Downloaded 51 times
Uploaded byMOHAMMAD NOUR AL SAEED
SLE
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems. It is more common in women and typically presents in the 2nd to 3rd decade of life. SLE results from a loss of self-tolerance by the immune system and is characterized by autoantibody production and immune complex-mediated tissue damage. Diagnosis is based on clinical criteria involving symptoms in organs like the skin, joints, kidneys, and heart. Treatment involves managing symptoms with medications like corticosteroids, antimalarials, and immunosuppressants. Prognosis has improved in recent decades but SLE can still lead to organ damage or failure if not properly treated.
More Related Content
More from MOHAMMAD NOUR AL SAEED
SLE
- 1.
- 2. A chronicmultisystem autoimmune disease of protean manifestation and variable behavior Lots of organs affected, affect any organ but skin, kidneys, serosal membrane, joints and heart stand out Lots of autoantibodies and variable clinical presentation with so many overlaps with other autoimmune diseases Reason for the development of the criteria with features ≥ 4 = diagnostic during interval of observations F : M = 9:1 Just like all autoimmune diseases Affects any age, even early childhood but common in 2nd/3rd decade of life (15-44 years), 1 in 700 women of childbearing age, 15-50 in 100, 000 of general population. Blacks > Hispanics > Asians Its all about the failure of the body to maintain self tolerance (self-tolerance means that lymphocytes should not incite an immune response against human cellular antigens i.e. non-responsiveness of immune system to substance or tissue with capacity to elicit an immune response)
- 3. PATHOPHYSIOLOGY Inherited susceptibility genes Class II MHC HLA-DQ, DR3 Complement Others Environmental triggers e.g. UVR, drugs, sex hormones, infectious agents, stress Increased burden of nuclear protein fragments, other self antigens Cellular apoptosis Activation of T helpers and B cells specific for self antigens IgG autoantibody production Immune complex and autoantibody mediated tissue injury
- 4. DIAGNOSTIC CRITERIA/CLINICAL PRESENTATION DOPAMIN RASH criteria by ACR has been supplanted by SLICC In 2015, revised criteria, both ACR/SLICC = combined. The patients with 4 points out of 16, have definite diagnosis of SLE. With 3 points highly suggestive SLE, with 2 points probable SLE and with one point possible SLE are the diagnosis.
- 5. Radiological CBC Hormonal assay HLA Renal/Skin biopsy Autoantibody screening (serology, IF, ELISA) Urinalysis LE bodies/cells in 70% patients, now history, not in use anymore. It’s a neutrophil or macrophage that has engulfed the denatured nucleus of another injured cell by the immune complex in vitro. Damaged nucleus lose their chromatin pattern = homogenous = hematoxylin/LE bodies in vivo The highly specific markers Anti-dsDNA antibodies Anti-sm antibodies (99% of people without SLE lack it)
- 7. THE AUTOANTIBODIES ANAssubtypes All ANAs – SS, Scl., MCTD, DM/PM (inflammatory myopathies) anti-nuclear RNP antibodies (U1RNP) – Sharp’s syndrome(MCTD) anti-Sm antibodies (core proteins of small nRNP particles – Smith antigen), anti-Scl-70 antibodies (DNA topoisomerase1) – Scl. anti-dsDNA antibodies (Native DNA), anti-histone antibodies – Scl. RA, DIL, MCTD antibodies to nuclear pore complexes, anti-centromere antibodies – Scl., PBC anti-sp100 antibodies - PBC anti- Jo 1 antibodies (Histidyl-Trna synthetase) - DM Each of these antibody subtypes binds to different proteins or protein complexes within the nucleus. They are found in many disorders including autoimmunity, cancer and infection. This allows the use of ANAs in the diagnosis of some autoimmune disorders like SLE, SS, scleroderma, MCTD, AIH, inflammatory myopathies (PMs, DMs) and drug induced lupus. So ANA = sensitive but not specific
- 8. Anti cytoplasmicantibodies Ribosomes (P proteins) Mitochondria Lysosomes anti-Ro (SS-A) antibodies (RNP) – SS, PBC, Celiac disease, PM, neonatal lupus + congenital heart block anti-La (SS-B) antibodies (RNP) – SS, PBC Antibodies react with various complexes of phospholipids with proteins = secondary APLS Anti-cardiolipin Lupus anticoagulant Antibodies to beta2-glycoprotein 1 Others Rhematoid factors (antibody reactive with self - IgG) C1q Heat shock proteins (hsp 70, 90) Anti-cellular antibodies; RBCs - Anemia Platelets - Thrombocytopenia WBCs – Leukopenia, lymphopenia Thyroid - Hypothyroidism Neurons – diffuse CNS lupus
- 9. DDX Overlapping autoimmunediseases – difficult to differentiate e.g. MTCD = features of SLE, RA, PMs, Scl. + high titers of anti-RNP RA lupus arthritis causes less destruction of the joints than rheumatoid arthritis. Various forms of dermatitis Neurologic disorders e.g. epilepsy, MS, psychiatry disorder Hematologic diseases e.g. ITP Drug-induced Lupus-like syndrome – chronic use and depends on drug acetylation. ANA/Anti-histone antibodies but no antibodies to dsDNA and hypocomplementemia which are all present in idiopathic SLE Infections e.g. bacterial endocarditis, histoplasmosis Primary/Idiopathic APLS – HLA DR7
- 10. MANAGEMENT/TREAMENT No cure Complete sustained remissions are rare Early diagnosis and treatment manages the symptoms and lessen the chance of permanent damage to organs or tissues. For drugs to work effectively, higher doses are needed = more side effects Non life threatening manifestations/Mild/Remittent Fever, arthralgia, myaldia, mild serositis, fatigue NSAIDs – toxicities common in SLE especially ↑ Liver enzymes, aseptic meningitis, renal impairment – watch out for it Dermatitides, fatigue, lupus arthritis Anti-malarials (TLR antagonist) like hydroxychloroquine 400 mg daily, topical/intralesional corticosteroids, quinacrine, retinoids, dapsone.
- 11. Life threatening, severelydisabling manifestations Nephritis, CNS disease, Vasculitis Corticosteroids (high dose 1-2mg/kg/day). In SLE active (divided doses every 8-12h). In SLE controlled (just 1 morning dose), then convert to alternate-day therapy with a single morning dose of short acting glucocorticoids (prednisolone 0.02 mg/kg/d) to minimize side effects. For flare-ups on the off-days, use the lowest single daily dose. Immunizations against influenza/pneumococcal infections should be done to avoid the infections due corticosteroids-induced immunosuppression. Give calcium 1000mg/day and vit D 50,000 units 3 times/week or calcitonin or bisphosphonates (alendronate) to minimize osteoporosis. To avoid steroids side effects and for those unresponsive to steroids in active SLE, agents can be used Azathioprine (least toxic) 3mg/kg/day PO, methotrexate 20 mg once/week PO or SC, Cyclophosphamide (most effective/toxic) 15 mg/kg once/month IV. PO = increase side effects give with MESNA 250 mg, mycophenolate mofetil 2.5 g/kg/day PO N.B Side effects = BM suppression, increased infection with opportunistic organism. After active SLE is controlled for a few months, taper the dose, then discontinue NB – give Ondansetron 0.15 mg/kg/dose before/after the chemotherapy to prevent chemotherapy-induced nausea and vomiting.
- 12. Some manifestationsof SLE don’t respond to immunosuppression (clotting disorders, behavioral abnormalities, end stage GN), Give anticoagulants high dose warfarin with INR maintained at 2.5-3.0, psychoactive drugs (duloxetine), renal transplantation/hemodialysis Combination therapy high dose IV of glucocorticoids + cyclophosphosmaide + azathioprine = increase risk of infections Plasmapharesis + cytotoxic agents + intravenous Immunoglobulins New/experimental therapies in patients with no response to above treatments Induce tolerance to DNA by DNA vaccination to modulate immune responses affecting the Th1, Th2 and, importantly, the T Helpers cell Interruption of T/B cell second signals with antibodies to CD40L, Immunoablation with high dose cyclophosphamide + or - autologous stem cell transplantation, anti IFN alpha (Rontalizumab , rhuMAb IFNalpha), BENLYSTA (belimumab) inhibits B-cell activating factor Voclosporin, cyclosporine analog, calcineurin inhibitor, were twice as likely to achieve complete remission than other drugs, Rituximab (treat diseases which are characterized by having too many B cells, overactive B cells, or dysfunctional B cells with CD20 on their surfaces)
- 13. Prognosis Survival inpatients with SLE is; 90-95% at 2 years 82-90% at 5 years 71-80% at 10 years 63-75% at 20 years Factors with poor prognosis are; Serum creatinine > 124 μmol/L, hypertension, nephrotic syndrome (> 2.6 g excretion of protein/24h, anemia (hb > 12.5 g/dl), hypoalbuminemia, hypocomplementemia at the time of diagnosis, low socioeconomic status Thrombocytopenia, serious CNS involvement, antibodies to phospholipids, African- American race, Male sex Infections and active SLE (renal failure) = death in 1st decade of disease Thromboembolic events = death in the 2nd decade. N.B Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic = “Invisible disease”- 4-6 years before diagnosis. SLE = GREAT IMITATOR!!!
- 14. An ongoing research……. How We are Advancing Research on Lupus: Funding Promising Research - We fund groundbreaking studies into what causes lupus, how it progresses, and better to ways to manage lupus. Making Clinical Trials More Efficient and Effective - We lead scientific initiatives to streamline and modernize how clinical trials are designed and conducted so they can be more efficient and effective. Rallying Support to Increase Lupus Research Funding - We conduct comprehensive efforts to stimulate new federal funding and support for lupus research. - LUPUS FOUNDATION OF AMERICA, INC.
- 15. Reference Harrison’s principlesof internal medicine http://www.merckmanuals.com/professional/musculoskeletal-and-connective- tissue-disorders/autoimmune-rheumatic-disorders/systemic-lupus- erythematosus-sle. http://www.amjmed.com/article/0002-9343(65)90199-3/abstract. American Journal of Medicine. http://www.lupusresearchinstitute.org/lupus-news. Dhar JP, Sokol RJ. Lupus and pregnancy: complex yet manageable. Clin Med Res. 2006 Dec;4(4):310-21. Uva L, Miguel D, Pinheiro C, Freitas J, et al. Cutaneous Manifestations of Systemic Lupus Erythematosus. Autoimmune Diseases. 2012; 2012:15. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.
- 16.