URTICARIA

Department of Dermatology, School of Medicine, Jember University / Dr. Soebandi Hospital Jember

Upon Completion of This Presentation You Should be Able To

Define the current classification of urticaria and its importance on patients quality of life Explain the pathophysiology and proficiently diagnose the symptoms associated with urticaria Develop appropriate strategies to treat and effectively manage the symptoms of urticaria

Introduction : Urticaria and Angioedema

Urticaria

Angioedema

Prevalence
25% of the population affected at some time in their lives* 25% of urticaria cases chronic

> 6 weeks duration Affects 0.1% to 3% of population*

Over 75% of chronic cases idiopathic

* Strachan Greaves

DD, et al. Emedicine 2002. http://www.emedicine.com/DERM/topic443.htm. MW. N Engl J Med. 1995;332:1767-1772. Krishnaswamy G, et al. Postgrad Med. 2001;109:107-123.

Remission and Recurrence

Spontaneous remission rates

50% in 3 to 12 months 20% in 12 to 36 months 20% in 36 to 60 months 1.5% in 25 years

Recurrence rate

25% to 40%

Negro-Alvarez JM, et al. Allergol Immunopathol (Madr). 2001;29:129-132. Negro-Alvarez JM, et al. Allergol Immunopathol (Madr). 1997;25:36-51.

Impact on Quality of Life

Restricted normal daily activities Restricted sleep, mobility, energy Increased pain, social isolation, and emotional distress Reductions in quality of life similar to patients with heart disease
ODonnell BF, et al. Br J Dermatol. 1997;136:197-201.

URTICARIA
Frequent disease Heterogenous group of disease Decrease Quality of Life

CLINICAL APPEARANCE

URTICARIA
Central swelling of variable size surrounded by reflex erythema. Associated itching or, sometime, burning sensation. A fleeting nature, with the skin returning to its normal appearance, usually within 124 h.

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ANGIOEDEMA
Swelling of lips, face, hands, feet, penis or scrotum Facial swelling most prominent in periorbital area May be accompanied by swelling of the tongue or pharynx Larynx virtually never involved

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CLINICAL APPEARANCE

ANGIOEDEMA
A sudden, pronounced swelling of the lower dermis and subcutis Sometimes pain rather than itching Frequent involvement below mucous membranes Resolution is slower and can take up to 72 h

Photo Image of Angioedema of Face

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Spontaneous angio-oedema.

Hereditary angiodema. Intensive devolvement (A) is to be contrasted with the patients normal facies (B)

URTICARIA
Recurrent Generalized Erythematous Circumscribed border pruritic lesion

ANGIOEDEMA
Asymetric swelling pain

LOCALIZED EDEMA

LEAKAGE PLASMA into Subcutan / Submucous

ETIOLOGIES OF URTICARIA
( GRATTAN 2007 )

IDIOPATHIC IMMUNOLOGICAL
AUTO IMMUNE (ANTIBODIES AGAINST Fc e R I or Ig E) ALLERGIC (Ig E MEDIATED) COMPLEMEN DEPENDENT ( C1 ESTERASE INHIBITOR DEFICIENCY)

NON IMMUNOLOGICAL
DIRECT MAST CELL RELEASING AGENT ( eg OPIATES ) ASPIRIN, NSAID, DIETARY PSEUDO ALLERGENS ACE INHIBITORS

IgE Mediated

URTICARIA

Cross-linking of high affinity IgE receptors (FcRI) by allergen binding to specific cytophilic IgE, IgE itself or its receptor by functional autoantibodies results in mast cell and basophil degranulation

MAST CELL MEDIATORS

HISTAMINE LEUKOTRIENE PROSTAGLANDIN D PLATELLET ACTIVATING FACTOR EOSINOPHYL CHEMOTACTIC FACTOR OF ANAPHYLAXIS HISTAMINE RELEASING FACTOR

Histamine as a Mast Cell Mediator

Angioedema without weals : etio-pathophysiological subtypes

Histamine mediated AE
(Histaminergic)

Inhibition of the cyclo-oxygenase (COX) pathway by non-selective NSAIDS results in diversion of arachidonic acid metabolism from prostaglandins to leukotrienes. PGE2 normally has an inhibitory action on immunological mast cell degranulation and cysteinyl leukotriene production. Reduced PGE2 formation has a permissive effect on immunological mast cell degranulation that is not seen with selective COX-2 inhibitors

Bradykinine mediated AE
(Non histaminergic)

Inhibitors of angiotensin converting enzyme (ACE) block the angiotensinrenin system that controls blood pressure and the breakdown of bradykinin, which may lead to angio-oedema through stimulation of B2 receptors on blood vessels

Stimulation of Hageman factor XII activates the intrinsic coagulation system, generation of plasmin and production of bradykinin by the action of kallikrein on high molecular weight kininogen. There is a complex interconnecting system of feedback loops involving C1 esterase inhibitor, which has a controlling inhibitory infl uence on the complement, kallikrein, coagulation and fi brinolytic systems

Classification of urticaria subtypes (presenting with wheals and/or angioedema)

Differential diagnosis of urticarial symptoms. HAE, hereditary angioedema; AAE, acquired angioedema with C1 Esterase inhibitor deficiency; SA, spontaneous angioedema as manifestation of chronic urticaria with only deep swellings but no superficial wheals. *Duration of individual wheals; **duration of urticaria.

Recommended diagnostic test in frequent urticaria subtypes

Types Spontaneous urticaria Subtypes Acute spontaneous urticaria Chronic spontaneous urticaria Routine diagnostic tests (recommended) None Differential blood count and ESR or CRP omission of suspected drugs (e.g. NSAID) Extended diagnostic programme* (suggested) For identification of eliciting factors and for ruling out possible differential diagnoses if indicated None_ Test for (i) infectious diseases (e.g. Helicobacter pylon); (ii) type I allergy; (iii) functional autoantibodies; (iv) thyroid hormones and autoantibodies; (v) skin tests including physical tests; (vi) pseudoallergen-free diet for 3 weeks and tryptase_, (vii) autologous serum skin test, lesional skin biopsy Differential blood count and ESR/CRP cryoproteins rule out other diseases, especially infections

Physical urticaria

Cold contact urticaria

Cold provocation and threshold test (ice cube, cold water, cold wind) Pressure test (0.2-1.5 kg/cm2 for 10 and 20 min) Heat provocation and threshold test (warm water) UV and visible light of different wave lengths Elicit dermographism

Delayed urticaria

pressure

None
None Rule out other light-induced dermatoses Differential blood count, ESR/CRP None None

Heat contact urticaria Solar urticaria Dermographic urticaria / urticaria factitia

Other urticaria types

Aquagenic urticaria Cholinergic urticaria

Wet cloths at body temperature applied for 20 min

Exercise and hot bath provocation

Contact urticaria
Exercise-induced anaphylaxis/urticaria

Prick/patch test read after 20 min

According to history exercise test with/without food but not after a hot bath

None
None

Assessment of disease activity in urticaria patients

Diagonistic algorithm for differential diagnosis of angioedema

MANAGEMENT OF URTICARIA
IDENTIFICATION AND ELIMINATION OF

UNDERLYING CAUSES / ELICITING TRIGGERS SYMPTOM RELIEF

QUALITY OF LIFE

PATIENTPHYSICIAN COOPERATION

An Approach to the Treatment of Chronic Urticaria

IDENTIFICATION AND ELIMINATION OF THE UNDERLYING CAUSES AND TRIGGERS

DRUGS PHYSICAL STIMULI INFECTION / INFLAMMATORY PROCESSES FUNCTIONAL Auto Atb. DIETARY PSYCHOLOGICAL STRESS

IDENTIFICATION AND ELIMINATION OF THE UNDERLYING CAUSES AND TRIGGERS

SYMPTOMATIC THERAPY
SYMPTOM RELIEF

TO REDUCED THE EFFECT OF MAST CELL MEDIATORS ON TARGET CELL

HISTAMINE

H-1 RECEPTOR : ENDOTHELIAL CELL WHEAL SENSORY NERVES PRURITUS

H-1 ANTI HISTAMINE

1st GENERATION ANTI HISTAMINE

ANTI PRURITUS ANTI CHOLINERGIC SEDATIVE ACTION ( > 12 HRS) DRUG INTERACTION ANALGESIC, SEDATIVES HYPNOTICS IMPACT ON LEARNING AND PERFORMANCE

NOT RECOMMENDED FOR THE ROUTINE MANAGEMENT OF CHRONIC URTICARIA AS 1st LINE AGENTS

NON SEDATING H-1 ANTI HISTAMINE

LACK OF SIDE EFFECT HIGHER EFFICACY & DURATION ACTION MINIMALLY SEDATING FREE OF CHOLINERGIC EFFECT ANTI INFLAMMATORY EFFECT (?) CONCOMITANT ADMINISTRATION OF KETOCONAZOLE / ERYTHROMYCIN CARDIOTOXIC EFFECTS
RECOMMENDED AS FIRST LINE SYMPTOM TREATMENT

OTHER SYMPTOMATIC TREATMENT

CORTICOSTEROID
SEVERE EXACERBATION OF CHRONIC URTICARIA ESPECIALLY WHEN ACCOMPANIED BYANGIOEDEMA UNCONTROLLED URTICARIA BY ANTIHISTAMINES

SHORT COURSE THERAPY

OTHER SYMPTOMATIC TREATMENT

CYCLOSPORIN
UNCONTROLLED URTICARIA BY ANTIHISTAMINES COMBINE WITH NON SEDATING ANTIHISTAMINE RISK / BENEFIT > CORTICOSTEROID

INHIBIT MAST CELL / BASOPHIL DEGRANULATION

MEDIATOR RELEASE

OTHER SYMPTOMATIC TREATMENT

ADRENALIN ( EPINEPHRINE ) IM / AEROSOLIZED ACUTE MANAGEMENT OF EDEMA AFFECTING THE UPPER RESPIRATORY INTRA MUSCULAR ADRENALINE IS NOT INDICATED IN CHRONIC URTICARIA

OTHER SYMPTOMATIC TREATMENT

LEUKOTRIENE RECEPTOR ANTAGONIST (LTRA)

COMBINE WITH ANTIHISTAMINE
URTICARIA CAUSED BY ASPIRIN DELAYED PRESSURE URTICARIA CHRONIC AUTO IMMUNE URTICARIA

OTHER SYMPTOMATIC TREATMENT

TRANEXAMID ACID
INHIBIT PRODUCTION OF BRADYKININ BY INHIBITING CONVERSION PLASMINOGEN TO PLASMIN ANGIOEDEMA

OTHER SYMPTOMATIC TREATMENT

DAPSONE SULFASALAZINE METHOTREXATE INTERFERON PLASMAPHARESIS INTRAVENOUS IMMUNOGLOBULIN ANTI Ig E

UNCONTROLED TRIAL LAST OPINION

OTHER SYMPTOMATIC TREATMENT

DERMATOLOGIC PREPARATION
COOLING LOTION : 1% - 4 % MENTHOL IN AQUAEUS CREAM CORTICOSTEROID IS NOT USEFUL TOPICAL

TREATMENT SPECIAL POPULATION

CHILDREN 1ST GENERATION ANTIHISTAMIN IS BETTER KNOWN 2ND GENERATION ANTIHISTAMINE : > 6 MONTH > 12 YRS : NO CONTRA INDICATION RECOMMENDATION :
DISCOURAGE THE USE OF 1ST GENERATION ANTIHISTAMINE 1ST LINE TREATMENT / UPDOSING ( WEIGHT ADJUSTED ) AS ADULT

TREATMENT SPECIAL POPULATION

PREGNANT / LACTATING WOWEN

PREGNANT ESPECIALLY 1ST TRIMESTER AVOIDED NO REPORT OF BIRTH DEFECT IN WOMEN HAVING USED 2ND GENERATION ANTI HISTAMINE

SUGGESTION :
LORATADINE / DESLORATADINE INCREASED DOSE : CAREFULLY SUGGESTED