Systemic Lupus Systemic Lupus Erythematosus, Erythematosus,

ANA’s, etc.ANA’s, etc.Hermine Brunner, MD MSc

Assistant Professor of PediatricsDivision of Rheumatology

Cincinnati Children’s Hospital Medical Center

SYSTEMIC LUPUS SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)- ERYTHEMATOSUS (SLE)- DEFINITION/DIAGNOSISDEFINITION/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 - EPIDEMIOLOGYSLE - 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 Pediatric SLE versus Adult Onset SLESLE• 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 SLEGenetics 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 THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLEFOR CLASSIFICATION OF SLE

Malar rash SerositisDiscoid rash Renal disorderPhotosensitivity Neurologic disorderOral ulcers Hematologic disorderArthritis Immunologic disorder

Antinuclear antibody

Revised 1997

THE 1982 REVISED CRITERIA FOR THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLECLASSIFICATION 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%Sensitivity 96%– Specificity 96% in adults Specificity 96% in adults – Similar percentages in pediatric groupSimilar percentages in pediatric group.

MALAR RASHMALAR RASH

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

• tending to spare the nasolabial folds

DISCOID RASHDISCOID RASH

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

•Atrophic scarring may occur in older lesions

PHOTOSENSITIVITYPHOTOSENSITIVITY

• Skin rash as a result of unusual reaction to sunlight

• by patient history or physician observation

ORAL ULCERSORAL ULCERS•Oral or

nasopharyngeal ulceration

•Usually painless, observed by a physician

ARTHRITISARTHRITIS

•Nonerosive arthritis involving 2 or more peripheral joints

•Characterized by tenderness, swelling, or joint effusion.

SEROSITISSEROSITISA) Pleuritis - convincing history

of pleuritic pain or rub heard by a physician or evidence of pleural effusion

ORB) Pericarditis - documented by

ECG or rub or evidence of pericardial effusion

RENAL DISORDERRENAL DISORDERA) Persistent proteinuria greater

than 0.5 grams per day or greater than 3+ if quantitation not performed

ORB) Cellular casts - may be red

cell,hemoglobin, granular, tubular, or mixed

NEUROLOGIC DISORDERNEUROLOGIC DISORDER

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

ORB) Psychosis - in the absence of

offending drugs or known metabolic derangements, e.g. uremia, ketoacidosis, or electrolyte imbalance

HEMATOLOGIC DISORDERHEMATOLOGIC DISORDERA) Hemolytic anemia - with

reticulocytosisOR

B) Leukopenia - less than 4,000/mm3

total on 2 or more occasionsOR

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

ORD) Thrombocytopenia - less than

100,000/mm3 in the absence of offending drugs

IMMUNOLOGICIMMUNOLOGIC DISORDERDISORDER

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

ORB) Anti-Sm: presence of antibody to

Sm nuclear antigenOR

C) Antiphospholipid antibodies by positive IgG or IgM anticardiolipin

antibodies or positive test for lupus anticoagulant

ANTINUCLEAR ANTINUCLEAR ANTIBODYANTIBODY

•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 LupusDrug-Induced Lupus

• Minocycline (Minocin) • Phenytoin (Dilantin) • Carbamazepine (Tegretol) • Ethosuximide (Zarontin)

ANTINUCLEAR ANTIBODYANTINUCLEAR ANTIBODY• 1:20 - 1:40 Screening titer

– 1: x titer

• Pattern – speckled - + ENA’s– rim - ds DNA– homogeneous - DNA (LE prep)– nucleolar - Scl - 70

SLESLE

Tissue Specific Nuclear Antibodies AntibodiesATA Ro/SSAAnti ASMA La/SSBAnti-MITO RNPAnti-LKM SmAnti-PC ds DNAHep-2 ss DNA

Arthralgia and Positive ANA Arthralgia and Positive ANA or RFor 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 ANAPersistent 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 Outcome of Children referred to Pediatric Rheumatology Clinic with Pediatric Rheumatology Clinic with

a positive ANA but without AIDa 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 Clinical Utility of Antinuclear ANA Tests in ChildrenTests in Children

McGhee JL et al, BMC Pediatrics 2004, 4: 13McGhee JL et al, BMC Pediatrics 2004, 4: 13

• 110 pts referred to Rheum for +ANA110 pts referred to Rheum for +ANA– 80 children with musculoskeletal problems syndromes80 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 SLE - CLINICAL MANIFESTATIONSMANIFESTATIONS

Most common signs/symptoms•Unexplained fever, any

pattern•Malaise•Weight Loss•Arthralgia

SLE - MUCOCUTANEOUS SLE - MUCOCUTANEOUS INVOLVEMENTINVOLVEMENT

• “Butterfly Rash” - 1/3 at onset

• Angiitic papules• Periungual erythema• Urticaria / angioedema• Palatal ulcer / aphthous ulcer• Alopecia

SLE - MUCOCUTANEOUS SLE - MUCOCUTANEOUS INVOLVEMENTINVOLVEMENT

• Discoid lupus• Subacute cutaneous lupus• Livedo reticularis• Nailfold capillary changes• Vasculitic ulceration• Panniculitis• Nasal septal perforation

•Ulcerated

leukocytoclastic

vasculitis in SLE

SLE - MUSCULOSKELETAL DISEASESLE - MUSCULOSKELETAL DISEASE

• Arthralgia / Arthritis• Myalgia / Myositis• Ischemic necrosis of bone - AVN

SLE - VASCULOPATHYSLE - VASCULOPATHY

• Small vessel vasculitis

• Palpable purpura• Raynaud’s

phenomenon• Antiphospholipid

antibody syndrome

SLE - CARDIAC INVOLVEMENTSLE - CARDIAC INVOLVEMENT

• Pericarditis• Myocarditis• Endocarditis, Libman-Sacks• Accelerated atherosclerosis

SLE - PLEUROPULMONARY SLE - PLEUROPULMONARY DISEASEDISEASE

• Pleuritis/Pleural effusion• Infiltrates/Atelectasis• Acute lupus pneumonitis• Pulmonary hemorrhage• “Shrinking lung” - diaphragm

dysfunction• Subclinical restrictive disease

SLE - GASTROINTESTINAL SLE - GASTROINTESTINAL MANIFESTATIONSMANIFESTATIONS

• Anorexia, weight loss, nonspecific abdominal pain

• Pancreatitis• Mesenteric arteritis• Esophageal dysmotility

SLE – LIVER , SPLEEN & LYMPH SLE – LIVER , SPLEEN & LYMPH NODENODE

• Generalized lymphadenopathy

• “Lupoid hepatitis” vs SLE hepatic involvement

• Functional asplenia

SLE - NEUROPSYCHIATRIC SLE - NEUROPSYCHIATRIC MANIFESTATIONSMANIFESTATIONS

• 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 SLE - NEUROPSYCHIATRIC INVOLVEMENTINVOLVEMENT

Behavior/Personality changes, depressionCognitive dysfunctionPsychosisSeizuresStrokeChoreaPseudotumor cerebriTransverse myelitisPeripheral neuropathyTotal of 19 manifestations describedTotal of 19 manifestations described

SLE - RENAL INVOLVEMENTSLE - RENAL INVOLVEMENT

• Usually asymptomatic• Gross hematuria• Nephrotic syndrome• Acute renal failure• Hypertension• End stage renal failure

SLE - NEPHRITISSLE - NEPHRITIS

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

WORLD HEALTH ORGANIZATION WORLD HEALTH ORGANIZATION CLASSIFICATION OF LUPUS NEPHRITISCLASSIFICATION OF LUPUS NEPHRITIS

Class I NormalClass II Mesangial IIA Minimal alteration IIB Mesangial glomerulitisClass III Focal and segmental proliferative

glomerulonephritis

Class IV Diffuse proliferative glomerulonephritis

Class V Membranous glomerulonephritisClass VI Glomerular sclerosis

SLE - LABORATORY EVALUATIONSLE - LABORATORY EVALUATION

• Antinuclear antibody profile• Anti dsDNA abs, Sm abs• C3, C4, IgA, IgG, IgM• Direct Coomb’s, DAT• Antiphospholipid antibodies

ACLA - Anticardiolipin antibodiesLAC - Lupus anticoagulant

• CBC with Diff, U/A, CMP, TSH, ESR

Comprehensive Comprehensive Evaluation of a Child Evaluation of a Child

with SLEwith SLE• 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 Long-term Management IssuesIssues

• 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 Therapeutic Goals in SLE: Still Unmet SLE: Still Unmet

ExpectationsExpectations• 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 Treatment Regimens for LNLN

• 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- VSequential Therapies for WHO III- V• 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 Targeted Immune InterventionIntervention

• 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) blockadeCTLA41g, abatacept: binding to CD80

and CD86 prevents engagement to CD28 to T cells thereby prevents co-stimulation

• Cytokine blockadeIL10, INF-α

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

Major Clinical Syndromes Major Clinical Syndromes in SLE Requiring in SLE Requiring

VigilanceVigilance• 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 Case 1: 9 yo AAF with SLESLE

• 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 Case 1: Physical ExaminationExamination

• 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 Case 1: Laboratory InvestigationInvestigation

• Hgb 9.5 gm%, WBC 4.05, 55% PMNplatelets 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: CourseCase 1: Course• 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 Cognitive Dysfunction in SLESLE

• 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 Case 2: Learn from old experienceexperience

• 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: continuedCase 2: continued

• 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 Risk Factors of Premature CVD in cSLEcSLE

• 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, ↑ SDIStichweh, D , Curr Opin Rheumatol 16:577-587, 2004

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

Case 3: Clinical Case 3: Clinical PresentationPresentation

• 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 ResultsUltrasound Results

Clot

IVC

Clinical PresentationClinical Presentation• 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 EvaluationLaboratory Evaluation9.3 U/A: 1.015, pH 6.0,

9.7 137 >300 mg protein, moderate blood

30.7ALC – 1360

ESR - >140; CRP – 5.26C3 – 153; C4 - 21.2[Thrombotic Profile – normal][DAT – positive]ANA – positive at 1:2560; other autoantibodies all

negative[APA Profile – positive]

Pathology Findings : Pathology Findings : Class VClass V

Light Microscopy showing increased

mesangial cells.

Light Microscopy with Silver Stain

showing epimembranous

deposits.

Electron Microscopy showing

epimembranous deposits.

Antiphospholipid Antibodies in Antiphospholipid Antibodies in cSLEcSLE

• 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 Management Goals for cSLEcSLE

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

SELENASELENA• 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 SLEAdjunct Therapy for SLE• 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 Risk Factors for Damage in Childhood-Onset SLEChildhood-Onset SLE

• 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 ofLong-term Followup ofSLE Nephritis: Toronto*SLE 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 Long-Term Outcomes of Childhood-Onset SLEChildhood-Onset SLE

• 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 componentBrunner et al, Lupus 2006, in press

Conclusion(s)Conclusion(s)• 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.