UrticariaSharon Hulley

Clinical Nurse Specialist in DermatologyUniversity Hospital of Wales, Cardiff

UrticariaThe term urticaria is widely used to describe an eruption of weals. It is now also increasingly being used to define a disease characterized by short-lived itchy weals, angio-oedema or both together.

(BAD 2007)

Urticaria is a superficial swelling of the skin (epidermis and mucous membranes) that results in a red, raised, itchy rash. It is also known as hives, nettle rash, or weals.

(Clinical Knowledge Summaries 2011)

http://www.dermquest.com/ImageLibrary/images/HI-RES/037807VB.JPG

Angio-oedema• Angio-oedema is a deeper form of urticaria

oedema in the dermis and submucosal or subcutaneous tissues due to increased vascular permeability.

• Can involve the face, eyelids and/or lips.

• Less commonly the tongue and larynx.

• Onset can be dramatic.

Mechanisms• can be either:

– immune mediated - IgE on mast cells and basophils cross-link with the allergen and activates the cells e.g.- urticaria induced by medication (penicillin), foods

– complement mediated - mast cells are activated directly by complements ( mainly by C3a, C4a, and C5a) e.g.- serum sickness and transfusion reactions which cause the activation complement cascade leading to urticaria

– non-immune mediated - activation of mast cells by non IgE mechanisms e.g.- physical stimuli, alcohol, radiocontrast dye and medication

– autoimmune mediated - circulating auto-antibodies activate mast cells

• The mechanisms above lead to degranulation of dermal mast cells in response to a number of stimuli, which causes vasodilatation, dermal oedema and a perivascular infiltrate of lymphocytes and eosinophils . If deeper it causes angioedema.

• Substances released in urticaria include; histamine, prostaglandin D2, leukotrienes C4 and D4, platelet activating factor & cytokines.

• Most cases remain idiopathic

Definitions• Ordinary 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

– Thermal• Cholinergic urticaria• Cold contact urticaria• Localized heat urticaria

BAD (2007)

Definitions cont’d• Other

– Aquagenic urticaria– Solar urticaria– Exercise-induced anaphylaxis– Contact urticaria (contact with allergens or chemicals)

• Angio-oedema without weals– Idiopathic– Drug-induced– C1 esterase inhibitor deficiency

• Contact urticaria (contact with allergens or chemicals)

• Urticarial vasculitis (defined by vasculitis on skin biopsy)

• Autoinflammatory syndromes– Hereditary

• Cryopyrin-associated periodic syndromes (CIAS1 mutations)– Acquired

• Schnitzler syndromeBAD (2007)

Associated conditions

• Approximately 14% of patients with chronic urticaria also have thyroid disease

• Higher prevalence of chronic urticaria in children & adolescents with coeliac disease

• Resolution of chronic urticaria more likely when h. pylori treated with antibiotics than if not.

Drugs commonly implicated• NSAIDS

• Aspirin

• Codeine

• ACE inhibitors

• Statins

• Antidepressants

Investigations

• Diagnosis usually clinical but investigations dependent upon the history.

• Urticaria +/- angioedema unresponsive to H1 antihistamines– FBC, LFT, U&E, TFT, anti TPO, ESR (often raised in

urticarial vasculitis but not usually seen with chronic urticaria. Always raised in auto-inflammatory syndromes)

Investigations cont’d

• Angioedema only– FBC, LFT, U&E, TFT, C3, C4, C1 esterase inhibitor

• Suspicion of urticarial vasculitis– Skin biopsy, vasculitis screen, C3 & C4

(hypocomplementaemic carried worse prognosis)

Urticarial Vasculitis• Urticarial vasculitis is a variant of cutaneous

vasculitis

• 2 forms; normocomplementaemic or hypocomplementaemic

• Although both forms may be associated with systemic symptoms such as angioedema, abdominal or chest pain, fever, and joint pain, this is more apparent in the hypocomplementaemic form. This form has also been linked to the connective tissue disease systemic lupus erythematosus (SLE).

Urticarial Vasculitis

• The cause of urticarial vasculitis is unknown but it has been associated with the following conditions: – Inflammatory connective disorders such as SLE and Sjögren

syndrome. – Immunoglobulin disorders such as immunoglobulin A and

immunoglobulin M monoclonal gammopathies – Leukaemia and internal cancers – Viral diseases such as hepatitis B, hepatitis C and infectious

mononucleosis (glandular fever) – Drug-induced conditions from ACE inhibitors, penicillin,

sulfonamides, fluoxetine and thiazides.

• The majority of cases are idiopathic.

Dermnetnz.org (2011)

Treatment & Management• Avoid exacerbating factors e.g. medication, alcohol, salicylates etc.

• Modify dietary intake if known precipitant.

• Once daily non-sedating H1 antihistamines: – Cetirizine adult and child over 12 years 10 mg once daily,, 6–12 years 5 mg twice

daily, 2–6 years 2.5 mg twice daily, child 1–2 years 250 micrograms/kg twice daily (unlicensed but in BNF for children)

– Desloratadine 5 mg once daily [increasing to a max. 20mg (unlicensed)] 6–12 years 2.5 mg once daily, child 1–6 years 1.25 mg once daily,

– Fexofenadine adult and child over 12 years, 180 mg once daily– Levocetirizine adult and child over 6 years, 5 mg once daily Child 2–6 years 1.25

mg twice daily (unlicensed but in BNF for children)– Loratadine adult and child over 12 years 10 mg once daily; child 2–12 years,

body-weight under 30 kg, 5 mg once daily; body-weight over 30 kg, 10 mg once daily

– Mizolastine adult and child over 12 years 10mg– Acrivastine adult and child over 12 years, 8 mg 3 times daily

Treatment & Management cont’d• Consider withdrawal or reduced doses of anti-histamines if 28 consecutive

symptom free days

• BAD suggest that it has become usual practice to increase doses beyond licensed recommendations when patients not responding and benefits considered to outweigh risks. In some case up to 4x the dose have been used.

• Only consider a sedating H1 if symptomatic at night– Chlorphenamine 4 mg every 4–6 hours, max. 24 mg daily (elderly max. 12 mg daily); 6–12

years 2 mg every 4–6 hours, max. 12 mg daily, 2–6 years 1 mg every 4–6 hours, max. 6 mg daily, 1month – 2years 1 mg twice daily (syrup not licensed for use in children under 1 year; tablets not licensed for use in children under 6 years;)

– Hydroxyzine (to assist with sleeping – no direct impact upon urticaria) initially 25 mg at night increased if necessary to 25 mg 3–4 times daily; child 1–6 years initially 5–15 mg at night increased if necessary to 50 mg daily in 3–4 divided doses; Child 6 months–6 years initially 5–15 mg at night, increased if necessary to 50 mg daily in 3–4 divided doses (syrup not licensed for use in children under 1 year but dose in BNF for chldren)

• H2 antihistamine e.g Cimetidine ; can be helpful if used in combination with a H1 antihistamine rather than as monotherapy

• Anti-leukotrienes i.e. Montelukast can be used in addition to H1 in poorly controlled urticaria adult and child over 15 years, 10 mg once daily in the evening

Treatment & Management cont’d• Oral corticosteroids– not usually recommended for treatment of

chronic urticaria as most patients flare upon withdrawal but can be effective for shortening duration of acute urticaria at 50mg od for 3 days in adults (if considered necessary). Short course reducing dose over 3-4 weeks for urticarial vasculitis or severe delayed pressure urticaria if considered necessary

• IV hydrocortisone effective as an adjunct for severe laryngeal angioedema or anaphylaxis

Treatment & Management cont’d• Immunosuppressants/immunomodulators– Ciclosporin– Tacrolimus– Mycophenolate Mofetil– Methotrexate– Cyclophosphamide– Plasmaphoresis– IVIG

• IM adrenaline/epinephrine– life threatening anaphylaxis and severe laryngeal

angioedema. Auto injectors for self-administration e.g. EpiPen recommended if patient at risk of further life-threatening episodes

Incidentally…..

• Prior to the introduction of H1 non-sedating antihistamines, a survey in 1969 showed that 50% with chronic urticaria (wheals alone) cleared within 6 months, however, 50% of patients with wheals & angioedema were still troubled with disease activity after 5 years – suggesting a poorer outlook.

Referral• Consider referral when there is:– Urticaria with angio-oedema not involving the

airway.– Acute urticaria which is severe and thought to be

due latex allergy.– Chronic urticaria (usually lasting beyond 6 weeks)

which is persistent and troublesome despite the use of antihistamines and avoidance of known trigger factors.

– Suspected urticarial vasculitis

References• Clinical Knowledge Summaries– http://www.cks.nhs.uk/urticaria/management/

quick_answers/scenario_recurrent_or_persistent_urticaria#-254899

• British Association of Dermatologists Clinical Guidelines– http://www.bad.org.uk/Portals/_Bad/Guidelines/

Clinical%20Guidelines/Urticaria%20and%20Angiodema%20(2007).pdf

• DermNet NZ– http://www.dermnetnz.org/vascular/urticarial-

vasculitis.html