Vasculitis - Exam 2 Flashcards
_____ is an AI disorders characterized by inflammation of blood vessels. What organ
vasculitis
can affect any organ
What is vasculitis characterized by? How is it classified?
Size of blood vessel typically involved
Predilection for certain organ systems
Characteristic pathologic features
Large vessel aorta and great vessels
Medium vessel splanchnic vessels
Small vessel capillaries, arterioles, and venules to lungs, kidneys and skin
What 2 vasculariritic dz tend to occur together? What specific allele?
Polymyalgia Rheumatica and Temporal Arteritis
both associated with (HLA) DR4
Pain, stiffness in neck, shoulders, lower back, hips and thighs
Few have joint swelling
Frequently have fever, malaise, weight loss
What am I?
What will the pt complain of?
Polymyalgia Rheumatica
Trouble combing hair
Trouble putting on a coat
Difficulty rising out of a chair
What is the tx for polymalgia rheumatica? What labs should you order? When should you start to see improvement?
Prednisone 10-20mg po daily over 2-4 weeks with slow taper
CBC, ESR/CRP
should start to see improvement within 72 hours, if no improvement -> needs to be re-evaluated
_____ are common when tapering prednisone in a pt with polymalgia rheumatica. What is the tx? How can you monitor progress?
flares
tx flares with MTX while tapering the prednisone -> should refer to rheumatology
Can monitor progress with ESR
What is the epidemiology of temporal arteritis? What is the mean age of onset? What alelle is it associated with?
white women over the age of 50
mean age of onset is 79
Association with HLA-DR4
What type of vessels does temporal arteritis affect? What part specifically? What is the big artery it like to affect?
Systemic panarteritis affecting medium and large-size vessels
Proliferation of intima and fragmentation of internal elastic lamina
Involvement of one or more branches of the carotid artery but can involve the aorta and its branches
What layer of the vessel does temporal arteritis affect? What components of the immune system play a part?
Believed to be initiated in the adventitia
Antigen driven-activated T-lymphocyte macrophages and dendritic cells play critical role
What are the 3 layers of the blood vessel?
headache, scalp tenderness, visual symptoms (amaurosis fugax or diplopia), jaw claudication or throat pain
HA
What am I?
Why is this an emergency?
temporal arteritis
can lead to blindness because of the anterior ischemic optic neuropathy
What are the PE findings associated with temporal arteritis? What labs should you order? What lab value will NOT be elevated?
May have tender, thickened or nodular temporal artery
scalp or jaw pain
may have decreased pulses or bruits
ESR > 50 and often over >100, and Alkaline phosphatase may be elevated
Serum creatine kinase will NOT be elevated
_____ is the standard of dx for temporal arteritis. What imaging could you order?
temporal artery bx
Consider CTA or MRI that may show long stretches of narrowing
US of temporal artery
What is the tx for temporal arteritis without vision loss? What is the adjunct med?
Begin HIGH dose prednisone 40-60 mg/day for at least 1 month before tapering
consider adding ASA to reduce chance for vision loss/stroke
When dx is Tocilizumab used in? What is the prognosis?
temporal arteritis, to reduce prolonged use of prednisone
After one year 50% have corticosteroid free remission
What is the tx for temporal arteritis WITH vision loss?
IV methylprednisolone 1 gram daily x3 days
What are the complications of temporal arteritis?
Ischemic optic neuropathy
CVA, scalp or tongue infarction
Subclavian artery stenosis
thoracic aortic aneurysm -> so need to screen for this
Polyarteritis Nodosa (PAN) pts approximately 10% will also have ____
hep B
_____ is a multisystem necrotizing arteritis involving SMALL and MEDIUM sized MUSCULAR arteries in which involvement of the renal and visceral arteries is characteristic. Does it cause muscle weakness?
Polyarteritis Nodosa (PAN)
do NOT cause muscular weakness
aka the small and medium sized muscular arteries die
Does Polyarteritis Nodosa tend to affect the lungs?
NO!! but can affect the bronchial vessels
What is happening in the acute stages of Polyarteritis Nodosa?
Polymorphonuclear leucocytes infiltrate ALL layers of vessel wall and perivascular areas
Causes intimal proliferation and degeneration
Mononuclear cells then infiltrate area and lesions progress and lead to necrosis
What happens in Polyarteritis Nodosa (PAN) after the part of the vessel has died? What happens as a result?
Healing of lesions by collagen deposition that leads to further occlude vessel
Aneurysmal dilation up to 1cm in involved arteries are characteristic
weeks to months
Fever, malaise, weight loss, headache, abdominal pain, myalgias
Fever, abdominal pain extremity pain, livedo reticularis, mononeuritis multiplex
Arthralgia, myalgia (calves) or neuropathy
What am I?
What PE finding was discussed in class?
What are the earliest specific clues that lead to this dx?
Polyarteritis Nodosa (PAN)
livedo reticularis
Combination of mononeuritis multiplex + features of systemic illness
What are the 3 skin findings associated with polyarteritis nodosa (PAN)? What other organ is typically involved?
Combination of mononeuritis multiplex + features of systemic illness
Renal:
Arteritis without glomerulonephritis
Renal insufficiency/failure, HTN, hemorrhage from microaneurysms
Involvement of renal artery renin-mediated HTN
commonly presents with diffuse periumbilical pain that is precipitated by eating
N/V
Infarction can lead to acalculous cholecystitis, appendicitis and possibly acute abdomen
What am I?
What labs should you order? What will they show?
Polyarteritis Nodosa (PAN)
CBC, ESR, ANCA, Rh, antinuclear antibodies
CBC: anemia with leukocytosis
ESR: elevated
ANCA: negative
low titers for rheumatoid factor or antinuclear antibodies
If you suspect PAN need to test for ______ .____ or _____ are needed for dx confirmation
hep B
Tissue biopsy or angiogram needed for confirmation
What body sites should you pull your tissue bx from to confirm dx of PAN? Why?
Symptomatic sites have sensitivity ~70% and provide highest diagnostic yield
Nodular skin lesions, painful testes, nerve/muscle
Have the highest benefit-risk ratio
When should you order an angriogram in PAN? What do you expect to see?
If suspect with mesenteric ischemia or new onset HTN in setting of systemic illness
May see aneurysmal dilations in renal, mesenteric or hepatic arteries but do NOT have to be present for dx
What is the tx for PAN? What adjunct med? What if super sick?
High dose corticosteroids (up to 60mg/day)
Adding cyclophosphamide lowers risk of disease-related death and morbidity with severe disease
Critically ill at presentation-pulse methylprednisolone (1g IV daily x3d)
Once the pt is in remission for PAN induced by cyclophosphamide, ___ or ___ should be used for remission. What is the 5 year prognosis rate comparing untreated to treated?
MTX or Azathioprine
Untreated ~10-20%
Treated 60-90%
What are poor prognostic factors for PAN? What is death usually related to?
CKD, GI ischemia, CNS dz and cardiac involvement
Death is generally related to GI or cardiovascular causes
What are the complications of PAN?
GI-bowel infarction, hemorrhage
Cardiovascular
Cyclophosphamide treatment
Glucocorticoid toxicity
What is the MC pt for granulomatosis with polyangiitis? What is another name for it?
rare in general
equal sex, WHITE, mean age of onset is 40
Wegener’s
What is Granulomatosis with Polyangiitis characterized by?
Characterized by granulomatous vasculitis of the upper and lower respiratory tracts together with glomerulonephritis
Variable degrees of disseminated vasculitis involving small arteries and veins may occur
_______ hallmark is the necrotizing vasculitis of small arteries and veins together with granuloma formation; intravascular or extravascular
Granulomatosis with Polyangiitis
What is the classic triad of Granulomatosis with Polyangiitis?
Upper airway lesions
Lower airway (lungs) lesions
Renal lesions
______ is associated with higher relapse rates in Granulomatosis with Polyangiitis. A high percentage develop _____
Chronic nasal Staph aureus
High percentage develop ANCA
Often severe upper respiratory tract findings
May have saddle nose deformity
Serous otitis media
Subglottic tracheal stenosis
may have pulm, eye, cardiac, nervous system and skin involvement
Renal disease
purpura
Nonspecific symptoms-malaise, weakness, arthralgias, anorexia and weight loss
What am I?
What will the renal dz present like?
Granulomatosis with Polyangiitis
Mild glomerulonephritis and proteinuria, hematuria and RBC casts
How do you dx Granulomatosis with Polyangiitis? ____ have the highest diagnostic yield
Tissue biopsy-necrotizing granulomatous vasculitis
Pulmonary tissue has highest diagnostic yield
What part of the body when bx may NOT show vasculitis for Granulomatosis with Polyangiitis? What will the kidneys confirm?
Upper airway may not show vasculitis
Renal can confirm pauci-immune glomerulonephritis
What lab test will 90% of pts with Granulomatosis with Polyangiitis be positive? Especially with active _____
90% have positive ANCA
Specificity very high especially with active glomerulonephritis
_____ should NOT be used to assess dz activity in Granulomatosis with Polyangiitis and rise alone does NOT mean relapse
ANCA
What is the tx for Granulomatosis with Polyangiitis? What is the monitoring?
Cyclophosphamide induction with glucocorticoid and follow with gradual taper over 6-9 months
CBC every 1-2 weeks
How long can you safely use cyclophosphamide in GPA tx? Why?
Limit cyclophosphamide to 3-6 months
Long-term use associated with toxicity
When is Rituximab used? What do you need to screen for before starting tx?
used in the tx of GPA and with relapsing disease found to be statistically superior to cyclophosphamide
so use rituximab q week x4 weeks PLUS glucocorticoids
Hepatitis B-> Need to screen PRIOR to initiating treatment
What should you do for the LONG term tx of GPA? What is the 3rd line option?
Change cyclophosphamide after 3-6 months to either methotrexate or azathiprine
If unable to take either-> mycophenolate mofetil
When can methotrexate NOT be given?
CANNOT be given with renal insufficiency or chronic liver disease
and pregnancy
What is the tx for mild GPA? It is assumed to be severe unless stated
Not immediately life threatening or cyclophosphamide toxicity
MTX + glucocorticoid
What abx has show to have some benefit in GPA to help with the sinonasal tissue? What 2 complications in GPA tend to NOT respond to systemic immunosuppressive threatment?
bactrim
Subglottic tracheal stenosis and endobronchial stenosis -> may need to treat these organs specifically
How is Cyclophosphamide eliminated? What 3 things do you need to monitor for?
Monitor renal function closely
infertility, DVT, PE
_____ is necrotizing vasculitis of small and medium sized arteries and veins and the is MC cause of pulm-renal sydrome
microscopic polyangiitis
_____ is diffuse alveolar hemorrhaging + glomerulonephritis that often occurs simultaneously
pulmonary-renal syndrome
What is the mean age of onset for microscopic polyangiitis? What sex?
Mean age of onset is ~57 years old
Males slightly more affected than females
What is Pauci-immune nongranulomatous necrotizing vasculitis? What 2 organ systems? What lab value?
Affects small blood vessels
Often causing glomerulonephritis and pulmonary capillaritis
Associated with ANCA
microscopic polyangiitis overlaps with ______ and _______. What 2 organ systems?
Overlaps with polyarteritis nodosa and granulomatosis with polyangiitis (WG)
Tends to affect capillaries in lungs and kidneys
How is microscopic polyangiitis different from granulomatosis with polyangiitis?
microscopic polyangiitis differentiated from WG by absence of granulomatous inflammation
Palpable “raised” purpura and other signs of cutaneous vasculitis
May see fever, weight loss, musculoskeletal pain
Vasculitis neuropathy, mononeuritis multiplex are common
In cases of pulmonary-renal syndrome interstitial lung fibrosis is presenting condition
What am I?
What are some common lab findings?
Does it have a destructive upper respiratory component?
microscopic polyangiitis
ANCA -> Usually p-ANCA pattern
May have microscopic hematuria, proteinuria, RBC casts in urine
Kidney lesion
NO! MP does not have a destructive upper respiratory tract disease that is seen in GPA
Segmental, necrotizing glomerulonephritis
Often localized intravascular coagulation and intraglomerular thrombi on renal bx
These are describing the kidney lesion for ____
Microscopic polyangiitis
Is Polyarteritis nodosa (PAN) associated with ANCA? Is MPA associated with ANCA?
PAN no ANCA
MPA yes ANCA
What is the tx of microscopic polyangiitis?
tx the same as GPA
Urgent induction tx with corticosteroids + either cyclophosphamide or rituximab
Following remission- discontinue cyclophosphamide and initiate azathioprine, rituximab or MTX
What are the 3 complications of microscopic polyangiitis?
Pulmonary-renal syndrome
Vasculitis neuropathy
Renal insufficiency
_____ is the MC vasculitis in children. What time of the year? What sex?
Henoch Shönlein Purpura (HSP)
Peak incidence in spring
males> females
What is the etiology behind Henoch Shönlein Purpura (HSP)? What are some triggering factors?
Leucocytoclastic vasculitis with IgA deposition
Incited by URIs, drugs, foods, insect bites and immunizations
What 3 things characterizes HSP?
Characterized by palpable purpura,
polyarthralgia, GI s/s, glomerulonephritis
may also have abdominal pain
HSP and _____ are very commonly associated. What joints are the polyarthralgias most common?
Intussusception
Knees and ankles
What can HSP lead to? What will the renal bx show? ____ is usually only elevated in 1/2 of patients
CKD
Bx-segmental glomerulonephritis with crescents and mesangial deposition of IgA
IgA elevated in about ½ of patients
What is the tx of HSP in kiddos? What do you need to monitor these kiddos for moving forward?
Prednisone 1-2 mg/kg/day orally
monitor for kidney disease and screen for proteinuria
What is the tx of severe HSP? What are the complications?
Aggressive immunosuppressants
Mycophenolate mofetil
CKD and bowel obstruction (due to intusseception)
ANCA is the antibody directed against certain proteins in the cytoplasmic granules of ____ and _____. What is a normal test? What do most pts with WG have?
neutrophils and monocytes
normal= negative
Most patients with WG have circulating autoantibodies against neutrophil cytoplasm
What are the 2 types of ANCA?
C-ANCA (cytoplasmic)
P-ANCA (perinuclear)
_____ Shows diffuse, granular cytoplasmic staining pattern observed in immunofluorescence microscopy when serum antibodies bind to indicator neutrophils
C-ANCA
______ produces _____ pattern of staining in the neutrophil cytoplasm
P-ANCA
perinuclear
If the ANCA test is negative, what does that tell you?
Negative-symptoms probably not due to autoimmune vasculitis
