• anaphylaxis;
  • asthma;
  • children;
  • immunotherapy;
  • side-effects

Subcutaneous immunotherapy (SIT) has been proven to be effective for the treatment of respiratory or hymenoptera venom allergy in children (1). Nevertheless, potentially severe side-effects have been reported in the literature, mostly in the adult population (1–3). The aim of this study is to assess the incidence and risk factors of systemic reactions (SR) in an exclusively paediatric patient population.

We analysed all visits from 2001 to 2006 for immunotherapy at the Paediatric Allergic Outpatient Clinic of the Geneva University Hospital. During this time period, data were recorded in an electronic patient filing system allowing systematic retrieving of information on side-effects. At each visit, the dose and possible immediate or late side-effects were recorded. In case of a reaction after injection, the type of reaction and the treatment administered were reported. All data were treated confidentially. For further analysis, SR were categorized into immediate SR (appearing within 30 min after injection) and late SR (occurring after 30 min). In addition, the severity of SR was graded according to Malling et al. (4).

One thousand two hundred and seventy-eight injections were administered to 44 patients. A total of 173 reactions were identified (13.6%), out of which 120 (9.4%) were classified as large local and 53 (4.1%) as systemic. An average of 3.9 reactions per patient was observed (for an average of 29 injections per patient). Most of the SR (86.8%) were classified as mild or moderate. We have noted only seven severe SR in six patients (13.6% of the patients).

We then looked for factors in relation with a moderate or severe SR. In comparison to mild SR, severe SR were more frequent in asthmatic patients (P < 0.05). The largest number (107/173) of the reactions occurred during the maintenance phase. Nevertheless, SR were most frequent during the initial build-up period (ratio of reactions to the number of injections). Most importantly, we observed a 4.6 times higher probability (95% CI: 2.5–9.9) of a SR rather than a local reaction after the 30-min observation period in the clinic (P < 0.01). However, all severe SR requiring immediate treatment occurred within 30 min after injection (Table 1).

Table 1.   Severity of the reaction regarding the time of onset
Severity of the systemic reaction (SR) <30 min: n (%) >30 min: n (%)
  1. *Skin symptoms, mild rhinitis and/or mild asthma.

  2. †Non-life threatening: general itching, erythema, bronchial obstruction.

  3. ‡Anaphylactic shock.

Mild SR*14 (1.1)15 (1.2)
Moderate SR†10 (0.8)7 (0.5)
Severe SR‡7 (0.6)0 (0)

Subcutaneous immunotherapy is recognized as an efficient and safe treatment in children suffering from respiratory or insect venom allergy (1, 3). Its use is limited to physicians trained to treat side-effects. Severe SR are rare (0.5%), and in our study severe SR occurred within 30 min after the injection, confirming the adequacy of the EAACI recommendations in children (1).

As reported in the literature (5), the incidence of mild and moderate SR was 3.6% per injection. Interestingly, we have observed that a significant number (47.8%) of mild and moderate SR occurred after the 30-min observation period in the hospital. These SR were mostly urticaria or rhinitis, requiring either only minor treatment, and in some patients asthma exacerbations clearly linked to SIT. In the literature, delayed reactions occurring after the patient left the medical facilities are not well analysed (1, 6) and the potential severity of these reactions is underestimated. In this study, the delayed SR were systematically recorded. This might explain the higher incidence of mild and moderate SR in our study, compared to the smaller numbers reported in others studies. Patients should be clearly informed on potential delayed reactions (1.7% per injection in our study), and appropriate instructions for treatment should be given.


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