- Email: [email protected]
Intraoperative anaphylaxis likely due to Gelfoam in a pediatric patient undergoing liver biopsy
Letters / Ann Allergy Asthma Immunol 114 (2015) 522e536
531
Figure 1. Comparison of perennial and pre-co-seasonal absolute number and percentage of variation of treatment regimen renewals before (2009e2011) and after (2012e2014) the secretary-based organization system. NS, not significant.
telephone calls (approximately every 4e6 months) and messages by e-mail were carried out by the secretary to assess AIT adherence of all followed patients. At the telephone interview, patients were asked to count the tablets or vials remaining. A computerized program, based on the starting date of SLIT and the administration schedule, calculated the expected number of consumed tablets or vials and the expected number of remaining tablets or vials. The criterion for assessing the adherence rate was defined as the patient taking more than 80% of the prescribed medication. Through this new operational approach, we observed a high rate of AIT adherence (adherence was 89.6% in the mite group and 92.1% in the pollen group) and a marked and significant improvement of the rate of renewal of the AIT (Fig 1). From 2009 through 2011, we observed that 11 of 29 patients (62%) with perennial allergy and 31 of 127 patients (75.5%) with seasonal allergy did not renew the AIT; in contrast, after using the new organizational “secretary-based” system in 2012 through 2014, only 1 of 34 patients with perennial allergy (2.94% of total) and 4 of 134 patients with seasonal allergy (2.98% of total) did not renew the AIT. The reasons for nonrenewal of the AIT were “business reasons” (transfer to another region) in 2 cases and 3 cases of immigrants who dropped out because of language barriers or unavailability of the patients to call or send a notice by mail. In conclusion, compelling general medical data demonstrate that relationships improve adherence to therapy, increase clinical benefits, decrease health care usage, and decrease direct and indirect health costs. These results are applicable for AIT. We found that the use of frequent recalls by an efficient and simple secretary-based system and the steady use of a database can improve adherence to SLIT and follow-up of patients with allergy. Based on this “real-life” experience, we believe the level of organization of allergologic units and the support of administrative
staff can be important critical factors to improve levels of AIT adherence. Carlo Lombardi, MD Departmental Unit of Allergology Clinical Immunology & Pneumology Fondazione Poliambulanza Hospital Brescia, Italy [email protected]
References [1] Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296e1310. [2] Cox LS, Hankin C, Lockey R. Allergy immunotherapy adherence and delivery route: location does not matter. J Allergy Clin Immunol Pract. 2014;2:156e160. [3] Scurati S, Frati F, Passalacqua G, et al. Adherence issues related to sublingual immunotherapy as perceived by allergists. Patient Prefer Adherence. 2010;4: 141e145. [4] Kiel MA, Roder E, Gerth van Wijk R, Al MJ, Hop WC, Rutten-van Molken MP. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy. J Allergy Clin Immunol. 2013;132: 353e360. [5] Halken S, Agertoft L, Seidenberg J, et al. Five-grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents. Pediatr Allergy Immunol. 2010; 21:970e976. [6] Bufe A, Eberle P, Franke-Beckmann E, et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol. 2009;123:167e173. [7] Lombardi C, Gani F, Landi M, et al. Quantitative assessment of the adherence to sublingual immunotherapy. J Allergy Clin Immunol. 2004;113:1219e1220. [8] Senna G, Lombardi C, Canonica GW, Passalacqua G. How adherent to sublingual immunotherapy prescriptions are patients? The manufacturers’ viewpoint. J Allergy Clin Immunol. 2010;126:668e669. [9] Egert-Schmidt AM, Kolbe J-M, Mussler S, Thum-Oltmer S. Patients’ compliance with different administration routes for allergen immunotherapy in Germany. Patient Prefer Adherence. 2014;8:1475e1481.
Intraoperative anaphylaxis likely due to Gelfoam in a pediatric patient undergoing liver biopsy Serious allergic reactions have been described in the use of vaccines or intravenous colloid products containing bovine or porcine Disclosure: Authors have nothing to disclose.
gelatin, and some recent case reports have described intraoperative anaphylaxis to topical gelatin-based hemostatic products (all occurring in pediatric spinal surgical cases).1e4 We report on a case of intraoperative anaphylaxis to Gelfoam (Pfizer,
532
Letters / Ann Allergy Asthma Immunol 114 (2015) 522e536
New York, New York) in a pediatric patient undergoing a liver biopsy procedure. A 10-year-old girl with a history of orthotropic cardiac transplantation on chronic immunosuppression (tacrolimus and prednisone) complicated by post-transplantation lymphoproliferative disease presented for liver biopsy examination to evaluate hepatic dysfunction. She underwent induction of general anesthesia (propofol, lidocaine, and fentanyl), laryngeal mask airway placement, central line placement, and liver biopsy sample collection without event. Immediately after injection of Gelfoam at the biopsy site for hemostasis, the patient became hypotensive (to 55/39 mmHg) with hypoxia and development of facial edema and urticaria. She was treated with intravenous phenylephrine, hydrocortisone, and diphenhydramine and intramuscular epinephrine, with resolution of hypotension and urticaria. At intubation of the trachea for airway protection, significant edema was noted. Serum total tryptase was elevated at 16 ng/mL 1 hour 45 minutes after the onset of symptoms. The patient selfextubated later in the day and was urgently reintubated in the operating room, at which time ongoing edema of the epiglottis and pharynx was noted, in addition to edema of the face. The patient remained intubated for 2 days, and repeat serum tryptase was noted to be normal (<1 ng/mL) 6 days after the event. Complement levels and activity were normal (C3 111 mg/dL, C4 29 mg/ dL, C1 esterase inhibitor function >100%, C1 esterase inhibitor level 41 mg/dL). Specific IgE (ImmunoCap, Phadia, Uppsala, Sweden) testing demonstrated sensitivity to porcine gelatin (10.60 kUA/L), and IgE to bovine gelatin was 0.72 kUA/L and to pork meat was 0.11 kUA/L. The patient had 2 subsequent procedures involving sedation with fentanyl, propofol, and lidocaine that were entirely uneventful, with no symptoms suggestive of hypersensitivity noted. Given the lack of supportive evidence for mast cell activation disorder or mastocytosis, the patient’s history, complement levels inconsistent with isolated angioedema, the clear temporal relation with Gelfoam administration, and subsequent tolerance of propofol, fentanyl, and lidocaine, anaphylaxis in this case was most likely explained by the patient’s sensitivity to porcine gelatin and administration of the gelatin-containing hemostatic product. Gelfoam is derived from purified pork skin gelatin USP granules and can be applied during surgical procedures to control bleeding. Allergy to porcine collagen is a documented contraindication to its use.5 Although some reports of anaphylaxis to gelatin-containing hemostatic products have been associated with patients who report previous intolerance to gelatin-containing foods,2,3 the present patient had been consuming Jell-O and gelatin-containing yogurt on an almost-daily basis in the hospital immediately before the incident. She had no history of adverse reaction to gelatincontaining vaccines or foods, tolerated pork, and denied immediate or delayed hypersensitivity to any meats. Although she continued to consume gelatin after anaphylaxis to Gelfoam without incident, she should be considered at risk for future reactions at exposure to higher allergen loads, and avoidance of gelatin-containing vaccines, hemostatic agents, or intravenous products is warranted. Gelatin sensitivity should be suspected in cases of intraoperative anaphylaxis when a topical or intravenous gelatinbased product is used. Known sensitivity to any mammalian gelatin (ie, bovine or porcine) should prompt caution in the use of these products, given cross-reactivity.6,7 In addition, new development of food allergy has been increasingly recognized in children with recent solid-organ transplantation, representing patients at potential risk.7 Immunosuppression with tacrolimus
has been specifically implicated as a risk factor in posttransplantation development of food allergy, with hypothesized mechanisms including increased intestinal barrier permeability and skewing toward a T-helper cell type 2 cytokine profile.8,9 Oral tolerance to gelatin-containing food products and vaccines did not predict hypersensitivity to Gelfoam in this case, but this might not be surprising given the difference in route of administration with increased allergen exposure and contact with the highly vascular surface of the liver. Similar histories have been described in the context of anaphylaxis to gelatin-containing vaccines, in which prior reaction to gelatin ingestion might be absent.10 Still, some reports have described anaphylaxis to gelatin-containing hemostatic products in patients with histories of oral gelatin intolerance,2,3 indicating that prior symptoms, if present, could identify some patients at risk. Gelatin hypersensitivity could represent an under-recognized allergy, and cases such as this demonstrate that oral tolerance does not preclude severe reactions when higher allergen loads or different routes of administration are encountered. Gelatincontaining products are of biologic origin with the potential to induce IgE-mediated hypersensitivity reactions, as described in the present case. Given an existing cluster of case reports related to gelatin-containing hemostatic agents, consideration should be given for a systemic evaluation of overall risk (including reporting to the US Food and Drug Administration; http://www.fda.gov/ safety/medwatch/howtoreport/ucm053074.htm), study of future risk for reactions to other gelatin-containing products (including vaccines), and heightened awareness for those using these products in practice. Karen A. Robbins, MD* Corinne A. Keet, MD, PhDy *Division of Asthma, Allergy and Immunology Hasbro Children’s Hospital/Rhode Island Hospital Alpert Medical School at Brown University Providence, Rhode Island y Division of Pediatric Allergy and Immunology Johns Hopkins University School of Medicine Baltimore, Maryland [email protected]
References [1] Spencer HT, Hsu JT, McDonald DR, Karlin LI. Intraoperative anaphylaxis to gelatin in topical hemostatic agents during anterior spinal fusion: a case report. Spine J. 2012;12:e1ee6. [2] Luhmann SJ, Sucato DJ, Bacharier L, Ellis A, Woerz C. Intraoperative anaphylaxis secondary to intraosseous gelatin administration. J Pediatr Orthop. 2013; 33:e58ee60. [3] Khoriaty E, McClain CD, Permaul P, Smith ER, Rachid R. Intraoperative anaphylaxis induced by the gelatin component of thrombin-soaked Gelfoam in a pediatric patient. Ann Allergy Asthma Immunol. 2012;108:206e213. [4] Agarwal NS, Spalding C, Nassef M. Life-threatening intraoperative anaphylaxis to gelatin in Floseal during pediatric spinal surgery. J Allergy Clin Immunol Pract. 2015;3:110e111. [5] GelfoamÒ absorbable gelatin sponge, USP [package insert]. New York: Pfizer. http://labeling.pfizer.com/ShowLabeling.aspx?id¼624. Accessed September 15, 2014. [6] Bogdanovic J, Halsey NA, Wood RA, Hamilton RG. Bovine and porcine gelatin sensitivity in children sensitized to milk and meat. J Allergy Clin Immunol. 2009;124:1108e1110. [7] Sakaguchi M, Hori H, Ebihara T, Irie S, Yanagida M, Inouye S. Reactivity of the immunoglobulin E in bovine gelatin-sensitive children to gelatins from various animals. Immunology. 1999;96:286e290. [8] Frischmeyer-Guerrerio PA, Wisniewski J, Wood RA, Nowak-Wegrzyn A. Manifestations and long-term outcome of food allergy in children after solid organ transplantation. J Allergy Clin Immunol. 2008;122:1031e1033.
Letters / Ann Allergy Asthma Immunol 114 (2015) 522e536 [9] Maarof G, Krzysiek R, Decline J, Cohen J, Habes D, Jacquemin E. Management of post-liver transplant-associated IgE mediated food allergy in children. J Allergy Clin Immunol. 2011;127:1296e1298.
533
[10] Sakaguchi M, Nakayama T, Inouye S. Food allergy to gelatin in children with systemic immediate-type reactions, including anaphylaxis, to vaccines. J Allergy Clin Immunol. 1996;98:1058e1061.
Black and Hispanic perceptions of asthma medication in the School Inner-City Asthma Study Racial and ethnic minorities suffer a disproportionate rate of asthma morbidity.1 We aimed to determine racial and ethnic differences in the perception of asthma medications of caregivers of black vs Hispanic school children enrolled in the School Inner-City Asthma Study. Furthermore, we investigated whether these beliefs were associated with asthma morbidity. The School Inner-City Asthma Study is a prospective, observational study of home and school environments related to asthma morbidity in inner-city school children.2 Questionnaires completed by caregivers of enrolled students with asthma elicited selfidentified race and ethnicity, perception of asthma control, attitudes toward asthma medications, and asthma symptoms. Analysis was limited to black and Hispanic subjects because fewer than 5% of participants were white. The study was approved by the Boston Children’s Hospital investigational review board. Subject assent and parental consent were obtained for all subjects before enrollment. Univariate analysis examined the associations of race and ethnicity on reported asthma control (4-week recall), belief that asthma medications can be effective, belief the child receives too much medication, worry about side effects, reports that medications “do not really work,” use of alternative remedies, and modification of drug therapy owing to these concerns. Multivariate models evaluated the perception of asthma control and medication attitudes with race if the univariate P value was less than or equal to .05 and adjusting for age, sex, and potential sociodemographic characteristics if associated with the outcome (P < .2) and confounding to the main effect. Quantitative assessment of asthma morbidity was measured as the maximum number of asthma symptom days,2 defined as the largest of the following variables in the 2 weeks before the baseline survey: (1) daytime wheezing, chest tightness, or cough; (2) days on which child had to slow down or discontinue play activities owing to wheezing, chest tightness, or cough; and (3) nights with wheezing, chest tightness, or cough leading to disturbed sleep. Associations between attitudes toward medication and asthma morbidity were tested by the Wilcoxon rank-sum test. Race was reported by 268 subjects: 15 (4%) white, 120 (34%) black, 133 (38%) Hispanic, and 83 (31%) mixed or other. The average age was 7.8 years, and 46% were girls. There was no Dr Gaffin and Mr Landrum contributed equally to this study. Disclosure: Authors have nothing to disclose. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health Clinical Trial Service Unit Principal Investigator (Lee Nagler). Funding Sources: This study was supported by grants K23AI106945, R01 AI 073964, R01 AI 073964-02S1, K24 AI 106822, K23 AI104780, L40 AI107923, U01AI110397, and U10HL098102 from the National Institutes of Health. This work was conducted with support from Harvard Catalyst and The Harvard Clinical and Translational Science Center (National Institutes of Health award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic health care centers. This work also was supported in part by the American College of Allergy, Asthma, and Immunology Young Faculty Award and Respiratory Diseases Faculty Award; Boston Children’s Hospital Division of Immunology Clinical Research Advisory Group Research Grant; the American Lung Association; and the Deborah Munroe Noonan Memorial Award.
difference in perception of asthma control between blacks and Hispanics. However, caregivers of Hispanic children were 4.9 times as likely to report the child was on too much medication compared with caregivers of black children. Furthermore, Hispanic caregivers tended to be less confident medications could control the child’s asthma and were more likely to worry about side effects, report medications did not work, use alternative remedies, and cut back on asthma medications for these concerns (Table 1). After adjusting for age, sex, and caregiver education, Hispanics remained significantly more likely to believe the child was taking too much medication (odds ratio 4.9, 95% confidence interval 1.7e14.0, P ¼ .003). Negative perceptions of asthma medications were significantly associated with more asthma symptoms days. Report of “child gets too much medication” was associated with more asthma symptom days (median 4 days, interquartile range [IQR] 2,7, vs 1 day, IQR 0,3, P < .001), as were worry about side effects (median 3 days, IQR 0,5, vs 1 day, IQR 0,3, P ¼ .005) and believing the drugs were not effective (median 3 days, IQR 0,5, vs 1 day, IQR 0,3, P ¼ .007). There was no difference in asthma symptoms by alternative remedy use (median 2, IQR 0,4, vs 1, IQR 0,4, P ¼ .4). We found that caregivers of Hispanic children were almost 5 times as likely to be concerned their child took too much medicine and that medication concerns were strongly and consistently associated with poor asthma control. Although race, medication perception, and asthma control have been described separately, this study found the associations of Hispanic ethnicity, negative medication beliefs, and increased asthma symptoms within the same carefully studied cohort of inner-city school children with asthma. Our findings are consistent with prior studies reporting lower expectations and greater worry about minority children’s asthma,3 particularly Hispanic caregivers’ heightened concern over medication use.3 Hispanic ethnicity was associated with the belief that the child receives too much medication independent of caregiver education, income, or Medicaid status, suggesting racial and ethnic identification is the key influence on attitudes. These findings support that underuse of controller medication by minority populations is independent of sociodemographic factors.4,5 Medication concerns could be a key modifiable risk factor for suboptimal controller medication use6 because they directly influence adherence7 and could be the target of counseling interventions to improve outcomes. In addition, we found that negative beliefs linked to medication were associated with poor asthma control. Parental concern over medications can lead to poor adherence8 and thereby control,9 although similar findings have been found independent of adherence.10 In this context, the causal relation might be bidirectionaldparents of symptomatic children might have less confidence in the benefit-to-risk ratio of prescribed medications. This bears further investigation. Despite standardization of asthma care and efforts to improve minority access to health care, racial, ethnic, and cultural disparities in asthma persist.1 The present findings highlight the racial and ethnic differences in the perception of asthma medication and the effect of negative medication perceptions on asthma control.
531
Figure 1. Comparison of perennial and pre-co-seasonal absolute number and percentage of variation of treatment regimen renewals before (2009e2011) and after (2012e2014) the secretary-based organization system. NS, not significant.
telephone calls (approximately every 4e6 months) and messages by e-mail were carried out by the secretary to assess AIT adherence of all followed patients. At the telephone interview, patients were asked to count the tablets or vials remaining. A computerized program, based on the starting date of SLIT and the administration schedule, calculated the expected number of consumed tablets or vials and the expected number of remaining tablets or vials. The criterion for assessing the adherence rate was defined as the patient taking more than 80% of the prescribed medication. Through this new operational approach, we observed a high rate of AIT adherence (adherence was 89.6% in the mite group and 92.1% in the pollen group) and a marked and significant improvement of the rate of renewal of the AIT (Fig 1). From 2009 through 2011, we observed that 11 of 29 patients (62%) with perennial allergy and 31 of 127 patients (75.5%) with seasonal allergy did not renew the AIT; in contrast, after using the new organizational “secretary-based” system in 2012 through 2014, only 1 of 34 patients with perennial allergy (2.94% of total) and 4 of 134 patients with seasonal allergy (2.98% of total) did not renew the AIT. The reasons for nonrenewal of the AIT were “business reasons” (transfer to another region) in 2 cases and 3 cases of immigrants who dropped out because of language barriers or unavailability of the patients to call or send a notice by mail. In conclusion, compelling general medical data demonstrate that relationships improve adherence to therapy, increase clinical benefits, decrease health care usage, and decrease direct and indirect health costs. These results are applicable for AIT. We found that the use of frequent recalls by an efficient and simple secretary-based system and the steady use of a database can improve adherence to SLIT and follow-up of patients with allergy. Based on this “real-life” experience, we believe the level of organization of allergologic units and the support of administrative
staff can be important critical factors to improve levels of AIT adherence. Carlo Lombardi, MD Departmental Unit of Allergology Clinical Immunology & Pneumology Fondazione Poliambulanza Hospital Brescia, Italy [email protected]
References [1] Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296e1310. [2] Cox LS, Hankin C, Lockey R. Allergy immunotherapy adherence and delivery route: location does not matter. J Allergy Clin Immunol Pract. 2014;2:156e160. [3] Scurati S, Frati F, Passalacqua G, et al. Adherence issues related to sublingual immunotherapy as perceived by allergists. Patient Prefer Adherence. 2010;4: 141e145. [4] Kiel MA, Roder E, Gerth van Wijk R, Al MJ, Hop WC, Rutten-van Molken MP. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy. J Allergy Clin Immunol. 2013;132: 353e360. [5] Halken S, Agertoft L, Seidenberg J, et al. Five-grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents. Pediatr Allergy Immunol. 2010; 21:970e976. [6] Bufe A, Eberle P, Franke-Beckmann E, et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol. 2009;123:167e173. [7] Lombardi C, Gani F, Landi M, et al. Quantitative assessment of the adherence to sublingual immunotherapy. J Allergy Clin Immunol. 2004;113:1219e1220. [8] Senna G, Lombardi C, Canonica GW, Passalacqua G. How adherent to sublingual immunotherapy prescriptions are patients? The manufacturers’ viewpoint. J Allergy Clin Immunol. 2010;126:668e669. [9] Egert-Schmidt AM, Kolbe J-M, Mussler S, Thum-Oltmer S. Patients’ compliance with different administration routes for allergen immunotherapy in Germany. Patient Prefer Adherence. 2014;8:1475e1481.
Intraoperative anaphylaxis likely due to Gelfoam in a pediatric patient undergoing liver biopsy Serious allergic reactions have been described in the use of vaccines or intravenous colloid products containing bovine or porcine Disclosure: Authors have nothing to disclose.
gelatin, and some recent case reports have described intraoperative anaphylaxis to topical gelatin-based hemostatic products (all occurring in pediatric spinal surgical cases).1e4 We report on a case of intraoperative anaphylaxis to Gelfoam (Pfizer,
532
Letters / Ann Allergy Asthma Immunol 114 (2015) 522e536
New York, New York) in a pediatric patient undergoing a liver biopsy procedure. A 10-year-old girl with a history of orthotropic cardiac transplantation on chronic immunosuppression (tacrolimus and prednisone) complicated by post-transplantation lymphoproliferative disease presented for liver biopsy examination to evaluate hepatic dysfunction. She underwent induction of general anesthesia (propofol, lidocaine, and fentanyl), laryngeal mask airway placement, central line placement, and liver biopsy sample collection without event. Immediately after injection of Gelfoam at the biopsy site for hemostasis, the patient became hypotensive (to 55/39 mmHg) with hypoxia and development of facial edema and urticaria. She was treated with intravenous phenylephrine, hydrocortisone, and diphenhydramine and intramuscular epinephrine, with resolution of hypotension and urticaria. At intubation of the trachea for airway protection, significant edema was noted. Serum total tryptase was elevated at 16 ng/mL 1 hour 45 minutes after the onset of symptoms. The patient selfextubated later in the day and was urgently reintubated in the operating room, at which time ongoing edema of the epiglottis and pharynx was noted, in addition to edema of the face. The patient remained intubated for 2 days, and repeat serum tryptase was noted to be normal (<1 ng/mL) 6 days after the event. Complement levels and activity were normal (C3 111 mg/dL, C4 29 mg/ dL, C1 esterase inhibitor function >100%, C1 esterase inhibitor level 41 mg/dL). Specific IgE (ImmunoCap, Phadia, Uppsala, Sweden) testing demonstrated sensitivity to porcine gelatin (10.60 kUA/L), and IgE to bovine gelatin was 0.72 kUA/L and to pork meat was 0.11 kUA/L. The patient had 2 subsequent procedures involving sedation with fentanyl, propofol, and lidocaine that were entirely uneventful, with no symptoms suggestive of hypersensitivity noted. Given the lack of supportive evidence for mast cell activation disorder or mastocytosis, the patient’s history, complement levels inconsistent with isolated angioedema, the clear temporal relation with Gelfoam administration, and subsequent tolerance of propofol, fentanyl, and lidocaine, anaphylaxis in this case was most likely explained by the patient’s sensitivity to porcine gelatin and administration of the gelatin-containing hemostatic product. Gelfoam is derived from purified pork skin gelatin USP granules and can be applied during surgical procedures to control bleeding. Allergy to porcine collagen is a documented contraindication to its use.5 Although some reports of anaphylaxis to gelatin-containing hemostatic products have been associated with patients who report previous intolerance to gelatin-containing foods,2,3 the present patient had been consuming Jell-O and gelatin-containing yogurt on an almost-daily basis in the hospital immediately before the incident. She had no history of adverse reaction to gelatincontaining vaccines or foods, tolerated pork, and denied immediate or delayed hypersensitivity to any meats. Although she continued to consume gelatin after anaphylaxis to Gelfoam without incident, she should be considered at risk for future reactions at exposure to higher allergen loads, and avoidance of gelatin-containing vaccines, hemostatic agents, or intravenous products is warranted. Gelatin sensitivity should be suspected in cases of intraoperative anaphylaxis when a topical or intravenous gelatinbased product is used. Known sensitivity to any mammalian gelatin (ie, bovine or porcine) should prompt caution in the use of these products, given cross-reactivity.6,7 In addition, new development of food allergy has been increasingly recognized in children with recent solid-organ transplantation, representing patients at potential risk.7 Immunosuppression with tacrolimus
has been specifically implicated as a risk factor in posttransplantation development of food allergy, with hypothesized mechanisms including increased intestinal barrier permeability and skewing toward a T-helper cell type 2 cytokine profile.8,9 Oral tolerance to gelatin-containing food products and vaccines did not predict hypersensitivity to Gelfoam in this case, but this might not be surprising given the difference in route of administration with increased allergen exposure and contact with the highly vascular surface of the liver. Similar histories have been described in the context of anaphylaxis to gelatin-containing vaccines, in which prior reaction to gelatin ingestion might be absent.10 Still, some reports have described anaphylaxis to gelatin-containing hemostatic products in patients with histories of oral gelatin intolerance,2,3 indicating that prior symptoms, if present, could identify some patients at risk. Gelatin hypersensitivity could represent an under-recognized allergy, and cases such as this demonstrate that oral tolerance does not preclude severe reactions when higher allergen loads or different routes of administration are encountered. Gelatincontaining products are of biologic origin with the potential to induce IgE-mediated hypersensitivity reactions, as described in the present case. Given an existing cluster of case reports related to gelatin-containing hemostatic agents, consideration should be given for a systemic evaluation of overall risk (including reporting to the US Food and Drug Administration; http://www.fda.gov/ safety/medwatch/howtoreport/ucm053074.htm), study of future risk for reactions to other gelatin-containing products (including vaccines), and heightened awareness for those using these products in practice. Karen A. Robbins, MD* Corinne A. Keet, MD, PhDy *Division of Asthma, Allergy and Immunology Hasbro Children’s Hospital/Rhode Island Hospital Alpert Medical School at Brown University Providence, Rhode Island y Division of Pediatric Allergy and Immunology Johns Hopkins University School of Medicine Baltimore, Maryland [email protected]
References [1] Spencer HT, Hsu JT, McDonald DR, Karlin LI. Intraoperative anaphylaxis to gelatin in topical hemostatic agents during anterior spinal fusion: a case report. Spine J. 2012;12:e1ee6. [2] Luhmann SJ, Sucato DJ, Bacharier L, Ellis A, Woerz C. Intraoperative anaphylaxis secondary to intraosseous gelatin administration. J Pediatr Orthop. 2013; 33:e58ee60. [3] Khoriaty E, McClain CD, Permaul P, Smith ER, Rachid R. Intraoperative anaphylaxis induced by the gelatin component of thrombin-soaked Gelfoam in a pediatric patient. Ann Allergy Asthma Immunol. 2012;108:206e213. [4] Agarwal NS, Spalding C, Nassef M. Life-threatening intraoperative anaphylaxis to gelatin in Floseal during pediatric spinal surgery. J Allergy Clin Immunol Pract. 2015;3:110e111. [5] GelfoamÒ absorbable gelatin sponge, USP [package insert]. New York: Pfizer. http://labeling.pfizer.com/ShowLabeling.aspx?id¼624. Accessed September 15, 2014. [6] Bogdanovic J, Halsey NA, Wood RA, Hamilton RG. Bovine and porcine gelatin sensitivity in children sensitized to milk and meat. J Allergy Clin Immunol. 2009;124:1108e1110. [7] Sakaguchi M, Hori H, Ebihara T, Irie S, Yanagida M, Inouye S. Reactivity of the immunoglobulin E in bovine gelatin-sensitive children to gelatins from various animals. Immunology. 1999;96:286e290. [8] Frischmeyer-Guerrerio PA, Wisniewski J, Wood RA, Nowak-Wegrzyn A. Manifestations and long-term outcome of food allergy in children after solid organ transplantation. J Allergy Clin Immunol. 2008;122:1031e1033.
Letters / Ann Allergy Asthma Immunol 114 (2015) 522e536 [9] Maarof G, Krzysiek R, Decline J, Cohen J, Habes D, Jacquemin E. Management of post-liver transplant-associated IgE mediated food allergy in children. J Allergy Clin Immunol. 2011;127:1296e1298.
533
[10] Sakaguchi M, Nakayama T, Inouye S. Food allergy to gelatin in children with systemic immediate-type reactions, including anaphylaxis, to vaccines. J Allergy Clin Immunol. 1996;98:1058e1061.
Black and Hispanic perceptions of asthma medication in the School Inner-City Asthma Study Racial and ethnic minorities suffer a disproportionate rate of asthma morbidity.1 We aimed to determine racial and ethnic differences in the perception of asthma medications of caregivers of black vs Hispanic school children enrolled in the School Inner-City Asthma Study. Furthermore, we investigated whether these beliefs were associated with asthma morbidity. The School Inner-City Asthma Study is a prospective, observational study of home and school environments related to asthma morbidity in inner-city school children.2 Questionnaires completed by caregivers of enrolled students with asthma elicited selfidentified race and ethnicity, perception of asthma control, attitudes toward asthma medications, and asthma symptoms. Analysis was limited to black and Hispanic subjects because fewer than 5% of participants were white. The study was approved by the Boston Children’s Hospital investigational review board. Subject assent and parental consent were obtained for all subjects before enrollment. Univariate analysis examined the associations of race and ethnicity on reported asthma control (4-week recall), belief that asthma medications can be effective, belief the child receives too much medication, worry about side effects, reports that medications “do not really work,” use of alternative remedies, and modification of drug therapy owing to these concerns. Multivariate models evaluated the perception of asthma control and medication attitudes with race if the univariate P value was less than or equal to .05 and adjusting for age, sex, and potential sociodemographic characteristics if associated with the outcome (P < .2) and confounding to the main effect. Quantitative assessment of asthma morbidity was measured as the maximum number of asthma symptom days,2 defined as the largest of the following variables in the 2 weeks before the baseline survey: (1) daytime wheezing, chest tightness, or cough; (2) days on which child had to slow down or discontinue play activities owing to wheezing, chest tightness, or cough; and (3) nights with wheezing, chest tightness, or cough leading to disturbed sleep. Associations between attitudes toward medication and asthma morbidity were tested by the Wilcoxon rank-sum test. Race was reported by 268 subjects: 15 (4%) white, 120 (34%) black, 133 (38%) Hispanic, and 83 (31%) mixed or other. The average age was 7.8 years, and 46% were girls. There was no Dr Gaffin and Mr Landrum contributed equally to this study. Disclosure: Authors have nothing to disclose. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health Clinical Trial Service Unit Principal Investigator (Lee Nagler). Funding Sources: This study was supported by grants K23AI106945, R01 AI 073964, R01 AI 073964-02S1, K24 AI 106822, K23 AI104780, L40 AI107923, U01AI110397, and U10HL098102 from the National Institutes of Health. This work was conducted with support from Harvard Catalyst and The Harvard Clinical and Translational Science Center (National Institutes of Health award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic health care centers. This work also was supported in part by the American College of Allergy, Asthma, and Immunology Young Faculty Award and Respiratory Diseases Faculty Award; Boston Children’s Hospital Division of Immunology Clinical Research Advisory Group Research Grant; the American Lung Association; and the Deborah Munroe Noonan Memorial Award.
difference in perception of asthma control between blacks and Hispanics. However, caregivers of Hispanic children were 4.9 times as likely to report the child was on too much medication compared with caregivers of black children. Furthermore, Hispanic caregivers tended to be less confident medications could control the child’s asthma and were more likely to worry about side effects, report medications did not work, use alternative remedies, and cut back on asthma medications for these concerns (Table 1). After adjusting for age, sex, and caregiver education, Hispanics remained significantly more likely to believe the child was taking too much medication (odds ratio 4.9, 95% confidence interval 1.7e14.0, P ¼ .003). Negative perceptions of asthma medications were significantly associated with more asthma symptoms days. Report of “child gets too much medication” was associated with more asthma symptom days (median 4 days, interquartile range [IQR] 2,7, vs 1 day, IQR 0,3, P < .001), as were worry about side effects (median 3 days, IQR 0,5, vs 1 day, IQR 0,3, P ¼ .005) and believing the drugs were not effective (median 3 days, IQR 0,5, vs 1 day, IQR 0,3, P ¼ .007). There was no difference in asthma symptoms by alternative remedy use (median 2, IQR 0,4, vs 1, IQR 0,4, P ¼ .4). We found that caregivers of Hispanic children were almost 5 times as likely to be concerned their child took too much medicine and that medication concerns were strongly and consistently associated with poor asthma control. Although race, medication perception, and asthma control have been described separately, this study found the associations of Hispanic ethnicity, negative medication beliefs, and increased asthma symptoms within the same carefully studied cohort of inner-city school children with asthma. Our findings are consistent with prior studies reporting lower expectations and greater worry about minority children’s asthma,3 particularly Hispanic caregivers’ heightened concern over medication use.3 Hispanic ethnicity was associated with the belief that the child receives too much medication independent of caregiver education, income, or Medicaid status, suggesting racial and ethnic identification is the key influence on attitudes. These findings support that underuse of controller medication by minority populations is independent of sociodemographic factors.4,5 Medication concerns could be a key modifiable risk factor for suboptimal controller medication use6 because they directly influence adherence7 and could be the target of counseling interventions to improve outcomes. In addition, we found that negative beliefs linked to medication were associated with poor asthma control. Parental concern over medications can lead to poor adherence8 and thereby control,9 although similar findings have been found independent of adherence.10 In this context, the causal relation might be bidirectionaldparents of symptomatic children might have less confidence in the benefit-to-risk ratio of prescribed medications. This bears further investigation. Despite standardization of asthma care and efforts to improve minority access to health care, racial, ethnic, and cultural disparities in asthma persist.1 The present findings highlight the racial and ethnic differences in the perception of asthma medication and the effect of negative medication perceptions on asthma control.