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Urticaria Harijono Kariosentono

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Page 1: Copy of Cronic Urticaria Kuliah

Urticaria

Harijono Kariosentono

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Itch-scratch cycle

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Definition

An eruption of wheals as a result of transient leakage of plasma from the dermal vasculature

Characterized by short-lived, itchy, raised wheals due to dermal edema.

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Table 1. Clinical classification of the urticariasOrdinary urticaria

Acute (up to 6 weeks of continuous activity)Chronic (6 weeks or more of continuous activity)Episodic (acute intermittent or recurrent activity)

Physical urticarias (reproducibly induced by the same physical stimulus)Mechanical

Delayed pressure urticaria,Symptomatic dermographism, Vibratory angio-oedema

ThermalCholinergic urticaria,Cold contact urticaria, Localized heat urticaria

OtherAquagenic urticariaSolar urticaria

Contact urticaria (contact with allergens or chemicals)Urticarial vasculitis (defined by vasculitis on skin biopsy)

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Aetiology- classification-Idiopathic-Immunological

Autoimmune (autoantibodies against FcɛRI or IgE)Allergic (IgE-mediated type I hypersensitivity rx)Immune complex (urticarial vasculitis)Complement-dependent (C1 esterase inhibitor deficiency)

-NonimmunologicalDirect mast cell-releasing agents (e.g. opiates)Aspirin, nonsteroidal anti-inflammatories and dietary pseudoallergensAngiotensin-converting enzyme(ACE) inhibitors

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1. Chronic idiopathic urticaria (CIU) is defined as the occurrence of wheals (hives) of unknown origin for at least 6 weeks. CIU is usually a recurrent chronic condition, with a prevalence in the general population of 0.5-3.5%

Pruritus is a cardinal symptom of CIU, and combined with the unsightly appearance of the associated wheals, active CIU can have a major negative impact on daily activities and sleep.

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Quality of life

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Quality of life

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Quality of life

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Quality of life

Angioedema :

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> 40% relationship with partner suffers

> 50% don‘t sleep well

> 50% concentration ↓↓↓

> 55% can‘t work normally

> 60% moody and irritable

> 75% stop/reduce doing fun things

n = 362

What chronic urticaria does to your patient…

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Non-acute urticaria is a disabling disease.

Treat disease until it is gone!

What do we learn from this?

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Recruitment

Extravasation

Vasodilation

Activation PRURITUS

ERYTHEMA

WHEAL

INFILTRATE

FceRIKit

FcgRTLRs

CR1/2, CR3C3aR, C5aR

NK1ETA /ETB

CD48IL-3,4,15RCCR3OTRs

CysLT1RMC-1/MC5

EP1/EP3CB1/CB2

A2b/A3uPAR

VRPIRA/PIRB

IgESCF

IgGLPS

ComplementAnaphylatoxinsNeuropeptidesEndothelin-1

BacteriaInterleukinsChemokines

OxytocineLeukotriene

POMCsProstaglandins

CannabinoidsAdenosine

UrokinaseCapsaicin

?

MC

Mast cells are the key effector cells in the induction of urticaria symptoms.

IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, TNF,

MIPs, IFN-g, GM-CSF, TGF-b, bFGF,

VPF/VEGF, PGD2, LTB4, LTC4, PAF, histamine, serotonine,

heparin,chondroitin-

sulfate,chymase,

tryptase, CPA

Urticaria – Pathogenesis

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Mast Cells are the Key Effector Cells

in the induction of urticaria symptoms

Recruitment

Extravasation

Vasodilation

Activation

MC

Courtesy of Prof. M. Maurer.

IL-1, IL-2, IL-3, IL-4, IL-5, IL-6,

IL-8, IL-10, IL-13, TNFa, MIPs, IFN-g,

GM-CSF, TGF-b, bFGF,

VPF/VEGF, PGD2, LTB4,

LTC4, PAF,

histamine, serotonin,heparin,

chondroitin-sulfate,

chymase, tryptase, carboxy-peptidase

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Trigger

CauseMast cell-activating

signal

Mast cellactivation

Mast cellmediators

Urticaria reaction

Urticaria - Therapeutic Strategies

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Trigger

CauseMast cell-activating

signal

Mast cellactivation

Mast cellmediators

Urticaria reaction

causal symptomatic

Urticaria - Therapeutic Strategies

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Trigger

CauseMast cell-activating

signal

Mast cellactivation

Mast cellmediators

Urticaria reaction

causal symptomatic

Urticaria - Therapeutic Strategies

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Trigger

CauseMast cell-activating

signal

Mast cellactivation

Mast cellmediators

Urticaria reaction

causal symptomatic

Urticaria - Therapeutic Strategies

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Trigger

CauseMast cell-activating

signal

Mast cellactivation

Mast cellmediators

Urticaria reaction

causal symptomatic

Urticaria - Therapeutic Strategies

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Classification of Urticaria

Zuberbier, Bindslev-Jensen, Canonica et al. Allergy. 2005. .

Spontaneous urticaria

Physicalurticaria

Other urticaria disorders

Acute urticariaChronic urticaria

Cold contact urticariaDelayed pressure

urticariaHeat contact urticaria

Solar urticariaUrticaria factitia/

dermographic urticaria

Aquagenic urticariaCholinergic urticaria

Contact urticariaExercise-induced

anaphylaxis/urticaria

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Other Forms of Urticaria

Physical Urticaria

Acute Spontaneous UrticariaChronic Spontaneous Urticaria

Symptomatic DermographismCold Contact UrticariaSolar Urticaria Delayed Pressure UrticariaHeat Contact Urticaria

Contact UrticariaAquagenic UrticariaCholinergic UrticariaExercise-induced Urticaria / Anaphylaxis

SpontaneousUrticaria

Inducible

Not Inducible

Classification of Urticaria

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Treatment Options in Chronic Urticaria

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Mast Cells Are the Primary Immune Effector Cells in

Urticaria

Kovarova and Rivera. Curr Med Chem. 2004;11:2083.

• Mast cells are the major source of mediators– Histamine– Cytokines– Prostaglandins/leukotrienes

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First-Line Management of Chronic Urticaria:

EAACI/GA2LEN/EDF Guidelines’ Recommendations

TreatmentMethodologic

QualityLevel of

EvidenceGrade of

Recommendation

NS 2nd-G H1-AHAzelastineCetirizine*DesloratadineEbastineFexofenadineLevocetirizine*LoratadineMizolastineBepotastine besilate

++++++

++++++++

1++1-1+1+1-1+1+1+1+

A

*Increased sedation vs placebo.NS 2nd-G H1-AH = nonsedating 2nd-generation H1 antihistamine.Zuberbier, Bindslev-Jensen, Canonica et al. Allergy. 2005

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Management of Chronic Urticaria: EAACI/GA2LEN/EDF Guidelines

RecommendationsChronic urticaria diagnosis

Increase dose

Choose alternative therapy

Symptoms not controlled

Symptoms not controlled

Symptoms not controlled

Select another alternative treatment

First-line

Zuberbier, Bindslev-Jensen, Canonica et al. Allergy. 2005.

Nonsedating second-generationH1-antihistamine

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Non sedating H1-Antihistamine (nsAH)

nsAH updosing (up to 4x)

+Leukotrieneantagonist, change nsAH

Exacerbation: Systemic Steroid (for 3 – 7 days)

+H2-Antihistamine, Cyclosporine A, Dapsone, anti-IgE

Exacerbation: Systemic Steroid (for 3 – 7 days)

If symptoms persistafter 2 weeks

If symptoms persistafter 1-4 weeks

If symptoms persistafter 1-4 weeks

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Management strategy1. Explanation of the nature & prognosis of

urticaria

2. Individual respons to different AH are vary and tachyphylaxis is reported changing AH1 and increasing dose are warranted

3. Combining 2 different long acting AH1 12 hours apart or adding a short acting AH for relief the symptoms. Sedative AH can be useful at night

4. + Leukotriene antagonist (monteluklast) to AH1

5. Pseudoallergen–free diets may help

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6. A short course of prednisolone 20-30mg/d for 3 days

7. H2 antagonist combination with AH1 the benefit ?

8. Other drugs:

-doxepin, nifedipine, psoralen with UVA (PUVA), sulfasalazine and warfarin.

-stanozolon & tranexamic acid: for non- hereditair angiooedema

-dipyridamole + AH1

-thyroxine variant results

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• Immunosupressive:

- cyclosporin, plasmapheresis and IVIG are effective for severe condition the benefit may be short-lived.

-mycophenalate mofetil, tacrolimus and omalizumab for very severe symptoms.

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First line therapies

Non-sedating H1 antagonists

No

n s

eda

ting

H1

a

ntih

ista

min

cetirizine

desloratadin

Fexofenadine

Levocetirizine

Loratadin

mizolastine

Onc

e da

ily

sedating antihistamin (chlorphenamine 4-12 mg, hydroxyzine 10-50 mg) at

night

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Second-line Therapies

Leukotriene antagonists

Diet

Corticosteroids

H2 antagonists

Eradication of helicobacter

Doxepin

Nifedipine

PUVA

Sulfasalazine

Warfarin

Stanozolol

Tranexamic acid

Dipyridamole

Thyroid hormone

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Third-line Therapies

Ciclosporin Plasmapheresis Intravenous immunoglobulin Tacrolimus Omalizumab

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SUMMARY

1. Urticaria can be classified on the clinical presentation without extensive investigation.

2. Urticaria often remains idiopathic after allergic, infectious, physical and drug-related causes have been excluded as far as possible.

3. Advice and information on general measures can be helpful for most patients, especially if an avoidable physical or dietary trigger can be identified.

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4. It common practice to increase the dose of 2nd-generation AH1 above (4X) the manufacturer’s licensed recommendation for patients when the potential benefits are considered to outweigh any risks.

5. Combinations of nonsedating AH1 with other agents, such as AH2, sedating antihistamines at night or the addition of antileukotrienes, can be useful for resistant cases

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6. Oral corticosteroids should be restricted to short courses for severe acute urticaria or angio-oedema affecting the mouth, although more prolonged treatment may be necessary for delayed pressure urticaria or urticarial vasculitis.

7. Immunomodulating therapies for chronic autoimmune urticaria should be restricted to patients with disabling disease who have not responded to optimal conventional treatments.

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