5 month-old patient with a H/O hives that began about 24 hours after her 4 month old vaccines consisting of Rotarix, Pediarix, Prevnar and HIB. Hives resolved over several days on Benadryl. For now I suggested holding further vaccines. I know these hives may be idiopathic. We can get AB titers as well to see which vaccines can be avoided in the future. Do you have any additional suggestions for how you would handle this case?


Thank you for your inquiry.

In your case, I think that the fact the hives occurred 24 hours after the vaccines and lasted several days does indicate that none of the vaccines were responsible, but this of course cannot be demonstrated without further evaluation. Unfortunately, evaluations for reactions to vaccines, especially after receiving multiple vaccines, are tedious and can be complicated.

Questions about urticarial and anaphylactic reactions occurring after infants receiving vaccines are one of the most frequent submitted to our website. We have over 20 entries regarding this phenomenon, and I could pick most any of our previous entries and apply them to your case. I have copied below the most recent entry, and the discussion contained in this entry will give you the appropriate references which contain algorithms and instructions as to the evaluation of an infant who develops urticaria or anaphylaxis after immunizations. Basically, if one carries this out to its fullest, each vaccine should be tested using non-irritant concentrations as described in the references cited. A reference you will find particularly helpful is Wood RA, et al. Pediatrics 2008 (September); 122(3):e771-777. This article contains a particularly helpful algorithm, and the abstract of the article is copied below. In addition you can find discussions of similar patients by entering "vaccines" into the search window here.

Thank you again for your inquiry and we hope this response is helpful to you.

Anaphylactic reaction in a 15 month-old occurring 11 hours after receiving multiple vaccines
A local pediatrician called me about a 15 month old who received Prevnar, polio, MMR and Hep A and Hep B. 11 hours later had full blown anaphylaxis, went to ER and received epi, etc. He also has a known milk allergy but no known ingestion of milk at that episode. Any experience with this type of reaction and how to approach?

Thank you for your inquiry.

Unfortunately, the problem that you described is an extremely difficult one, and quite tedious to evaluate. It requires treating each individual vaccine separately and investigating each as a potential culprit. This in turn will necessitate the use of skin tests.

In your case, it will be important also to take a very thorough history to make sure that the anaphylaxis was not due to an exposure subsequent to the administration of the vaccines, more proximate to the onset of the reaction.

We have numerous entries on our website regarding anaphylactic reactions to vaccines. Many of the entries describe patients similar to your patient. I have copied an entry below which will give you a reference by Dr. Robert Wood that lists appropriate non-irritating skin tests to several vaccines. In addition, there is an excellent reference by Dr. Wood entitled "Allergic Reactions to Vaccines." It appeared in Pediatric Allergy and Immunology, September 2013; Volume 24(6):521-526. In this reference, Dr. Wood presents the strategy used to evaluate an infant who has had an anaphylactic reaction to immunization.

There is also another excellent reference which preceded the one mentioned above. It is entitled "An Algorithm for the Treatment of Patients with Hypersensitivity Reactions after Vaccines." Dr. Robert Wood was the lead author. It is the result of the endeavors of the Working Group of the Clinical Immunization Safety Assessment (CISA) Network. It appeared in Pediatrics, September 2008; Volume 122(3):E771-E777. I believe that you can obtain this article without charge online (doi: 10.152/peds.2008-1002).

Finally, there is not enough room for me to copy all of the entries on our website regarding this topic. You can pull them all up by simply typing "vaccine" into the search box here.

Thank you again for your inquiry and we hope this response is helpful to you.

Possible allergic reaction to vaccines
I consulted a nine month old female infant. Her pediatrician referred her to me because she had developed giant urticarial brash 14 hours after infant got immunizations of oral rotavirus vaccine, Pentacil which is combination of DPT, hep B and poliovirus vaccine and 11 valent pneumococcal conjugate vaccines. Infant went to Children’s hospital E.R day after because hives kept getting worse. She received oral steroid 2 mgm po q.d divided in 2 doses. After which urticaria got better and steroids were stopped after 3 days. Mom said baby had gotten bananas for the first time and also she had changed soap to Aloe. She will require at least one more dose of Pneumococcal vaccine and DPT, Polio vaccine and Hep B. Could you please give me your thoughts as to what guidance will be appropriate for the referring Pediatrician.

This is a difficult problem and I am afraid the potential solution may be quite tedious for you. First of all, however, I believe that we can probably eliminate with reasonable confidence if indeed this was urticaria, the change in soap. However, you could test this quite easily simply by applying a small amount of soap to the baby’s skin and observing for any possible reaction for the next hour. I doubt, however, that you will find the soap is the culprit.

In addition, it would be unlikely that banana was the culprit because of the length of duration of the hives. However, you can eliminate banana reasonably well by simply obtaining an ImmunoCAP. So, I would clearly suggest those two procedures.

This of course leaves you with the possibility that one of the vaccines (or perhaps more than one) was responsible for the urticarial reaction. Unfortunately, the approach to vaccine allergy in an infant is not so simple. The best way for you to attempt to discern whether or not a vaccine was culpable would be to perform skin tests and graded challenges if necessary to each vaccine separately. You, of course, should clearly do this for the vaccines for which a readministration is necessary.

Fortunately there are articles which will be of help to you in proceeding with skin tests and perhaps graded challenges. Perhaps the most notable of these is by Robert Wood and colleagues. I have copied the abstract from the Journal of Pediatrics, 2008, for you below. This article presents an algorithm to assist you in approaching each vaccine.

Two other articles by Dr. Wood and associates, both from The Journal of Allergy and Clinical Immunology, will also be helpful to you. They list the non-irritant skin test concentrations for several vaccines (1, 2).

Another document which would be helpful to you is the Practice Parameter entitled “Adverse Reactions to Vaccines” by Drs. Kelso and Li. This was published in The Annals of Allergy, Asthma, and Immunology, Volume 103, October 2009, Page S1.

The Parameters gives you a prototype for a suggested graded challenge to vaccines when they must be administered cautiously. I would suggest if skin tests are negative that you approach the vaccines separately by using this type of graded challenge.

In summary, the evaluation of potential vaccine allergy when multiple vaccines have been given simultaneously is unfortunately tedious and time-consuming. There are no large series or multi-tested protocols for each drug, and therefore the utilization of general principles based on empiric criteria and previous case reports are all we have to use to establish an approach. The most standard way of which I am aware to deal with such patients is to skin test separately, and do provocative challenges when skin tests are negative and the vaccine is needed. These need to be done individually and on different days.

Fortunately there are for most vaccines skin test concentrations that are non-irritating, and there is a generalized but very helpful protocol to perform these procedures in the references cited above.

On the other hand, the two other potential culprits (banana and the topical agent) should be easily ruled out as potential causes.

Thank you again for your inquiry and we hope this response is helpful to you.

Pediatrics. 2008 Sep;122(3):e771-7.
An algorithm for treatment of patients with hypersensitivity reactions after vaccines.
Wood RA, Berger M, Dreskin SC, Setse R, Engler RJ, Dekker CL, Halsey NA; Hypersensitivity Working Group of the Clinical Immunization Safety Assessment (CISA) Network.
Collaborators (10)
Johns Hopkins Hospital, CMSC 1102, 600 N Wolfe St, Baltimore, MD 21287, USA.
Concerns about possible allergic reactions to immunizations are raised frequently by both patients/parents and primary care providers. Estimates of true allergic, or immediate hypersensitivity, reactions to routine vaccines range from 1 per 50000 doses for diphtheria-tetanus-pertussis to approximately 1 per 500000 to 1000000 doses for most other vaccines. In a large study from New Zealand, data were collected during a 5-year period on 15 marketed vaccines and revealed an estimated rate of 1 immediate hypersensitivity reaction per 450000 doses of vaccine administered. Another large study, conducted within the Vaccine Safety Data link, described a range of reaction rates to >7.5 million doses. Depending on the study design and the time after the immunization event, reaction rates varied from 0.65 cases per million doses to 1.53 cases per million doses when additional allergy codes were included. For some vaccines, particularly when allergens such as gelatin are part of the formulation (eg, Japanese encephalitis), higher rates of serious allergic reactions may occur. Although these per-dose estimates suggest that true hypersensitivity reactions are quite rare, the large number of doses that are administered, especially for the commonly used vaccines, makes this a relatively common clinical problem. In this review, we present background information on vaccine hypersensitivity, followed by a detailed algorithm that provides a rational and organized approach for the evaluation and treatment of patients with suspected hypersensitivity. We then include 3 cases of suspected allergic reactions to vaccines that have been referred to the Clinical Immunization Safety Assessment network to demonstrate the practical application of the algorithm.

1. Wood RA, et al. Irritant skin test reactions to common vaccines. J Allergy Clin Immunol 2007 (August); 120(2):478-481.

2. Wood RA, et al. Assessment of irritant skin test reactions to common vaccines. J Allergy Clin Immunol 2007; 119(1):S271.

Phil Lieberman, M.D.

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