CHRONIC SINUSITIS REFRACTORY TO STANDARD MANAGEMENT IN PATIENTS WITH HUMORAL IMMUNODEFICIENCIES

Chronic refractory sinusitis is a common feature in patients with prim ary immunodeficiencies. The efficacy of standard therapeutic strategie s is questionable. In an open trial we evaluated the efficacy of azith romycin, N-acetylcysteine and topical intranasal beclomethasone (100 m u g twice daily for 6 weeks) in 16 patients with primary immunodeficie ncies (median age 13.5 years, range 5-32 years). All patients suffered from chronic sinusitis despite regular immunoglobulin replacement the rapy every 3 weeks. Magnetic resonance imaging (MRI) scans were perfor med before and after 6 weeks of treatment to evaluate morphological ch anges in the paranasal sinuses. Nasal swabs and washings were taken fo r microbial analysis and measurement of inflammatory mediators (IL-8, tumour necrosis factor-alpha (TNF-alpha), eosinophilic cationic protei n (ECP)) before and post therapy. Inflammatory mediators in nasal secr etions were significantly elevated in patients: IL-8 median 2436 pg/ml (range 441-5435 pg/ml), TNF-alpha 37.3 pg/ml (3.75-524 pg/ml) and ECP 33 ng/ml (1.5-250 ng/ml) versus age-matched healthy controls: IL-8 me dian 212 pg/ml (99-825 pg/ml), TNF-alpha 3.77 pg/ml (2.8-10.2 pg/ml) a nd ECP 1.5 ng/ml (1.5-14.8 ng/ml) (P < 0.0001). Inflammation of the ma xillary sinuses was confirmed by MRI scans in all patients, additional ly infection of the ethmoidal and frontal sinuses was recorded in five patients. Bacterial growth appeared in 11 out of 16 cultures. In spit e of therapy, no improvement in sinal inflammation visualized by MRT w as achieved. Moreover, no significant decrease in pathogens and levels of inflammatory mediators could be detected (IL-8 1141 pg/ml, 426-455 6 pg/ml; TNF-alpha 13.9 pg/ml, 4.1-291.6 pg/ml; ECP 32.3 ng/ml, 3.7-58 .4 ng/ml). Our results demonstrate that conventional management of sin usitis is of little benefit in patients with chronic refractory sinusi tis with an underlying immunodeficiency. More studies are needed to te st antibiotic regimens, probably combined with surgical drainage and a nti-inflammatory agents.