APPROACH TO VASCULITIS

DR.DEEP CHANDH RAJA.S

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 vessels

Presence 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