Vasculitis 7% Flashcards
1
Q
What is the DDx for aortitis?
A
Takayasu arteritis Lupus Behcet syndrome Spondyloarthritis Crohn disease (IBD) Cogan syndrome IgG4-RD Fibromuscular dysplasia Tuberculosis
2
Q
What clinical finding is more specific for children with GPA compared to adults with GPA, prompting its inclusion in EULAR/PReS classification criteria?
A
Laryngotracheal/Subglottic stenosis
3
Q
What is the pediatric incidence of Takayasu arteritis?
A
2.6 per million
32% of all TA present at age < 20
4
Q
What is the median age of onset and age range of onset for Takayasu arteritis?
A
Median 10.4 years
Range prenatal through teenage
5
Q
Is Takayasu more common in male or female?
A
Female 2: male 1
6
Q
What infectious etiology is linked to Takayasu but the relationship is still unclear?
A
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.
7
Q
What histocompatibility complex is associated with Takayasu?
A
HLA-Bw52 - may confer worse cardiac outcome
8
Q
Which serum cytokines are increased in Takayasu arteritis?
A
IL-6, IL-18
IFN-gamma, TNF which are essential components of granuloma formation
9
Q
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?
A
The patient has Takayasu arteritis.
MRI/MRA can identify the vasculitis and is the preferred imaging modality in children.
10
Q
What rashes are associated with Takayasu?
A
Livedo reticularis
Erythema nodosum
Purpura
Urticaria
11
Q
What are the symptoms of aortic arch disease?
A
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 😱
12
Q
What is the most common clinical manifestation in pediatric patients presenting with Takayasu arteritis involving the infradiaphragmatic portion of the aorta?
A
Renovascular hypertension due to renal artery involvement
13
Q
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?
A
IBD Takayasu arteritis Hepatitis: infectious vs autoimmune Malignancy Lupus ANCA associated vasculitis EBV mononucleosis Parvovirus infection
14
Q
What symptoms of Takayasu arteritis are more common in adults than children?
A
Claudication
Arthralgia, arthritis
Hypertension more common in kids
15
Q
What are common physical exam findings in Takayasu arteritis?
A
The most important and common findings are decreased/absent peripheral pulses, BP discrepancies between limbs, carotid or abdominal bruits, hypertension.
16
Q
What are the classification criteria for Takayasu?
A
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
17
Q
What laboratory studies maybe elevated in Takayasu arteritis?
A
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
18
Q
What is the first line imaging modality to evaluate for Takayasu arteritis?
A
MRI/MRA of the neck, chest, abdominal, pelvis, plus/minus head
19
Q
What is consider the gold standard imaging modality to evaluate Takayasu arteritis?
A
Conventional angiography with digital subtraction. This is rarely used because it is invasive and exposes a patient to ionizing radiation.
20
Q
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?
A
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.
21
Q
What are some imaging feature seen in Takayasu arteritis?
A
Large vessel wall edema, muscle wall thickening, vessel stenosis, vasodilation, fusiform and saccular aneurysms, mural thrombosis, dissection
22
Q
What is the classic histopathology seen In Takayasu arteritis?
A
Intramural multi nucleated giant cells in large artery walls
23
Q
What is the most common type of Takayasu arteritis in pediatric patients?
A
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
24
Q
What finding may be seen on ophthalmologic exam in Takayasu arteritis?
A
Retinal vasculitis
Recall Dr. Takayasu was an ophthalmologist!
25
What is the differential diagnosis for Takayasu arteritis?
Fibromuscular dysplasia, infectious vasculitis ( syphilis, pyogenic, Brucella, HIV ), Cogan syndrome, Blau syndrome, TB, IBD, PAN
26
What is the mainstay of therapy for Takayasu arteritis?
Corticosteroids - pulse then prednisone 1 mg/kg/day max 60 mg/day then taper
27
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.
28
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.)
29
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
30
What are poor prognostic factors for long-term remission and complications and Takayasu arteritis?
Low BMI, prior stroke, revascularization procedures, renal artery involvement
31
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
32
What is the characteristic histopathology of polyarteritis nodosa?
Necrotizing vasculitis with transmural fibrinoid necrosis and inflammatory infiltrate
33
What is the classic histopathology seen in GPA?
Palisading granulomas with central necrosis
34
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
35
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
36
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
37
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
38
```
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)
39
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)
40
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%
41
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
42
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
43
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.
44
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
45
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.
46
What is considered second-line after oral prednisolone in HSP IgAV nephritis?
Azathioprine
Mycophenolate mofetil
IV methylprednisolone pulse
IV cyclophosphamide if moderate nephritis. May use IV cyclophosphamide as first line in severe nephritis.
47
What fraction of patients with HSP have a self-limited course lasting < 4 weeks?
2/3
These patients usually have a good prognosis. Younger children have shorter course and fewer recurrences
48
What fraction of patients with HSP have at least 1 recurrence?
⅓ of children have at least 1 recurrence that commonly consists of a rash and abdominal pain
Most exacerbations take place w/in 6 weeks of dz onset but may occur as late as 2 years after onset. More severe dz course with GI or joint involvement is associated with a higher incidence of recurrence.
49
What portends poor prognosis in HSP with renal involvement?
Those with a a mixed nephritis-nephrotic syndrome w/in 6 months of onset or the occurrence of numerous exacerbations associated with nephropathy suggests a poor prognosis for renal function
Other poor prognostic factors: decreased factor XIII activity, HTN, renal failure at onset, increased number of glomeruli with crescents (if biopsy), macrophage infiltration and tubulointerstitial disease
50
In patients with IgAV nephritis, what is the prognosis?
With minimal lesions: >75% recover w/in 2 years
66% with crescentic GN in >80% of glomeruli progress to renal failure w/in the first year
Worst outcome is associated with presence of nephrotic or nephritic syndrome at onset
Extent of renal dz is important determinant of long term outcome
<5% of children progress to ESRD, IgAV accounts for <1% of children with renal failure from all causes
51
What is one distinguishing feature of serum sickness like reactions vs serum sickness reaction?
Serum-sickness-like reactions occur within 5-10 days of exposure. Further, most patients don't have true fever. Not associated with Ag-Ab complex formation. No immune complex formation and deposition. Complements will be normal. Raji cell test can test for IC's.
Serum sickness reaction occurs within 7-14 days of exposure
Both can present with fever, rash, joint symptoms.
52
What are some viruses that can cause encephalitis?
Mycoplasma, influenza A, parainfluenza, enterovirus, Epstein Barr virus, varicella zoster virus, cytomegalovirus, and herpes simplex virus
53
A 7 year old boy presents with headache that quickly progresses to focal motor/sensory deficits. CBC with diff, ESR, CRP, UA, CMP are normal. What diagnostic test has the highest diagnostic yield to identify the cause of his symptoms?
MRI, MRA, CTA are the imaging modalities with the highest diagnostic field when considering CNS vasculitis
54
A 13 year old female presents with a three month history of headache, behavioral changes, academic decline. She is admitted to the PICU with new ones that seizures. MRI/MRA of her brain is normal. Conventional angiography evaluating her cerebral vessels is normal. What is the diagnostic gold standard for evaluating for the underlying cause of her presentation?
Brain biopsy
Small vessel childhood primary angiitis of the CNS is suspected.
Histopathology may show direct invasion of one or more layers of the vessel wall by inflammatory cells with Hyalinization/destruction of the vascular endothelium. In small vessel disease, non-granulomatous lymphocytic infiltration of small vessels is the most common finding. This is distinct from adult studies. Microglia activation, often termed microglial nodules, is commonly seen in children with long-standing inflammatory disease but can also be seen in an infection.
Biopsies should be an adequate size (1 x 1x 2 cm3), include all layers (including the meninges, green matter, white matter), and processing should include the snap-frozen section for electron microscopy
55
What is the incidence, sex ratio, and mean age a diagnosis for primary angiitis of the CNS?
Incidence of childhood arterial ischemic stroke is 3.3-7.9 per 100,000. 40 to 60% of arterial ischemic stroke’s are thought to be related to CNS vasculitis.
Males are more commonly affected with medium- large vessel CNS vasculitis. Females are more commonly affected with small vessel CNS vasculitis.
Mean age of onset is 7.2 years
56
What is recommended for induction treatment of CNS vasculitis by the brainworks network?
Prednisone at 2 mg/kg/day, maximum 60 mg/day, tapering monthly
Cyclophosphamide 500- 750 mg/meter squared every four weeks for seven doses
PCP PJP prophylaxis with Bactrim
57
What is recommended for maintenance treatment of CNS vasculitis by the brainworks network?
Taper off of prednisone by 12 to 14 months
Mycophenolate mofetil or mycophenolic acid or azathioprine
Case reports of Remicade, Actemra, or IVIG being used
If refractory to standard treatment, can try monthly Remicade x 6 months, IVIG, and methotrexate
Severe relapse with cyclophosphamide reinduction
58
What is the median age of onset and sex ratio in microscopic polyangiitis?
Mean age 9-12
| 70-90% female except in Turkish and Italian study where 1:1
59
What auto-antibodies are most seen in microscopic polyangiitis?
75% of adult patients with MPA have pANCA with specificity for MPO
MPO found in up to 70% of MPA patients but also in about 10% of GPA pt’s. And PR3 found in mostly GPA pt’s but up to 30% of MPA pt’s
60
What are some associated triggers of microscopic polyangiitis?
propylthiouracil and hydralazine
| infectious triggers not associated (like it is in GPA)
61
What is the classic renal and pulmonary histopathology in microscopic polyangiitis?
Necrotizing vasculitis with few or no immune deposits (pauci-immune) predominantly affecting small vessels.
Necrotizing glomerulonephritis and pulmonary capillaritis are common and granulomatous inflammation is negative.
In 2 Chinese series, 93%-100% of pt’s had crescentic GN on renal biopsy.
62
What is a finding on BAL in MPA or GPA that would be evidence of pulmonary hemorrhage?
Hemosiderin-laden macrophages in pulmonary hemorrhage in MPA and GPA
63
How can you distinguish MPA from Good Pasture (anti-GBM disease)?
⅓ of patients with anti-GBM disease may have anti-GBM and ANCA; differentiate from MPA by immunofluorescence microscopy on renal biopsy that shows linear deposition of IgG along the glomerular BM
64
How can you distinguish GPA from MPA?
Presence of granulomatous inflammation, URI involvement (nasal septal perforation and/or saddle-nose deformity), chest imaging with nodules, nodular infiltrate, or cavitation representing granulomatous inflammation rather than capillaritis, presence of PR-3 more common in GPA.
65
How can you distinguish PAN from MPA?
Absence of ANCA/MPO and rapidly progressive GN, and lung hemorrhage and presence of microaneurysms and other angiographic findings
66
How can you distinguish HSP from MPA?
Clinical course or histopath with well-defined or prominent IC deposits of IgA
67
What is the incidence of GPA in the US?
1.8 cases per 1 million children
68
A teenage male presents with hemoptysis and glomerulonephritis. CXR has lung nodules. He has a history of recurrent upper respiratory infections. What condition is this triad of symptoms suggestive of?
Granulomatosis with polyangiitis (GPA)'s classic triad is: respiratory tract inflammation, lower respiratory tract inflammation, renal disease.
69
What other clinical features are suggestive of GPA?
Saddle nose deformity, nasal septal perforation, subglottic stenosis, dacryocystitis, proptosis associated with periorbital tumor, lung nodules, or presence of granuloma on bx
70
In a patient with pulmonary hemorrhage and renal disease, what diagnostic evaluation is indicated to work up GPA?
```
Urinalysis
Urine protein/Cr ratio
CXR
HRCT chest
PFT's
ENT consult for evaluation of upper respiratory tract involvement
```
71
What finding may be seen on PFTs in GPA?
Increase in DLCO could indicate pulmonary hemorrhage
72
What is the classic finding on renal biopsy in GPA?
Pauciimmune immunofluorescence necrotizing vasculitis
73
What autoantibodies are classically associated with GPA?
Iin one cohort, 95% of children had ANCA
Cytoplasmic-ANCA, PR-3 → exact value not listed in book 67-80%
Perinuclear-ANCA, MPO 10-26%
The classic antibody associated with GPA is PR-3
50% of localized GPA is ANCA negative
74
In what percentage of patients with GPA is ANA or RF present?
ANAs present in ⅓ children. RF 50% of children
75
What is the classic finding on HRCT chest in GPA with pulmonary involvement?
“Halo sign” for hemorrhage and ground glass opacities around lesions, nodules
76
What is the classic histopathology seen in GPA?
Necrotizing granulomas of upper and lower resp tract with necrotizing or granulomatous vasculitis involving small arteries and veins
Granulomata show acute and chronic inflammation with central necrosis and histiocytes, lymphocytes and giant cells. Eosinophils in small numbers.
77
What is the classic renal histopathology seen in GPA?
Focal segmental necrotizing glomerulonephritis
Most commonly reported renal lesions are extracapillary proliferation (w/w/o fibrinoid necrosis) and crescent formation found in a focal and segmental pattern followed by necrotizing glomerulonephritis
Renal glomeruli infiltrated by lymphocytes and histiocytes
Earliest renal change may be glomerular thrombosis
Renal granulomata rare
Immunofluorescence is pauci-immune with scanty deposition of Ig and complement
Dense subendothelial deposits are visible on EM
78
What is the differential diagnosis for GPA?
Goodpasture syndrome/anti-GBM disease - has linear immunofluorescence instead of pauciimmune
Microscopic polyangiitis
EGPA
IgG4 related dz
ANCA positive UC patients can have pulm manifestations similar to GPA
Lupus
MCTD
IgAV
Polyarteritis nodosa
Infection: Mycobacteria, fungal, helminthic ---> may have granulomatous vasculitis as well
Where lung biopsy would be useful to evaluate for infection
Saroidosis (non necrotizing)
Chronic granulomatous disease in young children
Cancer
79
What is the reported outcome in children with GPA?
In kids, reported 7% overall mortality rate at follow up of 4-55 months. Another 6% over 5.2 years.
Remission rate in kids reported at 40-90%
1-year mortality in adults of untreated disease is 80% and in adults with Cytoxan protocol treatment, 5-7 year mortality is now 10-25%.
80
What is the reported prognosis in children with GPA?
GPA has relapsing course
For relapsing GPA, rituximab > cyclophosphamide (RAVE Trial)
81
What are complications of GPA?
Increased risk of cardiac disease and cardiovascular related events (CV death, stroke, CAD, MI)
Malignancy likely low (may be from CYC exposure)
Osteoporosis, CKD, ESRD, infertility, cystitis, diabetes, hearing loss and avascular necrosis
In peds, ENT damage common: hearing impairment, nasal/septal/upper airway deformities, 25% airway stenosis (predominantly subglottic)
82
For a patient with eosinophilic granulomatosis with polyangiitis (EPGA) with cardiac involvement,
Of the following, in addition to steroids, the medication with the MOST data to support its use for this patient is:
A. azathioprine
B. cyclophosphamide
C. omalizumab
D. rituximab
B. cyclophosphamide
There have been no large trials assessing the most effective agent to add to steroids in these cases. However, cyclophosphamide has the most favorable data to support its use.
Only case reports for rituximab and EGPA was excluded in the trials that of rituximab in GPA and MPA.
Omalizumab is a monoclonal antibody to IgE that is used in the treatment of severe allergic asthma but has not shown efficacy thus far in EGPA
azathioprine for maintenance therapy not induction
mepolizumab, an IL-5 antagonist, has shown promising results in a randomized, placebo-controlled trial. Based on this trial, mepolizumab was approved by the Food and Drug Administration for treating adult patients with EGPA in December 2017.
83
A patient presents with interstitial keratitis, tinnitus, ataxia and was found to have bilateral hearing loss that ended up being fluctuating but progressive. What is the diagnosis?
Cogan syndrome
1. Interstitial keratitis
2. Bilateral sudden hearing loss that is fluctuating but progressive
- Meniere like symptoms
Associated with vasculitis. 10% will have aortitis.
84
What is the rheumatologic differential for patients with both vision loss and hearing loss?
```
Behcet
Sarcoidosis
Antiphospholipid syndrome
Lupus
Sjogren
PAN
GPA
Cogan
VKH syndrome
RA
Relapsing polychondritis
IBD
Susac
DADA2
```
85
What syndrome can present with CNS dysfunction, sensorineural hearing loss, and branch retinal artery occlusion?
Susac syndrome
86
If a teen girl presents with auto-immune encephalitis what part of her body should you image after the brain and why?
The abdomen and pelvis
An ovarian teratoma is present in approximately 30% of adolescent girls with anti-NMDAR encephalitis, and prompt excision of the teratoma is essential to treat the central nervous system disease. Imaging of the abdomen and pelvis is thus critical for any adolescent with suspected or confirmed autoimmune encephalitis.
87
What disease in the heart can mimic vasculitis?
cardiac myxoma
88
What preceding event is seen in some patients with PAN?
Strep infection
Treat Strep and consider prophylaxis. 25% of patients will have recurrence of PAN with Strep exposure
89
What conditions are associated with PAN?
FMF
| DADA2
90
What is seen on histopath in PAN?
Necrotizing nongranulomatous vasculitis of small to medium artery with fibrinoid necrosis and marked inflammatory response within or around Edsel wall. May be patchy.
91
What is the age of onset and sex ratio in Kawasaki disease
77% of cases < 5 years old
Average age 3
Sex ratio 1.36-1.63 M to 1 F
92
What inflammatory mediators are elevated in KD?
TNF-a and IL-1
93
What are risk factors for coronary artery involvement in KD?
Incomplete KD
Age < 12 months. Consider KD in any infant with prolonged, unexplained fever with low threshold for echo (recall PREP question)
Older children
94
When do coronary artery aneurysms typically present themselves in KD?
In subacute phase when periungal desquamation occurs and arthritis can occur. Platelets and ESR resolve.
95
How does myocarditis present in KD?
Tachycardia out of proportion to fever, S3 gallop, +/- CHF and dysrhythmia
96
How does Kawasaki disease shock syndrome present?
Systolic hypotension >= 20% decrease in baseline SBP or sign of poor perfusion
1/3 had impaired LVSF
2/3 had coronary artery abnormalities
IVIG resistance common
97
How long must one wait before giving live vaccines in a child who has been treated for Kawasaki disease?
Wait 11 months after receiving IVIG for KD
98
What % of patients with HSP develop glomerulonephritis by:
Week 4?
Week 6?
6 months?
Week 4: 85%
Week 6: 91%
6 months: 97%
Patients must be followed at minimum 6 months by PCP for recurrent BP checks and UAs.
99
What are risk factors for glomerulonephritis in HSP?
Age of onset > 7
Persistent purpura,
Severe abdominal symptoms,
Decreased factor 13 activity
100
A 20 month old male presents with low grade fever, purpura and ecchymoses of arms/legs, ears, and face. His hands and feet are mildly swollen. His labs were normal except mildly elevated WBC and plt. His symptoms resolved by day 7. What is the diagnosis?
Acute hemorrhagic edema of infancy
101
True or False: glucocorticoids prevent the onset of HSP nephritis
False
There may be a benefit of using an ACE-I or ARB in children with HSP and persistent proteinuria beyond 3 months though.
102
are these symptoms associated with long term renal disease in HSP?
Hematuria w/wo non-nephrotic range proteinuria
Elevated creatinine, HTN, nephrotic range proteinuria
Hematuria w/wo non-nephrotic range proteinuria not associated with long term renal disease
Elevated creatinine, HTN, nephrotic range proteinuria associated with long term renal disease
103
What type of hypersensitivity are hypersensitivity vasculitis and serum sickness?
Type 3 hypersensitivity - immune complex mediated
104
A 6 year old male presents with fever, rash, ankle and knee swelling, and tummy ache. He had an ear infection a little over a week ago and had started amoxicillin 10 days ago. What is the diagnosis?
Serum sickness
Occurs 7-14 days after primary exposure
Lasts a few weeks
Involves ankles, knees, wrists, MCPs
105
What are the differences between serum sickness and serum sickness like reaction?
Serum sickness:
7-14 days after exposure
Immune complex mediated
May have true fever
```
Serum sickness like reaction:
5-10 days after exposure
No immune complex deposition
Most don’t have true fever
Complements normal
```
106
hypocomplementemic urticarial vasculitis (HUV) is associated with what antibody?
C1q antibodies
Hypocomplementemic urticarial vasculitis presents with recurrent episodes of often painful urticaria that last several days. Residual skin hyperpigmentation can occur.
Diagnosis of hypocomplementemic urticarial vasculitis is based on typical skin findings, low complement levels, and minor criteria including C1q antibodies.
107
A female patient presents with recurrent urticaria that lasts for 3 days at a time with fever, abdominal pain, and arthralgias. The urticaria is described as burning rather than itchy and leaves behind residual pigmentation. What lab tests are consistent with the diagnosis?
Diagnosis is hypocomplementemic urticaria vasculitis.
Complements may be normal or low
May have positive C1q Ab
108
A patient with DiGeorge syndrome presents with purpura of his distal extremities after cold exposure. Labs reveal elevated liver enzymes, elevated, Cr, and urinalysis with proteinuria and hematuria. His C4 is low and RF is positive. What is the diagnosis and treatment?
Vasculitis associated with Mixed Cryoglobulinemia
Tx: steroids, cyclophosphamide, plasmapheresis, IVIG
Rituximab seems to work well too
A vasculitis with immune complex deposits in capillaries, venules, arterioles of the skin and kidneys with cryoglobulins in the serum
Usually secondary to Hepatitis C infection but also associated with DiGeorge, chronic Salmonella, sickle cell anemia, thalassemia, end HSP
Distal extremity purpura triggered by cold exposure can ulcerate. It’s the earliest and most common (> 75%) sign
Arthralgia is also common. Frank arthritis in 10%. Polyneuropathy, Ryanair phenomenon, liver enzyme abnormalities. MPGN and HTN occur later in disease course (> 50%).
Labs with Type II (monoclonal IgM) and Type III (polyclonal IgM) cryoglobulins and
Low C4
Positive RF
Hematuria, proteinuria
109
What are possible triggers of eosinophilic granulomatosis with polyangiitis?
Vaccines
Allergens
Infections
Drugs
110
True or False: EGPA may have ANCA antibodies.
True - 0-30% of EGPA have positive ANCA
ANCA positive phenotype: GN, alveolar hemorrhage, ENT involvement, peripheral nerve involvement, biopsy proved vasculitis
ANCA negative phenotype: cardiac involvement
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A child severe persistent asthma often requiring steroids and chronic allergic rhinitis with nasal polyposis presents with petechiae, palpable purpura, abdominal pain, nausea, arthralgias. Labs remarkable for eosinophilia of > 10% of WBCs. CXR with bilateral pulmonary infiltrates. What would skin biopsy show? What is the diagnosis?
Eosinophilia Granulomatosis with Polyangiitis
Histopath shows eosinophilic infiltration of granulomas and vasculitis.
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A full-thickness skin biopsy of a lesion reveals necrotizing vasculitis with staining for IgM and C3.
What does the patient have?
What meds can you use for treatment
cutaneous polyarteritis nodosa (cPAN)
with the presence of tender, erythematous/violaceous, subcutaneous nodules.
Diagnosis is typically made by excisional or full-thickness skin biopsy, which reveals necrotizing vasculitis, fibrinoid necrosis of the affected vascular walls, neutrophilic infiltration with nuclear fragmentation, and erythrocyte extravasation in the medium-sized vessels with staining for IgM and C3. Biopsy should ideally be performed on new lesions that are 24 to 48 hours old, because immunofluorescence will likely be absent after 72 hours. Additionally, systemic involvement must be ruled out.
Treatment: Treatments that have been used with varying success include nonsteroidal anti-inflammatory drugs, steroids, methotrexate, dapsone, mycophenolate mofetil, intravenous immunoglobulin, colchicine, azathioprine, cyclophosphamide, pentoxifylline, and chloroquine. Severe cases may also be treated with infliximab or etanercept. Possible treatments for patients with necrosis, infarction, and gangrene include anticoagulation or vasodilation with aspirin, calcium channel blockers or systemic vasodilators, or pentoxifylline.
Cyclosporine has NOT typically been shown to be useful in the initial treatment of cPAN
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What infection is a common cause of angiography-positive nonprogressive primary angiitis of the central nervous system?
latent varicella infection
