5.8 Autoimmune diseases Flashcards
Presentation of Lupus
varried, you’ll see many different things like buterfly rash of malar eminences
Lupus is typically found in
Females – female preponderance 9:1 ratio at childbearing ages. Much lover in older pts or children. Presentation extremely variable. Classically young female with butterfly rash, multiple peripheral joint pain, no deformity, fever, photosensitivity, pleuritic chest pain
why is there photosensitivity in lupus
bc the rash becomes worse on sulight exposure
what is pleuretic chest pain
it is a sharp pain due to wrinkle in the pleura, ppl with MI or heart attack describe crushing pain, people with epigastric pain describe burning
what race is lupus more common in
more common and severe in black women
what kind of antibodies do you find in lupus
nuclear, ss-DNA, ds-DNA, histones, plasma protine, phospholipid, RBC, platelets, and other cells
Which Ab are cross reactive
Anti-PL ab will cross react
what problem dose Anti PL ab cause
Anti-pl will interfere with clotting. Counter intuitively it will increase PTT but what is really happening is that Anti-PL ab bind to platelets making them sticky making you prone to thrombosis. So anti-PL are actually prothrombotic. But you see a longer PTT bc the Anti-PL ab acutally interferes with the test itself.
Lupus and genetics
familial, 20% concordance in monozygotic twins. Non- affected twin often has same autoantibodies
Drugs that induce lupus
hydralizine, chelating agents, antihypertensives
Sex hormones affecting lupus
important bc of fluctuations of female predominance depending on age?
Lupus - type of hypersensitivity
Type II bc there are antibodies directed at plateltes clearing or lysing them, and Type III due to complex fromation and deposition especially in kidneys
Organs affected in lupus
many organs affected, small vessel vasculitis (type III) common mechanism. Renal manifestations are frequent cause of death
Genetic factors affecting Lupus
twins (20% concordance in monozygous twins), specific alleles in HLA-DQ locus, 6% of patients have inherited deficiencies in early complement components (C1q, C2, or C4), C4 KO mice get lupus like disease, NZBxNZW F1 mice have lupus and changes in over 20 loci
Environmental factors affecting Lupus
drugs, UV light, sex hormones
immunologic factors affecting lupus
large number of irregularities, polyclonal b cell activation, analysis of anti ds-DNA ab suggests specific autoreactive clones. CD4 cells the villain. Impaired clearing of apoptotic cells, Type II and III types of damage, Epitope spreading
sequence of events in lupus
defect in apoptotic body clearance –> exposure to sequestered ag (eg. DNA) –> genetic predisposition (MHCII polymorphisms) –> presentation of self ag –> generation of auto-ab
Why is it called systemic lupus erythematosis
bc almost all organsystems are affected _ renal are usually almost always present
Renal problems in lupus
glomerulonephritis – normal by light microsope, mesangial, focal proliferative, diffuse proliferative, or membranous
Skin problems in lupus
buterfly rash on face but may be on extremities; liquifactive degeneration of basal layers causing blistering or bulla formation, vasculitis with fibrinoid necrosis
Joint problems in lupus
non-erosive synovitis
CNS problems in lupus
vasculities, occlusion of small vessels from intimal proliferation
Heart problems in lupus
pericarditis, endocarditis, coronary artery disease – due to hypercoaguable state
Lung problems in lupus
pleurities
Spleen problems in lupus
enlargement, onion skinning of arterioles
what is always see in lupus patients
hematologic disorders
Diagnosis of Lupus (4/11) MD SOAP BRAIN
Malar rash, Discoid rash, Serositis, Oral ulcers (includes oral or nasopharyngeal ulcers), Arthritis, Photosensitivity, Blood–hematologic symptoms, Renal disorder, Antinuclear ab test positive, Immunologic disorder, Neurologic disorder
If you see a healthy woman with seizures and have ruled everything else out what should you think of
brain tumor or lupus
Problem with Anti PL
false positive on you VDRL. The VDRL test lets you know if you should test for presence of spirochetes. If you test positive on VDRL, but then test neg when you check for Ab to spirochetes you might have lupus.
in lupus, diffuse nuclear ab can be directed towards
chromatin, histons, and ds-DNA
in lupus, rim or peripheral ab can be directed toards
ds-DNA
in lupus, speckled ab can be directed towards
non-DNA components RNP, SS-A, SS-B
in lupus, nucleolar pattern ab can be directed towards
RNA proteins. Usually systemic sclerosis
slide 59
v. important chart
many autoimmne disease like SLE, systemic sclerosis, limited scleroderma, sjogren syndrome, and inflammatory myopathies have
ANA - anti nulcear ab –> sensitive test not specific —lots of false positives —lupus is the highest though
in 40-60% of lupus pts you find
anti ds-DNA ab –> specific but you get lots of false negatives. If they have the ab, they pretty much have lupus, but if they don’t have ab, they might still have lupus
In 20-30% of lupus pts you find
anti smith ab
What diseases do you see Ro/L (SS-A/B RNPs)
Sjorgren > SLE
What disease do you see anti Histidyl-t-RNA synthetase (Jo-1)
inflammatory myopathies – 25%
What disease do you see anti centromere ab
Limited scleroderma > Systemic sclerosis
What disease do you see anti DNA topoisomerase ab
Systemic slerosis > Limited Sleroderma
What disease do you see anti U1RNP ab
SLE >Systemic sclerosis> Limited Scleroderma
clinical course of lupus
variable and unpredictable, ranging from severe to mild, treatemtn with steroids and immunosuppression yeilds long term remissions with occasional flare-ups, prone to infection
what is the survival rate of lupus
90% 5 yr survival, 80% 10yr survival
what is the most common cause of death in lupus
renal failure – coronary vasculuar disease is becoming a more important cause of death
Renal manifestations of Lupus
With light microscopy up to 70% of pts show changes, but with EM and immunofluoresecne 100% of pts show changes –> diffuse proliferative, focal proliferative, mesangial GN, membranous, **wire loop lesions with extensive deposits
what do you see in end stage glomerulonephritis
lots of scarred glomeruli, will present as no more pee, inc creatinine
where do you see skin changes histologically in lupus
the dermal epidermal border – formation of blisters and bulli
what do you see in the spleen histologically in lupus
onion skinning around the arteriole
Libman-Sacks endocarditis in lupus
anti PL makes person hypercoaguable and you can get deposits of thrombi in endocardium of the heart on the underside of the leaflets, these are sterile and not due to any infectious agents, they have a bead like appearance, they aren not usually that symptomatic but on the left side they can break off and cause stroke
chronic discoid lupus
confined to skin lesions, some develop systemic disease later, only 35% positive for ANA rare anti ds-DNA, same immunofluorescnece findings as SLE
subacute cutaneous lupus
skin involvement with mild systemic disorder
Drug induced lupus
hydralazine, procainamide, isoniazid, D-penicillamine (chelating agent) induces SLE and disease stops on drug withdrawal
What are you worried about in lupus
the hypercoagualbe state theat you’re in due to the Anti PL(remember will give a flase + VDRL) bc if you have clotting and thrombosis when you’re pregnant that can lead to damage to placenta and abortion of the baby
Sjorgren Syndrome
50-60 y/o females, dry eyes (keratoconjunctivites, sicca syn), dry mouth (xerostomia), immunologically mediated destruction of lacremal and salivary glands, can occur as an isolated disorder but commonly secondary in other AI disorders such as lupus and rheimatoid arthritis
Histologically what do you see in Sjorgren Syndrome
lymphocytic infiltration of glands (CD4, Bcells, and plasma cells), over time dominant clone of B cells emerges
what kind of Abs do you see in sjorgren syndrome
several ANAs and RNP ab but SS-A and SS-B positive in 90% of pts (also 30-50% of lupus), many rheumatoid factor positive
what cells are defective in Sjorgren
CD4s
high titers to SS-A predict what in Sjorgren
extraglandular involvment including nose, respiratory system
what secondary effects do you see in Sjorgren
ulcerated cornea, cracks and fissures in mouth
what cancer is there a high incidence of in Sjorgren
B-cell lymphomas
why do you do a lip biopsy for sjorgren
bc the lips have minor salivary glands for you to look at and see if affected
Systemic Sclerosis (Scleroderma)
diffuse and localized forms of interstitial fibrosis in skin and other organs
CREST syndrome (localized) in Systemic Sclerosis stands for
calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasia
Systemic sclerosis is seen in
females 50-60
what kind of malfunctions are see in systemic sclerosis
GI, myocardial, and renal malfunctions
What kind of Renal involvement is related to Systemic sclerosis
renal involvement is vascular (not glomerular) due to vasculites that will cause an infarct and reanl failure leading to death in 50% of ts. Also inductino of malignant hypertension.
What other systems are affected in Systemic sclerosis
Pulmonary vessel involvement puts SS in differential for pulmonary hypertension, GI tract affected in 90% especially esophagus. Loss of villi in small bowel can induce malasorption.
What kind of antibodies are seen in Systemic slerosis
Anti-topoisomerase and centromere ab
What happens to the skin in Systemic sclerosis
skin gets stretched, and the skin becomes attenuated and shiny, and there is a loss of wrinkles
What can happen to the mouth in Scleroderma
cheilosis at the corners of the mouth from riboflavin deficiency as a result of the malabsorbtion that can occur with scleroderma
Why is peristalsis affected in Systemic sclerosis
normally the submucosa should be thin, but in this condition there it is thick with lots of connective tissue interfering with peristalsis. There is also loss of villi affecting absorption
Dermatomyositis
lilac discoloration of eyelids and periorbital edema, slow onset muscle weakness, bilateral, symmetrical, proximal, climbing steps affected before digital fine motor control, increased risk of cancer —> bilateral conditions tend to be systemic, attack large muscle first
Age of onset of Dermatomyositis
any age
in Dermatomyositis what is happening on a deeper level
perivascular and perimysial inflammation with some atrophic fibers. Quantitatively, dramatic decrease in number of capillaries –> vessels are being killed in the muscle
Polymyositis
very similar to dermatomyositis but no skin involvement, occurs mainly in adults, killing of muscle fibers by CD8 lymphosytes, necrotic regenerating fibers, puter type 4 hypersensitivity, thends to be in big muslces first so strength is a problem
Inclusion body Myositis
begins in distal muslces, affects pts over 50, CD8 cells present but antiinflammatory therapy doesn’t work, inclusion bodies in muscle diagnostic, some stain with congo red i.e. amyloid positive, fine motor control affected first, steroids don’t work here
What ab do you see in myopathies
anti histidyl RNA syntetase ab
Mixed connective Tissue Disease
pts have symptoms of SLE, polymoyosits, and systemic sclerosis, very little renal disease and good responses to steroids, bc of overlap of disease many question if this is a separate disease
In mixed connective tissue disease what do you find high titers of
RNP particles containing RNP U1
