role of corticosteroids in allergic diseases

Role of Corticosteroids in Allergic Diseases

Prof DR Dr Ariyanto Harsono SpA(K)

Prof DR Dr Ariyanto Harsono SpA(K) 1

Factors of the occurrence of Allergy

Several factors affect the occurrence of allergy are:

• genetic• exposure to Allergens• Mucosal barrier


4 Sorts of Allergens


FruitsMilkEggsFishNuts

3

Alergen

APC MHC-II Th0

IL-12/ IL-1

Th-2

Th.1

IL-1 IL-2, IFN-γ

B-Cell

IL-4

IL-5

SEL PLASMASEL MEMORI

IL-6

IL-10

A

Memory Cells


ACTIVAtion of IMUNOCOMPETENCE Cells by ANTIGENS

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BACTIVATION of STRUCTURAL CELLS

Nature Rev Immunol 2003; 3: 867-78

Neutrophil

Eosinophil

Prof DR Dr Ariyanto Harsono SpA(K)5

CMEDIATORS RELEASE


Granule contents:Histamine,TNF-Proteases, Heparin Lipid mediators:

ProstaglandinsLeukotrienes

Cytokine production:Specifically IL-4, IL-13


D EFFECTS of MEDIATORS RELEASE to TARGET ORGAN

Nature Rev Immunol 2004: 3:234-237Prof DR Dr Ariyanto Harsono SpA(K)

Pada Kulit:-Urticaria -Dermatitis Atopika -Udema Quinke

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D EFECTS of MEDIATORS RELEASE to TARGET ORGAN


Pada Paru:-Asma -Batuk kronik Berulang

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D EFECTS of MEDIATORS RELEASE to TARGET Organ


Pada Hidung:-Rinitis Alergika -Sinusitis

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DNature Rev Immunol 2004: 3:234-237Prof DR Dr Ariyanto Harsono SpA(K)

Pada Mata:-Conjunctivitis vernalis

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EFECTS of MEDIATORS RELEASE to TARGET ORGAN


Pada vaskuler:-Anafilaksis

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Pada GI:-Protein loosing enteropati -GI haemorrhage -Eosinophilic Gastroenteritis

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CE Symptoms


Oral allergy syndrome


Atopic Dermatitis

Asthma

Prof DR Dr Ariyanto Harsono SpA(K)Prof DR Dr Ariyanto Harsono SpA(K)

17

Urticaria


Quinke’s oedem


HSP


Fixed Skin Eruption

Serum Sickness


Steven Johnson Syndrome


Toxic Epidermal Necrolysis


Diagnosis

anamnesisphysical examinationExamination Support:Skin testTotal IgESpecific IgEPrausnitz- Kustner TestElimination-Provocation Test


Management

General Procedure: Find the Cause, avoidancePrimary preventionSecondary preventionTertiary prevention


Management

General Procedure: Find the Cause avoidPrimary preventionSecondary preventionTertiary prevention


Drugs and therapy used to treat allergies can be divided into broad groups:

• Drugs that block the activity of chemicals that are released in the body during allergic reactions - antihistamines and leukotriene antagonists;

• Drugs which relax the constricted muscle around the airways of the lungs, or shrink congested tissue, or reverse the effects of the chemicals released during allergic reactions - bronchodilators, decongestants and epinephrine; anti acetylchloline

• Drugs that prevent the activation of cells that are involved in the allergic reaction - anti-allergic agents;

• Drugs which possess a more general action in reducing inflammation - corticosteroids;

• Therapy which modifies the immune response - allergen immunotherapy.


Molecular Mechanism of Cortico Steroid


All Allergy Immunology Association agreed Cortico steroid use in the treatment of allergies

• Unless Urticaria


Mild Moderate Severe

Mild to Moderate Potency Topical Steroids

Pimecrolimus

Tacrolimus

Cyclosporine, mycophenolate

Light treatment


Treatment Strategy in AD

Emolient

Dry skin Itching and/or early sign of inflammation

Flare

IVIG

Oral Steroids

Dermatologic Diseases

• For control of severe or incapacitating allergic conditions (e.g., contact dermatitis, atopic dermatitis) intractable to adequate trials of conventional treatment.


ARIA = Allergic Rhinitis and its Impact on Asthma.Bousquet et al. J Allergy Clin Immunol. 2001;108 (5 suppl):S147.

ARIA Guidelines: Recommendations for Management of Allergic Rhinitis

Mildintermittent

Moderatesevere

intermittent

Mildpersistent

Moderatesevere

persistent

Immunotherapy

Allergen and irritant avoidance

Intranasal decongestant (<10 days) or oral decongestant

Second-generation nonsedating H1 antihistamine

Leukotriene receptor antagonists

Local cromone

Intra-nasal steroid

37Prof DR Dr Ariyanto Harsono SpAK

Prof. DR.Dr.Ariyanto Harsono SpA(K) 40

Management of Anaphylaxis1. Primary treatment

• Adrenaline 1:1000 with a dose of 0.001 ml / kg maximum: 0.3 ml subcutaneously

2. Complimentary MedicineIntended for complications:• Seizures: diazepam, phenobarbital• Spasm bronchi: Aminophylline 7 mg dissolved in 10-20 ml of 0.9% NaCl

followed 9 mg/kg/24 hours (divided into 3 doses)• b-2 agonist: Ventolin nebulizer

3. Additional treatment• Antihistamines (H1 receptor antagonist): Benadril 2 mg / kg im continued

3 mg/kg/24 hours orally (divided into 3 doses)• H-2 receptor antagonist: Simetidine• corticosteroids: Solukortef 4-7 mg/kg i.v.

Followed with 4-7 mg/kg/24 hours oral (divided 3 dosis)

GINA Asthma guideline


Asthma

• Used by oral inhalation for the long-term prevention of bronchospasm in patients with asthma.

• Used orally for severe bronchial asthma intractable to conventional treatment.• Used orally for treatment of moderate to severe acute exacerbations of asthma (oral

prednisone usually preferred). Speeds resolution of airflow obstruction and reduces rate of relapse.

• Because onset of effects is delayed, do not use alone for emergency treatment.• Early systemic glucocorticoid therapy particularly important for asthma exacerbations in

infants and children.• In hospital management of an acute asthma exacerbation,

systemic adjunctive glucocorticoids if response to oral inhalation therapy is not immediate, if oral corticosteroids were used as self-medication prior to hospitalization, or if the episode is severe.

• For severe persistent asthma once initial control is achieved, high dosages of inhaled corticosteroids are preferable to oral corticosteroids for maintenance because inhaled corticosteroids have fewer systemic effects.



Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids

When switching from systemic corticosteroids to orally inhaled triamcinolone acetonide in patients with asthma, asthma should be reasonably stable before initiating treatment with the oral inhalation.Initially, administer the aerosol concurrently with the maintenance dosage of the systemic corticosteroid. After about 1 week, gradually withdraw systemic corticosteroid by reducing the daily or alternate daily dosage. Generally, decrease dosage in decrements of ≤2 mg of triamcinolone acetonide after intervals of 1–2 weeks, depending on patient response.Death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly.During withdrawal of oral therapy, symptoms of systemic corticosteroid withdrawal may occur, despite maintenance or even improvement in pulmonary function; continue oral inhalation therapy but monitor for objective signs of adrenal insufficiency. If evidence of adrenal insufficiency occurs, increase systemic corticosteroid dosage temporarily and then continue withdrawal more slowly.If exacerbations of asthma occur during oral inhalation therapy after systemic corticosteroids have been withdrawn, administer short courses of systemic corticosteroids, then taper dosage as symptoms subside. Supplemental systemic corticosteroid therapy may also be required during periods of stress.

• Maintenance therapy with low doses of an orally inhaled corticosteroid is preferred treatment for adults and children with mild persistent asthma (i.e., patients with daytime symptoms of asthma more than twice weekly but less than once daily, and nocturnal symptoms of asthma more than twice per month).

• A long-acting β2-agonist (e.g., formoterol, salmeterol) added to low- to medium-dose inhaled corticosteroids is the preferred therapy in patients with moderate persistent asthma (i.e., patients with daily asthmatic symptoms); alternatively, may increase (e.g., double) maintenance dosage of inhaled corticosteroid within medium-dosage range in such patients.

• Orally as an adjunct to other therapy to speed resolution of all but the mildest exacerbations of asthma when response to a short-acting inhaled β2-agonist is not prompt or sustained after 1 hour or in those who have a history of severe exacerbations.

• Oral glucocorticoids with minimal mineralocorticoid activity and relatively short half-life (e.g., prednisone, prednisolone, methylprednisolone) are preferred.

• Do not use oral inhalation for the treatment of nonasthmatic bronchitis or for relief of acute bronchospasm.


Dosage: Pediatric Patients

• Base pediatric dosage on severity of the disease and patient response rather than on strict adherence to dosage indicated by age, body weight, or body surface area.

• Usual Dosage• Oral• Some clinicians recommend 0.117–1.66 mg/kg daily or 3.3–50 mg/m2 daily, administered in 4

divided doses.• IM• Triamcinolone acetonide in children <6 years of age: Dosage not established; insufficient

clinical experience to recommend use in this age group.• Triamcinolone acetonide in children 6–12 years of age: Initially, 40 mg depending on the

severity of the condition. Some clinicians recommend 0.03–0.2 mg/kg or 1–6.25 mg/m2 at 1- to 7-day intervals.

• Triamcinolone acetonide in children >12 years of age: Initially, 60 mg (using the 40-mg/mL sterile suspension). May administer additional doses of 20–100 mg (usually 40–80 mg) when signs and symptoms recur; some clinicians recommend administration at 6-week intervals, if possible, to minimize HPA suppression.c Some patients may be well controlled on doses ≤20 mg.


AsthmaOral Inhalation• Triamcinolone acetonide in children <6 years of age: manufacturer does not

recommended use in this age group.• Triamcinolone acetonide in children 6–12 years of age: Initially, 100 or 200 mcg (1

or 2 sprays) 3 or 4 times daily (300–800 mcg total) or 200–400 mcg (2–4 sprays) twice daily (400–800 mcg total); adjust dosage according to patient response. Maximum dosage recommended by manufacturer is 1200 mcg (12 sprays) daily; some experts state that higher dosages may be used in children with severe persistent asthma.

• Continually monitor patients for signs that indicate dosage adjustment is necessary (e.g., remissions or exacerbations of disease and stress [surgery, infection, trauma]). (See Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids under Dosage and Administration.)


Prof Dr Ariyanto Harsono dr SpAK

CURICULUM VITAE

Tempat /tgl lahir : Kediri, 3- JuliAgama : Islam

Status Perkawinan: MenikahPendidikan

S-1: Lulus Dokter : FK UNAIR, 1972

S-2: Spesialis Anak : FK UNAIR, 1982

S-3: Program Pascasarjana UNAIR, 2004 Pendidikan tambahan : Sertifikat “Fellowship on Food Allergy”, Academisch Ziekenhuis Utrecht, Nederland, 1990-1991Jabatan sekarang : Guru Besar Ilmu Kesehatan

Anak, Dep IKA FK UNAIR/RSU Dr.Soetomo, Surabaya.

Konsultan Alergi/Imunologi: 1992


Thank YouProf DR Dr Ariyanto Harsono SpA(K) 52

role of corticosteroids in allergic diseases

Education

dnature rev immunol

target organnature rev

d efects of mediators

d effects of mediators

heparinlipid mediators

quinkes oedem

activity of chemicals

treatment of allergies