Pediatric systemic lupus erythematosus

Pediatric SLE

1. Pediatric Systemic Lupus Erythematosus Dr.C.S.N.Vittal Associate Professor of Pediatrics ASRAM

2. SLE has been classically described as a prototypic autoimmune disease with a wide array of clinical manifestations and characterized by the production of auto-antibodies to components of the cell nucleus. Gilbert et al . Pediatric Rheumatology 2014, 12:16 Systemic Lupus Erythematosus

3. SLE - Historical Classical Neoclassical Modern First description of the cutaneous disorder; term "lupus" was coined. "lupus" that means wolf in Latin. 13 th Century physician Rogerius 1872: Moriz Kaposi : description of the disease’s systemic or disseminated manifestations, two forms of the disease — what we know as systemic lupus erythematosus and discoid lupus Discovery of the LE cell in bone marrow in 1948   by Malcolm Hargraves 1957 : first anti-DNA antibody

4. Female:Male = 9:1, but before puberty it is 3:1 5 pSLE makes 20% of all cases 1 Incidence <15 yrs : 0.5-0.6 per 100,000 persons 2 Prevalence 4 – 250 cases per 100, 000 persons 3 More than 90% cases of SLE occur in women 4 SLE - Epidemiology

5. SLE - ETIOPATHOGENY IRF 5 ,

6. SLE

7. SLE Pathology The LE cell is a neutrophil that has engulfed the antibody-coated nucleus of another neutrophil. LE cells may appear in rosettes where there are several neutrophils vying for an individual complement covered protein. Immune complexes within the dermal–epidermal junction. “lupus band test” which is specific for SLE.

8. Malar rash Naso -oral ulcers Photosensitive rash Discoid rash Arthritis Pleuritis or pericarditis Proteinuria (>500 mg/d) or evidence of nephritis in urinalysis Hemolytic anemia, thrombocytopenia , leukopenia , or lymphopenia Seizure or psychosis Positive ANA finding IMMUNOLOGIC ABNORMALITIES: Positive anti– dsDNA , anti-Smith, or antiphospholipid antibody / lupus anticoagulant The Systemic Lupus International Collaborative Clinics (SLICC) recently published a modification of the ACR criteria .   Lupus patients meet 4 criteria with at least 1 clinical and 1 immunologic criterion or with biopsy-proven nephritis in association with positive ANA and anti- dsDNA The ACR’s ( American College of Rheumathology ) diagnostic criteria for SLE :

9. S erositis O ral ulcers A rthritis P hotosensitivity B lood disorders R enal manifestations A NAs I mmunological phenomena N eurological disorder M alar rash D iscoid rash ACR mnemonic of SLE diagnostic criteria ----" SOAP BRAIN MD " 

10. Systemic lupus erythematosus (SLE), most common form (70%) Cutaneous lupus erythematosus (CLE) – (about 10%) Drug-induced lupus Neonatal lupus  Lupus – Types

11. SLE

12. SLE – Clinical Mucocutaneous Manifestations: 76% Joint Problems : Malar rash - butterfly-like redness Discoid lupus Vasculitis (purpura, petechiae) Raynaud ’ s phenomenon Nail involvement Alopecia Periungual erythema/ Livedo reticularis Photosensitivity Oral/ nasal ulcers Intermittent arthralgias to sudden inflammation of multiple joints occur in about 90% of people In long-standing disease, marked joint deformity may occur ( Jaccoud's arthropathy ) but is rare. Symptoms may remain

13. Malar rash - butterfly-like redness

14. Vasculitis in SLE

15. Discoid rash

16. SLE – Clinical Pulmonary Findings ( 5-67%) Cardiovascular Findings May be subclinical (abnormal PFTs) Pleuritis Pleural effusion Pneumonitis Pulmonary hemorrhage Pulmonary hypertension Restrictive lung disease Pericarditis Myocarditis Sterile valvular vegetations ( Libman Sach’s ) Arrhythmias Cor pulmonale Vasculitis Atherosclerosis / Coronary Heart disease Dyslipoproteinemias

17. SLE – Clinical Neuropsychiatric Manifestations ( 20-40% ) Second to nephritis as most common cause of morbidity & mortality Can occur at any time; even at presentation COMMON Depression, organic brain syndrome, functional psychosis, headaches, seizures, cognitive impairment, dementia, coma OCCASIONAL Cerebral vascular accidents, aseptic meningitis, peripheral neuropathy, cranial nerve palsies RARE: Paralysis, transverse myelopathy, chore

18. SLE – Clinical Hematologic Findings Leukopenia, especially lymphopenia Anemia mild to moderate, due to chronic disease and mild hemolysis severe, uncommon (5%), due to immune mediated hemolysis (Coombs +) Thrombocytopenia Bone marrow suppression / arrest -- very rare Coagulopathy – prolonged PTT

19. SLE – Clinical Renal Findings Most common cause of morbidity & mortality Glomerulonephritis – at least 75% Microscopic or gross hematuria Proteinuria, including nephrotic syndrome Hypertension Decreased GFR Renal failure (up to 30-50% of children prior to 1980) Renal biopsy predictive of potential for renal damage

20. International Society of Nephrology 2003 Revised Classification of SLE Nephritis Class Classification Features Class I Minimal mesangial Normal light microscopy findings; abnormal electron microscopy findings Class II Mesangial proliferative Hypercellular on light microscopy Class III Focal proliferative < 50% of glomeruli involved Class IV Diffuse proliferative =50% of glomeruli involved; classified segmental or global; to be treated aggressively Class V Membranous Predominantly nephrotic disease may occur with class III or IV Class VI Advanced sclerosing =90% of glomeruli involved without residual activity   Chronic lesions and sclerosis

21. Neonatal Lupus Passive transplacental transfer of maternal anti-Ro/SSA and anti-La/ SSB antibodies causes the transient skin lesions Characteristic annular or macular rash typically affecting the face, trunk & scalp – usually clear by 6 mo age Ultraviolet light may exacerbate or initiate cutaneous lesions. Cytopenias and Cholestatic liver disease Congenital heart block (30%)- most feared complication Annular plaque

22. SLE - Laboratory Findings Cytopenias (anemia, thrombocytopenia, leukopenia) Elevated ESR, CRP, Immunoglobulins Hypoalbuminemia Proteinuria; RBCs, casts in urine Decreased creatinine clearance Low complement levels (C3/ C4) Autoantibodies

23. Auto-antibodies ANA - Sensitive but not specific, 95-98% pts positive Against nuclear components of the cell Other : Anti dsDNA : high specificity for lupus (over 80%) RNP assoc w/ MCTD ( Mixed connective-tissue disease ) , Anti Smith Abs : specific for SLE Ro/ La (SS-a/ SS-b): neonatal lupus, Sjogren ’ s Anti Histone Abs : drug induced lupus

24. SLE - Treatment MILD DISEASE: Rashes, arthralgias, leukopenia, anemia, arthritis, fever, fatigue Treatment: NSAIDs low dose corticosteroids (< 60 mg/day) antimalarials (hydroxychloroquine)

25. SLE - Treatment MODERATE DISEASE: MILD + OTHER SYSTEM INVOLVEMENTS Treatment: Prednisone 1-2 mg/kg/day, NSAIDS, Antimalarials, Azathioprine

26. SLE - Treatment SEVERE DISEASE: Severe, life-threatening organ system involvement (e.g. Class IV lupus ne­phritis, myocarditis, encephalopathy) High dose corticosteroids (2-3 mg/kg/day) Immunosuppressives : IV pulse methyl prednisolone / dexamethasone OR Monthly pulses of Cyclophosphamide), Plasmapheresis, Anticoagulation where appropriate

27. Management of Pediatric SLE General Use high-SPF sunscreen throughout the year. Encourage good sleep and nutritional patterns. Address psychological aspects of disease/treatment. Prescribe calcium and vitamin D supplements Immunize against pneumococcus . Anticoagulant if evidence of antiphospholipid antibody is present Perform annual ophthalmologic evaluations Treat dyslipoproteinemia when present. Maintain good blood pressure control in those with hypertension

28. Summary

29. Dr C.S.N.Vittal Thank You