3. WHICH BLOOD VESSELS
ARE AFFECTED?
• ANY BLOOD VESSEL CAN BE AFFECTED:
–
–
–
–
–
ARTERIES
ATERIOLES
CAPILLARIES
VENULES
VEINS
• CAN DAMAGE VIRTUALLY ANY ORGAN OR TISSUE
9. Pathogenesis
Antigens
(Microbes, drugs, tumor, autoantigens)
+
Antibodies
Formation of immune complexes
↓
Deposition of complexes in and around
blood vessels
↓
Activation of complement cascade and
generation of C3 and C5a (anaphylatoxins)
↓
Mast cell degranulation and generation of
chemokines and cytokines
10. cont…..
Increased vascular permeability, neutrophil
chemotaxis, further deposition of
immune complexes
↓
Appearance of neutrophils with phagocytic
activity, and release of proteolytic enzymes (e.g. collagenase and
elastase)
↓
Destruction of vessels, formation of
platelet thrombi
↓
Ischmia, hemorrhage, and necrosis
of tissues involved
↓
Clinical signs and symptoms
12. •
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
diagnostic process.
13. 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.
14. • Persistent headache with sudden visual impairment
(monocular blindness) in elderly.
• Jaw claudication
• Sudden appearance of peripheral neuropathy - wrist drop,
foot drop.
• Cerebrovascular/cardiovascular events in young.
• Unexplained finding of pulmonary nodular/cavitatory lesions.
15. Clinical presentation
Predominantly cutaneous vasculitis
• Usual presentation is in the form of palpable
purpura, urticaria, bullous ulcers or splinter
haemorrhages.
• Mainly limited to lower extremities.
• Salient features are:•
•
•
•
Absence of systemic involvement.
Negative serology
Small vessel leucocytoclastic vasculitis
Better prognosis
27. Laboratory Findings
• Erythrocyte
sedimentation rate > 50
• 22% of patients with
biopsy-proven GCA have
normal ESR
• Therefore, normal ESR
does NOT rule out GCA
• Mild-moderate anemia of
chronic disease
• Deranged LFT(1/3)
• CRP- Raised
28. GIANT CELL ARTERITIS
Histopathology
• Granulomatous cell
infiltration
• Giant cells
• Disruption of internal
elastic lamina
• Proliferation of intima
• Occlusion of lumen
29. Treatment
• Goal: Reduce the symptoms and to prevent visual loss
• If clinical suspicion is high, treatment should NOT be
delayed for biopsy
•
•
•
•
•
•
Glucocorticoids
Methotrexate
Infliximab
Azathioprine
Imatinib mesylate
Surgery
31. Polyarteritis nodosa
• 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
characteristic
• involvement of the arterioles of the renal glomeruli or the
pulmonary arteries does not occur but can involve bronchial
arteries
• 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
32.
33.
34. •
•
•
•
•
•
•
•
•
•
•
ACR classification
Otherwise unexplained weight loss >4 kg
Livedo reticularis
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
antigen serology
Characteristic arteriographic abnormalities not resulting from
noninflammatory disease processes
A biopsy of medium- or small-sized artery containing
polymorphonuclear cells
3/10 sensitivity/specificity-82-87%
35. TREATMENT
• Less severe cases - glucocorticoids
• Severe cases - combination of prednisone and
cyclophosphamide
• PAN with hepatitis B - antiviral therapy in
combination with glucocorticoids and plasma
exchange.
37. 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.
38.
39. • Histopathology.
• swelling of endothelium
• fibrinoid necrosis of vessel
walls
• Extravasation of erythrocytes
• Infiltrate of neutrophils with
karyorrhexis of nuclei(i.e.
leukocytoclasia)
40. Clinical features
•
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
pustules.
•
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.
41.
42.
43.
44. Wegener’s Granulomatosis
Classical triad •
•
•
systemic small vessel vasculitis
Necrotizing granulomatous inflammation of both the upper and lower
respiratory tracts, and
Glomerulonephritis
Pathology
•
•
•
•
•
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
infections
Predominant cell type is CD4+ T cells and macrophages
45. • Upper
•
Respiratory tract
– Purulent sinus drainage
– Nasal mucosal ulceration with epistaxis / necrosis/perforations of nasal
septum
– Saddle nose deformity
– Otitis media / hearing loss
Tracheal inflammation and sclerosis of subglotic region : stridor and airway
stenosis
• Lower
•
– Fleeting focal infiltrates
Cavitary lesions
Massive pulmonary hemorrhage and hemoptysis - caused by alveolar
capillaritis 80% will progress to paucimmune GN
• Renal
•
GN is characterized by
– Focal fibrinoid necrosis
– Crescent formation
– Absent/paucity of Ig/C3/C4 deposits
46. Other signs and symptoms
• Cutaneous manifestations –
– Most common -palpable purpura
– II most common- Oral ulcers
• Other skin lesions– Tender subcutaneous nodules
– Papules
– Vesicles and petechiae
– Non-specific ulcer
– Pyoderma gangrenosum.
• Migratory arthritis, ocular involvement (scleritis, corneal
ulceration and orbital disease)
• Peripheral (mononeuritis multiplex) or central nervous
system involvement
• Risk of venous thrombosis
47.
48. Treatment
• Induction
– Oral cyclophosphamide 2mg/kg with prednisone 1mg/kg
– Usually for 3 to 6 months
– IV cyclophosphamide 15mg/kg as monthly pulse
• Maintenance
– Azathioprine 2mg/kg and prednisone 5 to 10mg(low dose)
– Methotrexate 15 to 20mg per week and low dose prednisone
• Relapse
– 80% experience one or more within 10yrs
– Usually when treatment is being tapered or stopped
– Need to re-start cyclophosphamide
49. •
•
•
Churg Strauss syndrome
Also known as Allergic Granulomatosis
Small vessel autoimmune vasculitis leading to necrosis
Site: Blood vessels of the lungs (MC)
GI Tract
Peripheral nerves
Heart, skin, and kidneys
• ACR criteria for the diagnosis of
Churg-Strauss syndrome
• 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
51. Clinical manifestation
• Prodromal phase –
– seen in second and third decades
– characterized by atopic disease, allergic rhinitis, and
asthma.
• 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.
52. •
•
•
•
•
•
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
bleeding.
Musculoskeletal — Myalgias, migratory polyarthralgias, and frank
arthritis.
•
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
hematuria.
53. •
•
•
•
•
•
Management
Striking eosinophillia >1000 cells/µl (80%)
Anaemia
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)
54. Henoch-Schönlein Purpura
•
•
•
•
•
Also referred to as anaphylactoid purpura
characterized by
– palpable purpura (most commonly distributed over the buttocks and
lower extremities)
– arthralgias
– gastrointestinal signs and symptoms
Glomerulonephritis
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
55. Pediatric patients
Clinical features
– palpable purpura (nearly all cases)
– polyarthralgias
Gastrointestinal involvement (70%)
•
•
•
•
•
colicky abdominal pain
nausea, vomiting
diarrhea, or constipation
passage of blood and mucus per rectum
bowel intussusception
Renal – 10-50%
Mild GN,proteinuria,microscopic hematuria
Adults
– Cutaneous vasculitis
– Arthritis
– Peripheral neuropathy
– Glomerulonephritis (MPGN)
– Life-threatening RPGN or vasculitis of the CNS, gastrointestinal tract,
or heart occurs infrequently
57. •
Management
•
Skin/renal biopsy( IFA)– Leucocytoclastic vasculutis with IgA and c 3 deposition
Lab studies
– Mild leucocytosis
– Normal platelet count and complement level
– Eosinophilia
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
ranitidine
RPGN - intensive plasma exchange combined with cytotoxic drugs.
•
Disease recurrences have been reported in 10–40% of patients.
•
58. Urticarial Vasculitis
•
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).
Pathology
– Histopathological features are those of leukocytoclastic
vasculitis with a perivasculer neutrophilic infiltrate
59. C/F
• Fixed annular wheals
• >24 hr
• pain and burning
sensation rather then
itching
• hyperpigmentation on
resolution
• Systemic symptoms and
signs
60. Treatment
• majority of patients respond to systemic
corticosteroids.
• indomethacin 25mg three times daily to 50mg four
times daily.
• Colchicine 0.6mg two or three time daily.
• Dapsone up to 200mg / day
• Low dose oral methotrexate
• Dapsone plus pentoxifylline
