APPROACH TO VASCULITIS
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APPROACH TO VASCULITIS
Introduction
• Vasculitis- Inflammation of blood vessels characterised by leucocytic infiltration of the vessel walls
• Different patterns of vessels’ involvement in different entities
• Vessel lumen compromisedischemia of the corresponding organ
Pathogenesis
• 3 main groups of pathogenetic mechanisms behind vasculitis-
1.Immune complex formation2.ANCA mediated3.T lymphocyte mediated with Granuloma
formation
Immune complex formation
• Henoch Schonlein purpura- IgA mediated• SLE & other collagen vascular diseases-
ANA• Serum sickness• Polyarteritis Nodosa- Hepatitis B ag• Essential Mixed Cryoglobinemia- Hepatitis
C virion*deposition of immune complexes in the
blood vesselsactivation of complementsdestruction of vessel wall (acute & chronic inflammation)
ANCA
• P-ANCA (anti-proteinase 3)- Wegener’s• C-ANCA (anti-MPO)- Churg Strauss vasculitis- Microscopic Polyangiitis- Wegener’s granulomatosis* Aberrant expression of proteinase 3 and MPO
over the surface of the neutrophilsformation of antibodiesdestruction of neutrophilsvessel wall damage
Granuloma formation (T lymphocyte mediated)
• Giant cell arteritis• Takayasu’s arteritis• Wegener’s granulomatosis• Churg Strauss vasculitis*classical granuloma formation (giant cells and
epitheloid cells in a backround of fibrinoid necrosis) can be demonstrated in the corresponding vessel biopsy
APPROACH TO VASCULITIS
STEP 1
“LEARN TO RECOGNISE VASCULITIS”
Know the common features of vasculitis!!!
• Palpable purpura (cutaneous vasculitis)• Pulmonary infiltrates• Glomerulonephritis (microscopic hematuria)• Mononeuritis multiplex• Unexplained ischemic events- Myocardial
Infarction, Stroke, Raynaud’s phenomena, Digital gangrene, Mesentric Ischemia
Palpable purpura
Pulmonary infiltrates
Microscopic hematuria
STEP 2
RULE OUT SECONDARY CAUSES OF VASCULITIS!!i.e- diseases where vasculitis is one of the clinical manifestations of the respective disease
Secondary Vasculitis
• Infections• Malignancies• Thrombotic Microangiopathies• Drugs• Others
Infections
• Bacterial endocarditis• Gonococcal Infection• Syphilis• Rickettsial diseases• Histoplasmosis• Coccidiomycosis• Whipple’s • Lyme’s
Malignancies• Atrial Myxomas• Carcinomatosis• Lymphomas
Thrombotic Microangiopathies
• TTP• HUS
Drugs
• Cocaine• Phenytoin• Sulfa drugs• Penicillins• Hydralazine• Allopurinol• Propylthiouracil• Thiazides
Others
• SLE• Amyloidosis• Sarcoidosis• Migraine• Atheroembolic Disease
STEP 3
THE PATTERN OF VESSEL INVOLVEMENT (Large vessel, Medium vessel, Small vessel)
Large vessel vasculitis
• Giant cell arteritis
• Takayasu’s arteritis
Medium vessel Vasculitis
• Poly Arteritis Nodosa
• Kawasaki’s vasculitis
Small vessel Vasculitis
Pauci-immune (ANCA mediated)Wegener’s GranulomatosisChurg Strauss vasculitisMicroscopic PolyangiitisImmune complex mediatedHenoch Schonlein PurpuraEssential Mixed CryoglobulinemiaSLE and other collagen c=vascular diseases related vascultis
Other primary vasculitides
• Thromb Angiitis Obliterans• Behcet’s disease• Idiopathic Cutaneous vasculitis• Isolated Vasculitis of CNS• Relapsing Polychondritis• Polyangiitis overlap syndromes (features of
more than 1 vasculitis)
STEP 4
Learn the characteristic presentations of each vasculitis !!!
Giant cell arteritis
• Temporal arteritis• Elderly persons more than 50 yrs. of age• Non specific symptoms, Headache, Elevated
ESR• BLINDNESS-most serious complication• Jaw claudication, Scalp pain, Scalp Tenderness• Polymyalgia Rheumatica- different end of the
spectrum of Giant Cell Arteritis
Takayasu’s Arteritis
• Pulseless Disease• Middle aged females• Aorta and its branches mainly involved• Subclavian vessels, Carotid vessels, Mesentric
vessels• Chronic and Relapsing course
Poly Arteritis Nodosa
• Renal arteries most commonly involved leading to renovascular hypertension
• Pulmonary vessels NEVER involved• Association with patients ofo Hepatitis Bo Hairy cell leukemia
Kawasaki’s Vasculitis
• MucoCutaneous Lymph node syndrome• Children < 5 years of age mostly• Desquamative erythematous rashes involving
the skin, mucus membranes, cervical lymphadenopathy
• 25 % develop coronary artery aneurysms in the convalescent stage of the illness
Pauci immune Vasculitis
Usually Pulmonary capillaritis PLUS Glomerulonephritis•Granulomas +, Asthma + Churg Strauss•Granulomas +, NO asthma Wegener’s•NO granulomas, NO asthma Microscopic Polyangiitis
Wegener’s Granulomatosis
• Classical triad URT + LRT + renal• Chronis sinusitis, Pulmonary nodules,
Pulmonary cavities, Rapidly Progressive Glomerulonephritis
• Cutaneous vasculitis, Eye lesions may be present
• Non specific symptoms may predominate
Churg Strauss Vasculitis• Asthma, Eosinophilia with pulmonary infiltrates ,
glomerulonephritis• Myocardial involvement most common cause
of death
Microscopic Polyangiitis• Pulmonary alveolar capillariitis,
glomerulonephritis
Henoch Schonlein Purpura
• 2nd decade• Palpable purpura over lower limbs,• Gastrointestinal complaints (abd.colicky pain,
blood in stools),• Fever, polyarthralgia• Increased IgA levels in blood
Essential Mixed Cryoglobulinemia• 5 % of Chronic Hepatits C pts. Have EMC• Cryoglobulins formed agianst HCV RNA• Pulmonary, renal ( MPGN ), cutaneous
vasculitis
Thromb Angiitis Obliterans• Chronic heavy Smokers• Inflammation of arteries, veins, nerves• Upper and lower limb gangrene, Instep
claudication, rest pain
Other primary vasculitides
• Behcet’s disease (Recurrent OculoOroGenital ulcerations with vasculitis)
• Idiopathic Cutaneous vasculitis• Isolated Vasculitis of CNS• Relapsing Polychondritis• Polyangiitis overlap syndromes (features of
more than 1 vasculitis)
Summary of 4 steps
• Step 1- Recognise vasculitis• Step 2- Rule out Sec. Vasculitis• Step 3- Study the pattern of vessels involved
in the patient• Step 4- Remember the characteristic
presentations of each primary vasculitis
Step 5
How to diagnose vasculitis???
Common Blood Counts• Mild Anemia – Anemia of Chronic Disease• Differential Leucocyte Count:Predominant eosinophils- Churg Strauss, HSP
ESR• Non specific• But useful test to suggest presence of
underlying inflammatory process
• Acute Phase Reactants Highly sensitive C reactive Protein, Alpha 2
globulin• Chest X ray / HRCT thorax:-Pulmonary infiltrates- small vessel vasculitis-Pulmonary cavities- Wegener’s granulomatosis• Xray Para Nasal Sinuses-Sinusitis of Wegener’s
• Urine routine- RBCs with active sediments suggest Glomerulonephritis (Renal involvement of small vessel vasculitis)
• Viral Markers- Hep. B Poly Arteritis Nodosa- Hep.C Essential Mixed Cryoglobulinemia
• Immunoglogulin levels (IgG, M, A)- Usually hyper gammaglobulinemia seen- Elevated IgA levelsHenoch Sconlein Purpura
• Cryoglobulins- Essential Mixed Cryoglobulinemia
• Rheumatoid Factors-To detect secondary vasculitisRheumatoid
Arthrits-Significantly raised in Essential Mixed
Cryoglobulinemia also
• Complement levels (reduced in immune compex mediated diseases)- EMC, HSP
• ANCAP-ANCA: Wegener’s GranulomatosisC-ANCA: Microscopic polyangiitis, Churg Strauss,
Wegener’s vasculitis
• ANA-screening of SLE, collagen vascular disorders in
suspicion of secondary vasculitis
BIOPSY
• Renal Biopsy- to detect glomerulonephritis especially in small vessel vasculitis
RPGN- seen in pauci immune vasculitisMPGN- seen in EMC
• Skin Biopsy- to detect “leukocytoclasis” in cutaneous vasculitis all small vessel and secondary vasculitides
BIOPSY• Temporal Artery Biopsy- Giant Cell Arteritis• Pulmonary tissue Biopsy- Small vessel vascultides• Upper Airway biopsies- Wegener’s Vasculitis
* Main purpose of biopsy is to study presence of leukocytoclasis, characterisitc pathological alterations in tissues, GRANULOMAS
* Immunofluorescence also helps to study immune complex deposition, IgA deposition, Complement deposition
ARTERIOGRAPHYHelps specially in in arteries that cannot be biopsied
easily like Aorta, Coronary artery, Mesentric vesselsPresence of vascular patency, Aneurysms
• Aortic Angiography- Takayasu’s• Cerebral Angiography- Isolated CNS vascultis• Renal Angiography- PAN • Coronary Angiography- Kawasaki’s• Lower limb arteriography-Buerger’s Disease (TAO)
The last step-STEP 6
TREATMENT
Principles of Treatment
• Immuno SuppressionGlucocorticoids- oral / IV methyl prednisoloneCyclophosphamideMethotrexateAzathioprineCyclosporineRituximab- anti CD 20 abAntiTNF therapies- Infliximab, Adalimumab,
Etanacerpt, Certulizumab
Principles of Treatment• Choice of therapy depends on Severity of organ damageExtent of Multi System InvolvementThe vascular bed involved (renal, ocular,
coronary)
• Cyclophosphamide + Glucocorticoid therapy preferred for severe / serious complications
• Glucocorticoids alone will suffice for isolated mild vascultis like “idiopathic cutaneous vascultis”
Principles of Treatment
• Wherever possible secondary causes (infections, malignancies) should be sought and treated
• Anti viral therapy (HCV, HBV)• ASPIRIN therapy – Kawasaki’s, Giant cell
arteritis• Intravenous Immunogloguloin Therapy-
Prevents coronary aneurysms in Kawasaki’s
Principles of Treatment• Major toxic side effects of all prescribed drugs
need to be kept in mind (Osteoporosis, growth retardation, bone
marrow suppression, hepatic toxicity, renal toxicity, bladder cancer, cystitis …)
• Long term toxicities need to be prevented• Long term prescription of a single group of
drug to be avoided change over to a drug with lesser toxicity profile as soon as symptoms are controlled
Principles of Treatment
• Regular Monitoring of Blood Counts, Renal and hepatic functions
• Most of the Primary vasculitides have one thing in common “Chronic, Responsive to treatment, But
Notoriously Relapsing”
SUMMARY OF STEPS
• Step 1- Recognise vasculitis• Step 2- Rule out Sec. Vasculitis• Step 3- Study the pattern of vessels involved
in the patient• Step 4- Remember the characteristic
presentations of each primary vasculitis• Step 5- How to Diagnose• Step 6- Principles of treatment
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