Allergic Disorders in Children

Dr Faten Zaidan

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Allergy Assessment & Hypersensitivity

Gell and Coombs Classification

Table 77.1: Gell and Coombs Classification of Hypersensitivity Disorders

TYPE	INTERVAL BETWEEN EXPOSURE AND REACTION	EFFECTOR MOLECULE	TARGET OR ANTIGEN	EXAMPLES OF MEDIATORS	EXAMPLES
I Immediate (Late phase)	<30 min (2-12 hr Acute response)	IgE	Pollens, food, venom, drugs	Histamine, tryptase, leukotrienes, prostaglandins, platelet-activating factor	Anaphylaxis, urticaria, allergic rhinitis, allergic asthma
II Cytotoxic antibody	Variable (min-hr)	IgM, IgG, IgA	Red blood cells, platelets	Complement	Hemolytic anemia, thrombocytopenia, Goodpasture syndrome
III Immune complex	1-3 wk after drug exposure	Antigen-antibody complexes	Blood vessels, liver, spleen, kidney, lung	Complement, anaphylatoxin	Serum sickness, hypersensitivity pneumonitis
IV Delayed type	2-7 days after drug exposure	Lymphocytes	Mycobacterium tuberculosis, chemicals	Cytokines (IFN-γ, TNFα, GM-CSF)	TB skin test reactions, contact dermatitis, graft-vs-host disease

• Abbreviations: GM-CSF, Granulocyte-macrophage colony-stimulating factor; IFN-γ, interferon-γ; TB, tuberculosis; TNFα, tumor necrosis factor-α.

Table 16.2: Hypersensitivity reactions (Gell-Coombs classification) and how these relate to inappropriate hypersensitive responses

Type 1 Hypersensitivity Reactions

• The classic allergies are type 1 hypersensitivity reactions.
• Examples: urticarial, allergic rhinitis, allergic asthma, reactions to insect stings, drugs such as penicillin, allergy to food such as wheat, eggs, milk, peanuts and seafood.
• Mechanism: Symptoms are mainly caused by mediators which are histamine, leukotrienes and cytokines; released by mast cell degranulation. This reaction is mediated by IgE antibodies.

Histamine Receptors and Effects:

H receptor	What does it cause?
H1	Wheal, bronchoconstriction, pruritus
H2	Increased gastric acid secretion
H3	Decreased histamine synthesis and release
H4	Creates a chemotactic pathway for eosinophils

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Diagnostic Approach

Following a focused history, the following lab tests will help in identifying the cause of allergy:

1. Skin Prick Testing

• Usually the first-line test.
• Indications:
  • Identification for specific allergen
  • Allergic rhinitis not controlled
  • Food allergy
  • Vaccine, drug or latex allergy
  • Evaluation for moderate to severe atopic dermatitis
• Precaution: Systemic antihistamines must be excluded in the previous 72 hours prior to skin prick testing as they will reduce the intensity of any allergic response.

2. Specific IgE Testing (ELISA)

• Should be directed at suspected trigger foods.
• Not for foods which the patient is consuming on regular basis without consistent symptoms after every ingestion.

3. Other Tests

• Elevated levels of IgE eosinophilia: Absolute eosinophil count of >250 eosinophils/mm³ (sensitive not specific).
• Elevated tryptase level: Produced by mast cells (indicated in chronic cases not acute).

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Anaphylaxis

Diagnosis of Anaphylaxis

Anaphylaxis is diagnosed when any 1 of the following 3 criteria is fulfilled:

1. Sudden onset with involvement of the skin or mucosal tissue AND either:
   • Sudden respiratory symptoms, OR
   • Hypotension
2. Hypotension after exposure to a known allergen.
3. ≥ 2 of the following occur suddenly after exposure to likely allergen:
   • Skin or mucosal tissue involvement
   • Respiratory involvement (cough, wheeze, shortness of breath)
   • Hypotension
   • GI symptoms (diarrhea, vomiting)

Treatment and Management

Immediate Response:

• The immediate response to a child with acute anaphylaxis is the administration of Intramuscular (IM) Epinephrine (0.01mg/kg, max 0.5 mg).
• Repeat Dose: A second dose of IM adrenaline can be given after 15-20 minutes if the patient has shown little or no evidence of clinical improvement.
• Stop Causative Agents: Identify and stop the trigger immediately.

Medication Details:

• Adrenaline Concentration:
  • 1:1000 (IM use): 1mg in 1ml (e.g., 0.3 mg is 0.3 ml). This is for IM injection only.
  • 1:10,000 (IV use): 1mg in 10 ml (e.g., 0.3 mg is 3 ml). Note: Intravenous adrenaline for anaphylaxis is to be given only by experienced specialists in an appropriate setting.

•  A: stridor may be developed indicating upper airway obstruction, therefore secure airway
•  B: wheezing may be heard , therefore give bronchodilator, give oxygen if desating
•  C: hypotension may develop, therefore secure two iv lines, give fluids  D: GCS may drop
•  E: look for other signs of anaphylaxis
•  Other medications: Diphenhydramine (H1 and H2 antagonist) and hydrocortisone (for late-phase reactions)

Life-threatening Problems (ABC)

• Airway: Hoarse voice, stridor (indicates upper airway obstruction - secure airway).
• Breathing: Work of breathing, wheeze, fatigue, cyanosis, SpO₂ <94% (give bronchodilator, oxygen if desating).
• Circulation: Low blood pressure, signs of shock, confusion, reduced consciousness (secure two IV lines, give fluids).
• Disability: GCS may drop.
• Exposure: Look for other signs of anaphylaxis.

IM Adrenaline Dosing: Z

Patient Group	Dose	Volume (1:1000)
Adult and child >12 years	500 micrograms	0.5 mL
Child 6–12 years	300 micrograms	0.3 mL
Child 6 months to 6 years	150 micrograms	0.15 mL
Child <6 months	100–150 micrograms	0.1–0.15 mL

Adjunctive Therapy:

• Diphenhydramine: H1 and H2 antagonist.
• Hydrocortisone: For late-phase reactions.

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Food Allergy

Common Foods (WEMPS): Wheat, Eggs, Milk/Soy, Peanuts, Seafood.

Clinical Evaluation

Focused Clinical History:

1. Family and personal history of atopy.
2. Relevant signs and symptoms.
3. How signs and symptoms related to the food ingested in terms of onset.
4. Details of previous management of the condition.

Types of Food Allergy:

1. IgE mediated: e.g., urticaria, angioedema, anaphylaxis.
2. Mixed IgE and cell mediated: e.g., asthma, atopic dermatitis.
3. Cell-mediated (non-IgE mediated): e.g., celiac disease, contact dermatitis.

Differential Diagnosis:

1. Gastrointestinal disorders (e.g., peptic ulcer disease, pancreatic insufficiency, reflux).
2. Contamination, toxins.
3. Intolerance (e.g., milk).
4. Psychological (food phobia).

IgE vs. Non-IgE Mediated Food Allergy

Feature	IgE mediated food allergy	Non-IgE mediated food allergy
Typical symptoms	• Oral: tingling of lips, odd taste in mouth, ‘lump in the throat’, swelling of lips or face • Respiratory: hoarse voice, throat tightness, asthma* • Cardiovascular: syncope, lightheadedness* • Cutaneous: flushing, urticaria, pruritus • Gastrointestinal: nausea, abdominal cramps, vomiting, diarrhoea	• Usually isolated to gastrointestinal symptoms (nausea, vomiting, diarrhoea, abdominal cramps)
Timing after oral intake	• Usually seconds to minutes (usually within 2 hours)	• Usually hours to days
Severity	• May proceed to anaphylaxis	• Variable, life threatening is extremely rare
Pathogenesis	• Type 1 hypersensitivity (IgE mediated)	• Type 3 or 4 hypersensitivity
Examples	• Peanut, tree nuts, seafood, milk	• Coeliac disease

* The presence of respiratory or cardiovascular symptoms indicate a life threatening reaction indicative of anaphylaxis.

(Left: Allergic (IgE)-mediated hypersensitivity; Right: Non-allergic (pseudoallergic)-mediated hypersensitivity)

Management & Prevention

Vaccination in Egg-Allergic Individuals:

1. MMR vaccine: Okay to give (negligible amount of egg protein).
2. Influenza vaccine: In mild to moderate cases, give inactivated form or intranasal live attenuated form.
3. Yellow fever vaccine: Contraindicated.

Prevention Strategies:

• Maternal Diet: Maternal dietary restrictions during pregnancy do not prevent the development of an atopic disease.
• Breastfeeding: At least 4 months prevents or delays the occurrence of atopic dermatitis, cow milk allergy, and wheezing.
• Hydrolysed Formulas: Babies with cow milk allergy are given hydrolysed formulas containing broken peptides to facilitate digestion and prevent immune response.
• Introduction of Foods: Delaying introduction of certain foods such as peanuts actually increases the prevalence of food allergies.

Weaning & Reintroduction:

• Weaning Age: Should be initiated between 4–6 months of age (but no earlier than 17 weeks). Delaying introduction of allergenic foods increases risk in high-risk infants (family history of atopy/early onset eczema).
• Reintroduction: Children with non-IgE mediated food allergy may start a programme of food reintroduction if there have been no reactions in the preceding 6 months and there is general improvement in eczema and gut symptoms.

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Allergic Rhinitis & Conjunctivitis

Definitions:

• Rhinitis: Inflammation of the nasal epithelium characterized by sneezing, pruritus, rhinorrhea, and congestion. Nasal polyps may be seen.
• Allergic Rhinitis (Hay Fever): Caused by an IgE-mediated allergic response.
• Allergic Conjunctivitis: Characterized by bilateral conjunctival injection, periorbital edema, and excessive tearing.

normal allergic rhinitis

Clinical Manifestations

maybe confused with asthma or insomnia

• Hallmark Symptoms: Clear thin rhinorrhea, nasal congestion, sneezing paroxysm s, and pruritus of the eyes, nose, ears, and palate.
• Postnasal Drip: May result in frequent attempts to clear the throat, nocturnal cough, and hoarseness. z
• Allergic Salute: Frequent nasal itching and rubbing of the nose with the palm of the hand, leading to a transverse nasal crease.
• Physical Exam Findings:
  • Pale nasal mucosa and oedematous turbinates; watery secretions.
  • Allergic Shiners: Blue-gray to purple discoloration below the lower eyelids (attributed to venous congestion).
  • Swollen eyelids or conjunctival injection.
  • Cobble-stoning of the posterior oropharynx. Z

cobble stoning of posterior oropharynx z

Types of IgE Mediated i.e. Allergic Rhinitis

1. Seasonal Allergic Rhinitis:
   • Caused by airborne pollens with seasonal patterns.
   • Spring: Trees.
   • Late Spring to Summer: Grasses.
   • Summer and Fall: Weeds.
2. Perennial (Persistent) Allergic Rhinitis:
   • Primarily caused by indoor allergens (house dust mites, animal dander, mold, cockroaches).
3. Episodic Rhinitis:
   • Occurs with intermittent exposure to allergens (e.g., visiting a friend with a pet).

Treatment

1. Intranasal Steroids: (e.g., beclomethasone) - max 5 days
   • Side effects: Local irritation, burning, nasal bleeding from improper technique (spraying the nasal septum).
2. Antihistamines:
   • Treat rhinorrhea, sneezing, nasal itching, and ocular itching (less helpful for congestion).
   • First-generation (e.g., diphenhydramine, hydroxyzine): Cause sedation, dry mouth, blurry vision.
   • Second-generation (e.g., cetirizine, desloratadine): Aimed for H1 receptor. Do not cause sedation because they do not cross the blood-brain barrier.
3. Decongestants:
   • Oral (pseudoephedrine, phenylephrine) or intranasal.
   • Relieve nasal congestion.

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Atopic Dermatitis (Eczema)

• Definition: Chronic, relapsing, dry, highly pruritic, inflammatory skin disease.
• Onset: Usually 2-6 months, but can present later.
• Associations: ~80% of children develop other allergic diseases (asthma, allergic rhinitis, food allergies). Egg allergy is the most common cause of food-induced eczematous reactions.
• Pathogenesis: Multifactorial (genetics, immunologic abnormalities, impaired skin barrier, environmental interactions, infectious triggers).
  • Genes encoding epidermal structural proteins (filaggrin) play a major role.
• Contraindication: Live smallpox vaccine is contraindicated.

Distribution by Age

1. Infant (Birth - 2 Years) / Infantile Type

• Locations: Face (cheeks), scalp, ears, trunk, extensor surfaces of extremities.
• May overlap with seborrheic dermatitis.

2. Childhood (2 Years - Puberty) / Childhood Type

• Locations: Face (cheeks), flexural extremities (antecubital, popliteal fossa), neck, ankles.

3. Teenager - Adult / Adult Type

• Locations: Localized flexural extremities, hands, dorsum feet, upper arms, back, wrists, fingers, toes.
• Appearance: Lichenified plaques in flexural areas and head/neck regions.

Stages of Atopic Dermatitis y

1. Erythema
2. Papules formation
3. Excoriation (due to scratching)
4. Lichenification (lines of hard thickened areas)

Flexural atopic dermatitis)*

Acute stage Chronic Stage

Treatment

Goals: Reduce number/severity of flares and increase disease-free periods.

1. Skin Hydration with Emollients (1st Line):
   • Use ointments or creams (preferred over lotions).
   • Lotions contain water/alcohol and may cause drying; ointments have better penetration.
2. Immunomodulatory Creams (2nd Line):
   • Topical corticosteroids.
   • Calcineurin inhibitors (tacrolimus used in ≥2 years old).
3. Oral Antihistamines (3rd Line):
   • First generation is more effective than later generation.
4. Oral Corticosteroids (4th Line)
5. Trigger Avoidance: Identification and avoidance of triggers.
6. Antibiotics: Required for superinfection, mainly Staphylococcus aureus.

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Urticaria & Angioedema

• Urticaria (Hives): Swelling of the dermis.
• Mechanism: Mast cells degranulate when antigen cross-links cell surface IgE. Release of mediators causes vasodilation, increased vascular leak, and pruritus.
• Angioedema: Similar process but reaction extends below the dermis.
• Classification:
  • Acute: Symptoms < 6 weeks.
  • Chronic: Symptoms > 6 weeks.

#OSPE

Table 81.1: Etiologies of Acute and Chronic Urticaria

ACUTE URTICARIA	CHRONIC URTICARIA
Food	Physical
Medication	Chronic spontaneous (formerly idiopathic)
Insect sting or bite	Autoantibody associated
Infection	Neoplastic
Contact allergy	Idiopathic
Transfusion reaction	Autoinflammatory diseases
Idiopathic

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Hereditary Angioedema (HAE)

• Autosomal dominant disease due to a deficiency of C1-esterase inhibitor.
• Characteristics: Unpredictable, recurrent attacks of episodic swelling (face, peripheral extremities, genitalia, abdomen, oropharynx, pharynx).
• Triggers: Episodes often triggered by trauma.
• Risk: Asphyxiation from laryngeal attacks is a significant cause of mortality.

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Drug Allergy

Common Examples:

1. Beta lactams: Penicillin, cephalosporin.
2. Sulfa-containing drugs.
3. NSAIDs: Ibuprofen, aspirin, naproxen.
4. Anticonvulsants: Carbamazepine.

Types of Reaction

IgE Mediated (Type I):

• Mechanism: Mast cell degranulation.
• Duration: Short (1hr to 6hr post exposure).
• Presentation:
  1. Skin reactions (most common): Erythema, Urticaria.
  2. Bronchospasm, rhinitis.

Non-IgE Mediated:

• Timing: Reactions/symptoms may take up to one day to occur.
• Presentation: Maculopapular (morbilliform) skin rash.
• Examples:
  • Vasculitis (Type III).
  • SJS/TEN (Type IV).

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Stevens-Johnson Syndrome (SJS) & Toxic Epidermal Necrolysis (TEN)

• Definition: Life-threatening, severe syndromes of vascular reaction representing hypersensitivity to medications or microorganisms.
• Clinical Features:
  • Skin lesions start as tender, ill-defined erythematous macules with purpuric center.
  • Formation of vesicles and bullae.
  • Sloughing of skin within days (Nikolsky sign).
  • Mucosal involvement (eyes, mouth, lips).

Diagnosis (by Epidermal Detachment BSA):

• SJS: < 10% epidermal loss.
• SJS/TEN overlap: 10–30% epidermal loss.
• TEN: > 30% epidermal loss.

Risk Factors:

• Drugs: NSAIDs, sulfonamides, anticonvulsants, antibiotics.
• Infections: Mycoplasma pneumoniae.