Lec 15 & 16: Sjogren Syndrome, Scleroderma, Polymyositis, Antiphospholipid Syndrome Flashcards
What is ANTIPHOSPHOLIPID SYNDROME? Features?
LABS in APS? (Antibodies, tests, and one more)
APS is thrombosis in both veins and arteries
Very rarely bleeding
Thrombocytopenia
Fetal loss
Occurs with SLE or with other connective tissue disease or also without any !
LABS
-Antibodies — anti-cardiolipin, anti B2 glycoprotein-1, lupus anticoagulant
-false positive VDRL syphilis test
-increased PTT
—be careful: the lupus anticoagulant and inc PTT may be false positive if the pt is on anticoagulation when testing!!!! So always cross check meds with labs before making a diagnosis
Clinical Presentation of APS?
Manifestations?
Treatment?
What if surgery is needed?
—History!
Hx of skin changes (livedo reticularis), pulmonary emboli or DVT, miscarriages, endocarditis, GERD, seizures, and leg ulcers
—vascular occlusions: venous thrombosis (DVT, esp. in unusual locations!) & arterial thrombosis (CVA or TIA)
Pregnancy loss (live birth rate w APS is 70% so this is a big one) & pregnancy complications like premature, pre-eclampsia, placental infarct
or HELLP (Hemolysis Elevated LFTs Low Platelets
Tx
anyone with multiple miscarriages should be on aspirin! any one with any connective tissue dz should be on aspirin
-Primary prophylaxis: Aspirin 81mg first line
-Avoid exogenous estrogen, SERMS, thalidomide
-for pt’s with past thrombotic episodes: Warfarin with INR>2.6, ASA + Heparin, Antiplatelet therapy
-if there is an acute/ongoing thrombotic event, treat with thrombolytics
-If surgery is needed, switch to low molecular weight heparin, stop immediately preop and restart afterwards.
-ALSO warfarin is CI in pregnancy so depending on history, just do
ASA alone (no prior bad pregnancies or just 1 loss) ASA + Heparin (hx of multiple losses or late fetal demise)
ASA + therapeutic Hep (past thrombosis)
Catastrophic APS
Diagnostic criteria , 2 things
DDx
Treatment (2 main drugs)
3 or more organ/systems/tissues involved
Diagnostic criteria is: Lab confirmation of antiphospholipid antibodies AND Histo shows small vessel occlusion
Very high mortality rate
DIC, HIT, thrombotic, microangiopathies
Tx
Treat the cause! Drugs, SLE, trauma
Life threatening case: IV heparin + high dose steroids + plasma exchange + cyclophosphamide
Non-life threatening: IV heparin + high dose steroids
Scleroderma
Localized
Systemic
Limited cutaneous scleroderma
Diffuse cutaneous scleroderma
Chronic fibrosis disorder w the highest M&M of any rheumatic dz
Localized - morphea, linear, en coup de sabre
Systemic
Limited cutaneous scleroderma
-Centromere antibody
-Good short term prognosis, but long term there is a 30-40% change of developing pulm HTN which carries a 50% 5 yr mortality rate. MAIN RISK IS PULMONARY DZ rarely involves heart or kidneys
-CREST - calcinosis or centromere, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasia
Diffuse cutaneous scleroderma
-SCL-70 (anti-topoisomerase antibody) carries worst prognosis! :(
-skin involvement has better prognosis than if internal organ
-lung cancer risk increased w pulm fibrosis so should have yearly CXR
-interstitial lung dz AND renal involvement
Compare/contrast limited vs diffuse cutaneous scleroderma?
Limited has higher risk of pulm HTN and
Diffuse has higher risk of Interstitial lung dz and RENAL involvement
Limited AND diffuse dz is worse if there is internal organ involvement
Scleroderma
History
LABS (specific serologies/antibodies - 4, and routine labs)
How to monitor internal disease in scleroderma?
Hx - look for rash or skin changes, Raynaud’s, SOB, abd sx (GERD, constipation) or history of arthritis!
Specific serologies
Centromere antibodies, anti-topoisomerases (SCL-70), anti-RNA polymerase III, anti-U3 RNP
Of course, routine labs:
CBC, CMP, UA, ANA
Monitor internal disease w CXR, PFt, CT scan, echo and biopsy of skin, lungs and kidneys
Pt has elevated ANA. You immediately suspect what disease (s)?
Elevated ANA means
**80% = SS **
20% = SLE
Skin involvement/Localized Scleroderma features ( there are 5 ) !
Diffuse features and treatments..
what is the first sign of renal involvement in Diffuse pt’s?
What is SRC? And what do you need to monitor when a patient has this, what do you treat the pt with
ALWAYS AVOID THIS __________ IN PT’s WITH DcPSS
What is the leading cause of death in scleroderma? And again we avoid treating with this ______ but instead administer this 1,2,3
What is the treatment for pulmonary hypertension if they have Interstitial lung dz, and what if they do not have ILD?
-Raynaud’s (cRest)
Most of pts with +ANA and Raynaud’s have = SS !
-Digital Ulcers > can lead to osteomyelitis/gangrene
-Calcinosis Cutis > late manifestation containing calcium phosphate - hands, forearms, elbow, knees
-Telangiectasia > dilated blood vessels, +blanching, on face, oral mucosa and fingers
-Skin thickening
Other manifestations in Diffuse: MSK, GI, Renal, PULM, Cardiac
renal involvement is only in diffuse. First sign is hypertension which is abnl bc normally the they are low blood pressure patients
SRC=scleroderma renal crisis
Need to monitor BP in all DcPSS pts and treat with ACEi (if >20 mmHg rise in BP), *always avoid steroid in pts with DcPSS
Pulmonary involvement — interstitial lung dz is the leading cause of death in scleroderma
Avoid steroids
Cytotoxic agents like MMF, CYC, AZA
DMARDs like Nintedanib
Biologics like Tocilizumab (IL-6
Pulmonary hypertension
-mean PAP >20 mmHg
-treatment:
W/ ILD - tx ILD, O2 and diuretics
W/O ILD - PDE-5 inhibitors, prostacyclin therapy and endothelin receptor antagonists
just avoid steroids in any diffuse scler issue
POLYMYOSITIS AND DERMATOMYOSITIS
Diagnostic criteria: what type of symptom, what enzymes are elevated, EMG abnormalities
Changes on muscle biopsy
LABS: routine, and what is elevated ( 4 things and 1 in urine)
Always check _________ as it could be a sign of weakness and myopathy
Serology: ESR high or low? Specific antibodies in myositis:
STUDIES
EMG (triad), muscle imaging, and muscle biopsy showing _________________________
POLYMYOSITIS requires 4/5 criteria and DERMATOMYOSITIS requires a rash with 3/4 criteria
-symmetric proximal muscle weakness
-elevated muscle enzymes (CPK, aldolase, transaminases, LDH)
-Myopathic EMG abnormalities
a triad: 1. insertional & spontaneous activity, 2. small polyphasic motor unit potentials, 3. early recruitment
-changes on muscle biopsy - peripheral atrophy, perimyseal inflammation
-rash typical of DM
LABS
Routine labs: CBC, CMP, UA
Elevated aldolase, AST, LDH, and myoglobin in urine
Elevated CPK
TSH could be a cause of weakness and myopathy
Serology
Normal ESR
ANA in some cases
Specific antibodies in myositis
**Jo-1 (MC and a/w ILD) **
MI-2
MDA 5, TIF1-y, NXP-2
STUDIES
-EMG- can differentiate between myopathic and neuropathic source of weakness remember the triad??????!!!!!
-muscle imaging
-muscle biopsy showing > peripheral atrophy and perimysial inflammation around the vessel
What are individuals with myositis at increased risk of developing? What does this mean that you as the physician must do?
Increased risk of CANCER, esp lung and ovarian
-should have regular screening!
-full malignancy eval on diagnosis w CXR and CT scan of abdomen and pelvis, then yearly exams thereafter !
Besides the top ones for muscle in the diagnostic criteria, what are some other skin findings in myositis?
Gottron’s papules, V-neck rash, and heliotrope rash
Treatment for Myositis
Prognosis for Myositis
-what antibodies mean a poor prognosis, and what disease, and what type of myositis?
What is the morbidity of myositis due to?
High dose steroids x 6 hrs, monitor CPK and strength, increase dose if needed
High dose Methotrexate or Azathrioprine if slow response
You won’t believe this but
Morbidity is usually due to the steroids side effects! WOW.
Poor prognosis in *ANTIsynthetase antibodies (Jo-1, PM-1), lung disease and inclusion body myositis
SJOGREN’s SYNDROME
Manifestations
-glandular
-extra-glandular
-increased risk of _____________.
-increased activity of _____________ and ______________ of exocrine glands
Diagnosis and Diagnostic Criteria
Positive histopath on lip biopsy for _____________________
Presentation
What antibodies are poor prognosis?
Treatment
Autoimmune exocrinopathy
-glandular: dry eyes, dry mouth, swollen glands (esp.parotid)
-extra-glandular: arthritis, ILD, neuro issues
-increased risk of lymphoma —> mostly B-cell. Makes sense bc increased activity of B lymphocytes and lymphocytic infiltration of exocrine glands!
Diagnosis probable with 3/6 and definite w 4/6 + Ro/La antibodies
Dx criteria include: dry eyes, documented hx of dry eyes with tear assessment (<5mm wetting on schirmer’s test), dry mouth, evidence of dry mouth, positive histopath on lip biopsy for lymphocytic infiltration in the gland (sublabial)
AUTOantibodies
ANA and RF +++++ !
Anti-SSA (Ro) and Anti-SSB (La) are most specific but only seen in 60%
Can present with a rash that worsens in the sun ,dry eyes or mouth, swollen glands and arthritis
poor prognosis with Jo-1 and PM-1, lung dz and inclusion body myositis too
Treatments depend on symptoms
Dry mouth —> muscarinic antagonists (pilocarpine & cevimeline), dry eyes —> synthetic tears, muscarinic agonists, arthritis —> HCQ, systemic manifestations (corticoids)
Which connective tissue disorder is an absolute CI to get LASIK surgery?
Sjogren’s
MIXED CONNECTIVE TISSUE DISEASE
Presentation
Overlapping clinical features of multiple diseases with a very high anti-ribonucleotide antibody titer (required for dx)
usually presents with myopathy, Raynauds, arthritis, esophageal dysmotility, pulmonary disease
Mixed CTD = RNP is the specific Ab + features of SLE, RA, PSS, and PM
Undifferentiated CTD = no specific lab or features
Overlap CTD = multiple specific ab & meets criteria for several CTDs!
