Urticaria and Angioedema

Case Studies

Liz Drewe

Clinical Immunology and Allergy

Nottingham

Clinical Conditions - Urticaria

• Very common condition - 20% of people develop it during their lives

• Urticaria is Latin for nettle rash

• anywhere - trunk and limbs

• diverse morphology - wheal and flare

• blanch with pressure

• May or may not be associated angioedema

• Due to plasma leakage from blood vessels in skin

• Causes: Food, drugs, viral, latex, idiopathic/spontaneous

• Acute or chronic

Hypersensitivity ReactionsType 1 Reactions may cause Urticaria

• Type I Hypersensitivity:

Mast cell activation

Resting and activated

states

• Note – other

mechanisms can

activate mast cells

• Not all urticaria is due

to any allergy

Angioedema

• Due to plasma leakage deeper dermis / subcutaneous tissues

• In isolation or with urticaria (causes same as urticaria)

• Angioedema alone:

• Idiopathic / spontaneous

• ACE inhibitors - bradykinin

• Hereditary angioedema (HAE) / C1 inhibitor disease

• Acquired C1 inhibitor disease

Allergy History

• TAKE A DETAILED HISTORY

• Symptoms and severity (urticaria, angioedema, wheeze, collapse etc)

• What were they doing when reaction occurred eg: latex?

• Relationship to food, drugs eg:NSAID, exercise

• Intercurrent illness or stress

• Family + personal history of atopy eg: hayfever , and swellings

Case 1:

• 21 year male

• Attends ED

• Midnight before bed ate some bread not

eaten before

• 1 AM awakes itchy rash all over, nausea and

mild diarrhoea, wheezing and difficulty

breathing

Case 1: Examination

• Angioedema face, lips, tongue

• Widespread urticaria

• Audible wheeze

Immediate management?

Anaphylaxis

• Serious Type I reactions• Laryngeal oedema• Hypotension/collapse• Bronchospasm• Feeling of impending doom• Onset usually within

minutes/seconds• Almost invariably

symptoms begin within 60 mins

• Generally the later the onset the less severe the symptoms

• 30% have a biphasic reaction 1-4 hours

NICE Guideline Anaphylaxis – Assessment and

Referral after Emergency Treatment

• Document clinical features, time reaction,

circumstances immediately before

• Mast cell tryptase ASAP, 1-2 hours, (+ at Fup)

• Observe 6-12 hours

• Referral pathway Specialist Allergy service

• Offer adrenaline autoinjector (AAI)

• Inform anaphylaxis, biphasic reactions, AAI,

avoidance, referral, patient support groups

Case 1 : Further history:

• Ate breads and butter with seeds on at midnight ? Sesame, sunflower seeds

• PMH: Asthma – 2 admissions last 6 years

• Young child touched egg ���� swollen eyes but could eat cake

• Peanuts ���� abdo pain, vomiting and diarrhoea since infancy

• No previous anaphylaxis

• Mild hayfever

• Sister allergic milk, nuts, eggs

• CAUSE ?

So pointers to food allergy:

• Onset typically within 1 hour eating (prawns

may be delayed)

• Usually resolved 12 hours

• May have severe symptoms

• May be atopic: asthma, hayfever, nuts, eggs

• May be family history atopy

• Usually symptoms every time has food - few

exceptions when cofactor needed eg:wheat

dependant exercise induced anaphylaxis

OutPatient Referred to Allergy

clinic: Skin testing

Skin testing – commercial solutions

and prick prick testing

Negative 0 mm Hazelnut 1

Grass 9 Brazilnut 1

Trees 1 Cashew 10

Egg 4 Fresh sesame 6

Peanut 10 Fresh sunflower

3

Almond 4 Fresh pinenut 1

Positive 3

Longer Term Management

1. Avoid the allergen

2. Anti-histamines for

mild episodes

3. Carry adrenaline and

educate

4. MedicAlert device

5. Optimum treatment

of asthma

6. Desensitisation - only

available in certain

instances (venoms)

Food allergy

• Food allergy is

increasing

• 4% children food allergy

• 3% adults food allergy

• 15% people think they

have a food allergy

• Different from

intolerance, aversions

Common Culprits

Adults

• Peanut

• Tree nuts

• Fish

• Shellfish

• Wheat

Children

•Milk (1st 3 years) *

•Hen’s egg (1st 5 years) *

•Peanut

•Tree nuts

•Soya

•Wheat

•Fish

* Often outgrown

Case 2

• 30 year male

• Widespread urticaria

last 4 days

• Urticaria moving around

the body

• Then develops swollen

lips and eyelids and

attends emergency

department

Case 2: History

• Normally well although has had patches

urticaria over last 6 weeks

• No recent infections

• Not eaten anything different

• Not on any medication

• DIAGNOSIS AND MANAGEMENT ?

Other Differentials Urticaria

• SPONTANEOUS / AUTOIMMUNE: 30-40% of chronic urticaria is autoimmune

eg: autoantibodies to IgE receptor on mast cells (increased in thyroid disease)

• VIRAL: May be due to intercurrent viral infection

• INDUCIBLE: Pressure, exercise, cold

• NEURO: Stress may excacerbate

Case 2: ManagementSpontaneous Urticaria and Angioedema

• Rarely needs admission

• Daily anti-histamine eg: cetirizine 10 mg daily

• Higher dose anti-histamine eg: Up to 40 mg

cetirizine

• Tranexamic acid may help angioedema eg: 1g

tds

• Not an allergy, may not need skin testing

Case 2

• Symptoms continue

• Sees GP 5 days later and referred allergy clinic

• Diagnosis – Chronic Spontaneous Urticaria

• 0.1% population

• Rarely due to allergy

• May move around the body with each wheal lasting <24 hours

• Often disabling, interfering with patient’s QOL

• Worse at night - interrupts sleep

Case 2 – allergy clinic

• Blood tests if severe: LFTs, TFTS, ferritin If indicated immunoglobulins, complement, ANA

• Skin tests rarely helpful

• Skin biopsy e.g. urticarial vasculitis

• Lifestyle and stress

• NICE Guidance CSU:

• Add in montelukast 10 mg daily

• Fill in UAS7 scores

NICE Since – 2015

Chronic Spontaneous Urticaria not resolved with high

dose anti-histamine and montelukast

• Omalizumab – IgG antibody to IgE

• UAS7 score > 28

• 4 weekly subcutaneous injections

• Stop 6 doses see if remission / not disease modifying

• Course £3073

• Mechanism action unclear

Case 3

• 56 year male Afrocarribean

• Referred for investigation chest pain

• History hypertension

• Not diabetic

• No previous angina / MI

• Cholesterol normal

• Reports mild lip swelling ?? cause

Drugs

• Ramipril 5mg

• Aspirin 75mg

• On both for 7 months

• Diagnosis??

Options ??

• 1) Continue ACE inhibitor as mild swellings

only ?

• 2) Stop ACE inhibitor / Don’t start ARB?

• 3) Swap ACE inhibitor for ARB?

ACE inhibitor angioedema

• 0.1 – 6% users

• Increased females and

black Americans

• 25% present in 1st

month but may start

after years on drug

• Swellings lip, face and

tongue

• No urticaria

• Need for tracheostomy

• Deaths

ACE induced angioedema due to defective

breakdown of bradykinin

ACE inhibitor continued

• Concomitant use of NSAIDS may increase severity swellings

• ACE inhibitors may worsen angioedema of CSU and C1 inhibitor disease

• Swellings may continue after stopping

Case 4

• 17 year old attends ED

• Swollen hand

• Previous mild lip

swelling

• Started OCP 4 weeks

ago

• Childhood history

abdominal pain

• No FH of swellings

• INVESTIGATION /

DIAGNOSIS?

C1 inhibitor disease

• HEREDITARY

• Type 1: Autosomal

dominant low level C1

inhibitor

• Type 2: Autosomal

dominant have C1

inhibitor but doesn’t

function

• ACQUIRED

• Autoantibodies or

paraprotein leads to

breakdown of C1

inhibitor

• Secondary to:

• Rheumatoid, lupus,

Sjogrens,

• lymphoproliferative

disease and MGUS

Summary C1 inhibitor

• No urticaria (sometimes erythema marginatum)

• Angioedema face, gut, peripheries

• May mimic acute abdomen

• Laryngeal attacks can be fatal

• Family history may be absent

• Bloods: C3, C4 and C1 inhibitor

• A normal C4 in attack excludes

• If C4 low but normal C1 inhibitor need functional C1 inhibitor checking

Treatment C1 Inhibitor Disease

• Anti-histamines, steroids and epipen DON’T help

• Treat C1 inhibitor concentrate eg: Berinert 20 units / kg

• Can discharge if symptoms resolve / admit if laryngeal

• Some patients have Icatibant home therapy

Case 5

• 64 year old

• Known DLE having had facial rash 6 years

• Weakly positive ANA

• Also hypothyroid

• On hydoxychloroquine

Attendance 1: Surgical

• Abdominal pain 9 weeks

• Weekly waking from sleep vomiting,

lightheaded, sweating, suprapubic and central

colicy abdominal pain

• Bloating after meals, BO 1x day

• Lap chole 4 years ago

• No alcohol, previous smoker 30/day

Examination, Ix

• HR 80

• Tender midline, guarding, quiet bowel sounds, mild rebound

• Managed NBM, IV fluids and analgesia

• Hb 13.4 WC 5.8 Plat 187

• Na 136 K 3.7 U 5.4 Cr 100 CRP 20

• AXR: Gas in transverse colon, long loop small bowel visible ? Subacute obstruction

Attendance 2: ED

• Awoke lip and facial swelling

• No urticaria

• Observed 6 hours

• Treated 5 days piriton, prednisolone and given epipen

• Bloods pancytopaenia ? SLE

• Tryptase and C1 inhibitor sent

• Referred haematology and immunology

• Patient cancelled clinic appointment April due bereavement

Attendance 3

• Few months later awoke swollen face, lips ���� chin ���� eyes

• SOB and couldn’t speak

• 999 ���� epipen

• A+E: Gross swelling lips, cheeks, eyes, tongue not swollen

• BP 120/60 Chest Clear

• Hb 11.1 WC 3.2 Plat 113 NP 2.1 Ly 0.8

• Blood sent tryptase, C3 and C4, C1 inhibitor

Cont:

• Diagnosed in ED 1) allergic reaction

2) pancytopaenia due SLE / HCQ

• Comment in notes “C1 esterase level on

computer from previous admission”

• Immunology OPD made August but again

DNA’d. Notes came through, result looked up

and patient contacted.

Immunology Clinic Review

• Swellings as previously

• Lost 2 stone in 4 months, sweats one year

• SOBOE, arthralgia knees and ankles 1 year

• Bloods: C3 normal C4 undetectable

C1 inhibitor level undetectable

Back to case 4:

• So age suggests Acquired C1 inhibitor disease

• Lupus? Lymphoma?

• ANA weak positive

• Raised IgM with small IgM kappa paraprotein

• Lymphopaenia: CD4 and CD8 T cells , B cells

• CT scan: bulky spleen

• Bone marrow lymphoid aggregates B cells ? Lupus or marginal zone lymphoma

Management Case 4

• Diagnosed marginal zone lymphoma

• Systemic features such as weight loss, sweats and pancytopaenia are unlikely to be due to lupus without bad skin, hair loss, renal involvement

• Treated 4 infusions rituximab

• One further episode facial and lip swelling treated C1 inhibitor concentrate