: 13

  • 110 pts referred to Rheum for +ANA

    • 80 children with musculoskeletal problems syndromes

  • 10 pts subsequently dx’d SLE, 1 MCTD, 1 Prim Raynaud’s, 18 with JIA

    • Nonurticarial rash more common in SLE, p=0.007

    • Children with SLE were older 14.2 vs 11 yrs, p=0.001

    • ANA > 1:640 was +predictor for SLE while titers of <1:360 were negative predictors

  • Conclusion:

    • Age and ANA titer assist in Dx SLE, no diagnostic value in Dx JRA

    • Remember the AID have objective evidence of disease!!!!!!!


Sle clinical manifestations
SLE - CLINICAL MANIFESTATIONS Clinic with a positive ANA but without AID

Most common signs/symptoms

  • Unexplained fever, any pattern

  • Malaise

  • Weight Loss

  • Arthralgia


Sle mucocutaneous involvement
SLE - MUCOCUTANEOUS INVOLVEMENT Clinic with a positive ANA but without AID

  • “Butterfly Rash” - 1/3 at onset

  • Angiitic papules

  • Periungual erythema

  • Urticaria / angioedema

  • Palatal ulcer / aphthous ulcer

  • Alopecia


Sle mucocutaneous involvement1
SLE - MUCOCUTANEOUS INVOLVEMENT Clinic with a positive ANA but without AID

  • Discoid lupus

  • Subacute cutaneous lupus

  • Livedo reticularis

  • Nailfold capillary changes

  • Vasculitic ulceration

  • Panniculitis

  • Nasal septal perforation


Ulcerated Clinic with a positive ANA but without AID

leukocytoclastic

vasculitis in SLE


Sle musculoskeletal disease
SLE - MUSCULOSKELETAL DISEASE Clinic with a positive ANA but without AID

  • Arthralgia / Arthritis

  • Myalgia / Myositis

  • Ischemic necrosis of bone - AVN


Sle vasculopathy
SLE - VASCULOPATHY Clinic with a positive ANA but without AID

  • Small vessel vasculitis

  • Palpable purpura

  • Raynaud’s phenomenon

  • Antiphospholipid antibody syndrome


Sle cardiac involvement
SLE - CARDIAC INVOLVEMENT Clinic with a positive ANA but without AID

  • Pericarditis

  • Myocarditis

  • Endocarditis, Libman-Sacks

  • Accelerated atherosclerosis


Sle pleuropulmonary disease
SLE - PLEUROPULMONARY DISEASE Clinic with a positive ANA but without AID

  • Pleuritis/Pleural effusion

  • Infiltrates/Atelectasis

  • Acute lupus pneumonitis

  • Pulmonary hemorrhage

  • “Shrinking lung” - diaphragm dysfunction

  • Subclinical restrictive disease


Sle gastrointestinal manifestations
SLE - GASTROINTESTINAL MANIFESTATIONS Clinic with a positive ANA but without AID

  • Anorexia, weight loss, nonspecific abdominal pain

  • Pancreatitis

  • Mesenteric arteritis

  • Esophageal dysmotility


Sle liver spleen lymph node
SLE – LIVER , SPLEEN & LYMPH NODE Clinic with a positive ANA but without AID

  • Generalized lymphadenopathy

  • “Lupoid hepatitis” vs SLE hepatic involvement

  • Functional asplenia


Sle neuropsychiatric manifestations
SLE - NEUROPSYCHIATRIC MANIFESTATIONS Clinic with a positive ANA but without AID

  • Must be differentiated from infection or hypertensive or metabolic complications

  • Any level of the CNS/PNS can be affected

  • Thorough evaluation necessary - CSF, EEG, CT, MRI, EMG / NCV, NP testing


Sle neuropsychiatric involvement
SLE - NEUROPSYCHIATRIC INVOLVEMENT Clinic with a positive ANA but without AID

Behavior/Personality changes, depression

Cognitive dysfunction

Psychosis

Seizures

Stroke

Chorea

Pseudotumor cerebri

Transverse myelitis

Peripheral neuropathy

Total of 19 manifestations described


Sle renal involvement
SLE - RENAL INVOLVEMENT Clinic with a positive ANA but without AID

  • Usually asymptomatic

  • Gross hematuria

  • Nephrotic syndrome

  • Acute renal failure

  • Hypertension

  • End stage renal failure


Sle nephritis
SLE - NEPHRITIS Clinic with a positive ANA but without AID

Nephritis remains the most frequent cause of disease-related death.


World health organization classification of lupus nephritis
WORLD HEALTH ORGANIZATION CLASSIFICATION OF LUPUS NEPHRITIS Clinic with a positive ANA but without AID

Class I Normal

Class II Mesangial

IIA Minimal alteration

IIB Mesangial glomerulitis

Class III Focal and segmental proliferative glomerulonephritis

Class IV Diffuse proliferative glomerulonephritis

Class V Membranous glomerulonephritis

Class VI Glomerular sclerosis


Sle laboratory evaluation
SLE - LABORATORY EVALUATION Clinic with a positive ANA but without AID

  • Antinuclear antibody profile

  • Anti dsDNA abs, Sm abs

  • C3, C4, IgA, IgG, IgM

  • Direct Coomb’s, DAT

  • Antiphospholipid antibodies

    ACLA - Anticardiolipin antibodies

    LAC - Lupus anticoagulant

  • CBC with Diff, U/A, CMP, TSH, ESR


Comprehensive evaluation of a child with sle
Comprehensive Evaluation of a Child with SLE Clinic with a positive ANA but without AID

  • Cumulative medication burden

  • Serial DEXA while on corticosteroids

  • Lipid panels

  • Repeat APA profile, ? Frequency

  • HRQL and damage indices, SLEDAI, SDI

  • Neuropsychiatric testing ?

  • ECHO

  • Complement factor deficiency (C1q)


Long term management issues
Long-term Management Issues Clinic with a positive ANA but without AID

  • Long term morbidity of corticosteroids:

    short stature, cataracts, osteoporosis

  • How to manage ongoing active disease after multiple medications during childhood

  • Long term morbidity of immunosuppressive agents

    • Non-sustained durable disease: ? remission

    • Cumulative risk re: malignancy and premature ovarian failure


Therapeutic goals in sle still unmet expectations
Therapeutic Goals in SLE: Still Unmet Expectations Clinic with a positive ANA but without AID

  • Rate of renal remission after first line therapy still 81% at best

  • Renal relapse in 1/3 pts mostly still immunosuppressed

  • 5- 20% experience ESRD 5-10 yrs after disease onset

  • Treatment related toxicity remains a concern; osteoporosis, premature ovarian failure, severe infections, etc.

  • Prognostic factors have been identified but are difficult to modify in order to improve outcomes


Treatment regimens for ln
Treatment Regimens for LN Clinic with a positive ANA but without AID

  • Glucocorticoids plus cyclophosphamideinduction & maintenance for 3 years

    • NIH protocol

  • Glucocorticoids plus low dose cyclophosphamide with maintenance with MMF or AZA

  • Immunoablative doses of cyclophosphamide

  • Autologous stem cell transplantation

  • Plasmapharesis is not recommended

  • Reviewed: Houssian FA, J Am Soc Nephrol 2004; 15: 2694


Sequential therapies for who iii v
Sequential Therapies for WHO III- V Clinic with a positive ANA but without AID

  • 60 adult SLE pts randomized 3 groups

    • 12 Class III, 46 Class IV and 1 Class Vb

  • All received initial therapy with Cyclophosphamide 0.5-1.0 gm/m² up to 7 pulses

    • Cont’d on 1) cyclophosphamide, 2) azathioprine 1-3mg/kg, or 3)M ycophenolate mofetil (Cellcept, MMF) 0.5-3.0 gm/d for 1-3 years

  • 5 pts died- 4CYC, 1 MMF; 5 CRF- 3 CYC,1 AZA, 1 MMF

  • 72 month event free survival rate higher in MMF and AZA than in CYC (P=0.05 and P=0.009, respectively)

  • Incidence of hosp, amenorrhea, infections, nausea and vomiting lower in the MMF and AZA groups than in the CYC group

Contreras, G et al: NEJM 350(10): 971-980, 2004


Targeted immune intervention
Targeted Immune Intervention Clinic with a positive ANA but without AID

  • Directed against B Cells: Rituximab, anti-CD20 B cell depleting monoclonal antibody

  • LJP 394, anti-dsDNA-producing B cells

  • Co-stimulatory signals CD40-CD40L (CD154) blockade CTLA41g, abatacept: binding to CD80 and CD86 prevents engagement to CD28 to T cells thereby prevents co-stimulation

  • Cytokine blockade IL10, INF-α

Houssian FA, J Am Soc Neprol, 2004; 15: 2694-2704


Major clinical syndromes in sle requiring vigilance
Major Clinical Syndromes in SLE Requiring Vigilance Clinic with a positive ANA but without AID

  • Antiphospholipid Antibody Syndrome with thrombosis

  • Premature atherosclerosis and marked risk of myocardial infarction

  • Neurocognitive dysfunction with deterioration of mental capacity

  • Iatrogenic syndromes of osteoporosis and premature ovarian failure 2° therapy


Case 1 9 yo aaf with sle
Case 1: 9 yo AAF with SLE Clinic with a positive ANA but without AID

  • Fever T 101-102, 3-4 x/week

  • Weight loss

  • Swollen fingers

  • Facial, malar, and eyelid rash

  • Weakness

  • Gradual decline in school performance

  • Family history positive for “arthritis” in mother & maternal aunt


Case 1 physical examination
Case 1: Physical Examination Clinic with a positive ANA but without AID

  • T 101.8, Wt 27.1 kg (30%), Ht 130.6 (40%)

  • BP 90/50

  • Scleral/conjunctival injection

  • Nasal and oral ulcerations

  • Patchy parietal alopecia

  • Shoddy lymphadenopathy

  • Symmetric PIP swelling

  • Depressed affect


Case 1 laboratory investigation
Case 1: Laboratory Investigation Clinic with a positive ANA but without AID

  • Hgb 9.5 gm%, WBC 4.05, 55% PMN

    platelets 257,000

  • U/A “essentially negative”

  • RF negative

  • ANA 1:5120, diffuse, membranous

    Ro (SSA) , La (SSB) , RNP , Sm ,

    ds DNA 1:5120, APA negative

  • ↓C3-55 (83-177),↓C4-4 (21-75),↑IgG 3260 (608-1572)

  • DAT 


Case 1 course
Case 1: Course Clinic with a positive ANA but without AID

  • Within 6 months:

    • pleural effusion, pulmonary infiltrates (prednisone)

    • Episodic photosensitive cutaneous flares (Plaquenil)

    • Digital angiitis

  • DPGN (WHO IV)  progressive renal involvement  HBP (cyclophosphamide, prednisone)

  • School failure, psychosocial disruption

  • Marked non-adherence to medication regimen

  • ESRD, TTP, cerebritis, hemodialysis, depression

  • Shunt infections, on/off transplantation registry


Cognitive dysfunction in sle
Cognitive Dysfunction in SLE Clinic with a positive ANA but without AID

  • Variable between pts with overt NPSLE and nSLE

  • 52-80% NPSLE vs 27-40% nSLE

  • Verbal and non-verbal long-term memory, and visuospatial memory in both groups; and visuoconstructional abilities in NPSLE

  • Coexistent depression amplifies the deficits

  • Maybe present without overt active SLE sxs

Monastero R, et al, J of the Neurological Sci 2001; 184:33-39


Case 2 learn from old experience
Case 2: Learn from old experience Clinic with a positive ANA but without AID

  • 17 yo WF initially evaluated for rheumatoid arthritis with polyarthritis and +ANA

  • History of photosensitive rash and subsequent development of pericarditis led to dx of SLE

  • Renal biopsy done: WHO class II

  • Off/on low C3 and C4 and elevated dsDNA abs

  • Notable elevated cholesterol, LDL and triglycerides PLUS tobacco smoking for >10 years


Case 2 continued
Case 2: continued Clinic with a positive ANA but without AID

  • Had a full term normal pregnancy with healthy infant; followed by a Bacteroides sepsis 5 days postpartum

  • Approximately 1 year later developed chest pain

  • Several ED visits later at adult ED’s she was dx’d with MI; unable to stent 2º distal disease

  • Now cardiac invalid, continues to smoke tobacco and has active SLE

  • Multiple cholesterol lowering agents, Plaquenil


Risk factors of premature cvd in csle
Risk Factors of Premature CVD in cSLE Clinic with a positive ANA but without AID

  • Elevated levels of homocysteine

  • Metabolic syndrome with hyperinsulinemia

  • Hypertension

  • Nephrotic range proteinuria

  • Dyslipoproteinemia/hyperlipidemia

  • Arterial vasculitis

  • Antiphospholipid antibodies

  • Increased oxidative state, anti-Ox-LDL IgG ab

  • Steroid induced obesity and hyperlipidemia, etc.

  • Sustained SLE disease activity, ↑SDI

Stichweh, D , Curr Opin Rheumatol 16:577-587, 2004

Schanberg LE, Sandborg C, Current Rheum Reports 2004;6:425-433


Case 3 clinical presentation
Case 3: Clinical Presentation Clinic with a positive ANA but without AID

  • Patient is a 10 yo WF who was admitted to inpatient psychiatric team for treatment of PTSD/depression

  • Due to worsening abdominal pain, decreased oral intake, and peripheral edema she was evaluated by abd U/S which showed clot in IVC as well as edematous/ enlarged kidneys.

  • Further evaluation by CT scan of her abdomen/thorax showed the clot went from her right atrium to her infrarenal IVC; there was extension of clot into renal veins bilaterally.


Ultrasound results
Ultrasound Results Clinic with a positive ANA but without AID

IVC

Clot


Clinical presentation
Clinical Presentation Clinic with a positive ANA but without AID

  • Anticoagulation with heparin.

  • Laboratory evaluation to help determine the etiology of her clot was undertaken. Rheumatology service consulted.

  • HPI: abd pain since beginning of June; no fevers, skin rashes, mucosal changes, joint pain/swelling.

  • PMH: no h/o thrombotic events; depression, PTSD thought to be secondary to alleged abuse and diagnosed during this admission.

  • Family Hx: Maternal grandmother diagnosed with lupus at 23 years of age.


Laboratory evaluation
Laboratory Evaluation Clinic with a positive ANA but without AID

9.3 U/A: 1.015, pH 6.0,

9.7 137 >300 mg protein,

moderate blood

30.7

ALC – 1360

ESR - >140; CRP – 5.26

C3 – 153; C4 - 21.2

[Thrombotic Profile – normal]

[DAT – positive]

ANA – positive at 1:2560; other autoantibodies all negative

[APA Profile – positive]


Pathology findings class v
Pathology Findings : Class V Clinic with a positive ANA but without AID

Light Microscopy with Silver Stain showing epimembranous deposits.

Electron Microscopy showing epimembranous deposits.

Light Microscopy showing increased mesangial cells.


Antiphospholipid antibodies in csle
Antiphospholipid Antibodies in cSLE Clinic with a positive ANA but without AID

  • Associated with venous and arterial thrombosis, thrombocytopenia, neurologic disorders and fetal loss

    • Found in 65% of children with SLE

  • +LAC, ACLA and false positive VDRL

  • Prolonged partial thromboplastin time

  • All are associated with thrombosis; esp LAC and ACLA

  • Anticoagulation required if a patient has a thrombotic event

  • Aspirin in everybody else

Seaman DE, et al, Pediatrics. 1995; 96: 1040-5


Management goals for csle
Management Goals for cSLE Clinic with a positive ANA but without AID

  • Counseling, education

  • Recommend adequate rest and activity

  • Decrease inflammation; prevent end-organ injury failure

  • Preserve renal function; provide HBP Rx; prevent flare

  • Provide photo protection

  • Maintain up-to-date immunizations

  • Management of infection

  • Minimize osteoporosis

  • Identify patients at risk of thrombo-occlusive events

  • Evaluate and treat ASHD risk; dyslipoproteinemia, etc.

  • Family planning/contraceptive issues


Combined Oral Contraceptives Are Not Associated with an Increased Rate of Flare in SLE Patients in SELENA

  • SELENA- Safety of Estrogen in Lupus Erythematosus-National Assessment

  • 183 premenapausal pts, mean age 30 y

  • Inactive 76%, stable/active 24%

  • Randomized, double blind OC vs placebo for 12 28-day OC cycles

  • Primary end point, severe flare, rare; 7/91 (7.7%) OC vs 7/92 (7.6%) placebo

  • Mild/moderate flares 1.41 vs 1.40 flares/person-year (OC vs P) RR= 1.01, P= 0.96

  • 3 or more mild/moderate flares 15% vs 16%

  • OC does not increase rate of severe or mild/moderate flare in SLE

Petri,M, Arthritis Rheum 2004, 50(9): S239, abstract 523


Adjunct therapy for sle
Adjunct Therapy for SLE Increased Rate of Flare in SLE Patients in SELENA

  • Antimalarials; hydroxychloroquine

  • Nonsteroidal anti-inflammatory drugs

  • ASA

  • Folic Acid

  • ACE Inhibitors

  • Glucocorticoids; variable dose ranges

  • Immunosuppressives non CYC, azathioprine, mycophenalate mofetil MMF, cyclosporin, methotrexate

  • Herpes Zoster prophylaxis

  • Vaccinations

  • Organ specific medications; e.g. anti-HTN, osteoporosis, infection, etc.


Risk factors for damage in childhood onset sle
Risk Factors for Damage in Childhood-Onset SLE Increased Rate of Flare in SLE Patients in SELENA

  • Disease activity and damage in 66 pts

  • SLICC/ACR Damage Index 1.76 (mean FU 3.3 y)

  • Cumulative disease activity single best predictor of damage (R2 = 0.30)

  • Corticosteroid treatment, APA, acute thrombocytopenia

  • Immunosuppressive agents protective

Brunner, HI, et al. Arthritis and Rheumat.2002;46:436-44.


Long term followup of sle nephritis toronto
Long-term Followup of Increased Rate of Flare in SLE Patients in SELENASLE Nephritis: Toronto*

  • 67 pt, M:F 1:3.8, FU mean 11 y

  • 15 Class II, 8 Class III, 32 Class IV, 11 Class V

  • 4/67 died, 6/67 ESRD, 94% survival rate

  • Non-Caucasian pts may be at increased risk for renal failure

  • Azathioprine most commonly employed immunosuppressive agent

Hagelberg, S. J Rheumatol. 2002;29:2635-42.


Long term outcomes of childhood onset sle
Long-Term Outcomes of Childhood-Onset SLE Increased Rate of Flare in SLE Patients in SELENA

  • 77 pts (prev 9.6/100,000; F:M 10:1), 39 interviewed

  • Mean age at dx 14.6 yrs, 57% Cauc, 40% AA and 3% Asian

  • 8 pts died (86.9% survival) mean F/U 7.6 yrs

  • Mean SLEDAI score 6.2 (range: 0-26),

  • 42% SDI>0, mean 1.4 (0-10)

    • NPL, renal, ocular, and MS accounted for 79% of damage

  • AA had higher SLEDAI and SDI scores

  • cSLE pts develop 2 times damage of adults and continue to have active disease

  • CYC used in 39%,

    • higher rate of ovarian damage (36%); dose related

  • HRQL compared to healthy controls much lower mental and physical component

Brunner et al, Lupus 2006, in press


Conclusion s
Conclusion(s) Increased Rate of Flare in SLE Patients in SELENA

  • SLE in children has the same clinical expression as in adults but a more aggressive disease course.

  • Numerous potential complications loom behind the scenes and must be anticipated and monitored.

  • Better understanding of the pathogenesis will enable better targeted and safer therapy.

  • Multiple trials are ongoing at CCHMC to investigate better health outcomes for cSLE.


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