- Email: [email protected]
Probability curves for predicting symptom severity during oral food challenge with milk
Letters / Ann Allergy Asthma Immunol 115 (2015) 244e255
showed a forced expiratory volume in 1 second of 1.92 L, or 60% of expected, and a forced vital capacity (FVC) of 2.59 L, or 67% of expected. The ratio of forced expiratory volume in 1 second to forced vial capacity was 0.74. The patient had similar values before starting omalizumab. Her serum IgE concentration decreased to 1,507 IU/mL. The prognosis of ABPA can be quite variable and 14% to 45% of patients will have chronic steroid dependence.3,4 In addition, most patients with ABPA presenting with central bronchiectasis do not respond to antifungal medications.5,6 The effect of surgery on ABPA also appears variable and evidence is limited to case studies. Some case studies in which ABPA was treated with lobectomy noted that oral steroids were needed even after resection.7,8 One case with a 2-year follow-up showed resolution of symptoms and radiographic opacities after resection; however, the patient was not treated initially with antifungals or oral steroids and might have responded to these therapies before surgery.8 Other case reports have shown a favorable surgical outcome in localized ABPA. These patients required no oral steroids after resection, but their follow-up was limited or not mentioned in the case report.9,10 Given the variable response of ABPA to various treatments, it is reasonable to seek additional therapies for patients with refractory disease. Recent studies have suggested omalizumab is effective in ABPA. These include case series and randomized controlled trials.2,11 Omalizumab has been shown to improve asthma control test scores and has a positive steroid-sparing effect. It also has been observed to decrease hospitalizations, asthma exacerbation frequency, fractional exhaled nitric oxide, and nighttime wakenings.2,11 It is noteworthy that in these studies the maximum dose of omalizumab was used and no adverse events were reported. It might be puzzling that omalizumab is effective in the setting of such high levels of serum IgE because the dosing is not predicted to decrease IgE to normal limits. However, Tillie-Leblond et al11 noted that aside from binding IgE, omalizumab downregulates the cell-surface high-affinity IgE receptor (FcεR1) on basophils. They found that omalizumab decreases basophil sensitivity and reactivity to A fumigatus. This case represents recalcitrant ABPA. It supports the use of omalizumab in the setting of postsurgical stage V disease. This case is unique given the patient’s ongoing disease despite lobectomy, oral steroids, and systemic antifungal medications. Fortunately, after initiation of omalizumab, the patient tolerated a decrease in steroid dose with the elimination of oral steroids. At this time, the
251
evidence supporting the use of omalizumab in ABPA appears to be greater than the evidence supporting surgical intervention for ABPA. Among the rapidly growing evidence supporting the efficacy of omalizumab in ABPA, this case provides additional evidence for the use of omalizumab in ABPA in the setting of recalcitrant, stage V disease. Martin Oman Evans, II, DO* Michael J. Morris, MD* Christopher Albert Coop, MD* Sara Ellen Evans, BSy *San Antonio Military Medical Center San Antonio, Texas y College of Osteopathic Medicine of the Pacific-Northwest Lebanon, Oregon [email protected]
References [1] Denning DW, Pleuvry A, Cole DC. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Med Mycol. 2013;51:361e370. [2] Voskamp AL, Gillman A, Symons K, et al. Clinical efficacy and immunologic effects of omalizumab in allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol Pract. 2015;3:192e199. [3] Bains SN, Judson MA. Allergic bronchopulmonary aspergillosis. Clin Chest Med. 2012;33:265e281. [4] Agarwal R, Gupta D, Aggarwal AN, Behera D, Jindal SK. Allergic bronchopulmonary aspergillosis: lessons from 126 patients attending chest clinic in north India. Chest. 2006;130:442e448. [5] Greenberger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol. 2002;110:685e692. [6] Stevens DA, Schwartz HJ, Lee JY, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med. 2000;342:756e762. [7] Hart RJ, Patterson R, Sommers H. Hyperimmunoglobulinemia E in a child with allergic bronchopulmonary aspergillosis and bronchiectasis. J Pediatr. 1976; 89:38e41. [8] Ishiguro T, Takayanagi N, Takaku Y, et al. Allergic bronchopulmonary aspergillosis with repeated isolation of nontuberculous mycobacteria. Intern Med. 2013;52:1721e1726. [9] Koh WJ, Han J, Kim TS, Lee KS, Jang HW, Kwon OJ. Allergic bronchopulmonary aspergillosis coupled with broncholithiasis in a non-asthmatic patient. J Korean Med Sci. 2007;22:365e368. [10] Sauter B, Speich R, Russi EW, Weder W, Vogt P, Follath F. Cavernous destruction of an upper lung lobe in a healthy young man. An unusual roentgenographic presentation of allergic bronchopulmonary aspergillosis. Chest. 1994;105:1871e1872. [11] Tillie-Leblond I, Germaud P, Leroyer C, et al. Allergic bronchopulmonary aspergillosis and omalizumab. Allergy. 2011;66:1254e1256.
Probability curves for predicting symptom severity during oral food challenge with milk Oral food challenges (OFCs) have been used for the accurate diagnosis of food allergies in patients with an allergic history or may have a complete tolerance to certain food allergies. Currently, OFCs are performed in Japan to assess the risks of ingesting causative food agents and prepare treatment plans tailored to the individual.1 Patients at low risk of severe allergic reactions when consuming allergenic food can evade strict avoidance and might outgrow their food allergy.2 Nonetheless, life-threatening events during OFCs should be avoided and anticipated, if possible, before starting the OFC. Although the serum-specific IgE level is a useful parameter in predicting a positive OFC result for several allergenic
Disclosures: Authors have nothing to disclose.
foods, including cow’s milk (CM),3,4 it has not been effective in predicting symptom severity during OFCs.5 To address this clinical concern, basophil activation tests have been reported as a reliable parameter in predicting severe allergic reactions to peanuts6; however, this test remains impractical in clinical settings.7 Recently, we reported the use of ovomucoid-specific IgE levels to predict severe allergic reactions during egg white OFCs.8 In the present study, we present probability curves predicting induced symptom severity during CM OFCs based on milk-specific IgE levels and report the utility of this approach in food allergy practice. The present study included Japanese children 0 to 2 years old who underwent CM OFCs at pediatric clinics or during hospital admissions from October 2012 through March 2015, with serum
Letters / Ann Allergy Asthma Immunol 115 (2015) 244e255
milk-specific IgE levels measured within 3 months. Fourteen institutions participated in this study and used the following OFC protocol: 1, 2, 5, 10, and 20 mL of unheated CM was consumed at 15- to 30-minute intervals. We performed OFCs for a definitive diagnosis of food allergy or to determine tolerance after ingesting an allergic food.1 Indications for OFC were determined by personal physicians based on the clinical history of food allergy and related specific IgE levels.1,3,4 We assessed the severity of the induced symptoms using the grading system of the Japanese Guideline for Food Allergy1 based on the anaphylaxis severity score of Sampson9 and prospectively recorded the results in a single database system. Mild objective symptoms, such as an extremely localized rash, or ambiguous subjective symptoms, such as abdominal pain, that could not be judged as a specific symptom of an OFC were temporarily considered indecisive. Symptoms were carefully assessed with each subsequent dose during the challenge or after symptom recurrence at home. We considered the OFC result negative when at least 38 mL of CM was consumed without any symptoms. Patients without allergic symptoms but unable to consume a sufficient dose were excluded from the study. Milk-specific IgE levels were measured using the ImmunoCAP test (Phadia AB, Uppsala, Sweden) within 3 months of the OFC. In statistical analyses, milk-specific IgE antibodies were considered 0.17 kUA/L if the level was lower than 0.35 kUA/L and 100 kUA/L if the level was at least 100 kUA/L. The present study was approved by a local research ethics committee and was conducted according to the principles of the Declaration of Helsinki. We used logistic regression analysis to assess the association between milk-specific IgE levels and the outcome of OFC. Milkspecific IgE levels were used as a linear parameter in the statistical analyses. Statistical analyses were performed for OFC severity grades higher than 1, 2, and 3. There were no indecisive cases in this study population. Probability curves were drawn based on the results of logistic regression analysis. Statistical analyses were performed using JMP 8.0.2 statistical software (SAS Institute, Cary, North Carolina). In our study population (n ¼ 153, with 1 missing data [n ¼ 152] for eczema and asthma), 53 patients (34.9%) had active atopic eczema, 9 (5.9%) were taking medications for asthma, and 6 (3.9%) had a history of anaphylaxis after consumption of CM. Fifty children (32.7%) in our study consumed CM for the first time during the OFC. The median milk-specific IgE level was 1.83 kUA/L (range 0.17e69.7 kUA/L). During OFC, induced symptoms higher than grades 1, 2, and 3 were seen in 88 children (57.5%), 47 children (30.7%), and 8 children (5.2%), respectively. According to OFC outcomes, 3 different probability curves were constructed from the same population to predict the results of OFC according to milk-specific IgE levels (Fig 1). A milk-specific IgE level of 52.1 kUA/ L had a 95% probability of predicting symptoms higher than grade 1, and a level of 7.3 kUA/L had a 5% probability for predicting symptoms higher than grade 3. The goodness of fit of the regression model assessed using the HosmereLemeshow test showed no deviation between the model and the observed event rate (P > .05). We demonstrated that our strategy of using serum-specific IgE levels as an instant parameter to predict severe allergic reactions during OFC8 could be applied to CM allergy in Japanese children. A 5% probability for predicting symptoms higher than grade 3 was proposed as a useful indicator for performing OFC in a less intensive setting8 and was estimated in the present study of CM allergy. The results of the present study strengthen our strategy in food allergy practice. A limitation of the present study is the target age of the study population. When we extended the target age to at least 3 years, the probability of
1 0.9 0.8 0.7
Probability
252
0.6 0.5 0.4 grade 1 grade 2 grade 3
0.3 0.2 0.1 0 0
20
40
60
Milk-specific IgE (kUA/L)
80
100
Figure 1. Probability curves for milk-specific IgE levels in patients 0 to 2 years old (n ¼ 153). Fitted predictive probability curves predicting the outcomes after an oral food challenge with cow’s milk are shown.
severe allergic reactions was not well estimated by specific IgE levels. This could be due to an inclusion bias, that is, some patients with milk allergy are remitted before 3 years of age and older patients are a high-risk group for severe reactions, although the probability depends on the characteristics of the study population. Apart from this limitation, many CM OFCs are performed before 3 years of age1 and our study population was comprised of patients from many first-line institutions of food allergy, demonstrating the applicability of this strategy to a common clinical practice. Using this strategy, we are able to provide more accurate preOFC risk guidelines to patients with CM allergy. Mizuki Yoneyama, MD* Takayasu Nomura, MD, PhDy Taisuke Kato, MDz Takehiro Sobajima, MDx Hisashi Tanida, MDy,k Takehiro Morishita, MD{ Shiro Sugiura, MD, MPH# Yuichiro Suda, MD** Yasutaka Hirabayashi, MDyy Chieko Misawa, MDzz Naomi Kamioka, MD*,y Hidenori Tanaka, MDxx Mihoko Mizuno, MDkk Akihiko Terada, MD, PhD{{ Yasushi Kanda, MD, PhD## Shinji Saitoh, MD, PhDy *Department of Pediatrics Nagoya City West Medical Center y Department of Pediatrics and Neonatology Graduate School of Medical Sciences Nagoya City University Nagoya, Japan z Department of Pediatrics Gamagori City Hospital Gamagori, Japan x Department of Pediatrics Seirei Mikatahara General Hospital Hamamatsu, Japan
Letters / Ann Allergy Asthma Immunol 115 (2015) 244e255 k
Department of Pediatrics Holy Spirit Hospital Nagoya, Japan { Department of Pediatrics Shizuoka Saiseikai General Hospital Shizuoka, Japan # Department of Pediatrics Toyohashi Municipal Hospital Toyohashi, Japan **Department of Pediatrics Miyoshi Municipal Hospital Miyoshi, Japan yy Hibarigaoka Kids Allergy Clinic Nagoya, Japan zz Department of Pediatrics Gifu Prefectural Tajimi Hospital Tajimi, Japan xx Department of Pediatrics Komaki City Hospital Komaki, Japan kk Department of Pediatrics Daido Hospital Nagoya, Japan {{ Terada Kid’s Allergy & Asthma Clinic
253 ## Department of Pediatrics Japanese Red Cross Nagoya Daini Hospital Nagoya, Japan [email protected]
References [1] Urisu A, Ebisawa M, Ito K, et al. Japanese Guideline for Food Allergy 2014. Allergol Int. 2014;63:399e419. [2] Leonard SA, Caubet J-C, Kim JS, et al. Baked milk- and egg-containing diet in the management of milk and egg allergy. J Allergy Clin Immunol Pract. 2015;3:13e23. [3] Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol. 2001;107:891e896. [4] Komata T, Soderstrom L, Borres MP, et al. The predictive relationship of foodspecific serum IgE concentrations to challenge outcomes for egg and milk varies by patient age. J Allergy Clin Immunol. 2007;119:1272e1274. [5] Sicherer SH, Wood RA; American Academy of Pediatrics Section on Allergy And Immunology. Allergy testing in childhood: using allergen-specific IgE tests. Pediatrics. 2011;129:193e197. [6] Santos AF, Du Toit G, Douiri A, et al. Distinct parameters of the basophil activation test reflect the severity and threshold of allergic reactions to peanut. J Allergy Clin Immunol. 2015;135:179e186. [7] Bird JA, Lack G, Perry TT. Clinical management of food allergy. J Allergy Clin Immunol Pract. 2015;3:1e11. [8] Nomura T, Kanda Y, Kato T, et al. Probability curves focusing on symptom severity during an oral food challenge. Ann Allergy Asthma Immunol. 2014;112: 556e557. [9] Sampson HA. Anaphylaxis and emergency treatment. Pediatrics. 2003;111: 1601e1608.
Multiple reasonably tolerated percutaneous coronary interventions in a patient with iodide mumps Although some adverse reactions to radiocontrast media may be IgE-mediated hypersensitivity, most are due to pharmacologic toxicity or other pseudoallergic causes.1,2 Radiocontrast media agents are all tri-iodinated benzene derivatives,3 and although iodine sensitivity was once believed to be a major cause, adverse reactions to contrast are now thought to be largely unrelated to iodine content.2 An exception is iodide sialadenopathy, or iodide mumps, which is characterized by acute or delayed swelling of the submandibular or parotid glands after exposure to iodinated radiocontrast media.4 The condition was originally described in 1956 in a case series of patients who developed symptoms after intravenous urography.5 Despite its seemingly rare occurrence, iodide sialadenopathy may actually be underdiagnosed; a study performed by McCullough et al6 assessing for the incidence of immediate and delayed reactions to contrast media found symptoms consistent with parotitis in approximately 1% to 2% of the 1,381 patients evaluated. Although most iodine is renally excreted, the remainder is excreted through salivary, sweat, and lacrimal glands.7 The exact mechanism of iodide mumps is unclear, but it has been postulated that iodine accumulation in the salivary secretions leads to mucosal edema, ductal obstruction, and subsequent sialadenitis. Pancreatitis has been reported in rare instances.4 Further supporting the role of iodine in the pathogenesis of iodide sialadenopathy, a study examining the role of iodine in radiocontrast media reactions found 2 patients with histories of likely iodide sialadenopathy to have reproducible submandibular swelling on oral ingestion of potassium iodide.3 Because iodide mumps is not thought to be mast cell or leukocyte mediated, premedication with antihistamines and/or corticosteroids has not been found to be successful.4 Other Disclosures: Authors have nothing to disclose. Funding: This study was funded by the Jeffrey Modell Foundation.
unsuccessful treatments include hyperhydration, given the renal excretion of iodine, and blocking thyroid iodine uptake.4 Kalaria et al8 reported an expedited resolution of swelling in one patient with the use of dialysis, suggesting that this intervention could be considered to hasten improvement of severe cases. With no proven prophylactic treatment available, avoidance of contrast media is the only preventive measure for patients with a history of iodide mumps. However, avoidance may not be possible for patients with significant coronary artery disease who require repeated percutaneous coronary interventions. Although iodide sialadenopathy associated with percutaneous coronary intervention has generally been reported as self-limited, the safety of repeated angioplasty in such patients has not been assessed.9,10 Herein, we describe a woman with a history of iodide mumps and significant coronary artery disease requiring percutaneous coronary intervention on 3 separate occasions. The patient is a 76-year-old woman with a history of coronary artery disease who presented with unstable angina. She additionally reported a history of anaphylaxis, characterized by facial swelling and respiratory distress, to contrast media 50 years ago. She denied exposure to contrast media since her reputed anaphylaxis decades ago. Given the history of anaphylaxis to contrast media, the patient was premedicated with prednisone and diphenhydramine before percutaneous coronary intervention for which she received 150 mL of iopamidol (a nonionic, lowosmolality, iodinated contrast agent). The procedure was uncomplicated; however, approximately 12 hours after completion she developed bilateral submandibular swelling that was nonindurated, nonerythematous, firm, and mildly tender to palpation. The patient was otherwise able to tolerate oral intake and was without respiratory distress or other abnormalities on physical examination. Flexible fiberoptic laryngoscopy revealed a patent airway with no abnormalities seen. She had no history of atopy,
showed a forced expiratory volume in 1 second of 1.92 L, or 60% of expected, and a forced vital capacity (FVC) of 2.59 L, or 67% of expected. The ratio of forced expiratory volume in 1 second to forced vial capacity was 0.74. The patient had similar values before starting omalizumab. Her serum IgE concentration decreased to 1,507 IU/mL. The prognosis of ABPA can be quite variable and 14% to 45% of patients will have chronic steroid dependence.3,4 In addition, most patients with ABPA presenting with central bronchiectasis do not respond to antifungal medications.5,6 The effect of surgery on ABPA also appears variable and evidence is limited to case studies. Some case studies in which ABPA was treated with lobectomy noted that oral steroids were needed even after resection.7,8 One case with a 2-year follow-up showed resolution of symptoms and radiographic opacities after resection; however, the patient was not treated initially with antifungals or oral steroids and might have responded to these therapies before surgery.8 Other case reports have shown a favorable surgical outcome in localized ABPA. These patients required no oral steroids after resection, but their follow-up was limited or not mentioned in the case report.9,10 Given the variable response of ABPA to various treatments, it is reasonable to seek additional therapies for patients with refractory disease. Recent studies have suggested omalizumab is effective in ABPA. These include case series and randomized controlled trials.2,11 Omalizumab has been shown to improve asthma control test scores and has a positive steroid-sparing effect. It also has been observed to decrease hospitalizations, asthma exacerbation frequency, fractional exhaled nitric oxide, and nighttime wakenings.2,11 It is noteworthy that in these studies the maximum dose of omalizumab was used and no adverse events were reported. It might be puzzling that omalizumab is effective in the setting of such high levels of serum IgE because the dosing is not predicted to decrease IgE to normal limits. However, Tillie-Leblond et al11 noted that aside from binding IgE, omalizumab downregulates the cell-surface high-affinity IgE receptor (FcεR1) on basophils. They found that omalizumab decreases basophil sensitivity and reactivity to A fumigatus. This case represents recalcitrant ABPA. It supports the use of omalizumab in the setting of postsurgical stage V disease. This case is unique given the patient’s ongoing disease despite lobectomy, oral steroids, and systemic antifungal medications. Fortunately, after initiation of omalizumab, the patient tolerated a decrease in steroid dose with the elimination of oral steroids. At this time, the
251
evidence supporting the use of omalizumab in ABPA appears to be greater than the evidence supporting surgical intervention for ABPA. Among the rapidly growing evidence supporting the efficacy of omalizumab in ABPA, this case provides additional evidence for the use of omalizumab in ABPA in the setting of recalcitrant, stage V disease. Martin Oman Evans, II, DO* Michael J. Morris, MD* Christopher Albert Coop, MD* Sara Ellen Evans, BSy *San Antonio Military Medical Center San Antonio, Texas y College of Osteopathic Medicine of the Pacific-Northwest Lebanon, Oregon [email protected]
References [1] Denning DW, Pleuvry A, Cole DC. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Med Mycol. 2013;51:361e370. [2] Voskamp AL, Gillman A, Symons K, et al. Clinical efficacy and immunologic effects of omalizumab in allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol Pract. 2015;3:192e199. [3] Bains SN, Judson MA. Allergic bronchopulmonary aspergillosis. Clin Chest Med. 2012;33:265e281. [4] Agarwal R, Gupta D, Aggarwal AN, Behera D, Jindal SK. Allergic bronchopulmonary aspergillosis: lessons from 126 patients attending chest clinic in north India. Chest. 2006;130:442e448. [5] Greenberger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol. 2002;110:685e692. [6] Stevens DA, Schwartz HJ, Lee JY, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med. 2000;342:756e762. [7] Hart RJ, Patterson R, Sommers H. Hyperimmunoglobulinemia E in a child with allergic bronchopulmonary aspergillosis and bronchiectasis. J Pediatr. 1976; 89:38e41. [8] Ishiguro T, Takayanagi N, Takaku Y, et al. Allergic bronchopulmonary aspergillosis with repeated isolation of nontuberculous mycobacteria. Intern Med. 2013;52:1721e1726. [9] Koh WJ, Han J, Kim TS, Lee KS, Jang HW, Kwon OJ. Allergic bronchopulmonary aspergillosis coupled with broncholithiasis in a non-asthmatic patient. J Korean Med Sci. 2007;22:365e368. [10] Sauter B, Speich R, Russi EW, Weder W, Vogt P, Follath F. Cavernous destruction of an upper lung lobe in a healthy young man. An unusual roentgenographic presentation of allergic bronchopulmonary aspergillosis. Chest. 1994;105:1871e1872. [11] Tillie-Leblond I, Germaud P, Leroyer C, et al. Allergic bronchopulmonary aspergillosis and omalizumab. Allergy. 2011;66:1254e1256.
Probability curves for predicting symptom severity during oral food challenge with milk Oral food challenges (OFCs) have been used for the accurate diagnosis of food allergies in patients with an allergic history or may have a complete tolerance to certain food allergies. Currently, OFCs are performed in Japan to assess the risks of ingesting causative food agents and prepare treatment plans tailored to the individual.1 Patients at low risk of severe allergic reactions when consuming allergenic food can evade strict avoidance and might outgrow their food allergy.2 Nonetheless, life-threatening events during OFCs should be avoided and anticipated, if possible, before starting the OFC. Although the serum-specific IgE level is a useful parameter in predicting a positive OFC result for several allergenic
Disclosures: Authors have nothing to disclose.
foods, including cow’s milk (CM),3,4 it has not been effective in predicting symptom severity during OFCs.5 To address this clinical concern, basophil activation tests have been reported as a reliable parameter in predicting severe allergic reactions to peanuts6; however, this test remains impractical in clinical settings.7 Recently, we reported the use of ovomucoid-specific IgE levels to predict severe allergic reactions during egg white OFCs.8 In the present study, we present probability curves predicting induced symptom severity during CM OFCs based on milk-specific IgE levels and report the utility of this approach in food allergy practice. The present study included Japanese children 0 to 2 years old who underwent CM OFCs at pediatric clinics or during hospital admissions from October 2012 through March 2015, with serum
Letters / Ann Allergy Asthma Immunol 115 (2015) 244e255
milk-specific IgE levels measured within 3 months. Fourteen institutions participated in this study and used the following OFC protocol: 1, 2, 5, 10, and 20 mL of unheated CM was consumed at 15- to 30-minute intervals. We performed OFCs for a definitive diagnosis of food allergy or to determine tolerance after ingesting an allergic food.1 Indications for OFC were determined by personal physicians based on the clinical history of food allergy and related specific IgE levels.1,3,4 We assessed the severity of the induced symptoms using the grading system of the Japanese Guideline for Food Allergy1 based on the anaphylaxis severity score of Sampson9 and prospectively recorded the results in a single database system. Mild objective symptoms, such as an extremely localized rash, or ambiguous subjective symptoms, such as abdominal pain, that could not be judged as a specific symptom of an OFC were temporarily considered indecisive. Symptoms were carefully assessed with each subsequent dose during the challenge or after symptom recurrence at home. We considered the OFC result negative when at least 38 mL of CM was consumed without any symptoms. Patients without allergic symptoms but unable to consume a sufficient dose were excluded from the study. Milk-specific IgE levels were measured using the ImmunoCAP test (Phadia AB, Uppsala, Sweden) within 3 months of the OFC. In statistical analyses, milk-specific IgE antibodies were considered 0.17 kUA/L if the level was lower than 0.35 kUA/L and 100 kUA/L if the level was at least 100 kUA/L. The present study was approved by a local research ethics committee and was conducted according to the principles of the Declaration of Helsinki. We used logistic regression analysis to assess the association between milk-specific IgE levels and the outcome of OFC. Milkspecific IgE levels were used as a linear parameter in the statistical analyses. Statistical analyses were performed for OFC severity grades higher than 1, 2, and 3. There were no indecisive cases in this study population. Probability curves were drawn based on the results of logistic regression analysis. Statistical analyses were performed using JMP 8.0.2 statistical software (SAS Institute, Cary, North Carolina). In our study population (n ¼ 153, with 1 missing data [n ¼ 152] for eczema and asthma), 53 patients (34.9%) had active atopic eczema, 9 (5.9%) were taking medications for asthma, and 6 (3.9%) had a history of anaphylaxis after consumption of CM. Fifty children (32.7%) in our study consumed CM for the first time during the OFC. The median milk-specific IgE level was 1.83 kUA/L (range 0.17e69.7 kUA/L). During OFC, induced symptoms higher than grades 1, 2, and 3 were seen in 88 children (57.5%), 47 children (30.7%), and 8 children (5.2%), respectively. According to OFC outcomes, 3 different probability curves were constructed from the same population to predict the results of OFC according to milk-specific IgE levels (Fig 1). A milk-specific IgE level of 52.1 kUA/ L had a 95% probability of predicting symptoms higher than grade 1, and a level of 7.3 kUA/L had a 5% probability for predicting symptoms higher than grade 3. The goodness of fit of the regression model assessed using the HosmereLemeshow test showed no deviation between the model and the observed event rate (P > .05). We demonstrated that our strategy of using serum-specific IgE levels as an instant parameter to predict severe allergic reactions during OFC8 could be applied to CM allergy in Japanese children. A 5% probability for predicting symptoms higher than grade 3 was proposed as a useful indicator for performing OFC in a less intensive setting8 and was estimated in the present study of CM allergy. The results of the present study strengthen our strategy in food allergy practice. A limitation of the present study is the target age of the study population. When we extended the target age to at least 3 years, the probability of
1 0.9 0.8 0.7
Probability
252
0.6 0.5 0.4 grade 1 grade 2 grade 3
0.3 0.2 0.1 0 0
20
40
60
Milk-specific IgE (kUA/L)
80
100
Figure 1. Probability curves for milk-specific IgE levels in patients 0 to 2 years old (n ¼ 153). Fitted predictive probability curves predicting the outcomes after an oral food challenge with cow’s milk are shown.
severe allergic reactions was not well estimated by specific IgE levels. This could be due to an inclusion bias, that is, some patients with milk allergy are remitted before 3 years of age and older patients are a high-risk group for severe reactions, although the probability depends on the characteristics of the study population. Apart from this limitation, many CM OFCs are performed before 3 years of age1 and our study population was comprised of patients from many first-line institutions of food allergy, demonstrating the applicability of this strategy to a common clinical practice. Using this strategy, we are able to provide more accurate preOFC risk guidelines to patients with CM allergy. Mizuki Yoneyama, MD* Takayasu Nomura, MD, PhDy Taisuke Kato, MDz Takehiro Sobajima, MDx Hisashi Tanida, MDy,k Takehiro Morishita, MD{ Shiro Sugiura, MD, MPH# Yuichiro Suda, MD** Yasutaka Hirabayashi, MDyy Chieko Misawa, MDzz Naomi Kamioka, MD*,y Hidenori Tanaka, MDxx Mihoko Mizuno, MDkk Akihiko Terada, MD, PhD{{ Yasushi Kanda, MD, PhD## Shinji Saitoh, MD, PhDy *Department of Pediatrics Nagoya City West Medical Center y Department of Pediatrics and Neonatology Graduate School of Medical Sciences Nagoya City University Nagoya, Japan z Department of Pediatrics Gamagori City Hospital Gamagori, Japan x Department of Pediatrics Seirei Mikatahara General Hospital Hamamatsu, Japan
Letters / Ann Allergy Asthma Immunol 115 (2015) 244e255 k
Department of Pediatrics Holy Spirit Hospital Nagoya, Japan { Department of Pediatrics Shizuoka Saiseikai General Hospital Shizuoka, Japan # Department of Pediatrics Toyohashi Municipal Hospital Toyohashi, Japan **Department of Pediatrics Miyoshi Municipal Hospital Miyoshi, Japan yy Hibarigaoka Kids Allergy Clinic Nagoya, Japan zz Department of Pediatrics Gifu Prefectural Tajimi Hospital Tajimi, Japan xx Department of Pediatrics Komaki City Hospital Komaki, Japan kk Department of Pediatrics Daido Hospital Nagoya, Japan {{ Terada Kid’s Allergy & Asthma Clinic
253 ## Department of Pediatrics Japanese Red Cross Nagoya Daini Hospital Nagoya, Japan [email protected]
References [1] Urisu A, Ebisawa M, Ito K, et al. Japanese Guideline for Food Allergy 2014. Allergol Int. 2014;63:399e419. [2] Leonard SA, Caubet J-C, Kim JS, et al. Baked milk- and egg-containing diet in the management of milk and egg allergy. J Allergy Clin Immunol Pract. 2015;3:13e23. [3] Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol. 2001;107:891e896. [4] Komata T, Soderstrom L, Borres MP, et al. The predictive relationship of foodspecific serum IgE concentrations to challenge outcomes for egg and milk varies by patient age. J Allergy Clin Immunol. 2007;119:1272e1274. [5] Sicherer SH, Wood RA; American Academy of Pediatrics Section on Allergy And Immunology. Allergy testing in childhood: using allergen-specific IgE tests. Pediatrics. 2011;129:193e197. [6] Santos AF, Du Toit G, Douiri A, et al. Distinct parameters of the basophil activation test reflect the severity and threshold of allergic reactions to peanut. J Allergy Clin Immunol. 2015;135:179e186. [7] Bird JA, Lack G, Perry TT. Clinical management of food allergy. J Allergy Clin Immunol Pract. 2015;3:1e11. [8] Nomura T, Kanda Y, Kato T, et al. Probability curves focusing on symptom severity during an oral food challenge. Ann Allergy Asthma Immunol. 2014;112: 556e557. [9] Sampson HA. Anaphylaxis and emergency treatment. Pediatrics. 2003;111: 1601e1608.
Multiple reasonably tolerated percutaneous coronary interventions in a patient with iodide mumps Although some adverse reactions to radiocontrast media may be IgE-mediated hypersensitivity, most are due to pharmacologic toxicity or other pseudoallergic causes.1,2 Radiocontrast media agents are all tri-iodinated benzene derivatives,3 and although iodine sensitivity was once believed to be a major cause, adverse reactions to contrast are now thought to be largely unrelated to iodine content.2 An exception is iodide sialadenopathy, or iodide mumps, which is characterized by acute or delayed swelling of the submandibular or parotid glands after exposure to iodinated radiocontrast media.4 The condition was originally described in 1956 in a case series of patients who developed symptoms after intravenous urography.5 Despite its seemingly rare occurrence, iodide sialadenopathy may actually be underdiagnosed; a study performed by McCullough et al6 assessing for the incidence of immediate and delayed reactions to contrast media found symptoms consistent with parotitis in approximately 1% to 2% of the 1,381 patients evaluated. Although most iodine is renally excreted, the remainder is excreted through salivary, sweat, and lacrimal glands.7 The exact mechanism of iodide mumps is unclear, but it has been postulated that iodine accumulation in the salivary secretions leads to mucosal edema, ductal obstruction, and subsequent sialadenitis. Pancreatitis has been reported in rare instances.4 Further supporting the role of iodine in the pathogenesis of iodide sialadenopathy, a study examining the role of iodine in radiocontrast media reactions found 2 patients with histories of likely iodide sialadenopathy to have reproducible submandibular swelling on oral ingestion of potassium iodide.3 Because iodide mumps is not thought to be mast cell or leukocyte mediated, premedication with antihistamines and/or corticosteroids has not been found to be successful.4 Other Disclosures: Authors have nothing to disclose. Funding: This study was funded by the Jeffrey Modell Foundation.
unsuccessful treatments include hyperhydration, given the renal excretion of iodine, and blocking thyroid iodine uptake.4 Kalaria et al8 reported an expedited resolution of swelling in one patient with the use of dialysis, suggesting that this intervention could be considered to hasten improvement of severe cases. With no proven prophylactic treatment available, avoidance of contrast media is the only preventive measure for patients with a history of iodide mumps. However, avoidance may not be possible for patients with significant coronary artery disease who require repeated percutaneous coronary interventions. Although iodide sialadenopathy associated with percutaneous coronary intervention has generally been reported as self-limited, the safety of repeated angioplasty in such patients has not been assessed.9,10 Herein, we describe a woman with a history of iodide mumps and significant coronary artery disease requiring percutaneous coronary intervention on 3 separate occasions. The patient is a 76-year-old woman with a history of coronary artery disease who presented with unstable angina. She additionally reported a history of anaphylaxis, characterized by facial swelling and respiratory distress, to contrast media 50 years ago. She denied exposure to contrast media since her reputed anaphylaxis decades ago. Given the history of anaphylaxis to contrast media, the patient was premedicated with prednisone and diphenhydramine before percutaneous coronary intervention for which she received 150 mL of iopamidol (a nonionic, lowosmolality, iodinated contrast agent). The procedure was uncomplicated; however, approximately 12 hours after completion she developed bilateral submandibular swelling that was nonindurated, nonerythematous, firm, and mildly tender to palpation. The patient was otherwise able to tolerate oral intake and was without respiratory distress or other abnormalities on physical examination. Flexible fiberoptic laryngoscopy revealed a patent airway with no abnormalities seen. She had no history of atopy,