Clinical Review & Education

JAMA | Review

Allergic Rhinitis
A Review
Jonathan A. Bernstein, MD; Joshua S. Bernstein, MD; Richika Makol, MD; Stephanie Ward, MD

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IMPORTANCE Allergic rhinitis affects an estimated 15% of the US population (approximately CME at [Link]
50 million individuals) and is associated with the presence of asthma, eczema, chronic or
recurrent sinusitis, cough, and both tension and migraine headaches.

OBSERVATIONS Allergic rhinitis occurs when disruption of the epithelial barrier allows
allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2
inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically
presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and
itching of the eyes, nose, and throat. In an international study, the most common symptoms
of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with
nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently
associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube
dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic
rhinitis typically have physical examination findings of edematous and pale turbinates.
Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates
with serous secretions that appear similar to other forms of chronic rhinitis at physical
examination. Patients with nonallergic rhinitis have negative test results for specific IgE
aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4
consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is
defined as symptoms occurring more often than 4 consecutive days/week and for more than
4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In
addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may
include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine,
loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with
persistent moderate to severe allergic rhinitis should be treated initially with an intranasal
corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in
combination with an intranasal antihistamine. In contrast, first-line therapy for patients with
nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination
with an intranasal corticosteroid.

CONCLUSIONS AND RELEVANCE Allergic rhinitis is associated with symptoms of nasal

congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis
should be instructed to avoid inciting allergens. Therapies include second-generation H1
antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal
antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone,
triamcinolone, budesonide, mometasone) and should be selected based on the severity and
frequency of symptoms and patient preference.
Author Affiliations: Division of
Rheumatology, Allergy, and
Immunology, Department of Internal
Medicine, College of Medicine,
University of Cincinnati, Cincinnati,
Ohio (J. A. Bernstein, J. S. Bernstein);
Division of Allergy and Immunology,
Department of Pediatrics, Cincinnati
Children’s Hospital Medical Center,
Cincinnati, Ohio (Makol, Ward).
Corresponding Author: Jonathan A.
Bernstein, MD, College of Medicine,
University of Cincinnati, 231 Albert
Sabin Way, Cincinnati, OH 45267
(bernstja@[Link]).
Section Editor: Kristin Walter, MD,
JAMA. 2024;331(10):866-877. doi:10.1001/jama.2024.0530 Deputy Editor.

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 Allergic Rhinitis Review Clinical Review & Education

A
llergic rhinitis may be defined as intermittent or seasonal quality, and approximately 92% of children have impaired school
allergic rhinitis and as persistent or perennial allergic rhi- performance.3,7-9 Allergic rhinitis is associated with increased di-
nitis. Symptoms of allergic rhinitis include sneezing; itch- rect costs (eg, medications, office visits, and procedures for comor-
ing of the eyes, nose, and throat; rhinorrhea; and nasal congestion bid illnesses) and indirect costs (eg, work or school absenteeism).10
with positive IgE test results for specific aeroallergens (such as the
seasonal allergens of tree, grass, and ragweed and the perennial al- Pathogenesis
lergens of dust mite, cat, dog, and cockroach droppings). Aeroallergen sensitization occurs when an allergen enters the nasal
Allergic rhinitis affects approximately 15% of the US popula- mucosal epithelial barrier and is processed by antigen-presenting
tion (approximately 50 million individuals) and 500 million indi- cells (eg, dendritic cells), causing differentiation of naive T cells
viduals worldwide.1,2 Allergic rhinitis is associated with comorbid to T-helper type 2 cells that are capable of releasing cytokines
conditions including asthma, eczema, chronic or recurrent sinus- (eg, IL-4, IL-5, IL-13).11,12 This process promotes B-cell production of
itis, cough, and both tension and migraine headaches.3,4 Allergic IgE specific to the allergen, which binds to high-affinity IgE recep-
rhinitis is associated with impaired quality of life and significantly tors on mast cells, Langerhans cells, monocytes, and basophils.
increased health care costs.3,4 This review summarizes evidence Upon reexposure to the sensitizing allergen, the relevant anti-
regarding the diagnosis and treatment of allergic rhinitis in adults. genic determinant (ie, 7-8 amino acid peptides) is recognized by
the specific IgE antigen–binding site region of the IgE molecule
(bound to mast cells and basophils), causing mast cell activation
and release of bioactive mediators including histamine, leukotri-
Methods
enes, and platelet-activating factor. These mediators bind to recep-
The PubMed database was searched from 1995 through June tors on blood vessels, mucous-secreting glands, and sensory
2023 for meta-analyses, consensus guidelines, Delphi-based con- nerves, inducing physiological responses that are associated with
sensus reports, randomized clinical trials, longitudinal observa- allergic rhinitis symptoms (eg, sneezing, itching, rhinorrhea, nasal
tional studies, cross-sectional studies, and systematic and narra- congestion).13
tive reviews. Of 300 articles identified, 50 were included in this Epithelial cell disruption also releases alarmin cytokines (eg, thy-
analysis (3 practice guidelines, 1 report of expert consensus, 23 mic stromal lymphopoietin, IL-25, IL-33), further promoting the in-
review articles, 8 cross-sectional studies, 6 systematic reviews flammatory response. Eosinophils are type 2 inflammatory cells that
and meta-analyses, 2 systematic reviews, 3 randomized clinical enter the nasal mucosa in response to IL-4 and IL-5 and release cy-
trials, 3 longitudinal observational studies, and 1 online health tokines, chemokines, leukotrienes, prostaglandins, and toxic pro-
technology report). teins or enzymes perpetuating inflammation (Figure).13 In addi-
tion, trigeminal neurons express neuropeptides, cholinergic sensory
receptors, and transient response potential receptors that can be
activated by mechanical, osmotic, thermal, and chemical stimuli.
Discussion
These neurogenic pathways play an important pathogenic role in
Patients with allergic rhinitis may present with symptoms that mixed and nonallergic rhinitis.14
occur at about the same time each year, precipitated by aeroaller-
gens to pollen (from tree, grass, or ragweed) when the pollen is Differential Diagnosis
most prevalent in the environment. Perennial rhinitis occurs The differential diagnosis of allergic rhinitis includes localized aller-
throughout the year and is triggered by allergens (such as dust gic rhinitis, nonallergic rhinitis, occupational rhinitis, infectious rhi-
mites, molds, cockroach droppings, and pet dander). The fre- nitis, and medication-induced rhinitis (Box and Table 1). In an inter-
quency of symptoms varies between individuals and studies, but national study, the most common symptoms of allergic rhinitis
patients with seasonal allergic rhinitis typically report symptoms were rhinorrhea (90.38%) and nasal congestion (94.23%).5 Local-
of sneezing, rhinorrhea, and itching that are most severe in the ized allergic rhinitis is associated with symptoms similar to allergic
spring (51.92%) followed by fall (28.85%), summer (15.38%), and rhinitis and responds to similar treatments, but specific IgE testing
winter (13.46%); patients with perennial rhinitis most commonly to aeroallergens show no reactivity. The diagnosis is confirmed by
exhibit yearlong symptoms of nasal congestion and postnasal a positive nasal challenge in which a dose of specific allergen is
drainage (26.92%).5 placed in the nose followed by measurement of total nasal symp-
Allergic sensitization is confirmed by specific IgE testing (sero- tom scores and the presence of increased nasal resistance using an
logical or skin testing), which correlates with allergic rhinitis symp- acoustic rhinometer or anterior rhinometry to confirm a localized
toms upon exposure to the inciting agents.4 Allergic rhinitis is asso- response. On a separate day, the patient is challenged with a nega-
ciated with poorer quality of life.6-9 National telephone and online tive saline control that should not elicit symptoms or changes in
questionnaire studies of adults and children with allergic rhinitis re- nasal resistance.15,16
ported that allergic rhinitis was associated with fatigue because of Nonallergic rhinitis consists of 7 chronic rhinitis conditions
poor sleep quality (40%), which was associated with poorly con- (drug-induced rhinitis, hormone-induced rhinitis, senile rhinitis,
trolled symptoms and adverse effects related to medications.6-9 gustatory rhinitis, atrophic rhinitis, idiopathic rhinitis, and vasomo-
Allergic rhinitis is associated with impaired physical and social tor rhinitis) that are associated with nasal symptoms in the absence
functioning. Approximately 30% of people with allergic rhinitis have of specific IgE sensitization to aeroallergens by skin or serological
cognitive and memory impairment, approximately 30% have anxi- testing.17,18 Approximately 71% of people with nonallergic rhi-
ety and depression, approximately 82% of adults have impaired work nitis have been classified as having vasomotor rhinitis caused by

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 Clinical Review & Education Review Allergic Rhinitis

Figure. The Pathogenesis of Allergic Rhinitis

A Allergic sensitization
Allergic rhinitis begins when allergens enter the nasal cavity and penetrate the epithelial barrier, inducing a simultaneous innate and adaptive immune response

Innate immune response Adaptive immune response

Allergen

NASAL
EPITHELIUM
1 Allergen crosses
Increased mucous epithelial barrier
production via and is engulfed by
1 Allergen disruption goblet cells Dendritic dendritic cell
TSLP cell Nasal gland
of nasal epithelium IL-25
causes release of IL-33
alarmin cytokines 2 Dendritic cell
presents allergen Mast
2 Alarmin cytokines Naive to CD4 T cell
stimulate group 2 cell
CD4
innate lymphoid cells ILC2 T cell
FcεRII Basophil
(ILC2) to produce
type 2 cytokines 3 T cell differentiates
into TH2 effector cell
IL-4 in the presence of IL-4
LAMINA IL-4 6 IgE binds FcεRII
PROPRIA IL-5 TH2 IgE receptors on mast
IL-13 cell cells and basophils,
IL-31 4 TH2 cell releases type 2 sensitizing them
3 Cytokines recruit cytokines which
basophils, eosinophils, to allergen
activate B cell
and fibroblasts IL-4
IL-5 Plasma cell
Basophil IL-13
Fibroblast IL-31 5 B cell differentiates into
B cell plasma cell and secretes
Eosinophil
LY M P H O I D allergen-specific IgE
TISSUE

B Allergic reaction
3 Early-phase response: occurs 30 min-1 h after exposure

Rhinorrhea

Edema
and swelling
1 Allergen penetrates
nasal epithelium and
cross-links IgE-FcεRII
receptor complexes Sternutation (sneezing) Repeated allergen exposure
on mast cells Vasodilation of Nasal pruritus (itching) over time leads to irreversible
and basophils nasal blood vessel Rhinorrhea mucosal hypertrophy and
Mast cell Histamine nonspecific hypersensitivity
Histamine from
mast cell
Proallergic Sensory nerve
2 Release of histamine mediators of CN V
and proallergic mediators
leads to early- and late-
phase symptoms Basophil 4 Late-phase response: occurs 4-24 h after exposure

Inflammatory cell infiltration

Nasal congestion
Proallergic and inflammatory mediators Inflammatory Vasodilation
Eosinophil NK mediators Edema
• Leukotrienes • Platelet-activating factor cell
• Thromboxane • Cytokines Swelling
T cell Inflammation
• Prostaglandins • Chemokines

Adapted from Zhang et al.11 CN V indicates fifth cranial nerve (trigeminal nerve); to the antigen on high-affinity receptors of mast cells, leading to activation and
NK, natural killer; TSLP, thymic stomal lymphopoietin. When antigen disrupts release of preformed bioactive mediators (ie, histamine) and generation of
the epithelial barrier, enhanced T-helper type 2 (TH2) cytokine production cytokines, leukotrienes, and other mediators. Mast cell mediators induce
occurs through innate immunity, mediated by alarmin cytokines, and through early-phase rhinitis symptoms within 30 to 60 minutes of exposure by acting
adaptive immunity via antigen presenting cells. The TH2 signaling recruits on sensory nerves, nasal glands, and nasal blood vessels. In addition,
allergic cells, increases mucous production via goblet cells, and increases inflammatory cells promote late-phase reaction symptoms 4 to 12 hours after
production of IgE through B cells. Allergic sensitization occurs as IgE coats and exposure, leading to nasal edema and congestion. Repeated inflammation over
primes mucosal mast cells. Upon reexposure to the antigen, IgE antibody binds time leads to nonspecific hypersensitivity and irreversible mucosal hypertrophy.

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 Allergic Rhinitis Review Clinical Review & Education

neuropathic mechanisms.19 Symptoms are caused by nonspecific

chemicals, irritants, and weather changes that induce vasodilation Box. Commonly Asked Questions
(leading to nasal congestion, eustachian tube dysfunction, head- How is allergic rhinitis distinguished from mixed or nonallergic
ache, sinus pressure, ear plugging, muffled sounds, and pain) and rhinitis?
increased mucus secretion (leading to postnasal drainage and ante- Allergic rhinitis is associated with positive skin prick testing or
rior rhinorrhea).20 with positive serological testing for IgE aeroallergens.
Occupational rhinitis is defined as rhinitis symptoms that begin Nonallergic rhinitis does not have these characteristics.
A history of symptoms in association with the patient exposure
or are exacerbated while at the workplace in association with expo-
to sensitizing allergens suggests allergic rhinitis. Nonallergic
sure to either high-molecular-weight protein allergens that elicit
rhinitis is associated with exposure to chemicals (such as
IgE-mediated sensitization or low-molecular-weight chemical cleaning agents or solvents) or irritants (such as tobacco smoke
agents that typically elicit irritant-induced nasal symptoms. The or perfumes) and with exposure to abrupt changes in the
most common causes of occupational rhinitis are chemical cleaning temperature.
agents (such as detergents, degreasers, abrasives, and acids) and What are the risk factors for allergic rhinitis?
sterilizing agents (such as antiseptics or disinfectants) used in the The risk factors include a family history of allergic rhinitis,
janitorial services and health care industries, but this problem can asthma, or atopic dermatitis and the presence of other allergic
develop in any industrialized or office setting.21 Occupational rhini- disorders such as asthma or atopic dermatitis.
tis frequently precedes occupational asthma.21 Avoiding irritants or What comorbid conditions are associated with allergic rhinitis?
allergens by wearing either an N95 particulate mask or a more fit- Viral and bacterial sinusitis, conjunctivitis, otitis media,
headache, asthma, sleep disturbances (such as obstructive
ted respirator can eliminate or improve symptoms if worn properly
sleep apnea), and eczema.
and continuously.21
Infectious rhinitis is primarily caused by viral upper respiratory
tract infections such as rhinoviruses, coronaviruses, and influenza Comorbid Conditions
viruses. Medication-induced rhinitis is a known adverse effect Comorbid conditions associated with allergic rhinitis include aller-
of several types of medications, including nonsteroidal anti- gic conjunctivitis, acute and chronic sinusitis, recurrent otitis me-
inflammatory agents, antihypertensives (β-blockers and cal- dia in children, eustachian tube dysfunction, and chronic cough due
cium channel blockers), and estrogen-containing oral contra- to postnasal drainage and asthma. These upper respiratory condi-
ceptives.3,17,22 The mechanisms of drug-induced rhinitis are poorly tions develop due to persistent inflammation and increased mucus
defined, but are understood to involve vasodilation through neuro- production. Inflammation leads to blockage of the lacrimal duct,
genic pathways.22 osteomeatal complex, and eustachian tube as all these structures
converge in the nasal cavity and posterior pharynx.
Risk Factors The link between allergic rhinitis and asthma may be due to in-
Newborns are predisposed toward a type 2 inflammatory response flammation produced by local allergic processes in the nose that ex-
characterized by increased production of IL-4, IL-5, and 13 cyto- tend into the lungs. Neurological reflex mechanisms (responses to
kines via T-helper type 2 lymphocytes or innate lymphoid type 2 external stimuli signaling neural pathways in the central nervous sys-
cells that promote development of allergic diseases like allergic rhi- tem, which respond with signals transmitted between neurons within
nitis. The normal gut microbiome is characterized by increases in the spinal cord) may also be involved, forming connections with mo-
Bifidobacterium during the first 3 to 6 months of life, followed by tor neurons responsible for activating muscles or mucus-secreting
colonization with clostridial species. This microbiome protects the glands involved in the neural reflex.23,26,27
infant from developing a type 2 inflammatory response to typical Treating allergic rhinitis with allergen immunotherapy may pre-
environmental exposures. vent progression to asthma. In a meta-analysis28 that included 18
Factors that maintain a normal gut microbiome include vaginal clinical trials (randomized and uncontrolled trials), allergen immu-
delivery, full-term gestational age, breastfeeding, early exposure to notherapy was associated with a lower incidence of developing
pets in the home (eg, dogs and possibly cats), having 2 or more sib- asthma (relative risk, 0.75 [95% CI, 0.64-0.88]; absolute rates not
lings in the home, and a rural environment.23 These factors protect provided). However, this meta-analysis28 had evidence of publica-
against the development of atopy, which is defined as the genetic tion bias, heterogeneity was moderate, and the results did not re-
predisposition to produce specific IgE sensitization to environmen- main statistically significant in the sensitivity analysis.
tal allergens.23 Factors that disrupt the normal gut microbiome and Approximately 30% of patients with allergic rhinitis may have
predispose children to atopy include (1) early antibiotic exposure, chronic rhinosinusitis with or without nasal polyposis, approxi-
(2) urban living associated with decreased biodiversity due to habi- mately 13.5% may have migraine or tension headaches, and ap-
tat destruction and increased CO2 emissions, (3) cesarean delivery, proximately 25% may have sleep disturbances such as obstructive
(4) preterm gestational age, and (5) having 1 sibling or 0 siblings in sleep apnea.29-32 For these patients, treating allergic rhinitis may im-
the home.23 prove the coexisting medical condition.3
A family history of atopy is also associated with allergic rhinitis.
Clinical manifestations of early sensitization usually begin as atopic Diagnostic Evaluation
dermatitis due to epithelial barrier dysfunction (which is also asso- Certain clinical features help differentiate allergic rhinitis from mixed
ciated with food allergy) and subsequent development of other al- rhinitis, which is characterized by features of both allergic rhinitis and
lergic disorders such as allergic rhinitis, asthma, and eosinophilic nonallergic rhinitis. For example, a questionnaire was distributed to
esophagitis.24,25 100 randomly selected patients with chronic rhinitis (multivariable

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 870
Table 1. Differential Diagnosis of Allergic Rhinitis
Description of allergic rhinitis and other rhinitis
Differential diagnosis conditions Clinical characteristics Pathophysiology Treatment
Seasonal allergic Inflammation of the nasal passages and upper airways • Childhood onset • IgE-mediated type 1 • Second-generation antihistaminesa
rhinitis due to seasonal aeroallergens (eg, environmental • Worse in spring, summer, and fall; improves during winter hypersensitivity • Intranasal corticosteroidsb
pollens) months • Intranasal antihistaminesb
• Common symptoms: itching, sneezing, rhinorrhea, nasal • Leukotriene receptor antagonistc
congestion, and postnasal drainage • Allergen immunotherapyd
Perennial allergic Inflammation of the nasal passages and upper airways • Associated with perennial allergen (skin test, positive • IgE-mediated type 1 • Second-generation antihistaminesa
rhinitis due to allergens causing yearlong symptoms serum-specific IgE test) hypersensitivity • Intranasal corticosteroidsb
(eg, dust mite, animal aeroallergens) • Improves with allergen avoidance • Intranasal antihistaminesb
• Common symptoms: itching, sneezing, rhinorrhea, nasal • Leukotriene receptor antagonistc
Clinical Review & Education Review

congestion, and postnasal drainage • Allergen immunotherapyd

Localized allergic Clinical history of perennial or seasonal rhinitis, negative • Consider nasal allergen provocation test if high suspicion • IgE-mediated type 1 • Second-generation antihistaminesa
rhinitis (entopic skin test, negative serum-specific IgE antibodies but for this condition hypersensitivity • Intranasal corticosteroidsb
rhinitis) positive nasal allergen provocation test for aeroallergens • Symptoms are similar to classic allergic presentation, but • Intranasal antihistaminesb
negative skin test • Leukotriene receptor antagonistc
• Allergen immunotherapyd
Vasomotor rhinitis Subtype of nonallergic rhinitis characterized by chronic • Nonallergic symptoms of nasal congestion and postnasal • Neuropathic (attributed to • Intranasal antihistaminesb
nasal congestion, postnasal drainage, and negative drainage with or without eustachian tube dysfunction increase in neural efferent • Intranasal corticosteroidsb
serum-specific IgE test for aeroallergens; symptoms traffic to the nasal mucosa with • Anticholinergic agents to control drainagee

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triggered by chemical irritants or weather changes an imbalance between
parasympathetic and
sympathetic innervation)
Nonallergic rhinitis Perennial nonallergic rhinitis with elevated nasal • Exclude other causes of persistent nasal eosinophilia • Neuropathic • Intranasal antihistaminesb
with eosinophil eosinophils >20% (allergic, fungal infection, eosinophilic granulomatosis • Intranasal corticosteroidsb
syndrome with polyangiitis, and chronic rhinosinusitis with or • Anticholinergic agents to control drainagee
without nasal polyps)
Occupational rhinitis Inflammation of the upper airways due to exposures • No prior history of rhinitis • IgE-mediated reactions • Depend on whether causative agent is
(work-related rhinitis) from the occupational environment (differs from • Symptoms are worse during the workweek; improve on • IgE or neuropathic pathways sensitizing or induced by irritant

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work-exacerbated rhinitis, which is preexisting rhinitis weekends or during vacations • Avoidance of work environment
that worsens from workplace exposures) • For IgE-mediated reactions, treat with
high-molecular-weight agents
• For IgE or non-IgE (neuropathic) pathways,
treat with low-molecular-weight agents
Drug-induced rhinitis Medication-induced symptoms of the upper airways • Causes include prolonged use of topical nasal • Mediated by specific receptor • For topical nasal decongestants,
induced by local inflammatory, neurogenic, and decongestants as monotherapy, oral contraceptives, downregulation of α receptors leads to
idiopathic pathways nonsteroidal anti-inflammatory drugs, antihypertensive tolerance of medication
medications (β-blockers) • Avoidance of medication
Infectious rhinitis Rhinitis symptoms are usually caused by viral organisms • Suspect bacterial infection when symptoms persist >10 d • Multifactorial involvement of • If viral, self-limiting

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that are self-limiting but can progress to a secondary • Biphasic illness when symptoms initially improve then toll-like receptors, epithelial • If bacterial, requires antibiotics
bacterial infection; can also be caused by fungal worsen, or if there are severe symptoms (eg, thick barrier disruption, mediation of • If fungal, requires immediate surgical
organisms, particularly in immunocompromised patients mucopurulent discharge with high-grade fever) innate immune response evaluation
a c
Examples of second-generation antihistamines include cetirizine, fexofenadine, desloratadine, and loratadine. An example is montelukast.
Less than 5% of patients experience the adverse effects of somnolence, dry mouth, fatigue, and dizziness. d
Examples of allergen immunotherapy include subcutaneous immunotherapy and sublingual immunotherapy.
b
Examples of intranasal antihistamines include azelastine and olopatadine. Examples of intranasal corticosteroids e
Examples of anticholinergic agents include diphenhydramine, brompheniramine, and chlorpheniramine.
include fluticasone, triamcinolone, budesonide, and mometasone. The adverse effects include (in descending
order) headache, epistaxis, and hyposmia (range, 0.5%-6% of patients experience adverse effects).
Allergic Rhinitis

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 Allergic Rhinitis Review Clinical Review & Education

logistic regression analysis and maximum likelihood estimates were Unproven or unvalidated allergen diagnostic testing include but
used to analyze the questionnaire results) and the following char- are not limited to skin end-point titration (Rinkel method), provo-
acteristics were most associated with nonallergic rhinitis: absence cation neutralization, the antigen leukocyte antibody test, and elec-
of seasonal (eg, spring) outdoor symptoms (odds ratio [OR], 7.76 trodermal testing.35 Approximately 30% of patients with allergic rhi-
[95% CI, 1.18-51.22]; P = .03), absence of a parental history of al- nitis have asthma, which may be subclinical, because patients with
lergy (OR, 5.16 [95% CI, 1.05-25.20]; P = .04), absence of symp- allergic rhinitis and asthma do not always perceive dyspnea or rec-
toms in the presence of cats (OR, 3.82 [95% CI, 0.59-24.83]; P = .16), ognize that asthma can manifest as a cough. Patients with allergic
presence of symptoms around perfumes and fragrances (OR, 4.88 rhinitis who present with a history of asthma or active asthma symp-
[95% CI, 1.05-22.60]; P = .04), and being older than 35 years of age toms (such as chest tightness, wheezing, shortness of breath, and
at symptom onset (OR, 1.08 [95% CI, 1.02-1.14]; P = .008) (abso- coughing) should be assessed for asthma with spirometry.
lute rates not provided).33
Up to 50% of patients with chronic rhinitis can have mixed Treatment
rhinitis in which the symptoms are precipitated by allergic and Environmental Interventions
nonallergic factors.17 However, the questionnaire study33 sug- First-line therapy for allergic rhinitis is removal of the environmen-
gested that patients reporting symptoms in the presence of cats and tal precipitants of symptoms. A thorough home and workplace en-
other furry pets may be a specific criterion for perennial allergic rhi- vironmental history can identify potential precipitants of allergic
nitis. Symptoms that occur in proximity to dust and cut grass are non- symptoms.36 Relevant indoor allergens include dust mites, pets (cats,
specific and less useful for distinguishing allergic rhinitis from dogs, other furry animals, and birds), mold spores, cockroaches, and
nonallergic rhinitis because these symptoms can be either allergic rodents. Patients allergic to pollen should keep windows closed. Air
or irritant-induced triggers. In contrast, having an older age at symp- conditioning can reduce indoor exposure to outdoor aeroaller-
tom onset, not having a family history of allergies, and not having gens. Dust mites accumulate in bedding (eg, pillows, mattresses, box
symptoms seasonally or around cats or other furry pets makes al- springs), carpeting, and upholstered furniture. Generally, dust mite
lergic rhinitis less likely33 (Table 1). avoidance studies for allergic rhinitis are small and their method-
Diagnostic testing for a panel of seasonal and perennial aeroal- ological quality is poor, but placing dust mite impermeable encase-
lergens should be performed for any patient with chronic rhinitis ments on bedding may have some benefit.37 Maintaining indoor hu-
who has persistent or recurrent intermittent symptoms not con- midity levels between 30% and 50% (using air conditioning or an
trolled with medication to categorize allergic rhinitis, mixed rhinitis, external dehumidifier) prevents or decreases dust mite propaga-
or nonallergic rhinitis because treatments and outcomes differ tion, which thrive in humid environments.38
across these rhinitis subtypes. Testing by an allergy specialist in- Exposure to pet allergens can be reduced by keeping pets out of
cludes either skin prick tests or serological testing relevant to the the bedroom and using high-efficiency particulate air filters in the bed-
patient’s geographic location. room and in the main rooms of activity to remove airborne allergens.
Skin prick testing involves placing a drop of a specific allergen Dogs with hair (eg, poodles, bichon, Maltese) instead of fur tend to
on the patient’s back or forearm and pricking it with a bifurcated shed less and are less likely to cause allergic symptoms in people with
needle, which will elicit a wheal and flare reaction within 15 min- dog allergies. Extermination is needed to eliminate cockroaches and
utes if the patient is sensitized. For specific aeroallergens, IgE sero- rodents, followed by thorough cleaning to reduce the allergen
logical testing uses an enzymatic assay to assess for sensitization. load.39-41 Effective environmental control requires multicomponent
Both types of tests usually include tree, grass, and weed pollens rel- interventions and maintenance, which can be expensive.
evant to the patient’s geographic location, outdoor (Alternaria spe- The indoor air pollutants that can aggravate allergic and nonal-
cies) and indoor (eg, Aspergillus niger, Penicillium notatum) molds, lergic rhinitis and asthma include nitrogen dioxide from gas stoves and
dust mite, cat, dog, and cockroach. A positive test that correlates kerosene heaters, ozone from electrical appliances, and chemical vola-
with symptoms in response to the allergen exposure is necessary tileorganiccompoundssuchascleaningagents,paints,andsolvents.42
to confirm a diagnosis of allergic rhinitis. Improving air filtration systems and maintaining adequate indoor and
A meta-analysis34 of 7 studies with 430 patients from Health outdoor air exchange should generally be implemented in the home
Canada (using nasal provocation to the specific allergen as the gold and workplace of patients with chronic rhinitis and asthma to reduce
standard) reported that the skin prick tests had an 85% sensitivity these exposures and improve indoor air quality.42
and a 77% specificity for confirming allergic rhinitis. If skin prick tests
are negative, conducting a select number of intradermal (also known Pharmacotherapy
as intracutaneous) tests, which involves injecting a small volume of Current treatment recommendations consist of an algorithmic ap-
the suspected allergen underneath the forearm skin to elicit a wheal proach to titrating medications based on disease severity (Table 2)
and flare response within 10 to 15 minutes, may be appropriate if with the objective of complete or near-complete elimination of symp-
the patient’s symptoms suggest specific exposures (eg, cat or dog). toms (Table 3). This may allow discontinuation of treatments after
However, these tests are less sensitive and specific as a primary test the allergy-inducing season is over for patients with seasonal aller-
for the diagnosis of allergic rhinitis.34 Two of the studies included in gic rhinitis; however, patients with perennial allergic rhinitis may re-
the meta-analysis34 compared the accuracy of intradermal testing quire yearlong therapy.
(as the gold standard stand-alone diagnostic test for allergic rhini- First-line treatments for intermittent allergic rhinitis include
tis) vs nasal provocation (with the specific allergen) and reported a oral second-generation antihistamines such as fexofenadine,
sensitivity ranging between 60% and 79% and a specificity rang- cetirizine, levocetirizine, and desloratadine. A meta-analysis47 of
ing between 68% and 69%. 12 double-blind, placebo-controlled, randomized clinical trials

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 Clinical Review & Education Review Allergic Rhinitis

Table 2. Treatments for Intermittent or Persistent Allergic Rhinitis in Patients Aged 12 Years or Oldera

Treatments for mild symptoms Treatments for moderate or severe symptoms

Intermittent allergic rhinitisb
First line • Oral second-generation antihistamines • Oral second-generation antihistamines
• Intranasal antihistamines • Intranasal antihistamines
Second line • Oral second-generation antihistamines plus • Intranasal corticosteroidsd
pseudoephedrinec
• Intranasal corticosteroidsd
Third line • Combination of intranasal corticosteroids with
intranasal antihistaminese
Persistent allergic rhinitisf
First line • Intranasal corticosteroids • Intranasal corticosteroids
• Intranasal antihistamines
• Combination of intranasal corticosteroids with
intranasal antihistamines
Second line • Intranasal corticosteroids and second-generation • If intranasal corticosteroids ineffective, use intranasal
antihistamines or intranasal antihistamines antihistamines
Third line • Second-generation antihistamines plus
pseudoephedrinec
• Intranasal decongestant in conjunction with
intranasal corticosteroids up to 4-6 wk as tolerated
for severe congestion
Fourth line • Add intranasal cromolyn sodium to third-line
treatments
a
Based on data from Dykewicz et al.3 e
May add oral pseudoephedrine or intranasal decongestant for moderate to
b
Defined as experiencing symptoms lasting only during a season in response to severe nasal congestion.
f
a sensitizing allergen (occurring 2-3 days/week for <3 months within the year). Defined as experiencing symptoms lasting throughout the year in response to
c
Pseudoephedrine should be used with caution due to the known adverse a sensitizing allergen (occurring >4 days/week for most weeks of the year).
effects of increased blood pressure, palpitations, insomnia, and restlessness.
d
Intranasal decongestants can be used safely in conjunction with intranasal
corticosteroids for up to 4 to 6 weeks without rebound congestion.

investigating the efficacy and safety of fexofenadine for treatment whereas the incidence approaches 20% and 28% with yearlong use.
of patients with allergic rhinitis reported an association of fexofena- Correct technique involves directing the spray away from the nasal
dine treatment (n = 1910 patients) with reduced total symptom septum, toward the middle of the eye. Some intranasal corticoste-
scores compared with placebo (n = 1777) (standardized mean dif- roids have also been demonstrated to control ocular symptoms in
ference for change from baseline score, –0.33 [95% CI, –0.47 to 0.18]; patients with allergic rhinitis.3,43 Intranasal corticosteroids may raise
P < .001), consistent with a small effect size. No definitive direct com- intraocular pressure slightly in some patients who are at risk for glau-
parisons of different oral second-generation antihistamine thera- coma or who have glaucoma, but intranasal corticosteroids are not
pies for allergic rhinitis are available. contraindicated in patients with glaucoma.3
Current allergic rhinitis guidelines3 recommend use of second- Second-generation antihistamines are generally well tolerated
generation antihistamines before using leukotriene-modifying because they are selective H1-receptor antagonists that do not cross
agents, such as montelukast, which have effect sizes that are simi- the blood-brain barrier or bind to cholinergic receptors, making them
lar to oral second-generation antihistamines. Montelukast has a less sedating and drying, respectively. Intranasal antihistamines are
boxed warning for increased anxiety, depression, and nightmares also well tolerated, but can cause excessive dryness of the nasal mu-
in some individuals who take this medication.48 Loratadine, ceti- cosa with epistaxis, and, in some cases, headaches.3 If patients do
rizine, and levocetirizine are available without a prescription. Addi- not respond to these medications, they may be using these medi-
tional first-line therapies include intranasal antihistamines (azelas- cations incorrectly, may not have allergic rhinitis, or have structural
tine or olopatadine) and intranasal corticosteroids (fluticasone, anatomic abnormalities such as a deviated septum or nasal turbi-
triamcinolone, budesonide, or mometasone).3 All of these thera- nate hypertrophy (defined as excessive growth or enlargement of
pies are available without a prescription. the turbinates) that impede the effectiveness of the medications.
Treatment of persistent allergic rhinitis may include com- Evaluation for anatomic abnormalities can be performed using a si-
bined therapy with intranasal antihistamines and intranasal corti- nus computed tomographic scan or nasal endoscopy. In general,
costeroids with or without a second-generation antihistamine.3,43 pharmacotherapy for children aged 6 years or older does not differ
Intranasal corticosteroids reduce nasal inflammation and are con- from adults except for the dosing of the medications.3
sidered by most consensus recommendations as first-line topical Intramuscular corticosteroids are not recommended to treat sea-
monotherapies for moderate to severe allergic rhinitis.3 The most sonal allergic rhinitis or perennial allergic rhinitis due to the well-
common adverse effect of intranasal corticosteroids is nasal documentedcumulativeadverseeffectsofsystemiccorticosteroids.44
bleeding (epistaxis); less commonly, they cause septal erosions For a severe, acute, seasonal allergic rhinitis exacerbation manifest-
and ulcerations. ing as persistent sneezing attacks, rhinorrhea, and itching with or with-
The incidence of epistaxis with intranasal corticosteroids ranges out nasal congestion, sinus pressure, and pain, a short course of high-
between 4% and 8% with short-term use (between 2 and 12 weeks), dose oral corticosteroids (35-40 mg for 5-7 days) may be appropriate,

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 Table 3. Medications for Allergic Rhinitis
Onset of

[Link]
Description of therapy Examples of adult dosing action Maximal effect Efficacy Adverse effects
Allergic Rhinitis

Combination of intranasal • Fluticasone (50 μg) with azelastine (137 μg) per actuation: 5 min ≥2 wk • More effective than intranasal corticosteroids or • Nasal irritation and epistaxis
corticosteroids with 1 puff in each nostril twice/d monotherapy with intranasal antihistamines and • Increased cost for combination
intranasal antihistamines • Mometasone (25 μg) with olopatadine (665 μg): 2 puffs in placebo for improving nasal symptoms, ocular formulation
each nostril twice/d symptoms, and quality of life43,44
Alcohol-based intranasal • Fluticasone propionate (50 μg): 1-2 puffs/d in each nostril 2-12 h 2 wk • First-line treatment for moderate or severe seasonal • Nasal irritation and epistaxis
corticosteroids allergic rhinitis and for persistent, allergic, or (risk increased with alcohol-based
nonallergic rhinitis in those aged >15 y formulations)
• Strong recommendation with high certainty of
evidence3
Aqueous-based intranasal • Fluticasone furoate (27.5 μg): 1-2 puffs/d in each nostril 8h 2-4 wk • Recent meta-analysis showed superiority vs placebo, • Short-term use may decrease
corticosteroids but similar efficacy as intranasal corticosteroids for short-term growth velocity, but no
• Mometasone furoate (50 μg): 2 puffs/d in each nostril 2-5 h 4 wk improving total nasal and ocular symptom scores45 effect on long-term growth velocity;
• Ciclesonide (50 μg): 2 puffs/d in each nostril 1-6 h 2-4 wk • Non–alcohol-based nasal corticosteroids (such as use lowest effective dose and monitor
triamcinolone) are associated with less nasal irritation growth
• Budesonide (32 μg): 1-4 puffs/d in each nostril 3-8 h 2-4 wk than alcohol-based formulations (such as fluticasone) • Theoretical concern for increased
• Triamcinolone acetonide (55 μg): 1-2 puffs/d in each 12 h 2-4 wk intraocular pressure; prescribe with
nostril caution in patients with glaucoma or
cataracts
Intranasal antihistamines • Azelastine 0.1% (137 μg): 1-2 puffs in each nostril twice/d 15 min 1 d to 4 wk for • First-line treatment for seasonal allergic, intermittent, • Bitter taste (worse taste with
for perennial allergic rhinitis and vasomotor rhinitis both drugs and nonallergic rhinitis azelastine)
• Azelastine 0.15% (205.5 μg): 2 puffs in each nostril daily • Strong recommendation with high certainty of • Nasal irritation and epistaxis
for seasonal allergic rhinitis and twice daily for perennial evidence3
allergic rhinitis
• Olopatadine 0.6% (665 μg): 2 puffs in each nostril twice/d 30 min
for seasonal allergic rhinitis
Intranasal anticholinergics • Ipratropium bromide 0.03% (21 μg): 2 puffs in each nostril 15 min 1h • Consider for treatment of anterior rhinorrhea in • Nasal irritation and epistaxis
2-3 times/d for perennial allergic rhinitis and nonallergic patients with nonallergic rhinitis (moderate evidence) • Prescribe with caution in patients with

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rhinitis or perennial rhinitis (low level of evidence)3 glaucoma
• Ipratropium bromide 0.06% (42 μg): 2 puffs in each nostril
4 times/d for seasonal allergic rhinitis and 3-4 times/d for
the common cold
Second-generation oral • Desloratadine (5 mg) once/d 30-90 min 1-8 d • More effective than placebo in alleviating allergic • Minimal adverse effect profile; may
antihistamines rhinitis symptoms cause nasal or ocular dryness
• Levocetirizine (2.5-5 mg) once/d 45 min • Less effective than intranasal corticosteroids3 • For patients with kidney failure, can
• Cetirizine (5-10 mg) once/d as needed 60 min use loratadine and first-generation
antihistamines (eg, diphenhydramine)
• Loratadine (10 mg) once/d as needed 60-75 min • For patients with hepatic failure, can

© 2024 American Medical Association. All rights reserved.

• Fexofenadine (180 mg) once/d as needed 60 min use first-generation antihistamines
(eg, diphenhydramine or
fexofenadine), although dose may
need to be reduced
First-generation oral • Diphenhydramine (25-50 mg) every 4-6 h as needed 20-30 min 1h • No existing double-blind, placebo-controlled trials to • Attributed to nonspecific cholinergic
antihistamines evaluate therapeutic efficacy of first- vs and α-adrenergic receptor binding
second-generation oral antihistamines • Can lead to sedation, increased risk of
dementia, dry eyes, dry mouth, urinary
retention, dose-dependent
tachycardia, and risk of arrhythmias

(continued)
Review Clinical Review & Education

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873
 874
Table 3. Medications for Allergic Rhinitis (continued)
Onset of
Description of therapy Examples of adult dosing action Maximal effect Efficacy Adverse effects
Intranasal decongestants • Oxymetazoline 0.05%: 2-3 puffs every 10-12 h as needed <10 min Within 60 min • For short-term benefit of nasal congestion • Rhinitis medicamentosa as soon as 3 d
• If used longer than 5-7 d, administer with intranasal • Should not be prescribed for >3 d after use
corticosteroids • Studies show coadministration of
intranasal corticosteroids helps to
prevent rhinitis medicamentosa
for ≤4 wk
Second-generation oral • Loratadine (5 mg) with pseudoephedrine (120 mg) every 30 min Unknown • More effective than individual components alone • Pseudoephedrine may cause increased
antihistamines with 12 h as needed blood pressure, palpitations, insomnia,
Clinical Review & Education Review

a decongestant • Loratadine (10 mg) with pseudoephedrine (240 μg) once/d and restlessness
as needed
• Fexofenadine (60 mg) with pseudoephedrine (120 mg)
every 12 h as needed
• Fexofenadine (180 mg) with pseudoephedrine (240 μg)
once/d as needed
• Cetirizine (5 mg) with pseudoephedrine (120 mg) every
12 h as needed
• Cetirizine (10 mg) with pseudoephedrine (240 μg) once/d
as needed

JAMA March 12, 2024 Volume 331, Number 10 (Reprinted)

Leukotriene receptor • Montelukast (10 mg) once/d Within 5 h By second • Montelukast is more effective than placebo for • Upper respiratory tract infection, fever,
antagonist week improving daytime nasal score, nighttime nasal headache, pharyngitis, cough,
symptoms, and composite symptom scores46 abdominal pain, diarrhea, otitis media,
• Oral antihistamines are superior to montelukast in influenza, rhinorrhea, sinusitis, and
improving daytime nasal symptoms and composite otitisa
symptom scores, daytime eye symptoms, and quality • Boxed warning for neuropsychiatric
of life adverse effectsb
• Montelukast is superior to oral antihistamines in
improving nighttime nasal symptoms46

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Intranasal mast cell • Cromolyn sodium (5.2 mg): 1 puff in each nostril 2 wk ≥2 wk • Improves symptoms of seasonal allergic rhinitis vs • Low adverse effect profile
stabilizers 3-4 times/d placebo, but not symptoms of perennial allergic • Safe during pregnancy
rhinitis
• May be most helpful immediately before allergen
exposure (very low level of evidence)3
a
Compared with placebo, these adverse effects occur more often (ⱖ5%) in treated patients. abnormalities, hallucinations, insomnia, restlessness, somnambulism, suicidal thinking and behavior (suicide),
b tic, obsessive-compulsive symptoms, and dysphemia or stuttering.
Includes agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, dream

© 2024 American Medical Association. All rights reserved.

Allergic Rhinitis

[Link]
 Allergic Rhinitis Review Clinical Review & Education

but subsequent treatment with intranasal corticosteroids alone or in Patients receiving cluster allergen immunotherapy protocols
combination with intranasal antihistamines beginning before the start must be pretreated with medications (eg, H1 antihistamines, H2 an-
of an allergy season should prevent severe exacerbations and the need tihistamines, leukotriene-modifying agents) to prevent local and sys-
for systemic corticosteroids.3,49 Although most allergic rhinitis medi- temic reactions.54 If allergen immunotherapy is determined to be
cations can be obtained without a prescription, clinicians should over- effective by the patient and physician, it should be continued for up
see their use to ensure optimal efficacy. to 3 to 5 years.54,55 The cost of allergen immunotherapy varies, but
Low or high volumes of isotonic or hypertonic saline irrigation the 5-year course costs approximately $5000.56 In contrast, sub-
solutions via a variety of devices available over the counter, may re- lingual immunotherapy is approved for home use after the first dose
duce allergic rhinitis symptom severity, and are relatively inexpen- is safely administered at a medical facility.
sive. A meta-analysis50 that pooled data from 7 studies (including The rate for a systemic adverse reaction (eg, isolated nasal con-
data from 112 adults and 332 children) reported that saline irriga- gestion, sneezing, wheezing, nausea, vomiting, diarrhea) to subcu-
tion compared with no saline irrigation was associated with im- taneous immunotherapy is approximately once for every 1000 injec-
proved patient-reported disease severity up to 4 weeks (standard- tions (0.1%); for life-threatening anaphylaxis involving 2 or more organ
ized mean difference, −1.32 [95% CI, −1.84 to −0.81]), which is systems, the rate is once for every 160 000 injections.57 These pa-
consistent with a large effect. Pooled data from 6 of these studies tients should have an epinephrine injector available in case of a sys-
(407 participants) demonstrated that saline irrigation was associ- temic reaction. Approximately 50% of patients treated with sublin-
ated with significant benefit compared with placebo at follow-up pe- gual immunotherapy can experience oral palatal itching, which can be
riods between 4 weeks and 3 months (standardized mean differ- uncomfortable and provoke anxiety.58 However, this reaction has not
ence, −1.44 [95% CI, −2.39 to −0.48]), which is consistent with a large been reported to progress to laryngeal angioedema or systemic
effect size. However, the evidence50 supporting this treatment in- reactions.58 Clinicians prescribing subcutaneous immunotherapy and
tervention was graded as low or very low because of the small sample sublingual immunotherapy must educate and monitor patients on
sizes, variable scoring systems for symptoms, and high rates of bias. these therapies for tolerability, safety, and effectiveness.

Immunotherapy Prognosis
Patientswhoaresensitizedtoaeroallergensaccordingtoskinpricktest- When diagnosed and treated appropriately, allergic rhinitis has an
ing or serological testing and who have persistent symptoms despite excellent prognosis. Patients who remain symptomatic despite medi-
optimal medical therapy and interventions to reduce environmental cation use may have received an incorrect diagnosis (such as mixed
exposures should be considered for allergen immunotherapy. Allergen rhinitis or nonallergic rhinitis, chronic sinusitis, or nonallergic nasal
immunotherapy induces tolerance to allergens and prevents progres- turbinate hypertrophy) or have poor medication adherence. Alter-
sion of comorbid conditions (such as sinusitis and asthma in children natively, patients who do not improve may have ongoing exposure
and adults).3,28,51 Patients who may benefit from allergen immuno- to allergens such as pets in the home, dust or irritant occupational
therapy are those who also want to minimize medication use and are exposures, or exposure to pollen outdoors. If symptoms do not re-
committed to adhering to allergen immunotherapy. spond as expected to pharmacotherapy, referral to an allergy spe-
Several routes of allergen immunotherapy are available, but the cialist is recommended.3
greatest evidence of efficacy exists for subcutaneous immuno-
therapy and sublingual immunotherapy, which are both approved Limitations
by the US Food and Drug Administration. The proposed mecha- This review has several limitations. First, non-English language ar-
nism of action for these immunotherapies include modulation of the ticles were not included. Second, some relevant publications may
innate immune system by decreasing local mast cells, basophils, eo- have been omitted. Third, the quality of all the included studies was
sinophils, and type 2 innate lymphoid cells. These immunothera- not assessed formally.
pies may affect the adaptive immune system by inducing allergen-
specific IgG blocking antibodies, immunosuppressive cytokines,
T-regulatory cells, and B cells.52,53 However, the specific mecha-
Conclusion
nism of action for immunotherapy remains unclear.28
Subcutaneous immunotherapy should be administered by an Allergic rhinitis is associated with symptoms of nasal congestion,
experienced allergist or otolaryngologist in an office setting where sneezing, and itching of the eyes, nose, and throat. Patients with al-
emergency medications (eg, epinephrine) can be administered if a lergic rhinitis should be instructed to avoid inciting allergens. Thera-
systemic allergic reaction occurs. With the use of conventional pro- pies include second-generation H1 antihistamines (eg, cetirizine,
tocols, attaining a maintenance dose with efficacy may require up fexofenadine, desloratadine, loratadine), intranasal antihistamines
to 6 months. Cluster protocols have faster dosing because they con- (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, flu-
sist of administering multiple injections each day over 3 to 4 days54 ticasone, triamcinolone, budesonide, mometasone) and should be
to achieve higher concentrations and confer faster and increased selected based on the severity and frequency of symptoms and pa-
therapeutic benefits compared with conventional regimens. tient preference.

ARTICLE INFORMATION Author Contributions: Dr J. A. Bernstein had full Conflict of Interest Disclosures: Dr J. A. Bernstein
Accepted for Publication: January 15, 2024. access to all of the data in the study and takes reported receiving grants from AstraZeneca,
responsibility for the integrity of the data and the ALK-Abelló, GSK, Sanofi Regeneron, Novartis,
accuracy of the data analysis. Optinose, Allergy Therapeutics, and Genentech;

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 Clinical Review & Education Review Allergic Rhinitis

receiving personal fees from the American exacerbation of allergic and other chronic a systematic review and meta-analysis of
Academy of Allergy, Asthma, and Immunology inflammatory diseases. Asia Pac Allergy. 2023;13(1): randomized and non-randomized controlled
(AAAAI) for serving as president; receiving 28-39. studies. Allergy. 2022;77(6):1719-1735. doi:10.1111/
nonfinancial support from the World Allergy 13. Okano M, Fujieda S, Gotoh M, et al. Executive all.15295
Organization for serving on the board of directors, summary: Japanese guidelines for allergic rhinitis 29. Bernstein JA, Fox RW, Martin VT, Lockey RF.
from the AAAAI for serving on the Joint Task Force 2020. Allergol Int. 2023;72(1):41-53. doi:10.1016/j. Headache and facial pain: differential diagnosis and
on Practice Parameters, and from Interasma; and alit.2022.11.003 treatment. J Allergy Clin Immunol Pract. 2013;1(3):
holding a patent for a therapeutic agent but does 242-251. doi:10.1016/[Link].2013.03.014
not receive royalties. No other disclosures were 14. Ulusoy S, Bayar Muluk N, Scadding GK, et al.
reported. The intranasal trigeminal system: roles in rhinitis 30. Martin VT, Fanning KM, Serrano D, et al.
(allergic and non-allergic). Eur Rev Med Pharmacol Chronic rhinitis and its association with headache
Submissions: We encourage authors to submit Sci. 2022;26(2)(suppl):25-37. frequency and disability in persons with migraine:
papers for consideration as a Review. Please results of the American Migraine Prevalence and
contact Kristin Walter, MD, at [Link]@ 15. Cho SH, Nanda A, Keswani A, et al; Rhinitis,
Rhinosinusitis, and Ocular Allergy Committee of the Prevention (AMPP) Study. Cephalalgia. 2014;34(5):
[Link]. 336-348. doi:10.1177/0333102413512031
AAAAI. Nasal allergen challenge (NAC): practical
REFERENCES aspects and applications from an EU/US 31. Martin VT, Taylor F, Gebhardt B, et al. Allergy
perspective—a work group report of the AAAAI and immunotherapy: are they related to migraine
1. Cox L. The role of allergen immunotherapy in the Rhinitis, Rhinosinusitis and Ocular Allergy headache? Headache. 2011;51(1):8-20. doi:10.1111/j.
management of allergic rhinitis. Am J Rhinol Allergy. Committee. J Allergy Clin Immunol. 2023;151(5): 1526-4610.2010.01792.x
2016;30(1):48-53. doi:10.2500/ajra.2016.30.4253 1215-1222.e4. doi:10.1016/[Link].2023.02.014 32. Nguyen DK, Liang J, Durr M. Topical nasal
2. Ozdoganoglu T, Songu M. The burden of allergic 16. Mortada MM, Kurowski M. Challenges in local treatment efficacy on adult obstructive sleep apnea
rhinitis and asthma. Ther Adv Respir Dis. 2012;6(1): allergic rhinitis diagnosis, management, and severity: a systematic review and meta-analysis. Int
11-23. doi:10.1177/1753465811431975 research: current concepts and future perspectives. Forum Allergy Rhinol. 2021;11(2):153-161. doi:10.
3. Dykewicz MS, Wallace DV, Amrol DJ, et al; Medicina (Kaunas). 2023;59(5):929. doi:10.3390/ 1002/alr.22658
Chief Editor(s); Joint Task Force on Practice medicina59050929 33. Brandt D, Bernstein JA. Questionnaire
Parameters; Workgroup Contributors. Rhinitis 17. Bernstein JA. Characterizing rhinitis subtypes. evaluation and risk factor identification for
2020: a practice parameter update. J Allergy Clin Am J Rhinol Allergy. 2013;27(6):457-460. doi:10. nonallergic vasomotor rhinitis. Ann Allergy Asthma
Immunol. 2020;146(4):721-767. doi:10.1016/[Link]. 2500/ajra.2013.27.3983 Immunol. 2006;96(4):526-532. doi:10.1016/S1081-
2020.07.007 1206(10)63546-6
18. Settipane RA, Lieberman P. Update on
4. Greiwe JC, Bernstein JA. Allergic and mixed nonallergic rhinitis. Ann Allergy Asthma Immunol. 34. Health Quality Ontario. Skin testing for allergic
rhinitis: diagnosis and natural evolution. J Clin Med. 2001;86(5):494-507. rhinitis: a health technology assessment. Published
2019;8(11):2019. doi:10.3390/jcm8112019 May 2016. Accessed February 9, 2024. https://
19. Bernstein JA, Singh U. Neural abnormalities in
5. Passali D, Cingi C, Staffa P, Passali F, Muluk NB, nonallergic rhinitis. Curr Allergy Asthma Rep. 2015; [Link]/Portals/0/Documents/
Bellussi ML. The International Study of the Allergic 15(4):18. doi:10.1007/s11882-015-0511-7 evidence/reports/[Link]
Rhinitis Survey: outcomes from 4 geographical 35. Burks AW, O’Hehir RE, Broide DH, et al, eds.
regions. Asia Pac Allergy. 2018;8(1):e7. doi:10.5415/ 20. Settipane RA. Epidemiology of vasomotor
rhinitis. World Allergy Organ J. 2009;2(6):115-118. Middleton’s Allergy. 9th ed. Elsevier; 2020.
apallergy.2018.8.e7
doi:10.1097/WOX.0b013e3181ac91ae 36. Schwab AD, Poole JA. Mechanistic and
6. Meltzer EO, Blaiss MS, Derebery MJ, et al. therapeutic approaches to occupational
Burden of allergic rhinitis: results from the Pediatric 21. Shao Z, Bernstein JA. Occupational rhinitis:
classification, diagnosis, and therapeutics. Curr exposure-associated allergic and non-allergic
Allergies in America survey. J Allergy Clin Immunol. asthmatic disease. Curr Allergy Asthma Rep. 2023;
2009;124(3)(suppl):S43-S70. doi:10.1016/[Link].2009. Allergy Asthma Rep. 2019;19(12):54. doi:10.1007/
s11882-019-0892-0 23(6):313-324. doi:10.1007/s11882-023-01079-w
05.013
22. Alromaih S, Alsagaf L, Aloraini N, et al. 37. Nurmatov U, van Schayck CP, Hurwitz B,
7. Meltzer EO, Blaiss MS, Naclerio RM, et al. Burden Sheikh A. House dust mite avoidance measures for
of allergic rhinitis: allergies in America, Latin Drug-induced rhinitis: narrative review. Ear Nose
Throat J. 2022;0:0. doi:10.1177/01455613221141214 perennial allergic rhinitis: an updated Cochrane
America, and Asia-Pacific adult surveys. Allergy systematic review. Allergy. 2012;67(2):158-165. doi:
Asthma Proc. 2012;33(suppl 1):S113-S141. doi:10. 23. Donald K, Finlay BB. Early-life interactions 10.1111/j.1398-9995.2011.02752.x
2500/aap.2012.33.3603 between the microbiota and immune system:
impact on immune system development and atopic 38. Arlian LG, Platts-Mills TA. The biology of dust
8. Meltzer EO, Farrar JR, Sennett C. Findings from mites and the remediation of mite allergens in
an online survey assessing the burden and disease. Nat Rev Immunol. 2023;23(11):735-748.
doi:10.1038/s41577-023-00874-w allergic disease. J Allergy Clin Immunol. 2001;107(3)
management of seasonal allergic (suppl):S406-S413. doi:10.1067/mai.2001.113670
rhinoconjunctivitis in US patients. J Allergy Clin 24. Vlastos IM, Kalentakis Z, Doulaptsi M,
Immunol Pract. 2017;5(3):779-789.e6. doi:10.1016/j. Karatzanis A, Prokopakis EP. Multimorbidities in 39. Eggleston PA, Butz A, Rand C, et al. Home
jaip.2016.10.010 allergic rhinitis-current evidence from environmental intervention in inner-city asthma:
epidemiological studies, treatment trials, and a randomized controlled clinical trial. Ann Allergy
9. Meltzer EO, Nathan R, Derebery J, et al. Sleep, Asthma Immunol. 2005;95(6):518-524. doi:10.
quality of life, and productivity impact of nasal molecular data. Curr Allergy Asthma Rep. 2023;23
(2):133-140. doi:10.1007/s11882-022-01063-w 1016/S1081-1206(10)61012-5
symptoms in the United States: findings from the
Burden of Rhinitis in America survey. Allergy 25. Gabryszewski SJ, Dudley J, Shu D, et al. 40. Gergen PJ, Mortimer KM, Eggleston PA, et al.
Asthma Proc. 2009;30(3):244-254. doi:10.2500/ Patterns in the development of pediatric allergy. Results of the National Cooperative Inner-City
aap.2009.30.3230 Pediatrics. 2023;152(2):e2022060531. doi:10.1542/ Asthma Study (NCICAS) environmental
peds.2022-060531 intervention to reduce cockroach allergen exposure
10. Derebery J, Meltzer E, Nathan RA, et al. Rhinitis in inner-city homes. J Allergy Clin Immunol. 1999;
symptoms and comorbidities in the United States: 26. Corren J. The relationship between allergic 103(3 pt 1):501-506. doi:10.1016/S0091-6749(99)
burden of rhinitis in America survey. Otolaryngol rhinitis and bronchial asthma. Curr Opin Pulm Med. 70477-X
Head Neck Surg. 2008;139(2):198-205. doi:10.1016/ 1999;5(1):35-37. doi:10.1097/00063198-199901000-
[Link].2008.05.019 00006 41. Rao D, Phipatanakul W. Impact of
environmental controls on childhood asthma. Curr
11. Zhang R, Zhang L, Li P, Pang K, Liu H, Tian L. 27. Pawankar R, Mori S, Ozu C, Kimura S. Overview Allergy Asthma Rep. 2011;11(5):414-420. doi:10.
Epithelial barrier in the nasal mucosa, related risk on the pathomechanisms of allergic rhinitis. Asia 1007/s11882-011-0206-7
factors and diseases. Int Arch Allergy Immunol. Pac Allergy. 2011;1(3):157-167. doi:10.5415/apallergy.
2023;184(5):481-501. doi:10.1159/000528969 2011.1.3.157 42. Wimalasena NN, Chang-Richards A, Wang KI,
Dirks KN. Housing risk factors associated with
12. Kucuksezer UC, Ozdemir C, Yazici D, et al. 28. Farraia M, Paciência I, Castro Mendes F, et al. respiratory disease: a systematic review. Int J
The epithelial barrier theory: development and Allergen immunotherapy for asthma prevention:

876 JAMA March 12, 2024 Volume 331, Number 10 (Reprinted) [Link]

© 2024 American Medical Association. All rights reserved.

Downloaded from [Link] by Pontificia Universidad Javeriana user on 01/20/2026
 Allergic Rhinitis Review Clinical Review & Education

Environ Res Public Health. 2021;18(6):2815. doi:10. on the efficacy and safety issues of fexofenadine. 54. Greiwe J, Bernstein JA. Accelerated/rush
3390/ijerph18062815 World Allergy Organ J. 2023;16(7):100795. doi:10. allergen immunotherapy. Allergy Asthma Proc.
43. Chitsuthipakorn W, Hoang MP, Kanjanawasee 1016/[Link].2023.100795 2022;43(4):344-349. doi:10.2500/aap.2022.43.
D, Seresirikachorn K, Snidvongs K. Combined 48. Wei C. The efficacy and safety of 210108
medical therapy in the treatment of allergic rhinitis: H1-antihistamine versus montelukast for allergic 55. Rodriguez-Plata E, Callero Viera A, Ruiz-Garcia
systematic review and meta-analyses. Int Forum rhinitis: a systematic review and meta-analysis. M, Gomez-Cardenosa A, Nieto E, García-Robaina
Allergy Rhinol. 2022;12(12):1480-1502. doi:10.1002/ Biomed Pharmacother. 2016;83:989-997. doi:10. JC. House dust mite subcutaneous immunotherapy
alr.23015 1016/[Link].2016.08.003 has sustained long-term effectiveness on allergic
44. Lugogo N, Chipps BE, Panettieri RA Jr, Trudo F, 49. Mygind N, Laursen LC, Dahl M. Systemic rhinitis and asthma: a 10-year follow-up. Immun
Ambrose CS. Long-term use of maintenance corticosteroid treatment for seasonal allergic Inflamm Dis. 2023;11(10):e1004. doi:10.1002/iid3.
systemic corticosteroids is associated with multiple rhinitis: a common but poorly documented therapy. 1004
adverse conditions in a large, real-world cohort of Allergy. 2000;55(1):11-15. doi:10.1034/j.1398-9995. 56. Bernstein JA. Pharmacoeconomic
US adults with severe asthma. J Asthma Allergy. 2000.00108.x considerations for allergen immunotherapy. Clin
2022;15:1753-1761. doi:10.2147/JAA.S375005 50. Head K, Snidvongs K, Glew S, et al. Saline Allergy Immunol. 2004;18:151-164.
45. Soe KK, Krikeerati T, Pheerapanyawaranun C, irrigation for allergic rhinitis. Cochrane Database 57. Dhamija Y, Epstein TEG, Bernstein DI. Systemic
Niyomnaitham S, Phinyo P, Thongngarm T. Syst Rev. 2018;6(6):CD012597. allergic reactions and anaphylaxis associated with
Comparative efficacy and acceptability of licensed 51. Penagos M, Durham SR. Allergen allergen immunotherapy. Immunol Allergy Clin
dose intranasal corticosteroids for immunotherapy for long-term tolerance and North Am. 2022;42(1):105-119. doi:10.1016/[Link].
moderate-to-severe allergic rhinitis: a systematic prevention. J Allergy Clin Immunol. 2022;149(3): 2021.09.012
review and network meta-analysis. Front Pharmacol. 802-811. doi:10.1016/[Link].2022.01.007 58. Dhulipalla S. Ragweed sublingual
2023;14:1184552. doi:10.3389/fphar.2023.1184552 immunotherapy (SLIT) tablets in allergic
52. Alvaro-Lozano M, Akdis CA, Akdis M, et al.
46. Krishnamoorthy M, Mohd Noor N, Mat Lazim EAACI allergen immunotherapy user’s guide. rhinoconjunctivitis: a systematic review and
N, Abdullah B. Efficacy of montelukast in allergic Pediatr Allergy Immunol. 2020;31(suppl 25):1-101. meta-analysis. Eur Arch Otorhinolaryngol. 2022;279
rhinitis treatment: a systematic review and (6):2765-2775. doi:10.1007/s00405-022-07270-5
meta-analysis. Drugs. 2020;80(17):1831-1851. doi: 53. Drazdauskaitė G, Layhadi JA, Shamji MH.
10.1007/s40265-020-01406-9 Mechanisms of allergen immunotherapy in allergic
rhinitis. Curr Allergy Asthma Rep. 2020;21(1):2.
47. Gómez RM, Moreno P, Compalati E, Canonica doi:10.1007/s11882-020-00977-7
GW, Ansotegui Zubeldia IJ. Update meta-analysis

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