systemic vasculitis are heterogeneous group of diseases characterized by inflammation and necrosis of blood vessel wall , often associated with organ involvement

systemic vasculitis Large vessel: Medium vessel: Small vessel: large cell arteritis Takayask’s arteritis Medium vessel: classical polyarteritis nodosa Kawasaki disease Small vessel: microscope polyangitis Wegener’s granulomatosis Churg - strrauss syndrome Henoch - schonlein purpura Mixed essential cryoglobulinaemia

polymyalgia rheumatica (PMR) Clinical syndrome of muscle pain and stiffness and classically an increased ESR Predominantly disease of elderly means age 70 Female 3: 1 male

Clinical features Muscle stiffness and pain, symmetrically affecting the proximal muscle of the neck, upper arm and less commonly the buttock and thigh Early morning stiffness, wt loss, fatigue, depression and night sweating On examination there may be stiffness and painful restriction of active shoulder movement but passive movement are preserved Muscle tenderness may be elicited

Investigations Elevated ESR, CRP Normocitic, normochromic anemia

Management Prednisolone 15 mg /day, dramatic response within 3 days Need steroids for 18 months Some patients require steroids sparing agents as MTX or azathioprine 15-20 % of patients develop features of GCA

Giant cell arteritis   Large vessel vasculitis predominantly affecting branches of the temporal and ophthalmic arteries Mean ages 70 years Female 4:1 male

Clinical features Abrupt onset, but may be insidious Headache localized to the temporal or occipital region with scalp tenderness Jaw pain brought on by chewing or talking and due to ischemia of the masseters

Clinical features Visual disturbance, damage to the optic nerve result in loss of the visual acuity and field, reduced color perception and pupillary defect, complete blindness of one eye Anorexia, fatigue, wt loss, depression, and malaise Neurological complication include TIA, brain - stem infarct and hemi paresis

Investigations Elevated ESR (may be normal) Elevated CRP Temporal artery biopsy (fragmentation of the internal elastic lamina with necrosis of the media with mixed inflammatory cell infiltrate (lymphocyte, plasma cell, eosonophils)) Skip lesions are common and negative biopsy does not exclude the diagnosis

Management Systemic steroids (60 mg /day) to prevent visual loss, reduction should be guided by symptoms and ESR, aiming for 10 mg daily for 6 weeks, and then decreased by 1 mg / month Maintenance therapy is required for at least one year Relapse occur in 30 % and is an indication to restart high dose steroid with additional immunosuppressive agents typically azathioprine or methotrexate

Classical polyarteritis nodosa (PAN) Is a necrotizing vasculitis characterized by transmural inflammation of medium - sized to small arteries All ages can be affected (peak incidence 40 -50, f 1: 2 m) Hepatitis B is a risk factor for PAN Myalgia arthralgia, fever and wt loss, associated with manifestations of multisystemic disease

Classical polyarteritis nodosa (PAN) Palpable purpura, ulceration, inflammation , digital skin infarctions and livedo reticularis Symmetrical polyneuropathy due to arteritis of the vasa nervorum (70 %) Severe hypertension and / or renal impairment may occur due to multiple renal infarctions, GN is rare

Digital skin infarctions

Digital skin infarctions with gangrene

Tissue necrosis

Wrist drop (mononeuritis multiplex )

Diagnosis by: Mesenteric, hepatic or renal angiography, which shows multiple aneurysm and smooth narrowing Tissue biopsy (muscle or sural nerve)

Treatment Steroids and cyclophosphomide are the treatment of choice for idiopathic disease Antiviral therapy used for hepatitis B related to remove the source of the antigen Mortality is less than 20 %, relapse occur in up to 50 % of patients   Small vessel disease of arterioles, venules and capillaries:

Microscopic polyangitis (MPA) is more common than PAN Rapidly progressive GN with alveolar hemorrhage Cutaneous and GI involvement similar to PAN Neuropathy 15 % Pleural effusion 15 % Patient are usually P-ANCA (myeloperoxidase) - positive

wegner's granulomatosis (WG) Upper airway involvement (typically epistaxis, nasal crusting and sinusitis),saddle shape deformity , haemoptasis, mucosal ulceration and deafness due to serous otitis media Ocular involvement as proptosis due to inflammation of the retro - orbital tissue, diplopia, loss of vision due to optic nerve compression Migratory pulmonary infiltrate and nodules occur in 50 % of patients Minority of patients present with GN Patients usually C- ANCA - positive

Saddle shape deformity

ocular manifestations

pulmonary infiltrate and nodules with cavitations

Churge - Strauss syndrome (CSS) Most patients have a prodromal period for many years characterized by allergic rhinitis, nasal polyposis and late onset asthma that is often difficult to control Typically there is triad of skin lesion (purpura or nodules), asymmetric mononeuritis multiplex and eusinophilia or back ground of resistant asthma

Typical skin lesions

Churge - Strauss syndrome (CSS) Pulmonary infiltrates and pleural or pericardial effusion due to serositis may be present 50 % have abdominal symptoms due to mesenteric vasculitis Either C-ANCA or P-ANCA is present in 40 % of cases

Pulmonary infiltrate

Management The aim of treatment is to induce a remission and then to maintain remission with minimum drug toxicity Remission induced either with oral Prednisolone (1 mg /Kg/day) and continuous oral cyclophosphamide (2 mg/Kg/day) or with bullous IV methylprednisolone (10 mg /kg) and cyclophosphamide (15 mg/kg) initially fortnightly and subsequently monthly

Management Cyclophosphamide is usually continued for 6-12 months followed by maintenance with azathioprine Mensa is used with cyclophosphamide to reduce the risk of hemorrhagic cystitis Co-trimoxazole is used for prophylaxis against pneumocystis pneumonia Plasma exchange used in severe and resistant cases IV gamaglobulin and anti T cell therapies are consider

Henoch- Schonlein purpura (HSP) Occur in children and young adult Has good prognosis Suffered from purpura over the buttocks and lower legs, abdominal symptoms (pain and bleeding), arthritis (knee and ankle) following an upper respiratory tract infection

Palpable purpura

Henoch- Schonlein purpura (HSP) Nephritis occur in 40 % of cases, 4 weeks after the onset of symptoms The diagnosis confirmed by the demonstrating IgA deposition within and around blood vessel walls Bad prognosis signs: hypertension, abnormal renal function and protein urea >1.5 g/day

Treatment Steroids for GI and joint involvement Pulse IV steroids and immunosupression for nephritis

Behcet’s syndrome More common in Japan and eastern Mediterranean countries where it has an association with HLA-B51 Characteristically targets venules Oral ulcers are universal, usually deep and multiple, last for 10- 30 days Genital ulceration is less common 60- 80 % Skin lesions in form of erythema nodosum, acneiform lesions, migratory thrombophlebitis and vasculitis

Behcet’s syndrome Pathergy reaction is hyper reactivity at the site of minor trauma (positive if a pustule develops within 48 hours) Ocular involvement, anterior or posterior uveitis or retinal vasculitis Neurological involvement in 5 %, cause hemiparesis, recurrent thrombosis Renal involvement is rare

Criteria for the diagnosis of Behcet's syndrome Oral ulceration: minor aphthous, major or herpitiform ulceration at least 3 times in 12 month period Plus 2 of: Recurrent genital ulceration Eye lesion Skin lesion Positive Pathergy test

Treatment Topical steroid for oral ulceration Colchicine for erythema nodosum, arthralgia and oral ulceration Thalidomide for oral and genital ulceration Oral steroid in combination with other immunosuppressive drugs in systemic disease