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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
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Urticaria look alikesRashes which mimick Urticaria
Maculopapularexanthems(drug, virus)
Urticated eczema
Insect bitereactions
Erythemamultiforme
Secondarysyphilis
Virus exanthem Urticated eczema
8/8/2019 Dr. MGs Presentation
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Insect bite
reactionsErythema multiforme
Rash of secondary syphilis
Urticaria look alikesRashes which mimick Urticaria
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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)
8/8/2019 Dr. MGs Presentation
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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
8/8/2019 Dr. MGs Presentation
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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
8/8/2019 Dr. MGs Presentation
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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 ?
8/8/2019 Dr. MGs Presentation
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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
8/8/2019 Dr. MGs Presentation
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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
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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 ?
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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
8/8/2019 Dr. MGs Presentation
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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
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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
Recommended