Seminar-pediatric Systemic Lupus Erythematosus.pptx

Introduction
Etiology
Pathogenesis
Clinical manifestation
Diagnosis
Investigations
Treatment
Prognosis

1. Systemic Lupus Erythematosus Dr Mohiuddin Ahmad Masum Medical Officer Pediatrics, CuMCH

2. Introduction A chronic autoimmune disease Multisystem involvement Presence of circulating autoantibodies against self antigens Involves nearly every organ, most frequently- skin, joints, kidneys, blood forming cells, blood vessels, CNS

3. Epidemiology Adult 20-70/1,00,000 Children & adeloscents 1-6/1,00,000 Predominantly affects females F :M ratio 2-5 :1(Before puberty) 9 :1 (reproductive years) near pre-pubertal ratio (post- menopause ) Pediatric-onset SLE ( pSLE ) means symptoms onset before 16 or 18yrs pSLE – median age at diagnosis is 11-12yrs

4. Etiology Largely unknown Influencing factors: -Genetics -Hormonal factors -Environmental exposures Genetics: congenital deficiency of C1q, C2, C4 -Familial SLE or, other autoimmune diseases - occurance 2-5% in dizygotic twins & 25-60% in monozygotic twins

5. Hormonal : -Estrogens are likely to play role in SLE Environmental exposures: Largely unkonwn EB virus UV light exposure Drugs- procainamide , hydralazine etc.

6. Pathogenesis Dysregulation of both innate & adaptive immune system Type 1 interferon signature (85% of SLE pts): ↑ interferone - α by plasmacytoid dendritic cells → ↑expression of proinflammatory cytokines, chemokines , maturation of monocyte into myeloid dendritic cells, ↑ autoreactive B & T cells, loss of self-tolerance Other ↑ cytokines: IL-1, IL-2, IL-6, IL- 10, IL-12, IL-17, IL-21, antiTNF - α , interferon- δ , BLyS Impairment of B-cell function→imaired tolerance, ↑ autoreactivity → ↑autoantibody production Impairment of T-cell function→ ↑memory T cell, ↓T-regulatory cells →aberrant signaling & ↑ autoreactivity

7. UV ray → ↑skin cell damage/ impaired apoptosis → ↑expression of intracellular antigens(nucleic acids) → ↑autoantibody production by B-cell → immune complex formation by circulating autoantibodies & deposition in tissues → local complement activation → proinflammatory cascade → tissue damage

8. Clinical menifestations :

9. Diagnosis: ACR 1997 revised criteria Sensitivity: 77% Specificity: 99%

10. Diagnosis: SLICC 2012 classification criteria Sensitivity: 93% Specificity: 85%

11. Diagnosis: EULAR/ACR 2019 SLE classification criteria

12. Differential diagnoses:

13. Medications associated with Drug-induced lupus Definitive association : Minocycline , procainamide , hydralazine , isoniazide , penicillamine , diltiazem , interferon- α , methyldopa, chlopromazine , infliximab , adalimumab Probable association: Phenytoin , ethosuximide , carbamazepine , sulfasalazine , amioderone , quinidine , rifampine , nitrofurantoin , captopril , penicillin, tetracycline, gold, valproate , propylthiouracil

14. Investigations Complete blood count -Anemia -Leucopenia (<4000/mm³) - Lymphopenia (<1500/mm³) -Thrombocytopenia (<100,000/mm³) -ESR: raised C-reactive protein -may be mild elevated -significantly raised in associated infection Peripheral blood film -features of hemolysis may present (tear drop cells, pencil shaped cells, fragmented RBCs)

15. Direct Coomb’s Test: -may be positive Urinalysis: -R/M/E- Hematuria , proteiuria , RBC cast in lupus nephritis -24hr UTP >0.5gm/day in lupus nephritis Serum C3, C4, CH50(total hemolytic complement) -↓in active disease , improves with treatment

16. Serology : ANA- Sensitivity 95-99%, Specificity 50% Anti- dsDNA - Sensitivity 40-65%, Specificity 98%; correlate with disease activity Anti Smith antibody -Sensitivity 40-65%, Specificity 98%; doesn’t correlate with disease activity Anti- phospholipid antibody- ↑risk for venous & arterial thrombotic events Anti- histone antibody- present in majority of patients with drug induced lupus. May be present in SLE.

17. Principles of management Early diagnosis Objective disease assessment Therapy for disease burden Regular Follow up & monitoring Risk assessment for co-morbidities Patient education & partnership Therapy is individualized, practical & holistic.

18. Multidisciplinary approach needed including- Pediatrician Rheumatologist Ophthalmologist Nephrologist Psychiatrists Pulmonologist Cardiologist Management consists of 2 stages- induction of remission and maintenance

19. Treatment Counseling Sunscreen use for all patients and avoidance of prolonged direct sun exposure. Promt treatment of infection Immunization – -vaccination against influenza(annually), SARS-COV2, HPV -pneumococcal vaccination -no live vaccine Statin - primary prevention of atherosclerosis, in particularly pubertal patients with an elevated CRP Screening for depression, peer support and cognitive-behavioral therapy if needed

20. Hydroxychloroquine – recommended for all individuals with SLE when tolerated. -prevents SLE flares -improves lipid profiles -may improve mrtality and renal outcome -Potential toxicities: retinal pigmentation causing visual impairment. -annual ophthalmic examination recommended -recommended throughout pregnancy of all SLE patients -Dose : not more than 5mg/kg/day (max 400mg daily) -Duration: lifelong

21. NSAIDs - - Myalgia , arthralgia , arthritis –anti inflammatory dose e.g. Naproxen 10-15mg/kg/day -Low dose aspirin (81 mg daily)- SLE with antiphospholipid positive without h/o clot. Corticosteroids –treatment mainstay for significant menifestations of SLE Severe disease - high dose of iv methylprednisolone (30mg/kg/day upto max 1gm/day for 3 days) , followed by weekly pulses and/or high dose oral prednisolone (1mg/kg/day), upon disease impovement tapering over months.

22. Steroid sparing agents : * Persistent moderate disease including arthritis, significant cutaneous or hematilogic involvement & pleural disease- MTX, leflunomide , azathioprine . *lupus neohritis - cyclophospamide , MMF, azathioprine *significant hematologic menifestations - MMF, rituximab *most severe, life threatening SLE- iv cyclophospamide

23. Complications Renal: HTN, ESRD CNS: seizures, psychosis, organic brain syndrome, neurocognitive dysfunction CVS: atherosclerosis, myocardial infarction, cardiomyopathy , valvular disease Immune: recurrent infection, malignancy Musculoskeletal : Ostepania , avascular necrosis, compression fractures Ocular: cataracts, retinal detachment, glaucoma, blindness Endocrine: diabetes, obesity, infertility, growth failure

24. Cause of death/mortality : Within 1 st few years→infections , complications of glomerulonephritis , neuropsychiatric disease Over long term →complications of Atherosclerosis and malignancy

25. Prognosis Severity of pSLE is worse than adult onset SLE 5 yr survival rate: 99% (higher income countries), 85% (lower & middle income countries) 10 yr survival rate: 97% (higher income countries), 79% (lower & middle income countries)