Rate Of Systemic Reactions Research Articles

Circadian and seasonal variations in subcutaneous allergen immunotherapy reactions

Circadian and seasonal rhythms play an important role in many physiological responses involving the immune system and allergic diseases1,2 and may also have implications in the safety profile of subcutaneous immunotherapy (SCIT). Although rare after administration of conventional SCIT in a clinical setting, systemic reactions (SR) occur in approximately 1 in 1000 injections, with roughly 67% classified as mild, 29% as moderate, and 4% as severe.3 Our study aimed to determine if the time of immunotherapy administration, seasonality, or demographic factors impact the rate of SR after SCIT.

Safety of house dust mite subcutaneous immunotherapy in preschool children with respiratory allergic diseases

BackgroundAllergen immunotherapy (AIT) is the only causal therapy for IgE-mediated allergy. There is less evidence about the safety and efficacy of AIT especially subcutaneous immunotherapy (SCIT) in children under 5 years old. We aimed to investigate the side effects and associated risk factors of house dust mite (HDM) SCIT in preschool children with respiratory allergic diseases.MethodsThe preschool children who had HDM-related allergic rhinitis with/without asthma were enrolled and undergone standardized HDM SCIT in our department from June 2013 to December 2019. Local reactions (LRs) and systemic reactions (SRs) were recorded and categorized according to World Allergy Organization recommendations. Demographic data and other therapeutic-related parameters were also recorded to investigate potential risk factors for these side effects.ResultsA total of 91 children (60 boys, 65.93%; 31 girls, 34.07%; mean age 4.13 years old) were included in the study. Among the 91 patients, 3109 SCIT injections were recorded, 62/91 (68.13%) experienced 186 immediate LRs, 4 /91(4.40%) experienced 6 delayed LRs, 11/91 (12.09%) children experienced 44 immediate SRs, 21/44 (47.73%) were grade 1 SRs, 21/44 (47.73%) were grade 2, 2/44 (4.55%) were grade 3, no grade 4 or 5 SRs occurred. Furthermore, 1/91 (1.10%) experienced 1 delayed SRs, manifested by urticaria 2 days later after allergen injection. 9/91 (9.89%) experienced 2 or more times SRs. Multivariable logistic regression analysis showed BMI (OR 1.506; 95%CI 1.091 to 2.079; p < 0.05) and sIgE against HDM (OR 1.497; 95%CI 1.082 to 2.071; p < 0.05) were risk factors for LRs. No variable was found to correlate with SRs (all p > 0.05).ConclusionsHDM subcutaneous immunotherapy is considered to be safe in preschool children with respiratory allergic diseases. Higher BMI and HDM sIgE level in children are risk factors for developing LRs. The incidence of SRs and the rate of severe SRs are low in preschool children.

Adverse reactions to subcutaneous immunotherapy in patients with allergic rhinitis, a real-world study.

The efficacy of subcutaneous immunotherapy (SCIT) for allergic rhinitis (AR) have been proven but application is still limited by concerns about the safety. The aims of this study were to investigate the incidence of adverse reactions and to ascertain possible risk factors in patients treated with SCIT in central China. This study retrospectively analyzed the application of SCIT from 2016 to 2018, in 236 patients with AR. After each injection, allergen dosage and details about local reactions (LRs)/systemic reactions (SRs) were recorded. Totaling 236 patients received 5844 injections. The rates of LR were 3.0% per injection and 34.7% per patient, while the rates of SR were 0.48% per injection and 10.6% per patient. 86.9 percent LRs were small. Most SRs were grade 1 (16/57.1%), followed by grade 2 (8/28.6%), grade 3 (4/14.3%). No fatal SRs was recorded. Children, high sensitization and absence of premedication were identified as risk factors for LRs. Recurrent LRs increased the risk of SRs. Premedication could reduce the number and severity of LRs, but not SRs. Dual therapy with antihistamine and montelukast did not provide additional benefit when compared with antihistamine alone. The incidence of SRs was low while LRs were common in SCIT. Children may be prone to develop LRs, while pretreatments could reduce the number and severity of LRs. Recurrent LRs was a risk factor for SRs.

Epinephrine-coated syringe for SCIT reduced local reactions: A randomized, double-blind, placebo-controlled trial

Adverse reactions to subcutaneous immunotherapy (SCIT) were classified as local (LRs) and systemic reactions (SRs).1 The timing of adverse reactions was categorized as immediate (occurring ≤30 minutes after injection) and late reaction (occurring >30 minutes after injection).2 Large local reactions (LLRs) were defined as erythema and/or swelling (>25 mm) at the site of injection.3 Children had similar rates of LRs compared with adult patients, but had lower rates of severe SRs.4

Risk stratification of systemic reactions to subcutaneous immunotherapy: A retrospective study.

Background: Subcutaneous allergen immunotherapy (SCIT) is a very effective treatment modality; however, it can be associated with both local and systemic reactions (SR). Identifying patient factors that predict SR remains paramount. Objective: Our aim was to identify the rate of SRs to SCIT as well as identify patient risk factors associated with the development of SRs. Methods: We conducted an institutional review board approved 10-year retrospective chart review of 459 patients who received SCIT in our clinic. The patients were placed into cohorts according to age, which included pediatric (5-18 years), adult (19-64 years), and senior (>65 years) patients. Results: An SR (N = 177) was identified in 24.8% of the patients (n = 114). The incidence of SR per injection was 0.2% (177 SRs of 74,183 total injections). SRs were identified as class 1 (n = 152), class 2 (n = 21), class 3 (n = 2), and class 4 (n = 2) according to the 2010 World Allergy Organization's SR grading system. There were no observed differences in the number of SRs with respect to age group. Female patients were more likely to have an SR (p = 0.02) overall as well as more than one reaction (p = 0.002). Other risk factors included the following: a patient-reported history of food allergy (p = 0.05), drug allergy (p = 0.005), or positive skin test result to cat and/or dog (p = 0.01). In addition, patients who were receiving SCIT to cat and/or dog (p = 0.004) or to dust mite (p = 0.03) were more likely to have an SR. Conclusion: In our patient population, the majority of SRs to SCIT occurred in female patients, patients with a history of drug or food allergies, and those who were receiving pet or dust-mite SCIT.

The efficacy and safety of two commercial house dust mite extracts for allergic rhinitis: a head-to-head study.

Several studies have demonstrated the efficacy of house dust mite (HDM) immunotherapy in allergic rhinitis (AR). We aimed to compare the efficacy and safety of 2 commercial HDM extracts in a Chinese AR population. This was an open-label study. HDM-associated AR patients were randomized into Dermatophagoides pteronyssinus (Dp) extracts (Alutard SQ; ALK, Hørsholm, Denmark) and Dp/Dermatophagoides farinae (Df) extracts (NovoHelisen Depot [NHD]; Allergopharma, Reinbek, Germany) groups. All patients received subcutaneous injections for 1 year, and were followed every 3 months during that 1-year period. Symptom score, medication score, and adverse reactions were recorded. The primary endpoint was the total combined symptom and medication score (CSMS) during the efficacy evaluation period. Blood samples were taken for specific immunoglobulin E (IgE), IgG4, and IgE-blocking factor tests at baseline and after the 1-year treatment. A total of 230 AR patients were randomized; 29 patients dropped out. Analysis of the primary endpoint demonstrated significant reductions in CSMS of 1.8 vs 3.1 (p < 0.001) in the Alutard group and 1.8 vs 3.3 (p < 0.001) in the NHD group compared with baseline. The 2 groups presented equal effectiveness with regard to CSMS, symptom score, and medication score (p > 0.05). The treatment was well tolerated in both groups; 17 (14.8%) patients experienced systemic reactions (SRs) in the Alutard group and 13 (11.3%) in the NHD group. The rates of SRs showed no difference in the 2 groups (p > 0.05), and no anaphylaxis occurred. IgG4 and IgE-blocking factor to Dp and Df were increased significantly in both groups after the 1-year treatment. Our study confirmed the equal efficacy and safety profile of both commercial extracts in HDM-associated AR patients.

Systemic reaction rates with omalizumab, subcutaneous immunotherapy, and combination therapy in children with allergic asthma.

Background: For children with moderate-to-severe persistent allergic asthma, omalizumab is effective. However, it is expensive, and there are no current guidelines for discontinuation. Subcutaneous immunotherapy (SCIT) is the only approach that can provide persistent beneficial effects after treatment is discontinued. However, SCIT is contraindicated in poorly controlled asthma. Therefore, we performed, to our knowledge, the first U.S. study that exclusively compared the safety of omalizumab, SCIT, and combination (omalizumab and SCIT) therapy in children with allergic asthma. Objective: We hypothesize that the systemic reaction (SR) rates in children who receive combination therapy are comparable with omalizumab alone. Methods: We performed a retrospective study of children ages 6-18 years old with allergic asthma who, from July 2010 to June 2017, received SCIT, omalizumab, or combination therapy in our children's allergy clinic. Our primary end point was to determine the SR rate among each of these groups. Results: We reviewed the records of 89 patients: 30 patients with SCIT (1550 injections), 30 patients with omalizumab (729 injections), and 29 patients with combination therapy (954 injections). In the SCIT group, 19 SRs (1.2% of injections) occurred in 10 patients (33%). In the omalizumab group, three SRs (0.4% of injections) occurred in three patients (10%). Similarly, in the combination group, three SRs (0.3% of injections) occurred in three patients (10%). Compared with the SR rate in the SCIT group, both omalizumab and combination groups had significantly lower SR rates (p = 0.045 and p = 0.011, respectively). The SR rates in children who received omalizumab and children who received combination therapy were not statistically different (p = 0.73). Conclusion: Children with moderate-severe persistent allergic asthma who received omalizumab or combination therapy had significantly lower SR rates compared with children with allergic asthma who received SCIT alone. SCIT in children treated with omalizumab was safe and may serve both as an omalizumab-sparing treatment and as a bridge to safely administer SCIT.

DIFFERENCE BETWEEN STANDARDIZED MITE ANTIGEN AND HOUSE DUST EXTRACT IN RUSH SUBCUTANEOUS IMMUNOTHERAPY FOR CHILDREN

Standardized allergen extracts are recommended for allergen immunotherapy. Since 2015, for patients with house dust mite allergies, we used a standardized house dust mite extract for subcutaneous immunotherapy, rather than non-standardized house dust extract. This study hypothesizes that standardized house dust mite extract (HDM group) was superior to non-standardized house dust extract (HD group) for subcutaneous immunotherapy. In this noninterventional, retrospective study, we enrolled patients with allergic rhinitis and sensitization to house dust mites. The HDM group (27 patients) received subcutaneous standardized extract immunotherapy since 2015, and the HD group (37 patients) received non-standardized extracts before 2015. We assessed the safety and efficacy between the two groups; the safety was assessed by the systemic reaction (SR) rate. The efficacy was assessed by reductions in the allergic rhinitis symptom-medication score, and the asthma treatment score, over a year. The SR rate of the HDM group (44%) was significantly higher than that (14%) of the HD group. The HDM group displayed a 57% reduction in the allergic rhinitis symptom-medication score, which was markedly higher than the 40% reduction observed in the HD group. In the standardized group, there was a 66% reduction occurred in the asthma medication score, markedly higher than the 36% reduction observed among patients in the HD group. Standardized house dust mite extract was more effective than non-standardized house dust extract for subcutaneous immunotherapy; however, the establishment of safer methods is warranted.

A twenty-two-year experience with Hymenoptera venom immunotherapy in a US pediatric tertiary care center 1996-2018

BackgroundThe rate of systemic reactions (SRs) to venom immunotherapy (VIT) in children has not been well evaluated. ObjectiveTo evaluate the rate of SRs to VIT in pediatric patients age 5 to 18 years who were treated with a standard protocol. MethodsA retrospective chart review was conducted to identify patients who received VIT at Boston Children's Hospital from 1996 through 2018. Information on venom testing, severity of reaction to insect field sting, and SRs to VIT were retrieved. ResultsA total of 78 patients were included. Most had moderate to severe reactions to insect sting before VIT. The rate of SRs was 0.2% of injection visits, occurring in 9% of patients. The SRs from VIT were mild (mostly grade 1 and some grade 2), and no grades 3, 4, or 5 reactions were seen. Male sex was a significant risk factor for moderate to severe reactions to insect sting. Positive testing to vespinae was seen in 98.7% of patients, and none had exclusive sensitivity to honeybee. The severity of the initial, pre-VIT insect sting reactions in our patients did not correlate with the occurrence of SRs from VIT. Twenty-seven percent of the patients were subsequently stung while on VIT. Only 1 patient (5%) had a mild SR, while all others had only local or no reaction at all. ConclusionIn the largest US study evaluating the safety of VIT in children, SRs to VIT were mild, and none required epinephrine. Male sex was significantly associated with higher risk of moderate to severe reactions to insect sting. Larger multicenter studies are needed to further evaluate the rate of SRs to VIT in pediatric patients.

Systemic Reactions in Pediatric Patients Receiving Standardized Allergen Subcutaneous Immunotherapy with and without Seasonal Dose Adjustment

The 2003 Joint Task Force on Practice Parameters recommended standardizing allergen subcutaneous immunotherapy (SCIT). Data from longitudinal surveillance survey in North America reported a systemic reaction (SR) rate of 0.1% to 0.2% of injection visits. The rate of SR to standardized SCIT in pediatric patients has not been well evaluated. The objective of this study was to evaluate the rate of SRs to standardized SCIT in pediatric patients aged 5 to 18 years in a single tertiary care center in the United States. A retrospective chart review was conducted in 2 groups: group 1 started SCIT within a period extending from January 2009 to June 2012, whereas group 2 started SCIT within a period extending from January 2013 to June 2016. The protocol was modified in group 2 such that updosing and maintenance doses were adjusted in the spring for tree and grass pollen and in the fall for weed pollen. There were a total of 128 patients in group 1 and 118 patients in group 2. The rate of SR was 0.429% in group 1 and 0.364% in group 2, which was not significant. There was no difference in the severity of SR in the 2 groups with no-fatal or near-fatal SR noted. Asthma was a significant risk factor in the younger age subgroup aged 5 to 11 years. Standardized SCIT appears to be associated with an SR rate of 0.429% to 0.364% of visits in pediatric patients. Protocol modification did not lead to a significant drop in SR. Larger multicenter studies are required to further evaluate the rate of SRs from standardized SCIT.

Comparison of Pediatric and Adult Systemic Reactions to Subcutaneous Immunotherapy

Subcutaneous immunotherapy (SCIT) has been used to treat allergic rhinitis for over a century, and current regimens have wide variability with an array of practice styles and dosing strategies. Although there are some statements about contraindications and cautions, no specific formal age- or weight-based dosing guidelines are utilized when administering SCIT. The primary objective of this study was to estimate the overall incidence rate of any reaction to SCIT and to consider the severity of the reaction by grade in children and adults. A retrospective chart review was conducted to document the number and severity of episodes of systemic reactions (SRs) in pediatric and adult subjects. Crude incidence rates were estimated as the number of SRs relative to the total injections administered. Adjusted incidence rate ratios were generated using a generalized estimating equation approach, which accounted for multiple visits within subjects. The incidence rate for any SR was 0.2%. The unadjusted incidence rate of any SR was significantly higher in children compared with adults (P < .001), although not significant when adjusted for asthma, gender, and phase of SCIT (P < .054). However, the incidence rate for grade 1 and 2 SRs in children was 1.89 times the incidence rate for adults, adjusting for these variables (P < .015). These results suggest that current SCIT practices are associated with a higher rate of SRs, specifically of grade 1 and 2 SRs, in children than adults. Further studies are necessary to evaluate if changes in dosing strategies for children, such as a lower starting dose, a decrease in target maintenance dose, or a slower build-up phase, are warranted.

Risk factors for fatal and nonfatal reactions to subcutaneous immunotherapy: National surveillance study on allergen immunotherapy (2008–2013)

BackgroundIn 2008, an annual surveillance study of systemic reactions (SRs) from subcutaneous immunotherapy (SCIT) injections was initiated in North America. ObjectiveTo define the incidence of SRs to SCIT. MethodsFrom 2008 to 2013, 27% to 51% of American Academy of Allergy, Asthma, and Immunology and American College of Asthma, Allergy, and Immunology members completed an annual survey of SCIT-related SRs of varying severity. From 2012 to 2013, data were collected regarding SRs with off-label sublingual immunotherapy (SLIT), selection of patients with asthma for SCIT, and strategies for dose adjustment during pollen seasons. ResultsFrom 2008 to 2013, data were gathered on 28.9 million injection visits, including 344,480 patients for 2012 to 2013. Since 2008, a total of 2 confirmed fatalities were directly reported that occurred under the care of allergists. Two additional fatalities occurred under the care of nonallergists. The rate of SRs from SCIT remained stable, occurring in 1.9% of patients, with 0.08% and 0.02% experiencing grade 3 and 4 SRs. SRs occurred in 1.4% of patients receiving off-label SLIT, including 0.03% with grade 3 SRs. There were no SLIT-related grade 4 SRs or fatalities. Practices that never administered SCIT in patients with uncontrolled asthma (Asthma Control Test score <20) had significantly fewer grade 3 and 4 SRs (odds ratio, 0.7; 95% confidence interval, 0.5–1.0, and odds ratio, 0.3; 95% confidence interval, 0.1–0.8, respectively). Lowering doses during pollen seasons for patients with highly positive skin tests reduced SRs of all severity grades (P < .05). ConclusionsSCIT-related fatality rates may be decreasing, but continued vigilance regarding modifiable risk factors, including careful patient selection, is needed. Dose adjustment during pollen seasons for highly sensitive patients may reduce risks. Potential risk for SRs from off-label SLIT exists.

Angiotensin‐converting enzyme inhibitors do not impair the safety of Hymenoptera venom immunotherapy build‐up phase

There is an ongoing debate on whether angiotensin-converting enzyme inhibitors (ACEI) should be substituted prior to initiation of venom immunotherapy (VIT) for safety reasons. We aimed to assess the influence of ACEI medication on the incidence of systemic reactions (SR) during the build-up phase of VIT in a large and homogeneous cohort of patients. The frequency of SR during 775 consecutive cycles of VIT initiation was analyzed in relation to cardiovascular medication, age, sex, venom, reactivity in diagnostic tests, severity of preceding sting-induced anaphylaxis, comorbidities, latency before the initiation of VIT, and treatment protocols. ACEI were routinely maintained throughout VIT, beta-blockers replaced if appropriate. During VIT-initiation, 190 (24.5%) patients were on some kind of cardiovascular treatment, 90 (11.6%) on ACEI, 23 (3.0%) on beta-blockers. VIT-related SR rates were 11.7% (any documented reactions including subjective symptoms) and 3.0% (reactions fulfilling objective diagnostic criteria of anaphylaxis). Medication with ACEI (P=0.097) or beta-blockers (P=1.0) was not significantly related to the incidence of SR. A reduced rate of SR in patients taking cardiovascular drugs was not statistically significant in the final multivariate regression model. A prolonged latency before the initiation of VIT (P=0.018, odds ratio = 1.010), and use of 5-day compared to 3-day rush protocols (P=0.008, odds ratio = 3.522) increased the frequency of SR. Study data do not provide evidence of an ACEI-mediated increase of VIT-related SR, supporting the continued use of these valuable and hard-to-replace substances throughout VIT.

A 1-day imported fire ant rush immunotherapy schedule with and without premedication

BackgroundRush immunotherapy (RIT) schedules can expedite protection in individuals sensitive to imported fire ant (IFA) stings. ObjectiveTo evaluate the safety and efficacy of 1-day RIT with IFA whole body extract (WBE) and determine the benefit of premedication with antihistamines and prednisone. MethodsPatients with systemic reactions to IFAs and evidence of specific IgE by skin test or serologic test started a 1-day RIT protocol without premedication. The 1-day RIT protocol consisted of a total of 10 injections every 30 to 60 minutes to achieve a 0.3-mL 1:100 (wt/vol) dose. A higher systemic reaction rate (SRR) prompted protocol revision to include a 3-day course of oral 20 mg of prednisone twice daily, 150 mg of ranitidine, and 10 mg of loratadine started 2 days before the 1-day RIT. Patients returned on days 8 and 15 to receive a 0.5 mL 1:100 (wt/vol) maintenance injection. The effectiveness of the RIT was evaluated with a sting challenge on approximately day 22. ResultsEighty of the 96 patients enrolled initiated the 1-day RIT. The first nonpremedicated group exhibited a SRR of 24.3% (9 of 37 patients), whereas the revised premedicated group had a SRR of 9.5% (4 of 42 patients; P = .07). The most severe reaction during RIT included dizziness, angioedema, and urticaria. Sting challenges on 53 patients resulted in 1 mild rhinitis reaction (efficacy, 98.1%). ConclusionOne-day RIT with IFA WBE for IFA hypersensitivity is efficacious. Although there was a trend with premedications to reduce SRRs during the RIT, safety data with premedication require confirmation in a larger trial.

Safety of multiple aeroallergen rush immunotherapy using a modified schedule

Rush immunotherapy (RIT) accelerates the build-up phase of traditional IT. The biggest potential benefit of using RIT is decreased time to symptomatic improvement. However, aeroallergen RIT carries an increased risk of systemic reaction (SR) compared with traditional IT. This study was designed to assess the safety of a modified 1-day multiple aeroallergen RIT protocol. A retrospective chart review was performed of 138 patients from an outpatient, university-based allergy practice who underwent RIT between November 2007 and February 2011. The RIT protocol consisted of eight injections over 5 hours, and stopped at one 10-fold dilution below the maintenance vial. All patients were premedicated on the same day of RIT with prednisone and histamine 1 and 2 receptor blockers. Primary end point observed was rate of SR. One hundred thirty-eight patients received a total of 2911 RIT injections. Thirty- eight patients (28%) had SRs. The SR rate per injection was 1.3%. Most of the reactions (82%) occurred after the last dose of the protocol. No patients with SR had severe anaphylaxis requiring emergency department support or hospitalization. The post-RIT SR rate was within the range seen with traditional IT. Well-controlled asthmatic patients were not at increased risk of SR compared with nonasthmatic patients. Modification of RIT to end at one 10-fold dilution below the maintenance vial for multiple aeroallergen RIT did not significantly decrease the SR rate compared with other protocols that end at the maintenance vial. Unlike hymenoptera RIT, aeroallergen RIT continues to be associated with a high risk of SR compared with traditional IT.

Rate of Systemic Reactions to Standardized Allergen Subcutaneous Immunotherapy in Pediatric Patients

The Joint Task Force on Practice Parameters recommended the standardization of allergen subcutaneous immunotherapy (SCIT) and the administration of specific maintenance doses. Data from a longitudinal surveillance program in North America reported a rate of systemic reactions (SRs) of 0.1% of injection visits. However, the rate of SRs to standardized SCIT in pediatric patients in particular has not been well evaluated.

A 5-year study of systemic reactions using both shared and patient-specific vaccines.

The safety of shared specific vaccines (SSVs) has been questioned by some experts. The purpose of this study was to evaluate the safety of SSVs. Details of systemic allergic reactions after subcutaneous immunotherapy injections were captured on a standardized form from July 2005 to July 2010. Patient records were evaluated for factors that might be associated with increased rate of systemic reactions and, in addition, were examined for any errors. Systemic reaction rates (SRRs) using a combination of shared and patient-specific vaccines (PSVs) were similar to previously reported studies (0.23 reactions per 100 shots). There were no systemic reactions resulting from errors where the incorrect shared allergen was administered, but we did note one reaction after an erroneously administered PSV. There were two dosage errors associated with both shared and patient-specific immunotherapy. Most reactions were mild to moderate (World Allergy Organization grade, 1 or 2). Severe reactions with 911 activations were noted in six patients. Thirty percent of reactions occurred out of the office and the average time to reaction was 48 minutes. Epinephrine was administered in only 60% of patients. Epicutaneous reactivity to mites, cats, dogs, and pollen but not mold occurred significantly more in reactors. Differences in SRRs were encountered between satellite offices. Using a combination of SSV and PSV, SRRs were similar to previously reported studies; moreover, no systemic reactions occurred where a SSV was erroneously administered. SRR surveillance is a useful safety tool.

Systemic reactions to subcutaneous allergen immunotherapy and the response to epinephrine

The use of epinephrine for anaphylaxis to subcutaneous allergen immunotherapy (SCIT) is the standard of care, but its use for mild systemic reactions (SRs) is somewhat controversial. The objective of this study is to determine the rate of SR to SCIT, the symptoms reported, and the response to intramuscular (i.m.) epinephrine over a 1 year period. This retrospective study was designed to evaluate SRs to SCIT to any combination of approximately 20 allergens (pollens, animal emanations, molds, and Hymenoptera) in 773 subjects representing 14,707 visits, receiving approximately 28,000 injections over 1 year. Nurses were instructed to administer epinephrine (1:1000 v/v) 0.2 mL i.m. for signs or symptoms of a SR. SRs were graded using the universal grading system proposed by the World Allergy Organization (WAO) Joint Task Force for Grading SR to Immunotherapy. Thirty-one patients (4%) had 32 SRs, 22 (71%) female, average age 40 yr. Nineteen (61%) had a history of asthma; 7 (22.6%) had a history of a previous SR. SRs were reported on average 24 minutes after injection. Symptoms included: generalized pruritus, 34.4%; upper airway pruritus, 28.1%; cough, 25.0%; shortness of breath, 21.9%. Fourteen SRs were classified as Grade 1, thirteen Grade 2, two Grade 3, and three Grade 4. No Grade 5 or late phase reactions were reported. 29 (90.6%) reactions were treated with epinephrine, 27 (84.4%) glucocorticosteroid, and 30 (93.8%) H1 antihistamine. SRs occurred in 4% of patients receiving SCIT and all who received early intervention with epinephrine responded successfully. The WAO Grading system was useful.

Safety aspects of subcutaneous immunotherapy with multiple allergens—a retrospective analysis on polysensitized patients

Polysensitization against a multitude of different allergens is a common problem in the treatment of allergies with specific immunotherapy (SIT). The aim of this retrospective study was to investigate the risk of simultaneous administration of two allergen extracts during SIT with a conventional or Cluster regimen. Local (LR) and systemic reactions (SR) in 147 patients receiving different forms of SIT were compared. Patients received a total number of 2,758 injections during dose-increase phase and 3,412 injections during maintenance phase. During dose-increase phase, a higher rate of LR (for 1A 0.7% and for 2A 1.5%) was found with parallel injections of two allergen extracts (2A). The increase of SR was, however, not significant with conventional (for 1A 0% and for 2A 0.3%) or Cluster therapy (for 1A 0.3% and for 2A 0.5%). No increment of SR with injections of two allergen extracts did occur during maintenance phase (for 1A 0.3% and for 2A 0.1%). In conclusion, the results of the present study indicate that a higher rate of LR and SR must be considered during dose-increase phase independent of the kind of induction regime used. The rate of adverse events (AE) with two different allergen extracts, however, seems tolerable. After reaching maintenance phase, a higher rate of AE with parallel allergen injections did not occur.

A prospective Italian survey on the safety of subcutaneous immunotherapy for respiratory allergy

Subcutaneous immunotherapy is effective for the treatment of respiratory allergy, and it is largely used in Italy, but no systematic safety assessment has been carried out so far. To assess prospectively the safety of injection immunotherapy in a multicentre, real-life survey. Eleven Italian allergy departments recorded the clinical characteristics of systemic reactions (SRs) due to immunotherapy. Vaccines were prescribed according to guidelines; only standardized depot extracts were used. SRs were graded according to the EAACI recommendations, and were classified as immediate or delayed. One thousand seven hundred and thirty-eight patients (847 males, age range 5-71) received immunotherapy from eight different manufacturers, for a total of 2038 courses (300 patients received two extracts). A total of 60 785 injections were given over a mean immunotherapy duration of 3 years. Overall, 95 reactions were observed in 57 patients (3.28%), corresponding to 4.7% of the courses and 1.56/1000 injections. Twenty-five patients experienced more than one adverse event. There were 34 grade 2, 60 grade 3 and one grade 4 reactions and no fatality. SRs occurred more frequently in patients with asthma than in patients with rhinitis alone (4.1% vs. 1.1%), and were equally distributed between the build-up and the maintenance phase. Ragweed and grass extracts caused significantly more side effects than other allergens. In this large prospective study, the rate of SRs was low, thus confirming that injection immunotherapy has an acceptable risk/benefit ratio when prescribed and carried out according to recommendations.