Ricky Yue , M.D.

Allergic Rhinitis Dept of ENT-HNS

School of Medicine, Atma Jaya
Catholic University of Indonesia
Lisa M. Wheatley, M.D., M.P.H. and Alkis Togias, M.D.
Allergy, Asthma, and Airway Biology Branch, Division of Allergy, Immunology, and
Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of

CASE 1
Health, Bethesda, MD

Abstract
A 35-year-old woman has a history of nasal congestion on most days of the year, dating back to
her late teens. She has chronic nasal drainage, which is clear and thick. Her congestion is worst in
the late summer and early fall and again in the early spring; at these times, she also has sneezing,
nasal itching, and cough. Five years ago, she had an episode of shortness of breath with wheezing
on a day when her nasal symptoms were severe, but this episode resolved spontaneously and has
not recurred. Her eyes do not bother her. Over-the-counter oral antihistamines help her symptoms
a little, as do nasal decongestants, which she uses occasionally. Her 6-year-old son has similar
symptoms. How should this case be managed?

THE CLINICAL PROBLEM

Allergic rhinitis is defined as symptoms of sneezing, nasal pruritus, airflow obstruction, and
mostly clear nasal discharge caused by IgE-mediated reactions against inhaled allergens and
involving mucosal inflammation driven by type 2 helper T (Th2) cells.1 Allergens of
importance include seasonal pollens and molds, as well as perennial indoor allergens, such
as dust mites, pets, pests, and some molds. The pattern of dominant allergens depends on the
Tumor, neoplasm nonallergic) or chronic sinusitis, and virtually all patients who complain of
Foreign body “sinus headaches” suffer from atypical migraines or other headache syn-
Cerebrospinal fluid leak dromes.5 Atypical migraines routinely produce headaches that occur in a
Atrophic (postsurgical or trauma) bilateral distribution involving the maxillary or ophthalmic branches of the

Approach to the Patient with Sneezing or Rhinorrhea

Intermittent Perennial

Sporadic Seasonal Nasal/palatal pruritus Nasal congestion

Purulent rhinorrhea
Irritant symptoms
(sore throat, pain, HA)
Nasal/palatal pruritus Paroxysmal sneezing Posterior pharyngeal drainage
Ocular symptoms Clear rhinorrhea
Paroxysmal sneezing
Clear rhinorrhea
Facial fullness/pressure Nasal No nasal polyps
“Sinus” headache polyps Minimal pruritus/sneezing
No headache
Specific IgE Specific IgE
No specific IgE
(prick skin test or (prick skin test or
IgE immunoassay) IgE immunoassay)
Nasal smear

No
Eosinophils
eosinophils

Rhinoscopy Rhinoscopy
or CT scan or CT scan

Normal Abnormal Abnormal Normal

Viral rhinitis SAR PAR Migraines Chronic sinusitis NARES Vasomotor

rhinitis

FIGURE 251-1. Approach to the patient with rhinitis symptoms. CT = computed tomography; HA = headache; IgE = immunoglobulin E; NARES = nonallergic rhinitis with eosino-
philia syndrome; PAR = perennial allergic rhinitis; SAR = seasonal allergic rhinitis.

The Rhinitis Universe
Immunol Allergy Clin N Am 36 (2016)
TABLE 251-2 DIFFERENTIAL DIAGNOSIS OF RHIN
ALLERGIC
Seasonal allergic rhinitis (SAR)
Perennial allergic rhinitis (PAR)
INFLAMMATORY
Infectious rhinitis (viral)
Nonallergic rhinitis with eosinophilia syndrome (NARES)
Chronic sinusitis with or without nasal polyposis
Laryngopharyngeal reflux
HORMONAL
Pregnancy, oral contraceptives, perimenopause
Hypothyroidism
Hyperthyroidism
RHINITIS MEDICAMENTOSA
Topical or, less commonly, oral decongestants
Antihypertensives
Antidepressants
Cocaine
VASOMOTOR
Irritant induced (pollution, cigarette smoke)
Cold air induced
Gustatory (food induced)
ANATOMIC
Nasal septal deviation
Tumor, neoplasm
Foreign body
Cerebrospinal fluid leak
Atrophic (postsurgical or trauma)
 What is allergic rhinitis?
• Clinical hypersensitivity of the nasal mucosa to
foreign substances mediated through IgE
antibodies.
• The prevalence is higher in children and
adolescents than in adults.
• Rarely in children younger than 2 years.
• Most have symptoms before age 20 years.

Flint,PW, Haughey BH, Lund V. Cummings Otolaryngology Head and Neck Surgery. 6th Ed. Elvesier.
 Risk Factors
• A family history of allergic rhinitis increases the
odds that a child will have the disease
• Atopy
• A history of asthma

Flint,PW, Haughey BH, Lund V. Cummings Otolaryngology Head and Neck Surgery. 6th Ed. Elvesier.
 Burden of Disease
• The 16th most common primary diagnosis for outpatient
office visits
• Poorly controlled : sleep loss or disturbance, increased
daytime sleepiness, children’s learning problems in
school
• The financial impact associated with the management of
AR

Flint,PW, Haughey BH, Lund V. Cummings Otolaryngology Head and Neck Surgery. 6th Ed. Elvesier.
2015.
Pathophysiology
270 AHMAD & ZACHAREK
Pathophysiology ALLERGIC RHINITIS AND RHINOSINUSITIS 271

Fig. 2. The early and late phase responses in allergic rhinitis. Pathophysiology of allergic in-
falmmation: clinical disease. (Adapted from Gwaltney JM Jr, Jones JG, Kennedy DW. Medical
 Sensitization and IgE Production
Initial stage :
Low-dose exposure leads to the
production of specific IgE antibodies

Antigen is engulfed by APCs and is partially

degraded within their phagolysosomes, then got
recognized by helper T cells and class II MHC
molecules.
 Sensitization and IgE Production

IL-1 activated TH2CD4+ then secrete cytokines

IL-4, IL-5, IL-13, which are all central to :
• Production of IgE
• Recruitment and survival of eosinophils at site

Antigen-specific IgE attaches to high-affinity

receptors on other cells à sensitizing the nasal
mucosa.
 Early Allergic Response
Cross-linking of adjacent IgE molecules on mast
cells leads to the release of inflammatory mediators
that stimulate nerves, glands, and blood vessels
sneezing, pruritus, rhinorrhea, nasal obstruction

Happens within minutes after exposure of

allergen
 Early Allergic Response
• Physiologic changes measured after antigen
provocation
• Increases in the levels of :
– Histamine
– Kinins
– Tryptase
– PGD2
– Leukotriene C4 and B4
– Platelet activating factors
 Late Allergic Response
Hours after antigen challenge à recurrence of
symptoms

• Chemotaxis and Migration of neutrophils,

basophils, eosinophils, T-lymphocytes, and
macrophages across the mucosal endothelium
into the nasal submucosa
• Elevations in nasal airway resistance 4 – 10
hours after antigen challenge (peak around 6
hours and resolution by 24 hours)
 Late Allergic Response
The effects of TH2 cytokines are all conductive to
the promotion of allergic inflammation :
• IL-5 promotes the differentiation, vascular adhesion,
and in vitro survival of eosinophils and enhances histamin
release from basophils
• IL-4 is a mast cell growth factor (B cells à IgE
production)
• IL-13 induces eosinophil recruitment, mucus
hyperproduction, airway hyperesponsiveness
 moderate-to-severe persistent seasonal rhinitis in June and July and be suitable
wa
PATHOGENESIS
for specific allergen immunotherapy. Reprinted from reference 25, with
permission of Wiley. lea
po
Allergen 2m
Viruses
Pollution Th
Cigarette smoke eve
Allergen: subsequent contact
TLRs
as
TSLP↑ Nasal epithelium pe
Allergen-specific IgE MC
age
OX40L↑
Immediate reaction if a
Histamine Sneeze
DC Sensitisation Leukotrienes Itch sh
Prostaglandins, Run foc
etc Blockage
B fun
Th₂ IL4 B
IL13
B tha
LN B
PC
qu
S
IL5 Late-phase reaction to
Blockage
Hyper-reactivity
ph
Hyposmia of
Eosinophils on
Neutrophils
Lymphocytes
Cla
Figure 2: Pathogenesis of allergic rhinitis Adapted from The Lancet 2016 All
Evaluation and Diagnosis
Clinical diagnosis of AR when patients present
with a history and physical examination
consistent with an allergic cause and ≥1 of the
classical symptoms :
Nasal congestion
Runny nose
Pale discoloration of the nasal mucosa
Red and watery eyes

AAO-HNS. Clinical Practice Guideline : Allergic Rhinitis. 2015. Vol. 152(IS) S1-S43.
 History
• Itching • Eustachian tube
Nose, palate, throat, eyes, dysfunction
ears Ear popping and clicking
• Rhinorrhea • Systemic symptoms
Clear, anterior à sniffing General malaise, fatigue,
and nose blowing, posterior irritability, snoring, sleep
à snorting, throat problems
clearing, postnasal drip • Family history of allergic
• Nasal obstruction diseases
• Ocular symptoms Allergic rhinitis, asthma,
Itching, tearing, conjunctival atopic dermatitis
infection

Flint,PW, Haughey BH, Lund V. Cummings Otolaryngology Head and Neck Surgery. 6th Ed. Elvesier.
 Classification
• Seasonal
Exposure to seasonal allergens (ragweed, grasses,
pollens)
• Perennial
More than 2 hours per day for more than 9 months per
year
Develop to house mites, indoor molds, animal dander
• Episodic
Exposure to allergens not normally present in the
enoirment (cat allergy)
WHO. Allergic Rhinitis and its Impact on Asthma 1st Edition. 2007.
 Physical Examination
• Allergic shiners
periorbital cyanosis and
puffiness of the eyelids
Dennie-Morgan lines
• Adenoid facies
• Allergic salute
frequent pushing upward of
the nasal tip
• Allergic crease
supratip crease at the junction
of the upper and lower lateral
cartilages
 Physical Examination
• Inferior turbinates are pale, bluish,
edematous, and coated with thin, clear
secretions
• Complete ENT examination
 Diagnostic Tests
• Skin testing • Serum levels of
– Puncture skin tests specific IgE antibodies
– Intradermal tests
Confirmation Test : Skin Prick Test / Allergen-specific Ig E
Diagnosing Allergic Rhinitis
( Based on symptoms)

Courtesy of ARIA 2008

 Treatment Options
From the evidence point of view
❖ Patient’s Education
❖ Allergen Avoidance
❖ Medical treatment
❖ Surgical Treatment
❖ Complimentary Medicine
 Allergen Avoidance
❖ Not all irritants can be avoided, newer technology in allergen prevention is not an
answered. “Possible but not mandatory”
❖ Allergen level is not directly proportional w/ patient’s symptoms.
In ARIA 2010 revision recommendation :
❖ The clinician DO NOT administer and patients DO NOT use currently available single
chemical or physical preventive methods aimed at reducing exposure to house dust mites
(strong recommendation / low-quality evidence) or their combination (conditional
recommendation / very low-quality evidence).
❖ Avoiding indoor Molds at home (conditional recommendation / very low-quality evidence).
❖ Avoiding animal dander (strong recommendation / very low-quality evidence)
❖ Immediate and total cessation of exposure to occupational allergen (strong
recommendation / very low- quality evidence). If not possible-> need specific strategies aimed
at minimizing occupational allergen exposure (conditional recommendation / very low-quality
evidence).
STATEMENT 4. ENVIRONMENTAL FACTORS: Clinicians may advise avoidance of
known allergens or may advise environmental controls (eg, removal of pets; the use of
air filtration systems, bed covers, and acaricides [chemical agents that kill dust mites])
in AR patients who have identified allergens that correlate with clinical symptoms.
Option based on RCTs with minor limitations and observational studies, with equilibrium of
benefit and harm.

CPG Allergic Rhinitis, AAOHNS, 2015

 356 Medical Treatment KROUSE

❖ Based
Fig. 1. on severity
Mechanism of AR
of action & symptom
of allergy based
medications. (From Marple BF, Fornadley JA, Patel AA,
et al. Keys to successful management of patients with allergic rhinitis: focus on patient confidence,
❖ single / appropriate
compliance, combination
and satisfaction. treatment
Otolaryngol Head Neck Surg 2007;136:S112; with permission.)

❖ Step up &been
generally stepunsuccessful
down therapyin demonstrating a significant benefit in patients
with rhinitis [23].
 Symptom-Based Treatment
ALLERGIC RHINITIS–PHARMACOTHERAPY 357

Table 3
Pharmacological properties of common medication classes
Agent Sneezing Itching Congestion Rhinorrhea Eye symptoms
Oral antihistamines þþþ þþþ # þþ þþþ
Nasal antihistamines þþ þþ þþ þ $
Intranasal corticosteroids þþ þþ þþþ þþ þ
Leukotriene modifiers þ þ þ þ þ
Oral decongestants $ $ þþþ $ $
Nasal decongestants $ $ þþþ $ $
Nasal mast-cell stabilizers þ þ # þ $
Topical anticholinergics $ $ $ þþþ $
þþþ, marked benefit; þþ, substantial benefit; þ, some benefit; #, questionable benefit;
$, no benefit.

In addition, consideration of the Otolaryngol Clin N Am

pharmacological 41 (2008) 347–358
properties of various
medication classes can assist in choosing agents for treating individual
symptoms (Table 3). Because medications do not all share similar profiles
 Evidences Summary on Medical Treatment
ARIA 2010 AAOHNS 2015
Recommendation Recommendation
New generation AH1 Strong Strong

Intra-nasal AH1 Conditional ( against PAR) Option

Conditional (SAR & PAR

LTRAs children ), Against -> adult Against
PAR
Strong ( adult ), Conditional
Intra-nasal CS Strong
( Children )

Oral CS Conditional (-) Short course

Ipratropium Bromide Conditional (-) rhinorrhea

INCS + AH1 Against Against

severe , uncontrolled w/ single
INCS + INAH1 Option agent

AH1 + Decongestant Conditional Option observe side effect

AH1 + LTRAs Option

INCS + LTRAs Against

Immunotherapy Conditional Recommendation no response w/ all medical th/

 Topical Steroids
• Triamnicolone
acetonide
• Budesonide
• Flunisolide
• Fluticasone propionate
• Mometasone furoate • Age 2-11 yo
1 spray per nostril everyday
• Ciclesonide
• Age ≥12 yo
• Fluticasone furoate 2 spray per nostril everyday
 Oral Antihistamines
• Cetirizine
– Age 2-5 y : 1-2 x 2.5 mg/day
– Age 6-12 y : 5-10 mg/day
– Age 12-65 y : 10 mg/day
• Loratadine
– Age 2-5 y : 5 mg/day
– Age ≥6 y : 10 mg/day
• Levocetirizine
• Fexofenadine
• Desloratadine
 “The Purpose of a doctor or any human in
general should not be to simply delay the death
of the patient, but to increase the person’s quality
of life “
= Patch Adams =

THANK YOU FOR YOUR

ATTENTION
 CASE
• 21 y.o female comes to your office with chief complaint of
sneezing every morning since 5 weeks ago. Pt also
complaining runny nose and nasal blockage that persist
approximately 2-3 hours every day. No limitation from
activity and sleep. these symptoms not associated with
fever, facial pain and loss of smell.
• No personal and family history of asthma
• Menstrual period regular
• Social history is unremarkable
• Medical history also unremarkable
• Pt feels the symptoms more severe since her family get a
pet from her father’s relatives.
Pathophysiology
• Early response
• Neuronal contribution
• Late response to allergen
• Cellular events
• Adhesion molecules and cellular recruitment
• Hyperresponsiveness
 Cellular Adhesion and Recruitment

Flint,PW, Haughey BH, Lund V. Cummings Otolaryngology Head and Neck Surgery. 6th Ed. Elvesier.
 Hyperresponsiveness
• Specific (Priming)
Shift in threshold of responsiveness à worsening of
symptoms as the allergy season progresses

• Non-specific
Increased reactivity to irritant stimuli