Urticaria & Angiodema Flashcards
What is the definition of urticaria?
a dermatological manifestation characterised by the sudden appearance of itchy hives (wheals), angioedema or both
What is meant by a ‘hive’?
superficial swelling with a pale centre surrounded by a red flare
What are the 3 typical features of a hive?
- central swelling surrounded by a reflex erythema
- associated itching (pruritus) and sometimes a burning sensation
- usually resolves in a few hours and always resolves by 24 hours
What is meant by erythema and what is it caused by?
redness of the skin caused by hyperemia (increased blood flow) in superficial capillaries
What are the 4 main characteristics of angioedema?
- sudden pronounced swelling of the lower dermis and subcutis
- sometimes pain rather than itching
- frequent involvement below mucous membranes
- up to 72 hours for resolution
What are the primary effector cells in urticaria and angioedema?
Where are they found?
Mast cells
Widely distributed in skin, mucosa and other areas of the body
What type of receptors are present on the surface of mast cells?
high affinity IgE receptors
What inflammatory mediators are released when a mast cell degranulates?
There is rapid release of histamine, leukotrienes, prostaglandins
There is delayed release (4-8 hr) of inflammatory cytokines
e.g. TNF, IL-4/5
What is the physiological outcome of mast cell degranulation?
Vasodilation and leakage of plasma in/below the skin
What happens for the first time when someone is exposed to an allergen?
The body makes large amounts of IgE antibody against the allergen
The IgE molecules attach themselves to mast cells
What happens when someone is exposed to an allergen for the second time?
IgE primed mast cells release granules and chemical mediators
These cause the characteristic symptoms of allergy
How can mast cell activation lead to the symptoms of urticaria?
The trigger can be heat, cold, exercise, undefined
Mast cells release mediators in response to drugs, peptides, etc.
Mediators cause symptom induction
What are the 2 types of acute urticaria?
- IgE-mediated urticaria
2. Non-IgE-mediated urticaria
What are the 4 typical triggers of IgE-mediated urticaria?
- drug allergy
- food allergy
- insect toxin allergy
- aeroallergies
What are the 4 typical triggers of non-IgE-mediated urticaria?
- infection
- medications (e.g. NSAIDs)
- Stress (exercise)
- idiopathic
What are the 3 ways of classifying urticaria?
- duration
- frequency
- cause
What is the difference between chronic and acute urticaria?
Chronic - daily symptoms for 6 weeks or more
Acute - symptoms for less than 6 weeks
What are the 2 types of chronic urticaria?
- spontaneous
2. inducible
What is spontaneous urticaria?
There is no obvious external specific trigger
What is inducible urticaria?
Symptoms are induced by a specific trigger
e.g. temperature, pressure
What is the definition of chronic spontaneous urticaria (CSU)?
Spontaneous daily occurrence of itchy hives, angioedema or both, lasting for 6 weeks or more
When taking a history of someone thought to have CSU, what are the 6 main areas that should be explored?
- timing/frequency/duration of attacks
- shape, size and distribution of lesions
- family and medical history - including allergies
- correlation to any triggers
- work/hobbies/smoking habits
- previous therapy and response to treatment
Typically for how long will someone with CSU suffer for?
It is a chronic disease which typically lasts between 1 and 5 years
What 4 factors suggest that CSU duration will be longer than 1-5 years?
- more severe disease
- concurrent angioedema
- concurrent inducible urticaria
- positive autologous serm skin test
What is the most severe impact of CSU on a patient’s life?
It severely impacts quality of life
In what ways does CSU typically affect a patient’s quality of life?
- unpredictability of attacks
- persistent lack of sleep
- fatigue
- disfigurement
Patients often have comorbidities such as depression and anxiety
What is the basic mechanism behind treatments for CSU?
Reducing the effect of mast cell mediators on target organs
This prevents the symptoms or urticaria
What are the 6 most common exacerbating factors in CSU?
- physical and emotional stress
- tight clothing and shoes
- NSAIDs
- Opiates
- Acute and chronic infection
- Pseudoallergens
What is meant by a pseudoallergy?
A condition that has a similar presentation to a true allergy, but is due to different causes
Usually due to alterations in the metabolism of histamine
What are examples of pseudoallergens?
colours, preservatives, aspirin
What are the 4 stages in escalating treatments for CSU?
- standard dose non-sedating H1 antihistamine
- higher dose of H1 antihistamine or add second antihistamine
- consider anti-leukotriene or tranexamic acid if angioedema is present
- consider immunomodulant
What is suggested to be the effect of increasing the dose of H1-antihistamines?
- reduction in mast cell activation
2. impact on cytokine and endothelial adhesion molecules
What “generation” are H1 antihistamines?
Second generation
What are the advantages in using second generation antihistamines?
- licensed and recommended in CSU
- trusted and in use for 25 years
- non-sedating
- very safe
What are the disadvantages of using H1 antihistamines?
They have a restricted use in young children
What are the advantages of using classical antihistamines?
- trusted and in use for over 50 years
- parenteral formulation
- cheap
- additional properties - anticholinergic
What are the disadvantages of using classical antihistamines?
- sedating - impairs REM sleep
- harmful in overdose
- not recommended in CSU
What is Omalizumab?
a monoclonal IgG antibody against IgE, with low immunogenicity
What component of the mast cell plays a key role in the pathophysiology of CSU?
high-affinity IgE receptor plays role in activation of mast cells and symptoms associated with CSU
Total IgE levels in patients with CSU are higher
How does Omalizumab work?
It inhibits binding of IgE to FceRI (IgE receptor) on the surface of mast cells and basophils
How does Omalizumab inhibit binding of IgE to mast cells?
What does this lead to?
It binds to IgE and reduces free IgE levels
This leads to down-regulation of FceRI on mast cells
When is Omalizumab used in treatment of CSU?
It is an add-on therapy that is used in patients with an inadequate response to HI antihistamine treatment
What is the recommended dose of Omalizumab in patients with CSU?
300 mg every 4 weeks
