Presenter-Dr Rahul Arya

Vasculitis is a clinicopathologic process characterized by inflammation and damage to blood vessels, leading to compromise of the vascular lumen resulting in ischemia of the tissues supplied by the involved vessels.

Inflammatory destruction of blood vessels• Infiltration of vessel

wall with inflammatory cells– Leukocytoclasis– Elastic membrane

disruption

• Fibrinoid necrosis of the vessel wall

• Ischemia, occlusion, thrombosis

• Aneurysm formation• Rupture, hemorrhage

ANCA are antibodies directed against certain proteins in cytoplasmic granules of neutrophils and monocytes.

Types-

i. Cytoplasmic ANCA

ii. Perinuclear ANCA

Cytoplasmic ANCA

◦ Stains cytoplasm (hence “c”)

◦ Main target antigen: proteinase-3

◦ Associated with wegner’sgranulomatosis(Granulomatosis with Polyangitis).

Perinuclear ANCA

◦ Stains perinuclear(hence “p”)

◦ Main target antigen: myeloperoxidase

◦ Associated with churg strauss and microscopic polyangitis.

Granulomatous vasculitis of upper and lower respiratory tracts with glomerulonephritis.

Mean age of onset-40 years

M:F= 1:1.

Histopathological hallmark-necrotizing vasculitis of small arteries and veins with granuloma formation.

Lung-multiple,bilateral,nodular, cavitary infiltrate

Renal-focal,segmentalglomerulitis that evolve into rapidly progressive crescentic glomerulnephritis

Upper airway (95%)-PNS pain, purulent/bloody nasal discharge,nasal septal perforation (saddle nose).

Pulmonary (85-90%)-cough, haemoptysis, dyspnea, chest discomfort.

Renal (77%)-proteinuria, hematuria, RBC cast.

Eye (52%) conjuctivitis, dacrocystitis, episcleritis, scleritis , ciliary vessel vasculitis, retroorbitalmass lesion.

Skin (46%)-papules, vesicles, palpable purpura, ulcer or s/c nodules.

Nervous system (23%)- cranial neuritis, mononeuritis multiplex, cerebral vasculitis.

Cardiac (8%)- pericarditis,coronary vasculitis, cardiomyopathy.

Nonspecific symptoms- malaise, weakness, arthralgia and weight loss.

Laboratory finding-ESR is raised, mild anemia, leukocytosis, mild hypergammaglobulinemia, mildly elevated rheumatoid factor.

Demonstration of necrotizing granulomatousvasculitis on tissue biopsy.

Pulmonary tissue-highest diagnostic yield.

Renal biopsy-paauci-immune glomerulonephritis.

Antibodies to cANCA-present in 90% pt with active disease; without active disease sensitivity is 60-70%.

Cyclophosphamide + Glucocorticoid- for induction of therapy in severe disease.

Prednisolone 1mg/kg/d for 1st month f/b gradual tapering on alternate day or daily schedule with discontinuation after 6-9 months.

Cyclophosphamide 2mg/kg/d orally for 3-6 months.

Remission maintanence-• Methotrexate 0.3 mg/kg single weekly (max 15 mg/week)• Azathioprine 2mg/kg/d• Mycophenolate mofetil- 1000 mg bd

Maintanence therapy given for min 2 years.

On t/t with cyclophosphamide

• marked improvement is seen in >90% patient;

• complete remission in 75% patient;

• 5 year patient survival is >80%.

It is a systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels.

Glomerulonephritis and pulmonary capillaritis is common.

No granuloma formation.

Mean age of onset- 57 years.

M>F

Mainly involves capillaries,venules along with small and medium sized arteries.

Paucity of immunoglobin deposition.

Associated with ANCA.

Onset may be gradual- fever, weight loss and musculoskelatal pain.

Glomerulonephritis (79%)-can be rapidly progressive leading to renal failure.

Alveolar haemorrhage (12%)- haemoptysis.

Mononeuritis multiplex, GI tract and cutaneous vasculitis.

Lab Findings-

ESR- raised

Anaemia

Leukocytosis

Thrombocytosis

ANCA- present in 75% (antimyeloperoxidase antibodies)

Based on histologic evidence of vasculitis or pauciimmune glomerulnephritis.

Sensitivity and specificity of ANCA is not established.

Cyclophosphamide with prednisolone.

5 year survival with t/t is 74%.

Also referred to as allergic angiitis and granulomatosis.

characterized by asthma, peripheral and tissue eosinophilia , extravascular granulomaformation, and vasculitis of multiple organ systems.

Incidence-uncommon (1-3/million)

Mean age- 48 years

M:F- 1.2:1.

Involves small and medium-sized muscular arteries, capillaries, veins, and venules.

characteristic histopathologic feature-granulomatous reactions associated with infiltration of the tissues with eosinophils.

Lung involvement is predominant.

Nonspecific-Fever, malaise,anorexia, and weight loss.Pulmonary finding-M/C manifestation Severe asthmatic attacks with pulmonary infiltration.Mononeuritis multiplex-2nd most common manifestation.Allergic rhinitis and sinusitis-61% Heart disease-14% ;important cause of mortality (CHF or Heart attack).

Skin lesions occur in 51% of patients and include purpura in addition to cutaneous and subcutaneous nodules.

The renal disease is less common and generally less severe.

Purpura

Subcutaneous Nodules

The characteristic finding-eosinophilia.

Evidence of inflammation-elevated ESR, fibrinogen, or α2-globulins

48% of patients have circulating ANCA that is usually antimyeloperoxidase(pANCA).

Lanham’s criteria (all of the following)◦ Asthma◦ Peak eosinophilia >1.5 x 109 cells/L◦ Systemic vasculitis, two or > extrapulmonary sites

American College of Rheumatology (4 of the following in the setting of vasculitis)◦ Asthma◦ Peak eosinophilia >10% total WBC◦ Peripheral neuropathy attributed to vasculitis◦ Transient pulmonary infiltrates◦ Paranasal sinus disease◦ Biopsy showing blood vessels with extravasular

eosinophils

Glucocorticoids -oral prednisolone 40-60 mg/day.

In glucocorticoid failure/fulminantmultisystem disease, the treatment of choice is a combined regimen of daily cyclophosphamide and prednisolone.

Prognosis-Without t/t-25%With t/t-72%

Multisystem, necrotizing vasculitis of small and medium sized muscular arteries.

Renal and visceral arteries are characteristically involved.

Uncommon.

Necrotizing inflammation of small and medium sized muscular arteries.

Lesions are segmental and involve bifurcation and branching of arteries.

Aneurysmal dilatation of upto 1cm along involved arteries is characteristic.

Pulmonary arteries are not involved; bronchial artery involvement is uncommon.

Kidney- arteritis without glomerulonephritis.

It may be associated with Hepatitis B.

Non-specific- fever, malaise, weight loss.

Renal (60%)- renal failure, hypertension.

Musculoskeletal (64%)- arthritis, arthralgia, myalgia.

Peripheral nervous system (51%)-peripheral neuropathy, mononeuritis multiplex.

GI (44%)-abd pain, nausea, vomiting.

Skin (43%)-livedo reticularis, rash, purpura, raynaud’s phenomena.

microaneurysms in the hepatic circulation.

Livido reticularis

Lab findings-

• Leukocyte counts is raised with neutrophilpredominance.

• Raised ESR

• Anaemia of chronic disease.

• Hypergammaglobulinemia.

• All patients must be screened for Hep B.

Severe Cases-Prednisolone + Cyclophosphamide

Less Severe- Prednisolone alone.

Patient with Hepatitis B- Antiviral therapy with glucocorticoids and plasma exchange.

Prognosis-

o Without t/t-5 year survival rate is 10-20%.

o Death is mainly b/s of GI complications and cardiovascular causes.

Cranial arteritis or temporal arteritis.

Inflammation of medium and large sized arteries.

Characteristically involves one or more branches of carotid artery-temporal artery.

It is closely assoc with polymyalgiarheumatica which is characterized by stiffness, aching and pain in muscle of neck, shoulder, lower back, hips and thigh.

Occurs in >50 years of age.

F>M

Has association with HLA-DR4.

Histopathologically- panarteritis with inflammatory mononuclear cell infiltrate with giant cell formation.

Antigen driven disease-activated T-lymphocytes, macrophages and dendriticcells.

Fever, anemia, high ESR and headache.

Malaise, fatigue, anorexia, weight loss, sweats, arthralgia, polymyalgia rheumatica.

Headache with tender thickened and nodular artery.

Scalp pain, claudication of jaw and tongue.

Ischemic optic neuropathy- most feared complication.

Stroke, scalp or tongue infarction.

Arm claudication, aortic aneurysm.

Lab Findings-

• Raised ESR.

• Normochromic or slightly hypochromic anemia.

• Increased levels of IgG and complements.

Confirmed by biopsy of temporal artery.

Segmental involvement-biopsy of 3-5 cm together with serial sectioning of biopsy specimen.

Large vessel disease- suggested by physical examination and confirmed by vascular imaging.

Glucocorticoids- Prednisone 40-60 mg/d for 1 month f/b gradual tapering.

Ocular involvement-methylprednisolone1000 mg/d for 3 days.

Treatment required for >2 years.

Aspirin 81 mg/d-reduce cranial ischemic complication.

Patient with isolated polymyalgia rheumatica-prednisone at lower dose.

ESR- for monitoring of therapy.

Inflammatory and stenotic lesion of medium and large sized arteries.

It has strong predilection for aortic arch and its branches.

Incidence- 1.2-2.6 cases/million.

Adolescent girls and young women.

Medium and large arteries.

Panarteritis with inflammatory mononuclear cell infiltrate.

Immunopathogenic mechanism.

Malaise, fever, night sweats, arthralgia, anorexia and weight loss.

Subclavian (93%)- arm claudication, raynaud’sphenomena

Common carotid (58%)- syncope, TIA, stroke.

Abdominal aorta (47%)- abdominal pain, nausea,vomiting.

Renal (38%)- hypertension, renal failure.

Lab findings-

Elevated ESR

Mild anemia

Elevated immunoglobulin levels.

Suspect in young women with decreased or absent peripheral pulses, discrepencies in BP with arterial bruits.

Diagnosis confirmed by- arteriography which shows– irregular vessel wall, stenosis, post stenotic dilatation, aneurysm formation, occlusion with increased collateral circulation.

Arteriogram demonstrating stenosis of the abdominalAorta.

Arteriogram of the aortic arch demonstrating completeocclusion of the left common carotid artery just after its originfrom the aorta.

Chronic and relapsing course.

Prednisone 40-60 mg/d alleviates symptoms.

Glucocorticoids therapy with surgical or arterioplastic approach– improved outcome.

Refractory to glucocorticoid- methotrexate25mg/week.

Mortality- CHF, MI, CVA, aneurysmal rupture or renal failure.

Also k/a anaphylactoid purpura.

Small vessel vasculitis.

Palpable purpura, arthralgias, GI signs and symptoms and glomerulonephritis.

Children-4-7 years.

Common.

M:F- 1.5:1

Peak incidence in spring.

Immune complex deposition.

Inciting antigens- URTI, drugs, foods, insect bites, immunizations.

IgA antibody-M/C seen.

Palpable purpura

Polyarthralgia

Colicky abdominal pain with nausea, vomting, diarrhoea or constipation accompanied by passage of blood and mucus per rectum.

Bowel intussusception.

Renal (10-50%)- mild glomerulonephritis-proteinuria and microscopic hematuria with rbc cast.

Lab studies-

mild leukocytosis, normal platelet count

Skin biopsy- leukocytoclastic vasculitis with IgA and C3 deposition.

Prednisone 1mg/kg/d-useful in decreasing tissue oedema, arthralgias and abdominal discomfort.

Rapidly progressive glomerulonephritis-intensive plasma exchange with cytotoxicdrugs.

Prognosis- excellent.

Cryoglbulins are cold precipitable monoclonal or polyclonal immunoglobulins

Idiopathic or associated with disorders like multiple myeloma, lymphoproliferativedisorder, connective tissue diseases, infections and liver diseases.

Hepatitis C is commonly related with it.

Skin biopsy- inflammatory infiltrate surrounding and involving blood vessel walls with fibrinoid necrosis, endothelial cell hyperplasia and haemorrhage.

Membranoproliferative glomerulonephritis is responsible for 80% of all renal lesions.

Cutaneous vasculitis, arthritis, peripheral neuropathy and glomerulonephritis.

Renal disease- 10-30%.

Lab Findings-

Raised ESR

Anemia

Circulating cryoprecipitates

Rheumatoid factor-always found

Hypocomplementemia- 90%.

Hepatitis C screening.

Glomerulonephritis- poor prognostic sign

15% end stage renal disease.

Hepatitis C infection- IFN-α and ribavarin.

Glucocorticoids- transient response.

Plasmapheresis, cytotoxic agents- carry significant risk.

Also called as Primary angitis of CNS.

vasculitis restricted to vessels of CNS without other systemic vasculitis.

Mononuclear cell infiltrate with or without granuloma formation.

Headache, altered mental function and focal neurological deficit.

Systemic symptoms are absent.

Diagnosis-

MRI Brain.

Arteriography

Cerebral arteriogram demonstrating beading alongbranches of the internal carotid artery

Confirmed by biopsy of brain parenchyma and leptomeninges.

Poor prognosis

Treatment-

glucocorticoid ± cyclophosphamide.

WEGNER’S GRANULOMATOSIS

Constitutional symptoms

PNS pain,bloody nasal discharge,septal perforation

Cough,haemoptysis

Proteinuria,haematuria,RBC cast

Conjuctivitis,dacrocystitis

Palpable purpura,papules,vescile

Mononeuritis multiplex

M=FAge-40 yr

anaemia

Raised ESR

leukocytosis

hypergammaglobulinemia

Diagnosis-necrotizing granulomatous vasculitison tissue biopsy

cANCA+ve90%

Treatmentcyclophosphamide+

glucocorticoid

Lab features C/F

1. Unexplained signs and symptoms

2. Multisystem involvement

3. Unexplained elevated ESR/CRP

4. Skin lesions (palpable purpura)

5. Ischemic vascular changes (Raynaud’s, gangrene, livedo, claudication)

6. Glomerulonephritis

7. Mononeuritis multiplex

8. Inflammatory ocular disease

9. Arthralgia's/arthritis, myalgia's

10. Sudden visual loss/headache