Anti-IgE (omalizumab): A new therapeutic approach for chronic rhinosinusitis

Article Outline

• References
• Copyright

To the Editor:

Chronic rhinosinusitis is a common but poorly defined disease characterized by inflammation of nasal mucosa and paranasal sinuses. Approximately 16% of the US population is affected.¹ Etiology and pathophysiology of chronic rhinosinusitis are unknown as yet. Allergic inflammation, mucociliary dysfunction, aspirin intolerance, immunodeficiency, cystic fibrosis, and nasal and paranasal sinus infections are discussed as relevant factors or underlying diseases. Chronic rhinosinusitis is known to be a notoriously difficult-to-treat disease, and established therapies are often ineffective.²

We provide preliminary data indicating anti-IgE may have efficacy in the treatment of refractory chronic rhinosinusitis.

A 68-year-old patient has a 20-year history of chronic rhinosinusitis, nasal polyposis, persistent asthma, and aspirin intolerance. Asthma was treated with inhaled corticosteroids and long-acting β₂-agonists. Therapies with antibiotics, antihistamines, corticosteroids (topically and systemically), and montelukast had been ineffective for his chronic rhinosinusitis. Each of 5 previous sinus surgeries was shortly followed by a relapse. When the patient was referred to our department in 2004, he had severe persistent rhinitis with persistent nasal obstruction, postnasal drip, relapsing bacterial nasal and sinus infections, and absence of sense of smell and taste. In spite of daily use of high dose inhaled fluticasone and salmeterol, asthma symptoms affected his activity and sleep. FEV₁ was decreased at 78.4% (2.76 L), and forced vital capacity was normal at 88.2% (4.03 L), according to Global Initiative for Asthma (GINA) III.³, ⁴ Skin prick tests showed a positive reaction only to house dust mite extract. Total serum IgE level as well as the specific IgE to house dust mite were elevated. A nasal challenge with house dust mite extract induced severe secretion, mucosal swelling, and total obstruction analyzed by rhinomanometry. Asthma symptoms and history met the criteria for anti-IgE therapy. In addition, a severe chronic polypoid sinusitis with subtotal swelling and inflammation of the entire paranasal sinus associated with a chronic but asymptomatic mastoiditis was diagnosed by magnetic resonance imaging (MRI; Fig 1).

• 
  • View Large Image
  • Download to PowerPoint

• Fig 1. 

  MRI scans demonstrate the improvement of mastoiditis, sinus ventilation, and mucosal edema after anti-IgE treatment (B, D) in contrast with pretreatment MRI (A, C). The reduction of mucosa swelling and the increase of nasal patency enables the patient to undergo a 20-minute closed-mouth scan without any difficulties (D), in contrast with the open-mouth scan necessary for the pretreatment condition (C).

Hence, in 2006 we initiated a therapy with 225 mg omalizumab biweekly (calculated for a body weight of 83 kg and total serum IgE level of 216 kU/L). Asthma symptoms clearly ameliorated within 2 months, and the patient reported a significant reduction of his sinus complaint. Chronic forehead and paranasal pressure as well as retronasal mucus were eliminated, and his sense of smell was restored. Four months after therapy initiation, a resolution of nasal mucosa swelling and a reduction of polypoid swelling and inflammation of the entire paranasal sinus were documented by MRI. The chronic mastoiditis had been completely eliminated (Fig 1). Thus MRI scan results coincide with the patient's report. Although computed tomography scans are the typical approach for the diagnosis of chronic rhinosinusitis, MRI scans were conducted in this case because of the lower radiation exposure with repeated examination.

Omalizumab is a humanized anti-IgE antibody approved for treatment of moderate to severe persistent asthma when a positive skin test or in vitro reactivity to a perennial aeroallergen is documented, and if symptoms are inadequately controlled by inhaled corticosteroids and inhaled long-acting β₂-agonists.⁵ The efficacy of omalizumab has been clearly demonstrated for this indication by several clinical studies.⁶ Furthermore, the benefit of omalizumab for patients with allergic asthma and associated allergic rhinitis has been demonstrated in the Study of Omalizumab in Comorbid Asthma and Rhinitis (SOLAR).⁷

Our report suggests that omalizumab can be effective in the treatment of chronic rhinosinusitis. We observed not only a resolution of nasal mucosa swelling (in accordance with the SOLAR study) but also a reduction of polypoid swelling and inflammation of the entire paranasal sinuses, and a complete healing of chronic mastoiditis. The anti-IgE therapy reduces the allergic inflammation, and our case report gives further evidence for an IgE-mediated mechanism (IgE antibodies to bacterial superantigens and aeroallergens) in the pathophysiology of chronic rhinosinusitis at least in some patients. To broaden the therapeutic applications of omalizumab, further studies must be conducted.

Back to Article Outline

References 

1. Pleis JR, Coles R. Summary health statistics for U.S. adults: National Health Interview Survey, 1998. Vital Health Stat 10. 2002;209:1–113
   • View In Article
2. Fokkens W, Lund V, Bachert C, Clement P, Helllings P, Holmstrom M, et al. EAACI position paper on rhinosinusitis and nasal polyps executive summary. Allergy. 2005;5:583–601
   • View In Article
3. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2005 Update. NIH publication no. 02-3659. Available at: http://www.ginasthma.org. Accessed August 26, 2006.
   • View In Article
4. Holgate ST, Polosa R. The mechanisms, diagnosis, and management of severe asthma in adults. Lancet. 2006;9537:780–793
   • View In Article
5. Strunk RC, Bloomberg GR. Omalizumab for asthma. N Engl J Med. 2006;25:2689–2695
   • View In Article
6. Walker S, Monteil M, Phelan K, Lasserson TJ, Walters EH. Anti-IgE for chronic asthma in adults and children. Cochrane Database Syst Rev. 2006;2;CD003559
   • View In Article
7. Vignola AM, Humbert M, Bousquet J, Boulet LP, Hedgecock S, Blogg M, et al. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR. Allergy. 2004;7:709–717
   • View In Article