Autoimmune diseases Flashcards
Libman-Sacks endocarditis
Sterile platelet vegetations occuring on mitral valve, leading to valve thickening + regurgitation sx; vegetations can be on either surface of valve (mainly undersurface)
Renal involvement in scleroderma and which type it’s more often associated w/
Scleroderma renal crisis (SRC)- characterized by sudden onset of malignant HTN, which causes acute renal failure
- Occurs mostly in diffuse scleroderma
Pattern of Raynauds
Pallor (white) –> cyanosis (blue) –> hyperemia (red)
Manometry of scleroderma and why
All the waves are flattened- smooth muscle of esophagus is replaced by collagen, resulting in decreased peristalsis
Presentation of antiphospholipid syndrome
Hypercoagulable state results in arterial and venous thrombosis (DVT, hepatic vein, placental, cerebral strokes)
Important player in scleroderma
In response to inciting endothelail injury, CD4+ T cells respond by releasing cytokines and other inflammatory cells/ fibroblasts, which results in widespread small blood vessel damage –> progressive fibrosis –> intimal thickening –> occlusion of organ supply –> fibrosis of organ/ skin
What is used to detect early scleroderma?
Distorted nailfold capillary loops - indicates vascular damage that’s happening all over the body
Types of lung involvement in scleroderma and which one is associated w/ which type (limited vs. diffuse)
1) Interstitial fibrosis- seen in diffuse scleroderma
2) Pulmonary arterial HTN- seen in limited scleroderma
Etiology of Sjogren
Primary- sicca syndrome
Secondary- associated w/ other autoimmune disorders (esp. RA)
Lupus anticoagulant’s effects on bleeding tmie
In vitro, causes elevated PTT; however, in vivo, produces hypercoagulable state
Difference in epidemiology between SLE and drug-induced lupus (2)
In drug induced lupus, older individuals are affected (e.g. 50-70), and there is no gender preference
Autoantibodies found in SLE and how they can be used for diagnosis
1) ANA: sensitive but not specific for lupus
2) Anti-dsDNA: specific for lupus; titers fluctuate w/ disease activty so levels can be used to manage pts; however, this level can be low when disease is quiescent
3) Anti-Sm: antibody against nuclear non-histone proteins; specific for lupus; titers are elevated regardless of disease activity
*Presence of Anti-dsDNA + Anti-Sm is virtually diagnostic for SLE
Epidemiology of Sjogren syndrome
Affects 40-60 year olds
Lab complement levels in SLE
Decreased C4, C5, CH50 due to immune complex deposition + activation of complement
Autoantibodies associated w/ scleroderma
1) ANA- sensitive but not specific
2) Anti-centromere antibodies- limited SSc
3) Anti-DNA topoisomerase I antibodies (Anti-Scl70) - diffuse SSc
4) Anti-RNA polyermase III antibody- diffuse SSc; increased risk for SR
Presentation of drug-induced lupus
Similar to SLE but CNS and renal sx are rare
Autoantibody asscociated w/ diffuse scleroderma
Autoantibody against DNA topoisomerase I (Anti-Scl70)
Autoantibodies found in drug-induced lupus
ANA, Anti-histone antibodies
Anti-ds DNA is rare
Autoantibodies associated w/ scleroderma renal crisis (SRC)
Autoantibodies to RNA polymerase III
Mechanisms of injury in SLE
1) Type III HSR- immune complex deposition in variety of tissues
2) Type II HSR- autoantibodies specific for RBC, WBC, platelets opsonize these cells
3) Antiphopsholipid autoantibodies- hypercoagulable state
Autoantibodies present in Sjogren
1) ANA - sensitive but not specific
2) Anti-ribonucleoprotein antibodies (Anti-SSA/Ro, Anti-SSB/La)
3) RF- can be present w/o RA
Histology of SRC
Onion skinning appearance of arterioles (malignant HTN)
Unexplained spontaneous abortions, premature birth, pre-eclampsia
Antiphospholipid syndrome- due to placental thromboses
Types of antiphospholipid antibodies (3)
1) Anticardiolipin
2) Anti-beta2 glycoprotien 1
3) Lupus anticoagulant
Most specific antibodies for Sjogrens
Anti-ribonucleoprotein antibodies (anti-SSa/Ro and anti-SSB/La)
GI sx of scleroderma
1) Difficulty swallowing- Low esophageal peristalsis
2) Constipation alternating w/ diarrhea- small + large intestine smooth muscle affectd
3) GERD- decreased LES resting tone
Common drugs that cause drug-induced lupus
Hydralazine, isoniazid, procainamide
Presentation of pulmonary arterial HTN
dyspnea on exertion
prominent P2 component of S2
right ventricular heave
hepatosplenomegaly + lower extremity edema
Biopsy of Sjogren- where to look and findings
Look at labial salivary gland (minor salivary glands)- shows lymphocytic infiltration of minor salivary glands (sialadenitis)- assume that other glands are being attacked
Type of CA associated w/ Sjogren and presentation
Risk of B-cell lymphoma (MALT)- present as unilateral enlargement of parotid gland (both should normally be enlarged due to extra-glandular manifestations)
Why pregnant SLE patients should be screened for Sjogrens
If they have Anti-SSA antibody, they can be at risk for giving birth to babies w/ neonatal lupus/ congenital heart block
How do skin changes present in scleroderma
Insiduous swelling of distal extremities (puffiness) which leads to gradual thickening of skin of fingers –> atrophy of skin –> may cause digital ischemic ulcers
How is Primary Raynaud phenomenon (raynaud disease) different frmo Raynaud phenomenon due to scleroderma (raynaud syndrome)?
In primary Raynaud, it’s painless and symmetric w/ no evidence of microvascular disease.
In scleroderma pts, Raynaud can be painful, leading to digital ulcerations, gangrene, or even amputation.
Presentation of limited scleroderma
CREST
C: Calcinosis/ anti-centromere antibodies
R: Raynaud phenomenon (earliest sign)
E: Esophageal dysmotility –> dysphagia
S: Sclerodactyly- tightening, swelling, thickening of fingers
T: Telangiectasias
Pattern of skin involvement in diffuse scleroderma
Diffuse skin involvement
Pitted areas on distal finger w/ loss of digital pad
Scleroderma
Antiphospholipid antibody that gives false positive VDRL/RPR readings
Anticardiolipin
Presentation of Sjogren
1) Keratoconjunctivis sicca (dry eyes)- gritty sensation in eyes, blurred vision)
2) Dry mouth (xerostomia)- difficulty speaking, recurrent dental carries, oral candidiasis
3) Extraglandular manifestaiotns- bilateral parotid enlargement, neuorpathy, arthritis, renal damage, et.c
Autoimmune destruction of exocrine glands (lacrimal + salivary) by lymphocytic infiltrates
Sjogren syndrome
Why does Raynaud phenomenon occur?
Due to reduced blood flow to the skin from arteriolar (small vessel) vasospasm, occuring in response to stress or cold
Presentation of SLE
RASH OR PAIN
1+2) R: Malar/ discoid rash
3) Arthritis (non-erosive)
4) Serositis- inflammation of serosal surfaces (pleuritis, pericaditis, pericardial effusion)
5) Hematologic disroders- anemia, thrombocytopenia, leukopenia (Type II HSR)
6) Oral/nasopharyngeal ulcers
7 ) Renal disease (diffuse proliferative glomerulonephritis, membranous glomerulonephritis)
8) Photosensitivity- rashes get worse after exposure to sun
9) ANA
9) Immunologic disorders (Anti-ds DNA, anti-Sm, antiphospholipid)
10) Neurologic disorders (seizures, psychosis)
Libman-sacks endocarditis
Nonspecific sx: fever, fatigue, Raynauds
Main causes of mortality in SLE
1) Cardiovasculr disease (accelerated coronary atherosclerosis due to chronic inflammation)
2) Infections (immunosuppressants, pancytopenia)
3) Renal disease
Why is SLE associated w/ inherited deficiencies of early complement proteins? Which proteins?
Becuase lack of complement may impair removal of circulating immune complexes, which favors tisseu deposition.
Complement components deficient: C1q, C4, C2
Association between Anti-SSA and pregnant women
Pregnant women w/ anti-SSA are at risk of delivering babies w/ neonatal lupus + congenital heart block
Pattern of clinical involvement in limited scleroderma
Benign clinical course w/ late visceral involvement
Skin involvement pattern distribution in limited scleroderma
Confined to extremities distal to elbow + knees
Also the face
SLE arthritis vs. RA
Main problem w/ SLE arthritis is tendon sheath inflammation, leading to joint laxity w/ NO EROSION OF BONES; patients have deformities that are reducible
in RA, problem is synovitis
Anti-histone antibodies
Drug-induced lupus
Pattern of clinical involvement in diffuse scleroderma
Early visceral involvement
Antibodies to U1 RNP
Mixed CT disease
HSR related to Sjogren
Type IV HSR
Arthritic presentation of scleroderma
Non-erosive arthritis affecting small joints (loss of joint mobility can result due to skiin thickening/ fibrosis, not due to inflammation)
Most common form of renal disease in SLE pts
Diffuse proliferative glomerulonephritis
Autantibody associated w/ limited scleroderma
Anti-centromere antibodies
