Effect of venom immunotherapy and sting challenge on health-related quality of life measured by venom-allergy quality of life questionnaire (VQLQ) in Jack jumper ant allergic patients

Abstract

Health-Related quality-of-life (HRQoL) is an important component of the allergic morbidity suffered by patients. In contrast to the “direct” allergic morbidity experienced as part of the allergic reaction itself, “indirect” morbidity stems from the potential risk of reaction in the future and subsequent effects on patients' experience and participation in life. This indirect morbidity is distinct, and can have pervasive impact where the possibility of sting exists—even if actual stings may not have occurred for many years.

The VQLQ instrument as developed by Oude Elberink et al¹ has been widely used for this purpose. We report our use of this instrument in our patients with allergy to Myrmecia pilosula—or ‘Jack-Jumper Ant’(JJA)—a Hymenoptera species endemic to south-eastern Australia.²

JJA allergic patients were consented and surveyed with a venom-specific HR-QoL questionnaire, as approved by local ethics committee, before and after receiving 12 months of standard-of-care venom-immunotherapy (VIT). [See supplementary materials—Data S1 for validation information] A smaller subgroup also repeated this questionnaire after receiving JJA sting-challenge. Minimally important clinical difference (MID) was defined as an improvement in VQLQ of >0.5.³ Analysis was performed in Prism 10 for MacOS (GraphPad, Boston, MA) with a statistical significance α = 0.05.

53 patients (adults & children) were in the primary analysis cohort with pre- & post-VIT surveys. A smaller group of 22 patients were surveyed whilst established on VIT, and then after supervised sting-challenge. [See Table 1: Baseline characteristics].

When stratified by index reaction grade⁴ there was no apparent difference in HRQoL (mean Grade 1–2 = 3.6 vs mean Grade 3 = 3.7 (p = .98 ns) [See Figure 1A]) suggesting HRQOL has some independence of the severity of direct allergic reaction. Although not adequately powered for this, baseline gradient of impairment appeared to trend in reverse with those experiencing lower grades of index reaction have greater impairment at baseline. This may also bias as those with lower reaction grades and high baseline QoL may not proceed with (or even present for) VIT.

VIT strongly improved HRQoL, (3.7 to 5.5, mean change of 1.9; p < .0001) [See Figure 1B] and 85% achieved a MID of >0.5, giving a number needed to treat (NNT) of 1.2. [See Table S1] This is a greater change in HRQoL than previously demonstrated in vespid allergic patients, possibly due to more pervasive and surprising insect exposure in the environment compared to that of vespids, and/or due to properties of the venom reactivity itself in which JJA > Honey Bee > Wasp.

When stratified by age (adults vs children) there was no significant difference in baseline impairment, nor improvement – with a similar proportion benefiting. There did appear to be an apparent reduced baseline QoL females vs males (3.4 vs 4.0; p = ns). This effect became stronger in adult females vs males (3.1 vs 4.1; p < .05). There was a corresponding greater improvement with VIT – F vs M, but not statistically significant (5.2 vs 5.7; p = .099). [See Figure 1C] Previous studies have reported lower grades of index reaction appear associated with higher levels of anxiety when stratified by gender⁵ suggesting gender is a specific risk factor to be considered for more significant HRQoL impairment. [See also Table S2].

Supervised Sting-Challenge appeared to further improve patients HRQoL, in addition to that of VIT [see Figure 1D]. Mean HR-QoL improvement—over and above that already experienced from 12mo of VIT—was 0.7 (5.1 to 5.8) and 50% achieved a MID >0.5; therefore giving a ‘Number needed to sting’ for meaningful improvement in QoL = 2.0. Although not powered to analyse the <18 years old subgroup, excluding them from the analysis did not change the effect size, nor statistical significance. As previously demonstrated in in wasp-allergic patients,⁶ those with higher residual impairments post-VIT seemed to derive this benefit compared to those with minimal residual impairment prior to sting. [Shown in Figure S1].

In Summary, this study of HRQoL adults & children receiving JJA-VIT, extends and reinforces the literature of allergy-associated HRQoL in other hymenoptera species. Indirect Morbidity due to venom allergy, as measured by HRQoL, appears as a separate phenomenon from that of the direct morbidity associated with allergic reactions to Jack Jumper Ant venom. As with other Hymenoptera species, this appears to be independent of severity of Index allergic reaction, and patient specific factors such as gender, appear to be a risk factor. JJA VIT is associated with significant improvement on HRQoL, and Sting-challenge appears to be a potential additional treatment available for those with residual QoL impairments.

Study design, analysis and manuscript drafting by KS.

This work was funded from within the budget of the Department of Allergy, Monash Health.

The authors declare that they have no competing interests.