58 Non-Healing Nasal Granulomata
A granulomatous reaction is a specific type of chronic inflammation characterised by the local accumulation of macrophages and their morphologically and functionally diverse derivatives. These comprise the epithelioid cell and the multinucleate giant cell. Usually surrounding and interacting with these cells is a zone of lymphocytes. Most nasal granulomata are formed because of specific chronic infections. The most important of these are tuberculosis, atypical mycobacterial infection, syphilis, leprosy and fungal infections. Non-specific granulomata occurs when no infectious agent can be defined and comprises sarcoidosis and granulomatosis with polyangiitis (GPA), which, until the nomenclature changed in 2011, was previously known as Wegener’s granulomatosis.
58.1 Granulomatosis with Polyangiitis
Wegener in 1939 described a granulomatous disease of unknown aetiology comprising destructive lesions of the upper and lower respiratory tracts and glomerulonephritis. Histological examination showed granulomata formation and necrotising vasculitis. With GPA, there is usually multisystem involvement, affecting not only the three classical systems but also virtually every organ in the body including the ear. Occasionally, only a single system is affected by the disease.
Current knowledge suggests that an infection, perhaps of viral aetiology or due to Staphylococcus aureus, in susceptible individuals triggers an immunological response to produce the features of GPA.
58.1.2 Clinical Features
• In the nose, active GPA classically causes a sanguineous discharge, crust formation, friable, ulcerated mucosa and nasal obstruction. Septal cartilage may erode to cause a septal perforation. Loss of dorsal nasal support may occur resulting in a saddle deformity in advanced or untreated disease.
• Chest features comprise a cough, haemoptysis and dyspnoea. Oliguria and micro- or macroscopic haematuria suggest renal involvement.
• GPA may affect the external and middle and inner ear. External ear symptoms comprise inflammation of the pinna or external auditory canal with otalgia, canal oedema, canal ulceration with granulations and serosanguinous discharge. Middle ear involvement may cause myringitis, tympanic membrane perforation, a mucosanguinous discharge, ossicular erosion, fallopian canal inflammation and erosion, a facial nerve palsy, middle ear mucosal oedema, granulomata formation and a conductive hearing loss. Vertigo, tinnitus and a sensorineural hearing loss suggest vestibulocochlear involvement.
• There may also be laryngeal, pharyngeal and oral cavity ulceration with mucositis and friable lesions. The appearances of active areas of involvement are similar to a carcinoma and the diagnosis can only be made by a representative biopsy.
• Secondary infection may occur with malaise, lethargy, loss of appetite and weight loss. Untreated, there is a 93% 2-year mortality.
• A chest radiograph may show single or multiple opacities up to 5 cm in diameter compatible with areas of infarction with or without cavitation. Alveolar infiltrates, pleural opacities or atelectasis may be present.
• Urinalysis may show red cells, protein and casts. Creatinine clearance declines. Renal biopsy, if indicated, shows focal necrotising glomerulonephritis and vasculitis.
• Cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) is usually positive in GPA. Recent meta-analysis looking at patients with active GPA, for c-ANCA, calculated a sensitivity of 91% and a specificity of 78 to 100% for patients with disseminated disease but just 60 to 70% for those with upper aerodigestive tract disease without lung, renal or other system involvement. Between 20 and 40% patients have raised titres against perinuclear ANCA (p-ANCA). Both antibodies are detected by indirect immunofluorescence. Both antibodies are directed against proteinase 3 and therefore low-titre samples can be checked by an antigen-specific enzyme-linked immunosorbent assay. Titres parallel changes in disease activity.
• A representative biopsy of an active area of inflammation with symptoms and signs of either isolated or systemic GPA is necessary and sufficient to make the diagnosis. Random biopsies of normal-looking upper respiratory mucosa in subjects suspected of having GPA will never show features of GPA and therefore the biopsy of an active area is stressed.