Case 1: Immunizations: Are their administration and reactions ever ‘routine’?

A previously healthy five-year-old boy presented to a community paediatrician's office for a well-child visit with his mother and younger sister. Parental concerns at the time included nightmares and intermittent nocturnal enuresis. No other issues were identified. In the past, the patient was treated for several conditions: recurrent otitis media (bilateral myringotomies and tube insertion at 21 months of age), asthma (salbutamol and fluticasone propionate as required) and eczema (in infancy). The patient was also recently investigated for food allergies after developing one hive on his face following ingestion of pine nuts. He had previously tolerated other tree nuts, eggs, milk and fish with no untoward reactions. Skin testing for pine nut allergy was negative. He was on no medications and had no drug allergies to date. His immunizations were up to date. Both parents had seasonal allergic rhinitis and the patient's sister had eczema. There were no pets or smokers in the home. Physical examination revealed a happy, well-looking boy with growth parameters on the 50th percentile (height and weight). The rest of the examination was entirely normal. The visit concluded with the administration of the five-year-old diphtheria, tetanus and acellular pertussis (DTaP)-poliomyelitis booster. On explanation of the possible side effects, the patient immediately became anxious, screaming and crying even after the procedure was completed. Within 5 min, the patient's mother returned to the office and said that there was something wrong with her son. He was complaining of burning eyes and lips. A brief examination revealed increasing angioedema of the eyelids (and lips to a lesser extent), and widespread urticarial lesions on the abdomen, back, arms and legs. There was no wheezing on auscultation of the chest and no tongue swelling. Due to the urgency of the clinical situation, pulse and blood pressure were not measured because the doctor was attending to the preparation and administration of epinephrine. Both the patient and his mother were very distraught. Due to the boy's anxiety and lack of cooperation, it took four adults, including the doctor, to administer 0.15 mg of epinephrine intra-muscularly in the left thigh. A total of 30 mL (75 mg) of diphenhydramine elixir was then given by mouth, again with the aid of several adults. The child was transported to the closest hospital for further assessment and treatment. He did not require any further epinephrine and received only diphenhydramine on an as-needed basis on discharge. A retrospective, population-based assessment of medically attended injection site reactions (1) reported an incidence of four same-day urticaria reactions following the administration of 76,133 DTaP vaccines (incidence of 0.005%). Similarly, a recent update on side effects from common vaccines (2) described a 0.001% incidence of immunoglobulin (Ig) E-mediated anaphylaxis following administration of the DTaP vaccine. Although these reactions are rare, they can be unpredictable and it is essential to be prepared. One study of eight children with systemic immediate allergic reactions to routine immunizations indicated that they had all received previous DTaP vaccinations and had no previous allergic reactions to earlier doses (3). While it has been previously documented (4) that children who display immediate systemic allergic reactions to DTaP vaccinations have antigelatin IgE, this study found no antigelatin IgE in any of the patients. Rather, they described detectable levels of anti-DTaP toxoid IgE, indicating that children can develop unexpected hypersensitivity to the toxoids in the vaccines themselves (3). In light of these facts, we recommend that all paediatricians routinely ensure they have an up-to-date supply of epinephrine that is easily accessible in their offices, should such a reaction occur. While it is virtually impossible to monitor all children receiving routine immunizations postadministration, there may be a role for monitoring the most ‘high-risk’ children. A report by Skov et al (5) of a child exhibiting hypersensitivity to the diphtheria component in the DTaP vaccine also described a child with a history of atopic dermatitis and hay fever, as well as a family history of atopic disease. Like our case, this child had received several DTaP vaccinations in the past and displayed no symptoms of hypersensitivity. On receiving his third vaccination, he developed urticaria (5). This suggests that there could be a role to triage highly hypersensitive patients differently. All the children who developed a reaction to the DTaP vaccine in the study by Sakaguchi et al (3) exhibited initial symptoms between 5 min and 30 min following vaccine administration, with an average time to initial symptoms of 13 min. Thus, based on the limited data available on systemic allergic reactions to DTaP in children who have previously tolerated the vaccine, one could consider asking highly atopic/multiallergenic children to stay in the waiting room for 30 min following their immunization to ensure no hypersensitivity reaction occurs. In addition, an unexpected reaction in children who have tolerated previous vaccinations may indicate a potential role for further workup of the etiology of their hypersensitivity reaction. However, further study is required because adverse reactions to vaccines are very rare in general paediatric practices compared with allergy practices. Interestingly, our patient's symptoms appeared to be compounded by an intense anxiety surrounding both the initial immunization and the subsequent management of his hypersensitivity reaction. In a review of anxiety in allergy and atopic dermatitis, Hashizume and Takigawa (6) described the relationship between anxiety and hypersensitivity responses. They described a vicious cycle between anxiety and clinical hypersensitivity symptoms, explaining a dysregulation of T helper cell type 2 responses due to dysregulation of the neuroimmune system, leading to worsening of allergic symptoms. Furthermore, they described successes in the adult population with use of tandospirone, a 5-hydroxytryptamine 1A receptor agonist with anxiolytic and antidepressant effects at attenuating itchiness in hypersensitivity reactions. These data indicate that psychological interventions, such as attempting to alleviate anxiety, may be helpful in the management of allergic patients. Clearly, the reaction described in our patient is very rare, and the only such reaction observed in our busy clinical practice over the past 25 years. However, because immunizations are such an integral part of daily practice, we believed it was important to remind clinicians that this kind of reaction can happen. Unexpected allergic reactions to DTaP vaccinations may occur, albeit rarely, and paediatricians must be prepared to treat them. One could consider triaging highly atopic patients differently when administering vaccinations, perhaps observing them in the office for 30 min postvaccination.

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