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- Penicillin -
12/7/05 re: Characteristics of ampicillin/amoxicillin rashes Hi, I have a question regarding infectious mononucleosis rash in association with amoxicillin (Trimox) use. Where on the body does the rash usually start? And does it necessarily have to be generalized from head to toe? I have seen one patient with a rash only on the trunk after ampicillin use. Of course, the medication was almost immediately discontinued after the rash appeared. Is the locality of the rash a diagnostic factor?
To help respond to your question, I obtained input from Dr. Franklin Adkinson of the Johns Hopkins Medical Institutions, an expert in penicillin allergy. His comments are enclosed below.
Dr. Adkinson's comments:
Re: aminopenicillin rashes/monorashes/interactive rashes. I agree that I am not aware of any diagnostic characteristics of these rashes which are usually described as "morbiliform." Most I have seen are highly variable in distribution and some tend to migrate over hours to days. Trunk is commonly involved, but face and extremities can also be part of it. My clinical bias (non-EBM based) would be to be skeptical of rashes that are exclusively head and neck and involve more erythema than papules, as well as exclusively lower extremity rashes. Best guess on immunopathogenesis would be that they are T cell mediated, and it has been speculated that the epitope may involve some penicillin polymers, since the highest rate is with the aminopenicillins (amox and amp) which are the only penicillins that can spontaneously polymerize.2/8/02 re: Protocol for skin testing to amoxicillin Do you know of a good and reliable protocol for amoxicillin or ampicillin testing? I had one which went up to 3 mg/ml by ID and 10 mg/ml by prick, but I can't find the reference for it (?from a lecture by Timothy Sullivan). The only references I can find are from the groups in Spain and they use up to 20 mg/ml, which I'm afraid would be irritant concentrations. I consulted Dr. Franklin Adkinson, a leading expert in penicillin allergy, to obtain his current approach in the area of your question. His response is enclosed below. You may wish to start intradermal testing with lower concentrations of ampicillin (perhaps 0.03 mg/ml, then 0.3 mg/ml before the final testing with 3 mg/ml, the top concentration suggested by Dr. Franklin Adkinson. I also suggest that you read Dr. Adkinson’s chapter about drug allergy in the most recent edition of the "Allergy, Principles and Practice" textbook to get additional background material. Dr. Adkinson’s comments:
"From our experience, ampicillin at 3mg/ml is well tolerated and probably sufficient for top-dose id testing. CF studies in the US and the Spanish allergists use up to 20mg/ml id which allegedly produced specific responses, but I have no personal experience with this high a concentration. Amoxicillin would be the used the same way except there is no IV prep, so a non-approved source would have to be used, or capsule contents dissolved. The latter produces flocculants from excipients so we try to avoid using this. Hope this helps."1/17/02 re: Resensitization to penicillin Is there concern about resensitizing a previously (remotely) PCN allergic patient by skin testing or oral challenge who has since lost sensitivity? I am assuming that the individuals to whom you refer had a valid immediate (IgE mediated) reaction to penicillin therapy in the past and were penicillin skin test reactive at that time. I have previously discussed the questions you now raise with Dr. Franklin Adkinson of Johns Hopkins Allergy and Asthma Center, one of the leading experts in penicillin allergy. Based on the information he provided, my responses would be:
1) Skin testing with PPL (Pre-pen) should not resensitize the patient
2) Skin testing with the penicillin G solution could theoretically boost a dormant penicillin sensitivity, although this has really not been documented to any extent. However, it is for this reason that most investigators recommend carrying out the penicillin G skin tests shortly before the repeat penicillin therapy is attempted.
3) Some studies have shown that some individuals previously allergic to penicillin but now penicillin skin test negative will become transiently skin test reactive after receiving a course of tolerated penicillin. Although this transient conversion to penicillin skin test positivity generally presents no problem with future therapy, some investigators recommend re-skin testing to penicillin before attempting future penicillin therapy in such individuals.
4) Of course, the skin testing approaches to penicillin sensitivity may be limited at present by the shortage of PPL supplies and the lack of an FDA-approved MDM preparation for clinical use.
7/10/01 re: What to do in absence of Pre-Pen Now that Pre-Pen is not available for the time-being, what would you suggest for those of us who are already out of Pre-Pen? Is there any good evidence that a RAST would be a decent substitute until the FDA resolves the issue? And if so, any better laboratory to recommend? There is no easy answer in this very unfortunate situation. I have enclosed below the input I solicited several months ago from Dr. Franklin Adkinson, a respected authority in the area of penicillin allergy. Dr. Adkinson has also told me that commercially available RAST for anti-penicillin IgE antibodies of which he is aware are not sufficiently sensitive/reliable to use in making therapeutic recommendations. The only things I can suggest to you now are: 1) Check with allergist colleagues in your geographic area to see if they can spare a small part of their Pre-Pen supply. They may have material in excess of their needs which will be reaching expiration dates within the next several months. Perhaps you can purchase that material from them with the understanding that you will return any unused material if their needs unexpectedly increase
2) Skin test with penicillin G in the appropriate concentrations, if you have this reagent. This will pick up some (but not all) those who would react positively to Pre-Pen skin tests.
Dr. Adkinson's comments
The situation with supply of "Pre-Pen" is now a crisis for allergists and their patients. I am faxing you minutes from the Academy's Adverse Reactions to Drugs Committee which outlines the relevant history, and a letter from the academy, college and JCAAI to a Deputy Commissioner asking for a meeting to resolve this crisis. In short, the answer to your pharmacist's inquiry is that there is no remedy for this depletion of supply and impending shortage unless the FDA and the licensee (Hollistier Steir) can reach some accommodation to allow production to continue under current approvals.2/4/00 re: Penicillin (PCN) challenge As you know PCN G is not currently available. I realize that about 93% of allergic cases are picked up by prepen. But what can we do about the other 7% now ? Lets say a patient only had a skin reaction to PCN in the past and is prepen neg. Do we give pcn or a challenge dose? Minor determinants are not available.
You have addressed an important problem for which there is no ready solution. As you likely know, some investigators find that sensitivity to the minor PCN determinants, while responsible for only a small percentage of PCN allergies, tend to be associated with more severe reactions. Therefore, the current pre-pen skin test negative status in your patient does not rule out the small likelihood of potentially serious PCN sensitivity (potentially more serious upon rechallenge than the earlier reaction ). Unfortunately, despite a major effort by the AAAAI leadership, the FDA has not approved a minor determinant mix because they have felt that further supporting evidence is required. Some groups, including mine, have "home made" penicilloate-penilloate preparations for skin testing. Therefore, I have no personal experience with the clinical scenario you describe. In the situation you describe. I would lean to the cautious side and challenge the patient with graded increasing doses of the therapeutic penicillin preparation under medical observation.
12/6/99 re: penicillin G for testing We are having difficulty getting penicillin-G for testing . We have been told it is not available. Have you heard anything about this and if yes is there any other procedure for penicillin testing. Only a small percentage of immediate allergic reactions are directed against the native penicillin G itself. Most reactions are against the catabolic products of the beta-lactam core portion of penicillin agents,- penicilloyl (the "major determinant") and the "minor determinants" (penicilloate, penilloate). It is still uncertain how often, if ever, IgE mediated reactions are directed against side chain determinants specific for certain members of the penicillin group. Previously there was some enthusiasm for using, as skin test material, reconstituted penicillin G which had been allowed to stand at room temperature to presumably allow decay into the metabolites noted above. However, such a practice is unreliable because of the inconsistent catabolism of penicillin G. For skin testing , penicilloyl polylysine (which detects probably about 85% of allergic individuals) is commercially available (Pre-Pen, Schwarz Biopharma). However, a "minor determinant mix" is not available commercially because it has not yet been approved by the Food and Drug Administration in the USA.
8/9/97 re: amoxicillin specific rash vs true penicillin allergic reaction Quite often infants who are prone to develop many viral upper respiratory infections are given amoxicillin because of the difficulty in distinguishing them from true bacterial infections and due to parental pressure. Many times such infants develop fine red erythemaotous rashes after a few days, which are most likely due to the underlying illness rather than due to a true penicillin allergy. It could very well be also due to the innocuous ampicillin specific rash which is not IgE mediated. The problem arises when the practitioner unwittingly labels these as penicillin rash and thereafter necessating use of other antibiotics which are more expensive and more likely to produce allergy. What is the solution to this common problem? The questioner raises several very important points. Over the years, I have seen many teen-agers and adults previously labeled as "penicillin-allergic" based upon a history similar to that described by the questioner. I agree that, in most cases, the rash described is most likely associated with the underlying viral infection. One would hope that education of primary care physicians and pediatricians about this situation would reduce the frequency of such "loose statements" about penicillin allergy as a cause of the rash. However, some practitioners may feel obliged to raise the possibility of an allergic reaction because they cannot prove that the rash was viral infection -related. Fortunately, allergists with appropriate skin testing materials can determine with fair certainty at a later date whether an individual has IgE antibodies against penicillin antigens and is at an increased risk of an immediate IgE-mediated reaction following treatment with penicillin agents. Unfortunately, some of the skin testing materials (the "minor determinant" antigens) are not yet available for general clinical use. AThose allergists using them have "home-made" supplies. I suggest that you obtain consulatation with a certified allergist in your region, if needed. If you wish, you can obtain names of such allergisy-immunologists by calling the American Academy of Allergy, Asthma, and Immunology Executive Office at 1-800-822-2762.
5/6/97 re: cephalosporin allergy If a patient develops type 1 allergic reaction to a cephalosporin, what are the chances of his or her developing similar reaction to penicillin? It is estimated that there is about a 15-20% incidence of cross-reactivity between penicillin and cephalosporin, as detected by immune testing. Most cases involve a previous reaction to penicillin and subsequent treatment with cephalosporin. It is not yet clear how many of the individuals with cross-reactive sensitivity actually manifest acute allergic clinical reactions during the subsequent challenge. This cross-reactivity is to a beta-lactam component common to penicillins and cephalosporins. Also, there are scattered reports of possible "side-chain specific" sensitivity to particular cephalosporins. The best practical approach to the situation you describe is to have the patient skin tested with a panel of penicillin antigens by a qualified allergist. 3/11/97 re: EBV mono syndrome and rash to Augmentin 17 y/o female with pharyngitis given Augmentin and developed erythematous macular papular rash within 24 hours. Patient was switched to Ceclor and rash worsened. Throat culture negative. Infectious disease consult negative to EBV and multiple other viruses and patient labeled as EBV -negative Mono syndrome with ampicillen rash. Question- is the rash associated with mono and ampicillen specific to EBV? Is it worth doing penicillin skin tests to determine if this patient is in fact at risk to developing a systemic reaction if rechallenged with a penicillin derivative ? I should mention patient did have minor LFT elevations within a week after her first presentation. She continues to have fatigue 2 months after initial presentation. Thanks for any help you can offer. Ampicillin-induced macular-papular delayed onset rashes are increased, but not confined to those with EBV infection. These rashes differ from true allergic reactions to the beta-lactam ring common to all penicillin agents. The latter generally present as "immediate" (onset within hours) urticarial and/or anaphylactic reactions. Negative responses to skin testing with an appropriate panel of penicillin antigen preparations indicates that the individual is not at increased risk of an immediate anaphylactic response to any penicillin agent but does not predict the likelihood of the ( generally milder) delayed - onset macular-papular rash.
