Non-infectious Inflammatory Lesions of the Sinonasal Tract

Sinonasal involvement in sarcoidosis is usually part of multisystem disease, but patients may present with chronic rhinosinusitis, nasal obstruction and nasal crusting. The clinico-pathologic features required for diagnosis [1] are:Four clinical patterns of disease are identified: mucosal hypertrophy, mucosal atrophy, nasal destruction and nasal enlargement [2]. Histological and other laboratory investigations may be required to resolve some of the clinical differential diagnoses, although biopsies are often non-specific (Table 1).

EGPA is a rare systemic vasculitis that was first described in patients diagnosed as polyarteritis nodosa with necrotising vasculitis, but who showed tissue and blood eosinophilia and extravascular granulomas [10]. Patients have symptoms of allergic rhinitis, polyposis and sinusitis and a history of asthma [11]. Clinically significant disease often affects the lungs, skin and kidneys, although severe renal disease is uncommon. Consensus recommendations for evaluation and management have been published [12]. Diagnosing EGPA implies biopsy-proven vasculitis or a strong clinical surrogate, but either can be difficult to obtain. Within the clinical contexts of asthma with eosinophilia, asthma with systemic manifestations or with extrapulmonary disease, a biopsy demonstrating small- or medium-sized-vessel vasculitis or pauci-immune crescentic glomerulonephritis, strongly supports a diagnosis of EGPA. Mucosal biopsies typically show an eosinophil-rich inflammatory infiltrate and may also show vasculitis and granulomatous inflammation (Fig. 2a) [11].

Relapsing polychondritis is a rare disease of young and middle aged adults with recurrent painful episodes of acute inflammation that destroy the nasal and aural cartilages. Tracheal chondritis leads to airway obstruction and pneumonia. Other manifestations include migratory arthritis, ocular inflammation, cardiac and neurological disease [13]. About one-third of patients have other autoimmune diseases and there is overlap with Behcet’s disease—the so-called MAGIC syndrome of mouth and genital ulcers with inflamed cartilage [14]. Relapsing polychondritis is a T_H1 mediated disease and, although the target antigens are not known, human and experimental studies suggest that collagen type II and the cartilage matrix protein matrilin-1 are likely candidates [13]. Biopsies of involved cartilage shows loss of mucopolysaccharide matrix, disruption of elastic fibres and microcysts, with erosion by CD4+ T lymphocytes (Fig. 2b). Neutrophils may be present in the early stages and there is usually perichondrial granulation tissue and fibrosis [13, 15].

Eosinophilic angiocentric fibrosis is an uncommon, idiopathic inflammatory condition of the nose affecting middle-aged adults with progressive fibrosis leading to nasal obstruction. EAF is considered to be one of the IgG4 related diseases which are typified by storiform fibrosis, obliterative phlebitis, many IgG4-positive plasma cells, a ratio of IgG4:total IgG plasma cells of >40 % and raised serum IgG4 [16, 17]. In the early stages, there is an eosinophil-rich inflammatory exudate around vessels. In later stages the inflammatory infiltrate is more patchy and mixed (eosinophils, neutrophils, lymphocytes and plasma cells) and progresses to onion-skin perivascular fibrosis (Fig. 3). The clinical and imaging features are non-specific and the diagnosis is made histologically [18].

Chronic rhinosinusitis (CRS) is a common disease, defined clinically as inflammation of the sinonasal mucosa leading to symptoms of nasal obstruction and discharge for more than 3 months. Many factors are implicated in chronic rhinosinusitis, including genetic, immunological and environmental factors [19]. Although antimicrobial treatment has little effect on the symptoms of CRS, bacteria and fungi are implicated in the pathogenesis of CRS through their involvement in the biofilms that form on the surface of the sinonasal mucosa. Biofilms are collections of micro-organisms that grow in a self-produced matrix, conditions that lead to modifications in gene expression. Sinonasal biofilms contain Staphylococcus aureus, Streptococcus pneumonia and Pseudomonas aeruginosa, sometimes associated with fungi such as Aspergillus sp. [4].

The inherited disorders associated with CRS are cystic fibrosis and primary ciliary dyskinesia. Cystic fibrosis is caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene (7q31.2) leading to a defect in chloride transport and thick mucin. As the life expectancy of patients with cystic fibrosis has increased in recent years, most patients develop CRS and nasal polyposis. Histologically, polyps in patients with CF are similar to those in other forms of CRS and there is a similar pattern of gene expression in mucosal glands, with the exception of increased expression in CF patients of the orthodenticle homeobox 2 gene, OTX2 [4, 20].

Primary ciliary dyskinesia syndrome is a group of conditions in which structural and functional abnormalities of cilia lead to CRS with polyps and recurrent infections. About 50 % of patients have Kartagener syndrome with CRS, situs inversus and bronchiectasis [21].

Inhaled water-soluble irritants such as formaldehyde, ammonia and sulphur dioxide readily dissolve in the surface mucus and may cause changes in the structure and function of the mucosa leading to olfactory dysfunction, sensory irritation and rhinosinusitis. Occupational rhinitis is associated with a wide range of chemicals and may be non-allergic or allergic in pathogenesis [22].

Nasal septal perforation may be caused by local trauma (‘nose-pickers’ perforation), inhalation of toxic substances such as cocaine or intranasal steroid and decongestant sprays, infective and non-infective granulomatous diseases and nasal malignancies [31]. Occupational exposure to corrosive chemicals such as strong acids and alkalis, chromates used in the electroplating industry, nickel, arsenic and copper may lead to perforation [32]. Biopsies are taken from the mucosal edge of a perforation to exclude specific pathologies, and usually show non-specific acute inflammatory debris, inflamed granulation tissue and reactive changes in the adjacent epithelium.