Chapter 12 Management of allergy, rashes and itching
Introduction
The vast majority of skin problems that present in the community are minor in nature. Unfortunately, very occasionally, the development of seemingly innocuous symptoms such as a rash and/or itching can be the presenting symptoms of a life-threatening condition – namely anaphylaxis or meningococcal septicaemia. Whilst other clinical conditions can mimic both anaphylaxis and meningitis, especially in the early stages, there are usually clues in the presentation that help to minimise the delays in administering appropriate therapy. It is not possible in this chapter to cover all potential causes of a skin rash and/or itching. Rather, this chapter aims to focus on important conditions that require recognition, treatment and possible referral in the acute pre-hospital setting. The objectives of this chapter are listed in Box 12.1.
Basic physiology and pathology
Allergic reactions are linked to the release of chemical mediators, which are released from mast cells in a process known as degranulation.1 This occurs when an allergen cross links with immunoglobulin E (IgE) bound to receptors on mast cells. These chemicals are either released immediately (immediate allergic reaction), or after a few hours (late phase response) (Table 12.1). This timing helps to guide appropriate treatment.
| Timing of release | Examples | Treatment |
|---|---|---|
| Immediate | Histamine, tryptase, hydrolases | Anti-histamines (e.g. chlorpheniramine, cetirizine) |
| Delayed | Prostaglandins, leukotrienes, cytokines | Steroids (e.g. prednisolone) |
Primary survey
Assess for an ABC problem in patients with itching and/or a rash (Box 12.2). The recognition of developing airway obstruction is critical, particularly in the presence of anaphylaxis. Patients may complain initially of a feeling of tightening in the throat, be unable to complete sentences or have audible airway noise (stridor or wheeze). If airway obstruction becomes complete, then prompt initiation of a surgical airway will be required.
Box 12.2 Primary survey
Arrange immediate treatment and transfer to hospital if any of the following are present:
Patients with a normal primary survey with obvious need for hospital admission
The history and findings on examination should help to establish whether you are faced with such a scenario. Although these patients may not have abnormal clinical signs at the time of assessment, this should not lull you into a false sense of security since they may deteriorate rapidly. In the case of suspected meningococcal septicaemia, early administration of appropriate antibiotic therapy is safe and associated with an improved prognosis.2 Whenever there is a suspicion of anaphylaxis, epinephrine for intramuscular injection should be readily available.3 If the above situations present, based on the history and examination findings as described in this chapter, then appropriate treatment should be administered and hospital admission arranged.
Secondary survey (including history taking)
History
Onset of symptoms
Did the symptoms come on suddenly over the course of a few minutes/hours or more gradually over the course of several days? Has there been recent injury to the area affected (especially a laceration)? Can symptoms be related to a particular event? In particular, the patient may be able to associate the symptoms with a specific trigger, e.g. consumption of a particular meal, use of a new shampoo, etc. The common potential triggers for an anaphylactic reaction are listed in Table 12.2.
| Cause | Examples |
|---|---|
| Foods | Nuts and seeds, eggs, seafood, kiwi fruit, bananas |
| Venom/stings | Bees, wasps, jellyfish, ants, snakebites |
| Drugs | Antibiotics, aspirin/NSAIDs*, vaccines, radio contrast dye |
| Physical contacts | Latex rubber |
| Other | Cold temperatures, exercise |
* Non-steroidal anti-inflammatory drugs (e.g. ibuprofen, diclofenac, naproxen, etc.)
Previous episodes
Ask whether a similar episode has affected the patient before. Previous episodes of anaphylaxis are unlikely to be easily forgotten! Unfortunately, a history of a previous allergic reaction (mild or severe) does not predict the likelihood of an anaphylactic reaction – a reaction can still occur despite a long history of previous safe exposure.4
Risk factors
Exposure to certain triggers is associated with an increased incidence of allergic reactions (Table 12.2).
Past medical history/drug history
Any past history of similar events should be noted. Many drugs can be implicated in the development of allergic reactions and anaphylaxis. Aspirin accounts for about 3% of anaphylactic reactions and symptoms may occur hours after ingestion.5 Those allergic to aspirin may also be sensitive to NSAIDs, which may cause a similar reaction. A similar allergic relationship can occur with penicillins and cephalosporins. Even people who have had no previous problems with penicillins may experience an anaphylactoid reaction after taking them. Diabetics are at a higher risk of cellulitis.
Examination
See Chapter 2 relating to patient examination. It is always advisable to check and document the vital signs of any patient who presents with a possible allergic reaction or rash. This includes the measurement of temperature, pulse, blood pressure and respiratory rate. An elevated temperature and/or the presence of enlarged (and often painful) lymph glands in the submandibular and/or cervical regions suggests the possibility of an infective process. It is sensible to test for neck stiffness in any patient who presents with a rash and systemic upset. The patient’s neck should be passively flexed forwards towards the chest wall, a manoeuvre that should not be painful to complete. If neck flexion causes pain, then Kernig’s and Brudzinski’s signs should be tested:
Kernig’s sign. Extend the knee with the hip flexed – positive test if hamstrings contraction occurs as a result
Examination of the skin
As previously mentioned, it is important to ensure adequate exposure of the skin, especially in younger children who may be less able or likely to bring the presence of a rash to your attention. In a significant proportion of patients with meningococcal septicaemia, the rash starts on the palms of the hands and/or the soles of the feet so be sure to examine these carefully. Is the rash painful to the touch? Document any swelling of the tissues, especially around the face and the eyes. Gently examine inside the mouth looking for swelling of the tongue. Note the presence of any scratch marks on the body. Note the colour associated with any rash – does the rash disappear or change colour when pressure is applied? (Ideally this should be done with the base of a clear glass.) Table 12.3 lists the common terms used to describe physical changes in the skin associated with the presence of a rash.
| Terminology | Description | Clinical examples |
|---|---|---|
| Macular | Non-infiltrated flat lesions which differ in colour from adjacent areas of skin | Erythema, purpura |
| Papular | Well demarcated raised lesions in the skin of varying sizes | Urticarial wheals, planar warts |
| Vesicular | Small protuberances with a central cavity containing clear liquid | Chickenpox |
| Excoriations | Very superficial wounds in the surface of the skin | Scratches |
| Purpura | Small patches of non-blanching discolouration caused by bleeding from small superficial blood vessels in the skin Petechiae – Small spots of purpura Ecchymoses – Large confluent patches of purpura | Meningococcal disease Idiopathic thrombocytopaenic purpura (ITP) Henoch–Schonlein purpura (HSP) |
Differential diagnosis
Table 12.4 lists the main important conditions to be distinguished in a patient presenting with a rash and/or itching. Further information is given later in this chapter specific to each condition.
Table 12.4 Conditions presenting with rash and/or itch or itch alone
| Rash ± itch | Itching alone |
|---|---|
| Immune system mediated Anaphylaxis Anaphylactoid reaction Allergic reaction – local Urticaria (‘hives’) and/or angioedema Idiopathic thrombocytopaenic purpura (ITP) Infective a. Bacterial Meningococcal septicaemia Cellulitis Impetigo Scarlet fever b. Viral Varicella zoster Primary infection (chickenpox) Reactivation (herpes zoster or ‘shingles’) Measles Rubella (German measles) Non-specific viral rash c. Other conditions Henoch–Schonlein purpura Psoriasis Eczema |
Immune system mediated Anaphylaxis Anaphylactoid reaction Systemic Systemic upset (e.g. uraemia, cholestasis, blood disorders) Other Senile itch Solid tumours HIV |
Management plan
Depending on the suspected diagnosis and clinical condition of the patient, the usual management plan can be summarised as one of the following five choices:
Group 1 – Features requiring hospital referral. Examples would be an unwell child with a suspected meningococcal rash, an anaphylactic reaction.
Where indicated, appropriate home management options are discussed for each condition.
Immune system mediated conditions
Anaphylaxis and anaphylactoid reactions
Anaphylaxis refers to a severe generalised allergic reaction, whereby specific triggers (e.g. insect stings, peanuts) stimulate the release of IgE immunoglobulin. This IgE release causes vasodilation, airway swelling and capillary leakage leading to hypotension. An anaphylactoid reaction results in an identical situation, but does not involve the release of IgE. An example of this is the reaction that can be seen to radiography dye.6 Whilst no universally accepted definition exists, a good working definition is ‘a severe allergic reaction to any stimulus, (usually) having sudden onset and generally lasting less than 24 hours, involving one or more body systems and producing one or more symptoms such as hives, flushing, itching, angio-oedema, stridor, wheezing, shortness of breath, vomiting, diarrhoea or shock’.7 The rate of anaphylaxis in the UK has risen from 6 per million in 1990/91 to 41 per million in 2000/01.8
Symptoms and signs of anaphylaxis
The diagnosis of anaphylaxis is clinical. Symptoms usually begin within minutes of exposure to the trigger(s), but may be delayed by several hours. Many of the symptoms and signs of anaphylaxis may mimic other clinical conditions, thus leading to a delay in diagnosis (Table 12.5). For this reason, the first attack is particularly dangerous. Having experienced the symptoms once, a surviving patient is likely to recognise their occurrence in the future thus aiding earlier diagnosis and treatment. Over 90% of patients with anaphylaxis will develop cutaneous symptoms such as urticaria (see later), itching and angio-oedema that can help to distinguish the condition from other diagnoses. A vasovagal reaction, perhaps the commonest mimic of an anaphylactic episode, does not involve cutaneous changes, tachycardia or bronchospasm. Patients often describe a non-specific but frightening feeling of ‘impending doom’.Untreated, anaphylaxis will steadily worsen and a progressive deterioration in the patient’s clinical condition should alert an observer to the possibility of this diagnosis. Patients with significant cardiovascular collapse may be unable to give a coherent history, adding to the potential for diagnostic delay.
| Symptom/signs of anaphylaxis | Differential diagnosis(es) |
|---|---|
| Respiratory compromise (shortness of breath, wheeze, stridor) | Asthma, COPD, inhaled foreign body, pulmonary embolism |
| Loss of consciousness (LOC) | Vasovagal reaction, seizures, cardiac event (e.g. arrhythmia) |
| Hypotension | Vasovagal reaction, shock (cardiogenic/septic/hypovolaemic) |
| Collapse | As for hypotension/LOC plus panic attack, hyperventilation syndrome, Munchausen’s syndrome |
| Cutaneous skin flushing | Vasovagal reaction, carcinoid syndrome, postmenopausal flushing |
| Gastrointestinal (diarrhoea, abdominal cramps, nausea and vomiting) | Hereditary angio-neurotic oedema (HANE), food poisoning |
Management of anaphylaxis
Epinephrine
Epinephrine (adrenaline) 0.5 mg (0.5 ml of 1:1000) should be injected intramuscularly, preferably into the antero-lateral aspect of the upper arm or thigh. This route of administration has been shown to be superior to subcutaneous injection.9 Epinephrine should be re-administered every 5 minutes until clinical improvement occurs. Individuals taking beta-blockers may have a suboptimal response to epinephrine, with possible persistent severe hypotension and bradycardia.10 The latter can be treated with atropine (0.3–0.5 mg IM every 10 minutes to a maximum of 2 mg). Glucagon (as a 1 mg IV bolus) may also be effective for patients taking beta-blockers although it is not licensed for this indication.6,10
Anti-histamines
Histamine is one of the prime chemical mediators of the anaphylactic reaction. Anti-histamine drugs may therefore provide rapid relief of distressing symptoms. A H1 antagonist drug such as chlorpheniramine (10–20 mg IM or slow IV) may be combined with a H2 antagonist such as ranitidine (150 mg orally, if able to take) to effect maximal histamine blockade.11
Corticosteroids
Corticosteroids, in the form of hydrocortisone 200 mg (IV or IM) or prednisolone (oral) 50 mg should be administered to minimise the likelihood and severity of second-phase reactions. The benefits of administering steroids can take 6–12 hours to be realised, and it is emphasised that their main therapeutic influence is upon recurrent or protracted episodes. Even so, it is recognised that patients who have received steroids may still develop severe biphasic or prolonged reactions.12,13
Admission to hospital
Although most episodes of anaphylaxis will occur and recover within 1–8 hours, the potential for a second-phase reaction remains. As a consequence, all patients who have sustained an anaphylactic reaction should be observed and monitored in a hospital setting. Local hospital policies may vary, but second-phase reactions can occur up to 24 hours after the initial episode, regardless of the response to treatment.10,14 For the next 48 hours after discharge, it is recommended that the patient remain in an environment that permits easy access to medical attention should symptoms recur. This has important implications for those patients who live in isolated rural communities.
Allergic reactions – local
A far more common occurrence than anaphylaxis is the development of a localised reaction to an allergen without the development of serious generalised symptoms. The reaction seen after an insect bite is a classic example of this. There is usually (but not always) a history of exposure to a potential allergen, following which the patient may notice the development of skin changes such as rash, itching, swelling and/or pain. If the affected area involves the mouth or neck then the potential for airway compromise must be considered. There are three simple but important differentiations to be made which help to distinguish these less serious local reactions from those that may lead to a patient’s deterioration:
Urticaria (‘hives’) and angioedema
Urticaria and angioedema are related conditions and occur together in about 50% of cases, with urticaria a single entity in 40% and the remaining 10% being angioedema alone. The British Association of Dermatologists offers useful online information for both patients and doctors.15
Angioedema and urticaria
This condition, which is more common in females, tends to affect the extremities (e.g. lips, eyelids and digits) and is often painful rather than itchy. The majority of episodes are acute and self-limiting but up to 10% will become chronic in nature. In the majority of cases, no definite causal agent is found although any of the substances in Table 12.1 may be implicated in some cases. The majority of symptoms will settle by 6 weeks and the patient can be reassured about the benign nature of the condition. Treatment in the acute phase involves avoidance of any obvious trigger(s) and the use of an oral H1 antihistamine agent such as chlorpheniramine or cetirizine. In the event that one agent is ineffective, another should be substituted.16 In the longer term, other agents including oral steroids may be required if the condition becomes chronic.
Angioedema without urticaria
The commonest cause of isolated angioedema is hereditary angio-neurotic oedema (HANE). This condition is characterised by recurrent acute swelling affecting the cutaneous tissues and mucous membranes of any part of the body. Most patients inherit the condition as an autosomal dominant gene and experience their first episode in childhood. The defect is a lack of C′1 esterase inhibitor protein which leads to inappropriate activation of the complement pathway. Triggers may include allergens but a reaction can also occur following fright or physical trauma. Patients are usually familiar with the pattern of their symptoms, which makes the diagnosis easier as their experience grows. Although the symptoms of swelling usually develop gradually over many hours, involvement of the upper airway tissues can cause concern. Management of an acute episode depends on its severity. Whilst peripheral swelling does not require active treatment, airway involvement requires active management including the administration of C′1 inhibitor concentrate.17 Some patients may carry an auto-injector containing this drug, which should be administered immediately if available. Otherwise, urgent transfer to an alerted hospital is indicated.
Idiopathic thrombocytopaenic purpura (ITP)
This is a condition where the body’s immune system attacks platelets, the blood cells that help form blood clots. This leads to a low platelet count in the blood (detected through a full blood count). As a result, ITP causes small amounts of bleeding into the skin tissues. Its cause is unknown, but there are two forms – one that affects children (usually between 2–4 years old and frequently after a viral infection) and one that affects adults (usually women). It results in a non-blanching purpuric rash, sometimes with more extensive patches of bruising, but is not acutely life-threatening. Usually, individuals with ITP show no other signs of illness other than their rash – in contrast to patients with meningococcal disease. If in doubt as to the cause of purpura in the pre-hospital setting, further medical advice should be obtained or hospital admission arranged.
Infective conditions
Bacterial
Meningococcal septicaemia
Meningococcal septicaemia is a life-threatening condition with high morbidity and mortality. In 2005, 721 cases were reported in England and Wales.18 Unfortunately, particularly in its early stages, its symptoms are fairly non-specific and may mimic those of a common viral illness. Although it may not occur at all, the development of a rash is an important clinical sign, especially in the presence of systemic upset (e.g. headache, vomiting and/or altered mental status). The Meningitis Research Foundation (www.meningitis.org.uk) is one of many resources with practical advice and information for health professionals.
The classical rash of meningococcal septicaemia may consist of any of the following:
The rash is usually described as ‘non-blanching’ – i.e. if a glass tumbler is pressed firmly against a septicaemic rash, the marks will not fade. In its initial phase, the rash may not have any of the classical features described. In the case of any patient with a rash, the patient and/or their carers should be educated about features of possible concern and advised to seek advice again if the nature of the rash changes. It often starts first on the sole of the feet or the palm of the hands. The rash may not be as distinct in patients with darkly coloured skin, in whom areas such as the conjunctiva and the roof of the mouth should be checked carefully. Patients with septicaemia will usually become seriously ill, often within a short time frame. Symptoms may be very subtle in infants and may include irritability, poor feeding, weak cry and mottled skin. If in doubt, the infant should be admitted for observation. In the case of suspected meningococcal septicaemia, appropriate antibiotic treatment should be administered as soon as possible. Pre-hospital antibiotic administration has been shown to reduce the mortality in meningococcal meningitis by approximately 50%. The incidence of true anaphylactic reactions to penicillin is extremely low and treatment should not be delayed unless there is a clear personal history of such.19 In these circumstances, ceftriaxone is the preferred alternative.20 The recommended doses of each drug are given in Table 12.6.
Table 12.6 Recommended dosages of antibiotics in the treatment of meningococcal septicaemia
| Patient’s age | Penicillin V | Ceftriaxone |
|---|---|---|
| Infant | 300 mg | 100 mg/kg |
| Child (1–9 years) | 600 mg | 100 mg/kg |
| Child (10+ years) | 1.2 g | 1 g |
| Adult (16+ years) | 1.2 g | 1 g |
Cellulitis
Cellulitis is an acute bacterial infection of the skin and subcutaneous tissues. Most commonly it involves the lower leg although any part of the body may be affected. Untreated, infection can spread and lead to septicaemia. Cellulitis involving the peri-orbital or orbital areas is of particular concern as infection may spread to the sagittal sinuses. The commonest clinical sign initially is a hot, raised and erythematous area of skin which is tender to the touch. As the cellulitis develops, the patient may develop systemic signs of infection (raised temperature, sweats, tachycardia and a feeling of malaise). The usual organisms involved are haemolytic streptococci and Staphylococcus aureus.21 The history may indicate the portal of entry for the bacteria such as a laceration, abrasion or recent surgery. The mainstay of treatment is a combination of antibiotic therapy, analgesia, elevation of affected limbs and treatment of any underlying condition.
Antibiotic therapy
The standard antibiotic combination for cellulitis is benzyl penicillin and flucloxacillin (both 500 mg 6-hourly for adults – see the BNF or MIMS for paediatric dosing). An alternative for those hypersensitive to penicillin is erythromycin 500 mg 6-hourly. Hospital admission for intravenous antibiotics is recommended for patients with involvement of the (peri)orbital tissues, systemic symptoms and those unable to tolerate oral treatment.
Impetigo
Impetigo is a highly contagious bacterial infection of the superficial tissues of the skin. It is spread by direct contact and is common amongst children. The most frequently implicated organisms are Staphylococcus aureus and group A beta-haemolytic streptococcus. Although healthy skin can be affected, these bacteria usually enter the skin through a cut, scratch or abrasion. The nose and peri-oral regions, being susceptible to minor trauma, are the usual sites of presentation. A red sore that oozes fluid or pus usually heralds the start of the infection. As the infection spreads, other lesions appear nearby which may be painful or itchy. The patient does not usually have a temperature but there may be swelling of the lymph glands nearby. Treatment has traditionally been with either topical or oral antibiotics. A recent meta-analysis highlighted the lack of a quality evidence base for the most effective treatment for impetigo.22 The authors concluded that the use of a topical antibiotic (such as mupirocin [Bactroban] or fucidic acid [Fucidin]) for 7 days should be recommended in a patient with limited disease and no systemic upset.22Oral antibiotics are reserved for more severe infections. The agents of choice are cephalexin, co-amoxiclav or erythromycin – all available in suspension form.23
Viral
Varicella zoster – chickenpox and shingles
Varicella zoster presents as two clinical entities. Primary infection results in the rash known as chickenpox, a highly contagious illness, usually occurring in childhood outbreaks. The virus then lies dormant in nerve cells but may reactivate to cause herpes zoster, also known as ‘shingles’. The risk of developing shingles increases with age and reduced immunocompetence (e.g. immunosuppressive drugs, HIV infection, cancer).24
Chickenpox (notifiable in Scotland)
In Scotland in 2001 there were 21 894 notifications of chickenpox (428 per 100 000 population). The classic symptoms of chickenpox are a rash, fever and the general feeling of malaise seen with other viral infections. The rash usually appears within 2 weeks of exposure to the virus, with superficial spots that soon develop into blisters that burst and crust over. It is often intensely itchy and (a diagnostic pointer) spreads above the face and into the hair line. The rash remains a source of infection until all the blisters have crusted over. Chickenpox can spread to any individual who has not been previously infected or vaccinated. Although in childhood it is usually a mild illness, it can lead to complications including cellulitis, pneumonia and encephalitis.
Measles (notifiable)
Measles is the most frequent cause of vaccine-preventable deaths in childhood.25 It is primarily a viral respiratory tract infection, which can have serious or even fatal consequences for infants and small children. In 2003, there were 2488 cases notified to the Health Protection Agency.18 Protection is currently offered through the MMR vaccination. Unfortunately, since a link between this vaccine and the development of autism was suggested in 1998,26 reduced public confidence has resulted in a decreased uptake in vaccination, heralding the possibility of a major measles outbreak. Whilst subsequent studies have conclusively shown no association and some of the authors of the original study have also conceded that MMR has no causal role,27 vaccine uptake remains as low as 61% in the UK.
Non-specific viral rashes
Virtually any viral infection can result in the development of a rash, usually on the face, chest or back. The rash is usually very fine, red in colour and blanches on pressure. It usually appears several days into the illness, often around the time the fever and other symptoms are improving. It may itch slightly but should not be painful. Care should be taken to exclude more serious causes of rashes (as outlined above). The individual affected may have symptoms such as a sore throat, runny nose, cough or lethargy but has no symptoms of concern. The rash itself is not infectious and symptomatic treatment only is required.
Other causes of isolated itching
Itching in isolation may be the presenting feature of a wide range of other clinical conditions (Table 12.7). All can be managed in the out- of-hours setting by the use of basic symptomatic measures and the patient should be advised to seek medical assessment thereafter.
| Cause | Comment |
|---|---|
| Senile itch | Occurs without an obvious cause in more than 50% of those aged >70 years and is thought to be linked to drying of the skin with age1 |
| Cholestasis | Common symptom in jaundiced patients |
| Uraemia | Associated with chronic renal failure and affects approx 25% of those on haemodialysis. It may be limited to the site of a haemodialysis shunt |
| Solid tumours | Specific tumours are associated with localised itching: |
Basic symptomatic measures for the relief of itching
No universally effective drug or cream exists for the relief of itching. Anti-histamine preparations in particular are only effective for itching caused by the release of histamine (e.g. insect bites). Creams containing a 1–2% mixture of menthol or phenol with aqueous cream can be applied topically several times a day for symptomatic relief of itching.1
Formulating a safe and effective management plan
Assess the patient’s symptoms and signs to decide whether your patient needs emergency admission, semi-urgent admission or whether they can be safely treated at home:
1 Twycross R, Greaves MW, Handwerker H, et al. Itch: scratching more than the surface. Q J Med. 2003;96:7-26.
2 Woodward CM, Jessop EG, Wale MC. Early management of meningococcal disease. Commun Dis Rep CDR Rev. 1995;9:R135-R137.
3 McLean-Tooke AP, Bethune CA, Fay AC, Spickett GP. Adrenaline in the treatment of anaphylaxis: what is the evidence? BMJ. 2003;327:1332-1335.
4 Brown AF, McKinnon D, Chu K. Emergency department anaphylaxis: a review of 142 patients in a single year. J Allergy Clin Immunol. 2001;108:861-866.
5 Kemp SF, Lockey RF, Wolf BL, Lieberman P. Anaphylaxis. A review of 266 cases. Arch Intern Med. 1995;155:1749-1754.
6 Noone MC, Osguthorpe JD. Anaphylaxis. Otolaryngol Clin North Am. 2003;36:1009-1020.
7 Simons FER, Chad Z, Gold M. Real-time reporting of anaphylaxis in infants, children and adolescents by physicians involved in the Canadian Pediatric Surveillance Program. J Allergy Clin Immunol. 2002;109:S181.
8 Gupta R, Sheikh A, Strachan D, Anderson HR. Increasing hospital admissions for systemic allergic disorders in England: analysis of national admissions data. BMJ. 2003;327:1142-1143.
9 Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol. 2001;108:871-873.
10 Tang AW. A practical guide to anaphylaxis. Am Fam Phys. 2003;68:1325-1332.
11 Lieberman P. The use of antihistamines in the prevention and treatment of anaphylaxis and anaphylactoid reactions. J Allergy Clin Immunol. 1990;86:684-686.
12 Stark BJ, Sullivan TJ. Biphasic and protracted anaphylaxis. J Allergy Clin Immunol. 1986;78:76-83.
13 Ellis AK, Day JH. Diagnosis and management of anaphylaxis. Can Med Assoc J. 2003;169:307-311.
14 Hogan C. Anaphylaxis. The GP perspective. Aust Fam Phys. 2002;31:807-809.
15 British Association of Dermatologists Urticaria and Angioedema, Available online, 2004 http://www.bad.org.uk/patients/disease. (5 March 2007)
16 Grattan C, Powell S, Humphreys F. Management and diagnostic guidelines for urticaria and angio-oedema. Br J Dermatol. 2001;144:708-714.
17 Fay A, Abinun M. Current management of hereditary angio-oedema (C′1 esterase inhibitor deficiency). J Clin Pathol. 2002;55:266-270.
18 Health Protection Agency NOIDs Annual Totals 1994–2005. Available online http://www.hpa.org.uk/infections/topics_az/noids/annualtab.htm (5 Mar 2007)
19 Surtees SJ, Stockton MG, Gietzen TW. Allergy to penicillin: fable or fact? BMJ. 1991;302:1051-1052.
20 Begg N, Cartwright KA, Cohen J, et al. British Infection Society Working Party Consensus statement on diagnosis, investigation, treatment and prevention of acute bacterial meningitis in immunocompetent adults. J Infect. 1999;39:1-15.
21 Baxter H, McGregor F. Understanding and managing cellulitis. Nurs Stand. 2001;15(44):50-56.
22 George A, Rubin G. A systematic review and meta-analysis of treatments for impetigo. Br J Gen Pract. 2003;53:480-487.
23 Hedrick J. Acute bacterial skin infections in pediatric medicine: current issues in presentation and treatment. Paediatr Drugs. 2003;5(Suppl 1):35-46.
24 Gnann JWJr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002;347:340-346.
25 Duke T, Mgone CS. Measles: not just another viral exanthema. Lancet. 2003;361:763-773.
26 Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998;351:637-641.
27 Murch S. Separating inflammation from speculation in autism. Lancet. 2003;362:1498-1499.
Allergy UK (UK). www.allergyuk.org. (5 Mar 2007)
American Academy of Allergy, Asthma and Immunology. www.aaaai.org. (5 Mar 2007)
Anaphylaxis Canada. www.anaphylaxis.org. (5 Mar 2007)
British Association of Dermatologists (UK). www.bad.org.uk/about/. (5 Mar 2007)
Food Allergy and Anaphylaxis Network. www.foodallergy.org. (5 Mar 2007)
Health Protection Agency. http://www.hpa.org.uk. (5 Mar 2007)
Medic Alert Foundation (UK). www.medicalert.co.uk. (5 Mar 2007)
Meningitis Research Foundation (UK). www.meningitis.org.uk. (5 Mar 2007)
Platelet Disorder Support Association – Comprehensive web resource on ITP. http://www.pdsa.org/. (5 Mar 2007)
Scottish Centre for Infection and Environmental Health. www.show.scot.nhs.uk/scieh. (5 Mar 2007)
UK-based Anaphylaxis campaign. www.anaphylaxis.org.uk/. (5 Mar 2007)
World Allergy Organisation – List of worldwide allergy links. http://www.worldallergy.org/links.shtml. (5 Mar 2007)
