Safety of subcutaneous immunotherapy in patients with severe asthma.

BACKGROUND: Severe asthma (SA) has been identified as a risk factor for severe systemic reactions (SR) to allergen subcutaneous immunotherapy (SCIT). However, the incidence and characterization of SRs in SA in comparison to less severe or no asthma is not known. OBJECTIVE: The objective of this study was to characterize the incidence of SRs in patients with SA receiving SCIT in comparison to patients with no asthma or less SA. METHODS: A retrospective cohort study was performed on patients receiving SCIT from a multicenter national network of private allergy practices between January 2015 and December 2019. Demographics, asthma severity (International Classification of Diseases-10 codes), concomitant medications, aeroallergen skin testing, measures of asthma control with the asthma control test and forced expiratory volume in 1 second values, SCIT prescription, and an SR standardized form were assessed. RESULTS: A total of 65,855 patients, with 1072 patients having SA receiving SCIT, were included with a total of 4415 SRs (19.9 SR per 10,000 injection visits). Severe asthma had 23.9 SRs per 10,000 injection visits (incidence rate, 0.239; 95% confidence interval [0.189-0.298]). There were 155 grade III or IV SRs; 5 (3.2%) occurred in the SA group. There was no difference in rates of grade III or IV SRs between SA and no asthma and in rates of total SRs between SA and less SA. CONCLUSION: In a large cohort of patients with SA undergoing multiallergen SCIT drawn from a diverse outpatient allergy population, the diagnosis of SA was not associated with increased moderate-severe SRs compared with patients without asthma and any severity of asthma.

Safety of subcutaneous allergen immunotherapy.

Subcutaneous allergen immunotherapy (SCIT) is a unique treatment option for managing patients with allergic rhinitis, asthma, atopic dermatitis, and stinging insect allergy. Although systemic reactions to allergen injections are rare, near-fatal, and fatal anaphylactic reactions can occur. Patients with asthma are at greatest risk for more severe reactions as are those with previous systemic reactions. Treating allergists should institute best clinical practices to prevent and manage severe systemic reactions to SCIT, including the following: (1) prescreening patients with asthma for recent increases in asthma symptoms, (2) not prescribing SCIT to patients with severe and uncontrolled asthma, (3) instituting clinic protocols to prevent dosing errors, (4) considering modifying allergen doses during peak allergy seasons in patients at high risk, (5) instituting measures that require all patients on SCIT to be observed for at least 30 minutes after injections, and (6) regular training of all clinical staff in the recognition and expeditious treatment of anaphylaxis.

Risk factors for fatal and nonfatal reactions to immunotherapy (2008-2018): postinjection monitoring and severe asthma.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is highly effective but risks exist. OBJECTIVE: To identify practices that influence systemic allergic reactions (SRs) to SCIT and SCIT-associated infections. METHODS: Members of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology completed an annual survey of SCIT-related SRs of varying severity (2008-2018). Injection-related infections were queried (2014-2018). Strategies to enforce postinjection waiting times and to reduce risks from asthma/severe asthma were queried (2016-2018). RESULTS: Data were gathered on 64.5 million injection visits. Ten confirmed fatalities occurred since 2008, including 3 new fatalities since 2017. One fatal reaction occurred per 7.2 million injection visits (2008-2018). No infections occurred. Practices that tracked the time after injections, and required checking out with office personnel, had significantly lower total (P < .001), grade 3 (severe) (P < .001), and grade 4 (very severe) SRs (P < .001). Having more individuals with asthma on SCIT was associated with more grade 3 SRs (P < .02). Not prescribing SCIT in individuals with uncontrolled asthma was associated with fewer grade 3 SRs (P = .02). Having individuals with more severe asthma on SCIT was associated with more total, grade 1, and grade 2 SRs (P < .001); 50% of grade 3 and 4 SRs occurred in individuals with severe asthma. CONCLUSION: SCIT-related fatalities have declined since 2008, with a slight increase in recent years. SCIT is not associated with an increased risk of infections. Tracking the time after injections and checking out with office staff confer significantly lower risks of severe SRs. Asthma, especially severe asthma, is a major risk factor for severe and fatal SRs. Strategies that reduce risks for individuals with asthma, such as not prescribing SCIT to patients with uncontrolled asthma, may lower the risks.

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

BACKGROUND: In 2008, an annual surveillance study of systemic reactions (SRs) from subcutaneous immunotherapy (SCIT) injections was initiated in North America. OBJECTIVE: To define the incidence of SRs to SCIT. METHODS: From 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. RESULTS: From 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). CONCLUSIONS: SCIT-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.

Significant predictors of poor quality of life in older asthmatics.

BACKGROUND: Morbidity and mortality from asthma are high in older adults and quality of life (QOL) might be lower, although standardized measurements of QOL have not been validated in this population. OBJECTIVE: To determine predictors of asthma-related QOL in older adults. METHODS: Allergy and pulmonary outpatients (n = 164) at least 65 years old with an objective diagnosis of asthma completed the Mini-Asthma Quality of Life Questionnaire (mAQLQ). Demographics, medical history, and mean value for daily elemental carbon attributable to traffic, a surrogate for diesel exposure, were obtained. Regression analysis was used to determine predictors of mAQLQ scores. RESULTS: Total mAQLQ (mean ± SD 5.4 ± 1.1) and symptom, emotional, and activity domain scores were similar to those of younger populations, whereas environmental domain scores (4.4 ± 1.7) appeared lower. Poorer mAQLQ scores were significantly associated with emergency department visits (adjusted ß [aß] = -1.3, where ß values indicate the strength and direction of association, P < .0001) and with poorer scores on the Asthma Control Questionnaire (aß = -0.7, P < .0001). Greater ECAT exposure (aß = -1.6, P < .02), female sex (aß = -0.4, P < .006), body mass index of at least 30 kg/m(2) (aß = -0.4, P < .01), gastroesophageal reflux (aß = -0.4, P < .01), nonatopic status (aß = -0.5, P < .002), and asthma onset before 40 years of age (aß = -0.5, P < .004) were significantly associated with poorer mAQLQ scores. CONCLUSION: The mAQLQ scores in older adults with stable asthma were similar to those in younger populations and were predictive of other measurements of asthma control, verifying that the mAQLQ is an appropriate tool in older adults with asthma. Traffic pollution exposure was the strongest predictor of poorer asthma-related QOL in older adults with asthma.

AAAAI and ACAAI surveillance study of subcutaneous immunotherapy, Year 3: what practices modify the risk of systemic reactions?

OBJECTIVE: To define the incidence of and clinical practices associated with subcutaneous immunotherapy (SCIT)-related systemic reactions (SRs). METHODS: From 2008-2011, American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma & Immunology members completed an annual survey of SCIT-related SRs of varying severity (with grade 1 indicating mild; grade 2, moderate; and grade 3, severe anaphylaxis). From 2010-2011 (year 3) data were collected regarding SCIT-related procedures, including screening of patients with asthma, dose adjustment during peak pollen seasons, build-up regimens (conventional, cluster, or rush), and premedication. RESULTS: No fatal reactions were directly or indirectly reported from 2008-2011. The SR rates were similar for all 3 years (0.1% of injection visits; 83% of practices), as were severity grades. On average, for all 3 years, there were 7.1 grade 1, 2.6 grade 2, and 0.4 grade 3 SRs per 10,000 injection visits. Screening for worsening asthma symptoms was highly prevalent (86% always screened). Practices that always reduced doses during peak pollen season were significantly less likely to report grade 2 or 3 SRs (44% vs 65%; P = .04). Cluster and rush build-up were associated with significantly more SRs (P < .001). Practices that premedicated were significantly more likely to report grade 2 and 3 SRs (P < .01). CONCLUSION: Fatal reactions to SCIT appear to be declining, possibly related to almost universal screening of asthmatic patients. Adjusting doses during the pollen season may be associated with decreased risk for severe SRs. Cluster and rush immunotherapy were associated with increased risk for SRs. Premedication by practices reporting SRs likely reflects past experience with SRs.

Immunotherapy safety: what have we learned from surveillance surveys?

Subcutaneous allergen immunotherapy (SCIT) is beneficial for the treatment of allergic rhinitis, asthma, and in preventing stinging insect anaphylaxis, but is not without risks. Four retrospective surveillance surveys and one on-going national prospective study have attempted to characterize the incidence and risk factors for fatal and non-fatal SCIT reactions. These studies have contributed significantly to currently recommended SCIT safety guidelines. Recent surveillance studies indicate stable SR rates, and a possible decline in the incidence of fatal reactions since the implementation of evidence-based safety guidelines. This review will provide a detailed summary of the evidence from surveillance studies for risk factors associated with SCIT reactions, including: uncontrolled asthma, prior systemic reactions, dosing during peak pollen seasons, epinephrine being delayed or not given, dosing or administration errors, inadequate waiting times, reactions occurring more than 30 min after injections, injections given in medically unsupervised settings, concomitant beta-blocker and angiotensin-converting enzyme inhibitor (ACEi) use, and accelerated build-up regimens.

Chronic traffic pollution exposure is associated with eosinophilic, but not neutrophilic inflammation in older adult asthmatics.

OBJECTIVE: Airway inflammatory patterns in older asthmatics are poorly understood despite high asthma-related morbidity and mortality. In this study, we sought to define the relationship between exposure to traffic pollutants, biomarkers in induced sputum, and asthma control in older adults. METHODS: Induced sputum was collected from 35 non-smoking adults ≥65 years with a physician's diagnosis of asthma and reversibility with a bronchodilator or a positive methacholine challenge. Patients completed the Asthma Control Questionnaire (ACQ), and Elemental Carbon Attributable to Traffic (ECAT), a surrogate for chronic diesel particulate exposure, was determined. Equal numbers of subjects with high (≥0.39 µg/m(3)) versus low (<0.39 µg/m(3)) ECAT were included. Differential cell counts were performed on induced sputum, and myeloperoxidase (MPO) and eosinophil peroxidase (EPO) were measured in supernatants. Regression analyses were used to evaluate the relationship between sputum findings, ACQ scores, and ECAT. RESULTS: After adjustment for potential confounders, subjects with poorly controlled asthma based on ACQ ≥ 1.5 (n = 7) had significantly higher sputum eosinophils (median = 4.4%) than those with ACQ < 1.5 (n = 28; eosinophils = 2.6%; ß = 10.1 [95% CI = 0.1-21.0]; p = 0.05). Subjects with ACQ ≥ 1.5 also had significantly higher sputum neutrophils (84.2% versus 65.2%; ß = 7.1 [0.2-14.6]; p = 0.05). Poorly controlled asthma was associated with higher sputum EPO (ß = 2.4 [0.2-4.5], p = 0.04), but not MPO (p = 0.9). High ECAT was associated with higher eosinophils (ß = 10.1 [1.8-18.4], p = 0.02) but not higher neutrophils (p = 0.6). CONCLUSIONS: Poorly controlled asthma in older adults is associated with eosinophilic and neutrophilic inflammation. Chronic residential traffic pollution exposure may be associated with eosinophilic, but not neutrophilic inflammation in older asthmatics.

Poor asthma control and exposure to traffic pollutants and obesity in older adults.

BACKGROUND: Environmental and host predictors of asthma control in older asthmatic patients (>65 years old) are poorly understood. OBJECTIVE: To examine the effects of residential exposure to traffic exhaust and other environmental and host predictors on asthma control in older adults. METHODS: One hundred four asthmatic patients 65 years of age or older from allergy and pulmonary clinics in greater Cincinnati, Ohio, completed the validated Asthma Control Questionnaire (ACQ), pulmonary function testing, and skin prick testing to 10 common aeroallergens. Patients had a physician's diagnosis of asthma, had significant reversibility in forced expiratory volume in 1 second or a positive methacholine challenge test result, and did not have chronic obstructive pulmonary disease. The mean daily residential exposure to elemental carbon attributable to traffic (ECAT) was estimated using a land-use regression model. Regression models were used to evaluate associations among independent variables, ACQ scores, and the number of asthma exacerbations, defined as acute worsening of asthma symptoms requiring prednisone use, in the past year. RESULTS: In the adjusted model, mean daily residential exposure to ECAT greater than 0.39 µg/m(3) was significantly associated with poorer asthma control based on ACQ scores (adjusted ß = 2.85; 95% confidence interval [CI], 0.58-5.12; P = .02). High ECAT levels were also significantly associated with increased risk of asthma exacerbations (adjusted odds ratio, 3.24; 95% CI, 1.01-10.37; P = .05). A significant association was found between higher body mass index and worse ACQ scores (adjusted ß = 1.15; 95% CI, 0.53-1.76; P < .001). Atopic patients (skin prick test positive) had significantly better ACQ scores than nonatopic patients (adjusted ß = -0.39; 95% CI, -0.67 to -0.11; P < .01). CONCLUSION: Higher mean daily residential exposure to traffic exhaust, obesity, and nonatopic status are associated with poorer asthma control among older asthmatic patients.

Genetic variation in small proline rich protein 2B as a predictor for asthma among children with eczema.

BACKGROUND: Small proline rich protein 2B (SPRR2B) is a skin and lung epithelial protein associated with allergic inflammation in mice that has not been evaluated in human atopic diseases. OBJECTIVE: To determine whether single-nucleotide polymorphisms (SNPs) in SPRR2B are associated with childhood eczema and with the phenotype of childhood eczema combined with asthma. METHODS: Genotyping for SPRR2B and filaggrin (FLG) was performed in 2 independent populations: the Cincinnati Childhood Allergy & Air Pollution Study (CCAAPS; N = 762; birth-age, 4 years) and the Greater Cincinnati Pediatric Clinical Repository (GCPCR; N = 1152; ages 5-10 years). Eczema and eczema plus asthma were clinical outcomes based on parental report and clinician's diagnosis. Genetic analyses were restricted to whites and adjusted for sex in both cohorts and adjusted for environmental covariates in CCAAPS. RESULTS: Variants in SPRR2B were not significantly associated with eczema in either cohort after Bonferroni adjustment. Children from both cohorts with the CC genotype of the SPRR2B rs6693927 SNP were at 4 times the risk for eczema plus asthma (adjusted odds ratio, 4.1; 95% confidence interval, 1.5-10.9; P = .005 in CCAAPS; and adjusted odds ratio, 4.0; 95% confidence interval, 1.8-9.1; P < .001 in the GCPCR), however. SNPs in SPRR2B were not in strong linkage disequilibrium with the R501X and del2282 FLG mutations, and these findings were independent of FLG. CONCLUSIONS: An SNP in SPRR2B was predictive of asthma among white children with eczema from 2 independent populations. SPRR2B polymorphisms may serve as important predictive markers for the combined eczema plus asthma phenotype.

Effectiveness of Hydroxychloroquine and Omalizumab in Chronic Spontaneous Urticaria: A Real-World Study.

BACKGROUND: Chronic spontaneous urticaria (CSU) not controlled by optimized doses of antihistamines is referred to as refractory CSU. Add-on therapies recommended by guidelines include omalizumab, immunosuppressive, and anti-inflammatory agents. OBJECTIVES: The objective of the study was to assess the real-world effectiveness of different add-on treatment options for refractory CSU in 2 large clinical practices. METHODS: A retrospective chart review was conducted in 264 patients with refractory CSU not adequately controlled for ≥6 weeks with optimized doses of second-generation histamine-1 blockers. Omalizumab and hydroxychloroquine were the most frequently prescribed add-on therapies, allowing comparisons of clinical outcomes for these 2 agents. Complete response included absent or infrequent urticaria and patient satisfaction with treatment. Partial response was reduced hives, but requiring a second add-on therapy. Sustained response was complete response to an add-on therapy for ≥1 year. RESULTS: Omalizumab add-on treatment was significantly more likely to be associated with a complete response versus hydroxychloroquine. Complete sustained response at 1 year was observed in 82% (111 of 134) of patients on omalizumab and 66% (73 of 111) on hydroxychloroquine as the first add-on therapy (P < .01). Patients with thyroid disease had a poorer response to add-on treatments (45% responded vs 63%; P = .03). In patients with incomplete responses to first add-on interventions (n = 45), 65% and 62% subsequently had complete responses to omalizumab and hydroxychloroquine, respectively. CONCLUSIONS: Although omalizumab was superior, hydroxychloroquine achieved a complete response in two-thirds of treated patients. Given a favorable safety profile, hydroxychloroquine should be considered as an add-on treatment for refractory CSU.

Opposing effects of cat and dog ownership and allergic sensitization on eczema in an atopic birth cohort.

OBJECTIVE: To examine risk factors for eczema at age 4 years. STUDY DESIGN: Beginning at 1 year of age, infants of atopic parents (n = 636) had annual clinical evaluations and skin prick tests (SPTs) to 15 aeroallergens and milk and egg. Parents completed validated surveys on eczema and environmental exposures. House dust samples were evaluated for allergens and endotoxin. Eczema was defined as a parental report of scratching, and redness, "raised bumps," or dry skin/scaling for 6 of the last 12 months. RESULTS: At age 4 years, a total of 90 children (14%) had eczema. Not having a dog before 1 year of age and being dog SPT+ at 1, 2, or 3 years of age conferred a 4-fold higher risk for eczema at age 4 years (adjusted odds ratio [aOR] = 3.9 [1.6-9.2]; P = .002). Among dog owners, however, dog SPT+ was not associated with significantly increased risk (aOR 1.3 [0.3-6.8]; P = .8). Among children with cats before 1 year of age, cat SPT+ conferred significantly increased risk for eczema (aOR = 13.3 [3.1-57.9]; P < .001). Among non-cat owners, cat SPT+ was not associated with increased risk (aOR = 1.1 [0.5-2.7]; P = .8). CONCLUSION: Dog ownership significantly reduced the risk for eczema at age 4 years among dog-sensitized children, cat ownership combined with cat sensitization significantly increased the risk.

Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections: ACAAI/AAAAI surveillance study of subcutaneous immunotherapy: year 2.

BACKGROUND: Incidences of subcutaneous immunotherapy (SCIT) related systemic reactions (SRs) and fatal reactions (FRs) are not well defined, nor are delayed-onset SRs and their treatment. OBJECTIVES: To estimate SCIT-related SRs/FRs, and the incidence and treatment of delayed-onset SRs. METHODS: In 2008 and 2009, American Academy of Allergy, Asthma & Immunology (AAAAI) and American College of Allergy Asthma & Immunology (ACAAI) members completed a survey about SCIT-related SR severity (grade 1 = mild; grade 2 = moderate; grade 3 = severe anaphylaxis). In 2009, members reported the time of onset and use of epinephrine (EPI), with early onset defined as beginning ≤30 minutes, and delayed onset beginning more than 30 minutes after injections. RESULTS: As in year 1, no FRs were reported during year 2 (630 total practices responded). Among 267 practices providing data on the timing of SRs, 1,816 early-onset SRs (86%) and 289 (14%) delayed-onset SRs were reported. Fifteen percent (226/1,519) of grade 1, 10% (54/538) of grade 2, and 12.5% (9/72) of grade 3 SRs were delayed-onset. Among early-onset SRs, EPI was given for 71% of grade 1, 93% of grade 2, and 94% of grade 3s. Among delayed-onset SRs, EPI was given for 56% of grade 1, 67% of grade 2, and 100% of grade 3s (P = .0008 for difference in EPI administration based on severity; P = .07 based on time of onset). CONCLUSIONS: Delayed-onset SRs are less frequent than previously reported. Epinephrine was given less frequently for grades 1 and 2 (but not grade 3) delayed-onset SRs compared with early-onset SRs. Further study of prescribing self-injectable EPI for SCIT patients in the event of delayed-onset SRs may be warranted.

AAAAI/ACAAI Subcutaneous Immunotherapy Surveillance Study (2013-2017): Fatalities, Infections, Delayed Reactions, and Use of Epinephrine Autoinjectors.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is highly effective but safety risks exist. OBJECTIVE: The aims of this study were to: (1) identify clinical practices that could influence fatal and nonfatal systemic allergic reactions (SRs) to SCIT, and (2) identify SCIT-associated infections. METHODS: From 2008 to 2016, 27% to 51% of American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology members completed an annual survey of SCIT-related SRs of varying severity. Injection-related local cutaneous and systemic infections were queried for 2014-2016. For 2014-2016, respondents were queried about timing of onset of SRs, postinjection waiting times, and prescription/use of epinephrine autoinjectors. RESULTS: Data were gathered on 54.4 million injection visits (2008-2016). Two confirmed fatalities from SCIT occurred between 2008 and 2014. An additional 5 confirmed fatalities occurred between 2015 and 2017. No infections occurred in 17.3 million injection visits (2014-2016). Among practices monitoring patients for at least 30 minutes, 15% of SRs occurred after 30 minutes. Practices prescribing an epinephrine autoinjector >90% of the time (29% of practices) did not experience lower rates of delayed grade 3/4 SRs. Of patients experiencing grade 3/4 delayed SRs, 26% and 8% used prescribed self-injectable epinephrine devices during 2014-2015 and 2015-2016, respectively. CONCLUSIONS: There is an unexplained slight increase in SCIT-related fatalities for 2015-2017, although mean annual reported events over 9 years (0.8 fatal reactions per year) have declined. SCIT-related infections were not identified during 2 years of surveillance. The 15% incidence of delayed-onset SRs (>30 minutes) is similar to a prior annual survey. Prescribing epinephrine autoinjectors for SCIT does not appear to improve outcomes, possibly due to low rates of self-administration.

Current and emerging management options for hereditary angioedema in the US.

Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of swelling that may involve multiple anatomical locations. In the majority of patients, it is caused by a functional or quantitative defect in the C1 inhibitor (C1-INH), which is an important regulator of the complement, fibrinolytic, kallikrein-kinin and coagulation systems. Standard treatments used for other types of angioedema are ineffective for HAE. Traditional therapies for HAE, including fresh frozen plasma, epsilon-aminocaproic acid and danazol, may be well tolerated and effective in some patients; however, there are limitations both in their safety and efficacy. Several novel therapies have completed phase III trials in the US, including: (i) plasma-derived C1-INH replacement therapies (Berinert P and Cinryze); (ii) a recombinant C1-INH replacement therapy (conestat alfa; Rhucin); (iii) a kallikrein inhibitor (ecallantide [DX-88]); and (iv) a bradykinin-2-receptor antagonist (icatibant). Both Berinert P and Cinryze are reported to have excellent efficacy and safety data from phase III trials. Currently, only Cinryze has been approved for prophylactic use in the US. US FDA approval for other novel agents to treat HAE and for the use of Cinryze in the treatment of acute attacks is pending.

Current Evidence on Safety and Practical Considerations for Administration of Sublingual Allergen Immunotherapy (SLIT) in the United States.

Liquid sublingual allergen immunotherapy (SLIT) has been used off-label for decades, and Food and Drug Administration (FDA)-approved grass and ragweed SLIT tablets have been available in the United States since 2014. Potentially life-threatening events from SLIT do occur, although they appear to be very rare, especially for FDA-approved products. Practice guidelines that incorporate safety precautions regarding the use of SLIT in the United States are needed. This clinical commentary attempts to address unresolved issues including controversy regarding the FDA mandate for the prescription of epinephrine autoinjectors for patients on SLIT; how to approach polysensitized patients; optimal timing and duration of SLIT administration; how to address gaps in therapy; whether antihistamines can prevent local reactions, if certain patient populations (such as persistent asthmatics) should not receive SLIT; and when to instruct patients to self-administer epinephrine. Key points are that physicians should focus on educating patients regarding: (1) when not to administer SLIT; (2) how to recognize a potentially serious allergic reaction to SLIT; and (3) when to administer epinephrine and seek emergency care.

AAAAI/ACAAI surveillance study of subcutaneous immunotherapy, years 2008-2012: an update on fatal and nonfatal systemic allergic reactions.

BACKGROUND: Before 2002, there were an estimated 3.4 fatal reactions per year to subcutaneous allergen immunotherapy (SCIT). Recent incidences of SCIT-related systemic allergic reactions (SR) and fatal reactions are not well defined. OBJECTIVE: To define the incidence of and clinical practices associated with SRs to SCIT and skin testing. METHODS: From 2008 to 2012, 27% to 49% of the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma, and Immunology members completed an annual survey of SCIT-related fatal and nonfatal SRs of varying severity. A shortened version of the World Allergy Organization (WAO) classification system for SRs was adopted in 2011 (grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, very severe). From 2011 to 2012, data were collected regarding nonfatal SRs to skin testing and strategies to lower the risk of SRs from SCIT. RESULTS: Between 2008 and 2012, data were gathered on 23.3 million injection visits. One confirmed fatality occurred in 2009. Overall SR rates remained stable at 0.1%. The rate of very severe, WAO grade 4, SRs was similar to previously reported rates of near-fatal reactions (1 in 1 million injections). Although almost one-third of practices experienced at least 1 SR from skin testing, no WAO grade 3 or 4 SRs from skin testing were reported. A lower target dose during cluster buildup before transitioning to maintenance may be associated with a lower risk of WAO grade 3 SRs (P = .07). Dose adjustment during pollen seasons was associated with fewer WAO grade 3 or 4 SRs (P < .001). CONCLUSIONS: Although SR rates have remained stable and fatalities appear to be declining, continued vigilance regarding SCIT safety is recommended. Additional surveillance and study regarding methods to decrease the risk of severe SRs is warranted.