This document provides an overview of systemic lupus erythematosus (SLE) in children and adolescents. Key points include: SLE is an autoimmune disease affecting multiple organs, most commonly the skin, joints, kidneys, blood cells, blood vessels and central nervous system. Diagnosis requires meeting 4 out of 11 classification criteria. Management involves controlling disease activity and flares with corticosteroids and immunosuppressive drugs like hydroxychloroquine and azathioprine. Prognosis has improved over time but organ involvement like lupus nephritis can be severe and require aggressive treatment.

1. SYSTEMIC LUPUS
ERYTHEMATOSUS
BY DR. MADHURI REDDY
PAEDIATRICS 1STYR PG

2. OBJECTIVES
 EPIDEMIOLOGY
 ETIOPATHOGENESIS
 CLINICAL MANIFESTATIONS
 CRITERIA FOR DAIGNOSIS
 LABORATORY FINDINGS
 TREATMENT
 PROGNOSIS
 NEONATAL LUPUS

3.  Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized
by multisystem inflammation and the presence of circulating autoantibodies
directed against self-antigens .
 Nearly every organ may be affected, most commonly involved are the skin, joints,
kidneys, blood-forming cells, blood vessels, and the central nervous system
 children and adolescents with SLE have more severe disease and more widespread
organ involvement.

4. EPIDEMIOLOGY
 Pediatric SLE (pSLE) represents approximately 15-20% of all SLE patients
 It is more common in females than in males, with a female to male ratio varying
from 2.3:1 to 9:1.
 incidence of SLE with onset before age of 19 years is between 6 and 18.9 cases
per 100,000 .
 Diagnosis of SLE is rare before the age of 10, and the average age at
presentation is 12.1 years6-11.
 The survival rate for SLE has improved dramatically over the past 50 years, with a
5-year survival rate increasing from 50% in 1955 to more than 90% in 20048

5. ETIOPATHOGENESIS
 Genetic factors
1. congenital deficiencies of C1q , C2 and C4
2. HLA B 8, HLA DR 2, HLA DR3
 Immune alterations :
1. The ability to produce pathogenic autoantibodies;
2. lack of T-and B-lymphocyte regulation.
3. Defective clearance of autoantigens and immune complexes by the immune system.
 Hormonal factors
 Environmental factors

7. CLINICAL FEATURES
 Clinical characteristics and organ involvement very depending on age of onset,
gender and race .
 Constitutional Fatigue, anorexia, weight loss, fever, lymphadenopathy.

8. MUSCULOSKELETAL
 Arthritis, myositis, tendonitis, arthralgias, myalgias, avascular necrosis, osteoporosis
 Arthritis occurs in more than ¾ of pediatric patients with SLE - symmetric non erosive,very
painful polyarthritis.
 Arthritis can be only presenting manifestation of SLE
 Treatment-induced musculoskeletal complications include avascular necrosis, osteoporosis and
growth failure.

10. CUTANEOUS MANIFESTATIONS
 Malar rash hall mark of SLE
 discoid (annular) rash
 photosensitive rash
 cutaneous vasculitis (petechiae, palpable purpura, digit ulcers, gangrene, urticaria)
 livedo reticularis
 periungual capillary abnormalities
 Raynaud phenomenon, alopecia
 oral and nasal ulcers, panniculitis, chilblains .

12. RENAL MANIFESTATIONS
 Renal involvement represent the first clinical manifestation of the disease in 60-80%
of children with SLE
 About 80% of children and adolescents develop renal abnormalities generally in
the first year after diagnosis
 Renal Hypertension, proteinuria, hematuria, edema, nephrotic syndrome, renal
failure

13. WHO CLASSIFICATION OF LUPUS NEPHRITIS
 I.Minimal mesangial LN : No renal findings
 II. Mesangial proliferative LN : Mild clinical renal disease; minimally active urinary
sediment; mild to moderate proteinuria (never nephrotic) but may have active
serology
 III. Focal proliferative LN <50% glomeruli involved
A. Active
A/C. Active and chronic
C. Chronic
More active sediment changes; often active serology; increased proteinuria
(approximately 25% nephrotic); hypertension may be present; some evolve into class
IV pattern; active lesions require treatment, chronic do not

14.  IV. Diffuse proliferative LN : (>50% glomeruli involved); all may be with segmental
or global involvement (S or G)
A. Active
A/C. Active and chronic
C. Chronic
Most severe renal involvement with active sediment, hypertension, heavy proteinuria
(frequent nephrotic syndrome), often reduced glomerular filtration rate; serology very
active. Active lesions require treatment
 V. Membranous LN glomerulonephritis : Significant proteinuria (often nephrotic)
with less active lupus serology
 VI. Advanced sclerosing LN : More than 90% glomerulosclerosis; no treatment
prevents renal failure

16. CARDIOVASCULAR
 Pericarditis ( most common form of cardiac involvement )
 Myocarditis,
 Conduction system abnormalities
 Libman-Sacks endocarditis
 Identified risk factors for premature atherosclerosis in pSLE include: Dyslipidemia,
high levels of homocystein, presence of aPL, LAC, hypertension, hyperinsulinemia,
nephritic range proteinuria, upregulated CD40-CD40 ligand interactions and
steroid-induced obesity.

17. LIBAMAN - SACKS ENDOCARDITIS
 Small ( 1-4 mm)
 Single or multiple
 Pink warty ( verrucous ) vegetations
 sterile
 Located on undersurface of AV
valves , chords , mural endocardium.

18. NEUROLOGIC
 Neuropsyciatric SLE occuring in 20-45% of children and adolescents, is the third most
common cause for mortality in Psle
 CNS involvement occurs within the first year of disease in approximately 75% to 80% of
patients.
 Seizures
 Psychosis
 Cerebritis
 Stroke, transverse myelitis, depression, cognitive impairment
 Headaches, migraines, pseudotumor,
 Peripheral neuropathy (mononeuritis multiplex) , chorea, optic neuritis,
 Cranial nerve palsies, acute confusional states, dural sinus thrombosis

19. PULMONARY
Pleuritis ( most common )
Interstitial lung disease
pulmonary hemorrhage
pulmonary hypertension
pulmonary embolism
 Pulmonary function abnormalities were found in up to 40% of pSLE patients with no
evidence of clinical symptoms or radiographic changes .
 The most frequent pattern observed was lung restrictive disease.

20. HEMATOLOGIC
 Immune-mediated cytopenias (hemolytic anemia, thrombocytopenia or
leukopenia)
 Autoimmune thrombocytopenia is the initial manifestation in up to 15% of the
pediatric cases
 Anemia of chronic inflammation
 Hypercoagulability
 Thrombocytopenic thrombotic microangiopathy
 Antiphospholipid antibodies (aPL) are present in 75% of pSLE patients
 patients with SLE and aPL, specifically lupus anticoagulant (LAC), are at high risk of
developing thromboembolic events.

21. Gastroenterology :
 Hepatosplenomegaly
 pancreatitis,
 vasculitis affecting bowel
 protein-losing enteropathy, peritonitis
Ocular
 Retinal vasculitis, scleritis, episcleritis
 papilledema, dry eyes, optic neuritis

22. ACR REVISED CLASSIFICATION CRITERIA
 PRESENCE OF 4 OUT OF FOLLOWING 11 CRITERIA :
 Malar rash
 Discoid rash
 Photosensitivity
 Oral or nasal ulcers
 Arthritis Nonerosive, ≥2 joints
 Serositis Pleuritis, pericarditis or peritonitis
 Renal manifestations : Consistent renal biopsy
Persistent proteinuria or renal casts
 Seizure or psychosis
 Hematologic manifestations : Hemolytic anemia ,Leukopenia (<4,000 leukocytes/mm3)
Lymphopenia (<1,500 leukocytes/mm3) , Thrombocytopenia (<100,000 thrombocytes/mm3)
 Immunologic abnormalities : Positive anti–double-stranded or anti-Smith antibody False-
positive rapid plasma regain test result
positive lupus anticoagulant test result, or elevated anticardiolipin immunoglobulin (Ig) G or IgM
antibody
 Positive antinuclear antibody test result

23. SLICC CRITERIA
 CLINCAL CRITERIA :
 The presence of 4 criteria ( including atleast 1 clinical and 1 immunological crieteria )
 Acute cutaneous lupus : Malar rash, bullous lupus, toxic epidermal necrolysis variant of
SLE, maculopapular lupus rash, photosensitive lupus rash, or subacute cutaneous lupus
 Chronic cutaneous lupus : Classic discoid rash, lupus panniculitis, mucosal lupus, lupus
erythematous tumidus, chilblains lupus, discoid lupus/lichen planus overlap
 Oral or nasal ulcers
 Nonscarring alopecia
 Synovitis (≥2 joints)
 Serositis : Pleurisy or pericardial pain ≥1 day, pleural effusion or rub, pericardial
effusion or rub, ECG evidence of pericarditis

24.  Renal : Presence of red blood cell casts or urine protein/creatinine ratio representing >500
mg protein/24 hours
 Neurologic : Seizures, psychosis, mononeuritis multiplex, myelitis, peripheral or cranial
neuropathy, or acute confusional state
 Hemolytic anemia
 Leukopenia (<4,000/mm3) or lymphopenia (<1,000/mm3)
 Thrombocytopenia (<100,000/mm3

25. IMMUNOLOGIC CRITERIA
 Positive antinuclear antibody
 Positive double-stranded DNA antibody
 Positive anti-Smith antibody
 Antiphospholipid antibody positivity
Positive lupus anticoagulant
false-positive test for rapid plasma regain
medium to high titer anticardiolipin antibody level (IgA, IgG, IgM)
or positive anti–B2-glycoprotein I antibody (IgA, IgG, IgM)
 Low complement Low C3, C4, or Ch50 level
 Positive direct Coombs test (in the absence of hemolytic anemia

26. DIFFERENTIAL DIAGNOSIS
 Infections ( sepsis, EBV , parvovirus B 19 , endocarditis )
 Malignancies ( leukemia and lymphoma )
 Post streptococcal glomerulonephritis
 Systemic onset juvenile idiopathic arthritis
 Drug induced lupus.

27. DRUG INDUCED LUPUS
DEFINITE ASSOCIATION
 Minocycline
 Procainamide,
 Hydralazine
 Isoniazid
 Penicillamine,
 Diltiazem
 Interferon-α
 Methyldopa
 chlorpromazine
 Etanercept
 Infliximab,
 Adalimumab

28. PROBABLE ASSOCIATION
 Phenytoin, ethosuximide, carbamazepine
 Sulfasalazine, amiodarone, quinidine, rifampin
 Nitrofurantoin, beta blockers, lithium, captopril, interferon-γ
 Hydrochlorothiazide, glyburide, docetaxel, penicillin, tetracycline
 Statins, gold, valproate, griseofulvin, gemfibrozil, propylthiouracil
 Drug-induced lupus affects males and females equally.
 A genetic predisposition toward slow drug acetylation may increase the risk of drug-
induced lupus
 Hepatitis, which is rare in SLE, is more common in drug-induced lupus.
 Circulating anti histone antibodies

29. LABORATORY FINDINGS
 Anti nuclear antibody – high sensitivity , poorly specific
 Anti–double-stranded DNA - Correlates with disease activity, especially nephritis, in
some with SLE
 Anti-Smith antibody -Specific for the diagnosis of SLE
 Antiribonucleoprotein antibody -
Increased risk for Raynaud phenomenon and pulmonary hypertension
High titer may suggest diagnosis of mixed connective tissue disorder
 Anti-Ro antibody (anti-SSA antibody)
Associated with sicca syndrome
May suggest diagnosis of Sjögren syndrome

30.  Anti La antibody
Increased risk of neonatal lupus in offspring (congenital heart block)
May be associated with cutaneous and pulmonary manifestations of SLE
May be associated with isolated discoid lupus
 Antiphospholipid antibodies (including anticardiolipin antibodies) Increased risk
for venous and arterial thrombotic events
 Antihistone antibodies Present in a majority of patients with drug-induced
lupus
May be present in SLE

31. EACH CLINIC VISIT
 CBC with differential count
 ESR and CRP
 Creatinine / albumin/ electrolytes
 Urinalysis
 Aldolase and CPK
 Liver function
 CH 50 / C3 /C4
 Anti ds DNA antibody
 Blood pressure

32. EVERY 6 MONTHS
 24 hr urine test
 Anti cardiolipins
 Lupus anticoagulant
 Phophatidyl serine
 Apolipoporoteins
 Beta 2 glycoproteins
 PT / APTT
 Lipid profile
 Eye examination

33. EVERY 12 MONTHS
 CXR
 ECG
 CHEST CT
 PFTS with diffusion coefficient
 MRI BRAIN
 DEXA SCAN

34. MANAGEMENT
 Goals of treatment are to:
prevent flares
treat flares when they occur
minimize organ damage and complications
 Corticosteroids (Mainstay of SLE treatment)
 To rapidly suppress inflammation
 Usually start with high-dose IV pulse and convert to PO steroids with goal of
tapering .
 Commonly used: prednisone, hydrocortisone, methylprednisolone, and
dexamethasone
 Steroid sparing immunosuppressive drugs - methotrexate , leflunomide
,azathioprine , mycophenolate mofetil ,cyclophosphamide , belimumab.

35. CONSERVATIVE MANAGEMENT
 For those w/out major organ involvement.
 NSAIDs: to control pain, swelling, and fever
 Caution w/ NSAIDS though. SLE pts are at increased risk for aseptic meningitis
 Antimalarials: Generally to treat fatigue joint pain, skin rashes, and inflammation of
the lungs
 Commonly used: Hydroxycholorquine
 Used alone or in combination with other drugs
 Statins – for primary prevention of atherosclerotic disease in pubertal pts with
elevated CRP .
 Routine immunization – annual influenza and pneumococcal vaccines .

36.  Corticosteroids Disease flare, major organ involvement
 Hydroxychloroquine Prevention of disease flares, skin and joint manifestations
 Azathioprine Lupus nephritis,
 Cyclophosphamide Life-threatening complications (nephritis, NP-SLE, pulmonary
hemorrhage)
 Methotrexate Arthritis, lupus nephritis (in conjunction with CYC)
 Aspirin Positive anti-antiphospholipid antibodies
 NSAIDS Joint manifestations , pleuritis, pericarditis
 Cyclosporin Lupus nephritis
 Vitamin D , calcium Prevention of osteoporosis
 Biphosphonates Osteoporosis
 MMF Lupus nephritis

37. TREATMENT OF LUPUS NEPHRITIS
 prednisone at a dose of 1-2 mg/kg/day in divided doses followed by a slow
steroid taper over 4-6 mo beginning 4-6 wk after achieving a serologic remission.
 For severe forms of nephritis (WHO classes III and IV), induction therapy consists
of 6 consecutive monthly intravenous infusions of cyclophosphamide at a dose of
500-1,000 mg/m2
 Pulse intravenous methylprednisolone (1000 mg/m2) is also used in addition to
oral corticosteroids.
 Maintenance therapy of lupus nephritis – mycophenolate mofetil , every 3 mo IV
cyclophosphamide , or azathioprine for 12 months .

38. COMPLICATIONS AND PROGNOISIS
 Most common cause of death in SLE include infections , lupus nephritis ,
neuropsychiatric disease .
 Over long term ,most common causes of mortality include complications of
atherosclerosis and malignancy .
 Severity of pediatric SLE is worse than adult onset SLE .
 5 yr survival rate for pediatric SLE is 95 % with 10 yr survival rate 80 – 90 %.

39. NEONATAL LUPUS
 Characteristic annular or macular rash typically affecting the face (especially the
periorbital area), trunk, and scalp.
 The rash - 1st 6 wk of life after exposure to ultraviolet light
 lasts 3-4 mo; however, it can be present at birth.
 Infants may also have cytopenias and hepatitis
 most feared complication is congenital heart block
 Conduction system abnormalities range from prolongation of the PR interval to
complete heart block, with development of progressive cardiomyopathy in the most
severe cases.
 The noncardiac manifestations of neonatal lupus are usually reversible, whereas
congenital heart block is permanent.

41.  With cardiac pacing, children with conduction system disease in the absence of
cardiomyopathy have an excellent prognosis.
 If the conduction defect is not addressed, affected children are at risk for exercise
intolerance, arrhythmias, and death .

42. SUMMARY
 Pediatric systemic lupus erythematosus (pSLE) is a chronic mutisystemic
autoimmune disease with complex clinical manifestations .
 Pathogenesis of SLE involves a combination of environmental, hormonal and
genetic factors .
 Malar rash is the hall mark of SLE.
 Arthritis occur in more than ¾ th of patients with SLE .
 Class 1V is the most common and most severe type of lupus nephritis .
 Anti ds DNA Ab are more specific .
 Corticosteroids are main stay of treatment. 5 yr survival rate for pediatric SLE is 95
% with 10 yr survival rate 80 – 90 %.

43. REFERENCES
 NELSON TEXTBOOK OF PEDIATRICS SOUTH ASIAN 1ST EDITION
 ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE 9 TH EDITION