(Microbes, drugs, tumor, autoantigens)
Formation of immune complexes
Deposition of complexes in and around
Activation of complement cascade and
generation of C3 and C5a (anaphylatoxins)
Mast cell degranulation and generation of
chemokines and cytokines
Increased vascular permeability, neutrophil
chemotaxis, further deposition of
Appearance of neutrophils with phagocytic
activity, and release of proteolytic enzymes (e.g. collagenase and
Destruction of vessels, formation of
Ischmia, hemorrhage, and necrosis
of tissues involved
Clinical signs and symptoms
The vasculitic syndrome display a multitude of variable presentations.
Hence there can be no uniform laid down guidelines or evaluation scale
for the diagnosis of these disorders.
High degree of suspicion, a detailed history,meticulous physical
examination and appropriate laboratory tests to determine organ systems
involved and the extent of involvement are the components of the
When to suspect vasculitis
Presence of following findings alone or in combination
or other bizarre systemic manifestations should raise
the suspicion of vasculitis –
Occlusive arterial disease or hypertension in young adults.
Unexplained fever, weight loss.
Unexplained proteinuria with or without casts.
Splinter haemorrhages in nails
cutaneous lesions - palpable purpura, erythema, subcutaneous
nodules or urticaria.
– Sudden retinal vascular disease without hypertension or diabetes.
• Persistent headache with sudden visual impairment
(monocular blindness) in elderly.
• Jaw claudication
• Sudden appearance of peripheral neuropathy - wrist drop,
• Cerebrovascular/cardiovascular events in young.
• Unexplained finding of pulmonary nodular/cavitatory lesions.
Predominantly cutaneous vasculitis
• Usual presentation is in the form of palpable
purpura, urticaria, bullous ulcers or splinter
• Mainly limited to lower extremities.
• Salient features are:•
Absence of systemic involvement.
Small vessel leucocytoclastic vasculitis
sedimentation rate > 50
• 22% of patients with
biopsy-proven GCA have
• Therefore, normal ESR
does NOT rule out GCA
• Mild-moderate anemia of
• Deranged LFT(1/3)
• CRP- Raised
GIANT CELL ARTERITIS
• Granulomatous cell
• Giant cells
• Disruption of internal
• Proliferation of intima
• Occlusion of lumen
• Goal: Reduce the symptoms and to prevent visual loss
• If clinical suspicion is high, treatment should NOT be
delayed for biopsy
• Inflammatory necrotizing vasculitis
• Tends to occur at bifurcations & branchings of small and
medium sized muscular arteries but not venules
• Involvement of the renal and visceral arteries is
• involvement of the arterioles of the renal glomeruli or the
pulmonary arteries does not occur but can involve bronchial
• Mediated by deposition of circulating immune complexes
• Age 40-60 yrs
• Association--hepatitis B ,Hairy cell leukemia
• fibrinoid necrosis occlusion of the vessel lumen, thrombosis,
and ischemia of the tissue supplied by the vessel.
• Produces aneurysmal dilatation ( upto 1 cm ) of the artery
Otherwise unexplained weight loss >4 kg
Testicular pain or tenderness
Myalgias (excluding that of the shoulder and hip girdle),
weakness, or polyneuropathy
Mononeuropathy or polyneuropathy
New onset diastolic blood pressure >90 mmHg
Elevated levels of serum blood urea nitrogen (>40 mg/dL) or
creatinine (>1.5 mg/dL)
Evidence of hepatitis B virus infection via serum antibody or
Characteristic arteriographic abnormalities not resulting from
noninflammatory disease processes
A biopsy of medium- or small-sized artery containing
• Less severe cases - glucocorticoids
• Severe cases - combination of prednisone and
• PAN with hepatitis B - antiviral therapy in
combination with glucocorticoids and plasma
Cutaneous small vessel vasculitis
SYN : Cutaneous leukocytoclastic vasculitis
• Hypersensitivity angiitis/vasculitis
• Cutaneous necrotizing venulitis.
• Affect mainly cutaneous post-capillary venules,
• cutaneous small vessel vasculitis (CSVV) is the most common
type of vasculitis in dermatology.
• 50% of cases – idiopathic
• 15–20% - infection
• 15–20% - inflammatory diseases (collagen vascular disorders)
• 10–15% - medications
• 5% - malignancy.
• swelling of endothelium
• fibrinoid necrosis of vessel
• Extravasation of erythrocytes
• Infiltrate of neutrophils with
karyorrhexis of nuclei(i.e.
The major cutaneous manifestation of CSVV is palpable purpura, ranging
in size from 1 mm to several centimetres.
Purpura may progress to papules, nodules, vesicles, plaques,bullae or
Other cutaneous findings include oedema, livedo reticularis and urticaria.
Lesions typically occur in areas prone to stasis (ankles and lower legs).
Typically spare intertriginous regions.
Usually asymptomatic,pruritus,pain or burning may be experienced, as
well as systemic symptoms including fever, arthralgia, myalgia and
anorexia may occur.
Classical triad •
systemic small vessel vasculitis
Necrotizing granulomatous inflammation of both the upper and lower
respiratory tracts, and
Preferentially involves venules, capillaries and arterioles
may involve medium sized arteries
Characterized by the presence of granulomatous inflammatory lesions
– Focal accumulations of lymphocytes, macrophages, epithelioid cells
and multinucleated giant cells
Granulomas are similar to granulomas associated with intracellular
Predominant cell type is CD4+ T cells and macrophages
– Purulent sinus drainage
– Nasal mucosal ulceration with epistaxis / necrosis/perforations of nasal
– Saddle nose deformity
– Otitis media / hearing loss
Tracheal inflammation and sclerosis of subglotic region : stridor and airway
– Fleeting focal infiltrates
Massive pulmonary hemorrhage and hemoptysis - caused by alveolar
capillaritis 80% will progress to paucimmune GN
GN is characterized by
– Focal fibrinoid necrosis
– Crescent formation
– Absent/paucity of Ig/C3/C4 deposits
Other signs and symptoms
• Cutaneous manifestations –
– Most common -palpable purpura
– II most common- Oral ulcers
• Other skin lesions– Tender subcutaneous nodules
– Vesicles and petechiae
– Non-specific ulcer
– Pyoderma gangrenosum.
• Migratory arthritis, ocular involvement (scleritis, corneal
ulceration and orbital disease)
• Peripheral (mononeuritis multiplex) or central nervous
• Risk of venous thrombosis
– Oral cyclophosphamide 2mg/kg with prednisone 1mg/kg
– Usually for 3 to 6 months
– IV cyclophosphamide 15mg/kg as monthly pulse
– Azathioprine 2mg/kg and prednisone 5 to 10mg(low dose)
– Methotrexate 15 to 20mg per week and low dose prednisone
– 80% experience one or more within 10yrs
– Usually when treatment is being tapered or stopped
– Need to re-start cyclophosphamide
Churg Strauss syndrome
Also known as Allergic Granulomatosis
Small vessel autoimmune vasculitis leading to necrosis
Site: Blood vessels of the lungs (MC)
Heart, skin, and kidneys
• ACR criteria for the diagnosis of
• Presence of 4 or more criteria:(1) H/O Bronchial asthma
(2) Eosinophilia >10% in Peripheral Blood
(3) Paranasal sinusitis
(4) Pulmonary infiltrates (Transient)
(5) Histology: vasculitis with extravascular eosinophils
(6) Mononeuritis multiplex or Polyneuropathy
Necrotising vasculitis of small vessels
Granulamatous reaction present in
tissue and in the wall of vessels
• Prodromal phase –
– seen in second and third decades
– characterized by atopic disease, allergic rhinitis, and
• Eosinophilic phase –
– peripheral blood eosinophilia
– eosinophilic infiltration of multiple organs, especially
the lung and GIT.
• Vasculitic phase –
– third & fourth decades
– life-threatening systemic vasculitis of small vessels.
Severe asthmatic attacks and migratory pulmonary infiltrates (MC)
Mononeuritis multiplex (72%)
Allergic rhinitis and sinusitis (60%)
Skin lesions: Palpable purpura, cutaneous & subcutaneous nodules
Gastrointestinal tract — abdominal pain , diarrhea , gastrointestinal
Musculoskeletal — Myalgias, migratory polyarthralgias, and frank
Cardiovascular — Heart failure and cardiac rhythm abnormalities
Renal involvment: 50% patients have rapidly progressive or acute renal
insufficiency , while the others isolated proteinuria or microscopic
Striking eosinophillia >1000 cells/µl (80%)
Raised ESR, Raised fibrinogen
P-ANCA : Positive (48%)
RFT:Elevated serum BUN and creatinine level
Urine: proteinuria, microscopic hematuria & RBC casts
• Corticosteroids - clinical remission in 90%
• Severely affected patients, recalcitrant disease or
those with poor prognostic factors such as cardiac,
GI, renal or CNS involvement– Cyclophosphamide+ Corticosteroids
– Intravenous immunoglobulin (IVIG)
Also referred to as anaphylactoid purpura
– palpable purpura (most commonly distributed over the buttocks and
– gastrointestinal signs and symptoms
Usually seen in children
most patients range in age from 4 to 7 years;
may also be seen in infants and adults
male-to-female ratio is 1.5:1
– palpable purpura (nearly all cases)
Gastrointestinal involvement (70%)
colicky abdominal pain
diarrhea, or constipation
passage of blood and mucus per rectum
Renal – 10-50%
Mild GN,proteinuria,microscopic hematuria
– Cutaneous vasculitis
– Peripheral neuropathy
– Glomerulonephritis (MPGN)
– Life-threatening RPGN or vasculitis of the CNS, gastrointestinal tract,
or heart occurs infrequently
Age at onset ≤20 years
No new medication
• 3/6 carry sensitivity/specificity-87%
Skin/renal biopsy( IFA)– Leucocytoclastic vasculutis with IgA and c 3 deposition
– Mild leucocytosis
– Normal platelet count and complement level
IgA level elevated
Prognosis is excellent and most patients recover completely
1–5% of children progress to ESRD
Treatment is similar for adults and children.
Glucocorticoids - prednisone, in doses of 1 mg/kg per day and tapered according to clinical response
effective in the treatment of abdominal pain and arthritis
– not benefit in skin or renal disease
– does not appear to shorten the duration of active disease or lessen the chance of recurrence.
Dapsone (100 mg once daily)- shorten the duration, beneficial effect on the cutaneous lesions
factor XIII replacement
RPGN - intensive plasma exchange combined with cytotoxic drugs.
Disease recurrences have been reported in 10–40% of patients.
5–10% Of patients with chronic urticaria have urticarial vasculitis (UV).
Chronic disease,presents as urticarial lesions that most often occur on the
trunk or proximal limbs, frequently with associated angio-oedema
Lesions persist for greater than 24 h, often demonstrate purpura and
post-infl ammatory pigmentation.
Two types –
UV associated with hypocomplementaemia, and
UV without hypocomplementaemia(normocomplementaemic UV).
– Histopathological features are those of leukocytoclastic
vasculitis with a perivasculer neutrophilic infiltrate
• Fixed annular wheals
• >24 hr
• pain and burning
sensation rather then
• hyperpigmentation on
• Systemic symptoms and
• majority of patients respond to systemic
• indomethacin 25mg three times daily to 50mg four
• Colchicine 0.6mg two or three time daily.
• Dapsone up to 200mg / day
• Low dose oral methotrexate
• Dapsone plus pentoxifylline