Exploring the link between nasal allergy and sinus infection
Published on Patient Care Online (http://www.patientcareonline.com)
Exploring the link between nasal allergy and sinus infection
October 01, 2006 | Asthma [1], Seasonal Allergies [2], Otorhinolaryngologic Diseases [3], Infection
[4]
By Shih-wen Huang, MD [5]
Abstract: There is solid evidence that a positive association exists between nasal allergy and acute
or chronic sinusitis in both adults and children. Patients with perennial allergic rhinitis--especially
those with significant sensitivity to molds and/or house dust mites--are particularly susceptible to
acute sinusitis. It therefore seems reasonable to assume that controlling rhinitis by controlling
allergens in the home environment will minimize recurrences of acute sinusitis. Conversely, many
patients with chronic sinusitis also have nasal allergy. Thus, management of nasal allergy should be
included in the treatment strategy for chronic sinusitis. (J Respir Dis. 2006; 27(10):435-440)
The prevalence and incidence of sinusitis are increasing. Sinusitis affects an estimated 31 million
persons in the United States each year, and this number is expected to grow. It is one of the most
common reasons patients seek a physician's care. If left untreated, sinusitis can cause significant
symptoms and can negatively affect quality of life by substantially impairing the daily functioning of
sufferers. For children, this can mean learning difficulties at school and for adults, a loss of efficiency
at work.
Understanding the science behind sinusitis can help clinicians effectively treat affected patients in
their daily practice.
Acute sinusitis is usually characterized by the abrupt onset of viral respiratory infection and
subsequent insidious onset of cold-like symptoms that may last for weeks. Conversely, chronic
sinusitis is not usually associated with an acute onset, and it may last for months or more--even after
aggressive treatment. Acute sinusitis is often treated with antibiotics for the recommended time of 2
to 3 weeks. Chronic sinusitis usually does not respond to antibiotic therapy; the treatment of choice
is usually topical or systemic corticosteroids.
The nature of the relationship between allergic rhinitis and sinusitis (acute or chronic) remains a
dilemma for clinicians. Allergic rhinitis may affect 10% to 12% of the general population. Because of
the anatomic proximity of the nasal passages and the sinus cavities, an association between allergic
rhinitis and sinusitis has often been suggested. However, a cause-and-effect relationship between
the two has not been clearly defined. Furthermore, the term "sinusitis" is very often not defined
properly.
Here I review the evidence relating to the association between allergic rhinitis and acute sinusitis,
and to that between allergic rhinitis and chronic sinusitis. I also examine the cause, pathophysiology,
and implications of treatment for all of these conditions.Epidemiology: the clinical association
Allergic rhinitis is often listed as a predisposing factor for acute sinusitis, and the association
between the two is often cited in the literature. However, there have not been any solid
epidemiologic studies of this association.
Because the number of persons who suffer from allergic rhinitis is far greater than those who have
sinusitis, many studies determine the prevalence of allergic rhinitis in patients with an established
sinus infection. True acute sinusitis is typically diagnosed on radiographs.
Children with allergies frequently have sinusitis.1 Various studies have reported a high correlation
between these disorders in children.2 One study reported the incidence of allergy to be 25% in adults
with acute maxillary sinusitis, which was significantly greater than the 16% incidence in the control
group.3 The prevalence of sinusitis is significantly higher in children with allergic rhinitis than in
children without it.4
One study found that the prevalence of sinusitis was significantly higher in patients with perennial
allergic rhinitis than in those with seasonal allergic rhinitis (P < .001).5 More important, when the
subset of patients with perennial allergic rhinitis was compared, patients with mold allergy showed a
higher risk of sinusitis than those with non-mold allergy (relative risk, 2.49 vs 1.50, respectively).5
This observation was supported by another study involving adults with recurrent acute sinusitis, 5%
of whom had a positive allergy test result.6 In that specific patient group, 92% demonstrated
sensitivity to one or more perennial allergens--usually molds and house dust mites.
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Exploring the link between nasal allergy and sinus infection
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Holzmann and colleagues7 investigated whether allergic rhinitis is a potential risk factor for orbital
complications characteristic of acute sinusitis. They found allergic rhinitis in 64% of children with
preseptal cellulitis and in 76% of children with subperiosteal abscess. Similarly, when adults with
acute sinusitis were examined, 43% had previously been suffering from allergic rhinitis.8
The definition of chronic sinus-itis varies somewhat, depending on the individual clinician's view on
the duration of symptoms. However, most reports state that symptoms lasting more than 30 days
should be considered evidence of chronic sinusitis.
The symptoms of chronic sinusitis are often a bit more subtle than those attributed to acute
infection. Nasal discharge (variable in character), postnasal drip, nasal obstruction, and cough (day
and night) are common.
Because of the chronic nature of the illness, behavioral changes--such as irritability and acting
out--are frequently evident in children. Adults who have chronic sinusitis frequently complain of
chronic fatigue and general malaise at work. Again, even though adequately controlled studies are
lacking, multiple observations support the association between chronic sinusitis and nasal allergy.
Benninger9 reported that 54% of outpatients with chronic sinusitis also had allergic rhinitis. A 50%
incidence of positive allergy skin test in adults who had undergone sinus surgery has been shown,10
and atopy has been demonstrated in 94% of adults who had undergone spenomastoidectomy.11
van Dishoeck and Franssen12 reported allergy as an underlying factor in 40% to 67% of patients with
chronic sinusitis. Several studies have demonstrated similar results in children; in children who have
symptoms of allergic rhinitis and/or asthma, there is a higher frequency of sinusitis,1 and 37% of
those children with sinusitis have skin test results positive for allergy.13
Based on clinical observations made by both primary care physicians and specialists, we can
conclude that a positive association exists between nasal allergy and acute or chronic sinusitis in
both adults and children.Pathogenesis of acute sinusitis in patients with allergic rhinitis
Although many clinical observations support the contention that patients with allergic rhinitis are
vulnerable to acute sinusitis, a unified hypothesis that would aid in the understanding of the
pathophysiology of sinusitis is still lacking. However, if we trace the underlying pathogenic
mechanism, it may be possible to arrive at a reasonable conclusion.
Clinical evidence indicates that acute sinusitis is usually preceded by a viral infection.14-16 During the
initial stages, there is increased mucus because of infection. Patients with rhinitis often sneeze and
blow their nose to get rid of nasal discharge. One study suggests, however, that as the discharge is
expelled, as much as 17% of it is sucked into the sinus cav-ities by force.17 This fluid contains
allergen(s), viral particles, and bacteria; once inside the sinus cavities, the bacteria adhere to the
mucosal lining. The stimulation of epithelial cells by bacterial products (lipopolysaccharide by
Gram-negative bacteria or lipoteichoic acid by Gram-positive bacteria) causes the production of
interleukin (IL)-8, tumor necrosis factor a, and mucin.18 Chemotactic factors are then released to
recruit inflammatory cells, especially polymorphonuclear cells.
As mentioned, acute sinusitis is more likely to develop in patients who have perennial allergic
rhinitis--especially those who are sensitive to molds. Does mold allergy contribute to the
pathogenesis of sinusitis? In their study of the interaction between fungal allergens and epithelial
cells, Kauffman and coworkers19 reported that the possibility exists. They found significant
desquamation of epithelial cells and cytokine production (IL-6 and IL-8) and concluded that damage
to the epithelial cells by the proteases of fungi may result in further enhancement of the passage of
macromolecules of antigens over the mucosal membrane. This results in more mast cell activation
and recruitment of eosinophils and neutrophils. Locally produced mucin and lectin contribute to the
high viscoelasticity of mucus seen with sinusitis.20
Interestingly, an animal experiment also supports the contention that allergic rhinitis could be an
important factor in the development of acute sinusitis. Mice were first sensitized with ovalbumin and
then infected with Streptococcus pneumoniae--one of the organisms most commonly isolated in the
sinus fluid of patients with sinusitis. Once eosinophilia had developed in these mice because of
allergy, more neutrophils and bacteria were recovered from the sinus cavities. This suggests that it
was an ongoing allergic reaction in the sinuses, and not at distant sites, that made the animals prone
to an established sinus infection.21
The overall inflammatory process enhances the production of mucopurulent material in the sinus
cavities, which is a hallmark of sinus pathology. The sequence of this pathology is illustrated in
Figure 1.Pathogenesis of chronic sinusitis in patients with allergic rhinitis
One of the common beliefs in the evaluation of patients with chronic sinusitis and nasal allergy is
that allergic rhinitis leads to edema of the nasal passages and interferes with adequate drainage
from the sinus cavities. The problem with this hypothesis is that the treatment of allergic rhinitis
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does not always eliminate chronic sinusitis. Another common belief is that allergens somehow
penetrate the sinus cavities of persons with allergies. However, a study using radiolabeled antigen
(ragweed) demonstrated how difficult (in this case, impossible) it is for allergens to penetrate the
sinus cavities.22
Recent understanding of the intricate immune network allows us to explore the immunopathology of
chronic sinusitis. The immune balance between helper T cells subtype 1 (TH1) and TH2 cells may
explain the resultant pathology. Both cells use distinct cytokines to modulate immune responses. For
example, TH1 cells produce TH1 cytokines, primarily interferon-g and IL-2, which induces
cell-mediated immunity. TH2 cells induce eosinophil-mediated inflammatory responses and
counterregulate the TH1 response by TH2 cytokines (IL-4, IL-5, and IL-13).23
The immunopathology of chronic sinusitis is very much the result of the TH2 cytokine response.
There is a high level of IL-524 or IL-3, IL-4, IL-5, and granulocyte-macrophage colony-stimulating
factor (GM-CSF)25 in the sinuses of patients with chronic sinusitis.
The cellular response plays an important role in the imunopathology of chronic sinusitis. In children
with chronic sinusitis, eosinophils are abundant in those who have nasal allergy.26
Similar observations have been made in adults.27 The eosinophils are not just present in the mucosa, they are also activated,24 leav-ing very potent, cell-damaging molecules on the mucosa.27
Therefore, eosinophils are active players in the inflammation that occurs with chronic sinusitis, and
this is more common in patients with active allergic rhinitis.
T lymphocytes have also been studied in sinus cavities. Although CD4+ cells were increased at the
apical portion of the sinus mucosa--suggesting the possible release of chemotactic or growth factors
from the epithelium to attract inflammatory cells--the significance of this to allergy is unclear.28
The most interesting hypothesis about chronic sinusitis is that it is the result of neurogenic
inflammation within the sinuses. To investigate this possibility, a model of allergen challenge to the
nose was developed, and the maxillary sinus secretion sampled.29
The investigators found that after a challenge in one nostril with either grass or ragweed pollens, a
significant influx of eosinophils was found in the bilateral sinus cavities compared with controls. They
concluded that either hom-ing of eosinophils occurred in both sinus cavities or neurogenic
inflammation occurred via the triggering of afferent nerves, leading to an inflammatory response not
only in the ipsilateral sinus but also in the contralateral sinus through either central reflexes or
axonal reflexes.29
One final hypothesis about the possible interaction between allergic rhinitis and sinusitis is that
allergic rhinitis causes priming of the circulating leukocytes, with up- regulation of adhesion
molecules, which makes those leukocytes more likely to migrate to sites of ongoing inflammation
such as those caused by viral sinusitis.30 The sequence of this pathogenesis is illustrated in Figure
2.Effect of nasal allergy treatment on sinusitis
Nasal allergy, if left untreated, can cause significant morbidity in both children and adults,
substantially affecting quality of life. Treatment includes preventive measures, pharmacotherapy,
and immunotherapy with allergy vaccine.
In comparing the incidence of sinusitis among patients with nasal allergy, patients with perennial
allergic rhinitis--particularly those with significant sensitivity to molds and/or house dust mites--were
most susceptible to the development of acute sinusitis. Therefore, it is reasonable to assume that
controlling rhinitis by controlling allergens in the home environment will minimize the recurrence of
acute sinusitis. Unfortunately, although its importance is well recognized, outcome studies of acute
sinusitis are scarce.31,32
Similarly, many patients who have chronic sinusitis also have nasal allergy. As is the case with
preventing acute sinusitis, the management of nasal allergy should be included in the treatment
strategy for chronic sinusitis. Clearly, there is an immediate need to establish national,
evidence-based practice guidelines to assist clinicians in diagnosing and managing aller- gic rhinitis
coexisting with other airway diseases, such as acute or chronic sinusitis.
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