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Friday, September 30, 2011

Refining the phenotypes and diagnosis of chronic sinusitis

Payne, Borish, and Steinke (J Allergy Clin Immunol 2011;128:710-720) characterize chronic sinusitis (CS), its presentation, diagnosis and treatment in the “Mechanisms of allergic diseases” section in this issue. Pointing out that CS has been considered a single clinical presentation in the past, the authors make clear that it is a complicated disease entity requiring clinical distinction for effective treatment. Definitionally, they state that the cardinal features of CS are nasal irritation, anterior and posterior rhinorrhea, and nasal blockage with pressure or pain in a sinus pattern that lasts more than 12 weeks. Payne et al. emphasize that, fundamentally, CS is an inflammatory disease of the sinus that occurs with and without nasal polyps (NP). Importantly, eosinophilia distinguishes two subsets of CS and they note that NP is predictive of eosinophilic CS, but not diagnostic.

Chronic infectious sinusitis. Payne et al. point out that all forms of CS are associated with barrier and immune disruption that compromise the sterility of the sinus. Chronic infection is not causally related to CS, but instead, CS is associated with abnormal microbial colonization as a result of loss of sterility. Clinically, patients with chronic infectious sinusitis (CIS) have neutrophilia and profound bacterial load within their sinuses. Additionally, the presence of biofilms (bacterial and DNA matrices embedded with bacteria) is critical to the pathology of CIS, providing a source for superinfection and constant inflammatory factors. The authors note that biofilms are probably involved in most forms of CS.

Noneosinophilic sinusitis (NES). NES is an idiopathic form of CS resulting from chronic or recurrent obstruction of the sinus ostia by any number of causes such as anatomic variation and allergic rhinitis. Clinically, NES is associated with significant mononuclear cell infiltrate with few neutrophils, and remodeling with dense collagen and matrix deposition. Also, B cell and plasma cell infiltrations are seen in conjunction with B-cell activating cytokines. Increased numbers of connective tissue-associated mast cells are common, which contrasts with eosinophilic forms of CS. Payne et al note that NES+NP is associated with increased expression of hypoxia-inducible factor (HIF) 1α which supports the idea that chronic obstruction of the ostia causes hypoxic damage to the sinus. The authors report that limited genetic work has been published, though an early study from their research group identified plasminogen activator inhibitor 1 (PAI-1) gene as a possible candidate. They note that surgical treatment for both CIS and NES is effective when conservative therapies have failed.

Chronic hyperplastic eosinophilic sinusitis (CHES). As the name implies, CHES is characterized by dominant eosinophilia of the sinuses and NP, if present. Immunohistochemistry has demonstrated increases in cytokines, chemokines, and inflammatory mediators that reinforce the eosinophilia. Payne et al describe it as a self-perpetuating syndrome and note that surgery is insufficient for mitigation or resolution. CHES patients are allergen sensitized and experience exacerbation of sinus inflammation and eosinophilia after aeroallergen exposure. Abnormal colonization of the sinus may contribute to the pathology as well. The authors note that CHES patients often have asthma and that CHES shares pathological features with asthma, suggesting that CHES and asthma are manifestations of the same dysfunctional immune process. Initial treatment for CHES involves nasal saline irrigation with and without surfactants, and add-on therapies, such as oral and topical steroids, that are effective in asthma patients are often effective in CHES patients as well.

Payne, Borish, and Steinke extensively discuss clinically distinct features of two other forms of CS, allergic fungal sinusitis and aspirin-exacerbated respiratory disease, and current knowledge of their phenotypes, genetics and effective management. The authors emphasize in their conclusion the primary requirement to determine the presence or absence of eosinophilia, regardless of NP presence, to predict treatment outcomes. They suggest that tissue biopsy from the sinus or NP may be the most appropriate step to confirm diagnostic classification.

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