Wegener’s granulomatosis

(redirected from Midline granulomatosis)

Wegener’s granulomatosis

A rare condition characterised by granulomatous inflammation of the respiratory tract, antineutrophil cytoplasmic antibodies (ANCAs) and necrotising vasculitis of small-to-medium-sized vessels (e.g., capillaries, arteries, arterioles, and venules).
 
Epidemiology
Male:female ratio 2:1; middle-aged population.

Aetiology
Hypersensitivity and/or autoimmunity.
 
Clinical findings
Anorexia, weight loss, fatigue, malaise, prostration, persistent fever, night sweats, cough, haemoptysis, splenomegaly, migratory polyarthritis, granulomas of oral cavity and periorbital regions.

• Neurology
Aseptic meningitis, nonhealing granulomas of CNS, peripheral neuropathy.

• Eyes
Nasolacrimal duct obstruction, episcleritis, conjunctivitis, proptosis.

• Ears
Chondritis of external ear, serous or purulent otitis media, hearing loss.
 
• Heart
Myocardial infarction due to vasculitis.

• Kidneys
From asymptomic to focal glomerulitis; may progress to progressive necrotising crescentic glomerulonephritis with hypertension uremia, and end-stage renal failure.
 
• Lung
Upper-respiratory tract complaints—ulcers, pneumonia, pulmonary lesions with cavitation, pleuritis, progressive dyspnoea requiring O2.

• Nose
Granulomas, paranasal sinusitis; nasal mucosa is red, raised, granular, friable and ulcerated, with 2º bacterial infection, and may perforate; haemorrhagic rhinorrhea.

• Skin
Granulomatous, eventually; a disseminated vascular phase may develop and is associated with lesions, diffuse leukocytoclastic vasculitis and necrotising skin lesions.

Diagnosis
Renal biopsy determines extent of renal involvement, which may include necrotising glomerulonephritis; open-lung biopsy of a solid or cavitating lesion.
 
DiffDx
Granulomatous disease, polyarteritis, renovascular phase of SBE, progressive glomerulonephritis, SLE, lethal midline granuloma (i.e., lymphoma).
 
Lab
Anaemia may be profound, normal/increased complement, increased ESR, leukocytosis, increased ANCAs.
 
Urinalysis
Proteinuria, hematuria, RBC casts. 

Management
Corticosteroids (e.g., prednisone); methotrexate, azathioprine, cyclophosphamide induce remission in 75%; long-term prophylactic trimethoprim-sulphamethoxazole may be effective for upper-respiratory tract lesions; kidney transplant if renal failure.
 
Management side effects
Cyclophosphamide—leukopenia, ergo infections; haemorrhagic cystitis; gonadal dysfunction; hair loss, which is reversible on discontinuing the drug.
 
Prognosis
Dramatically improved by immunosuppressants; there is an increased risk of solid tumors post-high-dose cyclophosphamide; complete Wegener’s granulomatosis usually progresses rapidly to renal failure once diffuse-vascular phase begins; patients with the limited Wegener’s granulomatosis may have nasal and pulmonary lesions, with little or no systemic involvement.