McGowan: Connective Tissue Diseases Flashcards
What lab value will autoimmune disease have?
- ANA
- NOT SPECIFIC for individual AI disorders
- Titer of <1:40 is normal
What is cANCA?
-PR3-ANCA
What is pANCA
-MPO-ANCA
What does a homogenous ANA staining pattern mean?
- the entir nucleus is diffusely staidned
- Antibody includes those directed against chromatin, histone, proteins, and DNA
- Drug induced SLE
- Sjogren’s
- SLE
What does speckled staining pattern mean?
- fine or caorse speckles are seen throughout the nucleus
- many different antibodies, including those directed against UI RNP, Sm, and La antigens
- -Mixed CT disease
- Diffuse Systemic sclerosis
- Sjogren’s syndrome
- SLE
What does the Centremromere pattern mean?
- refers to the presence of 30 to 60 uniform speckles distributed throughout the nucleus of resting cells
- inmitotic cells, the speckles localize to the chromosomes at the metaphase plate
- Limited systemic sclerosis (CREST)
Nucleolar pattern
- refers to homogenous or speckled staining of the nucleoulus
- Ab directed against RNA
- Diffuse systemic sclerosis
- SLE
What will we see in SLE?
- Pleural effusions
- Heart problems
- Lupus nephritis
- Arthritis
- Raynaud’s phenomenon
- butterfly rash
What are the antibodies directed against in SLE?
- Auto antibodies to nuclear antigens
- immune complexes (Type 3 hypersensitivity
SLE serology
- +ANA
- +anti- ds DNA
- +Sm
- Complement activation promotes inflammation
- C3 or C4 lowered, meaning increased consumption: suggests disease activity
- returns towards normal when in remission
Anti phospholipid antibody syndrome (APS)
- 1/3 of SLE patients
- can also be present w/o a dx of SLE
- 3 types of antibodies
Tx of APS
- Warfarin to acheive INR of 2-3
- Pregnancy= low molecular weight heparin + aspirin
- ***Warfarin contraindicated in preggo!
Type one Antiphospholipi antibody
-causes biologic false-positive tests for syphilis!
Type 2
- Lupus anticoagulant
- risk factor for venous and arterial thrombosis and miscarriage
- prolongation of the activated partial thromboplastin time (aPTT)
- presence is confirmed by an abnormal Russell viper venom time (RVVT) that corrects with addition of phosphohlipid but not normal plasma
Type 3
- Anti-cardiolipin antibodies
- directed at a serum cofactor beta-2-glycoptn I
- Beta2GPI***
What will we see in the retina with SLE/APS
-cotton wool spots
What is the lupus-like syndrome/drug induced?
- Promote demethylation of DNA
- no renal or neuro symptoms
- ANA
- anti histone antibodies (95%)
- **Sulfa abx…. SLE flare
What drugs will in induce the lupus like syndrome
- hydralazine
- isoniazid
- Minocycline
- TNG inhibitors
- Quinine
Lupus: Prgnancy and neonatal
- gestaional HTN, fetal growth restriction, fetal distress….fetal losss or premature delivery
- Neonatal lupus
- affects children born of mothers with Anti Ro (SSA) or La (SSB) Abs
- Permanent complete heart block
What is a sign of transient neonatal lupus?
- rashes
- thrombocytopenia
- hemolytic anemia
- arthritis
Tx for SLE
- Avoid sun exposure, wear sunscreen
- NSAIDS
- Corticosteroids
- Hydroxycholoquine
SLE Ddx
- RA
- Systemic vasculitis
- scleroderma
- inflammatory myopathies
- viral hepatitis
- sarcoidosis
- acute drug rxn
What kind of endocarditis will we see with SLE?
- Libman sacks endocarditis
- non infectious
- causes detachment of the chordae tendonae it looks like
If someone has discoid lupus, what other diseases should we think about?
- Tinea infeaction (ring worm)
- Psoriasis
- morphea (limited scleroderma)
Scleroderma
- thickening and hardening of skin
- microangiopathy and fibrosis of the skin and visceral organs
- secondary raynaud phenomenon
- Obliteration of eccrine sweat and sebaceous glands….dry itchy skin
- no approved isease modifying therapy
tx for scleroderma
-controls sx and slows progression to improve quality of life and prolong survival
Diffuse scleroderma
- systemic
- diffuse involvemtn
- including proximal extremities and trunk
- early and progressive internal organ involvement: especially kidney, cardiac, and interstitial lung disease
- worst prognosis
Limited scleroderma
- fingers, toes, face, disatal extremities
- raynaudes commonly precedes other sx
- pulmonary htn
- CREST syndrome
- indolent course
- good prognosis
What is CREST syndrome
- calcinosis cutis
- Ranaud’s (secondary): usually first sx
- esophageal dysmotility
- sclerodactyly
- telangiectasia
Localized scleroderma
- benign skin conditions
- affects children
- discrete areas of discolored skin induration
- NO raynaud’s
- NOT systemic
- histologically indistinguishable form SSc
- pathces= morphea
- coalesced patches= generalized morphea
Scleroderma (SSc) serology
- +ANA
- Diffuse cutaneous: + anti Scl 70 ( anti DNA topoisomerase 1, anti RNA polymerase 3
- Limited cutaneous: + anti centromere
Is there a tx for scleroderma?
no not yet
-so just manage organ system involvement
In limited cutaneous systemic sclerosis, what will we find?
- long standing h/o raynaud’s
- vascular manifestations are more pronounced with digital ischemia and progressive pulmonary artery Htn
Which kind of cutaneous sytemic sclerosis do we find renal crisis?
- diffuse kind
- may see hemolytic anemia on labs during renal crisis
What things will we find with the skin in scleroderma?
- hyper/o pigmented
- dry and itchy (glands obliterated b y fibrosis)
- masklike facies/wrinkles
- calcium deposits
- raynaud’s
GI things with scleroderma
- Malnutrition: fat, protein, B12 and vitamin D deficiency
- Barret esophagus (high risk for esophageal adenoCA)
- Gastric antral vascular ectrasia (GAVE): watermelon stomach
- Primary biliary cirrhosis
What antibody will we find in primary biliary cirrhosis?
-anti mitochondrial ab
What is the primary cause of morbidity and mortality in scleroderma?
- Pulmonology
- Interstitial lung disease: diffuse
- Pulmonary artery htn (PAH): limited
- use right heart cath to confirm dx
- increased incidence of bronchoalveolar CA
Renal things with SSc
- CKD
- renal crisis uncommon but life-threatening
- abrupt onset of malignant htn, hemolytic anemia, and progressive renal insufficiency
MSK things with SSc
- carpal tunnel syndrome
- hypothyroid from thyroid fibrosis
Cardiac things with SSc
- Myocardial fibrosis
- carditis
- pericardial effusion
Sjogren syndrome
- females
- Sicca sx: immune mediated dyfunction of lacrimal and salivary glands… dry everything
- keratoconjuctivitis sicca
- inflammatory destruction of exocrine glands
What cancer has a strong associated with Sjogren’s?
-B cell non hodgkin lymphoma
Dx for sjogrens?
- Lip biopsy
- reveals characteristic lymphoid foci in accessory salivary glands
- essential for dx
Serology for sjogrens
- +ANA
- +RF
- hypergammaglobulinemia
- anti SSA/Ro
- anti SSB/La (never present without Ro)
tx of sjogrens
- symptomatic
- Artificial tears
- no immunomodulatory drug has proved efficacious
Inflammatory myopathies
- myalgias
- symmetrical bilateral proximal muscle weakness
- difficulty rising form a chair or bathtub or climbing stairs
- elevation of serum muscle enzymes
- ESR and CRP often normal
- Characteristic Muscle bx!!!!**
Typical drmal features of inflammatory myopathies
- Gottron’s patches/papules: raise violaceous lesions overlying the dorsa of DIP, PIP, and MCP joint
- heliotrope rash
- periungual erythrema
- V neck erythema
Dermatomyositis (DM)
-weakenss w/o sensory sxs****
-increased risk of occult malignancy
-
What is the characteristic skin lesions of DM?
- heliotrope rash: periorbital edema, purplish suffusion over eyelids
- Shawl sign: erythema over neck/shoulders, upper chest and back
Dx of DM
- bx: perimysial and pervascular inflammation
- perifascicular atrophy*
- elevated CK, Aldolase
- Anti Jo-1, anti Mi2, and anti-MDA5, anti-P155/P140
Malignancies associated with DM
- Ovarian is most commone
- so make sure you check transvaginal US, CT, abd/pelvis, CA-125
- Some malignancies may not be evident for months after the initial presentation of DM and initial screenings
Polymyositis
- subacute prox muscle weaness
- NO SKIN CHANGES (there are skin changes with DM, but not this )
- Elevated serum CK
- Anti-Jo-1
What will we see on muscle bx of Polymyositis
-ENDOmysial inflammation with invasion of non-necrotic muscle fibers without features suggestive of another dx
Management of DM/PM
- Corticosteroids (bolded)
- MTX
- azathioprine……
Inclusion body myositis (IBM)
- white males
- finger flexion or quadriceps weakness
- CK is mild elevation or normal
what will we see on muscle bx for IBM?
- endomysial inflammation
- rimmed vacuoles
- invasion of non-necrotic muscle fibers
- anti-cN1A autoantibodies
Tx of IBM
-refractory to tx, so tx is just supportive
Takayasu Arteritis
- large vessel: subclavian and innominate most common
- long smooth tapered stenosis
- pulseless disease
- 50% pulmonary involvement
- Retinopathy, renal artery stenosis, aortic dilation, aortic regurg, aneurysm, aortic rupture
Dx of takaysu
MRI or CT angiography
-histology: granuloma with some giant cells, fibrosis in chronic stages
Tx of takayasu
-Glucocorticoids
What will we see on fundoscopic exam for takayasu arteritis
-Copper -wiring fundoscopic
IgAV aka Henoch schonlein purpura
- palpable purpura
- no thrombocytopenia
- arthritis
- abdominal pain
- glomerulonephritis
- any age, more common in kids
- Bx:IgA deposits
- Tx: supportive/ glucocorticoids
Anti GBM
- glomerular capillaries
- pulmonary capillaries
- deposition of anti-basement membrane autoantibodies in basement membrane
BEehcet syndrome
- silk rout (turkey, asia, mid east
- HLA -B51
- large vessel=aneurysms
- venous involvement…. DVT
- large joint arthralgia
- neuro involvement
- ulcers in distal ileum or cecum
- Tx: low dose glucocorticoids
What is the triad wtih BEhcet syndrome-
- recurrent mouth ulcers
- genital ulcers
- Eye inflammation (uveits)
In Behcet syndrome, what is pathergy?
-pustules at site of sterile needle pricks
Polarteritis nodosa
- medium vessel/segmental (may be ANCA+)
- associated with HBV
- males
- fever, malaise, weight loss
- foot drop
- **lungs are spared*
What will we find on bx with PAN
-infiltration and destruction of blood vessels by inflammatory cells…. fibrinoid necrosis, NO GRANULOMAS
What will angiogram show us for PAN?
- micro-aneurysm
- ANCA negative, (check HBsAg and HBeAg)
tx for PAN
-corticosteroids
Kawasaki disease
- Medium vessel
- Mucocutaneous lympho noe syndrome
- strawberry tongue***
- DDx: TSS and scarlet fever
- death from coronary involvement (aneurysm or MI- can occur years later)
Tx of kawasaki disease
-IVIG within 10 days of sxs and high dose ASA…. yes, aspirin in a pediatric patient
GPA (granulomatosis with polyangiitis: aka Wegener’s Granulomatosis)
- small vessel
- ANCA+ (cANCA aka PR3-ANCA)
- respiratory tract (90% nasal involvement)
- alveolar hemorrhage
- CSR: inflitrate/nodules/cavitary lesions
- kidney involvement *****
What nose do they have with GPA?
-saddle nose deformity
What are the hallmarks of GPA?
- Granulomatous inflammation
- necrotizing vasculitis
- segmental glomerulonephritis
Tx of GPA
- cyclophosphamide and high dose glucocorticoids or rituximab
- MTX can be considered if renal function is normal
Eosinophilic granulomatosis with polyangiitis (aka EGPA or Churg strauss syndrome)
- ANCA +: typically MP-ANCA
- Granulomas (with eosinophilia)
- prodromal phase: allergic disease… months to years
- Eosinophilia-tissue infiltration phase
- Vasculitis phase: palpable purpura.. ddx HSP
- Resp tract and other organs
- DDx: GPA
- Tx: glucocorticoids
Hallmarks of EGPA?
-asthma+eosinophilia…. vasculitis
Thromboangiitis obliterans (aka Buerger disease)
- medium vessel
- young males (<35 yo)
- only occurs in smokers**
- distal vessels…. then proximal
- thrombosis…. loss of digits… hands/feet
- segmental disease
Dx of thromboangiitis obliterans
-angiography “corkscrew” appearance
Tx of thromboangiitis obliterans
-Stop smoking (glucocorticoids and anticoagulation doesn’t work)
Primary raynaud
- benign, symmetric
- exaggerated physiologic response to cold or emotion
- women
- younger ppl
- thumbs rarely affected
- Naifold capillaraoscopy normal in primary
secondary raynaud
- occurs in CTD , hematologic and endocrine condtions, occupational disorders, use of beta blockers or cancer drugs cisplatin and bleomycin
- > 30 yo typically
- Unilateral
- More severe: ischemia
- Nailfold capillaroscopy: distorted with widened and irregular loops, dilated lumen and areas of vascular “dropout”
tx for raynaud
-wear freaking gloves
-lotions
-stop smoking
-limit use or stop sympathomimetic drugs
-calcium channel blockers
-surgery
-
Polymyalgia rheumatica (PMR) and Giant cell arteritis (GCA)
- women
- > 40
- white
- fequently co exist
- contituition sx: fever, malaise, weight loss, normal WBC count
GCA (aka temporal arteritis)
- Crainal arteries, aortic arch (large vessels)
- headache, jaw claudication, PMR, visual abnormalities, and raised ESR
- northern europena ancestry
- associated with PMR
What genetic thing goes with GCA?-
-HLA-DR4
What is the gold standard for dx of GCA?
- temporal artery bx
- segmental granulomatous vasculitis with multinucleated giant cells
What do we do right away if someone has GCA?
-sart corticosteroids (before biopsy)… dramatic improvement
What happens if GCA goes on untreated?
-blindness
Polymylagia Rhuematica
- Associated with GCA
- proximal severem symmetrical morning and daylong stiffness, soreness, and pain in shoulder, neck, and pelvic girdles
- feelings of weakness a result of pain, no true weakness
- no inflammation on muscle bx
- muscle enzymes and EMG normal
- elevated ESR and CRP
- Tx: corticosteroids
What is the most likely cause of mortality in a lupus patient?
-Atherosclerosis
IN tachyasu arteritis, what is the patient at highest risk of developing?
-Aortic rupture
