Chronic sinusitis refractory to standard management in patients with humoral immunodeficiencies.
Chronic refractory sinusitis is a common feature in patients with primary immunodeficiencies. The efficacy of standard therapeutic strategies is questionable. In an open trial we evaluated the efficacy of azithromycin, N-acetylcysteine and topical intranasal beclomethasone (100 microg twice daily for 6 weeks) in 16 patients with primary immunodeficiencies (median age 13.5 years, range 5-32 years). All patients suffered from chronic sinusitis despite regular immunoglobulin replacement therapy every 3 weeks. Magnetic resonance imaging (MRI) scans were performed before and after 6 weeks of treatment to evaluate morphological changes in the paranasal sinuses. Nasal swabs and washings were taken for microbial analysis and measurement of inflammatory mediators (IL-8, tumour necrosis factor-alpha (TNF-alpha), eosinophilic cationic protein (ECP)) before and post therapy. Inflammatory mediators in nasal secretions 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 median 212 pg/ml (99-825 pg/ml), TNF-alpha 3.77 pg/ml (2.8-10.2 pg/ml) and ECP 1.5 ng/ml (1.5-14.8 ng/ml) (P < 0.0001). Inflammation of the maxillary sinuses was confirmed by MRI scans in all patients, additionally infection of the ethmoidal and frontal sinuses was recorded in five patients. Bacterial growth appeared in 11 out of 16 cultures. In spite of therapy, no improvement in sinal inflammation visualized by MRI was achieved. Moreover, no significant decrease in pathogens and levels of inflammatory mediators could be detected (IL-8 1141 pg/ml, 426-4556 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 sinusitis is of little benefit in patients with chronic refractory sinusitis with an underlying immunodeficiency. More studies are needed to test antibiotic regimens, probably combined with surgical drainage and anti-inflammatory agents.
Buehring
I
I
Department of Pediatrics, Johann Wolfgang Goethe Universität, Frankfurt, Germany.
Friedrich
B
B
Schaaf
J
J
Schmidt
H
H
Ahrens
P
P
Zielen
S
S
D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000150:complications / Q000628:therapy; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001260:Ataxia Telangiectasia / Q000150:complications / Q000628:therapy; D017963:Azithromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D001798:Blood Proteins / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D017074:Common Variable Immunodeficiency / Q000150:complications* / Q000628:therapy; D047091:Eosinophil Granule Proteins; D015521:Ethmoid Sinusitis / Q000175:diagnosis / Q000382:microbiology; D005260:Female; D015522:Frontal Sinusitis / Q000175:diagnosis / Q000382:microbiology; D005938:Glucocorticoids; D006801:Humans; D007116:Immunization, Passive; D016209:Interleukin-8 / Q000032:analysis; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000628:therapy; D008279:Magnetic Resonance Imaging; D008297:Male; D017817:Nasal Lavage Fluid / Q000276:immunology / Q000382:microbiology; D010256:Paranasal Sinuses / Q000000981:diagnostic imaging; D011859:Radiography; D012260:Ribonucleases; D012852:Sinusitis / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D005938:Glucocorticoids; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D017963:Azithromycin; D012260:Ribonucleases; D001507:Beclomethasone; D000111:Acetylcysteine