Lecture 7 - Connective Tissue Disease and Vasculitits Flashcards
Path behind Lupus?
cell damage triggers apoptosis (normal in everyone)
defective clearance of apoptotic bodies
nuclear contents exposed
antigens recognized as foreign
B cells produced Anti-nuclear antibodies (ANA)
Is positive ANA diagnostic for lupus?
no
its highly sensitive but only about 57% specific
25-30% of the general population that does not have lupus has 1:40 ANA
we begin to be suspicious at 1:160 ANA (since that VA research about 50% that have 1:160 ANA will have lupus in 5 years)
LE Cells
seen with lupus
neutrophil eating another cell–seen in serous fluid
ANA
immunofluorescene test for lupus
reported by dilution
We know that 25-30% of the population potentially has positive ANA but does not have lupus, why is that?
There are multiple reasons for ANA to be elevated
Rheumatic diseases:
- SLE
- Sjogrens
- Scleorderma
Nonrheumatic:
- Chronic infection
- Hashimontos/Graves
What drugs can induce lupus?
Procainamide Sulfasalazine Hydralazine Minocycline Isoniazid Anti TNF agents (used in RA)
How can you tell the difference between true lupus and drug induced lupus?
both fulfill ACR criteria
drug induced is NOT seen in AA pts
Renal problems is RARELY involved in drug induced
resolves once the drug is stopped (may take months)
What will you see on immunoflouroscopy with drug induced SLE?
homogenous
Speckled immunoflouroscopy is seen with what?
Mixed connective tissue disease SLE Sjogrens Chronic Infection Malignancy
What immunoflouroscopy is seen with scleroderma?
nucleolar
limited scleroderma: centromere
Who is more likely to be affected by lupus?
Females
AA, hispanics
commonly 15-40 yo
Genetic
ACR criteria for lupus
MUCOCUTANEOUS malar rash discoid rash photosensitivity oral ulcers SYSTEMIC INFLAMMATORY arthritis serositis - pleuritis or pericarditis nephritis LABORATORY hematologic immunologic - dsDNA, Sm, or antiphopholipid antibodies ANA
Malar Rash
Seen with lupus
typically on the face
red +/- raised
spares the nasolabial folds
Discoid Rash
seen with lupus
erythematous raised patches keratotic scale follicular plugging heals with atrophic scarring commonly around ears or hair (alopecia)
Photosensitivity
seen with lupus
erythematous rash seen in sun exposed areas
might look like a sun burn or hives
may flare internal disease with arthralgias and fatigue
Mucocutaneous Ulcers
seen with lupus
oral or nasopharyngeal ulcers
painless
in order to count in the ACR criteria it must be seen by the provider at the time of exam
Lupus Arthritis
inflammatory
symmetrically
looks like RA but on Xray it is not erosive
this is reducible (can be fixed)
What are two things you MUST do for pts you suspect of Lupus in your ER (or in any office)?
Get XRAY and EKG
pleuritis and pericarditis
What scale is used to determine if the pt is in an acute flare of lupus?
SLEDAI
Mild flare >3 point change
Severe flare >12 point change
What are the components of SLEDAI?
Vasculitits (8) Arthritis (4) Urine Casts (4) Thrombocytopenia (1) Low complement (2)
8 + 4 + 4 +1 + 2 =19
How do you treat lupus?
Determine if its active or inactive (based on SLEDAI scoring system)
Inactive: Sxs tx Sunscreen Consider plaquenil NSAIDS
Active?
Are organs involved or life threatening?
Life threatening? Steroids (high dose or IV) Immunosuppression (cellcept, cytoxan, imuran) Benlysta Plaquenil Sunscreen
Not life threatening?
Plaquenil (hydroxychloroquine)
Lupus nephritis
50% of lupus pts develop renal disease
proteinuria >0.5g/d
Red Cell Casts
associated with dsDNA antibodies –track dsDNA antibodies in these pts –may show disease progression
THIS IS THE MOST LIFE THREATENING CONDITION OF LUPUS AND UNFORTUNATELY IS COMMON
there are 5 different types of nephritis related to lupus
4 (“diffuse”) being the worst type
always get a UA
hematuria is more worrisome than proteinuria
Types of lupus nephritis
Type 1 - minimal mesangial
Type 2 - mesangial proliferative
NEVER BIOSPY TYPE 1 AND 2
Type 3 - focal
Type 4 - diffuse (WORST type – dead kidney)
3 –> 4 spectrum
Type 5 - membranous
TREAT type 3,5 with DMARD
treat type 4 - dialysis
anti dsDNA
lupus – highly specific
very specific for renal involvement
helpful in predicting prognosis –> high when the disease is active, low when the disease in under control
not everyone with lupus has antiDNA –so it’s only helpful in determining progression of dz if they have been positive for it in the past
anti Sm
anti SMITH
seen in lupus - highly specific
antiphospholipid antibodies
positive lupus anticoagulant (raised aPTT)
anti-cardiolipin antibodies (IgG or M)
false positive test for syphilis >6 months
antiSS-A (Ro) and antiSS -B(La)
found in sjogrens, SLE, and neonatal lupus
SS-A associated with increased risk of neonatal heart block in pregnancy
What is the risk of CV disease in lupus pts?
5-8 times more likely to develop CAD than controls
stress the importance of exercise in these pts and get their BP under control
Scleorderma
systemic sclerosis
thickened skin
there is 4 ‘types’
localized –skin only, not systemic
limited (crest)
diffuse
mixed
scleroderma sine scleroderma (no skin manifestation but organ manifestations)
Crest
limited systemic scleroderma Centromere antibody Calcinosis cutis Raynauds Esophageal dysmotility disorder Sclerodactyly (claw hand) Slowly progressive Telangiectasia
low risk renal crisis
late pulmonary HTN
Diffuse scleorderma
Scl70 antibody Raynauds above elbows, above knees tendon rubs interstitial lung 20% renal crisis
What is the most common malignancy associated with scleroderma?
breast and lung
theory: auto antibodies against the pieces of the tumor cells that are being destroyed
Who is more likely to get scleroderma?
Female > Male (3:1)
increased risk during child bearing years
rare in children and over 80
all races
however... poor prognosis if: african american young age diffuse disease
Compared to lupus, how predictable is scleroderma?
scleroderma has a very predictable manifestation and complications
disease is still complex and difficult to treat
In regards to scleroderma, what is a common internal organ involved?
GI
Above the elbows or above the knee it is probably _________ scleroderma?
diffuse
diffuse –think trunk and proximal extremities
limited –think distal to knees and elbows
What are the phases of skin involvement in scleroderma?
Edematous phase:
- diffuse swelling of the hands
- tight puffy fingers
- swelling not just periarticular
Indurative Phase:
-edema replaced by thick skin
Atrophic phase:
- after several years
- reverts to normal thickness or becomes thin and atrophic
- telangiectsias
What is the underlying problem with scleroderma?
thick skin –too much collagen
How does the time course for diffuse scleroderma differ from limited scleroderma?
Diffuse starts steep, after 5 years if pt has survived renal crisis, the peak is over and it begins to decline
Limited stays with a relatively low steep but later one (15-20 years in) there is a risk for pulmonary HTN and malabsorption requiring TPN –so we screen these pts continually
What are the two types of digital ulcers seen in scleroderma?
atrophic skin ulcers overlying contractures – the skin is SO tight that it splits when the pts tries to flex their fingers
- heal slowly
- frequently secondarily infection
digital tip ulcers in association with sever raynauds
- heal as the raynauds improves
- sometimes progress to gangrene especially in smokers
these vasculopathy is at the end process of all scleroderma –regardless of which type —it is extremely important to get them to stop ALL smoking
Raynaud’s
paroxysmal vasospasm mediated by alpha 2 adrenergic receptors
pallor and cyanosis
White –> Blue –> Red
digits become cold, painful, and numb
hyperemia on rewarming
may predate all other sxs in limited scleoderma by several years
more common in premenopausal women
What drugs can cause raynauds sxs?
BB
ergots
Raynauds is likely NOT to be primary in which pts?
males
women before menarche or after 30-35yo
if the pts has significant digital ulcers
How do the joints of scleroderma pts appear?
can mimic RA
symmetric polyarthraligas
stiffness of fingers, wrists, knees, ankles
symptomatic relief with plaqueil
must be treated with PT within the first 5 years or else may be permanent (like they wont be able to move their fingers)
Calcinosis cutis is seen in limited scleorderma (crest), what does this look like?
often along the extensor surface of the forearm, olecranon bursae, pre-patellar area and buttocks
sometimes secondarily infected –typically staph
calcium hydroxapatitie —can be seen on xray
What is the first sx of renal crisis in scleroderma pts?
HTN
these pts need to be taught how to monitor their BP at home and go to the ER asap if they have visual changes or a bad HA –they are not to leave the ER until they have been seen by a rheum fellow (they need one treatment, without it they will die…ACEI?)
When does the renal crisis typically occur in scleroderma?
in the diffuse type during the first 3-5 years
there is an increased risk with prednisone use so when these pts have joint pain or swelling do NOT give them steroids
What is the treatment of renal crisis in scleroderma?
ACE inhibitor (captopril) given every 8 hours double the dose until their BP is under control their Creatinine will be elevated and they may even need dialysis but you must keep going because this is the only BP drug that might bring their kidney back --these pts are getting admitted
if they are allergic to ACEI (angioedema) they can use an ARB
