CAIMS

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