Systemic corticosteroids can effectively reduce the size of nasal polyps, and while the benefits of relieving nasal obstruction and improving olfaction often outlast the duration of therapy, the therapeutic effects are relatively short-lived. For management of acute exacerbations and for pulsed steroid therapy, there is no evidence-based consensus on optimal dosing, although the upper limit in most studies has been 60 mg of prednisone daily for 20 days. Gastrointestinal upset, insomnia, and transient adrenal suppression are among the potential side effects of orally administered corticosteroids. When given preoperatively, oral steroids improve visualization of surgical field and potentially decrease blood loss and operative time. The literature suggests that a daily dose of 30 mg of prednisone started 5–7 days preoperatively is a safe and effective starting point [41]. Postoperatively, systemic steroids can help to reduce postsurgical edema and inflammation and prevent early synechiae formation [42].

While oral corticosteroids have been found to be effective in treating patients with classic eosinophilic polyps, patients with neutrophilic polyps seem to respond less favorably. Wen et al. found that oral steroid therapy reduces eosinophil counts but not neutrophil counts in nasal polyps, and patients with eosinophilic polyps had significantly better oral steroid responses than those with neutrophilic polyps, in terms of reduction of polyp size, nasal congestion and total nasal symptom scores, and nasal resistance [13]. Understanding the histopathology of nasal polyps may thus help to individualize therapy and improve treatment responses.

In contrast to the short-term efficacy of systemic steroids, the role of topical steroids is to maintain long-term control of nasal polyps. There are a variety of drug delivery mechanisms, ranging from low-volume low-pressure systems (nasal drops and sprays) to high-volume high-pressure systems (nasal irrigation). There is general agreement that topical steroid therapy helps to alleviate symptoms, reduces polyp size, and prevents recurrence of polyps postoperatively [43]. Intranasal corticosteroid sprays have been the most well studied and have proven to be efficacious for nasal polyposis.

Intranasal steroid irrigations have become popularized but are less well studied. The potential benefit of delivering a higher dose of corticosteroids locally while minimizing systemic side effects is attractive, although there are few randomized trials to date that specifically look at this therapy. Safety studies have found no negative effect on the hypothalamus-pituitary-adrenal (HPA) axis after 6–8 weeks of continuous irrigations with budesonide [44, 45].

Despite nasal polyposis being largely an inflammatory condition, infectious sinusitis may be an associated condition. Antibiotics can play a role in treating the infectious portion of the disease, although there are few randomized trials looking at this. Short-term courses of antibiotics should be considered, particularly when pus is present and can be cultured, as an adjunct to maximal medical therapy and in acute exacerbations. Antibiotic therapy longer than 3 weeks is generally not recommended for infectious indications.

Doxycycline and macrolide antibiotics have been used in the treatment of nasal polyposis for their intrinsic anti-inflammatory properties, which are thought to be more effective for neutrophil-associated inflammation than eosinophilic inflammation. Treatment duration is often longer than for infectious indications, even up to 1 year. One study compared doxycycline with methylprednisolone and placebo and found significant reduction in polyp size and postnasal drainage associated with doxycycline, although there was no other symptom improvement or improvement in peak nasal inspiratory flow (PNIF) [46].

Studies of macrolides have been characterized by heterogeneous inclusion criteria and treatment outcome measures. The number of high-quality studies is limited, with the majority being prospective observational studies. One controlled study showed improved patient symptoms and endoscopic findings using roxithromycin 150 mg daily for 3 months in refractory CRS patients, especially in the subgroup with low IgE levels [47], while another controlled study using low-dose azithromycin did not show any difference from placebo [48]. Overall data from observational studies however show general improvements in patient symptoms, endoscopic findings, imaging findings, and reduction of inflammatory markers within nasal mucus secretions [49]. Macrolides are thus a therapeutic option in the treatment of CRSwNP. Whether the beneficial effects are truly due to the anti-inflammatory properties or the antimicrobial effects of macrolide antibiotics, or a combination of both, bears further study. The optimal subgroup of patients who may benefit most from this therapy also remains to be determined.

In contrast to topical corticosteroid therapy, topical antibiotic use in the management of nasal polyps is a lot more controversial. Theoretical benefits of topical antibiotics include eradication of biofilm and reduction of Staphylococcus superantigen load, although one small randomized trial showed only short-term improvement with mupirocin nasal rinses in recalcitrant Staphylococcal CRS which was not sustained in the longer term [50]. Studies have mostly focused on CRS and not specifically on nasal polyposis, so that it is not recommended for routine use in patients with CRSwNP.

Aspirin desensitization is a key treatment modality in managing nasal polyposis in patients with AERD, as an adjunct to surgery and medical therapy. The exact mechanism of action is unknown, although rapid induction of oral tolerance is associated with a decrease in serum cysteinyl leukotrienes and improvement in the dysregulation of arachidonic acid metabolism [51, 52]. Aspirin desensitization has been shown to improve symptoms and quality of life, prevent polyp regrowth, and reduce the need for oral corticosteroids and revision surgery and is optimally initiated within 4–8 weeks after sinus surgery [53–56]. Desensitization protocols vary, although most can be executed in an ambulatory setting, in contrast to earlier years in which desensitization was performed in the intensive care unit. Once desensitization has been achieved, maintenance doses are typically from 650 mg to 1,300 mg daily for life, with repeat desensitization needed if more than 96 hours has elapsed between doses. Our experience with aspirin desensitization is that the majority of patients are able to tolerate and complete it, with sustained endoscopic and symptom improvement over a prolonged period [57].

Given the possible link between fungi and CRS, people have studied using antifungal therapy in the treatment of CRS and its subtypes. The results so far have not shown benefit for antifungal therapy in either CRSwNP or AFS. Two clinical trials evaluating nasal amphotericin B sprays in patients with nasal polyps did not show benefit in symptom scores [58, 59]. A more recent systematic review looking at antifungal therapy for AFS also showed no overall benefit in topical or oral antifungal therapy on endoscopic scores or patient reported outcomes, with no significant differences between treatment and control groups [60].

Immunotherapy should be considered in atopic patients with CRSwNP, as this can help with symptomatic outcomes postoperatively [61]. Fungal immunotherapy is also an option in treating patients with AFS specifically, since the disease is characterized by an excessive immune response to fungi. Studies are limited to using dilute antigen concentrations in patients who have been operated upon to decrease the inflammatory load, although recent practice parameters have advocated higher allergen concentrations [62]. Recommendations have also been made to initiate fungal immunotherapy 4–6 weeks after surgery, to avoid exacerbation of symptoms in patients with active AFS [63]. The overall role of immunotherapy can thus be seen as adjunctive in the treatment of nasal polyposis.

Leukotrienes are mediators in the inflammatory cascade, and so it is unsurprising that increased levels of leukotrienes and its receptors have been shown in nasal polyps. Leukotriene antagonists have been shown to be effective in chronic inflammatory conditions of the airway such as allergic rhinitis and asthma, conditions which are commonly coexistent with nasal polyposis. Examples of CysLT1 receptor antagonists include montelukast and zafirlukast, while zileuton is an inhibitor of 5-lipoxygenase. Randomized controlled trials have shown that montelukast is effective in symptom reduction of nasal polyposis compared with placebo and equally effective compared with intranasal corticosteroid sprays in this respect [64]. Combination therapy of montelukast with budesonide sprays showed significant improvement in headache, facial pain, and sneezing, compared to monotherapy with budesonide sprays [65]. Lower evidence studies have also shown zafirlukast and zileuton to provide similar symptom improvement in CRSwNP [66, 67].

When considering AERD where the underlying mechanism is due to dysregulation of arachidonic acid metabolism with decreased inhibition of the 5-lipoxygenase pathway, drugs such as the 5-lipoxygenase inhibitor zileuton should theoretically be effective in treating the disease. Ulualp et al. looked at zileuton and zafirlukast in AERD patients and found significant improvement in symptom scores, subjective reports, and endoscopic examination [66]. Montelukast was also found to have improvement in both aspirin-tolerant and aspirin-sensitive patients with nasal polyps and asthma, with improvements in polyp score only present in aspirin-tolerant patients [68]. Based on current literature, while we know that leukotriene antagonists can help in the management of nasal polyposis, finding the optimal use in the correct patient population and setting still requires further investigation.

The newest anti-inflammatory agents being investigated in the treatment of nasal polyposis are antibodies targeting parts of the inflammatory cascade. Anti-IL5 agents – mepolizumab and reslizumab – are humanized monoclonal antibodies that target eosinophilic inflammation. One trial evaluating reslizumab showed a decrease in total nasal polyp score and decrease in blood eosinophil counts compared to placebo, although there was rebound hypereosinophilia posttreatment [69]. There was however no significant difference in symptom scores or nasal peak inspiratory flow (nPIF) between treatment and placebo groups. Another trial compared mepolizumab against placebo and similarly showed improved nasal polyp score, blood eosinophil counts, and computed tomographic score [70]. These improvements were seen in 60 % of treated patients, and there were no markers to suggest possible responders to anti-IL5 therapy. There were also improvements in some symptom scores, namely hyposmia, congestion, and postnasal drip, although these did not reach significance.

Omalizumab is a recombinant DNA-derived humanized IgG monoclonal antibody that selectively binds to IgE. It has been studied in the treatment of asthma and allergic rhinitis and more recently in CRS. One trial specifically looked at the effect of omalizumab in treating patients with nasal polyps and comorbid asthma and found that there was significant reduction in total nasal polyp score with corresponding improvements in Lund-Mackay scores on CT [71]. There was also significant improvement in symptom scores and the Short-Form Health Questionnaire SF-36 on physical health, although no difference was found in mental health. No differences were found in treatment outcomes between allergic and nonallergic patients. There are however concerns with prescribing omalizumab, such as the risk of anaphylaxis in 1 patient per 1,000 as well as potential cardiac effects and thrombocytopenia. There is also the potential of higher than expected arterial thrombotic events. Earlier concerns regarding malignancies related to omalizumab seem unfounded, as recent studies do not suggest an association between omalizumab therapy and an increased risk of malignancy [72].