3. Allergic Rhinitis
■ Allergic rhinitis (AR) is an inflammatory disorder of the nasal
mucosa marked by the following:
– Sneezing
– Rhinorrhea
– Nasal congestion
– Nasal pruritus, often accompanied by conjunctival and
pharyngeal itching; and lacrimation
4. Allergic Rhinitis
■ Children with AR often have conjunctivitis, sinusitis, otitis media,
serous otitis, hypertrophic tonsils and adenoids, and eczema
■ A 3-fold increase in risk for asthma at an older age
■ The symptoms may appear in infancy
– Diagnosis generally established by the time the child reaches
age 6 yr
– The prevalence peaks late in childhood
■ Risk factors include family history of atopy and serum IgE higher
than 100 IU/mL before age 6 yr
5. Allergic Rhinitis
ETIOLOGY and CLASSIFICATION
■ Two factors necessary for expression of AR
– Sensitivity to an allergen
– Presence of the allergen in the environment
■ AR classification
– Seasonal or Perennial
– Intermittent and Persistent
■ Inhalant allergens are the main cause of all forms of AR,
irrespective of terminology
8. Allergic Rhinitis
Clinical Manifestations
■ Typical complaints include intermittent nasal congestion, itching, sneezing, clear
rhinorrhea, and conjunctival irritation.
– Symptoms increase with greater exposure to the responsible allergen
■ Children with AR often perform the allergic salute
– an upward rubbing of the nose with an open palm or extended index finger.
This maneuver relieves itching and briefly unblocks the nasal airway It also
gives rise to the nasal crease , a horizontal skin fold over the bridge of the
nose.
allergic salute nasal crease
10. Allergic Rhinitis
Complications
■ Chronic sinusitis is a common complication
■ Rhinitis that coexists with asthma may be taken too lightly or completely
overlooked
– Up to 78% of patients with asthma have AR
– 38% of patients with AR have asthma
– Aggravation of AR coincides with exacerbation of asthma, and treatment of
nasal inflammation reduces bronchospasm, asthma- related emergency
department visits, and hospitalizations.
■ Postnasal drip associated with AR commonly causes persistent or recurrent cough
■ Eustachian tube obstruction and middle ear effusion are frequent complications.
■ Chronic allergic inflammation causes hypertrophy of adenoids and tonsils
13. Allergic Rhinitis
■ Oral antihistamines help reduce sneezing, rhinorrhea, and ocular symptoms.
– Classified as:
■ First generation (relatively sedating)
– brompheniramine, chlorpheniramine, triprolidine, diphenhydramine
■ Second generation (relatively nonsedating) - preferred because they cause less
sedation
– desloratadine, loratadine, cetirizine, levocetirizine, fexofenadine
■ Preparations containing pseudoephedrine, typically in combination with other
agents
– Used for relief of nasal and sinus congestion and pressure and other
symptoms such as rhinorrhea, sneezing, lacrimation, itching eyes,
oronasopharyngeal itching, and cough.
14. Allergic Rhinitis
■ Intranasal decongestants (oxymetazoline and phenylephrine)
– Used for <5 days and should not to be repeated more than once a month to
avoid rebound nasal congestion
■ Sodium cromoglycate
– Effective but requires frequent administration, every 4 hr
■ Leukotriene-modifying agents
– modest effect on rhinorrhea and nasal blockage
– Montelukast
■ Nasal saline irrigation
– A good adjunctive option with all other treatments of AR
15. Allergic Rhinitis
■ Intranasal corticosteroids
– More persistent, severe symptoms require
– The most effective therapy for AR, which may also be beneficial
for concomitant allergic conjunctivitis
– Beclomethasone, triamcinolone, and flunisolide, budesonide,
fluticasone, mometasone, and ciclesonide
■ More severely affected patients may benefit from simultaneous
treatment with oral antihistamines and intranasal corticosteroids
16. Allergic Rhinitis
■ Allergy immunotherapy (AIT)
– An effective treatment for AR and allergic conjunctivitis
– In addition to reducing symptoms, it may change the course of
allergic disease and induce allergen-specific immune tolerance.
– It should be considered for children in whom IgE-mediated allergic
symptoms cannot be adequately controlled by avoidance and
medication, especially in the presence of comorbid conditions.
– Immunotherapy for AR prevents the onset of asthma.
■ Omalizumab (anti- IgE antibody)
– effective for difficult-to-control asthma and is likely to have a
beneficial effect on coexisting AR.
18. Atopic dermatitis
■ Atopic dermatitis (AD) , or eczema, is the most common chronic
relapsing skin disease seen in infancy and childhood
– Affects 10–30% of children worldwide
– Frequently occurs in families with other atopic diseases
19. Atopic Dermatitis
Infants with AD are predisposed to development of food
allergy, allergic rhinitis, and asthma later in childhood,
a process called the atopic march
20. Atopic Dermatitis
■ Etiology
– AD is a complex genetic disorder that results in a
defective skin barrier, reduced skin innate immune
responses, and polarized adaptive immune
responses to environmental allergens and microbes
that lead to chronic skin inflammation
21. Atopic Dermatitis
Pathogenesis
■ Atopic eczema
– IgE-mediated sensitization
– Occurs in 70–80% of patients with AD
– produce increased levels of T-helper
type 2 (Th2) cytokines - IL-4 and IL-
13 which induce isotype switching to
IgE synthesis
– IL-5, plays an important role in
eosinophil development and survival
– + Eosinophilia
■ Nonatopic eczema
– not associated with IgE-mediated
sensitization
– seen in 20–30% of patients with AD
– Lower IL-4 and IL-13 but increased
IL-17 and IL-23 production than in
atopic eczema.
– + Eosinophilia
22. Atopic Dermatitis
Pathogenesis
■ Unaffected and Acute skin
lesions:
– Increased number of cells
expressing IL-4 and IL-13
■ Chronic AD skin lesions:
– Fewer cells that express IL-4
and IL-13
– Increased numbers of cells
that express IL-5,
granulocyte-macrophage
colony-stimulating factor, IL-
12, and interferon (IFN)-γ
– Infiltration of IL-22–expressing
T cells
■ correlates with severity of AD
■ blocks keratinocyte
differentiation
■ induces epidermal
hyperplasia
23. Atopic Dermatitis
Pathogenesis
■ Severely dry skin is a hallmark of
AD
– A compromise epidermal
barrier trans-epidermal
water loss, allergen
penetration, and microbial
colonization.
– Filaggrin , a structural
protein in the epidermis, and
its breakdown products are
critical to skin barrier
function, including
moisturization of the skin.
■ Genetic mutations in the
filaggrin gene (FLG) family
have been associated with
24. Atopic Dermatitis
Diagnosis
Clinical Features of Atopic Dermatitis
Major Features
• Pruritus
• Facial and extensor eczema in infants and children flexural eczema in adolescents
• Chronic or relapsing dermatitis
• Personal or family history of atopic disease
Associated Features
• Xerosis
• Cutaneous infections (Staphylococcus aureus, group A streptococcus,
• herpes simplex, coxsackievirus, vaccinia, molluscum, warts)
• Nonspecific dermatitis of the hands or feet Ichthyosis, palmar hyperlinearity, keratosis pilaris
• Nipple eczema
• White dermatographism and delayed blanch response Anterior subcapsular cataracts,
keratoconus
• Elevated serum IgE levels
• Positive results of immediate-type allergy skin tests Early age at onset
• Dennie lines (Dennie-Morgan infraorbital folds)
• Facial erythema or pallor
• Course influenced by environmental and/or emotional factors
25. Infants (0-2 years)
-Extensor surfaces of extremities
-Face (forehead, cheeks, chin)
-Neck, scalp, trunk
Childhood (2 years to puberty)
-Flexural surfaces of extremities
-Neck
-Wrists, ankles
Adolescence/Adulthood
-Flexural surfaces of extremities
-Hands, feet
AGE-RELATED CLINICAL
PICTURE
26. Atopic Dermatitis
Treatment
■ Cutaneous Hydration – due to impaired skin barrier and xerosis
– Moisturizers are first-line therapy
■ Topical Corticosteroids
– Topical corticosteroids are the cornerstone of
antiinflammatory treatment for acute exacerbations of AD
28. Atopic Dermatitis
Treatment
■ Topical Calcineurin Inhibitors
– The nonsteroidal topical calcineurin inhibitors:
■ Pimecrolimus cream 1% (Elidel) is indicated for mild to moderate AD
■ Tacrolimus ointment 0.1% and 0.03% (Protopic) is indicated for moderate to
severe AD.
– Approved for short-term or intermittent long-term treatment of AD in
patients ≥2 yr whose disease is unresponsive to or who are intolerant of
other conventional therapies
■ Antihistamines
– Reduces histamine-induced pruritus
– Since pruritus is usually worse at night, sedating antihistamines (hydroxyzine,
diphenhydramine) may offer an advantage when used at bedtime.
29. Atopic Dermatitis
Treatment
■ Systemic Corticosteroids
– Rarely indicated in the treatment of chronic AD
– Short courses of oral corticosteroids may be appropriate for an acute
exacerbation
■ Cyclosporine
– potent immunosuppressive drug that acts primarily on T cells by
suppressing cytokine gene transcription
■ Dupilumab
– monoclonal antibody that binds to the IL-4 receptor α subunit
■ Antimetabolites
– Mycophenolate mofetil, Azathioprine
30. Atopic Dermatitis
Complications
■ Exfoliative Dermatitis
– Extensive skin involvement
– Associated with generalized redness, scaling, weeping, crusting,
systemic toxicity, lymphadenopathy, and fever and is usually
caused by superinfection (e.g., with toxin-producing S. aureus or
HSV infection)
■ Atopic keratoconjunctivitis is usually bilateral and can have disabling
symptoms that include itching, burning, tearing, and copious mucoid
discharge
■ Keratoconus is a conical deformity of the cornea believed to result
from chronic rubbing of the eyes in patients with AD
31. Atopic Dermatitis
Prognosis
■ AD generally tends to be more severe and persistent in young children
– Those with null mutations in their filaggrin genes
■ Periods of remission occur more frequently as patients grow older
■ Spontaneous resolution of AD has been reported to occur after age 5 yr in 40–60%
of patients affected during infancy, particularly for mild disease.
■ Of those adolescents treated for mild dermatitis, >50% may experience a relapse
of disease as adults, which frequently manifests as hand dermatitis
■ Predictive factors of a poor prognosis
– widespread AD in childhood, FLG null mutations, concomitant allergic
rhinitis and asthma, family history of AD in parents or siblings, early age at
onset of AD, being an only child, and very high serum IgE levels
33. Urticaria and Angioedema
■ Urticaria - also known as hives
■ Pruritic, erythematous papules or plaques, with
superficial swelling of the dermis
■ Acute urticaria : < 6weeks duration
■ Chronic urticaria (CU) : > 6weeks duration
■ 10% have angioedema as their main
manifestation
34. Urticaria and Angioedema
■ Angioedema manifests itself as deeper
subcutaneous swelling
■ If tissue distention involves sensory nerves,
angioedema lesions may be painful or paresthetic
■ May occur with or without urticaria
■ If it involves the upper respiratory tract, life-
threatening obstruction of the laryngeal airway may
occur
– Particularly prone - hereditary or acquired
angioedema associated with C1 esterase
deficiency.
35. DIAGNOSIS
■ The goal is:
1) Identify urticaria type and subtype
2) Identify underlying causes
A detailed history of the circumstances preceding and
surrounding the onset of the condition is necessary
36.
37. DIAGNOSIS
Etiology
■ Food allergies
■ Medications: aspirin or other nonsteroidal anti-inflammatory drugs
(NSAIDs), hormones, antibiotics, herbals, supplementations
■ Physical factors such as pressure can exacerbate skin manifestations,
which include dermographism
■ Infections
■ Other immune diseases
– The presence (both recent and remote) of systemic signs and
symptoms such as fever, weight loss, and arthralgias also should
be ascertained
39. DIAGNOSIS
Laboratory Assessments
■ Complete blood count with differential
– Assess for eosinophilia
■ CRP or erythrocyte sedimentation ate (ESR)
– Identify the risk of underlying rheumatic disease
■ Thyroid-stimulating hormone (TSH) level, thyroid autoantibodies
■ Specific testing for drug allergy
– Removal of suspected offending drugs can be attempted, or
replacement with another class of compound can be tried.
46. ■ Acute urticaria occurs in up to 20% of the population and maybe
associated with a drug or food allergy, or with infection. It
generally is self-limited.
■ Chronic urticaria occurs in up to 1% of the population, and in
most cases, lesions are spontaneous without an identifiable
external trigger. One theory is that in a subset of patients, an
autoimmune process predisposes them to the disease.
■ Urticaria should be managed by elimination of trigger factors,
followed by symptomatic treatment with non-sedating
antihistamines. The diagnosis is made on clinical grounds.
56. DIAGNOSIS
■ Serum tryptase
– β-tryptase : best measured 1 and 2 hours, but no
longer than 6 hours after the onset of symptoms
■ Histamine
– Plasma histamine : measure between 10 minutes
and 1 hour after onset of symptoms
58. MANAGEMENT
■ Epinephrine 1:1000 - mainstay of therapy
– Children :
■ 0.01mg/kg / IM
– Adults :
■ 0.3 to 0.5 ml / IM
■ The initial dose can be repeated 2-3x as
needed at 5-15 minute interval
■ SEVERE HYPOTENSION – IV epinephrine
– Sublingual route: if iv access cannot be obtained
– Endotracheal route
59. MANAGEMENT
■ Antihistamine
– Adjunctive therapy
– Relief of itching and urticaria
– A combination of H1 and H2 antagonist (Ranitidine) is superior
to an H1 antagonist alone
■ Corticosteroids
■ Aerosolized Beta-adrenergic agents
– Wheezing unresponsive to epinephrine
■ Fluid therapy hypotension
– Crystalloid or colloids
60. MANAGEMENT
■ Patients may experience biphasic anaphylaxis
– When anaphylactic symptoms recur after apparent
resolution
– Unknown mechanism
– More than 90% of biphasic responses occur within 4 hr,
so patients should be observed for at least 4 hr
before being discharged from the emergency
department
61. Preventive Treatment
• Prescription for epinephrine autoinjector and antihistamine
• Provide written plan outlining patient emergency
management
• Follow-up evaluation to determine/confirm etiology
• Immunotherapy for insect sting allergy
Patient Education
• Instruction on avoidance of causative agent
• Information on recognizing early signs of anaphylaxis
• Stress early treatment of allergic symptoms to avoid
systemic anaphylaxis
• Encourage wearing medical identification jewelry
63. ADVERSE DRUG
REACTIONS
A-type
(dose dependent &
predictable)
Toxicity Side effects
Interaction
with other
drugs
B-type
(dose independent &
unpredictable)
Hypersensitivity
Allergy
Specific IgE
Cytotoxic
Reactions
Immune
Complexes
T-cells
Non-Allergic
reactions
Pseudoallergy Intolerance Idiosyncracy
64.
65. Organ specific
reactions
Clinical features Examples of causative
agents
Multiorgan Reactions
Anaphylaxis Urticaria/angioedema,
bronchospasm, gastrointestinal
symptoms, hypotension IgE- and
non–IgE-dependent reactions
β-Lactam antibiotics, monoclonal
antibodies
Drug rash with eosinophilia and
systemic symptoms (DRESS)
Cutaneous eruption, fever,
eosinophilia, hepatic dysfunction,
lymphadenopathy
Urticaria, arthralgias, fever
Arthralgias, myalgias, fever, malaise
Cutaneous or visceral vasculitis
Anticonvulsants, sulfonamides,
minocycline, allopurinol
Serum sickness Urticaria, arthralgias, fever Heterologous antibodies, infliximab
Systemic lupus erythematosus Arthralgias, myalgias, fever, malaise Hydralazine, procainamide, isoniazid
Vasculitis Cutaneous or visceral vasculitis Hydralazine, penicillamine,
propylthiouracil
66. Drug Allergy
Pathogenesis
Gell and Coombs Classifications:
• Type I – Immediate
hypersensitivity
reactions
• Type II – Cytotoxic antibody
reactions
• Type III – Immune complex
reactions
• Type IV - Delayed-type
hypersensitivity
reactions
67. Risk Factors for Hypersensitivity
Reactions
■ Prior exposure
■ Previous reactions
■ Age (20-49 yr)
■ Route of administration (parenteral or topical)
■ Dose (high)
■ Dosing schedule (intermittent)
■ Genetic predisposition (slow acetylators).
Atopy does not appear to predispose patients to allergic reactions to low-
molecular-weight compounds, but atopic patients in whom an allergic reaction
develops have a significantly increased risk of serious reaction.
Atopic patients also appear to be at greater risk for pseudoallergic reactions
induced by radiocontrast media.
68. Diagnosis
■ An accurate medical history is an important first step
– Suspected drugs need to be identified
■ Dose
■ Route of administration
■ Previous exposures
■ Dates of administration
69. Diagnosis
■ Skin testing
– the most rapid and sensitive method of
demonstrating the presence of IgE antibodies to a
specific allergen
– Reliable skin testing can also be performed with
penicillin, but not with most other antibiotics
■ Major determinant of penicillin testing reagent
benzylpenicilloyl polylysine (Pre- Pen) is available in the
United States
– Most immunologically mediated ADRs are caused by
metabolites rather than by parent compounds
70. Diagnosis
■ Patch testing
– is the most reliable technique for diagnosis of contact
dermatitis caused by topically applied drugs
■ Graded challenge
– The drug is given in an incremental fashion dosed faster
than used for desensitization (see later) until a
therapeutic dose is achieved.
– A means to prove that the drug is tolerated or to
identify an adverse or allergic reaction
71. Drug Allergy
Treatment
■ Specific desensitization
– progressive administration of an allergen to render effector
cells less reactive
– reserved for patients with IgE antibodies to a particular drug
for whom an alternative drug is not available or appropriate
– Performed in a hospital setting, usually in consultation with
an allergist and with resuscitation equipment available at all
times
72. ■ β-Lactam Hypersensitivity
– Penicillin is a frequent cause of anaphylaxis and is responsible for the
majority of all drug-mediated anaphylactic deaths in the United States.
– Varying degrees of in vitro cross-reactivity have been documented
between cephalosporins and penicillins.
■ Cross-reactivity is most likely when the cephalosporin shares the same side
chain as the penicillin
■ Red Man Syndrome
– nonspecific histamine release
– most often described with administration of IV vancomycin
– It can be prevented by slowing the vancomycin infusion rate or by
preadministration of H1 -receptor blockers
73. Vaccines
■ Measles-mumps-rubella (MMR) vaccine has been shown to be safe in
egg- allergic patients (although rare reactions to gelatin or neomycin
can occur)
■ The ovalbumin content in influenza vaccine is extremely low
– Egg-allergic patients do not appear to be at higher risk of reacting
to the influenza vaccine than those without egg allergy
– They may receive it in the usual manner with the same 15-min
waiting period suggested for other vaccinations and in a medical
setting prepared to treat anaphylaxis.
80. Food Allergy
Clinical Manifestations
■ Respiratory symptoms
– Uncommon as isolated symptoms
– Food-induced rhinoconjunctivitis consist of typical allergic rhinitis
symptoms (periocular pruritus and tearing, nasal congestion and
pruritus, sneezing, rhinorrhea)
■ Anaphylaxis
– a serious, multisystem allergic reaction that is rapid in onset and
potentially fatal
– Food-dependent exercise-induced anaphylaxis occurs more frequently
among teenage athletes
81. Food Allergy
Diagnosis
■ A thorough medical history
■ The following facts should be established:
(1) the food suspected of provoking the reaction and the
quantity ingested
(2) the interval between ingestion and the development of
symptoms
(3) the types of symptoms elicited by the ingestion
(4) whether ingesting the suspected food produced similar
symptoms on other occasions
(5) whether other inciting factors, such as exercise, are
necessary
(6) the interval from the last reaction to the food
83. Food Allergy
Diagnosis
■ There are no laboratory studies to help identify foods responsible for cell-
mediated reactions
■ Elimination diets followed by oral food challenges are the only way to
establish the diagnosis.
– Before a food challenge is initiated, the suspected food should be
eliminated from the diet
■ IgE-mediated food allergy - 10-14 days
■ Some cell-mediated disorders, such as EoE - Up to 8 wks
If symptoms remain unchanged despite appropriate elimination diets, it is
unlikely that food allergy is responsible for the child's disorder
85. Food Allergy
Prevention
■ Breastfeed exclusively for 4-6 mo.
■ Introduce solid (complementary) foods after 4-6 mo of exclusive
breastfeeding.
■ Introduce low-risk complementary foods 1 at a time.
■ Introduce potentially highly allergenic foods (fish, eggs, peanut, milk, wheat)
soon after the lower-risk foods (no need to avoid or delay). Infants with early-
onset atopic disease (e.g., severe eczema) or egg allergy in the 1st 4-6 mo of
life.
■ Do not avoid allergenic foods during pregnancy or nursing.
■ Soy-based formulas do not prevent allergic disease.
