In the name of God

Vasculitis Syndrome : An Approach JAPI VOL. 52 AUGUST Update Article Renu Saigal*, A Agrawal**, D Dadhich By:M.Asadollahi

INTRODUCTION Vasculitides are a hetrogenous group of conditions characterized by inflammation and necrosis of blood vessels. Vessels of any size and of any organ may be affected. This is reflected in the wide variety of signs and symptoms that characterize vasculitis. Clinically vasculitides range from a benign, regionally restricted process to a life-threatening systemic disorder. Thus, they can mimic or be mimicked by a variety of diseases. Therefore, a systematic approach to correct diagnosis is necessary.

IMMUNOPATHOGENESIS Vasculitic syndromes are immune-mediated diseases. Most are idiopathic. Pathogenesis of vasculitis involves two processes, namely 1. Inflammation of vessel wall 2. Ischaemia of tissues

Based on this vasculitic disorders can be primary or secondary (Table 1). The mechanism of vessel wall involvement1 could be: 1. Allergic angiitis with eosinophilia and raised IgE levels in blood and in tissues e.g. in Churg Strauss syndrome (CSS). 2. Antibody mediated (pauci-immune type) vasculitis which includes ANCA associated vasculitis (AAV) like Wegner’s granulomatosis (WG), CSS and microscopic polyangiitis (MPA). 3. Immune complex mediated with immune complex deposition or formation in situ. This is associated with low complement levels, e.g. Henoch-Schonlein purpura (HSP), polyarteritis nodosa (PAN). 4. T cell mediated hypersentivitiy characterized by an inflammatory infiltrate induced by Th1 cells, e.g. giant cell arteritis (GCA) and Takayasu’s arthritis (TA).

Table 1 : Classification of vasculitis Large 1. Giant cell arteritis (GCA)(G,p) vesel Vasculitis 2. Temporal arteritis (TA)(G,p) Medium Visceral arteries 1. PAN (p) 2.Kawasaki disease(p) Small Involves capillaries, A) ANCA associated 1. MPA (P) 2. WG (G,P) 3. CSS (G,P) 4. Drug-induced (S***) B. Immune complex mediated 1. HSP (P) 2. Essential cryoglobulinaemicssebvasculitis (ECV) (P) 3. Lupus vasculitis (S) 4. Rheumatoid vasculitis (S) 5. Sjogren’s syndrome vasculitis (S) 6. Hypocomplimentaemic urticarial vasculitis (P) 7. Behcet’s disease (S) 8. Goodpasture’s syndrome (S) 9. Serum sickness vasculitis (S) 10. Infection induced vasculitis (S) 11. Cutaneous leucocytoclastis vasculitis (P) 12. Drug-induced vasculitis C) Paraneoplastic small vessel vasculitis 1. Lymphoproliferative,myeloproliferative neoplasminduced vasculitis (S) 2. Carcinoma-induced vasculitis (S) D) Inflammatory bowel disease associated vasculitis (S)

APPROACH TO DIAGNOSIS OF VASCULITIC SYNDROMES Occlusive arterial disease or hypertension in youngadults. Unexplained fever, weight loss. Unexplained proteinuria with or without casts. Splinter haemorrhages in nails, and cutaneous lesions in the form of palpable purpura, erythema, subcutaneous nodules or urticaria. * Sudden retinal vascular disease without hypertension or diabetes.

* 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.

Clinical presentation Vasculitis may cause simultaneous involvement of various organ systems resulting in bizarre clinical presentations or with a disease process localized to skin only. Systemic vasculitis usually presents in individuals of 2-5th decade, the exceptions being HSP and Kawasaki disease which are common in children and Takayasu’s arteritis, which is more common in young females. The pattern of different organ system involvement may help in identifying the specific vasculitic syndrome.

Predominantly cutaneous vasculitis Usual presentation is in the form of palpable purpura,urticaria, bullous ulcers or splinter haemorrhages, mainly limited to lower extremities. The salient features are: * Absence of systemic involvement * Negative serology * Small vessel leucocytoclastic vasculitis * Better prognosis

Systemic vasculitis Systemic vasculitis involves various organ systems. Prognosis in general is poor.

Table 2 : Manifestations of systemic vasculitis in different organs/systems Organ/system involved Features Kidney -Affected in most of the vasculitis except PAN and TA. - Glomerulonephritis (absent in classical PAN) - Renal failure - Hypertension usually (not seen in WG) - Renal infarction Lungs - Involved in WG, CSS, MPA - Alveolar haemorrhage, characterized by haemoptysis, anaemia and bilateral evanescent lung opacities - Nodules with/without cavities - Infarction - Asthma (CSS)

Cardiovascular - Myocardial infarction - Ischaemic cardiomyopathy, CHF - Pulselessness/diminished arterial pulsation Musculoskeleta l -Arthralgia system - Arthritis - Myalgia Abdomen - Ischaemic mucosal necrosis with haemetmesis and melaena - Bowel infarction - Hepatic and pancreatic infarction

CNS - Focal neurological deficit - Altered mental state -Seizures Nerves: - Mononeuropathies (acute onset) -Mononeuritis multiplex Muscles - Jaw claudication as in GCA - Myalgia - Arm claudication as in TA - Weakness and stiffness of muscles

Genitourinary - Testicular pain - Epididymal pain - Ovarian involvement Skin rash, purpura, cutaneous infarcts, livedo reticularis, Raynaud’s phenomenon Constitutional (B symptoms); - Fever,malaise, anorexia, arthralgia, weight loss Ocular - conjunctivitis, scleritis,episcleritis, dacryocystitis, uveitis,proptosis ENT - Otitis media, nasal obstruction or epistaxis (in WG)

DIAGNOSTIC WORKUP Laboratory investigations Haemogram Urinalysis Serum proteins Antineutrophil cytoplasmic autoantibodies (ANCA): i. Cytoplasmic ANCA (c-ANCA) ii. Perinuclear ANCA (p-ANCA) iii. Atypical staining (A or x-ANCA) Angiography Renal and hepatic function tests Echocardiography Organ biopsy

Table 3 : Mimicks of vasculitis * Bacterial endocarditis * Antiphospholipid antibody syndrome * Viral infections like HIV, CMV, HBV, HCV etc. * Cholesterol emboli syndrome * Vasoconstrictor drugs (ergot poisoning) * Hypertensive arteriopathy * Thoracic outlet syndrome Sepsis, DIC Sarcoidosis* Thrombotic thrombocytopenic purpura (TTP) * Lymphoma, hairy cell leukaemia

CONCLUSION As the vasculitis syndromes are of heterogeneous nature, the approach to diagnosis, in a clinical situation raising suspicions of vasculitis, should proceed in a progressive stepwise manner to: (i) establish the diagnosis of vasculitis, (ii) ascertain, whether it is primary or secondary (iii) extent of vessel involvement and (iv) presence of an offending antigen if a diagnosis of secondary vasculitis is made.

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