Current state of follow-up care for patients with Hymenoptera venom anaphylaxis in southwest Germany

Insect venom is the most common cause of anaphylaxis in adults in Germany as documented by the German Anaphylaxis Register [1]. Systemic anaphylactic reactions to bee or wasp stings (hymenoptera venom allergy, HVA) are present in up to between 0.4–3.5% of the general population [2, 3, 4, 5, 6, 7, 8, 9]. These acute reactions often present as medical emergencies and the patients should receive the emergency medical treatment appropriate for an anaphylactic reaction. After the patient has recovered from the index event, patient treatment should continue. Long-term prophylactic treatment includes patient education on exposition prophylaxis, emergency medications for self-treatment, and allergen specific immunotherapy (venom immunotherapy, VIT).

Guidelines have been developed for the diagnosis and treatment of patients with bee or wasp venom allergies by the German, Austrian, and Swiss Societies for Allergy and Clinical Immunology in cooperation with the German Societies for Dermatology, Pediatric Allergy and Environmental Medicine, and Pediatric Medicine as well as the Association of German Allergists [10]. Among others, these guidelines provide specific recommendations for management in the emergency situation, diagnostic workup, prescription and use of emergency self-medications and for treatment with VIT. In addition an updated guideline for the management of insect venom allergy has been published by the insect venom allergy interest group of the European Academy of Allergy and Clinical Immunology [11].

While detailed recommendations for patient management exist, to our knowledge, there are no studies that evaluate the reality of patient care after the index event in Germany. Prior studies in the United States have found a wide range of rates for referral and follow-up with allergists. A single center study of patients with anaphylaxis found a rate of 31–38% [12, 13], studies of patients with HVA have ranged between 14 and 20% [14, 15]. These studies either used medical record review exclusively or insurance claims databases. Little is known about rates of VIT among patients with HVA under real-life conditions.

The objective of our study was to evaluate the follow-up care that patients receive with regard to emergency medications, allergist visits, diagnostics and VIT. A patient population with a history of insect sting anaphylaxis—that was otherwise unselected—was identified from the medical records of three regional emergency medical centers and queried directly via a written questionnaire in order to avoid selecting for patients who had received follow-up care.

In designing our study, the primary goal was to gain a comprehensive understanding of the follow-up care patients received during and after an anaphylactic insect sting reaction, including their attitudes toward the preventive care options and how the received follow-up care may have differed from the current guidelines. This study is unique in that patients were directly queried about their sting event and the follow-up care they received. This enabled us to capture allergist visits and treatment that was initiated after the acute treatment, as well as to ask patients about their attitudes regarding therapy options, and to gain insight into the reasoning behind the decision to not undergo treatment, and to understand the extent that patients continue to receive preventive care in the years following the index event. It was particularly important to capture follow-up treatment initiated by the primary care physician because the primary care physician often provides referrals in Germany. Prior studies that exclusively used medical records and chart reviews were limited to the chart documentation, and use of insurance claims databases enabled prior studies to accurately capture EAI prescriptions and allergist visits, but did not allow for inquiry into patient attitudes. These studies also did not investigate long-term care with regard to VIT [14, 15].

Emergency medications were initially well prescribed, with 77% of patients receiving EAIs. However, at the time of survey half of the EAIs had expired. This finding is comparable to that of Fisher et al. who reported that 54% of emergency kits contained expired medications and that 60% of EAIs were expired [17]. Furthermore, 61% of patients also reported that their physician did not check their emergency medications during follow-up consultations. Closer follow-up of prescriptions by primary care physicians could help to increase the number of patients with current emergency medications.

Previous studies have shown that the rate of referral to an allergist upon discharge from the emergency department is low [12, 14, 18]. These studies did not capture referrals from primary care physicians. The overall rate of allergist visits that we found (46%), while still not ideal, is much higher than those reported by earlier studies, in which only 14–23% of patients followed up with an allergist. It is important to note that these studies looked at a defined length of time and were conducted using medical and insurance records [15, 19]. The increased rate of allergist visits found in our study may be due to our method of asking patients to self-report and the self-selection of patients responding to our questionnaire. The allergist visit is key to receiving proper diagnostics and by implication when tested positive the recommendation for VIT. In addition, Campbell et al. [13] reported that in patients with anaphylaxis to an unknown trigger, the allergy visit resulted in the identification of the trigger in 32% of the cases.

Overall, 62% of patients reported receiving information on insect sting avoidance. This is much higher than the Clark et al. multicenter average of 20%; however, they also found a wide variance of between 0–69% among centers [14]. Informing the patient about how to avoid future stings is a low cost preventative measure that could be easily implemented in the form of a hand out.

In contrast to an earlier study, which found that patients with more severe episodes (cardiorespiratory failure) were less likely to receive preventative care after the index event with an odds ratio of 0.50 for any preventative care [15], we found the opposite to be true, with patients with grade 3 and 4 reactions more likely to receive VIT than patients with grade 1 and 2 reactions. However, in our study only 60% of patients with a grade 4 reaction received VIT. When indicated, VIT has a success rate of up to 95% [20, 21, 22]. Somewhat surprising was that 14 patients, 17% of those with a diagnosis of insect venom allergy, did not start VIT, despite receiving information about the therapy. An additional 6 patients reported receiving a diagnosis, but no information about VIT. For patients in Germany, there is a relatively low direct financial cost of receiving VIT; however, the treatment is time intensive, requiring multiple visits. This is reflected in the reasons that patients gave for not undergoing VIT, with 8 patients giving reasons related to the effort and commitment involved, compared with only one patient saying that VIT was too expensive. Another 5 patients reported that they did not undergo VIT because they only had one reaction.

Several studies have shown that on a sting challenge, 30% of children and as many as 60% of adults with a history of insect venom anaphylaxis will have a systemic reaction if they do not receive VIT [22, 23, 24, 25]. Studies have also shown that 30% of patients with systemic reactions to stings had experienced at least 2 systemic sting reactions [26, 27]. Additional patient education or a new approach to educating patients on insect venom allergy and the benefits of VIT could be beneficial in increasing the number of patients choosing VIT. Given that VIT can only be initiated if patients receive proper diagnostic testing [28], it is important for patients to follow-up not only with their primary care physician, but also with an allergist. Only half of patients who followed up with only a primary care physician received diagnostics, while following up with an allergist in a primary, secondary, or tertiary center essentially guaranteed that the patient received diagnostics, thus, enabling them to receive VIT if indicated.

One of the more striking findings of our study was the predictive value of an early recommendation for further follow-up during the acute treatment phase. Seventy percent of patients who received an early recommendation reported a visit with an allergist, compared with only 18% of those who did not. A key strategy to increase rates of VIT could be to increase awareness of VIT efficacy in emergency departments and in primary care providers.

It should be noted that an analysis of VIT for insect venom allergy in the UK suggested that VIT is only cost effective if patients are stung frequently (e. g., beekeepers), or if quality of life improvement is considered. While there is some debate surrounding the cost effectiveness of VIT, there is agreement that VIT becomes cost effective when quality of life is improved as a result [29, 30]. There are also several studies that have shown that a less severe systemic reaction is a risk factor for future severe reactions [31, 32]. Current German and European guidelines recommend VIT for all patients reactions of grade 2 severity or higher and for patients with a grade 1 reaction if they have any other risk factors or if their quality of life has been negatively impacted [10, 11, 33].

If the guidelines were followed, all patients would have been eligible to receive a diagnostic workup, and those tested positive would have been eligible to receive VIT. In contrast to guideline recommendations, only 60 patients with grade 2 or higher received VIT, which demonstrates a clear deficit in the real-life follow-up care of patients with HVA in the general population.

Our study has several limitations. First, there are inherent limitations of a medical record database, which include reliance on coding to identify cases of anaphylaxis and documentation of an insect sting. Additionally, our study is also limited by the inherent limitations of a retrospective questionnaire based study: patients had to both remember and accurately report. It is highly likely that many of the respondents were not completely accurate historians, as evidenced by some patients reporting that their last sting reaction leading to an emergency intervention happened before that identified in the emergency medical records. We also had a relatively small sample size, with a total of 126 patients. The small sample size is particularly notable when we look at the number of patients with a grade 1 or grade 4 reaction. Both of these groups have less than 10 individuals.

Finally, there may have been a significant population bias. Although we attempted to capture a representative population of patients with HVA by identifying patients based on emergency medical response center records, the patients included in our study ultimately needed to decide that they wanted to invest the time to participate. In addition, 27% of respondents had received treatment from our clinic, and their decision to respond may have also been driven by their recognition of the physicians conducting the study. Even patients with no relation to UKF may have been motivated by how affected they were by their HVA medical emergency. It is possible that patients who were more concerned about their allergy were more likely to respond, thus, increasing the likelihood that respondents had sought follow-up.

On the other hand, by asking patients directly we were able to capture information about care received from multiple providers, as well as to gain insight as to why patients chose not to receive VIT. Our findings can be used as an indicator of the follow-up care that patients in Germany currently receive after the initial emergency treatment of HVA.

To our knowledge, this is the first study to describe outcomes of allergy follow-up among patients with stinging insect anaphylaxis in Germany. While our study shows higher rates of emergency medication prescription, allergist follow-up, and VIT than previous studies in other countries, there is still plenty of room for improvement. First, there is an information deficit on the relevance of HVA and the correct follow-up care among Emergency Response Teams, primary care physicians and patients. This is reflected in the low rates at which patients received allergy identification cards, prescriptions for emergency medications, and recommendations for follow-up during the course of the acute treatment. From our results, it is clear that follow-up with an allergist essentially guarantees that a patient will receive diagnostic testing and information on treatment options and it is evident that a recommendation for follow-up does positively influence the likelihood that a patient will see an allergist. Thus, an important first step in improving follow-up care would be (1) to inform the patient already during the treatment phase of the index event about the need for diagnostic testing and the availability of a treatment that efficiently protects from recurrence of insect sting anaphylaxis and (2) to refer patients to an allergist.

After the index event, follow-up care does not adequately administer preventative measures such as educating patients on sting prevention, ensuring that emergency medications are kept current and encouraging patients to seek follow-up with an allergist. Structured information material on HVA and the recommended follow-up care should be made available for emergency response teams, emergency departments, and primary care physicians to provide the right information to the right patient at the right time.

Finally, a disappointingly high number of patients chose not to undergo VIT despite receiving diagnostics and information about the therapy. Here, more detailed studies with higher patient numbers are required that allow insight into potential hurdles or misconceptions that may prevent patients from receiving and/or accepting the recommended treatment.