2. SLE PRESENTATION Year 4 Internal Medicine Notes OmpathStudy

2. SLE PRESENTATION Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.3 / NGUGI -- Slide 1 SYSTEMIC LUPUS ERYTHEMATOSUS BETTLYNNE CHEPCHUMBA LEAH MUIRURI Slide 2 OBJECTIVES Definition Epidemiology Risk factors Pathophysiology Clinical features Diagnostic criteria Differential diagnosis Treatment Slide 3 Definition It is a Chronic Systemic autoimmune disorder, where the body produces autoantibodies against (ALL) most organs: skin, kidney, joints, blood cells and nerves. It is protean in its manifestation and follows a relapsing and remitting course(series of remissions and exacerbations) Slide 4 Epidemiology Prevalence: 1-6/100,000 Childhood onset – 20% of all cases below 15 yrs Peak incidence: 14 – 45 yrs Black White Female Male 10: 1 with 1 in 700 women of child bearing age affected Median age at diagnosis – 11 – 12 years Slide 5 Risk factors 1.ENVIRONMENTAL FACTORS Ultraviolet light(UVB)which drives apoptosis, increasing the amount of IL-1 production which causes the alteration of DNA, increasing its immunogenicity.\n2.FAMILY HISTORY -5-13% of SLE cases have been linked to a family history of a relative with SLE -The risk of a child developing SLE born from a mother or father with lupus is at around 2-5% 3.GENETIC FACTORS Mutation in HLA DR3, HLA B3 or a deficiency in C2,C4 and C4q. 4. ETHNICITY Most predisposed are Africans, African-American and Asian-American. Slide 6 5.IMMUNOLOGIC FACTORS -(Type 3 hypersensitivity)Circulation of immune complexes that then deposit in organs. Leads to inflammation and tissue damage due to complement activation. -Increased expression of molecules contributing to B and T cell activation. These cells become hyperactive -Overproduction of IL-6 and IL-10 -Failure of self tolerant B cells -Autoantibodies against DNA 6.INFECTION -Certain viruses such as EBV and CMV may initiate or flare SLE. These viruses cause activation of B and T cells by molecular mimicry of an external antigen 7.DRUGS -Isoniazid, hydralazine, procainamide, beta-blockers, penicillamine can lead to drug-induced lupus that may resemble SLE clinically, however renal and neurological complications are rarely seen. 8.HORMONES -Estrogen Slide 8 Pathophysiology -Specific cause is unknown. However the fundamental defect in SLE is a failure of the mechanisms that maintain self-tolerance. -Primarily there is formation and deposition of immune complexes in organs such as the kidney, brain and skin which leads to cell injury and tissue damage. This process results in apoptosis which causes increased cell death\nand disturbance in immune response by increasing the burden of nuclear antigens. -Defective cell tolerance leads to: B – cells: Activated and produce autoantibodies against the nuclear antigens T – cells: Auto reactive T cell activation. Slide 9 Subsequent TLR engagement causes further cellular activation, cytokine production and augments antibody synthesis causing more apoptosis. The most affected organs are; -Skin -Blood vessels -Kidneys(most severely affected) -Connective tissue Slide 10 Spectrum of autoantibodies in SLE ANAs are typically detected by indirect immunofluorescence i.e. homogenous, peripheral, speckled and nucleolar), though nonspecific, can suggest the type of circulating antibody. ANAs also occur in other autoimmune disorders and in up to 10% of normal individuals but anti-double –stranded DNA and anti-Smith antigen antibodies strongly suggest SLE. Beside ANAs, SLE patients produce antibodies directed against blood elements(WBCs, RBCs and platelets) Morever,40-50% of SLE patients have antibodies to phospholipid-associated proteins(antiphospholipid antibodies). Some bind to cardiolipidin antigen, giving rise to false-positive results for syphilis Others interfere with/prolong in vitro coagulation assays: these so-called lupus anticoagulants actually exert a procoagulant effect in vivo, causing recurrent vascular thrombosis, miscarriages and cerebral ischemia(secondary antiphospholipid antibody syndrome) Slide 11 Clinical features Slide 12 Clinical features – Constitutional Fever\nFatigue Anorexia Weight loss Lymphadenopathy\nRaynauds phenomenon Slide 13 Clinical features Mucocutaneous:\nAcute photosensitivity rash, malar rash Chronic discoid lupus erythematosus (DLE) Subacute cutaneous erythematosus (SCLE)\nPhotosensitivity rash. Cutaneous Vasculopathy:\nSmall vessel vasculopathy or raynaud’s phenomena - petechiae, palpable purpura, digit ulcers, gangrene,\nUrticaria\noral and nasal ulcers Panniculitis\nAlopecia Slide 14 Malar erythema Malar erythema /malar rash is a “butterfly shaped” red rash over the cheeks and across the bridge of the nose. -The rash are made worse by exposure to the sun. Slide 17 Ocular: Conjunctivitis Photophobia Blurred vision\nPapilloedema Retinal vasculitis Optic neuritis Episcleritis\nScleritis Endocrine\n-Steroid induced diabetes, -Menstrual abnormalities Slide 18 Cardiac: -Pericarditis(most common manifestation) -Myocarditis -Cardiac failure