Page 595 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 41 Immunological Mechanisms of Airway Diseases and Pathways to Therapy 573

positive skin testing to fungal antigens or elevated serum fungal- agents potentially useful in the management of rhinitis include
antigen-specific IgE titers. Imaging consistent with AFRS is oral steroids, oral leukotriene (LT) receptor antagonists, intranasal
obtained by CT and magnetic resonance imaging (MRI). Fulfilling chromones, and intranasal ipratropium bromide. 8
the remaining criteria for AFRS requires histological examination In addition to pharmaceutical approaches, allergen immu-
and microbiology for fungi within the mucin and tissue obtained notherapy offers a means of providing long-term relief from
at the time of surgery. 5 rhinitis (Chapter 91). Two types of immunotherapy are available:
subcutaneous immunotherapy (SCIT) and sublingual immu-
KEY CONCEPTS notherapy (SLIT). An important concern associated with the
use of SCIT is anaphylaxis, whereas this risk is probably much
Diagnosis of Chronic Rhinosinusitis (CRS) lower with SLIT. The antigens for SLIT are available in both
liquid formulation, which allows for customized combinations,
Chronic rhinosinusitis
• Presence of at least two of the following symptoms: and preformed tablets. Finally, intensive home and workplace
• Facial pressure or pain remediation directed at limiting allergen exposure is potentially
8
• Nasal obstruction or congestion beneficial in those with demonstrable environmental allergies.
• Anterior or posterior nasal drainage The treatment of CRS is more controversial than that of AR. In
• Hyposmia or anosmia general, treatment can consist of either medical or surgical therapy.
• Edema or discolored drainage within the sinus cavity or middle meatus CRS is currently viewed as primarily an inflammatory, rather than
• Or CT sinus showing fluid or mucosal thickening within sinus cavities
an infectious, disorder such that antibiotics are less frequently
CrS Without Nasal Polyps CrS With Nasal Polyps advocated and have largely been replaced with intranasal and oral
No evidence of nasal polyps within Presence of nasal polyps within antiinflammatory agents, such as steroids. In addition, daily sinus
the middle meatus as noted on the middle meatus as noted irrigations with physiological saline can counteract mucociliary
nasal endoscopy in a patient on nasal endoscopy dysfunction and promote antigen clearance.
with no history of previous Future therapies for CRS are likely to include biologics aimed
sinus surgery at the key cytokines, molecules, and cells that are important in
History of nasal polyps within the type 2 inflammatory responses which characterize CRSwNP.
sinus cavity in a previously These potential therapeutic targets include IL-33, IL-25, thymic
operated patient with CRS
diagnosis stromal lymphopoietin (TSLP), IL-5, IL-4, IL-13, siglec-8, and
IgE. However, these treatment options will require a more
sophisticated classification of CRS beyond the basis of nasal
The diagnosis of AERD requires meeting diagnostic criteria polyps. Endotyping based on immunological, molecular, or
for nasal polyps and asthma, along with a history of respiratory histological characteristics represents the future of CRS classifica-
symptoms exacerbated by oral intake of aspirin or other tion. We also need to better understand the role that environmental
cyclooxygenase-1 (COX-1) inhibitors on at least two occasions, fungi play in triggering the inflammatory cascade leading to
or a positive reaction on aspirin challenge. 6 particular CRSwNP subtypes and allergic asthma. The use of
Cystic fibrosis is typically diagnosed in early childhood as a antifungals in CRS seems logical, given the strong association
9
result of pulmonary symptoms. However, the presence of nasal between CRS and fungi, including yeasts and molds. This has
polyps in anyone under 18 years should prompt an evaluation been investigated through many clinical trials, most of which
for cystic fibrosis, which is confirmed either by sweat test or by are methodologically weak, failing to specify which patients
demonstrating a mutation in the cystic fibrosis transmembrane actually have fungal infection or at least fungal sensitivity and
conductance regulator gene. lacking adequate control populations. Despite these limitations,
the existing studies suggest that topical antifungal antibiotics
Therapy (e.g., amphotericin B) are not effective, whereas systemic anti-
The most effective and widely used drugs for controlling the fungals may significantly inhibit recurrent disease. 10
nasal and ocular symptoms of AR are glucocorticosteroids and Patients with persistent symptoms despite medical therapy
antihistamines. Intranasal glucocorticosteroids (steroids) are the may benefit from functional endoscopic sinus surgery (see Video
most efficacious medication class available for the management 1 online). Outcomes of medical therapy versus sinus surgery
of AR symptoms, particularly nasal congestion, and are considered combined with intranasal steroids showed similar improvements,
first-line medical therapy. They may also improve eye symptoms. but patients with CRSwNP achieved improved asthma control
Of the numerous formulations available, mometasone furoate with medical therapy. Endoscopic sinus surgery is mandatory
demonstrates the highest antiinflammatory potency and lowest for patients with AFRS in whom the sinuses are impacted with
systemic absorption compared with other commonly used copious thick mucus requiring manual extraction and patients
intranasal steroids. However, no studies have shown any differ- presenting with serious complications of CRS, such as vision
ences in clinical efficacy among the currently available intranasal loss or intracranial extension of disease.
steroids. 7
Oral antihistamines are also highly effective against the Asthma
histamine-driven symptoms of sneezing, pruritus, and rhinor- Epidemiology and Clinical Presentation
rhea. Second-generation antihistamines are recommended over After several decades of rising incidence, asthma is now the most
first-generation formulations for their lack of sedating effects common chronic disease of childhood and one of the most
and equivalent ability to reduce AR symptoms. Intranasal anti- common disorders of adults in the United States. Although most
histamines can be as effective as oral antihistamines for control frequently diagnosed initially in childhood, asthma can be first
of allergic and nonallergic rhinitis, but neither is as effective as diagnosed at any age. The widely prevalent and incurable nature
intranasal steroids for nasal congestion. Other pharmacological of asthma will continue to assure its position as one of the most