Vasculitis 7% Flashcards
What is the DDx for aortitis?
Takayasu arteritis Lupus Behcet syndrome Spondyloarthritis Crohn disease (IBD) Cogan syndrome IgG4-RD Fibromuscular dysplasia Tuberculosis
What clinical finding is more specific for children with GPA compared to adults with GPA, prompting its inclusion in EULAR/PReS classification criteria?
Laryngotracheal/Subglottic stenosis
What is the pediatric incidence of Takayasu arteritis?
2.6 per million
32% of all TA present at age < 20
What is the median age of onset and age range of onset for Takayasu arteritis?
Median 10.4 years
Range prenatal through teenage
Is Takayasu more common in male or female?
Female 2: male 1
What infectious etiology is linked to Takayasu but the relationship is still unclear?
Mycobacterium tuberculosis
Some studies show an increased incidence of LTBI or active TB or positive TB test and some studies don’t. The association of Takayasu with TB is rare in “developed” countries.
Also associated with HIV, post influenza, hepatitis B but rare in children.
What histocompatibility complex is associated with Takayasu?
HLA-Bw52 - may confer worse cardiac outcome
Which serum cytokines are increased in Takayasu arteritis?
IL-6, IL-18
IFN-gamma, TNF which are essential components of granuloma formation
A 10 year old female presents with fever, weight loss, fatigue, and abdominal pain. Her R arm BP is 160/100. Her labs are notable for normocytic anemia, thrombocytosis, ESR 78, CRP 20.
What diagnostic study could confirm the diagnosis?
The patient has Takayasu arteritis.
MRI/MRA can identify the vasculitis and is the preferred imaging modality in children.
What rashes are associated with Takayasu?
Livedo reticularis
Erythema nodosum
Purpura
Urticaria
What are the symptoms of aortic arch disease?
Supradiaphragmatic involvement
Headache, visual disturbance (amaurosis fugax), arterial ischemic stroke, syncope, dizziness, cognitive dysfunction, seizures, carotidynia
Dyspnea, chest pain, palpitations, valvular disease, cardiomyopathy leading to CHF
Rarely, patients may present with myocardial infarction 😱
What is the most common clinical manifestation in pediatric patients presenting with Takayasu arteritis involving the infradiaphragmatic portion of the aorta?
Renovascular hypertension due to renal artery involvement
A 15 year old female presents with fever, weight loss, fatigue, intermittent abdominal pain, diarrhea, vomiting. Her BP is 135/95. Her ESR and CRP are elevated. She has a mild normocytic anemia. She has a mild transaminitis. What is on the broad differential?
IBD Takayasu arteritis Hepatitis: infectious vs autoimmune Malignancy Lupus ANCA associated vasculitis EBV mononucleosis Parvovirus infection
What symptoms of Takayasu arteritis are more common in adults than children?
Claudication
Arthralgia, arthritis
Hypertension more common in kids
What are common physical exam findings in Takayasu arteritis?
The most important and common findings are decreased/absent peripheral pulses, BP discrepancies between limbs, carotid or abdominal bruits, hypertension.
What are the classification criteria for Takayasu?
Angiographic abnormalities and at least 1 of the following 5:
Decreased peripheral artery pulses and/or claudication of extremities
Blood pressure difference between limbs of more than 10 mmHg
Bruits over aorta and/or it’s major branches
Systolic/diastolic hypertension greater than 95th percentile for height
ESR greater than 20 or CRP greater than normal
What laboratory studies maybe elevated in Takayasu arteritis?
Inflammatory markers, von Willebrand factor Ag, platelets
1/3 of patients at presentation do not have elevate and inflammatory markers, likely representing patients with burned out disease
Anemia may also be present. There are usually no auto antibodies. ANA is detected in 22 to 36% of cases. In the few patients with ANCA positive, MPO and PR3 or negative
What is the first line imaging modality to evaluate for Takayasu arteritis?
MRI/MRA of the neck, chest, abdominal, pelvis, plus/minus head
What is consider the gold standard imaging modality to evaluate Takayasu arteritis?
Conventional angiography with digital subtraction. This is rarely used because it is invasive and exposes a patient to ionizing radiation.
A patient with the diagnosis of Takayasu arteritis has a repeat MRA documenting large vessel wall edema and wall thickening that is stable compared to previous imaging. Can we say that this patient has active disease? Can we say that this patient is not responding to therapy?
No, vessel wall edema and wall thickening are not always reversible, even in patients with clinically inactive disease. It may be difficult to use serial imaging to monitor response to treatment or disease activity. The development of new lesions in Takayasu arteritis is a more important sign of disease activity.
What are some imaging feature seen in Takayasu arteritis?
Large vessel wall edema, muscle wall thickening, vessel stenosis, vasodilation, fusiform and saccular aneurysms, mural thrombosis, dissection
What is the classic histopathology seen In Takayasu arteritis?
Intramural multi nucleated giant cells in large artery walls
What is the most common type of Takayasu arteritis in pediatric patients?
Type IV, where there is abdominal aorta and/or renal artery involvement
Type V, where there is ascending aorta, aortic arch and it’s branches, thoracic descending aorta, abdominal aorta, and/or renal artery involvement
What finding may be seen on ophthalmologic exam in Takayasu arteritis?
Retinal vasculitis
Recall Dr. Takayasu was an ophthalmologist!
What is the differential diagnosis for Takayasu arteritis?
Fibromuscular dysplasia, infectious vasculitis ( syphilis, pyogenic, Brucella, HIV ), Cogan syndrome, Blau syndrome, TB, IBD, PAN
What is the mainstay of therapy for Takayasu arteritis?
Corticosteroids - pulse then prednisone 1 mg/kg/day max 60 mg/day then taper
What is the most common biologic used in the treatment of Takayasu arteritis?
Infliximab > adalimumab
Infliximab was found to be equivalent to Cytoxan in efficacy with fewer side effects and easier steroid tapering
Tocilizumab has shown promise in pediatric TA though adult studies looking at abatacept and tocilizumab failed primary outcome of preventing flares with steroid taper.
Why should ACE-I be used with caution in Takayasu arteritis?
ACE-I decreased bilateral renal artery blood flow resulting in decreased renal function and can worsen outcome in child with aortitis. (ACE-I should be used with caution patients with renal artery stenosis because they have a hyper-renin situation where a drop in blood pressure from the ACE-I can lead to decreased perfusion to organs with stenosed vessels.)
What are risk factors for mortality in Takayasu arteritis?
Younger age of onset, higher disease damage score
Common causes of death: aortic dissection, cardiomyopathy, heart failure, hypertensive crisis, myocardial infarction, stroke, renal failure
What are poor prognostic factors for long-term remission and complications and Takayasu arteritis?
Low BMI, prior stroke, revascularization procedures, renal artery involvement
What is the characteristic histopathology of Henoch Schonlein purpura?
Leukocytoclastic vasculitis in dermal capillaries and post-capillary venules. Leukocytoclasis refers to infiltration of PMN’s into vessel walls, resulting in necrosis with scattered nuclear debris.
IgA deposition in lesions - may fail to detect if fsample is obtained in the middle of the lesion where proteolytic enzymes are
What is the characteristic histopathology of polyarteritis nodosa?
Necrotizing vasculitis with transmural fibrinoid necrosis and inflammatory infiltrate
What is the classic histopathology seen in GPA?
Palisading granulomas with central necrosis
What is the most common renal histopathology seen in GPA?
Extracapillary proliferation with or without fibrinoid necrosis and crescent formation in focal and segmental pattern.
Renal granulomata are rare.
Immunofluorescence: Pauciimmune pattern with scanty deposition of Ig and complement
What is the most common general and renal histopathology seen in MPA?
Pauci-immune necrotizing vasculitis predominantly affecting small vessels and necrotizing glomerulonephritis
Renal path may look like other types of ANCA-associated vasculitis
What is the histopathology seen in Churg-Strauss/Eosinophilic Granulomatosis with Polyangiitis (EGPA)?
Defining characteristic: large number of eosinophilic infiltrates with angiitis and extravascular necrotizing granulomas
Angiitis may be GRANULOMATOUS or nongranulomatous, involves arteries and veins, can include pulmonary and systemic blood vessels
Churg-Strauss granuloma – skin nodules and papules over extensor surfaces of joints
Also can have palisading granulomas with central necrosis, which also is seen in SLE, etc. and leukocytoclastic vasculitis
What is the most common finding on brain biopsy in primary angiitis of the CNS?
Nongranulomatous lymphocytic infiltration of small vessels. Can also see macs, PMNs, and occasional eosinophils
Microglial nodules (microglia activation) is commonly seen with long-standing inflammation
Brain biopsy should be adequate size (1x1x2 cm), include all layers (meninges, gray, and white matter) and processing should include snap-frozen section for EM
In contrast, adults have necrotizing, granulomatous lesions
What is the epidemiology of Henoch Schonlein Purpura? Age Gender Seasonal variation Relation to antecedent illness Incidence
Age: 3-15, mean 7
Gender: 1.5 M: 1 F
Seasonal variation: winter
Relation to antecedent illness: 30-50% preceded by URI
Incidence: Variable, 9-86 per 100,000 in a study by Farley et al
Highest amongst Hispanic children and lower socioeconomic status (69 per 100,000 vs. 9-11 per 100,000)
A 7-year-old male presents with a 7-day history of erythematous maculopapular rash on his lower extremities and buttocks that progressed into red/violaceous, raised patches. A few days ago, he started limping, and mother noticed generalized boggy swelling of his feet, ankles, and hands. Today, he has a tummy ache that comes and goes. What is the diagnosis?
Henoch Schonlein Purpura (HSP)
A 7-year-old male presents with a 7-day history of erythematous maculopapular rash on his lower extremities and buttocks that progressed into red/violaceous, raised patches. A few days ago, he started limping, and mother noticed generalized boggy swelling of his feet, ankles, and hands. Today, he has a tummy ache that comes and goes. What is a complication of this condition that the PCP should monitor for?
GLOMERULONEPHRITIS occurs in up to 1/3 of patients, but it is life-threatening in < 10%
Patients who present with HSP GN: within 4 weeks of onset 85% of patients, within 6 weeks in 91% of patients, and within 6 months in 97%
What changes in the complement pathway may occur in HSP?
C1q, C3, C4 usually normal but may have activation of alternative pathway during acute illness leading to elevated C3d, low CH50, properdin and factor B
What GI abnormality may be seen on US or Barium study in HSP?
Vasculitis of bowel wall resulting in edema and submucosal/intramural hemorrhage may lead to intussusception (usually ileo-ileal and confined to small bowel), gangrene, or perforation
What is the differential diagnosis for HSP?
PSGN ITP SLE Septicemia DIC HUS ANCA
Possible link between Crohn’s and IgA vasculitis-IgA can cause terminal ileitis or they can occur together. CD also can cause LCV.
Papular-purpuric gloves and socks syndrome-from viral infections
FMF can mimic or occur in association with HSP in areas where FMF is endemic
Infantile acute hemorrhagic edema (Finkelstein-Seidlmayer syndrome) affects infants between 4-24 months with fever, purpura, ecchymoses and inflammatory edema of the limbs, ears and face.
What are indications for use of corticosteroids in HSP?
Moderate-severe abdominal symptoms
Severe pain with orchitis
Cerebral vasculitis
Pulmonary hemorrhage
Prednisone of 1-2mg/kg/day for 2 weeks with taper over 1-2 week was effective in reducing the intensity of abdominal pain and joint pain.
UpToDate mentions that longer tapers over 4-8 weeks may be beneficial to prevent recurrence of abdominal sx with steroid taper
For GI dz, no clear advantage of prednisone over supportive tx. Could be a role for early use of steroids in pt’s with severe sx’s and in those with renal involvement.
Prophylactic steroids NOT effective in preventing glomerulonephritis
What treatment is indicated in pulmonary hemorrhage in HSP?
IV methylprednisolone pulsing and cyclophosphamide or cyclosporine. Maybe plasma exchange. Would assume the same for CNS dz.
