Update on vasculitis mechanisms and classification

Update on vasculitis

บุญธร ตันวรเศรษฐี
10 july 2009

Outline
 Definition
 Classification
 Pathogenesis
 Clinical features
 Treatment
 focus on vasculitic syndromes more likely to be
presented to allergist/immunologist in outpatient
setting

Definition
 inflammation of the blood vessels
 Pathology:destruction of the vessel wall
 Histology:fibrinoid necrosis
 necrotizing vasculitis

Classification
Dominant vessel Primary Secondary
involved
Large arteries Giant cell arteritis Aortitis associated with RA
Takayasu arteritis Infection (e.g. syphilis,
tuberculosis)
Medium arteries Classical PAN HBV-associated PAN
Kawasaki disease

Small vessels and Wegener’s granulomatosis Vasculitis secondary to RA, SLE,
medium arteries Churg–Strauss syndrome Sjogren’s syndrome
Microscopic polyangiitis Drugs (PTU,hydralazine)
Infection (e.g. HIV)
Small vessels Henoch–Schonlein purpura Drugs (sulfa,penicillin,thiazide)
(leukocytoclastic) Cutaneous leucocytoclastic Angitis Infection
Mixed essential cryoglobulinaemia HCV-induced cryoglobulinaemia

Best Practice & Research Clinical Rheumatology 23 (2009) 429–443

Classification
Size of dominant vessel Granulomatous Non-Granulomatous
affected
Large Giant cell arteritis
Takayasu arteritis

Medium Classical PAN
Kawasaki disease

Small Wegener’s granulomatosis Microscopic polyangiitis
Churg–Strauss syndrome Henoch–Schonlein purpura
Cutaneous leucocytoclastic
Angitis
Mixed essential
cryoglobulinaemia

Lancet 1997; 349: 553-58

Classification

Best Practice & Research Clinical Rheumatology Vol. 15, No. 2, pp. 259±279, 2001

Classification
 Antibody mediated
 CSS
 MPA
 WG
 Immune complex mediated
 CV
 Drug-induced vasculitis
 HSP
 Hepatitis B–associated PAN
 Pathogenic T-cell response mediated
 CSS
 GCA
 TAK
 WG

J ALLERGY CLIN IMMUNOL JUNE 2009

Classification
Dominant vessel Corticosteroids Cyclophosphamide Other treatments
alone and corticosteroids

Large arteries +++ - +

Medium arteries + ++ ++

Small vessels and + +++ +
medium arteries

Small vessels + +/- ++

Best Practice & Research Clinical Rheumatology 23 (2009) 429–443

Mechanisms of vascular
inflammation and remodelling

2009 British Society for Immunology, Clinical and Experimental Immunology, 156: 395–404

(a) Viable endothelial cells express P-selectin after
activation. P-selectin recognition prompts leucocyte
tethering and rolling,resulting in integrin activation
with firm adhesion and eventual trans-endothelial
migration. (b) Injured endothelial cells fail to
express the signals required for leucocyte
migration. Recruited platelets express P-selectin
and, besides limiting bleeding, substitute
endothelial cells in delivering signals to flowing
inflammatory leucocytes. (c) A neutrophil can be
identified easily on an atherosclerotic lesion in a
damaged human vessel, based on nuclear
characteristics (blue colour, Hoechst) and on the
expression of the CD66b (red). Endothelial cells
and activated platelets express P-selectin (pink).
The prototypic tissue pentraxin PTX3 (green) is
expressed within the lesion at extracellular sites.


(a) (b) (c)

The interaction between activated platelets and
flowing leucocytes yields heteroaggregates in the (d)
circulating blood, which are typical of several
inflammatory diseases.(a,b,c)
Confocal images of platelet–neutrophil hetero-
aggregates in whole blood samples from a patient
with acute myocardial infarction. Glycoprotein Ib
expression (red) reveals platelets, the CD66b
marker (green) neutrophils. Hoechst (blue) was
used to counterstain nuclei. (d) Electron
microscopy of the interaction between neutrophil
and platelet membranes.


Pathogenesis of AASV

NEPHROLOGY 2009; 14, 26–32

Schematic representation of the neutrophil
responses that are putatively involved in
the pathogenesis of ANCA-associated small
vessel vasculitis. (A) Proinflammatory
(A)
cytokines and chemokines (e.g. tumor
necrosis factor) that are released as a result of
local or systemic infection cause upregulation
of the expression of endothelial adhesion
molecules (e.g. selectins, intercellular
adhesion molecule 1 and vascular cell
adhesion molecule 1), and prime neutrophils.
(B) Neutrophil priming causes
upregulation of the expression of neutrophil
adhesion molecules (CD11b) and
translocation of the ANCA antigens from
their lysosomal compartments to the cell
surface. (C) Engagement of dimers of the
(C)
antigen-binding portion of ANCA with
ANCA antigens on the cell surface, and
interaction of the Fc part of the antibody with
Fc receptors, activates eutrophils and causes
increased transmigration and adherence of
neutrophils to vessel walls. (D) ANCA-
(D)
mediated neutrophil activation also
triggers production of reactive oxygen
radicals and possibly causes neutrophil
degranulation. The consequent release of
proteolytic enzymes leads to vasculitis.

KALLENBERG ET AL. NATURE CLINICAL PRACTICE RHEUMATOLOGY DECEMBER 2006 VOL 2 NO 12

The role of ANCA and cytokines in the
pathogenesis of neutrophil-
mediatedvascular injury. Infection or other
inflammatory stimulus leads to production
of proinflammatory cytokines (i.e., IL-1,
TNF-a, and IL-8), which induce resting
neutrophils to express proteinase-3 on their
cell surface. IL-1 and TNF-a also induce
neutrophils and endothelial cells to increase
their expression of adhesion molecules,
leading to adhesion of activated
neutrophils to the vascular endothelium.
Circulating ANCA binds to membrane-
associated proteinase-3 and the FcyRlla
receptor inducing neutrophil degranulation
and generation of oxygen radicals, which
results in endothelial cell injury and
inflammation

Medical Clinics Of North America Volume 81 Number 1 January 1997

Gateway–receptor interaction model. 1. In Wegener’s granulomatosis (WG), expression of PR3 in the extracellular space is increased.
PR3 stimulates the expression of PAR-2 on DC. 2. PR3 activates PAR-2 resulting in maturation of DC, as indicated by expression of
CD80, CD83, CD86, and HLA-DR. 3. These PR3-maturated DCs stimulate CD4+ T cells to generate increasedexpression of IFN-γ. 4.
increasedexpression
Expression of IFN-γ favors the development of a granulomatous inflammation as seen in WG. 5 Hypothetically, chronic T
cell activation by PR3-maturated DCs may finally promote the development of B-cells towards ANCA-producing plasma
cells.

Clinic Rev Allerg Immunol (2008) 34:300–306

Adhesion Molecules

Best Practice & Research Clinical
Rheumatology Vol. 15, No. 2, pp.
259-279, 2001

Chemokine and receptors

Best Practice & Research
Clinical Rheumatology Vol. 15,
No. 2, pp. 259-279, 2001

Cytokine
Cytokine Abbreviatio Cellular Source Biologic Effects
n

Interferon- IFN T cells, NK cells Increases expression of MHC class I and II
molecules;macrophage activation; antiviral a
gamma ctivity

Interleukin-I IL-1 Macrophages,neutrophils, Acts as costimulant for T and B
cell proliferation, activates
endothelial cells, T and B endothelial cells, induces
cells NK cells,fibroblasts, hepatic synthesis of acute
smooth muscle cells phase proteins, endogenous
pyrogen activity, increases
adhesion molecule expression
on endothelial cells

Interleukin-2 IL-2 T cells Induces proliferation and
differentiation of T cells and B
cells; stimulates cytotoxicity of
NK cells

Interleukin-6 IL-6 T cells, endothelial cells, Promote growth and differentiation of T and
B cell;induce hepatic synthesis of acute
macrophages, phase protein,endogenous pyrogen activity
fibroblasts

Cytokine
Cytokine Abbreviatio Cellular Source Biologic Effects
n

Interleukin-8 IL-8 T cells, NK cells Increases expression of MHC class I and II
molecules;macrophage activation; antiviral a
ctivity

Tumor TNF-α Macrophages,neutrophils, Acts as costimulant for T and B
necroti factor cell proliferation, activates
endothelial cells, T and B endothelial cells, induces
alpha cells NK cells,fibroblasts, hepatic synthesis of acute
smooth muscle cells phase proteins, endogenous
pyrogen activity, increases
adhesion molecule expression
on endothelial cells

Platelet- PDGF T cells Induces proliferation and
derived differentiation of T cells and B
cells; stimulates cytotoxicity of
growth factor
NK cells

T cells, endothelial cells, Promote growth and differentiation of T and
B cell;induce hepatic synthesis of acute
macrophages, phase protein,endogenous pyrogen activity
fibroblasts

Clinical signs
( primary systemic vasculitis )
 Fever of unknown origin
 Unexplained migratory polyarthritis
 Mononeuritis multiplex
 Rapidly progressive glomerulonephritis
 Palpable purpura
 Diffuse alveolar hemorrhage
 Unexplained infarction in multiple vascular
territories
 Unexplained multisystem disease


Giant cell arteritis
 “Temporal arteritis”
 Granulomatous large-vessel vasculitis
 Older than 50 years
 Headache ( ‘‘sinus’’ headache )
 Fever, jaw or tongue claudication, and scalp
tenderness
 Polymyalgia rheumatica ( 40-50%)
 Blindness from optic nerve ischemia (15-
20%) ,diplopia and ptosis
 Life-threatening aortic rupture or dissection


 Nodularity, tenderness or absent pulsations of the
temporal arteries and other involved vessels
 Bruits, and asymmetric extremity blood pressure
measurements
 ESR usually increased ,ncnc anemia, thrombocytosis,
and increased alk. phosphatase levels.
 Temporal artery biopsy (TAB) : granulomatous
inflammation of the media and adventitia, with histio
cytes and mononuclear cells, giant cells, irregular fra
gmentation of the internal elastic lamina, neointimal p
roliferation, and sometimes luminal thrombosis (25%
). positive 60-80%
 Contralateral TAB if first biopsy negative


 Prednisone at 40 to 60 mg/d
 Immediate symptomatic benefit and reduction in the risk
of blindness (1%)
 IV methylprednisolone (1 g for 3 days) in patients with
acute vision loss ( protect unaffected eye )
 Baby aspirin prevent ischemic complications
 MTX and Infliximab not shown benefit
 Relapse > 75%
 40-50% unable to taper prednisone
 Acute mortality is uncommon
 Late mortality :rupture or dissection of aortic aneurysms


Takayasu arteritis
 Granulomatous large-vessel vasculitis
 Affects aorta, its main branches, and pulmonary a.
 Predominantly in young women
 Headaches and dizziness
 Vascular hypoperfusion :limb claudication, double
vision or rapid decrease in VA,chest pain,CHF,TIAor
stroke
 HT , bruits (carotid or subclavian) diminished pulses,
asymmetric BP, AR, and arterial tenderness
 Glucocorticoids ,once-weekly MTX ,surgical
revascularization (while clinically inactive)

Takayasu arteritis

FIG 1. Magnetic resonance
angiography in a patient with TAK sho
wing multiple stenoses at the origin of
both common carotid arteries and the l
eft subclavian artery.


Wegener granulomatosis
 Granulomatous, necrotizing, small and medium vessel
 Involves upper,lower airways, and kidneys
 Any age (40-55 yrs.) Men and women equally
 Frequency of 3 per 100,000 persons
 Upper airways symptoms (recurrent or nonresolving sinusitis,
nosebleeds, nasal crusting
 Sinus pain, epistaxis, persistent otitis media with effusion or
decreased hearing, and cartilage ischemia with nasal septal
perforation (saddle nose deformity) subglottic stenosis.
 Single or multiple cavitating/noncavitating nodules or diffuse
alveolar hemorrhage


 Microscopic hematuria, proteinuria, and rapidly progressive
RF
 Skin rash, migratory arthritis
 Ocular involvement (scleritis, corneal ulceration,orbital dis.)
 Mononeuritis multiplex or CNS involvement with or without
pachymeningitis
 Risk of venous thrombosis (DVT,PE) mechanism unclear
 ANCA (180pt., 96%with severe dis.,83%with limited dis.)
 Lung biopsy yield 91% of cases
 Upper airway biopsy yield only 21%of cases
 Renal biopsy:focal, segmental necrotizing, crescentic
glomerulonephritis with few to no immune complexes


KALLENBERG ET AL. DECEMBER 2006 VOL 2 NO 12

 Active severe organ- or life-threatening (2 mkd CYC and 1
mkd prednisone) 91% improvement ,75% complete
remission, and 80%survival
 Fulminant disease (1 g/d iv methylprednisolone 3d and 3 to 4
mg/kg/d iv or oral CYC 3 d,reduced to 2 mg/kg/d after 4
weeks, if improvement, tape prednisone 6-9 mo.
 Maintainance at least 2 yrs.(MTX 15-25mg/wk,AZA 2
mkd),MMF,leflunomide (small data )
 Nonsevere (weekly MTX+daily prrednisolone)=> higher of
relapse rate
 TMP-SMZ reduce only relapses upper airways , prophylaxis
for Pneumocystis jiroveci infection


 Plasma exchange additional in severe renal vasculitis
(Cr>5.8mg/dl) reduced risk of progression to ESRD by 24%
over 1 year
 Etanercept (no benefit)
 Infliximab (absence of randomized control trial )
 Rithuximab (being studied)



FIG 2. WG involving the
lungs with pulmonary
nodules.



lungs with diffuse alveolar
hemorrhage and
pulmonary nodules



right orbit and paranasal
sinuses, resulting in an
orbital mass and
enophthalmos


Microscopic polyangiitis
 Nongranulomatous necrotizing small-vessel vasculitis,few or
no immune deposits
 More common in male , average age of onset is 50 years
 Persistent cough with or without hemoptysis
 Kidneys (79%), lungs (12- 29%), joints (65- 72%), skin (44-
58%), GI tract (32- 58%), peripheral nerves (14- 36%)
 Pulmonary pathology shows capillaritis and absence of linear
IF, differentiating from goodpasture syndrome
 Renal histology is similar to WG
 Severe disease (lung, kidney, or nerve) 2 mkd oral CYC
and 1 mkd prednisone 3- 6 mo., Followed by weekly
MTX or daily AZA

Churg-Strauss syndrome
 asthma, fever, hypereosinophilia, systemic vasculitis
 Prevalence 3 per million , all ages but rare in children and
adolescents and occurs equally between sexes
 recurrent allergic rhinitis, difficult-to-treat asthma,
nonresolving ‘‘pneumonia’’/pulmonary infiltrates, or
persistent eosinophilia
 most common presentation =>1.asthma 2. mononeuritis
 3 phases: prodromal phase (AR and asthma), eosinophilia and
eosinophilic tissue infiltrates, vasculitic phase with visceral
involvement
 Pulmonary imaging: subpleural ground-glass opacities, lobular
consolidation,centrilobular nodules, bronchial wall thickening,
mediastinal or hilar lymphadenopathy, and pleural or
pericardial effusion


Different presentation forms in Churg-Strauss syndrome. (A) Chest X-ray of a 22-year-old man who presented with asthma, allergic
rhinitis, eosinophilia and recurrent pulmonary infiltrates for 2 years until he developed cutaneous lesions which led to diagnosis. (B) A 48-
year-old man who had asthma and recurrent sinusitis for 12 years abruptly presented with abdominal angina, eosinophilia and severe
mononeuritis multiplex. Sural nerve biopsy revealed necrotizing vasculitis. The picture shows remaining right cubital and median palsy
several months after diagnosis.


 Peripheral eosinophilia (absolute eosinophil usually>1500)
 Increased ESR,CRP, and IgE level
 ANCA positive 50% of cases (predominantly MPO-pANCA)
 Histology: eosinophilic tissue infiltrates, extravascular
‘‘allergic’’ granulomas, and small-vessel necrotizing vasculitis
 Association between LTAs and CSS remains unclear
 62 pts. CSS take LTAs, 57 had CSS within first year
 Prednisone (1 mkd) alone is effective
 Life-threatening :glucocorticoids and oral CYC (2 mkd)
 IVIG, MTX, IFN-a (uncontrolled studies)
 Cardiac involvement:main cause of death


Potential targets for biologicals interfering with lymphoid neoformation in WG-granulomata as key to self-perpetuating
inflammation, autoimmunity and ANCAinduced vasculitis in WG: After hypothetical barrier dysfunction and potential exogenous
triggers (e.g., S. aureus), PR3 is released from neutrophil granulocytes. PR3 induces DC maturation via the protease-activated
receptor (PAR)-2. PR3 also enhances proinflammatory IL-32 action.39 Dendritic cells (DCs) and other antigen-presenting cells
(APCs) induce a Th1-type effector memory T-cell (TEM) response via cytokines such as IL-15 (?) and PR3-specific T cells.
Subsequent granuloma formation might provide the necessary “proinflammatory environment” for the break of tolerance. In this
environment the antiapoptotic capacity of IL-15 may counteract the mechanisms supporting self-tolerance. Lymphoid-like tissue
neoformation in WG-granulomata could sustain autoimmunity to PR3. PR3-ANCA formation results in PR3-ANCA–associated
vasculitis, giving rise to further inflammatory lesions. Genetic factors predispose to granulomatous inflammation (HLA-
DPB1∗0401) and PR3-ANCA seropositivity (PTPN22∗620W), thereby determining disease progression.40 Anti-TNF- treatment
may interfere with TNF--induced APC activation in granuloma formation, endothelial cell activation, and priming of neutrophils in
vasculitis induction.B cell depletion by anti-CD20 antibodies could interfere with PR3-ANCA production and
other B cell functions (cytokine production, interaction with T cells, APC function).

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES

Expert Opin. Investig. Drugs (2007) 16(5)

Polyarteritis nodosa
 medium-vessel disease
 Incidence 2- 9 per million annually
 Men = women
 constitutional symptoms, HT,musculoskeletal symptoms,
symptoms from vasculitic involvement of nerves, GI tract ,
skin, heart, and nonglomerular renal vessels
 suspected immunologic disease
 Biopsy specimens : necrotizing inflammation involving
medium-sized or small arteries,with abundant neutrophils,
fibrinoid changes, disruption of the internal elastic lamina
 Angiographic changes : microaneurysms ,stenoses, occlusion,
beaded pattern

Polyarteritis nodosa
 severe life-threatening disease ( GI tract, heart, or CNS
system): 2 mkd oral CYC and glucocorticoids
 non–life or non–organ-threatening : glucocorticoids alone
 Plasma exchange in severe cases
 5-year survival rate with treatment 80%
 Relapses are infrequent (8- 19%)
 PAN-like vasculitis ass. with viral inf. eg. HBV,HCV , HIV
 Rx with glucocorticoids , antiviral treatment , and plasma
exchange induced remission 81% , relapse 10%
 If clinical improvement , immunosuppression should be
withdrawn while continuing antiviral treatment


Clinics in Dermatology (2006) 24, 414– 429

Cutaneous vasculitis
 most commonly vasculitic manifestation in clinical practice
 presumed drug allergy or chronic urticaria
 palpable purpura, necrotic papules, cutaneous infarcts,
urticaria, hemorrhagic vesicles, indurated erythema, or
ulcerative lesions
 Histology: dermal small-vessel inflammation , often with
leukocytoclasis
 idiopathic or occur because of medications, infections,
allergies,malignancies, CNT dis., or primary vasculitis
 Diagnosis of exclusion
 Rx: observation and measures such as leg elevation.


Cutaneous vasculitis
 Glucocorticoids (no optimal regimen)
 Other medications : NSAIDs, dapsone, colchicine ,
antihistamines , and pentoxifylline
 severe idiopathic cutaneous vasculitis : MTX or AZA


Cryoglobulinemic vasculitis

Mixed cryoglobulinaemia may manifest with recurrent purpura and arthralgia only, as shown in(A), or may produce severe ischaemic
lesions and organ dysfunction as displayed in (B) where necrotic toes and peroneal palsy can be clearly appreciated


 Cryoglobulins : mono or polyclonal Ig precipitate at temp. <
37º C and redissolve on warming
 lymphoid neoplasms, chronic infections, and inflammatory
and autoimmune diseases
 Hepatitis C infection is leading cause of cryoglobulinemia
 Small vessel vasculitis caused by deposition of circulating
immune complexes (cryoglobulins and complement)
 drug-induced or other allergy-related skin rash
 clinical triad : recurrent palpable purpura (100%),
polyarthralgias (73%), and renal disease (55%)
 Pathology of glomeruli :deposition of IgG, IgM, and
complement, with coexistent renal arteritis


 Patients with HCV–associated CV, antiviral Rx=> first line
 Severe case (eg. Vasculitis )=> glucocorticoids, CYC, or AZA
 Plasma exchange serves to remove immune complexes
 Rituximab used for resistant CV or setting of B-cell
lymphoproliferative disorders
 Rituximab,with interferon and ribavirin : favorable results in
management of HCV–associated CV.


Kawasaki disease
 Acute vasculitis that affects children
 Primary cause of acquired heart disease in children from the
united states and japan
 80% of cases occur < 5 yrs. , Boys >1.5 times than girls
 Incidence in japan 112/100,000 among children <5 years old
 In US asian 32.5/100,000 , in white 9.1/100,000
 Fever at least 5 days, rash, conjunctival injection, and oral
mucosal changes. Extremity changes, including brawny
induration, followed by desquamation; cervical adenopathy
 Coronary artery abnormalities can be diagnosed
 Cardiac involvement is most of morbidity and mortality


Kawasaki disease
 IVIG (2 g/kg) single infusion prevent coronary aneurysm
formation (appear 1-4wks after onset,15-25% of untreated ),
lessen fever, and reduce myocardial inflammation
 Aspirin (80-100 mkd) concurrently with IVIG, but not affect
coronary artery aneurysm formation
 refractory case : anecdotal experience with glucocorticoids,
pentoxifylline, plasma exchange, ulinastatin, abciximab (for
large aneurysms), infliximab, and CYC
 Echocardiogram recommended at baseline and at 2, 6, and 8
weeks after onset of the disease
 MRI/MRA, ultrafast CT, stress test, myocardial perfusion
studies, and conventional angiography


Kawasaki disease
 aneurysms resolve within 1-2 yrs. depend on size, age of onset
of disease, shape of the aneurysm (fusiform more likely than
saccular), and location (distal more likely than proximal )
 Children with multiple aneurysms, giant aneurysms, or
coronary artery obstruction require close follow-up and
possible long-term anticoagulation


Henoch-SchÖnlein purpura
 small-vessel vasculitis
 predominantly affects children
 suspected drug allergy or immunologic condition
 Purpura (100%), arthritis (82%), abdominal pain (63%), GI
bleeding (33%), and nephritis (40%)
 Uncommon : bullous skin lesions, testicular involvement ,
seizures, intestinal obstruction
 Complication : intussusception , ESRD ( 2- 5%)
 Recurrence occurs in up to 40% ( mostly first 3 months)
 tissue Bx : leukocytoclastic vasculitis with IgA deposition
in blood vessel walls


Henoch-SchÖnlein purpura
 Typically self-limited
 Glucocorticoids might lessen tissue edema, arthritis, and
abdominal discomfort and decrease risk of intussusception ,
not prevent recurrence of abdominal symptoms, skin
involvement, or renal disease and not shorten duration or
lessen relapse
 Active glomerulonephritis and progressive renal
insufficiency : glucocorticoids combined cytotoxic agent
 Outcome usually excellent in children, in adults more severe
 Predictors of progression to ESRD: proteinuria (>1 g/d) , HT ,
renal impairment at presentation, age < 30 years, male sex ,
crescents < 50% of glomeruli, and TI fibrosis on renal Bx


Urticarial vasculitis
 Resembling urticaria
 Skin biopsy : inflammation of dermal capillaries and
postcapillary venules
 Chronic or subacute urticaria
 Urticaria (usually >24 hours), violaceous color ,burning pain
more frequent than pruritus, and residual pigmentation after
resolution
 Involve GI, musculoskeletal ,renal , and pulmonary (particularly
COPD) , less commonly in ocular and central nervous systems
 Confirmed by skin biopsy ( LCV, Ig, complement, fibrin
deposition at dermalepidermal junction and around blood
vessels


 classified as normo- or hypocomplementemic UV
 normocomplementemic UVare idiopathic(most), remainder
ass. With monoclonal gammopathy, neoplasia, UV light
sensitivity, or repeated cold exposure.
 Hypocomplementemic UV due to SLE,SjÖgren syndrome,
serum sickness reaction, or neoplasia or HUVS
 HUVS : specific autoimmune disorder involves >6 mo. of UV
with hypocomplementenia in presence of angioedema ,
moderate-to-severe COPD(occurs in 50%), ocular
inflammation (uveitis occurs in 30%), and glomerulonephritis.
 C3, C4, C1q levels are low , anti-C1q antibody levels (C1q
precipitins) are detectable


 Treatment based on the severity and underlying disease
 skin : antihistamines+/- short course of glucocorticoids ,
colchicine, dapsone, hydroxychloroquine, pentoxifylline,and
indomethacin
 montelukast, cyclosporine A, and AZA used in combinations
as sequential treatment if patients had suboptimal response to
treatment with cinnarizine and glucocorticoids for 6 months
 HUVS or systemic disease : require initial glucocorticoid
therapy


Semin Arthritis Rheum 38:348-360

Presentations of vasculitic syndromes to the allergist/immunologist
Vasculitic syndrome Presentation to allergist/immunologist

GCA ‘‘Sinus’’ headache

TAK Headache

WG Recurrent sinusitis, nosebleed and nasal crusting, otitis media, cough, hoarseness, nonresolving ‘‘pneumonia’’/
pulmonary infiltrates

MPA cough +/- hemoptysis, nonresolving ‘‘pneumonia’’/pulmonary infiltrates

CSS Allergic rhinitis, nasal polyposis, asthma, nonresolving ‘‘pneumonia’’/pulmonary infiltrates, eosinophilia

PAN Suspected immunologic disease, postprandial abdominal pain with suspected food allergy

KD Skin rash, soft tissue edema

Cutaneous Skin lesions in which an allergy or drug reaction might be suspected
vasculitis
CV Skin lesions in which an allergy or drug reaction might be suspected

HSP Purpura, soft tissue edema, or both in which an allergy might be suspected; food enterocolitis

UV Chronic or subacute urticaria, angioedema


Update on vasculitis mechanisms and classification

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