Allergy

Allergy: an up to date guide Learning outcomes This module should help you to: Identify common types of allergy Understand the symptoms and signs of allergy Know what investigations to do in patients with allergy Know how to manage patients with common allergic conditions. About the author Andrew McLean-Tooke is a specialist registrar in immunology in Newcastle upon Tyne. Why I wrote this module "Allergic disease is a common and increasing cause of morbidity in the UK. General physicians should be able to request initial investigations and set up a management plan before referring patients to an allergist, if this is necessary." Introduction Allergic diseases occur because of an exaggerated response of the immune system to external substances. The prevalence of allergic disease is increasing and affects about one in six people in the UK.1 Recent studies have put the rise at around threefold in the last 20 years, giving the UK one of the highest rates of allergic disease in the world.2 Provision of specialist allergy services in the UK is limited and general physicians therefore have a vital role in the management of patients with allergic disease. Allergic rhinitis Allergic rhinitis is the most common chronic allergic condition in adults and children. It is characterised by episodes of sneezing, itching, rhinorrhoea, and nasal obstruction. Unilateral symptoms or a purulent yellow or green discharge are not compatible with allergic rhinitis, and patients with these symptoms should have further investigations. Symptoms may be intermittent (seasonal) or persistent (perennial). Symptoms beginning in March or April are due to tree pollen allergy, those in June relate to grass pollens, and those in summer and early autumn are associated with weed and fungal spores.3 Patients with house dust mite allergy will notice that their symptoms are worse at night and on waking; this is associated with exposure to the mites' faeces.4 Nasal polyps may be associated with aspirin sensitivity: patients with nasal polyps and aspirin sensitivity often respond well to leukotriene antagonists. Medications such as oral contraceptives and antihypertensives (for example, reserpine, hydralazine, methyldopa, and prazosin) may be associated with rhinitis. If the allergen is identified, the first step in management is allergen avoidance. Antihistamines are the first line in drug treatment and should be used as and when symptoms arise. Patients with moderate to severe symptoms should use nasal sprays, ideally starting one month before the onset of their symptoms if they are seasonal. The most common reason for the failure of nasal sprays is technique; patients should breathe the medications gently through their nose rather than sniff them. They should also inhale them with their head tilted forward rather than back. Temporary use of nasal decongestants (less than a week) may be considered if nasal blockage prevents use of nasal steroids, but prolonged use may make symptoms worse (rhinitis medicamentosa). Patients with severe symptoms despite antihistamines and nasal steroids (or who are unable to tolerate these medications) may be considered for desensitisation; this involves introducing the allergen at increasing doses to induce tolerance. Desensitisation is carried out in hospital and needs considerable commitment from the patient; the patient will need to attend hospital appointments for three years. Local reactions are common although systemic reactions, including anaphylaxis, are rare.1 Recently sublingual desensitisation has been introduced which is better tolerated and requires less hospital attendance although questions regarding its efficacy in comparison to subcutaneous injection desensitisation remain. Urticaria and angio-oedema Urticaria is characterised by the appearance of wheals, which may accompany angio-oedema. Urticaria may be divided into acute or chronic types. Acute urticaria may be caused by sensitivity to: Foods Drugs, such as antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), and opiates Blood products Radiocontrast media. Note that urticaria can occur as a feature of viral infections or febrile illnesses. In 50% of patients the cause is not identified. The mainstay of management of acute urticaria is5: Allergen (or other cause) avoidance Treatment with antihistamines. Chronic urticaria is defined as urticaria occurring daily or almost daily for at least six weeks. Allergic causes of chronic urticaria are rarely identified. Physical urticaria may be caused by pressure (dermographism), cold, or sun exposure. Cholinergic urticaria may be caused by heat, emotion, or exercise. Urticarial vasculitis should be suspected in patients with6: Painful rather than itchy wheals Wheals lasting longer than 24 hours Residual bruising or pigmentation Prominent systemic features Poor response to antihistamines Raised inflammatory markers. Angio-oedema may be associated with urticaria in 50% of patients. Angio-oedema involving the upper respiratory tract may result in life threatening airway obstruction. In a patient presenting with angio-oedema in the absence of urticaria, you should consider: Adverse drug reactions (especially to angiotensin converting enzyme (ACE) inhibitors and NSAIDs) C1 esterase inhibitor deficiency. Remember that ACE inhibitor induced angio-oedema may present up to 10 years after the start of therapy, and ACE inhibitors should always be stopped in any patient with a history of idiopathic angio-oedema. Urticaria in the presence of angio-oedema virtually eliminates the possibility of C1 esterase inhibitor deficiency. Persistent angio-oedema of the face or upper limbs should alert you to obstructive causes, such as superior vena cava obstruction. Acute urticaria and angio-oedema need only minimal laboratory examination. Specific tests should focus on the findings of the history and physical examination. Patients with chronic urticaria or angio-oedema, or both, with minimal history or physical examination findings should be considered for a full blood count, erythrocyte sedimentation rate, thyroid function tests, and liver function tests. Patients with either chronic urticaria or recurrent acute urticaria should be referred to an allergy clinic for assessment.7 First line treatment should consist of the newer second generation antihistamines (cetirizine 10-20 mg daily, fexofenadine 180 mg daily, desloratidine 5 mg daily) because they are more potent and are much less sedating than the older antihistamines.8 Clinical response and tolerability may be better with one second generation over another so if patient’s symptoms are not controlled or side effects occur then a second drug should be tried.9 10 Adding a first generation sedating antihistamine (for example hydroxyzine 50 mg) or the tricyclic antidepressant doxepin may be useful at night for its soporific effects and to alleviate nocturnal pruritus. Adding a histamine-2 receptor blocker (for example cimetidine 800 mg nocte) may also be beneficial. Patients with predominant angio-oedema may benefit from tranexamic acid (1-4 g daily). A short course of prednisolone (20 mg po for two days) may be given for severe episodes.11 12 Drug allergy While many patients have reactions to drugs, only a few will present with allergic reactions. The initial assessment of these patients should be to determine whether the signs and symptoms are consistent with immune mediated reactions. A common problem is when a patient on multiple drugs presents. The first step is to evaluate what drugs the patient is on and when they started taking them, because most immune mediated reactions occur within a few weeks of administration. You should also ask the patient whether they are taking over the counter medications. In most patients it is sufficient to just avoid the implicated drug. If the patient needs to be treated with a drug that they have a history of reacting to (or with another in the same class), consider referring them for further assessment. You should also refer for further assessment any patient with a history of an allergic reaction under anaesthesia. Penicillin allergy is commonly encountered in clinical practice. But only 15% of patients claiming penicillin allergy have evidence of allergy on skin prick testing. The remainder have either lost the allergy over time or never had a true allergic reaction.13 Penicillins and cephalosporins share the same beta lactam ring and studies have shown a 2.0-4.4% risk of reaction to cephalosporins in patients with a history of penicillin allergy. Cross reactivity with other beta lactams varies by class.14 The carbapenems (for example meropenem) are closely related to penicillins and have a high risk (around 11%) of cross reactivity.15 Cross reactivity of monobactams (aztreonam) with penicillins or cephalosporins is rare and these drugs can be safely given to patients with a history of penicillin or cephalosporin allergy, although there is a risk of cross reactivity with ceftazidime.16 Food allergy The identification of IgE mediated food allergy is based on an appropriate history. Ask about17: Symptoms Timing from food ingestion Number of occasions that food has elicited symptoms Possible cross reactivity of foods Atopic history (increased risk of food allergy). Radioallergosorbent testing for specific IgE immediately following an acute reaction is not appropriate because levels will be depleted after an event and may lead to a false negative result. Patients should be referred to an allergy specialist for further assessment. Insect sting allergy Insect sting allergies may cause severe local swellings and can produce systemic reactions including anaphylaxis. Around 1% of children and 3% of adults have systemic reactions to insect stings. Patients who have had a severe systemic reaction to a sting have a 50-60% risk of anaphylaxis on re-sting compared with 10% of patients with large local reactions and 3% in patients with an unknown history.18 Venom immunotherapy (desensitisation) is effective in preventing future systemic reactions to stings, reducing the risk of anaphylaxis following insect re-sting to 2-4%.19 Any patient with a history of systemic allergic reaction to an insect sting should be referred to an allergist for assessment and consideration for desensitisation immunotherapy. A 35 year old man is admitted from the accident and emergency department with lip and neck swelling and urticaria, for which he has been treated with intravenous chlorphenamine and steroids. He is not on any regular medications but had taken 1 gram of paracetamol 12 hours before the attack. He had not eaten any food in the eight hours before the attack. For the last two days he has had a cold with coryzal symptoms and has a low grade temperature at 37.7°C. What is the most likely cause of his symptoms? Your answer a Nut allergy b Allergic rhinitis c Paracetamol allergy d Infection driven urticaria and angio-oedema Nut allergy The interval between the reaction and food ingestion is longer than one would expect for food allergy. Allergic rhinitis Allergic rhinitis is characterised by episodes of sneezing, rhinorrhoea, and nasal obstruction and is caused by an IgE mediated reaction to inhaled aeroallergens. Urticaria and angio-oedema are not features of allergic rhinitis. Paracetamol allergy Allergic reactions to paracetamol are very rare. The interval between the reaction and drug ingestion is greater than one would expect for a drug allergy. Infection driven urticaria and angio-oedema The clinical history is consistent with a viral infection, with a low grade temperature and coryzal symptoms. Infection alone including viral, bacterial, and parasitic infections may drive urticaria and angio-oedema that will resolve on resolution of the infective cause. In these cases patients will have evidence of an infectious process, such as raised inflammatory markers or an elevated white cell count.5 You see a woman in your clinic who has problems with hayfever to grass. She has had this since childhood but notes that it is much worse this year. She asks for your advice on which antihistamines she should use. She is concerned because her job involves driving and she had some antihistamine tablets when she was younger that made her very drowsy. Which one of the following antihistamines is least likely to cause drowsiness? Your answer a chlorphenamine b Hydroxyzine c Cetirizine d Doxepin chlorphenamine chlorphenamine is a sedating antihistamine. Hydroxyzine Hydroxyzine is a sedating antihistamine. Cetirizine Second generation antihistamines cause less sedation and psychomotor impairment than older antihistamines due to less penetration of the blood-brain barrier. Drowsiness with these is rare, although patients should be counselled that the drugs can affect the performance of skilled tasks and that this adverse effect will be made worse by alcohol. Older antihistamines are useful for nocturnal pruritus because of their sedating effects. Doxepin Doxepin is a sedating tricyclic antidepressant that may be useful in lower doses for its H1-receptor blocking activity. A 67 year old man is admitted to the high dependency unit with sepsis. Following bacterial cultures the microbiologists suggest treatment with meropenem. The nursing staff tell you his wife had mentioned he is allergic to penicillin, to which he previously developed immediate florid urticaria. What is the risk of cross reactivity with meropenem and penicillins? Your answer a 1% b 10% c 25% d 50% 1% Carbapenems (for example meropenem) have a modified version of the penicillin thiazolidine ring and the risk of cross reactivity is around 11%. 10% Patients allergic to penicillin may also be sensitive to other beta lactam antibiotics. Current data suggest there is a 2.0-4.4% cross reactivity with the second and third generation cephalosporins and these should be avoided in patients with a history of penicillin allergy. Monobactams (aztreonam) do not have a true beta lactam ring and cross reactivity with other beta lactams is rare. Aztreonam has a common side chain with ceftazidime and there is a potential for cross reactivity. Carbapenems (for example meropenem) have a modified version of the penicillin thiazolidine ring and the risk of cross reactivity is around 11%. 25% Carbapenems (for example meropenem) have a modified version of the penicillin thiazolidine ring and the risk of cross reactivity is around 11%. 50% Carbapenems (for example meropenem) have a modified version of the penicillin thiazolidine ring and the risk of cross reactivity is around 11%. A 28 year old man is admitted with anaphylaxis following a bee sting. He lives near to two beehives and asks what his risk of anaphylaxis is if he is stung again in the near future. What should you advise him his risk is? Your answer a 5% b 25% c 50% d 100% 5% The risk of anaphylaxis on rechallenge in patients with no known previous history is 3%, increasing to 10% in patients with a previous large local reaction and 50-60% in patients with previous anaphylaxis to insect stings. 25% The risk of anaphylaxis on rechallenge in patients with no known previous history is 3%, increasing to 10% in patients with a previous large local reaction and 50-60% in patients with previous anaphylaxis to insect stings. 50% The risk of anaphylaxis to insect venom is related in part to the severity of a previous reaction, although subsequent reactions could be the same, better, or worse. The risk of anaphylaxis on rechallenge in patients with no known previous history is 3%, increasing to 10% in patients with a previous large local reaction and 50-60% in patients with previous anaphylaxis to insect stings. This risk decreases to 2% in patients after desensitisation immunotherapy.18 Patients should be given practical advice about avoiding bees, including wearing shoes and socks outdoors, avoiding brightly coloured or flowerprint clothing, and avoiding flowery scents and perfumes. 100% The risk of anaphylaxis on rechallenge in patients with no known previous history is 3%, increasing to 10% in patients with a previous large local reaction and 50-60% in patients with previous anaphylaxis to insect stings. A 53 year old woman presents with an eight month history of recurrent urticarial rash. She has no significant past medical history. She is usually aware of attacks coming on because she feels "washed out" and tends to take to her bed. She then develops raised, pink, tender lesions over her arms and trunk that gradually resolve over two to three days, although they occasionally leave a bruise. Which one of the following is the most likely diagnosis? Your answer a Urticarial vasculitis b Chronic idiopathic urticaria c Hereditary angio-oedema d Undiagnosed food allergy Urticarial vasculitis The morphology of wheals resembles those of other causes of urticaria. Urticarial vasculitis wheals tend to persist for longer than 24 hours, may be painful rather than pruritic, and may result in residual purpura, bruising, or pigmentary change.6 In contrast to chronic urticaria, these patients have prominent systemic features and often have a poor response to antihistamines. Urticarial vasculitis is associated with raised inflammatory markers and complement consumption. Confirmation by skin biopsy is important because these patients will need further investigation to look for evidence of connective tissue disease (for example systemic lupus erythematosis) and internal organ involvement (for example affecting the kidneys or lungs) and these patients should be referred to a specialist. Chronic idiopathic urticaria The duration of wheals, systemic symptoms, and bruising is not consistent with chronic idiopathic urticaria. Hereditary angio-oedema Hereditary angio-oedema is not associated with urticaria. Undiagnosed food allergy The duration of wheals, systemic symptoms, and bruising is not consistent with food allergy. A 21 year old man with a history of systemic allergic reactions to peanuts presents to your clinic. He has found an over the counter cream that he thinks may help his eczema, but he has not used it because he noted that it contains peanut (arachis) oil. He asks you whether it would be safe for him to use it. What advice should you give him? Your answer a He can apply small doses without problems b He can use it until he notices a rash c He should not use the cream d He should slowly increase the amount of cream he uses starting with a small dose He can apply small doses without problems Patients with a history of peanut allergy should not use medications containing peanut (including creams) because of the risk of a local or even systemic reaction. He can use it until he notices a rash Patients with a history of peanut allergy should not use medications containing peanut (including creams) because of the risk of a local or even systemic reaction. He should not use the cream A variety of medications may contain peanut (arachis) oil, including topical creams and emollients, ear wax softening solutions, and enemas. Patients with a history of peanut allergy should not use medications containing peanut because of the risk of a local or even systemic reaction. He should slowly increase the amount of cream he uses starting with a small dose Patients with a history of peanut allergy should not use medications containing peanut (including creams) because of the risk of a local or even systemic reaction. A 43 year old patient develops tingling and discomfort of the mouth after eating raw carrots and celery. To which one of the following aeroallergens is she also likely to be allergic? Your