Urticaria Flashcards
Describe the model of urticaria (mast cells)
-Similar to basophils
-Bone marrow derived
-Found throughout the body (phenotype differs in different body sites)
=Skin and intestinal submucosa contain the proteases Tryptase and Chymase (MCTC)
=Alveolar wall and bowel mucosa contain only Tryptase (MCT)
=Skin mast cells might react to a particular stimulus, but the mast cells in your lungs or GI tract, might not.
-Inflammatory mediators: histamine, prostaglandins, leukotrienes, cytokines, proteases and heparin.
=In granules
=Mast cell is activated= granules degranulate= membranes join the external plasma membrane, releasing their contents externally.
=Some mediators are pre-stored; some are synthesised in response to activation.
=Degranulation may not always be ‘all or nothing’; sometimes release of mediators is only partial.
Describe a weal lesion
-Reflect release of a variety of chemicals from degranulation of mast cells
-Initial erythema (direct effect of histamine on vessel walls)
-Larger flare of erythema (axon reflex: stimulation by histamine of peripheral nerves is transmitted along sensory nerves and then travels ‘backwards’ along other sensory nerves causing release of mediators leading to vasodilation)
-Collection of dermal oedema (weal- increased permeability of post capillary venules leading to transient increase in local oedema until fluid reabsorbed)
=Triple response, resolves over a few hours
=Itch and pain
Complications of the urticaria model
-H1 blockade has partial benefit only: implies other mediators are important (non-H1 mediators)
-Many different types of agents/stimuli cause mast cell degranulation (cross-linking IgE)
-Urticaria can happen without mast cells (nettle stings due to vasoactive compounds in skin/ non immunologic contact urticaria with chemicals to skin, some angioedema)
Describe the classic antigen mediated type 1 hypersensitivity reaction
-Sensitised individual has circulating IgE molecules that bind to high affinity IgE receptors on mast cells
-The antigen causes crosslinking of the IgE receptors leading to a signalling cascade that activates the mast cell.
-The result is degranulation and release of a range of mediators (histamine and non-histamine mediators
=Immediate (0-20 mins)
=Peanut allergy
=Very sensitive= systemic reaction/ anaphylaxis
Describe acute urticaria and causes
-Urticarial episode lasts less than 6 weeks (longer= chronic)
=Most cases will not progress to chronic
=Most cases last less than two weeks
-Precipitant (recent infection, foodstuffs/particularly shellfish, drugs such as aspirin or NSAIDs, or insect bites/ wasps, bees)?
-Inpatient antibiotics (especially betalactam penicillin), or have the radiologists used enhancing dyes during any investigations?
-Children with atopic dermatitis and (allergic) contact urticaria may also occur in those who are sensitised to house dust mite or grass or pollens.
-Waves of weals will cease after a few days.
-Biopsy is not necessary in urticaria (except if you think the diagnosis is not urticaria, but vasculitis)
Treatment of acute urticaria
-Remove any precipitants (i.e. stop suspect drugs if possible; avoid further exposure to causative foodstuff)
-Commence non sedative H1 blockers (fexofenadine, cetirizine etc).
-Sedative antihistamine at night for sedative effects
-Short course of prednisolone: onset of any benefit will be slow, and the evidence of efficacy in the acute situation limited, so better to avoid.
-Parental route in anaphylaxis, with or without airway involvement (bronchospasm, swelling of the tongue and upper airways), or there is angioedema threatening the airway.
-Neither H1 blockade nor steroids will work over minutes.
-Use oxygen, fluids and adrenaline as per anaphylaxis protocols.
Investigation of acute urticaria
-Most cases do not require investigation beyond obtaining a detailed history, unless they are severe, or ongoing (i.e. becoming chronic).
-Severe reaction= dermatological allergy service for investigation, including antigen specific IgE testing, possible prick testing and, in the meantime, consider providing the patient with a self-injectable adrenaline pen (‘EpiPen’).
-Not all these episodes will be immunologically mediated and even fewer will be the result of a type 1hypersensitivity reaction
-Individual weals may be coming and going, and patients will sometimes say lesions last >24 hours, when in reality different lesions are appearing. Draw around a few weals, and review the patient the next day. If lesions are persisting >24 hours, consider an alternative diagnosis such as vasculitis
Describe chronic symptomatic urticaria
-Duration greater than six weeks.
-Associated with autoimmune disorders including thyroid disease, vitiligo, RA, and pernicious anaemia.
-Significant proportion of patients have IgG anti-IgE antibodies or IgE antibodies to the high affinity IgE receptor found on mast cells.
=causal in the disease process, causing activation and degranulation of the mast cell.
-Diagnosis: exclusion of other causes
-Trigger unknown
=In rare instances aspirin, or azo-dyes or low levels of penicillin in the diet, should be considered, and a specialist dietician input may be wise.
Management of chronic symptomatic urticaria
-H1 blockade (possibly supplemented with H2 blockade).
=If one H1 blocker does not work, try another with diary of efficacy
-Non-sedative anti-histamines
-Rarely immunosuppressives such as ciclosporin or corticosteroids may be used, or if aspirin is implicated, leukotriene antagonists
-A new anti-IgE monoclonal biologic, omalizumab, binds to circulating IgE and inhibits binding of IgE to mast cells
=Effective yet expensive, reserved for patients with severe symptoms who have failed H1 blockade.
Overview of contact urticaria
-Non-immunological contact urticaria
=Toxic agents from plants or animals/ weals directly.
=Jellyfish, arthropod bites,, chemicals such as fragrances, benzocaine, benzoic acid and alcohol
-Immunological contact urticaria
=Protein products that require prior sensitisation
=Animal amniotic fluid exposure in vets, latex in surgical gloves (positive prick test to latex) and almost any foodstuff in the right individual (e.g. Kiwi fruit, peanuts, onions, potatoes, spices)
Describe physical urticarias
-Dermographism (weal under applied pressure/ scratching) or delayed pressure urticaria (carrying shopping, sitting in chair, NSAIDs help)
-Solar urticaria (UV radiation, sudden reaction after recent infection or new drug)
-Cold urticaria (cold stress, airway problems eating ice cream, cold water shock as generalised collapse)
-Cholinergic (exercise, emotional stress, heat exposure- rash)
-Aquagenic (water causes urticaria regardless of temperature)
Describe angioedema
-Deeper swelling involving the subcutis and submucosae seen in sites such as the lips, eyes, tongue, and other body sites.
-It is not uncommon to see some degree of angioedema in many cases of urticaria, and in these instances it is also due to mediators released from mast cells.
=Patients with angioedema and urticaria should be managed as per patients with urticaria.
-Angioedema without urticaria is much more serious, and the clinical approach needs to be much more thorough.
=These reactions do not involve mast cells primarily
=ACEi induced/ C1 esterase inhibitor deficiency
Describe ACE inhibitor induced angioedema
-Abnormalities of kinin metabolism (e.g. bradykinin) are central to the production of angioedema.
-ACE inhibitors may cause angioedema, because ACE normally break down kinins
=These drugs are not uncommon causes of angioedema, and for reasons not understood, patients may only become symptomatic after they have been on an ACE inhibitor for a year or more.
=Patients may rarely present with life threatening airway obstruction
Describe C1 esterase inhibitor deficiency
-Acts so as to inhibit a range of proteases= inhibits the production of bradykinin (because you need proteases to produce bradykinin).
-Deficiency of C1 is therefore associated with excess bradykinin production.
=life threatening large airway obstruction secondary to excess bradykinin production.
=family history of sudden death
=past history of recurrent episodes of angioedema lasting several days, accompanied by abdominal pain, diarrhoea and upper airway obstruction.
=absence of urticaria
-Conventional treatments for urticaria have no effect on hereditary angioedema.
=Episodes should be treated with either C1 esterase inhibitor or subcutaneous Icatibant, a bradykinin B2 receptor antagonist.
=There are very rare acquired forms of C1 esterase inhibitor deficiency seen in some patients with connective tissue disorders or lymphoproliferative disorders
Describe anaphylaxis
-Urticaria is a feature of anaphylaxis, but urticaria rarely progresses to anaphylaxis.
-Widespread mast cell degranulation in anaphylaxis causes vasodilation, hypotension, bronchoconstriction and circulatory collapse.
-Treatment comprises intra-muscular adrenaline, oxygen and iv fluids. Intravenous antihistamines and corticosteroids may be given
-The clinical context often provides clues to the cause: after an IV injection in hospital; after a bee sting in the open air
-EpiPen and medic-alert bracelet
