Chronic sinusitis refractory to standard management in patients with humoral immunodeficiencies

Abstract

SUMMARYChronic 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 mg 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-a), 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-a 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-a 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-a 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.

Infectious and Noninfectious Pulmonary Complications in Patients With Primary Immunodeficiency Disorders

“…The most frequent PID associated with sinusitis is humoral immunodeficiency. This disorder includes selective IgA deficiency (SIgAD), common variable immunodeficiency (CVID), and specific antibody deficiency (SAD), which is characterized by normal IgG levels but an impaired response to polysaccharide vaccines [17][18][19][20][21]. One study reported considerable differences in the incidence of sinusitis in PIDs, such as agammaglobulinemia (11.52%), CVID (9.4%), SAD (1.8%), IgG subclass deficiency (13.41%), SIgAD (6.58%), and hyper-IgM syndrome (0.7%) [19].…”

“…Only a few studies have investigated the treatment of chronic sinusitis in patients with PIDs, although it seems that treatment involves both medical and surgical approaches, as occurs in immunocompetent individuals. In general, broad-spectrum antibiotics, saline nasal washes, anti-inflammatory agents, and immunoglobulin replacement therapy could reduce the frequency and severity of sinusitis in PID patients [18,25]. While the role of sinus surgery has not been well defined, it seems that PID patients experience similar benefits to immunocompetent populations in terms of symptoms and quality of life [26][27][28][29].…”

Pathogenesis, Diagnosis, and Management of Primary Antibody Deficiencies and Infections

“…The occurrence of a dermatomyositis-like syn-VOL. 22,2009 PRIMARY ANTIBODY DEFICIENCIES 401 drome, marked by peripheral edema, erythematous rash, and evidence of inflammation of the skin and muscle on biopsy specimens, has been associated with disseminated enteroviral disease in patients with XLA (84) (see below). At the time of diagnosis, most, but not all, patients have low serum immunoglobulin levels, with IgG levels of Ͻ200 mg/dl, IgA levels of Ͻ15 mg/dl, and IgM levels of Ͻ40 mg/dl (141).…”

“…22,2009 PRIMARY ANTIBODY DEFICIENCIES 405 (93). This is a result of an additional profound impairment of cellular immunity associated with these disorders, which are therefore better classified as combined immunodeficiencies.…”

“…If nasal cultures are obtained, they grow Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis for the majority of patients, often with evidence of more than one pathogen present. Concomitant infections with viruses, predominantly rhinovirus and enteroviruses, have been reported (22,65). Sinusitis is chronic in most patients and often refractory to conventional antimicrobial therapy.…”