Upper airway manifestations of granulomatosis with polyangiitis

The head and neck are the most common sites of involvement at initial presentation of granulomatosis with polyangiitis (GPA [Wegener’s granulomatosis]). Head and neck manifestations occur initially in 73% of patients, and eventually, up to 92% of patients with GPA are affected.¹ Many of these compromise the upper airway. Although treatment is multidisciplinary, the effects on the airway make it important to understand upper airway presentations and treatments. This article examines upper airway disease presentations, their assessment, and their advocated interventions.

DISEASE COURSE

Because head and neck involvement may be associated with a less aggressive form of GPA, outcomes for patients with predominantly head and neck involvement may be better compared with those who have involvement of other systems.²

The natural course of GPA may be indolent or rapidly progressive. Regardless, left untreated, it progresses to a generalized systemic disease that often leads to significant morbidity and likely mortality. Most patients (96%) achieve remission with immunosuppressive therapy, but nearly half (49%) have at least one relapse.¹ For this reason, systemic immunosuppressive medications play a dominant role in systemic and localized head and neck disease control. Patients often require maintenance medications along with additional therapies during disease exacerbation.³ Therefore, key partnerships between internists, rheumatologists, and otolaryngologists are paramount in the treatment and follow-up of these patients.

DIAGNOSIS: MAINSTAY IS SEROLOGIC EVALUATION

The differential diagnosis of GPA includes infection, lymphoproliferative disease (T-cell lymphoma), systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, and other granulomatous diseases such as eosinophilic GPA (Churg-Strauss syndrome), polyarteritis nodosa, and microscopic polyangiitis. Appropriate diagnosis is critical because treatment of these entities varies drastically.

The mainstay of GPA diagnosis is serologic evaluation for a cytoplasmic pattern of antineutrophil cytoplasmic antibodies (cANCA), which are reactive toward proteinase-3 (PR3) or myeloperoxidase (MPO). Testing for cANCA yields a pooled sensitivity of 91% and specificity of 99%. Sensitivity falls significantly (63%) when the disease is in nonacute stages, while the specificity remains high.⁴ These cANCA test characteristics allow a high positive predictive value for this rare disease.

Biopsy is typically reserved for cases in which serologic ANCA testing is nondiagnostic. Biopsy tissue may be readily accessible from the head and neck, but these biopsies may bear significant false-negative rates.^4–6 Diagnosis requires demonstration of palisading granulomas as vascular or extravascular lesions within the upper respiratory tract tissues. The specific site biopsied from within the head and neck has been shown to influence diagnostic yield, with sinonasal biopsies producing the highest yield.

SINONASAL MANIFESTATIONS

The nose and paranasal sinuses are the most frequently affected sites in the head and neck, noted in 64% to 80% of patients. Additionally, the nose is the only site of involvement in 30% of patients.⁷ Given the high frequency of sinonasal manifestations, GPA should be considered as a potential diagnosis among patients with persistent sinonasal disease.

Pathophysiology and disease course

The pathophysiologic mechanisms leading to the changes in the sinonasal tract in GPA have not been established. GPA is believed to be an immunologic disease that manifests as a vasculitis of small- and medium-sized vessels. Multiple potential causative factors have been identified, including fibrinoid necrosis of small blood vessels, epithelial granulomas, chronic inflammation, and prior surgical intervention.^8,9 The acute and chronic inflammation, coupled with the epithelioid granuloma formation, damages adjacent small- to medium-sized vessels. The vasculitis leads to diminished blood flow and subsequent avascular necrosis, which may promote tissue necrosis and bone destruction. This destructive process typically starts in the midseptum supplied by Kiesselbach plexus and in the turbinates. The process then eventually spreads to the paranasal sinuses.⁸

Patient evaluation

Examination of the nasal cavities is typically performed by rigid or flexible nasal endoscopy and often reveals nasal crusting, friable erythematous mucosa, granulation, and even signs of sinusitis. All or part of the cartilaginous septum may be involved, leading to significant septal defects. As the degree of cartilage destruction increases, nasal dorsal support decreases, leading to a visible depression of the external nose known as a “saddle-nose” deformity, which is present in 23% of patients with GPA.^7,10

Imaging assessment by computed tomography (CT) is needed to establish disease extent and involvement. Atypical findings may include bony erosion and destruction of the septum and turbinates; erosion of bony partitions within the ethmoid sinuses; neo-osteogenesis of the maxillary, frontal, and sphenoid sinuses; and complete bony obliteration of the maxillary, frontal, and sphenoid sinuses.^9,11

Clinical presentation

Sinonasal disease indicates the degree of disease activity.¹² Clinical findings may vary, but they have a significant impact on quality of life in these patients.¹³ Most patients with active disease present with nasal crusting (69%), chronic rhinosinusitis (CRS) symptoms (61%), nasal obstruction (58%), and serosanguinous nasal discharge (52%).¹⁰ Patients may also complain of foul-smelling rhinorrhea, recurrent epistaxis, hyposmia, anosmia, and epiphora (from granulomatous compression or obstruction of the lacrimal system). In a series of 120 patients with GPA, Cannady et al found that four (3.3%) patients had mucoceles and three (2.5%) had orbital pseudotumor.¹⁰

Any structure in the sinonasal cavity, including mucosa, septum, turbinates, and sinuses proper, may be affected because of the vasculitic involvement of mucosal blood vessels that causes diminished blood flow and subsequent necrosis. The area of the anterior septum supplied by Kiesselbach plexus is the most common site of active nasal disease, which can eventually lead to the common presentation of an anterior nasal septal perforation.

Otologic disease secondary to sinonasal GPA

Otologic involvement is observed in 19% to 38% of patients with GPA.^14,15 Most patients with GPA who exhibit otologic symptoms have middle ear or mastoid disease. It typically appears as chronic otitis media (COM) with conductive hearing loss.¹⁶ In most cases, the otologic involvement is secondary to Eustachian tube dysfunction caused by the presence of extensive disease in the nasopharynx.

Additionally, chronic mastoiditis can result from direct mastoid involvement with GPA. Facial nerve palsy secondary to infective bony destruction is a rare but repeatedly reported complication of GPA.^14,15

Inner ear involvement is a relatively common otologic presentation of GPA. Patients may experience sensorineural hearing loss (SNHL) as well as vertigo, which may mimic Cogan syndrome. Importantly, patients may exhibit inner ear involvement with or without middle ear and mastoid disease. The SNHL observed in patients with GPA may be responsive to steroid or immunosuppressive therapy.