Mild systemic reactions to Hymenoptera venom immunotherapy during maintenance phase – case report and review of the literature

Conclusions:

C Chopra, R Baretto, M Duddridge, MJ Browning

University Hospitals of Leicester NHS_ NHS Trust Leicester Royal Infirmary

IntroductionHymenoptera venom immunotherapy (VIT) is an effective, potentially life saving treatment modality in certain venom allergic patients. The use of VIT can be hampered by the occurrence systemic reactions during either the induction phase or in the maintenance phase of therapy.Systemic reactions were described to occur in 7.5% of weekly incremental VIT injections; and in 2.1% of monthly maintenance VIT injections (Youlten et al., 1995). In a large European multi centre study involving 840 patients on VIT, 20% of patients reported systemic side effects following injections. 1.9% of injections in the induction phase; and 0.5% of those in the maintenance phase led to side effects (Mosbech et al., 2000). From our own experience of VIT in Leicester, systemic reactions during the maintenance phase of therapy are not uncommon (~10%: personal communication with colleagues). Their occurrence can lead to discontinuation/ interruption of the immunotherapy course, and therefore treatment failure. The guidance on how to manage patients who have such reactions during therapy is not completely clear, and poses a challenge to clinicians. There are no specific recommendations in the literature on how to manage patients experiencing systemic reactions whilst on maintenance therapy.

Department of Immunology, University Hospitals of Leicester

CaseA 46 year old primary school teacher presented to Leicester Allergy services with a history of an episode consisting of generalised urticaria, blistering rash over her legs, chest tightness and wheeze following a wasp sting. Her total IgE level was 55.90 kU/L (0-122 kU/L) and wasp venom specific IgE titre was 0.37 kU/L (0-0.35 kU/L). Her basal mast cell tryptase was 2.6 ug/L (2-14 ug/L).She elected to be commenced on a wasp venom immunotherapy programme. The induction phase (12 weekly doses as per EAACI protocol) was well tolerated. She then went on to receive 100 micrograms of pharmalgen wasp venom injected subcutaneously as a single dose (maintenance therapy) every 4 weeks. There were no reported insect stings during this time.At maintenance dose number 53 (> 3 years into therapy), she had experienced facial itch, tingling and lip swelling which all responded to anti-histamines. Her serum specific IgE to wasp venom at this point was 0.41kU/L. She continued to receive maintenance wasp venom immunotherapy at 100mcg every four weeks as a single injection, and was pre-medicated with oral anti-histamine at each visit. This did initially help alleviate her symptoms, but, at maintenance visits 57-61, she continued to experience lip and ear pruritus as well as lip angioedema. She subsequently underwent intradermal skin tests with pharmalgen wasp venom. (see Table 1 – Results)

Table 1 – Results of intradermal skin tests to pharmalgen wasp venom

Time 0 mins Time 15 mins Interpretation

Albumin (0.02ml) 5mm wheal 5 mm wheal Negative

Pharmalgen wasp venom (0.02ml) @ 0.01mcg/ml

5 mm wheal 5 mm wheal Negative

Pharmalgen wasp venom(0.02ml) @ 0.1mcg/ml

5 mm wheal 9 mm wheal35 mm flare

Positive

It was agreed to updose her to 150 mcg wasp venom as maintenance every 4 weeks. The updosing schedule that was utilised (Fig 1) had been previously used in patients who had systemic reactions following field stings whilst on maintenance immunotherapy, and in the absence of any other formal clear guidance, was extrapolated for use here. During therapy this lady did initially require concurrent antihistamine therapy for similar mild systemic reactions as reported previously. However, in the later phases of therapy, she had reported no symptoms after the injections and had not required any treatment with antihistamines. Her serum specific IgE level to wasp venom was now 0.13 kU/L.

At 15 months of updosed maintenance wasp VIT, it was decided to cease therapy, after a total of 6 years of therapy.

Pharmalgen wasp venom (dose in mcg)

Time (hours)

100 0

20 0.5

120 2.0

30 2.5

Table 2 - Updosing schedule (ref Rueff et al., 2001; Bonfiazi et al., 2005)