Vasculitis Flashcards
HSP classification
Palpable purport with lower limb predominance plus at least one of the following:
- Diffuse abdominal pain
- Biopsy showing typical leukocytoclastic vasculitis OR proliferative glomerulonephritis with predominant IgA deposition
- Arthritis or arthralgia
- Renal involvement (any hematuria and/or proteinuria)
Indications for renal biopsy in HSP
- Impaired GFR
- Severe or persistent proteinuria
- Renal biopsy should be considered in cases of
- Acute kidney injury with worsening renal function as part of a rapidly progressing glomerulonephritis
- Nephrotic Syndrome (heavy proteinuria, hypoalbuminemia, and edema)
- Nephritis Syndrome (impaired GFR, HTN, hematuria/proteinuria)
Principle lesion found in HSP nephritis
Endocapillary proliferation with an increase in endothelial and mesangial cells
- IgA, fibrin, C3 and properdim in most involved glomeruli
- Peripheral capillary loops involved in more severe cases
Poor prognostic factors in HSP
- Mixed nephrotic nephritis syndrome within the first 6 months
- Decreased factor XIII activity
- HTN
- Renal failure at onset
- Increased number of glomeruli with crescents
- TI disease or macrophage infiltration
When do GI and renal manifestations typically occur in HSP
GI occur usually within a week
Renal usually develops within 6-8 weeks of rash but should monitor for 6 months
Lab findings in HSP
NORMAL platelet count Moderate leukocytosis Normochromic anemia May have positive stool guiac ANA/ RF negative UA abnormalities Hypoalbuminema with proteinuria Complements usually normal Ancas negative
Most common season for HSP
Winter
Classification criteria for hypersensitivity vasculitis/serum sickness
Need 3/6
- Age at onset >16
- Medication at disease onset
- Palpable purpura not related to thrombocytopenia
- Maculopapular rash
- Characteristic biopsy findings
Pathology of hypersensitivity
vasculitis
- Cellular infiltrate contains a large number of neutrophils and eosinophils
- Granulocytes present in perivascular or extravascular location
Labs associated with Hypersensitivity vasculitis
- leukocytosis
- Eosinophilia
- ESR is NORMAL
Classification criteria for PAN
1. Evidence of necrotizing vasculitis in medium or small arteries or angiographic abnormality showing aneursym, stenosis, or occlusion of a medium or small sized artery (histo or angio mandatory) plus at least 1 A. Skin involvement - Livedo - Skin nodules - Infarcts
B. Myalgia or muscle tenderness C. HTN - Systolic/diastolic blood pressure >95th percentile for height D. Peripheral neuropathy - Sensory - Motor mononeuritis multiplex E. Renal involvement - Proteinuria - Hematuria - Impaired renal function
Viral/bacterial trigger for PAN
Hepatitis B + Strep
Genetic mutation that may predispose to PAN
MEFV
Typical labs for PAN
Leukocytosis
Thrombosis
ESR/CRP
UA –> protein, hematuria
ANA and ANCA typically negative
Characteristic histopath of PAN
Fibrinoid necrosis of the walls of medium or small arteries with a marked inflammatory response within or surrounding the vessel wall
- Lesions tend to be focal and segmental
What increases risk of relapse in PAN?
Gi involvement
Symptoms of cutaneous PAN
Fever, nodular, painful non purpuric lesions with or without livedo racemosa, occurring predominantly in the lower extremities and with NO systemic involvement except for myalgias, arthralgia, and nonerosive arthritis
Skin biopsy of cPAN
necrotizing, non granulomatous small and medium sized vasculitis
Bacterial cause for cPAN
strep infection
Diagnostic Criteria for Kawasaki
Fever for more than 5 days plus 4/5 following signs CRASH Conjunctivitis Rash Adenopathy Strawberry tongue Hand and feet swelling
Acute febrile phase of KD
- Lasts 10-14 days
- Onset of fever is abrupt
- Irritability, vomiting decreased PO, diarrhea, abd pain, cough, rhinnorhea, weakness, arthralgia, arthritis, perineal desquamation in days leading up to presentation
- Over next 3-4 days, cervical LAD, conjunctivitis, changes in oral mucosa, pleomorphic rash, erythema and edema in hands and feet
- No particular order
- If untreated, clinical signs subside after about 12 days
- Myocarditis, pericarditis, abd pain, ascites and hydrops of gallbladder may occur during this phase
Subacute phase of KD
- 2-4 weeks
- May be entirely asymptomatic if given IVIG
- Desquamation of skin (digit) may be only clinically apparent residual feature
- May develop arthritis
- CAA most commonly first develop during this phase
- Irritability resolves
- Phase ends with return to normal of platelet count and ESR
Convalescent phase
- Most children asymptomatic
- Beau lines (horizontal ridging of nails) may appear
- Vessels undergo healing, remodeling and scarring
IVIG resistance in KD
- Higher CRP, LDH, bilirubin
- Hyponatremia
- ELEvated LFTs
- high percentage of bands
- platelets less than 300000
- SHort duration between fever and diagnosis
- <12 months at onset or older than typical
Incomplete KD
Seen more frequently in younger infants and older children
- Fever greater than or equal to 5 and 2 or 3 clinical criteria
- Check CRP and ESR >3/40
- Albumin <3
- Anemia for age
- Elevated ALT
- Platelets after 7 days >450k
- WBC >15
- Urine WBC >10
Pathology of KD coronaries
Systemic necrotizing vasculitis with fibrinoid necrosis
- Begins with neutrophilic vasculitis (saccular)
- Chronic vasculitis (lymphocytes, eosinophils, macrophages, IgA secretign plasma cells)– Fusiform anerurysms
- Smooth muscle cells may be converted to myofibroblasts
Markers for severe disease
significant neutropenia
thrombocytopenia
Infantile polyarteritis nodosa
onset before age 2, most commonly affects coronaries
- frequently presents with heart failure, may also have renal, GI, CNS manifestations
What is considered an abnormal coronary?
if age less than 5, >3, if 5 and up, >4
Aneursym if the diameter is 1.5x the size of the adajcent vessel
Signs of MAS in KD
Thrombocytopenia, anemia and modest elevation of the ESR
Small Aneurysm
Z score <= 2.5 to <5 (or less than 4mm)
Medium Aneurysm
Z score 5 to <10 (4-8mm)
Large Aneurysm
Z >= 10 (>8mm)
Antibody associated with MPA
Anti-MPO
Three phases of EGPA
- Very prolonged prodromal period over many years with asthma and other allergic manifestations (chronic rhinitis and nasal polyposis)
- Eosinophilic phase with eosinophilia and pulmonary infiltrates
- Vasculitis
ACR criteria for GPA
- Requires 2/4
- Nasal or oral inflammation
- Abnormal CXR
- ABnormal UA
- Granulomatous inflammation
Eular includes stenosis and ANCA
Limited granulomatosis
No kidney disease
Disease may just be limited to upper resp tract
First sign of pulmonary hemorrhage
increased DLCO
What differentiates MPA versus GPA?
- Upper airway disease (saddle nose deformity, nasal septal perforation, subglottic stenosis, dacryocytitis, proptosis, characteristic lung nodules, granulomas)
Common antibody associated with GPA
cANCA (PR3)
What biologic should NOT be used in GPA and why
- Etanercept
- Risk of cancer
GPA kidney disease
focal segmental necrotizing vasculitis
EGPA ACR criteria
4/7
- Asthma
- Eosinophil
- History of allergy
- Mononeuropathy/polyneuropathy
- Pulmonary infiltrates
- Paranasal sinus
- Extravascular eosinophils
Risk factors for worse prognosis of EGPA
- Renal insufficiency
- Proteinuria greater than 1g/day
- cardiomyopathy
- CNS involvement
- GI involvement
Diagnostic criteria for hypocomplementemic urticaria
Major criteria
- recurrent urticaria
- low complement levels
Minor Criteria (need at least two)
- Venulitis on skin biopsy
- Arthritis
- Ocular inflammation
- Abd pain
- positive c1q antibodies
- glomerulonephritis
Positive ANA, dsDNA are exclusion criteria
Criteria for Behcets
- Recurrent oral aphthosis (at least 3/year)
- Genital ulceration typically with a scar
- Skin features (Acneiform lesions, necrotic follicultis, erythema nodosum)
- Ocular involvement (anterior and or posterior uveitis, retinal vasculitis )
- Neurological signs (with the exception of headache)
- Vascular involvement (venous thrombosis, arterial thrombosis, arterial anersuym)
Potential triggers for Behcets
- Parvo
- HSV1
- Strep
Pathology of Behcets
Misfolding of HLA b51
ERAP1
IL-23/IL17
What is Pathergy?
Cutaneous pustular reaction occurring 24 to 48 hours after a needle puncture of the dermis
Indicators of poor prognosis in Behcets
young age at onset
male
Hallmark of Sarcoidosis
Non-caseating epitheliod giant cell granulomas in a variety of tissues and organ systems
Classic triad of Blau Syndrome (with NOD2 mutation)
- Poly arthritis
- Uveitis
- Dermatitis
Infantile onset Sarcoid without NOD2
- Infantile onset panniculitis with uveitis and systemic granulomatosis
- Panniculitis, severe systemic involvement, persistent fever, hepatosplenomegaly, granulomatous inflammation of joints, eyes, internal organs, CNS
- Progressive
Pediatric adult onset sarcoidosis
- Systemic features (pulm and LAD) rather than articular disease
- Malaise, fever, weight loss, lung involvement, hilar LAD, hepatosplenomegaly, cutaneous features, renal sarcoidosis, myositis etc
Neurosarcoidosis presenttion of sarcoid
Seizures ( cranial nerve palsy, most common complication in adults )
Lofgren’s syndrome
Acute onset arthritis (mainly of the ankles), e nodosum, and hilar adenopathy ( rare in peds
Mikulicz syndrome
parotid and lacrimal gland enlargement (rare in peds)
Uveitis of sarcoid
tightly packed corneal accumulations of lymphocytes with firm edges located in the peripheral cornea
may be confluent and form a snowbanking
- More involvement of posterior portion
Koeppe nodules
Present on Iris pupil margin
Other gene name for NOD2
CARD15
Cause of hypercalcemia and hypercalcuria
Overproduction of 25 hydroxyvitamin D1 alpha hydroxylase which convers 25 OHD to 1-25 by sarcoid macrophages
Symptoms of large vessel disease
- Seizures
- Headache
- Focal deficits (hemiparesis, gross and fine motor deficits, gait abnl)
- Cranial neuropathies
- Movement d/o
Angiographic appearance of non progressive large vessel disease
Focal segmental stenosis often with alternating areas of narrowing and dilatation with banded or striated appearance
Progressive large medium vessel disease
- Uncommon
- Less acute
- Longer standing
- Non focal
- Cognitive, seizures, headaches
Small vessel disease
Presentation gradual Headache Behavioral changes Atypical presentation of psych disease Cognitive decline seizures
Pathology of small vessel vasculitis
Non granulomatous, lymphocytic infiltration of small vessels; macrophages, PMNs and occasionally eosinophils
- Microglial activation
Small vessel vasculitis
Involves vessels throughout the brain and meninges that are not the primary branches of the circle of Willis
Large vessel
Targets major arteries, such as the anterior, middle, and posterior
Diagnostic criteria of Takayasu
Angiographic abnormalities of the aorta or its main branches demonstrated by angiography, CT or MRI
plus at least 1
- Decreased peripheral pulses and/or claudication of extremities
- Blood pressure difference between limbs >10
- Bruits over the aorta and or its major branches
- Systolic/diastolic HTN
- ER >20 or CRP above normal
Sweet syndrome
- Spiking fevers
- Crops of tender, raised, pseudovascular, erythematous plaques or nodules
- Arthritis
- Multifocal osteomyelitis
Supradiaphragmatic disease of TA
- Headaches
- Strokes
- Dizziness
- Syncope
- Seizures
Infradiaphragmatic disease of TA
- Mid aortic syndrome
- HTN
- Abdominal pain
- Abdominal bruits
What vessels are affected in Behcets
Arteries veins. Variable vessel vasculitis
Treatment for ocular behcets as opposed to ulcers
AZA for ocular ( thalidomide, dapsone, colchicine for the rest)
Mucha habarmann syndrome
Rare idiopathic dermatosis with red scaly papules
Papular, look like chicken pox
Can see fever and joint pain
Tx is steroids and MTX
Most common ANCA associated with EGPA
- MPO (<50 percent)
How many kids fail first dose of IVIG?
- 10-20 percent
How many kids progress to develop CAA?
- 5 percent
What pathway is activated in hSP?
- Alternative complement pathway
Cryoglobulinemic vasculitis
- 80-90 percent associated with Hep C
Labs - Low C4, positive RF, mixed II and III cyro, elevated LFTs
