Long-Term and High-Dose Glucocorticosteroids for the Treatment of Chronic Rhinosinusitis

Chronic rhinosinusitis is one of the more prevalent conditions in the US, affecting about more than 40 million people annually (about 14% of the population) and more than 50 million people each year in Europe (about 10.9% of the population), with marked geographical variations. The annual socioeconomic cost of chronic rhinosinusitis in the US is estimated to be $5.8 billion.

Symptoms associated with chronic rhinosinusitis include nasal drainage, nasal obstruction or blockage, and facial pain or pressure. Symptomatic treatment of chronic rhinosinusitis can include decongestants, antibiotics (to treat concomitant infection), mucolytics, glucocorticosteroids, and surgery.

Glucocorticosteroids have been shown to be “particularly effective for chronic sinusitis associated with allergic rhinitis, nasal polyps, and rhinitis medicamentos.” There are several formulations of topical and oral glucocorticosteroids available to clinicians, and these agents are now considered to be (along with antibiotics) the key to effective management of chronic rhinosinusitis.

Joaquim Mullol, MD, PhD, is an otorhinolaryngologist in the University Hospital Clinic, IDEBAPS, Barcelona, Spain. During a presentation at the 2014 Annual Meeting of the American Academy of Allergy, Asthma & Immunology, held February 28 — March 4, 2014, in San Diego, CA, he discussed the assessment of patients with chronic rhinosinusitis and addressed difficult issues in the use of glucocorticosteroids to treat this condition.

For the assessment and diagnosis of the two main phenotypes of the disease‑‑chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP)‑‑Mullol recommended nasal endoscopy and sinunasal CT if there are two or more nasal polyps. The European Position Paper on Rhinosinusitis and Nasal Polyps, published in Rhinology and recently updated in 2012, recommends ENT examination that includes endoscopy with an option to consider a CT scan.

Glucocorticosteroids have been shown to exert anti-inflammatory effects via glucocorticosteroids receptor (GRα) translocation and inhibition of the expression of pro-inflammatory genes and transactivation of anti-inflammatory genes such as MKP-1, GILZ, and TTP. Fernandez-Bertolin et al. have shown in The Journal of Allergy and Clinical Immunology that there is a deficit in anti-inflammatory gene induction in nasal polyp fibroblasts of asthmatic patients

Mullol pointed out that glucocorticosteroids are slow-acting agents that take effect about 7-12 hours after administration, with peak activity at 5 to 7 days. The most frequent side effects are dryness of mucus membranous tissues and epistaxis.

The evidence level for intranasal glucocorticosteroids (IGS) therapy is very high (designated 1a) with an A grade of recommendation. Long-term oral glucocorticosteroids treatment has been awarded a similar evidence level (1b) but is less strongly recommended (C).

Mullol said that he and his colleagues have achieved results using long-course oral glucocorticosteroids (6-12 months of treatment) that are equivalent to surgery. However, he cautioned that there are few well-controlled studies to support high-dose treatment with oral glucocorticosteroids.

He opined that the best results appear to be obtained with surgery followed by intranasal steroids. In one long-term, randomized, stratified, double-blind study in chronic rhinosinusitis conducted in the UK, researchers obtained five-year follow-up data for 109 patients who underwent functional endoscopic sinus surgery (77 patients had polyposis). The patients were then treated six weeks post-surgery with twice-daily fluticasone propionate aqueous nasal spray, with improvements in visual analogue scores, endoscopic findings, nasal mucociliary clearance times, and total nasal volumes compared to baseline.

Safety is a major concern when managing chronic rhinosinusitis especially regarding the effects of long-term or intermittent oral steroid therapy on the HPA and bone density.

Mullol concluded by recommending that the management of adults with chronic rhinosinusitis with nasal polyps be carried out using a three-step scheme. Mild nasal polyposis should be treated with intranasal glucocorticosteroid spray, moderate polyposis with intranasal glucocorticosteroid drops, and severe nasal polyposis by first-line topical and oral glucocorticosteroids followed by endoscopic sinus surgery if there is failure after three months. Treatment efficacy should be evaluated every 3-6 months.