ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Rush and ultra-rush venom immunotherapy for Hymenoptera allergy

Rush and ultra-rush venom immunotherapy for Hymenoptera allergy
Literature review current through: Aug 2023.
This topic last updated: Jul 06, 2022.

INTRODUCTION — Venom immunotherapy (VIT) to treat systemic allergic reactions to winged Hymenoptera (hornets, yellow jackets, honey bees, and wasps) may be administered according to several different schedules. Accelerated schedules include "rush" and "ultra-rush."

This topic review will discuss the advantages and disadvantages of rush and ultra-rush schedules for VIT, indications for accelerated VIT, and provide several specific examples of protocols that have been used successfully. Conventional schedules for VIT are discussed separately. (See "Hymenoptera venom immunotherapy: Technical issues, protocols, adverse effects, and monitoring" and "Stings of imported fire ants: Clinical manifestations, diagnosis, and treatment".)

BACKGROUND

Phases of immunotherapy — All forms of subcutaneous immunotherapy (SCIT) are divided into two phases: build-up and maintenance.

The build-up phase involves serial injections of increasing amounts of allergen, during which tolerance to the allergen is gradually induced and the patient's immune response to the allergen is modified from a T helper type 2 (Th2) phenotype to a T helper type 1 (Th1) phenotype [1,2]. In conventional VIT schedules, the build-up phase involves one or three injections per week and extends from 8 to 21 weeks. Conventional schedules for VIT are shown in the tables (table 1 and table 2). Th2 and Th1 immune responses are discussed separately. (See "The adaptive cellular immune response: T cells and cytokines", section on 'Cytokine profiles and functions of CD4+ T helper cell subsets'.)

The maintenance phase of allergen immunotherapy involves ongoing injections of an immunizing dose of allergen, usually at intervals of three to six weeks. During the maintenance phase, the immune transformation becomes complete. This phase is usually extended for a period of three to five years because shorter durations of treatment are associated with higher rates of recurrent systemic allergic reactions to subsequent stings. (See "Hymenoptera venom immunotherapy: Determining duration of therapy", section on 'Minimal duration of treatment'.)

Accelerated protocols for VIT are categorized as either rush or ultra-rush schedules, although these terms have not been strictly defined. Accelerated schedules of immunotherapy involve shortening the length of the build-up phase, while the maintenance phase remains the same. The length of the build-up phase depends upon the frequency of the injections and the incremental dose increase between consecutive injections. Thus, accelerated schedules either involve administering more injections per visit, increasing the dose more between consecutive injections, or both. The mechanisms of allergen immunotherapy are reviewed separately. (See "Allergen immunotherapy for allergic disease: Therapeutic mechanisms".)

Variability in terminology — The terms "rush" and "ultra rush" are used variably in the literature and are therefore ambiguous. Each term has been applied to several different accelerated schedules. We prefer instead to refer to different protocols by the duration of the accelerated schedule and the number of injections given. For example, a rush schedule that takes two days to complete with nine injections is referred to as "two-day rush with nine injections."

Rush — Rush VIT schedules involve administering the build-up phase over a period of days, until the maintenance dose is achieved (table 3) [3]. The maintenance dose is then given at one-week intervals for two doses, then two-week intervals for two doses, then three-week intervals for two doses, and then monthly thereafter.

Ultra-rush — As mentioned above, ultra-rush VIT uses a more rapid build-up phase. The final dose on the first day is typically slightly lower than the full maintenance dose, although the patient has received a cumulative dose of allergen close to the 100 mcg maintenance dose of an individual venom (table 4) [4]. On the next scheduled visit, the patient usually receives a full maintenance dose, which is repeated monthly thereafter. Compared with rush schedules, ultra-rush schedules expose the patient to a lower cumulative dose of venom during the build-up phase.

ADVANTAGES AND SAFETY OF ACCELERATED IMMUNOTHERAPY

Advantages — Advantages of accelerated VIT include increased patient convenience and more rapid induction of clinical protection from future stings:

Greater convenience – Inconvenience is the most common reason patients discontinue conventional immunotherapy. Accelerated schedules involve fewer office visits and are favored by many patients.

More rapid onset of clinical benefit – Accelerated schedules induce the immunologic changes that occur during the build-up phase more rapidly than conventional schedules. Thus, patients achieve clinical protection sooner. In most patients, protection from recurrent systemic allergic reactions appears to be established within one week of reaching maintenance doses and may improve further with time [5]. In a study of the ultra-rush protocol mentioned above, two patients with severe past reactions were restung 7 to 15 days after desensitization and developed only local erythema [4]. In addition, significant increases in venom-specific immunoglobulin G4 (IgG4) were noted 15 days after reaching maintenance. The immunologic changes induced by immunotherapy are reviewed separately. (See "Allergen immunotherapy for allergic disease: Therapeutic mechanisms", section on '"Blocking" IgG4'.)

Reduced risk of dosing errors – Dosing errors are one of the leading causes of systemic allergic reactions during subcutaneous immunotherapy (SCIT). Accelerated schedules involve fewer doses during the build-up phase, and these doses are administered over a more concentrated time period, so dosing errors are reduced.

Improved safety – Accelerated schedules for VIT usually have lower rates of systemic allergic reactions to the immunotherapy injections, compared with slower, conventional schedules. Note that this has been demonstrated in accelerated forms of VIT but does not appear to be the case with accelerated forms of aeroallergen immunotherapy. The reasons for this difference are not known. (See 'Rates of systemic allergic reactions' below.)

Safety — Accelerated VIT schedules were designed to be performed in the outpatient setting under the supervision of an experienced allergist and nursing staff. There are no data to suggest that patients should routinely be hospitalized to undergo accelerated VIT. However, patients should be screened appropriately before any form of SCIT is considered. (See 'Contraindications' below.)

Among the different Hymenoptera venoms, honey bee is the most likely to induce a systemic allergic reaction in both conventional and accelerated VIT schedules [6,7]. As an example, in a report of patients treated with a four-day rush protocol, systemic allergic reactions occurred in 12 percent of subjects receiving honey bee venom (although no patients required epinephrine) compared with 2 percent of those receiving yellow jacket venom [7].

Rates of systemic allergic reactions — Both rush and ultra-rush schedules for VIT usually demonstrate similar or lower rates of systemic allergic reactions during the build-up phase, compared with conventional schedules [4,7-12]. This reduced rate of reactions has been attributed to the use of fewer injections and lower cumulative doses of venom [9,13]. The specific rate depends upon the schedule used. As with conventional VIT, honey bee VIT is associated with higher rates of systemic reactions. (See 'Specific protocols' below.)

The relationship between systemic reactions, injection number, and cumulative venom dose has been demonstrated in several studies [9,14,15]:

In one report, 284 subjects underwent either a four-day, six-hour, or 210-minute VIT schedule, and systemic reactions occurred in 28, 29, and 7 percent, respectively [9].

In another report, 129 patients underwent a 210-minute VIT schedule. One hundred fourteen (88 percent) reached maintenance in 210 minutes. Systemic reactions occurred in 22 percent but 71 percent of those were mild, and there were no severe reactions. Systemic reactions were more common in those receiving honey bee VIT and patients with a previous severe systemic reaction [16].

A randomized trial of 76 patients compared VIT using an ultra-rush protocol with a rush protocol and with a slow protocol [14]. Systemic reactions occurred in 1.9 percent, 3.7 percent, and 3.9 percent of patients, respectively, during the build-up phase, and in 0.99, 1.46, and 2.7 percent, respectively, during the maintenance phase. Reactions to subsequent stings did not differ among groups (1.1 percent, 1.2 percent, and 1.1 percent).

A study of 31 patients with bee allergy and 82 with wasp allergy looked at systemic reactions during the build-up using ultra-rush, rush, and conventional protocols [15]. Systemic reactions occurred in 13.7, 14.3, and 26.5 percent of patients for ultra-rush, rush, and conventional VIT, respectively.

In a retrospective study of 143 patients with allergy to honey bee or wasp, patients were treated either with a half-day, three-day, or three-week protocol [17]. Systemic reactions occurred with honey bee VIT in 15.8 percent of the half-day rush patients, 8.7 percent of the three-day, and 25 percent of the three-week patients. Reactions with wasp occurred in 6.1 percent of the half-day rush patients, none of the three-day, and 12.5 percent of the three-week patients. Significant differences were found for higher reaction rates for honey bee and for the three-week protocol [17].

To determine whether the safety of accelerated venom schedules differed between adults and children, systemic reaction rates during VIT in 71 children (7 to 17 years) were compared with those in 981 adults. Bee-specific immunoglobulin E (IgE) was higher and tryptase was lower in the children when compared with the adults. The rate of systemic reactions was higher in children than adults (6.9 versus 2.5 percent). In addition, a five-day protocol was associated with an increased risk of systemic reaction compared with a three-day protocol (odds ratio [OR] = 2.65) [18]. A similar increase in systemic reactions in very young children has been noted in accelerated immunotherapy with aeroallergens. (See "Subcutaneous aeroallergen immunotherapy: Accelerated schedules (cluster and rush)", section on 'Contraindications'.)

Risk factors — Risk factors for the development of systemic reactions during accelerated VIT have not been extensively investigated. One study of 175 patients treated with a three-day rush VIT protocol reported a rate of systemic reactions of 10.9 percent [19]. Independent predictors of systemic allergic reactions included the use of angiotensin-converting enzyme (ACE) inhibitors, female sex, and receiving honey bee venom (versus other venoms). The safety of ACE inhibitors and beta-blockers in patients receiving immunotherapy is reviewed in more detail elsewhere. (See "Anaphylaxis induced by subcutaneous allergen immunotherapy", section on 'Factors associated with fatal and near-fatal anaphylaxis'.)

High-risk patients — The authors prefer the use of rush VIT in higher-risk patients, such as those with cardiopulmonary comorbidities or those taking certain medications, and some data exist to support this practice. In a study of 64 patients (ages 5 to 70 years) who had at least one of several conditions (ie, cardiovascular disease, uncontrolled asthma, elevated baseline tryptase) or who were taking beta-blockers or ACE inhibitors, subjects were treated with either rush or conventional VIT [20]. The rate of systemic reactions was similar in both groups (25.7 versus 27.5 percent), while the rate of reactions per injection was higher in the conventional group (5.6 versus 2.7 percent).

VIT with ant extracts — The rate of systemic reactions for accelerated schedules with ant whole body extract (WBE) is less defined than it is for purified venoms. In a study of 20 children treated with rush immunotherapy using WBE of Solenopsis invicta, there were six systemic reactions out of 324 injections, all of which were mild (grades 1 or 2) [21]. The risk of a reaction did not correlate with age, sex, atopy, or serum levels of ant-specific IgE.

An Australian study evaluated patients receiving immunotherapy for jack jumper ant hypersensitivity, which also uses whole body extract rather than purified venom. Still, this study compared the incidence of systemic reactions between a 3-visit and 10-visit schedule of venom immunotherapy (VIT) in 93 subjects sensitive to jack jumper ant (Myrmecia pilosula) [22]. Although the shorter schedule required fewer injections, it was associated with a higher rate of reactions (12 percent) compared with the slower schedule (no systemic reactions).

INDICATIONS — The indications for subcutaneous immunotherapy (SCIT) of any type are reviewed in detail separately. (See "Subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma: Indications and efficacy", section on 'Indications'.)

It is our approach to use accelerated schedules for VIT in preference to conventional schedules, since protection from future stings can be achieved with no increase in treatment-related risk. VIT practice parameters state that safe and effective accelerated schedules have been published and are no longer considered experimental [8,23].

Other specific indications for an accelerated VIT schedule include the following:

A desire by the patient to minimize the number of visits for treatment, either because of the patient's schedule or the distance that the patient lives from the treatment facility.

The inability to tolerate conventional VIT. Occasionally, accelerated VIT is used to achieve maintenance in patients who do not tolerate conventional build-up due to recurrent systemic reactions in response to the injections [3,12].

The literature describes the performance of accelerated VIT in children as young as two years of age [13,24]. In older children, maturity level and the ability to cooperate with the repeated injections required should be considered.

In theory, patients with mast cell disorders (eg, systemic mastocytosis or monoclonal mast cell activation syndrome) might tolerate accelerated VIT schedules better than traditional schedules, although this issue has not been formally studied.

Cost — The cost of an accelerated protocol varies by the length of the procedure and number of injections given. Accelerated protocols involve fewer injections and less venom but more staff contact time. At one of the author's (JP) institution, the cost of accelerated and conventional VIT are similar.

CONTRAINDICATIONS — Contraindications to accelerated VIT are the same as those for conventional VIT, since the safety is comparable or better. Patients with asthma should have their symptoms under good control prior to beginning any form of subcutaneous immunotherapy (SCIT).

Relative contraindications include medical conditions that would impair the patient's ability to survive anaphylaxis or treatment for anaphylaxis (eg, cardiovascular disease and severe chronic pulmonary diseases). However, in patients with venom allergy, cardiopulmonary disorders also put the patient at risk for a fatal outcome from a future sting, so each patient's situation must be considered individually. The issue of comorbidities, as well as in the use of beta-blockers or angiotensin-converting enzyme (ACE) inhibitors in patients needing VIT, are discussed in more detail elsewhere. (See "Anaphylaxis induced by subcutaneous allergen immunotherapy", section on 'Factors associated with fatal and near-fatal anaphylaxis' and "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action", section on 'Patients requiring ACE inhibitors or beta-blockers'.)

CONSENT, STAFFING, AND EQUIPMENT — The following recommendations about staffing, equipment, and consent are based upon the authors' clinical experience with administering rush VIT protocols over a period of 15 to 20 years. Practice parameters have not been developed specifically for accelerated forms of immunotherapy.

Informed consent — We obtain informed consent after a discussion of the risks and benefits of VIT and a review of the protocol to be used. For children and adolescents 18 years of age and younger, we obtain consent from a parent or legal guardian. The conversation should be documented, signed, and recorded in the patient's medical record.

Staffing and equipment — The clinic staff should be trained in administering accelerated VIT, be able to provide close monitoring, and be comfortable with the treatment of anaphylaxis.

The following supplies and equipment should be available when administering accelerated VIT:

The patient's venom extract(s), with the required dilutions.

VIT administration forms.

Injection supplies (syringe, alcohol wipes).

Peak flow meter and spirometry equipment.

Equipment for monitoring vital signs (blood pressure cuff, stethoscope, and thermometer).

Supplies to obtain intravenous access and administer medications and fluids.

Emergency medications (including weight-appropriate epinephrine autoinjectors and albuterol with nebulizer).

We also recommend having a dosing guide at the patient's bedside with precalculated doses of all anticipated emergency medications based on the patient's weight (particularly important for children), which have been reviewed by at least two health care professionals.

Premedication — We advise treating patients with an H1 antihistamine one hour prior to the accelerated protocol because there is some evidence that this can reduce the incidence of mild systemic reactions:

In a randomized trial of 121 patients treated with rush VIT, patients were pretreated with either an H1 antihistamine, the combination of an H1 and H2 antihistamine, or placebo [25]. Mild systemic reactions were observed in one and seven patients in the H1 and placebo groups, respectively. The addition of the H2 antihistamine did not provide additional protection. Local reactions were reduced in the groups receiving either H1 or combination premedication. Two other randomized trials reached similar conclusions [26,27]. However, H1 antihistamines did not appear to prevent serious systemic reactions (eg, hypotension) in any of these studies, although the incidence of such reactions was low.

At least one study also suggested that antihistamine premedication improves the efficacy of VIT [28].

The authors' practice is to begin accelerated VIT as soon as the diagnosis of venom allergy is made (ie, usually on the same day that the patient is skin tested) to avoid the risk of future stings. Whenever possible, we administer an H1 antihistamine prior to the start of the procedure. We typically give a second-generation nonsedating agent, such as cetirizine, loratadine, or fexofenadine, at standard age-appropriate doses. However, it is our experience that patients tolerate the accelerated schedule even without premedication. Thus, if it is practical to pretreat with an H1 antihistamine prior to starting the accelerated VIT schedule, then we suggest doing so because there may be some benefit as outlined in the above studies. However, this is not required in the practice parameters and should not otherwise delay administration of immunotherapy [8].

A more extensive premedication regimen (such as is used with accelerated aeroallergen immunotherapy) is unnecessary, based on the practice parameters [8], and further delays the administration of VIT.

The addition of prednisone and H2 antihistamines to H1 antihistamines appears to be more important for imported fire ant whole body extract (WBE) than for purified Hymenoptera venoms because the frequency of systemic reactions without premedication in patients receiving accelerated WBE immunotherapy is higher, at least based on one study of a one-day protocol. In that study, patients received either no premedication or three days of prednisone and H1 and H2 blockers [29]. Ten injections of fire ant WBE were given at 30- to 60-minute intervals to reach 0.3 mL of 1:100 (weight/volume [w/v]). Systemic reactions were observed in 24.3 and 9.5 percent of the nonpremedicated and premedicated patients, respectively. The efficacy of immunotherapy was similar in both groups based on sting challenge that showed 98 percent protection from recurrent systemic symptoms.

Treatment — A nurse obtains height, weight, vital signs, and a baseline pulmonary function test. The patient receives an H1 antihistamine one hour prior to the start of the procedure (preferred but not required based on the available literature and our experience). (See 'Premedication' above.)

The clinician examines the patient.

The clinician begins the immunotherapy as scheduled on the immunotherapy forms.

The patient is carefully monitored for signs of local and systemic reactions.

Follow-up vital signs and pulmonary function tests are done as needed throughout the procedure.

The patient is observed for at least two hours after the final injection. If stable, the patient is discharged with follow-up instructions to return at the next specified day for that particular protocol.

SPECIFIC PROTOCOLS — Studies of specific protocols for accelerated VIT are reviewed in this section. The composition of the immunotherapy prescription and preparation of the extracts for use in accelerated schedules are not typically different from what would be used for a traditional schedule. Only the dosing schedule is altered.

The protocols described here can be performed for one or more venoms. If a mixed vespid product is used, the volumes remain the same, and each dose contains the corresponding micrograms of each of the three vespid venoms.

In our practice, we use a dosing schedule that achieves subtherapeutic but significant doses in one day. When patients initially present for evaluation of possible venom allergy, we suggest that they return for skin testing, and if results are positive, we suggest that they remain in the office for desensitization immediately after skin testing.

135 minutes — The authors use a one-day protocol that reaches a dose of 20 mcg in 135 minutes, with or without premedication (as previously discussed) (table 5) [30]. After the initial injections are administered, the patient is observed for two hours and is discharged. Injections resume one week later, and the remainder of the build-up occurs over the next several weeks, continuing according to the schedule provided by the manufacturer of the venom extract (table 6). For example, one manufacturer recommends increasing weekly to 40 mcg, then 60 mcg, then 80 mcg, and then 100 mcg [31]. Injections of 100 mcg are then spaced every two weeks, then every three weeks, and then every four weeks thereafter. In the original report, 5 percent of patients developed mild systemic reactions, consisting of diffuse urticaria during the first day [30]. The patients we have treated have not developed systemic allergic reactions.

150 minutes — A 150-minute protocol was performed in 56 patients (ages 11 to 68 years) without premedications (table 4) [4]. All patients except one completed the ultra-rush desensitization. That patient stopped because of a hypertensive crisis unrelated to the immunotherapy. Seven percent had mild systemic reactions (generalized itching, dizziness without hemodynamic changes, malaise), which did not require epinephrine or discontinuation of the protocol. Mild and moderate local reactions were seen in 18 and 11 percent, respectively.

Four hours — A four-hour protocol was performed in 67 patients (ages 15 to 66 years) using either honey bee or wasp extract [6]. Pretreatment was with cetirizine or fexofenadine, starting three days prior to immunotherapy. The protocol involved administration of the following doses (in micrograms): 0.1, 1, 10, and 20 mcg at 30-minute intervals, followed by 30 and 50 mcg at 60-minute intervals. Subjects then received 100 mcg on days 7 and 14 and monthly thereafter. The protocol was performed 78 times and caused no hypersensitivity reactions in 83 percent of these. Systemic reactions developed in 17.5 percent, although none was severe enough to require epinephrine. Two patients had recurrent reactions and were converted to a conventional schedule. Four patients had large local reactions (>10 cm in diameter).

One day — In another study, 258 (51 children and 207 adults) underwent a one-day ultra-rush protocol [32]. The protocol involved administration of the following doses (in micrograms): 0.1, 1, 10, and 20 mcg at 30-minute intervals, followed by 30 and 40 mcg at 60-minute intervals. Subjects then received 50 mcg on day 15, and 100 mcg on day 45 and monthly thereafter. Thirty-three subjects (13 percent) experienced a systemic reaction on the first day of the protocol. Of those, 24 were grade 1 or grade 2, and 9 were grade 3 or grade 4. Systemic reactions on day 15 (two patients) and day 45 (one patient) were uncommon.

Two days — In another study, 403 subjects (57 bee-allergic and 346 wasp-allergic) underwent a two-day rush protocol [13]. The protocol involved administration of the following doses (in micrograms): 0.01, 0.1, 1, 10, 20, 40, and 80 mcg at 60-minute intervals. On day 2, subjects received 100 mcg at 8:00 AM and at 11:00 AM. Systemic reactions occurred in 8.8 and 11 percent of bee-allergic and wasp-allergic subjects, respectively, which were lower than rates with more prolonged protocols.

In a German study, 240 patients (allergic either to vespid [86 percent] or honey bee [14 percent]) underwent a two-day rush protocol consisting of seven injections on day 1 and two injections on day 2 [33]. All patients completed the buildup phase. Of these, 4 percent had urticaria and none experienced anaphylaxis.

Five days — In the same German study, 318 patients underwent a five-day rush protocol that consisted of between two and four injections per day for a total of 18 injections [33]. Since the final day resulted in administration of 180 mcg, patients received a much larger dose during buildup than they received subsequently on a monthly basis. Of these, 2.8 percent experienced either urticaria (5 patients) or a mild systemic reaction (2 patients). This 2.8 percent reaction rate was statistically significantly lower than the 4 percent rate that was observed in the two-day protocol, though its clinical importance is questionable.

MANAGEMENT OF ADVERSE REACTIONS

Systemic reactions — Systemic reactions to accelerated VIT are rare, and the best approach for continuing immunotherapy has not been formally studied. Empirically, there are two options for proceeding with treatment once the patient has been treated and returned to baseline:

Resume the accelerated schedule on the following day, which theoretically takes advantage of the patient's hyporesponsive state immediately after a systemic reaction

Convert to a conventional schedule

Since there are no studies evaluating either approach, the decision to try one approach over another requires a discussion between patient and clinician and considerations of the patient's preferences.

As with conventional immunotherapy, patients who develop systemic reactions should be treated for anaphylaxis and observed for a period of time once symptoms have resolved. Patients with mild-to-moderate reactions that respond promptly and completely to treatment can usually be observed in the clinic for two hours and discharged to home. However, it may be more appropriate to hospitalize a patient with a more severe reaction or with symptoms that do not respond promptly to treatment. Likewise, patients who live far from medical care or have little home support may be better served by hospitalization. There is a risk of biphasic reactions with anaphylaxis from any cause, and the risk factors for recurrent symptoms are unclear, although these have rarely been reported in the rush immunotherapy literature. Deciding on the best immediate aftercare for a patient with a systemic reaction requires clinical judgement. (See "Biphasic and protracted anaphylaxis", section on 'Possible risk factors'.)

The patient should then return at the next scheduled day based on the individual protocol (most commonly in one week) to resume injections. The authors believe it important not to extend this time period by even a few days, as it is their observation that patients who wait longer than one week tend to experience more systemic reactions in the remaining build-up. The authors resume treatment with the dose that caused the reaction. There is no utility based on the available literature for continuing antihistamine medications during the maintenance phase of therapy.

Another study evaluated 65 patients who experienced anaphylaxis during the initial build-up with a three-day (modified from the two-day protocol in [13]) VIT rush protocol, who were kept at a lower maintenance dose for 14 weeks and then later built up to the usual maintenance dose [34]. Using this approach, only three had a subsequent systemic reaction. Pretreatment of these individuals with antihistamine (1 patient) or omalizumab (2) permitted them to build up successfully.

Large local reactions — Local reactions at the site of the injections are seen in up to 20 percent of patients [4,6]. Some patients find the injections themselves painful, similar to a mild sting. Large local reactions are treated symptomatically (eg, with ice and acetaminophen), as with conventional immunotherapy. We do not terminate rush or ultra-rush VIT for large local reactions, unless the patient is too uncomfortable to continue. In most cases, we wait a few minutes longer between injections to allow treatment to start taking effect and then continue the protocol.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stinging insect allergy".)

INFORMATION FOR PATIENTS — Patients with venom allergy who are undergoing VIT should be equipped with at least two doses of self-injectable epinephrine. The patient should be educated about how and when epinephrine should be administered. The teaching record is signed by the patient and clinician.

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Anaphylaxis (The Basics)" and "Patient education: Epinephrine autoinjectors (The Basics)")

Beyond the Basics topics (see "Patient education: Anaphylaxis symptoms and diagnosis (Beyond the Basics)" and "Patient education: Anaphylaxis treatment and prevention of recurrences (Beyond the Basics)" and "Patient education: Using an epinephrine autoinjector (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Accelerated schedules involve a shortened build-up phase, while the maintenance phase remains the same as conventional immunotherapy. The build-up phase is shortened by administering more injections per visit, increasing the dose more between consecutive injections, or both. (See 'Background' above.)

Accelerated protocols for venom immunotherapy (VIT) are categorized as either rush or ultra-rush schedules, although these terms are not strictly defined. Rush VIT schedules involve administering the build-up phase over two to three consecutive days, until the maintenance dose is achieved (table 3). Ultra-rush VIT uses a more rapid one-day build-up phase, although the final dose on that day is usually lower than full maintenance (table 4). In both cases, the patient returns to complete the remainder of the injections weekly, then biweekly, and then monthly. (See 'Variability in terminology' above.)

Advantages of accelerated VIT include increased patient convenience and more rapid induction of clinical protection from future stings. In most patients, protection from recurrent systemic allergic reactions appears to be established within one week of reaching maintenance doses. (See 'Advantages' above.)

Rates of systemic allergic reactions with both rush and ultra-rush VIT are similar or lower than rates with conventional VIT. This has been attributed to the use of fewer injections and lower cumulative doses of venom during the build-up phase. The specific rate depends upon the schedule used. Accelerated VIT is performed in the outpatient setting. (See 'Safety' above.)

The indications and contraindications for accelerated VIT are the same as those for conventional VIT because the safety is similar. In addition, rush or ultra-rush VIT may be tolerated in patients who are having difficulty reaching maintenance with a conventional build-up schedule because of recurrent systemic reactions to the injections. (See 'Indications' above and 'Contraindications' above.)

We suggest premedicating all patients with an H1 antihistamine before beginning an accelerated VIT protocol (Grade 2B). We typically give a second-generation, nonsedating agent, such as cetirizine, loratadine, or fexofenadine, at standard age-appropriate doses. (See 'Premedication' above.)

Several rush and ultra-rush VIT schedules have been published. The authors use a one-day protocol that reaches a dose of 20 mcg in 135 minutes, with or without premedication, with which they have not seen systemic reactions (table 5). (See 'Specific protocols' above.)

Large local reactions are treated symptomatically (eg, with ice and acetaminophen), as with conventional immunotherapy. In patients who do develop systemic reactions, we suggest discontinuing the accelerated protocol and converting the patient to a conventional build-up schedule (Grade 2C). (See 'Management of adverse reactions' above.)

  1. Larché M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol 2006; 6:761.
  2. Jutel M, Akdis M, Blaser K, Akdis CA. Are regulatory T cells the target of venom immunotherapy? Curr Opin Allergy Clin Immunol 2005; 5:365.
  3. Goldberg A, Confino-Cohen R. Rush venom immunotherapy in patients experiencing recurrent systemic reactions to conventional venom immunotherapy. Ann Allergy Asthma Immunol 2003; 91:405.
  4. Schiavino D, Nucera E, Pollastrini E, et al. Specific ultrarush desensitization in Hymenoptera venom-allergic patients. Ann Allergy Asthma Immunol 2004; 92:409.
  5. Müller U, Hari Y, Berchtold E. Premedication with antihistamines may enhance efficacy of specific-allergen immunotherapy. J Allergy Clin Immunol 2001; 107:81.
  6. Roll A, Hofbauer G, Ballmer-Weber BK, Schmid-Grendelmeier P. Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy. J Investig Allergol Clin Immunol 2006; 16:79.
  7. Sturm G, Kränke B, Rudolph C, Aberer W. Rush Hymenoptera venom immunotherapy: a safe and practical protocol for high-risk patients. J Allergy Clin Immunol 2002; 110:928.
  8. Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011; 127:S1.
  9. Birnbaum J, Charpin D, Vervloet D. Rapid Hymenoptera venom immunotherapy: comparative safety of three protocols. Clin Exp Allergy 1993; 23:226.
  10. Gorska L, Chelminska M, Kuziemski K, et al. Analysis of safety, risk factors and pretreatment methods during rush hymenoptera venom immunotherapy. Int Arch Allergy Immunol 2008; 147:241.
  11. Kalogeromitros D, Makris M, Koti I, et al. A simple 3-day "rush" venom immunotherapy protocol: documentation of safety. Allergol Immunopathol (Madr) 2010; 38:69.
  12. Oren E, Chegini S, Hamilos DL. Ultrarush venom desensitization after systemic reactions during conventional venom immunotherapy. Ann Allergy Asthma Immunol 2006; 97:606.
  13. Brehler R, Wolf H, Kütting B, et al. Safety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections. J Allergy Clin Immunol 2000; 105:1231.
  14. Patella V, Florio G, Giuliano A, et al. Hymenoptera Venom Immunotherapy: Tolerance and Efficacy of an Ultrarush Protocol versus a Rush and a Slow Conventional Protocol. J Allergy (Cairo) 2012; 2012:192192.
  15. Bożek A, Kołodziejczyk K. Safety of specific immunotherapy using an ultra-rush induction regimen in bee and wasp allergy. Hum Vaccin Immunother 2018; 14:288.
  16. Cosme J, Spínola-Santos A, Pereira-Santos MC, Pereira-Barbosa M. Venom Immunotherapy: a 20-year experience with an ultra-rush protocol (210-min). Eur Ann Allergy Clin Immunol 2019; 51:122.
  17. Pospischil IM, Kagerer M, Cozzio A, et al. Comparison of the Safety Profiles of 3 Different Hymenoptera Venom Immunotherapy Protocols: A Retrospective 2-Center Study of 143 Patients. Int Arch Allergy Immunol 2020; 181:783.
  18. Stoevesandt J, Hosp C, Kerstan A, Trautmann A. Safety of 100 µg venom immunotherapy rush protocols in children compared to adults. Allergy Asthma Clin Immunol 2017; 13:32.
  19. Bernkopf K, Rönsch H, Spornraft-Ragaller P, et al. Safety and tolerability during build-up phase of a rush venom immunotherapy. Ann Allergy Asthma Immunol 2016; 116:360.
  20. Rosman Y, Confino-Cohen R, Goldberg A. Venom Immunotherapy in High-Risk Patients: The Advantage of the Rush Build-Up Protocol. Int Arch Allergy Immunol 2017; 174:45.
  21. Manuyakorn W, Benjaponpitak S, Kamchaisatian W, et al. Safety and efficacy of ant rush immunotherapy in children. Asian Pac J Allergy Immunol 2017; 35:156.
  22. Brown SG, Wiese MD, van Eeden P, et al. Ultrarush versus semirush initiation of insect venom immunotherapy: a randomized controlled trial. J Allergy Clin Immunol 2012; 130:162.
  23. Golden DB, Moffitt J, Nicklas RA, et al. Stinging insect hypersensitivity: a practice parameter update 2011. J Allergy Clin Immunol 2011; 127:852.
  24. Laurent J, Smiejan JM, Bloch-Morot E, Herman D. Safety of Hymenoptera venom rush immunotherapy. Allergy 1997; 52:94.
  25. Brockow K, Kiehn M, Riethmüller C, et al. Efficacy of antihistamine pretreatment in the prevention of adverse reactions to Hymenoptera immunotherapy: a prospective, randomized, placebo-controlled trial. J Allergy Clin Immunol 1997; 100:458.
  26. Berchtold E, Maibach R, Müller U. Reduction of side effects from rush-immunotherapy with honey bee venom by pretreatment with terfenadine. Clin Exp Allergy 1992; 22:59.
  27. Reimers A, Hari Y, Müller U. Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine: a double-blind, placebo-controlled trial. Allergy 2000; 55:484.
  28. Müller UR, Jutel M, Reimers A, et al. Clinical and immunologic effects of H1 antihistamine preventive medication during honeybee venom immunotherapy. J Allergy Clin Immunol 2008; 122:1001.
  29. Arseneau AM, Nesselroad TD, Dietrich JJ, et al. A 1-day imported fire ant rush immunotherapy schedule with and without premedication. Ann Allergy Asthma Immunol 2013; 111:562.
  30. Bernstein JA, Kagen SL, Bernstein DI, Bernstein IL. Rapid venom immunotherapy is safe for routine use in the treatment of patients with Hymenoptera anaphylaxis. Ann Allergy 1994; 73:423.
  31. HollisterStier, Spokane, Washington.
  32. Birnbaum J, Ramadour M, Magnan A, Vervloet D. Hymenoptera ultra-rush venom immunotherapy (210 min): a safety study and risk factors. Clin Exp Allergy 2003; 33:58.
  33. Stock R, Fischer T, Aẞmus K, et al. Safety and tolerability of venom immunotherapy: Evaluation of 581 rush- and ultra-rush induction protocols (safety of rush and ultra-rush venom immunotherapy). World Allergy Organ J 2021; 14:100496.
  34. Kranert P, Forchhammer S, Volc S, et al. Safety and Effectiveness of a 3-Day Rush Insect Venom Immunotherapy Protocol. Int Arch Allergy Immunol 2020; 181:111.
Topic 16131 Version 14.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟