Vasculitis SyndromeAn Approach

AndBasic Principles of Treatment

Dr. Sachin Verma MD, FICM, FCCS, ICFCFellowship in Intensive Care Medicine

Infection Control Fellows Course Consultant Internal Medicine and Critical Care

Ivy Hospital Sector 71 MohaliWeb:- http://www.medicinedoctorinchandigarh.com

Mob:- +91-7508677495

Introduction• Vasculitides are a hetrogenous group of

conditions characterized by inflammation and necrosis of blood vessels.

• A broad group of syndromes may result from this process,since any type,size, and location of vessel may be involved.

Classification of vasculitides:Various attempts made to create a classification of

vasculitides.

But it remains a matter of controversy.

Most classifications are based on: 1. Size vessels it involves. 2. Histological findings from involved vessels. 3.Combination of both vessel size and histological

findings. But all scheme of classification is imperfect.

Pathophysiology and pathogenesis Pathogenic immune-complex formation: 1.Most widely accepted mechanism 2.Casual role is not clearly established Examples- PAN, EMC Antineutrophilic cytoplasmic antibodies(ANCA): Two types- 1. c-ANCA, Examples; WG 2. p-ANCA,Examples;MPA, CSS, Crecentric

GN, GPS , WG Pathogenic T-Lymphocytes response and granuloma

formation: Examples; WG , Giant cell arteritis,Takayasu arteritis CSS

Etiopathogenic classification incorporating the modified CHCC Classification by Lie

DOMINENT VESSELS

PRIMARY VASCULITIS PATHOGENESIS

LARGE ARTERIES Temporal arteritisTakayasu’s arteritis

T cell mediated

MEDIUM ARTERIES Classical PAN

Kawasaki’s disease

Immune complex related

Antibody mediated hypersensitivity

SMALL AND MEDIUM SIZE ARTERIES

Wegener’s granulomatosisCSSMSA

Antibody mediated (ANCA)

SMALL VESSEL VASCULITIS(Leukocytoclastic)

HSPEMCCUTANEOUS LCV

Immune complex mediated

The most recent classification scheme proposed by the American College of Rheumatology (ACR)

• Uses both vessel size and type of inflammatory infiltrate.• It classifies vasculitis as follows: Polyarteritis nodosa (PAN), Churg-Strauss syndrome, Wegener's granulomatosis, Hypersensitivity vasculitis, Henoch-Schönlein purpura, Giant cell arteritis, Takayasu's arteritis, Granulomatous angitis of CNS, Berger's

disease, and Kawasaki disease

INDIAN PERSPECTIVE• Reliable epidemiological data from india is

not available• Takayasu’s arteritis is commonest

vasculitis described.• Temporal arteritis is extremly uncommon• Patients with WG are seen in significant

number in north,but rare in south.• Classical PAN has been described all over.

Frequency distribution of vasculitic disorders in India (N=1064)*

DISEASE NO. PERCENTAGE

Aortoarteritis 215 20.20Giant cell arteritis 35 3.36

Polyarteritis nodosa (PAN) 95 8.83

Cutaneous PAN 13 1.22

Wegener’s granulomatosis 147 13.83

Microscopic polyangiitis 42 3.94

Churg Straus syndrome 19 1.78

Henoch Schonlein purpura 232 21.80Small vessel vasculitis 61 5.73

Behcet’s disease 145 13.62

Kawasaki disease 05 0.46

Undiagnosed 50 4.69

Others** 6 0.56

CLINICAL MANIFESTATIONS

• The Vasculitides are truly a ‘multisystem’ diseases. No organ or system is spared.

• General Symptomatology : Fever Weight loss Malaise Fatigue Night sweats Anemia Generalised aches and pain

CLINICAL MANIFESTATIONS:CLINICAL MANIFESTATIONS : A GUIDE TO THE TYPE OF VESSELS INVOLVED

LARGE VESSELS MEDIUM VESSELS SMALL VESSELS

Limb claudication Red and blue Panniculitis Purpura

Asymmetric blood pressure Ulcer Vesicobullous lesions

Absence of pulses Livedo reticularis. Urticaria

Bruits Digital gangrene Glomerulonephritis

Aortic dilatation Mononeuritis multiplex Alveolar haemorrhage

Renovascular Hypertension Microaneurysm Splinter haemorrhage

Reno-vascular hypertension Uveitis,episcleritis,scleritis

Mucosal ulcer in bowel

Continue…• SKIN: Skin commonly involved.o Palpable purpura is commonest dermal

lesion.o Other specific lesions are: nodules and plaques which may ulcerate Infarcts Ulcers Pyoderma gangrenosum Wide spread skin necrosis and gangrene. Macules, papules,vesicles, blisters, and small

bullae has been described.

SKIN LESIONS

Muscles and Joints: Features are common, but nonspecific. Arthralgia and Arthritis Generalised Myalgia and Weakness Claudication, PainEye ,Ear ,Nose and Throat: Scleritis Scleromalacia Perforation of globe Uveatis Recurrent Otitis media Hearing loss Recurrent sinusitis, nasal septum damage Several and recurrent oral ulcerations

Airways and Lungs: Stridor Ventilatory compromise Cough Chest pain Expectoration and Hemoptysis Pulmonary lesions like: infiltrate nodules cavities mass lesions abscess

Gastrointestinal tract: most important G.I. manifestations are due to

bowel ischemia.

Kidneys: Great diversity of lesions: Renovascular hypertension Infarction and Hematoma of kidneys Mild GNs to rapidly progressive GNs

Nervous system: Peripheral Neuropathy, Stroke

Reproductive system: Testicular Infarction Scrotal ulcers Penile ulcers on Glans and Shaft

Cardiovascular system : Pericarditis, Myocardial infarction Aneurysmal rupture

Approach to the patient• Diagnosis of vasculitis is considered in an any

patient with unexplained illness.

• Certain clinical abnormalities when present alone or in combination suggest a diagnosis of vasculitis like…

1.Palpable purpura 2.Pulmanary infiltrates 3. Microscopic hematuria 4.Chronic inflammatory sinusitis 5.Unexplained ischemic events 6.Glomerulonephritis with evidence of multisystem disease

Laboratory Work-up• First to exclude the diseases which can

mimic vasculitis.• To establish the category of vasculitis

syndrome. Hemogram : Normocytic Normochromic anemia Leukocytosis(>10% Eosinophils in CSS)Acute phase reactants: Raised ESR, CRP, alpha-2 globulin,

fibrinogen, Thrombocytosis, ALP

Continue….Urine analysis: Hematuria ProteinuriaSerum proteins: Hypergammaglobulinemia (mostly IgG type, IgA in HSP, WG) Complements levels usually decreasedAntineutrophil cytoplasmic

autoantibodies (ANCA): c-ANCA p-ANCA A or x-ANCA

Continue….Organ biopsy: Gold standard for diagnosis of vasculitis.

Angiography : Especially for medium and large vessels. Others: X-rays, CT Scan, MRI of thorax MRA USG Studies

Basic principals of treatment • Glucocorticoids

• Glucocorticoids + cytototoxic drugs

• Antiviral therapy if indicated

• Plasma exchange and IV Ig + or aspirin

• Surgical correction and Angioplasty

Continue…• Sympotomatic mangement in cases of

hypersensitivity vasculitis

• White blood cell counts every 1-2wks and WBC count should be maintained above > 3000/microL.

• TMP-SMX should be given to every patient receiving glucocorticoids and cytotoxic drugs combination therapy.

SMALL AND MEDIUM SIZED

VASCULITIS SYNDROMES

WEGENNER’SGRANULOMATOSIS

CHURG SRAUSS SYNDROME

MICROSCOPICPOLYANGITIS PAN

M:F1:1

1:14(INDIA)

1.2:1NO MUCH DIFF. FROM WESTRN DATA

OVER ALL UNKNOWN

OVER ALL UNKNOWN

4.5:1(INDIA)

TYPE OF VESSELS INVOLVED

SMALL ARTERIES AND VEINS

SMALL AND MEDIUM SIZED VESSELS

SMALL VESSELS(ARTERIES,CAPILLARIES,VENULES)

SMALL AND MEDIUM SIZED ARTERIES ONLY

SPECIFIC FEATURE

TRIAD: UPPER AND LOWER AIR WAYS WITH KIDNEY LESIONS

EXTRA VASCULAR GRANULOMA

PULMONARY CAPILLARIES INVOLVED,GNs +NT

PULMONARY ARTERY NOTINVOLVED,ANEURYSMS

LABORATORY FINDINGS

C-ANCA(>90%) FALSE +VE REPORTED

p-ANCA (>48%) p-ANCA (75%) HEP B ANTIGENEMIA,HAIRY CELL LEUKEMIA

LARGE SIZED VESSELS VASCULITIS SYNDROME

TAKAYASU’S ATERITIS (NON-SPECIFIC AORTO-ARTERITIS)

GIANT CEL ATERITIS (TEMPORAL ARTERITIS)

SPECIFIC FEMALE SEX PREDILICTIONS

MORE COMMON IN ASIA M:F- 1:1.6 (INDIA) 1:9 (JAPAN)AGE: 15-25 YEARS

C/F: GENERAL SYMPTOMS WITH VASCULAR SYMPTOMS HYPERTENSION IS MOST COMMON PRESENTATION.

DISEAESE CLASSIFY ON THE BASIS OF SITE OF INVOLVEMENT OF AORTA AND ITS BRNCHES. MIXED INVOLVEMENT IS THE COMMONEST IN INDIA.

MORE COMMON IN FEMALE

MORE COMMON IN WESTERN COUNTRIESRARE IN INDIA

AGE: MORE THAN 50 YEARS

ASSOCIATED WITH POLYMYALGIA RHEUMATICA.

DISEASE INVOLVES CHARECTERISTICALLY ONE OR MORE BRANCHES OF CAROTID ARTERY.

CLASSIFICATION OF TAKAYASU’S ARTERITIS

SUMMARY• PATIENT SUSPECTED FOR PRIMARY VASCULITIS.

• RULE OUT THE CAUSES WHICH CAN MIMIC VASCULITIS.

• LOOK FOR DEMOGRAPHIC CHARACTERISTICS LIKE AGE,SEX, ETHINICITY,SMOKING STATUS.

• DETERMINE THE SIZE OF VESSELS INVOLVED AND CATEGORIES THE TYPE OF VASCULITIS.

• EXTENT OF ORGAN DAMGE TO BE ASSESSED.

• SPECIFIC LABORATORIES WORK UP REQUIRED FOR CONFIRMATION OF DIAGNOSIS.

• DECIDE THE APPOPRIATE TREATMENT

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