Dr. MGs Presentation

8/8/2019 Dr. MGs Presentation

1/13

How do I know if my patient has Urticaria?The clinical features of Urticaria

Wheals < 24h duration(excepturticarial vasculitisand delayed pressureurticaria)

No residual staining of skin(excepturticarial vasculitis)

No desquamation

Accompanied byangioedema in 50% of cases

Pruritus almost invariable(excepturticarial vasculitis)

Rubbing rather thanscratching


2/13

Urticaria look alikesRashes which mimick Urticaria

Maculopapularexanthems(drug, virus)

Urticated eczema

Insect bitereactions

Erythemamultiforme

Secondarysyphilis

Virus exanthem Urticated eczema


3/13

Insect bite

reactionsErythema multiforme

Rash of secondary syphilis

Urticaria look alikesRashes which mimick Urticaria


4/13

Acute Urticaria (+ / -angioedema)

Chronic Urticaria (+ / -angioedema)

Physical Urticaria

Chronic idiopathic Urticaria(autoimmune; non-

autoimmune) Urticarial vasculitis

Subsets of chronic Urticaria

UV 2-5%Chronic

Idiopathic

Urticaria 60% PhysicalUrticaria 35%

autoimmune non -

autoimmune

How should we classify Urticaria?(EAACI / GALEN / EDF guidelines: Allergy 2006; 61: 321-31)


5/13

Test for physical

Urticaria

by challenge test

If + , treat by

avoidance

of cause + H1

antihistamines;

no investigations

warrantedNo physical

Urticaria :

investigate for

urticarialvasculitis

urticarial vasculitis

confirmed

histologically : look forsystemic causes and

systemic involvement

No urticarial vasculitis :

do FBC and differential

wbc. serum TSH andthyroid microsomal

antibody assay

Treat for chronic idiopathic urticaria

ASST: worth while if

urticaria is severe and

recalcitrant; if +,should confirm by in

vitro HR test

Flow chart for investigation of Chronic Urticaria


6/13

What treatment should we offer Ms EYG with

Autoimmune Chronic Urticaria?

General measures

Initial treatment strategies

Avoidance

NSAIDS

Alcohol

Overtiredness Stress

Treat any associated thyroid disease


7/13

Antihistamines - inverse agonists of histamine - the mainstay of autoimmuneand non - autoimmune CIU treatment alike

Efficacy in urticaria is non controversial and has been reviewed Wedi, Exp Rev Clin Immunol. 2005;1: 459-73

More effective in relieving itch than abating wheals (late phase reaction)

Claims for anti-inflammatory activity additional to antihistamine activity, ifdemonstrable, require high doses, and should be treated with scepticism

Clinicians are spoilt for choice: considerations

efficacy - how effective in clinical setting

potency - can be very misleading

therapeutic index (therapeutic window) -ratio minimum effective / minimum toxic dose

My practice : Start with low sedation H1 antihistamine eg Allegra 180mg +/-nocturnal sedative antihistamine eg hydroxyzine 25mg

What antihistamine treatment should

we offer patient EYG ?


8/13

Allegra Desloratidine* L cetirizine(major metabolite of

hydroxyzine)

Licensed (yrs)

Europe

USA

Singapore

12

9

3

3

2

1

2

NA

< 1Prodrug

(CYP 3A4)

terfenadine loratidine (R enantiomer of

cetirizine)

Sedation 0 0 low

Anti-cholinergic low (greatly reduced muscarinicbinding in a murine model)

low low

Drug interactions low low low

Labeling >6m (15mg bd up to 2 y;

30mg bd up to 11y)

>1y > 6y

Ped susp. Yes, (India, USA) yes yes

*Long elimination life

New 2nd generation H1 antihistamines


9/13

Continuous dosage avoids subsensitivity (pseudotachyphylaxis)

no benefit from combining 2 different antihistamines

Medicolegal : Use of sedative antihistamines at night leads to

impairment of cognitive function equal to that of alcohol (Weiler

et al , Ann Int Med 2000) persisting throughout the following day

H2 antihistamines alone or in combination are redundant except

to treat hyperacidity oesophagitis in severe CIU, and when oral

steroids are prescribed

Pregnancy: No antihistamines are safe - although none have

been shown to be unsafe. Surprisingly only hydroxyzine is

specifically contraindicated in manufacturer`s data sheet.

Chlorpheniramine is usually chosen if use of an AH is imperative

Antihistamines special points


10/13

Use off- label dosages of low - sedation H1antihistamines is recommended by Europeanguidelines in selected cases (EAACI / GA LEN / EDF guidelines: Allergy 2006 ; 61: 321-31)

I use Allegra in off - label dosage which is notassociated with unwanted side effects due to widetherapeutic index Nelson et al, Ann Allergy Asthma Immunol 2000;

Asero, Clin Exp Dermatol. 2007)

Inadequate response ?


11/13

Agent Comment

Prednisolone 15 mg bd Short tapering courses for flare - ups only

Doxepin 10-30 mg Tricyclic anti-depressant, potent H1 antihistamine,Useful as night time dose in elderly, beware

underlying cardiac disease, concurrent use with

other antidepressants

Montelukast 10 mg Anti leukotrienes : controlled studies haveyielded variable outcomes; Works best in NSAID

reactive and ASST + patients

Cyclosporin 4mg/kg/d(Grattan et al. Br J Dermatol 2000; 143: 365-72)

Evidence based effectiveness in 2-3 month

courses in CIU, especially autoimmune chronic

urticaria; useful in patients already on steroids;

monitor renal function and BP.

Hydroxychloroquine, Dapsone,

Colchicine, Sulphsalazine

Worth trying in urticarial vasculitis, delayed

pressure urticaria

What to try if antihistamines dont work


12/13

Patient EYG`s further progress

Montelukast 10mg daily was added to existing off-label Allegra

(180mg bd) with no clear benefit and this was withdrawn after 2 weeks

She remained pruritic and had 2 episodes of angioedema of lips

In view of her impending overseas business trip she was commencedon cyclosporin 6mg / Kg / day in addition to Allegra 180mg bd. She

was also given a short tapering course of prednisolone to use if

required

Within a week the Urticaria and pruritus had subsided, although her

dermographism was still demonsrable

Cyclosporin was withdrawn after 2 months and she was maintained

on Allegra 180 mg alone, with occasional wheals and pruritus


13/13

Low sedation H1

AH eg Allegra

mane; sedative AH

nocte +short

tapering

prednisolone for

flare ups

Off - label dosage

Allegra; doxepin

nocte; + short

tapering

prednisolone for

flare ups

Add anti-

leukotriene

to existing regime

Withdraw

antileukotriene,

add cyclosporin

to existing regime

All patients : avoid

NSAIDs, Alcohol,

Overtiredness /

Stress

Standardcontraindications,precautions forcyclosporin apply.

Can use IVIG,plasmapheresis inASST + cases

My recommended flow chart for

management of difficult CIU

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Dr. MGs Presentation