APPROACH TO PATIENT WITH ALLERGIC DISEASES

Jovilia M. Abong, M.D. FPCP, FPSAAI, MsC

What is Atopy?
Atopy is the inherited tendency to develop IgEmediated response. It increases the: risk for developing certain allergic diseases likelihood of developing allergic disease after allergen exposure

ALLERGY

A disease or reaction caused by an immune response to one or more environmental antigens resulting in tissue inflammation and organ dysfunction.
Stytes 1994

Immediate hypersensitivity primarily mediated by IgE.

Family history is the single most important factor predisposing a child to the development of allergic disease

estimated risk of allergy:

50% with an atopic history for one parent 66% with an atopic history for both parents

Risk of developing atopy based on family history

Both parents atopic Both parents atopic with same manifestation One parent atopic One sibling atopic Neither parent or sibling atopic 40-60% 50-80% 20-40% 25-35% 5-15%

Diseases of the Atopic Diathesis

Allergic Rhinitis Asthma Atopic Dermatitis
Associated Disease: Rhinosinusitis Chronic or Recurrent Otitis Media
The Allergy Report, AAAI &NIAID 2000

Conditions That May Have an Allergic Component

Conjunctivitis Urticaria and Angioedema Contact Dermatitis Drug Reactions Food Reactions Insect Sting Reactions Latex Reactions Anaphylactic and Anaphylactoid Reactions
The Allergy Report, AAAI &NIAID 2000

SEQUENCE OF ACTION
Exposure to allergen Development of specific IgE Attachment of specific IgE on mast cell Re-exposure to allergens Bridging of two IgE on mast cell

Release of potent mediators

Immediate & Late Reactions in IgE-mediated Hypersensitivity

Immediate reactions Cells mediators symptoms

Late reaction

Step 1
sensitization

Step 2
early phase (minutes)

time

Step 3
late phase (hours)

Examples of allergens by route of exposure

Inhaled allergens Pollens molds
House dust mites Animal danders

Contact allergens plants drugs

Cosmetics

Ingested allergens foods drugs

Parenteral allergens drugs

Allergy injection

jewelry
Latex products occupational

Cockroach

latex

Site Determines the Clinical Response

Allergic Disease /Reaction
Rhinitis Asthma Dermatitis Conjunctivitis Anaphylaxis Food

Site
nose lungs skin eye

Signs/Symptoms
Sneezing,rhinorrhea,nasal Pruritus, congestion

Coughing, wheezing, shortness of breath Itching, rash Itching,redness, tearing

systemic Hypotension, shock, death gut Bloating,vomiting, diarrhea,cramping

Most common aeroallergens in the Philippines

1.

2.
3. 4. 5.

6.
7. 8.
1. 2. 3.

House dust mites House dust mites Cockroach Mold Spores Cat hair/ dander Kapok Dog hair/ dander Pollens
Grasses Weeds Trees

87% 83% 41% 37% 36% 35% 32%

26% 25% 2%

9.

Horse dander

27%

MAST CELLS

Perivascular connective tissue cells found in cell tissue has receptors with high affinity to IgE coated with IgE contain potent chemical mediators of immediate hypersensitivity and inflammation

Mast cell Mediators

Preformed Mediators Main actions
Histamine Vasodilation, increased vasopermeability, smooth muscle contraction, bronchospasms, increased mucous secretion Converts C3 to C3a; affects many coagulant proteins; unclear role in human allergy

Neutral proteases Tryptase Chymase Carboxypeptidase Lysosomal hydrolases b-Hexosaminidase b-D-Galactosidase b-Glucuronidase Arylsulfates A

Physiologic role in allergy uncertain.

Mast cell Mediators

Preformed Mediators
Other enzymes Superoxide dismutase Peroxidase Proinflammatory cytokines Chemotactic mediators ECF-A HMW-NCF Granule associated proteoglycans Heparin, chondroitin sulfate E Attacks eosinophils Attacks neutrophils Storage and release of mediators

Main actions
Generation of reactive O2 species Generation of reactive O2 species

Mast cell Mediators

Newly formed mediators

Arachidonic acid metabolites Leukotrienes B4, C4, D4, and E4

PGD2, PGI2, PGE2, PGF2a Thromboxane

Proinflammatory,vasoactive effects, chemotaxis (LTC4, D4, E4=SRS-A), bronchoconstriction, mucous hypersecretion Proinflammatory,vasoactive effects and chemotaxis
Vasoconstriction

Platelet-activating factor

Activates platelets, neutrophils, and eosinophils; vasoactive effects; bronchocon-

Mast cell Mediators

Newly formed mediators Adenosine Bronchoconstriction, potentiates IgEinduced mast cell mediator release
Increase vasopermeability, vasodilation,hypotension, pain, smooth muscle contraction, activation of arachidonic acid metabolites.

Bradykinin

Cytokines
Interleukines 1,2,3,4,5,6 Granulocyte-macrophage colonystimulating factor (GM-CSF) Monocyte chemotactic and activating factors Tumor necrosis factor

Proinflammatory, vasoactive effects, chemotaxis (IL-8) Activate neutrophils, inc. monocyte chemo taxis, enhances production of other cytokines by T lymphocytes

Cytokines Interleukines 1,2,3,4,5,6 Granulocyte-macrophage colonystimulating factor (GM-CSF) Monocyte chemotactic and activating factors Tumor necrosis factor a

Proinflammatory, vasoactive effects, chemotaxis (IL-8) Activate neutrophils, inc. monocyte chemotaxis, enhances production of other cytokines by T lymphocytes

ATOPIC DISEASES
1. Allergic Rhinoconjunctivitis most common atopic disorder IgE mediated locally in mucosa of nose and eye manifest with itchy eyes and nose , sneezing, rhinorrhea and congestion

Allergic Rhinitis may be associated with the development of other diseases due to common passageways:

Asthma Rhinosinusitis Otitis media Allergic conjunctivitis

Nasal blockage loss of sense of smell nasal hyperreactivity

Itch Sneezing Rhinorrhea Nasal congestion

ATOPIC DISEASES ... 2. Asthma

Immediate hypersensitivity of the lower airway characterize by cough, mucus production, difficulty of breathing and wheezes chronic, reversible inflammatory disease of lower airway

ATOPIC DISEASES ... CHRONIC INFLAMMATORY disorder of the airways in which many cells plays a role, including mast cells, eosinophils, T-lymphocytes and neutrophils

In susceptible individuals, the inflammation is usually associated with widespread but variable airflow obstruction which is often reversible either spontaneously or with treatment Associated increase in airway hyperresponsiveness to a variety of stimuli

Associated with personal and/or family history of allergic diseases

Positive wheal-and-flare skin reactions of airborne antigens Increased levels of IgE in the serum Positive response to provocation tests involving the inhalation of specific antigen

3. Atopic Dermatitis

Eczematous cutaneous eruption associated with asthma and allergic rhinitis Features familial association with asthma and allergic rhinitis, very high serum level of IgE, hypersensitivity aeroallergen and food antigen, eosinophilia

3.Atopic Dermatitis
pruritic disease of unknown origin Start in infancy Incidence 3% infants 1-2% adults

Clinical Features of AD
Major Features
1. pruritus
2. Facial and extensor involvement in infants & children 3. Flexural lichenification in adults 4. Chronic & relapsing dermatitis 5. Personal or family history of atopic disease

Clinical Features of AD
Minor Features
xerosis cutaneous infections nonspecific dematitis of hands or feet ichthyosis, palmar hyperlinearity, keratosis pilaris pityriasis alba nipple eczema white dermographism & delayed blanch pressure anterioir subcapsular cataract elevated serum IgE levels positive immediate-type allergy skin test

Clinical course of Atopic Dermatitis

1. Infantile eczema -2 months-2 years -predilectionf for face, scalp, neck, trunk & extensor surface of extremities -diaper area spared -resolve or abate ate 3 years of age, persist or recur

Clinical course of Atopic Dermatitis

2. Childhood eczema

- 2-12 years old - lesions localized, lichenified on flexor surface of extremities (antecubital, popliteal fossae, neck, wrist & ankles).

Clinical course of Atopic Dermatitis

3. Adolescent and Adult eczema
- 12-20 years old - lesions lichenified on flexor surface of extremities - hand dermatitis -most troublesome - facial involvement with pallor - chronic

ATOPIC DISEASES

4. Gastro-intestinal Allergy
immediate hypersensitivity localized in the GI tract. manifest with nausea, vomiting, cramps, diarrhea following food exposure within minutes

Adverse Reactions to Food

IgE mediated Non-IgE Mediated
Oral Allergy Syndrome Anaphylaxis Eosinophilic esophagitis Eosinophilic gastritis Urticaria Eosinophilic gastroenteritis Atopic Dermatitis Protein-induced Enterocolitis Protein-induced Enteropathy Eosinophilic proctitis Dermatitis herpetiformis

5. Urticaria and Angioedema

raised erythematous pruritic skin lesion and/or swelling of soft tissue of eye, lips and genitalia

ATOPIC DISEASES 5. Urticaria & Angioedema Urticaria - circumscribed raised areas of erythema and edema involving the superficial portions of the dermis; usually multiple and pruritic

Angioedema - welldemarcated swelling, nonpitting and rarely pruritic resulting from vascular reaction with leakage from post capillary venules; asymmetric edema not in dependent portions

Distribution
Urticaria

Angioedema

occurs on virtually any part of the body

involves the face, tongue, extremities, or genitalia do not characteristically occur in dependent areas asymmetrically distributed transient

Clinical Classification of Urticaria

Acute Urticaria with known cause idiopathic Chronic Urticaria with known cause idiopathic Physical Urticaria Contact Urticaria Exercise- induced anaphylaxis

Clinical Classification of Urticaria

Drug reactions Food or food additive Inhalation, ingestion of, or contact antigen Transfusion reactions Infections Insects Collagen Vascular disease Cutaneous vasculitis Serum sickness

Physical Urticaria

Cold Urticaria Cholinergic Urticaria Dermographism Pressure Urticaria (angioedema) Vibratory angioedema Solar urticaria Aquagenic urticaria

Malignancy Urticarial pigmentosa

Systemic mastocytosis Hereditary angioedema Familial cold urticaria

Hereditary diseases

Amyloidosis with deafness and urticaria

ATOPIC DISEASES ...

6. Anaphylaxis
systemic manifestation of immediate hypersensitivity Antigen often introduced parenterally (drug injection or bee sting) or orally massive mediator release resulting in bronchospasm, urticaria, hypotension and anaphylactic shock

Signs and Symptoms of Anaphylaxis

Signs or symptoms

No. (%)
88 (76) 87 (75) 81 (70) 32 (28) 30 (26) 17 (15) 7 (6) 7 (6) 5 (4) 5 (4) 18 (16)

dermatologic cardiovascular respiratory gastrointestinal laryngeal/pharyngeal rhinoconjunctivitis diaphoresis neurologic anxiety chills others

ATOPIC DISEASES ...

7. Adverse Drug Reaction

Any undesired and unintended response that occurs at doses of an appropriate drug given for the therapeutic, diagnostic or prophylactic benefit of the patient
Patterson

Adverse Reaction to Drugs

Predictable overdosage side effects secondary effects drug-drug interaction

Unpredictable idiosyncratic pseudoallergic

drug hypersensitivity type 1 reaction type 2 reaction type 3 reaction type 4 reaction

DIAGNOSIS OF ALLERGY

DIAGNOSIS OF IgE MEDIATED ALLERGY DISEASE

depends on the history,physical examination and laboratory procedures including result of skin test or in vitro tests such as RAST.

EXAMINATION OF THE ALLERGIC PATIENT

General appearance (look well or ill, good)

height, weight (failure to thrive) inspection of skin (dry skin, flexural, eczema, infection, urticaria/angioedema,rash Look for CS S.E. (striae, truncal obesity, hypertension, cataract)
Eyes look for allergic shiners, lacrimation, Denni Morgan signs

EXAMINATION OF THE ALLERGIC PATIENT

Nose deformity, transverse skin cease,

nasal mucosa, normal or pale bluish, swollen, structural problem?

Chest Inspection : Hyper inflation? Pigeon chest deformity Auscultation : Presence of stridor,
Wheezes?

Skin Testing

Indications

To diagnose or exclude allergy To identify the responsible allergen Patients on antihistamines Patients with skin lesions

Limitations

Allergy. 1999. Suppl 55 Vol 54

SKIN PRICK TEST

I. II.
I.

Name, Date, Age, Sex Clinical Illness

Present Illness
I. II. III. IV. V.

VI. VII. VIII.

Nature of Illness Age of Onset Frequency attacks Duration of Attacks Changes in Nature, frequency, or duration of attacks Time lost from school or work Previous evaluation and treatment Present treatment

II. III.

Family History Past Medical History

III. Environmental reactions

A. B. C. D. E.

Time of year and day of symptoms What produces symptoms? What relieves symptoms? Symptom at home, work vacation Reactions to dusty or moldy environments, pets, odors, foods, medicines, insects, colds, change in weather, smoke, exercise, emotion, mowing lawn

IV. Environmental Survey

A. B.

C. D. E.

F.

G.

H. I. J. K.

Occupation, where employed, unusual exposures Place and type of residence, basement, heating, air conditioning, etc. Carpets or rugs in home, type and age Pillow, blanket, and matress, type and age Exposure to barns, dead leaves, or other moldy environments Pets in home (indoors and/or outdoors), number and type Exposure to chemicals, insecticides, latex or rubber products, etc. Hobbies Medications Tobacco smoke Environmental control measures (anti-mite measures, H.E.P.A. filters, etc.)

A. B. C.

D.

Entire skin Conjunctivae Middle ear Nose A. Allergic crease and allergic salute B. Interior of the nose A. Mucosa and the structures it overlies (septum and turbinates) B. The quantity and quality of nasal secretions C. Presence of polyps or foreign bodies D. Patency of the nasal passages C. Mouth and Oropharynx D. Chest

Diagnosing Allergies

Medical history Family History Environmental History Physical exam Skin prick test Laboratories

CBC IgE total/RAST Provocative testing PFT X ray exam,others