General Flashcards
SLE
- Autoimmune disease that can affect and cause inflammation in any/ multi system.
- periods of flares and remissions
- most common connective tissue disease
- 90% women affected, aged 20-30
SLE pathogenesis
- Genetic and environmental.
- Gene present on chromosome 6
- activation of polyclonal B and T cells that results in autoantibodies
- Epstein Barr, UV rays, estrogen and drugs like Hydralazine
SLE CRITERIA
4 or more out of 11 of these:
1- Malar/ butterfly rash. OVER CHEEKS (spares nasolabial folds)
After sun exposure.
2- Discoid rash.
• CHRONIC ERYTHEMATOUS RASH
• SUN-EXPOSED AREAS (arms & legs)
• PLAQUE- LIKE or PATCHY REDNESS can SCAR
3- photosensitivity. Sun exposed areas, lasting a couple days.
4- ulcers of mouth and nose. (SLE can damage the inner membrane of organs)
5- serositis. Inflammation of serosa
* PLEURITIS - inflammation of lining of
lungs & chest cavity
* PERICARDITIS - inflammation of lining
of heart
* PERITONITIS - inflammation of lining of abdomen
Pericarditis of:
MYOCARDIUM -> MYOCARDITIS
ENDOCARDIUM -> LIBMAN-SACKS
ENDOCARDITIS ( VEGETATION in
MITRAL VALVE caused by the clumps of fibrin and immune cells)
6- arthritis of 2 or more joints.
7- kidney damage
• LUPUS NEPHRITIS leading to end stage kidney failure and leading cause of morbidity and mortality.
• Checked thru protein or cells in urine.
• glomerulonephritis, due to immune complex deposition along glomerular basement membrane.
8- Neurologic:
• Seizures or psychosis; Epilepsy; migraines, depression.
• Cranial and peripheral neuropathies; Stroke
9- Blood. Autoantibodies against blood components causing cell destruction- Hemolytic anemia; leukopenia, Lymphopenia; thrombocytopenia.
10- ANTINUCLEAR ANTIBODY (ANA) > NUCLEAR ANTIGENS
- high PROPORTION of PATIENTS with LUPUS HAVE THESE (test is sensitive, but isn’t specific)
11- other antibodies
• a) ANTI-SMITH > SMALL RIBONUCLEOPROTEINS
• b) ANTI-dsDNA > DOUBLE STRANDED DNA (seen during flares, esp. in individuals with Kidney involvement)
These 2 are specific for lupus
• c) ANTIPHOSPHOLIPID > PROTEINS BOUND to PHOSPHOLIPIDS
1. Anticardiolipin (false positive for syphilis)
2. Lupus anticoagulant (lupus antibodies)
3. Anti-Beta2 glycoprotein 1.
These antibodies may lead to patient developing APS which is an hyper-coagulable state prone to clots and complications. (eg. deep vein thrombosis, hepatic vein thrombosis. & stroke)
Systemic symptoms in SLE
• FEVER
• FATIGUE
• MYALGIA
• UNINTENTIONAL WEIGHT LOSS
• LYMPHADENOPATHY
• VASCULITIS: palpable perpura, panniculitis, perechiae, skin ulcers, splinter haemorrhages, and livedo reticularis
• REYNAUD’S PHENOMENON
Arterial spasm causing decreased blood flow to fingers
~ lasts for minutes
~ fingers turn white then blue
~ numbness or pain
~ as blood returns. red & burn
• THROMBOEMBOLIC DISEASE. Blood clot forms in blood vessels that’s breaKaway to plug smaller vessel
• ACTIVATION of COMPLEMENT SYSTEM during flair, it can cause consumption of complement factors like C3 and C4.
SLE investigations
•CBC= leukopenia, lymphopenia, thrombocytopenia
•ESR = elevated; but CRP is usually normal.
•Urea and creatinine & urinalysis = proteinuria, cellular casts, renal dysfunction
•Decreased complement levels (C3, C4):
They can correlate with disease activity.
They can drop further with acute disease exacerbations.
*ANTINUCLEAR
* ANTI-DOUBLE-STRANDED DNA
* ANTI-SMITH
* ANTIPHOSPHOLIPID
Antibodies for systemic inflammation
• radiograph to check for joint deformities
• ultrasound for synovitis and joint effusion
• chest X-ray for pleural effusion, interstitial lung disease and cardiac abnormalities
• echo and EKG for peri/myo/endo carditis
• MRI for neuro or cognitive dysfunction
• biopsy of affected organ to check stage and confirm disease
Lupus nephritis
Nephritic syndrome - Faster evolution towards end stage renal failure.
- Hematuria
- Hypertension
- Azotemia
Leading to renal failure.
nephrotic syndrome
- edema
- Protenuria
- Dyslipidemia
- Lipiduria
- Hypoalbumenemia
Lupus nephritis classification
WHO-Classification of Lupus Nephritis:
• I = Minimal mesangial glomerulonephritis
• II = Mesangial proliferative glomerulonephritis
• III = Focal proliferative glomerulonephritis
• IV = Diffuse proliferative glomerulonephritis
• V = Membranous glomerulonephritis
• VI = Advanced sclerotic glomerulonephritis
Drugs to avoid in SLE
~ isoniazid
~ hydralazine
~ procainamide
SLE Rx
Goal is to minimise damage from disease and drugs and to limit flares.
avoid sun, foods, smoking, certain drugs.
MILD, skin, joint and mucosa
- hydroxychloroquine
- chloroquine
- NSAIDS
- short course and low dose glucocorticoids (< 7.5 mg prednisone/day)
MODERATE, - constitutional cutaneous, musculoskeletal, hematologic
- hydroxychloroquine
- chloroquine
- short courses of <15mg prednisone/ day
SEVERE, major organ involvement
- treat in hospital
- short course of high dose systemic glucocorticoid (IV 1-2mg/kg/day prednisone)
-immunosuppressive agents ( cyclophosphamide, azathioprine, mycophenolate mefotil)
- followed by low dose glucocorticoid.
SLE Rx for pts not responding to glucocorticoids?
Biological medication:
BELIMUMAB - human monoclonal antibody that inhibits activation of B cells
RITUXIMAB - chimeric monocional antibody against CD20 (found on surface of B cells, triggers B cell death)
Rheumatoid arthritis
- chronic inflammatory disorder that primarily/ gradually affects synovial joints but may affect extra articular joints aswell
- linked to HLA-DR1 & HLA-DR4 gene
- pan is formation
- symmetric
- progressive
- causes joint deformity
- affects 3 or more joints
- morning stiffness lasts about 1 hour
Most common joint involved in RA?
Proximal interphalangeal joints and Metacarpophalangeal joints
Distal interphalangeal rarely involved due to v less synovial fluid in them
Articulatar manifestations of RA
- pain
- swelling
- loss of mobility
- no redness or warmth
- morning stiffness
joints affected in RA
- hand mentioned before
- foot: metatarsophalangeal joints
- ankles, knees, wrist, shoulders, elbows.
- hip involvement is later in the disease that causes pain in groin, thigh and lower back.
- **C1-2 involvement (only synovial joint in spinal cord) causes neck pain, spinal cord compression, tetraplegia.
Extra articular symptoms of RA
-Caused by the cytokines release.
CD4 T cells — macrophages — TNF alpha and IL-1 — other cytokines — fever, fatigue, anorexia, weightloss
- vasculitis leading to Atheromatous plaques that cause stroke and MI, (leading cause of death)
- Rheumatoid nodules. A central area of necrosis surrounded by macrophages and lymphocytes. Caused by cytokinic breakdown of muscles.
- increased hepcidin formation in liver causing decreased iron absorption in intestines — low serum iron
- pleural effusion in lungs caused by pulmonary fibrosis that occurs due to fibroblast activation by cytokines
