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| Issue 3 1999 |  |
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Leslie
Burnett Director, PaLMS Contact: Tel: 02 9926 8086 e-mail: lburnett@med.usyd.edu.au |
| I would like to take this opportunity to thank the many consultants who have provided us with such encouraging feedback on the first two issues of InfoLink and its usefulness in the clinical setting. I trust that you also find the article in this issue of interest and that if you have any further enquiries, please contact Dr Baldo on the numbers given below. | ||
PaLMS is undergoing rapid growth and our new referring consultants have requested more information on our collection facilities. Any patient with a PaLMS request form can visit any of our six collection facilities. Outpatients of a particular hospital do not need to return to that same facility for collection. For example a patient seen at a clinic, or even as an inpatient at any particular hospital, who requires a test to be performed 2 weeks later, can attend any of our centres for the follow-up collection. If the patient’s MRN is included on the request form, the results will also be linked to the existing results for that patient. This will facilitate your being able to gain access to all results in a single enquiry for that patient through our information system, AUSLAB. In this issue, we have included a map of the various specimen collection facilities including details of parking access for your patients. We are currently investigating a number of additional specimen collection facilities and we will advise you as these open. New PaLMS request forms are currently being designed which will include the collection centre information, including maps, on the reverse side. For your convenience, request forms can be pre-printed with your name and details. For hospital wards and clinics where many referrers, including junior medical staff on rotation, share the same forms, we will continue to use non-preprinted forms but we will be offering a simple labelling system to minimise the amount of handwriting. The PaLMS Department of Anatomical Pathology offers a Fine Needle Aspiration Biopsy (FNAB) service for lesions not requiring imaging localisation. FNAB can be arranged for inpatients and outpatients at Royal North Shore Hospital, North Shore Private Hospital and the Area District Hospitals. Please ring the Department on (02) 992 67345 to organise FNAB procedures. During October you will be sent a copy of our newly released Service Directory. The Directory should prove to be a valuable reference with descriptions of services provided, phone numbers, pathologist’s profiles and special interests and laboratory profiles and capabilities. There is also a comprehensive test directory with information on each test including reference intervals, test availability, patient pre-test preparation, collection tubes and turnaround times. If you wish to reserve extra copies, please phone PaLMS Administration on 9926 8086. |
| LABORATORY TESTS TO DETECT ALLERGIC REACTIONS TO DRUGS |
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Brian A Baldo Molecular Immunology Laboratory Kolling Institute of Medical Research, Royal North Shore Hospital Tel: +61 2 9926 7272 email: babaldo@med.usyd.edu.au |
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| Incidence of adverse drug reactions Adverse drug reactions are a common clinical problem and a significant source of morbidity and mortality. The very large variety and number of drug administrations throughout the world each day provides a seemingly never-ending source of potential deleterious reactions, many of which almost certainly remain undetected or misdiagnosed. Even so, adverse drug reactions are said to account for 2-3% of consultations in general practice and surveys of hospitalized patients have shown that 6-15% of beds are occupied by patients with a drug-related condition. The literature reveals that virtually all drugs, including corticosteroids, antihistamines and even vitamins, have been implicated in adverse reactions. It has been estimated that approximately 5% of adults in the U.S.A. may be allergic to one or more drugs but as many as 15% believe themselves to be “allergic” to medications and may therefore, rightly or wrongly, be denied treatment with an indicated drug. Given the lack of understanding of the many different drug-induced adverse reactions and consequent absence of specific diagnostic tests, the larger of the above two percentages may be closer to the real situation. In Europe, 10-30% of treated patients experience one or more untoward reactions and about 15% of patients who undergo a medical check-up have some history of drug allergy. Drugs may provoke a large variety of adverse reactions from life-threatening anaphylaxis to mild, transient skin rashes but other drug-induced side-effects, generally mediated by cells, include serum sickness, urticaria, haemolytic anaemia, interstitial kidney disease, hepatitis, Stevens-Johnson and Lyell syndromes, toxic epidermal necrolysis, fixed drug eruptions, different exanthemas and hypersensitivity myocarditis. At present, mechanisms of most of these reactions are not understood and specific diagnostic tests are available only for immediate (type 1, IgE-mediated) allergies. Since IgE antibodies are not involved in the cell-mediated reactions, testing for specific IgE is generally not warranted in such cases unless a concomitant type 1 allergic sensitivity is suspected or needs to be excluded. Anaphylaxis, the most severe and rapid adverse reaction, is mediated by IgE antibodies and is associated with the release of histamine and other vaso-active substances. It may appear clinically as pruritis, erythema, flushing, urticaria, angiodema, nausea with diarrhoea and vomiting, laryngeal oedema, bronchospasm, hypotension, cardiovascular collapse and death. An anaphylactoid reaction encompasses all reactions that are clinically indistinguishable from anaphylaxis but for which other mechanisms are responsible. In particular, specific IgE antibodies are not involved. |
Specimen Information
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| Tests available PaLMS offers specific tests for the detection of IgE antibodies to a range of drugs commonly suspected of causing immediate allergic reactions (Table 1) including b-lactam antibiotics and anaesthetic agents which provoke anaphylactic responses more often than any other drug. |
| Penicillins Benzylpenicillin (Penicillin G) Phenoxymethylpenicillin (Penicillin V) Ampicillin Amoxicillin Cloxacillin Flucloxacillin Ticarcillin etc2 [Clavulanic acid] Cephalosporins Cephalothin Cefaclor Cephalexin etc 2 |
Other
Antibacterials Trimethoprim Sulfamethoxazole Cinoxacin Anaesthetic Agents Neuromuscular blocking drugs Alcuronium Atracurium Succinylcholine Vecuronium Rocuronium etc 2 Induction agent Thiopentone |
Narcotics
Morphine Codeine Local Anaesthetics Procaine Lignocaine Analgesics Paracetamol Other Latex |
| 1.
Tests are in the form of immunoassays for the detection of drug-reactive
IgE antibodies. 2. Tests for other drugs in the group are either available or may be developed upon request. |
| Reactions to penicillins and cephalosporins
The b-lactams antibiotics, penicillins and cephalosporins, are the most commonly prescribed antibacterials but these compounds are also the most common cause of drug allergies seen clinically. The first reported case of penicillin-induced anaphylaxis and the first reported death occurred in the early years of usage in the 1940's. The frequency of allergic reactions is reported to be from 0.7-8% of treatment courses. Fear of an allergic reaction to penicillin is the major reason the antibiotic is withheld in the 5-20% of patients who state that they are allergic to the drug. This can have detrimental clinical consequences including treatment delay and failure, increased cost and side effects of alternative anti-bacterial therapy and, importantly, substitution of a "reserve" antibiotic such as vancomycin, valued and, ideally, retained for its activity against resistant organisms. For the practicing clinician, it is useful to classify adverse reactions to penicillins according to their time of onset (Table 2). Reactions occurring within the first hour include urticaria, rhinitis, laryngeal oedema, wheezing, hypotension and shock. Late reactions, that is those beginning more than 72 hours after onset of therapy, include maculopapular exanthemas, drug fever, haemolytic anaemia, nephritis, leukopenia, exfoliative dermatitis, Stevens Johnson syndrome and serum sickness which can involve fever, arthralgia, diffuse adenopathy, rash and renal involvement. Reactions occurring at times between these two extremes usually involve urticaria and, occasionally, laryngeal oedema. |
| Time | Clinical reactions |
| Immediate(up to 1 hour) | anaphylaxis hypotension bronchospasm/wheezing angioedema laryngeal oedema urticaria |
| Delayed (1-72 hours) |
urticaria angioedema laryngeal oedema wheezing |
| Delayed(>72 hours) | rash drug fever serum sickness neutropenia haemolytic anaemia Stevens-Johnson syndrome Lyell syndrome exfoliative dermatitis etc |
| The frequency of measles-like rash in patients treated with penicillin
is about 2% but rashes induced by ampicillin occur with greater frequency
(5.2-9.5%). The incidence of ampicillin-induced rash in subjects with Epstein-Barr
virus or cytomegalovirus infections may be up to 100%. The precise immunological mechanisms underlying exfoliative dermatitis and Stevens-Johnson syndrome are not known. Cephalosporins are structurally and pharmacologically related to penicillins and their propensity to cause adverse reactions appears to be at least as great as the latter drugs. Despite the alarmingly heavy and increasing use of these valuable antibacterials, including their routine administration before some surgical procedures, diagnostic procedures to confirm or predict their involvement in allergic and other adverse reactions are rarely employed This is primarily because suitable diagnostic reagents have not been available. Results of tests for b-lactam-reactive IgE antibodies will help to provide safer and reaction-free antibiotic therapy and thus preserve the effectiveness of those vitally important antibiotics (such as vancomycin) that should be reserved for dangerous resistant microbial strains. Other Antibacterials The combination of the antibacterial agents trimethoprim and sulfamethoxazole, also known as co-trimoxazole, is extensively used for the treatment of bacterial infections. Adverse reactions to this drug formulation are not uncommon and show a higher frequency of occurrence than almost any other drugs except the penicillins. Trimethoprim is a synthetic folate antagonist anti-infective agent widely used for the treatment of urinary tract infections and in AIDS patients for Pneumocystis pneumonia. Immediate hypersensitivity reactions to trimethoprim are well recognized clinically and can be confirmed in the laboratory by application of an immunoassay to detect drug-reactive IgE antibodies. An immunoassay to detect IgE antibodies to sulfamethoxazole has also been developed and is available through PaLMS. IgE antibodies detected in this test may cross-react with other sulfonamides. Narcotics The narcotic analgesics are among the most commonly prescribed drugs in hospitals and are administered to up to 40% of patients. Many of the narcotics, especially the opioids, are potent histamine releasers and to this effect has been attributed many of the reported anaphylactoid responses. Even so, IgE antibodies to pethidine have been reported and morphine- and codeine-reactive IgE antibodies have been detected and examinations for these antibodies are frequently requested. Anaesthetic Agents Studies over the last 15 years, principally in Australia, France and New Zealand, have shown that life-threatening allergic reactions to anaesthetic drugs occur much more commonly than previously recognised. In Australia, at least 200 such reactions, together with the occasional death, occur each year. If this incidence of allergic sensitivity is extrapolated world-wide and if satisfactory diagnosis is to be instituted and patients' and clinicians' fears of a possible reaction are to be allayed, it is clear that reliable, easy to use, relatively inexpensive tests giving a quick answer are needed. PaLMS offers laboratory-based serum tests for the detection of IgE antibodies to the neuromuscular blocking drugs (NMBDs) such as suxamethonium, atracurium, alcuronium, vecuronium, rocuronium etc and to the induction agent thiopentone. Most allergic reactions that occur under anaesthesia are due to the NMBDs and antibodies to one NMBD usually cross-react with all other NMBDs by virtue of recognition of the common specificity i.e. quaternary ammonium groups. |