Ear, nose, throat and airways disease in granulomatosis with polyangiitis

ENT disease is common in GPA (70–99% cases). ENT features, such as nasal pain, worsening nasal crusting, epistaxis/bloody rhinorrhoea, stridor or sudden hearing loss, are associated with vasculitic disease activity, particularly with onset in the past 4 weeks. Rigid nasendoscopic examination is sensitive for the detection of mucosal inflammation, ulceration, granulation or friable mucosa, which indicate active GPA. Flexible nasendoscopic examination is not reliable for evaluating the subglottis and is unable to visualize the distal respiratory tract, where distal airway stenoses often coexist. Sudden hearing loss should prompt ENT assessment and audiogram within 24 h and an urgent increase in immunotherapy. Where possible, surgical procedures for ENT manifestations of vasculitis should be deferred until the disease is in stable remission. This patient presented in her late 20s with a vasculitic rash, nasal crusting, bloody nasal discharge, facial pain and a positive PR3-ANCA. Granulomatosis with polyangiitis (GPA) was diagnosed and she initially responded to cyclophosphamide and methylprednisolone. She was maintained on azathioprine for 5 years then suffered an acute disease flare with chest, nasal and skin involvement. Further treatment with methylprednisolone, cyclophosphamide and rituximab induced remission for 1 year. Trials of mycophenolate and ciclosporin failed to prevent disease activity manifesting as recurrent chest infections, inflammatory arthritis, return of her vasculitic rash, collapse of her nasal dorsum and purulent bloody nasal discharge. A CT of the thorax was performed, showing a new left upper lobe cavitating lung lesion. While further cyclophosphamide and rituximab induced remission and repeat chest imaging suggested improvement to the lung cavity, she continued to remain short of breath and developed stridor. Flow volume loops showed a flattened, box-like curve suggestive of fixed extrathoracic airway obstruction and a bronchoscopy showed a Cotton–Myer grade of 2–3 subglottic stenosis. Despite rituximab every 6 months, she required her first episode of elective subglottic stenosis dilatation 6 months later and continued to have rituximab every 6 months and elective dilatations for the next 4 years. This stabilized her disease and subglottic stenosis, allowing her to undergo rhinoplasty with an L-shaped strut cartilage graft. Following a missed rituximab infusion, she returned 18 months later with worsening exertional dyspnoea, acute sensorineural hearing loss and a rising PR3-ANCA. After further rituximab and steroids, a tracheoscopy and dilatation (initially postponed due to a chest infection) showed a mild subglottic stenosis but a right main bronchus filled with secretions. Flexible bronchoscopy showed new right-sided bronchial stenoses, which were dilated. A further trial of maintenance azathioprine was initiated but was poorly tolerated and stopped, and she returned again 9 months later with worsening dyspnoea, stridor, wheeze and acute hearing loss. Flexible laryngoscopy suggested that the subglottic stenosis remained mild and uninflamed, but subsequent tracheoscopy showed a new severely inflamed 45% distal tracheal stenosis and a 90% right bronchial stenosis. Interval dilatation, after a week of high-dose corticosteroids and a further dose of rituximab, was performed successfully. She continues to undergo intermittent scheduled rituximab infusions and tracheoscopy and dilatation procedures every 6 months. (A)–(B) Rigid endoscopic view of subglottic stenosis with no overt features of disease activity. (A) Pre-dilatation and (B) post bougie dilatation. (C) Audiogram showing profound left-sided sensorineural hearing loss. Although right-sided hearing is within normal limits, there is a suggestion of a borderline low-frequency deficit in the right ear. (D) Coronal CT scan of the thorax showing distal tracheal stenosis with extension into the main proximal bronchi (A)–(B) Rigid endoscopic view of subglottic stenosis with no overt features of disease activity. (A) Pre-dilatation and (B) post bougie dilatation. (C) Audiogram showing profound left-sided sensorineural hearing loss. Although right-sided hearing is within normal limits, there is a suggestion of a borderline low-frequency deficit in the right ear. (D) Coronal CT scan of the thorax showing distal tracheal stenosis with extension into the main proximal bronchi ENT involvement occurs in 70–99% of GPA patients and is often an early feature. A respiratory tract–limited form of GPA, without systemic disease, has been described. Of the ENT manifestations, sinonasal involvement is most frequent (up to 83% of cases), with hearing loss affecting 23–37% of cases and subglottic stenosis affecting 1–23% [1]. Patients with acute or subacute hearing loss should have an ENT assessment within 24–48 h, including audiometry. Both conductive and sensorineural hearing loss may respond to prompt systemic immunosuppression [2]. In acute sensorineural hearing loss, high-dose corticosteroids should be initiated as soon as possible after onset. Patients with persistent sensorineural hearing loss (i.e. damage) should be offered hearing aids and those with severe loss and well-controlled disease should be considered for cochlear implantation [2]. Grommets can be considered for persistent conductive hearing loss resulting from middle ear effusion, although effusion resulting from active vasculitis may respond to immunosuppression alone. Nasal disease activity typically manifests as crusting, epistaxis and nasal pain with or without hyposmia. The nasal mucosa is crusted, inflamed and friable, with ulcerations or granulation. Nasal disease activity is best assessed by rigid nasendoscopy [3]. The addition of budesonide to nasal douching solution may be helpful in treating localized disease activity. Evidence in chronic rhinosinusitis suggests that the application of topical nasal corticosteroids via nasal irrigation is more effective than steroid nasal sprays [4]. Nasal disease damage typically takes the form of nasal septal perforation and/or external nasal (‘saddle nose’) deformity. Other nasal structures, such as turbinates, may also be eroded, but erosion of the maxilla should cause one to question the diagnosis. Septal perforations can cause whistling, blockage sensation, bleeding and crusting, even in the absence of disease activity. Patients should use twice daily nasal douching to keep crusting at bay. Dryness of the perforation edges can be treated with topical moisturizers (e.g. petroleum jelly). There is no good evidence that septal perforation repairs are effective in GPA [5]. Prompt medical treatment of nasal disease activity can prevent the development of this challenging problem. Early signs of impending saddle deformity include development of pain over the upper lateral nasal cartilages and a supratip depression. Should saddling occur, aesthetic rhinoplasty for reconstruction of saddle nose deformity should only be attempted during periods of stable remission. Although evidence remains limited, good long-term results are reported with L-shaped strut grafts fashioned from autologous costal cartilage [5]. Airway stenosis should be considered in patients with increasing shortness of breath on exertion and stridor. Hoarseness or chronic cough may also occur. As subglottic stenosis can occur in isolation, lack of other features of disease activity does not exclude the diagnosis [6], nor does inspection of the subglottis with a flexible nasolaryngoscope, given that this is often challenging in the outpatient department and >60% patients with airway stenosis have two or more distinct lesions [7]. CT scan of the neck and thorax and respiratory function testing are useful adjuncts in making the diagnosis. Where possible, acute inflammatory stenoses should initially be managed with systemic immunosuppression with or without nebulized budesonide, with concurrent acute dilatation reserved for critical/refractory cases. Delaying endoscopic intervention until subglottic inflammation has resolved appears to reduce the rates of restenosis and operative complications, as does perioperative high-dose corticosteroid treatment [8]. Chronic stenoses are typically pale, fibrotic and gradually progressive, while acute inflammatory stenoses are rapidly progressive, erythematous and friable. Therapeutic dilatations with bougies or balloons should be simultaneously performed with flexible bronchoscopy for identification, assessment and treatment of distal airway lesions. Patients will often require serial dilatations at planned intervals, with a decreasing need over time in some with well-controlled disease. Tracheostomy is rarely required and should be avoided if possible. Many thanks to the members of the Vasculitis and Lupus Service at Addenbrooke’s for their advice on the case and the article. Thank you to the patient for her consent to publish this article. Funding: M.L.C. is funded by the Addenbrooke’s Charitable Trust and the Wellcome Trust PhD Programme for Clinicians. This paper forms part of the supplement entitled ‘EUVAS Cambridge Vasculitis Course Case-Base Supplement’. This supplement is supported by the University of Cambridge. Disclosure statement: The authors declare no conflicts of interest. The data underlying this article will be shared on reasonable request to the corresponding author.