Autoimmune Disorders Flashcards
Systemic Lupus Erythematosus
Chronic, systemic autoimmune disease.
Flares and remissions.
Classically middle-aged females, esp African American and Hispanics.
Antigen-antibody complexes damage multiple tissues (type 3 HSR).
Tx: NSAIDs, steroids, immunosuppressants, hydroxychloroquine.
SLE Findings
Non-specific: fever, wt loss, fatigue, lymphadenopathy, Raynaud.
RASH OR PAIN:
-Rash (malar or discoid)
-Arthritis (non erosive)
-Serositis (pleurites or pericarditis)
-Hematologic disorders (anemia, thrombocytopenia, leukopenia - type 2 HSR)
-Oral/nasopharyngeal ulcers
-Renal disease (Lupus nephritis is glomerular deposition of anti-DNA immune complexes and can be nephritic w HTN and hematuria or nephrotic w proteinuria - most common is diffuse proliferative glomerulonephritis)
-Photosensitivity
-Antinuclear antibodies
-Immunologic disorder (anti-dsDNA, anti-Sm, antiphospholipid)
-Neurologic disorder (seizures, psychosis)
Libman-Sacks Endocarditis: nonbacterial verrucous thrombi on both sides of mitral or aortic valve
SLE Antibodies
Antinuclear antibodies (ANA) - sensitive, not specific
Anti-dsDNA antibodies - specific, poor prognosis (renal disease)
Anti-Smith antibodies - specific, not prognostic
Antihistone antibodies - sensitive for drug-induced lupus (hydrazine, procainamide, isoniazid)
Antiphospholipid antibodies - associated (in 1/3 of patients w SLE)
Also, decreased C3, C4, CH50 due to immune complex formation.
Antiphospholipid syndrome
Antiphospholipid antibody is autoantibody directed against proteins bound to phospholipids.
Primary or secondary autoimmune disorder.
Hypercoagulable state due to antiphospholipid antibodies.
Arterial and venous thrombosis.
-DVT
-spontaneous abortion - placental thrombosis
-stroke - cerebral thrombosis
Requires life-long anticoagulation.
Antiphospholipid antibodies:
-Anticardiolipin - false + of syphilis screening VDRL/RPR
-Anti-beta2-glycoprotein I
-Lupus anticoagulant - falsely elevated PTT
Sjogren syndrome
Autoimmune destruction of lacrimal and salivary glands.
Lymphocyte-mediated damage (type 4 HSR) w fibrosis.
Older females (40-50).
Dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia): “Can’t chew a cracker, dirt in my eyes.”
Inflammatory joint pain.
Bilateral parotid enlargement.
Complications: dental caries, MALT B cell lymphoma (unilateral parotid enlargement)
ANA and anti-ribonucleoprotein antibodies (anti-SSA/Ro, anti-SSB/La).
Lymphocytic sialadenitis (inflammation of salivary gland) on lip biopsy.
Anti-SSA is risk for delivering babies w neonatal lupus and congenital heart block.
Systemic Sclerosis (Scleroderma)
Triad: autoimmunity, noninflammatory vasculopathy, and collagen deposition w fibrosis.
Sclerosis of skin - puffy, taut, w/o wrinkles, fingertip pitting.
Sclerosis of renal, pulmonary (death!), cardiovascular, GI systems.
Diffuse and Limited types.
Diffuse Scleroderma
Widespread skin involvement.
Rapid progression.
Early visceral involvement.
Assoc w anti-Scl-70 antibody (anti-DNA topoisomerase I antibody).
Limited Scleroderma
Limited skin involvement - finger and face. More benign clinical course. Anti-centromere antibody. CREST syndrome: Calcinosis Raynaud Esophageal dysmotility Sclerodacty Telangiectasia
Mixed Connective Tissue Disease
Features of SLE, scleroderma, and polymyositis.
Assoc w anti-U1 ribonucleoprotein antibodies (speckled ANA analog).
Hyperacute rejection
Preformed antibodies react to donor antigens and activate complement.
Type 2 HSR.
Reaction within minutes.
Widespread thrombosis of graft –> ischemia and necrosis.
Removal of graft req’d.
Avoid by only transplanting with HLA or ABO compatible.
Acute rejection
Cellular mech: host cytotoxic T cells (CD8+) attack donor MHCs. Type 4 HSR.
Humoral mech: post-transplant generation of antibodies that target antigens on the donor tissue. Type 2 HSR.
Weeks-months in onset.
Vasculitis of graft vessel with dense interstitial lymphocytic infiltrate.
Tx: steroids and immunosuppressants.
Chronic rejection
CD4+ T cells respond to peptides presented by recipient APCs presenting donor peptides.
Type 2 and 4 HSR (cellular and humoral components).
Months-years.
T cells secrete cytokines –> proliferation of vascular smooth muscle and endothelial cells –> arteriosclerosis.
Parenchymal fibrosis.
Most common chronic rejections:
-bronchiolitis obliterans - lung
-accelerated atherosclerosis - heart
-chronic allograft nephropathy - kidney
-vanishing bile duct syndrome - liver
Think sclerosis and fibrosis and passageways becoming smaller.
Graft-vs-Host disease
Grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells –> severe organ dysfunction.
Type 4 HSR.
Usually seen in bone marrow or liver transplants.
Symptoms:
-maculopapular rash
-jaundice
-diarrhea
-hepatosplenomegaly
Used in bone marrow transplants for leukemia when trying to kill host tumor cells.
Rheumatoid Arthritis
Chronic, systemic autoimmune disease of joints.
Women late child-bearing age.
HLA-DR4.
Synovitis –> pannus (inflamed granulation tissue).
Type 3 (RF immune complexes in synovium) and 4 (activated CD4+ T cells in synovium) HSR.
Morning stiffness improves w activity.
Symmetric involvement of joints - PIP (swan-neck), wrists (radial deviation), elbows, ankles, knees - DIP spared.
Joint space narrowing, loss of cartilage, osteopenia.
Non-specific, systemic symptoms.
Rheumatoid nodules - central zones of necrosis surrounded by epithelioid histiocytes.
Vasculitis.
Baker cyst - bursa swelling.
Rheumatoid factor - IgM autoantibody against Fc portion of IgG - non-specific.
Anti-cyclic citrullinated peptide antibody - more specific.
Neutrophils and high protein in synovial fluid.
Complications: anemia of chronic disease, secondary amyloidosis.
