Diagnosis and management of anaphylaxis

In their timely review Allis and Day (1) rightly point out that many cases of anaphylaxis are undertreated, with potentially life- threatening consequences. For illustration we would like to add that EpiPen device was only used in 29% in children with recurrent episodes of anaphylaxis (2) and only 7% of children with peanut and tree nut allergy had a self-injection epinephrine device available (3). However, overtreatment and misuse of epinephrine is also a problem not mentioned by the authors.

As pointed out by Unsworth (4) "Death following anaphylaxis is most feared but fortunately remains a very rare event, currently estimated at less than one case per year per million of the UK population (5)" Recent large child population based study of fatal and severe reactions to food from UK yealded only 0,006 fatal events per 100 000 children per year over the period 1990-2000. (6) Nevertheless, over 100 000 epinephrine syringes have been prescribed throughout the UK for community use in the year 2001 (4) and there was 300% increase of EpiPen prescriptions in Australia over the 1998-2002 years (7)

No evidence exists that the more liberal community prescribing of EpiPen has saved lives significantly. Furthermore, epinephrine carries some risk of cardiac arrhytmia, even when given in recommended doses. (8) This danger increases in patients with cardiovascular comorbidity or who are taking an interacting medications. (9) Alarmingly, a study amongst senior house officers showed that only 5% were able to indicate the correct route and dose of epinephrine. (10) These safety concerns become more alarming when epinephrine is prescribed to non-medical individuals.

The potential for misdiagnosis was recognised by the authors of Resuscitation Council guidelines.(11) Accordingly, epinephrine should be given only if the life threating features such as hypotension and respiratory difficulty are present. Generalised urticaria, flushing, itching, and even angio-oedema, unless affecting the larynx, are not an indication for use of epinephrine (11, 12). To label such benign reactions as anaphylaxis may render the subject vulnerable to being overtreated. Furthermore, diagnostic value of these minor reactions is low, because severe anaphylaxis may proceed in their absence (13).

Finally, we would like to emphasise the importance of the history in the diagnosis of severe anaphylaxis. Epinephrine should be given to all patients with previous severe reactions. The majority of serious reactions in the community setting are caused by peanuts and tree nuts. (13) Additional risk factors include age over 5 years, a history of asthma, reactions induced by traces of allergen, a strongly positive skin prick test, and patients on beta-blockers or ACE inhibitors (7, 13)

References

1. Ellis AK, Day JH. Diagnosis and management of anaphylaxis. CMAJ 2003;169:307-11.

2. Gold MS, Sainsbury R. First aid anaphylaxis management in children who were prescribed an epinephrine autoinjector device (EpiPen). J Allergy Clin Immunol. 2000;106:171-6.

3. Sicherer SH, Munoz-Furlong A, Burks AW, Sampson HA. Prevalence of peanut and tree nut allergy in the US determined by a random digit dial telephone survey. J Allergy Clin Immunol. 1999;103:559-62.

4. Unsworth DJ. Adrenaline syringes are vastly over prescribed. Arch Dis Child. 2001;84:410-1.

5. Pumphrey RSH. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy 2000;30:1144-50

6. Macdougall CF, Cant AJ, Colver AF. How dangerous is food allergy in childhood? The incidence of severe and fatal allergic reactions across the UK and Ireland. Arch Dis Child. 2002;86:236-9.

7. Kemp AS. EpiPen epidemic: suggestions for rational prescribing in childhood food allergy. J Paediatr Child Health. 2003;39:372

8. van der Linden PW, Hack CE, Struyvenberg A, Kees van der Zwan J. Intentional diagnostic sting challenges: an important medical issue. J Allergy Clin Immunol 1994;94:563-4.

9. Johnston SL, Unsworth J, Gompels MM. Adrenaline given outside the context of life threatening allergic reactions. BMJ 2003;326:589-90.

10. Gompels LL, Bethune C, Johnston SL, Gompels MM. Proposed use of adrenaline (epinephrine) in anaphylaxis and related conditions: a study of senior house officers starting accident and emergency posts. Postgrad Med J 2002;78:416-8.

11. Project team of the Resuscitation Council (UK). Update on the emergency medical treatment of anaphylactic reactions for first medical responders and community nurses. Emerg Med J 2001;18:393-5.

12. Hourihane JO'B, Warner JO. Benign allergic reactions should not be treated with adrenaline. BMJ 1995;311:1434.

13. Sampson HA. Peanut allergy. NEJM 2002;346:1294-9.

Michal R Pijak Consultant in Rheumatology, Allergy and Clinical Immunology Frantisek Gazdik Research Fellow Division of Allergy and Clinical Immunology, Institute of Preventive and Clinical Medicine, Slovak Medical University Bratislava, Slovakia

Conflict of Interest:

None declared

About cross reactivity between cephalosporin and penicillin, do Ellis and Day include third generation cephalosporins (TGCs)?

There have been contradicting recommendations on this issue.

Kelkar and Li [1] say TGCs should NOT be prescribed in a review which does not prove their point based on extrapolation and inference.

Anne and Reisman [2]conclude that it is SAFE to administer cephalosporin antibiotics, especially TGCs, to penicillin-allergic patients after a throurough study of available data.

A more recent letter of Pumphrey and Davis to the Lancet [3]quoted by Kelkar and Li reports a retrospective record of 6 anaphylactic deaths in 5 years in the UK after a first cephalosporine dose with 3 of the patients having a reported penicillin allergy. The generation of the cephalosporin involved is not indicated. Furthermore another reason why this report cannot be interpreted is that what we'd need is the number of penicillin allergic patients given a TGC that would experience an anaphylactic reaction.

My current experience is that many physicians in hospitals in France are not reluctant to use third generation cephalosporins in penicillin allergic patients when indicated, in the hospital environment.

The comments of allergy specialists such as Ellis and Day (and hopefully others) would be useful in this era of increasing antibiotic resistance of bacteria and difficult antibiotic choices.

[1]Cephalosporin allergy. N Engl J Med 2001 Sep 13;345(11):804-809.

[2]Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol. 1995,74 : 167 -170.

[3]Under-reporting of antibiotic anaphylaxis may put patients at risk. Lancet 1999;353:1157-8.

Conflict of Interest:

None declared

I have a few questions to Drs Ellis and Day and would appreciate reading their comments:

1- Since there seems to be no clinical comparative study on which to base recommendations for ED discharge prescription, Ellis and Day recommend a 4 days prescription of prednisone and diphenhydramine and this a widespread attitude. But why do they not advocate a newer non sedative antihistamine since many patients have to drive or work, and why don't they recommend adding ranitidine for 48 hours based on the experimental evidence presented earlier in their paper and the risk for a severe biphasic reaction ? As they insist that second phase reaction may be more severe than the primary this might be safer, although unproved.

2- What dosage of prednisone do they recommend, do they taper the dose down ?

Conflict of Interest:

None declared