Wegener’s DEAPCIT
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