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REVIEW
Vasculitis
Clinicopathologic process characterized by
inflammation and necrosis of blood vessels
PATOGENESIS
classification
Vasculitis has been categorized by :-
• predominant sizes of the blood vessels
• presence or absence of antineutrophil
cytoplasmic antibodies (ANCA)
• pattern of organ involvement
• presence or absence of granulomas,
eosinophilic/ Lymphocytic infiltration
classification
Small vessel vasculitis
Medium-sized vessel vasculitis
Large vessel vasculitis
Small vessel vasculitis
• Cutaneous leukocytoclastic vasculitis
• Henoch–Schönlein purpura
• Urticarial vasculitis
• Wegener’s granulomatosis
• Churg–Strauss syndrome
• Microscopic polyangiitis (polyarteritis)
• Essential cryoglobulinaemia
• Vasculitis secondary to connective tissue disorders
• Vasculitis secondary to viral infection
• Eosinophilic vasculitis
• Erythema elevatum diutinum
• Rheumatoid nodules
• Reactive leprosy
• Septic vasculitis
Medium-sized vessel vasculitis
• Polyarteritis nodosa
• Kawasaki disease
• Isolated CNS Vasculitis
Large vessel vasculitis
• Giant cell arteritis
• Takayasu’s arteritis
Small vessel vasculitis
leukocytoclastic vasculitis
leukocytoclastic vasculitis
skin vasculitis with palpable purpura is
typically a major finding
1/3
c-ANCA WG
Sensitivity
• 66%
• 91% if only considering active disease
Specificity
• 98%
infections
• malaria, HIV
connective tissue disorders
• SLE, rheumatoid arthritis
GIT
• IBD, chronic autoimmune liver and biliary
tract disease
some apparently healthy individuals.
Perinuclear staining (p-ANCA)
• nonspecific
• frequently seen in patients with other
vasculitic syndromes
C-ANCA pattern
heavy staining in the cytoplasm while the
multilobulated nuclei (clear zones) are nonreactive
P-ANCA pattern
Staining is limited to the perinuclear region and
the cytoplasm is nonreactive
Wegener’s granulomatosis
Histologically
the
cutaneous lesions may
demonstrate a leukocytoclastic
vasculitis with or without
granulomatous inflammation
WEGENERS’ GRANULOMATOSIS
systemic
benign cutaneous
Organ involvement
PAN can affect virtually any organ, but
has a striking tendency to spare the lungs
kidney, GI tract, skin, muscles, joints,
genitourinary tract, peripheral and central
nervous system, heart, testes, epididymis
and ovaries
ETIOLOGY
Idiopathic most cases
HBV infection
• (particularly in patients with a history of intravenous drug
abuse)
Other associations
• Other viruses including HCV
• SLE
• IBD
• hairy cell leukemia
• Minocycline
Clinical features
• Fever
• Weakness
• Weight loss
• Malaise
• Myalgia
• Arthralgia
• Headache
• Abdominal pain and vague discomfort
SIGNS & SYMPTOMS
• Renal - hypertension, hematuria (usually
microscopic), proteinuria, progressive renal
failure
• Musculoskeletal - myalgia, migratory arthralgia
and arthritis
• Gastrointestinal - recurrent and severe pain,
hepatomegaly, nausea, vomiting and bleeding
• CNS - seizures, CVA's, headache, papillitis,
altered mental states
• Peripheral nervous system - mononeuritis
multiplex (most often manifested as foot drop)
• Cardiac - pericarditis, CHF associated with
hypertension and/or myocardial infarction
• Genitourinary - usually asymptomatic but may
have testicular, epididymal, ovarian pain.
Neurogenic bladder reported.
Polyarteritis nodosa
cutaneous manifestations
40% of patients
usually a subcutaneous nodule or
group of nodules along the course of a
blood vessel.
Typically seen around the knee, anterior
lower leg and dorsum of the foot
5–10-mm nodules may be tender,
pulsatile or secondarily ulcerated
POLYARTERITIS NODOSA
Erythematous
nodular lesion
along vessels
more
prominent on
lower limbs
livedo reticularis with or
without ulceration
digital gangrene
‘punched-out’ ulcers
purpura, urticaria,
subcutaneous hemorrhages
LABS
• Abnormal urine sediment
• High neutrophil count
• Anemia of chronic disease
• Elevated sedimentation rate
• Hypergammaglobulinemia
• Hepatitis B surface antigen positive in 30%
of cases
LAB finding
P-ANCA positive in 20%
C-ANCA not associated with PAN
Arteriography and cross-
sectional imaging
alternative to biopsy for diagnosis is
conventional mesenteric or renal
arteriography
multiple aneurysms and irregular
constrictions in the larger vessels with
occlusion of smaller penetrating arteries
Renal arteriogram
microaneurysms
Medications
infections
Diseases associated with immune
complexes
• connective tissue diseases
• malignancy
• inflammatory bowel disease
VASCULITIS
Diagnostic approach
History
Physical examination
Laboratory tests
History
Drugs
H/O Hepatitis B or C
H/O disease
• such as systemic lupus
erythematosus
Physical examination
to determine
• extent of vascular lesions
• distribution of affected organs
• presence of additional disease
Findings suggestive of an underlying
vasculitic process
• palpable purpura
• mononeuritis multiplex
Basic laboratory analysis
Blood CP/ESR Blood culture
urinalysis (if pyrexial)
CRP ASO titre
serum creatinine ANA
LFTs Complement
hepatitis serologies ANCA
muscle enzyme Tissue biopsy
chest x-ray IF studies
ECG
Other investigations
(When indicated)
Cryoglobulins
PFTs
CSF
CNS imaging
biopsies of artery, kidney, lung or nerve
Electromyography
Arteriography
• aortic arch or visceral vessels
baseline tests for possible corticosteroid
or immunosuppressive therapy
Glucose
G-6-PD status (dapsone)
TREATMENT
Treatment LCCV
Oral Steroids
• 30–80 mg once daily,
Remove triggering • tapered over 2–3 weeks
agent Colchicine
Minimize stasis • 0.6 mg twice daily
compression Dapsone
stocking Azathioprine
elevation of Methotrexate
dependent areas Biological agents
NSAIDs • Infliximab
Antihistamines • Rituximab
Treatment
LCV
Systemic disease
Symptomatic relief • Prednisolone
• Supportive therapy • Azathioprine
• Antihistamines • Cyclophosphamide
• Non-steroidal anti-infl
ammatory drugs
• Mycophenolate mofetil
• Ciclosporin
Skin lesions alone
• Colchicine • Interferon-α (if hepatitis
• Dapsone C-associated)
• Pentoxiphylline • Intravenous
gammaglobulin
Ulcerative skin lesions
• Extracorporeal
alone
immunomodulation
• Thalidomide
• Methotrexate • Infliximab
• Prednisolone • Rituximab
HSP
oral antihistamines
systemic corticosteroids
dapsone
• (100–200 mg once daily)
colchicine
• (0.6 mg twice to three times daily)
hydroxychloroquine
• (200 mg once to twice daily)
Dapsone plus pentoxifylline
mycophenolate mofetil
• (2 g once daily)
PAN Treatment (as per severity)
Mild PAN
• constitutional symptoms, arthritis, anemia, but
normal renal function, no gastrointestinal
involvement, and no neurologic deficits) and
those with isolated cutaneous disease
Moderate and severe PAN
• renal insufficiency, or gastrointestinal, cardiac
or neurologic involvement
Mild PAN
Prednisone
• 1 mg/kg per day (maximum 60 to 80 mg/day)
for approximately four weeks.
• On significant improvement prednisone is
tapered slowly for an overall course of
approximately nine months.
• who do not respond to glucocorticoids alone, or
who relapse as the dose of prednisone is
tapered, treatment is as described below for
severe PAN.
Moderate and severe
Prednisone
• 1 mg/kg per day, maximum of 60 to 80 mg
per day)
• The initial high dose is continued for two to
four weeks, until significant improvement is
observed.
• The dose should then be tapered slowly, for
an overall course of approximately six
months.
Oral cyclophosphamide, 1.5 to 2 mg per
kg
unable to tolerate an oral regimen
(eg, due to gastrointestinal involvement)
severe, life-threatening manifestations or
worsening mononeuropathy multiplex
TREATMENT
Prednisone –
• given initially in high doses (60-100 mg/day).
• After initial 2-4 weeks may be tapered to
alternate-day regimen.
• Then gradually discontinued over 2-6 months
in most patients, depending on clinical
course.
TREATMENT
Cyclophosphamide –
in critically ill patient
• initially at a dose of 4 mg/kg/day IV for 2-3
days, then continued at 2 mg/kg/day orally.
In stable patient
• may be started at 2 mg/kg/day orally.
• Dosage may need to be adjusted, based on
patient response and toxicity (usually bone
marrow suppression).
Cryoglobulinaemic vasculitis
Treatment of underlying cause
Treatment of HCV-associated
• Pegylated interferon-α with ribavirin
• usual initial choice
• immunosuppressive agents
• avoided, or relatively non-aggressive therapy can be used
(low-dose corticosteroids or Colchicine)
• Place in glomerulonephritis
• Rituximab
• Plasmapheresis