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SCIT: Standard schedules, administration techniques, adverse reactions, and monitoring

SCIT: Standard schedules, administration techniques, adverse reactions, and monitoring
Author:
Harold Nelson, MD
Section Editor:
Peter S Creticos, MD
Deputy Editor:
Anna M Feldweg, MD
Literature review current through: Aug 2023.
This topic last updated: Aug 29, 2022.

INTRODUCTION — There is significant variation in the way subcutaneous immunotherapy (SCIT) is administered around the world, including differences in schedules for injections, safety precautions, training requirements, and approaches to documentation. Over the past few decades, professional allergy societies in the United States have made attempts to reduce variations in practice across the United States and identify best practices. Practice parameters for SCIT have been published, and the practices described in this topic review are consistent with American guidelines [1].

This topic will review conventional schedules for the administration of SCIT, focusing on those used to administer inhalant allergens. Adjustments in schedules in response to adverse effects, injection techniques, safety requirements for facilities where immunotherapy is given, documentation, and patient monitoring will also be discussed. Accelerated schedules for SCIT (including rush, cluster, and ultra-rush) and schedules for Hymenoptera venom immunotherapy are reviewed elsewhere. (See "Hymenoptera venom immunotherapy: Technical issues, protocols, adverse effects, and monitoring", section on 'Choice of protocol'.)

CONVENTIONAL SCHEDULES — SCIT schedules differ in the number of injections per visit, number of visits per week, and the rapidity with which the patient reaches the maintenance dose. Conventional immunotherapy schedules involve one to three injections per week during a build-up phase that lasts a number of weeks, followed by a maintenance phase, during which injections are given every two to four weeks over a period of years.

Choosing a build-up schedule — There are faster and slower versions of conventional schedules. The clinician may choose a schedule with a slower (more gradual) build-up for the patient at increased risk for a systemic allergic reaction to the immunotherapy itself. The primary advantage of slower schedules is a presumed reduced risk of systemic allergic reactions. An example of a conservative build-up schedule is provided (table 1) [1].

Within the spectrum of conventional schedules, more conservative schedules are appropriate for patients with any of the following characteristics:

Multiple large reactions during allergen skin testing [2]

Systemic symptoms during skin testing

Persistent asthma

A history of systemic allergic reactions to previous immunotherapy

Patients without these characteristics usually tolerate a more moderate schedule, such as that shown in the table (table 2), which involves 14 fewer injections to reach maintenance than the slower schedule discussed above [3]. Advantages of faster schedules include patient and clinician convenience and a shorter time to maintenance and clinical improvement.

Clinicians may be reluctant to initiate pollen immunotherapy during times of the year when pollen counts are high. However, a systematic review found that rates of systemic reactions were not higher in patients beginning pollen immunotherapy during pollen seasons, compared with those starting therapy at other times [4].

Maintenance phase — During the maintenance phase, the interval between injections is usually increased from once weekly up to a maximum of once monthly for inhalant allergens [1]. Some clinicians give maintenance injections every two weeks, while others prefer every three to four weeks. Certain patients receiving maintenance injections at three- or four-week intervals may report that allergic rhinitis and conjunctivitis symptoms become bothersome before their next maintenance injection is due. In this situation, the interval can be shortened to see if better symptom control is achieved.

Total duration of therapy — The recommended duration of SCIT is three to five years of maintenance therapy. The data supporting this recommendation and studies addressing the persistence of benefit after discontinuing therapy are discussed separately. (See "Subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma: Indications and efficacy", section on 'Persistence of benefit after discontinuation' and "Subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma: Indications and efficacy", section on 'Duration of therapy'.)

ADMINISTRATION OF INJECTIONS — Issues surrounding the administration of SCIT injections include ensuring that the patient is given the correct injection, screening the patient for changes in health that might alter the safety of immunotherapy, and optimal injection techniques.

SCIT can induce a systemic reaction including anaphylaxis, and the risk factors and incidence of anaphylaxis during immunotherapy are reviewed in more detail separately. (See "Anaphylaxis induced by subcutaneous allergen immunotherapy", section on 'Frequency' and "Anaphylaxis induced by subcutaneous allergen immunotherapy", section on 'Factors associated with fatal and near-fatal anaphylaxis'.)

Safety precautions at every visit — Personnel responsible for administering immunotherapy injections should be trained to perform the following measures routinely at the beginning of each patient visit to increase safety.

A relatively common cause of systemic reactions to immunotherapy is the administration of an extract to the wrong patient. For this reason, it is critical to ensure that the allergen immunotherapy extract and dilution are the correct one for the patient before administering the injection. It is advised that patients be asked to provide two identifying pieces of information (eg, name and birth date) [1].

The patient should be questioned to determine if any local or systemic reactions developed following the previous injection(s).

If the patient has been instructed to take an antihistamine prior to the visit, staff should confirm that this was done. Premedication with a nonsedating H1 antihistamine is suggested for selected patients, including those experiencing recurrent large local reactions or systemic reactions to prior injections. (See "Anaphylaxis induced by subcutaneous allergen immunotherapy", section on 'Premedication'.)

The patient should be questioned to determine if there have been any changes in health status or in medications since the last injection. The onset of pregnancy or the introduction of beta-adrenergic blocker medication should be a cause for reevaluating the continuation of immunotherapy [1].

Consider routinely performing a peak expiratory flow test in patients with asthma. Patients experiencing an asthma exacerbation should not be given an injection that day [1]. In those who do receive injections, a repeat measurement of peak expiratory flow may be considered prior to discharge from the clinic, even in the absence of symptoms, because some patients are unaware of or ignore changes in lung function.

Patients should wait at the site where they received their immunotherapy injection for 30 minutes. The data supporting this are reviewed separately. (See "Anaphylaxis induced by subcutaneous allergen immunotherapy", section on 'Optimize safety'.)

Patients should be instructed not to exercise vigorously for at least several hours after receiving an immunotherapy injection. Some clinicians advise patients to avoid vigorous exercise for one or two hours before injections as well. This advice is intended to minimize rapid uptake of the allergen into the systemic circulation, although its utility in preventing systemic reactions has not been formally studied.

Injection technique — Immunotherapy injections should be given using a calibrated small volume syringe (usually a 1 mL syringe) with a 26- to 27-gauge nonremovable needle (usually three-eighths to one-half inch [0.9 to 1.3 cm] in length) [1]. In the United States, the Occupational Safety and Health Administration has mandated that needles with safety-engineered sharp injury protection be used.

The site should be wiped with an alcohol swab before giving the injection.

Injections should be given subcutaneously in the lateral or posterior middle portion of the arm [1]. The subcutaneous tissue has limited blood supply compared with other tissues and allows for slow absorption. Intramuscular injection is avoided because it would lead to more rapid absorption and increased risk of a systemic reaction.

The plunger of the syringe may be pulled back slightly to check for blood return before injecting as an extra safety step. However, a retrospective and prospective study failed to detect blood during 35,000 immunotherapy and immunization injections [1].

Occasionally, patients request that injections be administered somewhere other than the upper arm, usually because of large or persistent local reactions. In this situation, the thigh could be used, provided the patient has adequate subcutaneous tissue and the underlying muscle can be successfully avoided. The thigh is probably preferable to the buttocks, as it would not be possible in the latter circumstance to apply a tourniquet to slow systemic absorption in the event of a severe systemic reaction.

TRAINING AND PREPARATION FOR MANAGING SYSTEMIC REACTIONS

Personnel and site — Allergen immunotherapy should be administered in a setting where prompt recognition and treatment of a systemic reaction are optimized [1]. The preferred location of administration of allergen immunotherapy is in the office of the allergy expert who prepared the patient's immunotherapy extract. There should be a clinician or clinician extender (advanced registered nurse practitioner or clinician's assistant) appropriately trained in emergency treatment immediately available in the medical facility. These precautions are especially important for patients at high risk for systemic reactions (highly sensitive, severe symptoms, comorbid conditions, or history of recurrent systemic reactions) [1].

Equipment and medications — The following equipment and medications should be immediately available [1]:

Stethoscope and sphygmomanometer

Aqueous epinephrine 1:1000 weight/volume (ie, the primary treatment for anaphylaxis)

Tourniquet, syringes, large bore (14 gauge) needles, and intravenous catheters

Equipment to administer oxygen by mask

Intravenous fluid set-up

Antihistamine for injection (second-line treatment)

Glucocorticoids for intramuscular or intravenous administration (second-line treatment)

Equipment to maintain an airway appropriate for the supervising clinician's expertise and skill

Glucagon kit for patients on beta-blockers

ADVERSE REACTIONS TO IMMUNOTHERAPY — Adverse reactions to SCIT consist of local reactions at the site of injection and systemic allergic reactions.

Local reactions — Injection site reactions consist of redness, pruritus, and swelling. A local reaction can range from a few millimeters in diameter to swelling and erythema that encompasses most of the patient's upper arm. They may progressively increase in size over several hours and persist for over 24 hours. Local reactions to SCIT are common, with 30 to 80 percent of immunotherapy patients experiencing these at least some of the time. Consensus is lacking about what degree of local reaction is expected with SCIT. Some studies have characterized a local reaction as large if it exceeds 2.5 cm in diameter, while others have defined large as bigger than the patient's palm [5,6].

Several factors may contribute to local reactions. A single-site retrospective study found that higher rates of local reactions smaller than the patient's palm (although not larger local reactions) correlated with higher allergen concentration, greater number of allergens per extract, and larger injection volume [7]. Higher glycerin concentrations were not associated with local reactions, although glycerin is known to cause injection site pain, particularly as concentrations approach 50 percent and with higher injection volumes [8].

Prevention and treatment — Local reactions can be reduced by premedication with a minimally sedating oral antihistamine (eg, cetirizine, loratadine, others) taken one to three hours before the injection, and this is common practice [9].

Two small studies have examined rinsing the syringe used to administer SCIT with a solution of epinephrine (ie, drawing up a solution of epinephrine and then expelling it from the syringe/needle before drawing up the allergen solution for injection) [10,11]:

In a randomized trial of 74 adult and pediatric patients with local reaction to immunotherapy despite antihistamine premedication, rinsing the immunotherapy syringe with a solution of epinephrine significantly reduced the size of local reactions per patient report, while rinsing them in solutions of diphenhydramine or saline (placebo) did not [10].

In a second small randomized trial, 17 pediatric and adult patients who had a history of large local reactions after ≥20 percent of injections despite premedication received maintenance injections one month apart, once through epinephrine-coated syringes and once with untreated syringes [11]. Rinsing with epinephrine (1 mg/mL) reduced both the incidence and size of local reactions at multiple time points up to six hours (early and delayed local reactions). Three patients reported a transient burning sensation at the site of the epinephrine-coated needle, which resolved rapidly.

This practice of rinsing the syringe with epinephrine appears to reduce the size and occurrence of local reactions, with minimal adverse effects. It may be considered in patients in whom large local reactions are a consistent problem. Note that the effect of this practice on the incidence of systemic reactions, if any, was not reported.

Data are lacking on the utility of other interventions, such as the application of cold packs or topical corticosteroid preparations or dividing the dose between two arms. These measures can be tried for patients with recurrent and bothersome large local reactions. Montelukast was found in a small randomized pilot study of just 15 patients to be helpful in reducing the severity of local reactions [12], but another small study suggested that montelukast might reduce the effectiveness of SCIT [13], so more investigation is required regarding the impact of antileukotriene medications on SCIT.

One study found that a local reaction in response to an injection did not predict a repeat local reaction at the next visit, suggesting that dose reduction was not indicated for the prevention of recurrent local reactions [6].

Relationship between local and systemic reactions — Two large studies found that local reactions are not immediate harbingers of systemic reactions and that adjusting immunotherapy doses based on local reactions did not impact the incidence of systemic reactions [14,15]. In one study, no adjustment was made for local reactions less than the size of the patient's palm, and, in the other, no adjustment was made for local reactions of any size, compared with previous periods when adjustments in dose were made for local reactions. There was no increase in systemic reactions in either study. However, other studies found that systemic reactions, not with the next injection but during the course of immunotherapy, were more common in patients who experienced frequent moderate-sized local reactions (>2.5 cm) [5] and were three times as frequent in patients who experienced a local reaction greater than the size of their palm [16]. One interpretation of this finding is that the tendency to develop large local reactions with SCIT is a marker for a patient who is at higher risk (for undefined reasons) for systemic reactions at some point during therapy.

In summary, if a patient has developed a large local reaction (often defined as swelling and erythema bigger than the patient's palm), there is no evidence that decreasing the amount of extract used for the next injection helps prevent either a recurrent local reaction or a systemic reaction. However, many clinicians choose to be cautious and either repeat the same dose that caused the reaction or reduce the dose slightly. For patients experiencing frequent medium-to-large local reactions (≥2.5 cm) or a single large local reaction greater than palm sized, there is an increased risk for a systemic reaction sometime during the course of therapy, and, for patients in the build-up phase, clinicians may wish to change to a more gradually increasing schedule.

Systemic reactions — Systemic allergic reactions to SCIT involve organ systems distant from the injection site. Most serious systemic reactions occur within 30 minutes after the injection. Therefore, a 30-minute waiting period following injection is recommended. These reactions may range in severity from mild rhinitis to fatal cardiopulmonary arrest. A system for classifying the severity of these reactions has been developed, and its use is endorsed by the practice parameters (table 3) [1,17].

The incidence of, risk factors for, and measures to prevent systemic reactions to SCIT are reviewed in detail separately. (See "Anaphylaxis induced by subcutaneous allergen immunotherapy", section on 'Frequency'.)

Delayed and biphasic systemic reactions are also reported following SCIT injections. Because these typically occur after the patient leaves the treatment facility, patients should be warned about these reactions and be instructed about what action to take should symptoms occur. Some clinicians provide all or selected patients with autoinjectable epinephrine to use for these late-occurring systemic reactions.

Delayed systemic reactions occurring more than 30 minutes after the injection constitute 27 to 50 percent of all systemic reactions. However, these are usually not severe [1].

Biphasic systemic reactions, defined by resolution of the initial symptoms followed by recurrence of systemic symptoms 2 to 24 hours following the injection, have been reported in up to 23 percent of systemic immunotherapy reactions [1]. The recurrent symptoms are generally less severe than the initial reaction. Biphasic anaphylaxis from all causes is reviewed elsewhere. (See "Biphasic and protracted anaphylaxis".)

DOSE ADJUSTMENTS — In the section that follows, dose and volume are interchangeable when making changes within a given dilution of a patient's extracts. As an example, if a patient is receiving 0.5 mL of a maintenance solution (1:1 volume/volume [v/v]) and the dose is reduced by one-half, this means that 0.25 mL of the 1:1 v/v solution would be given.

Following systemic allergic reactions — It is common practice following a systemic reaction to reduce the next injection to the previously tolerated dose and, in cases of very severe reactions, to an even lower dose. However, there are wide variations in the degree to which clinicians reduce doses, and the issue has not been formally studied to identify the best approach. In the case of very severe reactions, the prescribing clinician should review the course of immunotherapy to determine whether the risk/benefit assessment justifies continuation of immunotherapy [1]. There are no established criteria regarding discontinuation of immunotherapy due to systemic reactions, and the decision must be made cooperatively with input from both clinician and patient.

Following large local reactions — This is discussed above. (See 'Local reactions' above.)

Missed injections — There are no studies to provide guidance for dose adjustments when patients have unscheduled gaps in immunotherapy. An empiric schedule for missed doses from the practice parameters is given in the table (table 4). An alternative schedule that has been employed at Wilford Hall Air Force Medical Center for over two decades is provided in the table (table 5) [18].

Restarting immunotherapy — In a group of patients who had previously received maintenance immunotherapy and had a relapse of symptoms after one to three years, immunotherapy was safely reinstituted with a course of 11 weekly injections [19]. An even more truncated up-dosing schedule may be possible in those whose interruption has been less than one year.

New vials — When new vials of allergen immunotherapy extract are provided, it is customary to reduce the dose by one-third to one-half, even though the same extracts from the same provider are used to compound the new extract and build back up to the dose the patient was previously receiving. The reason for this is concern that the fresh vials may be more potent due to gradual loss of potency in the old vials or variations in potency of different lots of extract.

New allergen added to therapy — If a new allergen extract is introduced, it can be given as a separate injection, built up to the maintenance dose, and then added to the allergen immunotherapy extract.

Change in supplier of allergen extracts — It may occasionally be necessary to change suppliers of extracts. There are no published recommendations on how best to transition patients from one brand of extract to another, and the approach described here is that of the author and editors of UpToDate.

Standardized extracts should be relatively similar among suppliers. We would suggest reducing the dose slightly when changing brands. As an example, if a patient was receiving standardized dust mite mix or cat, the initial dose from the new supplier could be reduced to approximately one-fifth of the previous dose, with build-up from there (eg, from 0.5 mL of 1:1 to 0.1 mL of 1:1).

Nonstandardized pollens have a greater range of variability, so one might reduce the dose by at least one dilution (eg, from 0.5 mL of 1:1 to 0.5 mL or even 0.25 mL of 1:10).

Cockroach and fungi extracts can be widely variable (even 100-fold or more), so one might reduce the initial dose by two dilutions or even further (eg, from 0.5 mL if 1:1 to 0.5 mL or even 0.25 mL of 1:100).

Clinical judgment may dictate a more cautious approach in some situations, depending upon a patient's history of systemic reactions to immunotherapy, the season in which the change is being implemented, or other factors.

High pollen and mold seasons — Some allergists reduce doses during periods of high pollen counts in patients receiving immunotherapy for pollen allergy. However, several studies suggest that routine dose reductions of pollen extracts during pollen season are not necessary:

Two large studies including over 600,000 injections did not find a correlation between pollen counts and systemic reaction rates (SRRs), although there was a correlation in one study with mean monthly mold counts from August to October [20,21].

In a study from the allergy clinic at Lackland Air Force base in San Antonio, Texas, SRRs to immunotherapy were compared between patients allergic to and presumably receiving mountain cedar pollen in their immunotherapy and those not allergic to mountain cedar pollen [22]. There was no difference in the SRRs between the two groups either during or out of the mountain cedar pollen season over a period of eight years, despite no adjustments in immunotherapy dosing being made during the mountain cedar pollen season.

The pediatric service at Boston Children's Hospital began reducing the immunotherapy dose in the spring if immunotherapy included tree or grass pollen extract and in the fall if it included weed pollen extract. After 42 months, the SRR was compared with that during a similar period of time before seasonal dose adjustments were instituted. The SRR prior to seasonal dose adjustment was 0.43 percent and during the period of seasonal adjustments, 0.36 percent, a difference that was not statistically significant. There was no difference in the severity of systemic reactions between the two time periods [23].

These studies suggest that routine immunotherapy dose reduction during pollen seasons of the component extracts does not reduce the overall rate of systemic reactions. Until the relationship between environmental exposure and risk of systemic reactions to SCIT is better defined, one option is to decrease the immunotherapy dose only in patients who are experiencing significant symptoms due to concomitant high pollen or mold spore levels.

DOCUMENTATION

Consent form — Clinicians should obtain informed consent before initiating allergen immunotherapy. Patients should be informed about the following issues:

The nature of the treatment and alternatives to treatment – The alternatives to SCIT include medications, sublingual forms of immunotherapy (available for a limited number of allergens), and continued and strict avoidance of those allergens that can be avoided. (See "Sublingual immunotherapy for allergic rhinitis and conjunctivitis: SLIT-tablets".)

Potential risks, including a description of how frequently local reactions and systemic reactions occur and including the possibility of death – The risks of SCIT include the inconvenience and discomfort of local reactions at the sites of injections, which occur in 30 to 80 percent of patients to varying degrees, and the risk of systemic allergic reactions that have been reported to occur in approximately 0.1 percent of injection visits [24] and 7 percent of treated patients. The rate of death from SCIT as practiced in North America was estimated at six fatal reactions in 54.4 million injection visits given in allergy practices from 2008 to 2016 [24]. Anaphylaxis induced by SCIT is reviewed in more detail separately. (See "Anaphylaxis induced by subcutaneous allergen immunotherapy", section on 'Frequency'.)

The requirement that the patient remain in the office under medical supervision for 30 minutes after each administration.

Costs associated with immunotherapy and who is responsible for these costs – The cost of immunotherapy is obviously dependent upon the care delivery structure in which it is administered. However, in both European and American studies, SCIT was found to be cost effective compared with medication-based management, particularly in patients who otherwise require both nasal and pulmonary inhaled medications. (See "Subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma: Indications and efficacy", section on 'Efficacy'.)

The anticipated duration of immunotherapy – Recommendations call for three to five years of maintenance injections. Once a patient has reached the end of this period, the patient and clinician should decide together whether to continue or stop treatment. Studies about the persistence of benefit after discontinuing SCIT are reviewed separately. (See "Subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma: Indications and efficacy", section on 'Persistence of benefit after discontinuation'.)

The anticipated success of immunotherapy – Allergen immunotherapy for inhalant allergens is expected to reduce a patient's allergic symptoms gradually over time [1]. SCIT does not "cure" a patient of allergies but rather reduces symptoms and often reduces the need for allergy medications. Different people experience different degrees of benefit, and it is difficult to predict with precision how much an individual patient will improve. Most patients see clear improvement in the first 6 to 12 months of treatment, which continues steadily thereafter as the treatment is continued.

As part of the education of the patient, they should be educated about signs and symptoms of systemic reactions and instructed to report symptoms immediately if in the office/medical facility or to report any delayed systemic reactions to their clinician.

SCIT administration form — The form provides a means to document each injection the patient receives. It should contain the patient's name, date of birth, telephone number, and, optionally, picture. The form also specifies the allergen immunotherapy extract contents, dilutions, and expiration dates. For each visit, there should be the date of the injection, the arm used, vial and delivered volume in milliliters, any reaction local or systemic, any change in health status or medication, and peak flow (if performed).

An example of an allergen immunotherapy administration form is provided (form 1) [1].

If systemic reactions occur, their severity should be recorded. A new grading system for systemic reactions to immunotherapy has been developed [17] and is included in the practice parameters (table 3) [1].

MONITORING — Patients should be reevaluated at least every 6 to 12 months while they are receiving immunotherapy. The following issues should be addressed at these visits:

If the patient is in the build-up phase of immunotherapy, are they progressing as expected toward maintenance?

Is the patient consistently keeping appointments?

Is the patient experiencing clinical improvement in allergic symptoms?

Has the patient experienced any untoward effects from the immunotherapy so far? Does the patient know what the signs and symptoms of a systemic reaction are?

Has the patient found it difficult to remain in the office for the required time after each injection?

Periodic visits also give the clinician an opportunity to reinforce safe practices and determine whether adjustments in immunotherapy dosing schedule or allergen content are necessary [1].

Objective testing — Neither laboratory tests nor repeat skin testing is routinely used to monitor a patient's progress during aeroallergen SCIT. However, changes in titrated prick skin tests (using the same extract used for initial testing) have been shown to correlate with clinical response and persistence of remission after discontinuation of therapy [25,26]. In contrast, simply repeating skin tests using the standard methods used for diagnosis with commercial extracts that may or may not be of the same lot is not sensitive enough to detect the changes induced by immunotherapy in most patients.

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: Allergen immunotherapy for the treatment of respiratory allergy".)

INFORMATION FOR PATIENTS — 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 email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

Basics topic (see "Patient education: Allergy shots (The Basics)")

SUMMARY AND RECOMMENDATIONS — Practice parameters for subcutaneous immunotherapy (SCIT) have been published, and the practices described in this topic review are consistent with American guidelines.

Conventional immunotherapy schedules involve one to three injections per week during a build-up phase that lasts a number of weeks, followed by a maintenance phase, during which injections are given every two to four weeks over a period of years. A minimum of three to five years of maintenance therapy is believed optimal for maximal clinical benefit. (See 'Conventional schedules' above.)

At each visit for immunotherapy, it is critical to ensure that the patient receives the correct extracts and doses, is questioned about reactions to past injections, and is screened for interim changes in health status that might increase the risk of a systemic allergic reaction to the injections that day. (See 'Administration of injections' above.)

SCIT should be given in a setting in which personnel are specifically trained in the recognition and management of systemic allergic reactions. In most instances, SCIT is best given in the office of the allergist who prescribed the therapy and with a clinician trained in anaphylaxis immediately available. Practice parameters specify the equipment and medications that should be present. (See 'Training and preparation for managing systemic reactions' above.)

Local reactions to SCIT are common and related to several factors, including allergen concentration, greater number of allergens per extract, and larger injection volumes. The preservative glycerin can cause pain at the injection site, although it does not appear to cause swelling and erythema. Patients who have more large local reactions or large local reactions larger than the palm of their hand appear to be at higher risk for systemic reactions during their course of immunotherapy, although local reactions are not immediate harbingers of systemic allergic reactions, and dose adjustments based on local reactions do not prevent systemic reactions with the next injection. (See 'Local reactions' above and 'Relationship between local and systemic reactions' above.)

A 30-minute waiting period following SCIT injections is recommended because most serious systemic reactions begin within this period of time. The incidence of, risk factors for, and measures to prevent systemic reactions to SCIT are reviewed in detail separately. (See "Anaphylaxis induced by subcutaneous allergen immunotherapy", section on 'Frequency'.)

Adjustments to immunotherapy injection schedules may be required for a variety of reasons: missed visits, new vials, high pollen or mold seasons in patients sensitive to those allergens, addition of a new allergen, or change in an extract supplier. It is common practice to reduce the dose of allergen administered following a systemic reaction, although the utility of this intervention in reducing further systemic reactions and the extent to which the dose should be reduced have not been studied. (See 'Dose adjustments' above.)

Important components of documentation include informed consent, which includes estimates of potential benefit, as well as a discussion of the risk of severe or fatal systemic reactions and a longitudinal record of each visit for injections and any reactions that occurred immediately after or between visits. (See 'Dose adjustments' above.)

Patients should be followed every 6 to 12 months while receiving immunotherapy to assess compliance, clinical improvement, and adverse reactions. Repeat skin testing and serial laboratory testing are not usually performed. (See 'Monitoring' above.)

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  24. Epstein TG, Liss GM, Berendts KM, Bernstein DI. AAAAI/ACAAI Subcutaneous Immunotherapy Surveillance Study (2013-2017): Fatalities, Infections, Delayed Reactions, and Use of Epinephrine Autoinjectors. J Allergy Clin Immunol Pract 2019; 7:1996.
  25. Bousquet J, Maasch H, Martinot B, et al. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. II. Comparison between parameters assessing the efficacy of immunotherapy. J Allergy Clin Immunol 1988; 82:439.
  26. Des Roches A, Paradis L, Knani J, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. V. Duration of the efficacy of immunotherapy after its cessation. Allergy 1996; 51:430.
Topic 15757 Version 18.0

References

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