Wegener’s

DEAPCIT

Definition

• WG is an necrotising granulomatous diseases leading to – inflammation of the upper and lower respiratory

tracts– Systemic vasculitis of small arteries and veins – Focal glomerulonephritis

Epidemiology

• prevalence of 5 per 100,000• males > females (except in laryngeal

manifestations)• wide age range but increased in 4-5th decade• all racial groups affected but predominantly

whites

Aetiology

• cause of WG is unknown-• ? viral related activation of ANCA• Increasing circumstantial evidence supports

the concept that WG is an autoimmune

Pathogenesis

• (ANCA) no direct evidence • Anti Neutrophil surface antibody → degranulation of the

leukocytes and the release of toxic oxygen radicals and lysosomal enzymes

• neutrophils activated by ANCA → directly damage endothelial cells → vasculitis

• Titres for ANCA correlate with disease activity and predict relapses

• granular cytoplasmic staining pattern ANCA (c-ANCA) has been strongly associated with WG

• a smaller number of patients with WG have a perinuclear staining pattern ANCA (p-ANCA)

pathology

• necrotising granulomatous vasculitis• vasculitis of small to medium-sized vessels and

polymorphous inflammatory infiltrate composed of lymphocytes, histiocytes and less frequently eosinophils and neutrophils

• “ischaemic” or “geographic” type necrosis with basophilic smudgy appearance

• multinucleated giant cells or non-necrotising granulomas

Clinical

• May be localised or systemic• H+N manifestations = initial symptoms in 75%• laryngx: – Upper airway findings include oedema, ulceration of

larynx (25%) and significant subglottic stenosis (8.5%)

– Hoarseness, cough, haemoptysis, dyspnoea, stridor and wheeze

– Flattening of both insp and exp phase in flow-volume loop

Clinical (ear)• External

– Rarely involves external ear– OE 2ry to OM– Auricular chondritis similar to RP

• Middle– Serous otitis media – most

common otologic manifestation• 2ry to ETD

– CHL– Suppurative otitis media possibly

with granulation tissue – CNVII palsy 2ry to otomastoiditis– TM perforation?

• Inner– SNHL = 2nd most common

L-T morbitidy (renal = 1st)• 35% affected• May develop rapidly• ? 2ry to vasculitis of

cochlear vasculature• ? Immune complex

deposition within cochlea– NB vertigo = rare– ? Tinnitus

Clinical (nose)

• Nose: – Non-specific

• Nasal congestion, rhinorrhoea, anosmia, epistaxis

– Cobblestone mucosa– Crusting, septal perforation, saddle nose deformity, dorsal

nasal pain (suggesting chondritis) and recurrent sinusitis– Anterior nasal septum in Kiesselbach’s plexus = commonly

involved– Nasal airway cicatricial stenosis– Nasal cavity > maxillary > ethmoid > frontal > sphenoid– NB often mistaken for NK cell lymphoma

Clinical

• Throat: – Oral cavity manifestations

(rare)– hyperplasia of gingiva

and gingivitis– Strawberry gingival

hyperplasia– Upper airway findings

include oedema, ulceration of larynx (25%) and significant subglottic stenosis (8.5%)

• H+N: – Salivary involvement

Sjögren syndrome– Can have massive

enlargement of the SMG or parotid glands

Clinical

• Pulmonary: – Classic chest

radiographic findings include bilateral multiple parenchymal nodes (+/- cavitation), or airway disease that simulates pneumonia

• Renal: – Usual cause of death in

WG and the most important prognostic feature

Investigation • Haematological

– Elevated ESR– ANCA (C-ANCA & p-ANCA)– WG → c-ANCA is +ve in 70% and p-ANCA in 25% – Patients with polyarteritis nodosa and Kawasaki disease may also test

positive • Radiological

– CXR: for pulmonary infiltrates • Pathological

– Biopsy vasculitis of small vessels, granulomatous changes, and focal necrosis

• Urinalysis– Performed to evaluate urinary sediment (eg, RBC casts, haematuria,

proteinuria)

Diagnosis

• New Criteria – all of:– Lack of eosinophilia– Biopsy verified

necrotising vasculitis – Glomerulonephritis– Granulomatous

inflammation – surrogate

– PR3 c-ANCA +ve

• Criteria– Nasal or oral

inflammation– Chest x-ray showing

nodules, infiltrates (fixed), or cavities

– Microscopic haematuria or red cell casts in urine

– Granulomatous inflammation on biopsy (within vessel wall or perivascular)

Treatment • untreated mortality rate of 90% at two years• consists of meticulous dental and nasal care, removal of crusts from

the nose and ET orifices and ME drainage• limited disease → prednisolone and methotrexate or prednisolone

and cyclophosphamide for 3 months → methotrexate and azathioprine

• systemic disease → prednisolone and cyclophosphamide for 3-12 months → methotrexate and azathioprine

• other options include mycophenolate, anti-TNF and IV Ig• for isolated sinus disease, treatment includes low dose steroids,

topical steroids, saline irrigations and antibiotics as needed• airway compromise is alleviated with systemic steroids and subglottic

stenosis may warrant tracheotomy

Treatment

• AIRWAY–Dilation and intralesional/inhaled steroid or

mitomycin C–CO2 laser treatment of stenosis– Silicone stenting of stenosis– laryngotracheal reconstruction–endoscopic longitudinal incision of stenosis– Tracheostomy / Tracheal resection