Letters to the Editor
DPT. Such a hyper-reactivity was not detected when the first BAT was performed in this patient. Five and a half hours after the beginning of the DPT to celecoxib (administered dose: 4.7 mg/kg for a cumulative dose of 235 mg), twin B started to present facial swallow. Tryptase blood levels were stable before and after the test (from 5.06 to 3.41 lg/l). Histamine concentration increased after the DPT (from 0.23 to 4.43 ng/ml). BAT for celecoxib resulted positive. Blood samples for BAT were collected 6 weeks after this second DPT. The fact that the two girls showed a hypersensitivity reaction even to an anti COX-2 drug, brought us to conclude that no NSAID alternatives could be found. The study conducted by Asero in 2002 showed that NSAIDs hypersensitivity may precede the onset of CU (7). In fact, we discovered that twin A had developed CU 2 weeks after the first positive DPT. CU is a skin disorder that can be elicited by numerous factors, and NSAIDs in particular. Furthermore, the pathogenesis of CU is not fully understood but genetic factors are believed to play a very important role in its development and progression (8). A study in a large population of patients with CU revealed a higher prevalence of CU in first-degree relatives than in the general population (8, 9). As for the CU presented by the twins, possible causes were investigated. They were both euthyroids with negative antithyroid antibodies. They had negative serology for Mycoplasma and Helicobacter Pylori infection. Their parents did not refer a history of CU. We also searched for the presence of autoantibodies directed towards the alpha subunit of the
high-affinity IgE receptor (FceRI) of mast cells and basophils which resulted negative in both twins. These autoantibodies were found in approximately 40% of subjects with CU in a study conducted by Saini (10). Although they are not specific for CU and the assays used for their detection are not specific for them, their presence is thought to be pathogenic for CU. Specific differences in the expression of FceRI-signaling molecules in the basophils or mast cells of CU patients may also lead to the onset of urticaria eruptions (10). In conclusion, the international literature reports that CU predisposes to hypersensitivity reactions to NSAIDs and is genetically inherited principally in first-degree relatives. On the other hand, NSAIDs hypersensitivity may lead to the onset of CU and is genetically determined. With our report we support the existence of a familial inheritance of the genetic mechanism causing NSAIDs hypersensitivity for which further investigations are needed. Silvia Maria Elena Caimmi1; Enrica Manca1; Davide Caimmi2; Gian Luigi Marseglia1 & Pascal Demoly3,4 1 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, opital Arnaud University of Pavia, Pavia, Italy; 2Department of Pediatrics, H^ de Villeneuve, University Hospital of Montpellier, Montpellier; 3Allergy Unit, D epartement de Pneumologie et Addictologie, H^ opital Arnaud Villeneuve, University Hospital of Montpellier, Montpellier; 4Sorbonne Universit es, UPMC Paris 06, UMR-S 1136, IPLESP, Equipe EPAR, Paris, France E-mail: [email protected] DOI:10.1111/pai.12300
References 1. Kim YJ, Lim KH, Kim MY, et al. Cross-reactivity to Acetaminophen and Celecoxib according to the type of nonsteroidal anti-inflammatory drug hypersensitivity. Allergy Asthma Immunol Res 2014: 6: 156–62. 2. Cornejo-Garcia JA, Blanca-L opez N, Do~ na I, et al. Hypersensitivity reactions to non steroidal anti-inflammatory drugs. Curr Drug Metab 2009: 10: 971–80. 3. Ag undez JA, Ayuso P, Cornejo-Garcıa JA, et al. The diamine oxidase gene is associated with hypersensitivity response to nonsteroidal anti-inflammatory drugs. PLoS ONE 2013: 7: e47571.
4. Kim SH, Sanak M, Park HS. Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs. Immunol Allergy Clin North Am 2013: 33: 177–94. € Aydın O, € Demirel 5. C ß elik GE, Erkekol FO, YS, Mısırlıgil Z. Are drug provocation tests still necessary to test the safety of COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity? Allergol Immunopathol 2013: 41: 181–8. 6. Caimmi S, Caimmi D, Bousquet PJ, Demoly P. How can we better classify NSAID hypersensitivity reactions?–validation from a large database. Int Arch Allergy Immunol 2012: 159: 306–12.
7. Asero R. Intolerance to nonsteroidal anti-inflammatory drugs might precede by years the onset of chronic urticaria. J Allergy Clin Immunol 2003: 111: 1095–8. 8. Losol P, Yoo HS, Park HS. Molecular genetic mechanisms of chronic urticaria. Allergy Asthma Immunol Res 2014: 6: 13–21. 9. Asero R. Chronic idiopathic urticaria: a family study. Ann Allergy Asthma Immunol 2002: 89: 195–6. 10. Saini SS. Basophil responsiveness in chronic urticaria. Curr Allergy Asthma Rep 2009: 9: 286–90.
Pre-treatment by omalizumab allows allergen immunotherapy in children and young adults with severe allergic asthma To the Editor, Subcutaneous allergen immunotherapy (SCIT) is a valuable treatment option for patients with controlled mild to
moderate allergic asthma (1). However, SCIT is contraindicated for patients with severe persistent asthma due to a potential systemic allergic reaction: in a cluster protocol,
Pediatric Allergy and Immunology 25 (2015) 817–837 ª 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
829
Letters to the Editor
the risk of serious adverse reactions, including anaphylaxis, was found to increase from 36% in patients treated by conventional immunotherapy and SCIT, respectively (2). Several studies in adolescents and adults with persistent allergic rhinitis and moderate persistent allergic asthma have shown that SCIT is better tolerated when combined with omalizumab, an anti-IgE antibody that blocks an early step in the allergic cascade (3–5). Nevertheless, no previous studies have been conducted in children and adolescents with severe asthma to assess the safety and efficacy of a combination treatment of SCIT and omalizumab, especially when SCIT is continued after stopping omalizumab. We report here the observations of six patients, aged 11–21 years, with severe persistent asthma controlled by omalizumab as add-on therapy who received SCIT under a cluster protocol during omalizumab treatment and then SCIT maintenance alone after discontinuation of omalizumab. Asthma severity in these patients was evidenced by severe and frequent exacerbations despite a high level of maintenance treatment: exacerbations were experienced once every 2 months (n = 1), once a month (n = 4) and once a week (n = 1) requiring hospitalization in an intensive care unit (n = 2) and needing systemic corticosteroids once a month (n = 2), 8 times a year (n = 1), 6 times a year (n = 1) and three times a year (n = 2). FEV1 for all the patients was normal, as frequently encountered in children with severe asthma. All the patients presented dyspnoea on exercise. All the patients were treated with a high dose of inhaled corticosteroid (>500 lg/day of equivalent of beclomethasone dipropionate) (Table 1) in combination with montelukast (n = 6), long-acting theophylline (n = 4) and/or long-acting b2-adrenoceptor agonists (LABA) (n = 6). House dust mite (HDM) allergy was defined by a positive skin prick test with concordant positive specific IgE and allergic symptoms during exposure to this inhaled allergen. After a median time of 8 months of omalizumab treatment (median dosage = 351 mg per month), asthma control was significantly improved in all the patients according to GINA asthma guidelines (6), and there was a significant decrease in exacerbations despite reduction of maintenance treatment (Table 1 and Fig. 1). After achieving asthma control, SCIT to HDM (ALK laboratory, France) was performed by the cluster method. Over 4 days, we were able to increase the SCIT dose to a monthly maintenance dose of 10 lg of Derp1 allergen. Although SCIT had to be discontinued for patient n°6 due to uncontrolled asthma, continued treatment by omalizumab resulted in regaining asthma control and pharmacologic treatment could be decreased. For the five remaining patients, asthma control continued to improve during the combined treatment with SCIT and omalizumab (median time duration = 8 months) despite a decrease in maintenance treatment for all of them (Table 1 and Fig. 1). Omalizumab was stopped after less than 1 year (n = 2), 2 years (n = 1). 3 years (n = 1) and 4 years (n = 1). SCIT was continued alone for a median time of 25.5 months and was well tolerated. For these patients,
830
asthma was totally controlled and therapeutic levels of maintenance treatment could be further reduced (Table 1 and Fig. 1). Discussion Our experience with these six children with severe allergic asthma indicates that pre-treatment with omalizumab seems to improve tolerability (during and after discontinuation of omalizumab) and efficacy of SCIT in this setting. Omalizumab decreases side effects of SCIT and improves efficacy Five of the six patients pre-treated with omalizumab presented no severe side effects of SCIT. This result is in accordance with the literature. Kuehr et al. (4) showed a reduction of 48% in symptom load in children with allergic rhinitis over the pollen seasons with a combination of SCIT with omalizumab compared to SCIT alone. More recently, Kopp et al. (7) reported in a review that omalizumab reduces systemic side effects and amplifies the therapeutic effect of SCIT for inhaled allergen in pollen-induced allergic rhinitis, mild–moderate allergic asthma and venom allergy. Furthermore, Massanari et al. (5) showed that omalizumab use in adult patients with moderate persistent allergic asthma was associated with fewer systemic allergic reaction to SCIT and enabled more patients to achieve the target. SCIT had to be stopped for one of our patients due to uncontrolled asthma. To better understand why SCIT failed in this patient despite pre-treatment with omalizumab, it would have been interesting to assess the patient’s HDM specific IgE-antibody fraction (specific IgE-ab/Total IgE) (8, 9) and CD-sens to HDM (10). Closer monitoring and a possible increase in the omalizumab dosage might have allowed SCIT to be continued. SCIT alone was well tolerated after discontinuation of omalizumab and asthma control continued despite reduction of maintenance treatment In an editorial, Casale et al. (11) noted that there are no data to date about the risks of continuing SCIT after discontinuation of omalizumab or about resulting asthma control. Our observations are a step towards completing this information void and indicate that SCIT is well tolerated after discontinuation of omalizumab despite a high dosage of injected allergen over a long follow-up. This could be the result of a possible induction of a tolerogenic mechanism by SCIT under omalizumab treatment. The persistence of asthma control under SCIT treatment alone could be explained by the remaining effect of omalizumab. However, this effect remains debatable when considering the duration of omalizumab treatment before cessation. Slavin et al. (12) have shown that asthmatic symptoms reappeared 16 weeks after stopping omalizumab. In the same manner, it has been shown that while one remaining effect of omalizumab exists, it does not last for more than a few months after treatment cessation. Furthermore, a longer duration of omalizumab
Pediatric Allergy and Immunology 25 (2015) 817–837 ª 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
400 200 400 200 700 200
6
400 200 400 200 700 200
Asthma control
5 4
Uncontrolled asthma
3
ParƟally controlled asthma
2
Totally controlled asthma
1 0
Decrease of maintenance treatment
400 400 700 400 700 400
Omalizumab and SCIT Omalizumab alone
7
Before Omalizumab SCIT and SCIT alone omalizumab alone omalizumab Montelukast n = 6, LAT n = 5
BDP 300 mcg/day
Figure 1 Asthma control and therapeutic level for the four periods. SCIT, Subcutaneous allergen-specific immunotherapy; BDP, Equivalent of beclomethasone dipropionate; LAT, Long-acting theophylline.
F, Female; M, Male; HDM, House dust mite allergen; SCIT, Subcutaneous allergen-specific immunotherapy.
1000 800 1000 800 1000 1000 300 750 235 300 300 225 >100 >100 50 25 10 >100 493 1796 288 101 529 288 99 100 118 97 58 100 11 21 15 16 15 16 1 2 3 4 5 6
F F M M M M
45 105 89 76 10 7
OmalizumabDoses (mg per month) Total IgE kU/l Gender Patients
FEV1% predictive value
FeNO at baseline (ppb)
IgE HDM (KU/l)
Before omalizumab
BDP 1000 mcg/day
Age (years)
Table 1 Characteristics of the population
Equivalent of beclomethasone dipropionate lg per day
SCIT alone
Letters to the Editor
treatment seems to induce a longer remaining effect. Nopp et al. (13) show a persistence of asthma control and the reduction of basophil allergen sensitivity during 3 years of follow-up after a discontinuation of 6 years of treatment with omalizumab. The duration of omalizumab treatment in the study we report here was short (10% between both values; 165 (71.1%) with higher Alt a 1; 67 (28.9%) with higher Alternaria. Table 1 shows the results of the two patients with negative Alternaria and positive Alt a 1, and of the ten patients with negative Alt a 1 and positive Alternaria. Component-resolved diagnosis permits a more accurate diagnosis of sensitization with potential impact on therapeutic approaches in the case of pollen, food, or even animal dander allergy (1, 2, 6–8). There is, however, scarce information on the potential impact of CRD on mold allergy (3–5). Most of our patients were sensitized to Alt a 1, and levels of specific IgE to this allergen were higher than to Alternaria (Fig. 1). On the other hand, there were some patients, with long distances plotted under the diagonal, who had much higher values with Alternaria than with Alt a 1, meaning that sensitization to other allergens might be relevant. Overall, the number of positive cases was higher, not significantly, with Alternaria (84.7% vs. 81.6%), so this would
Pediatric Allergy and Immunology 25 (2015) 817–837 ª 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
DPT. Such a hyper-reactivity was not detected when the first BAT was performed in this patient. Five and a half hours after the beginning of the DPT to celecoxib (administered dose: 4.7 mg/kg for a cumulative dose of 235 mg), twin B started to present facial swallow. Tryptase blood levels were stable before and after the test (from 5.06 to 3.41 lg/l). Histamine concentration increased after the DPT (from 0.23 to 4.43 ng/ml). BAT for celecoxib resulted positive. Blood samples for BAT were collected 6 weeks after this second DPT. The fact that the two girls showed a hypersensitivity reaction even to an anti COX-2 drug, brought us to conclude that no NSAID alternatives could be found. The study conducted by Asero in 2002 showed that NSAIDs hypersensitivity may precede the onset of CU (7). In fact, we discovered that twin A had developed CU 2 weeks after the first positive DPT. CU is a skin disorder that can be elicited by numerous factors, and NSAIDs in particular. Furthermore, the pathogenesis of CU is not fully understood but genetic factors are believed to play a very important role in its development and progression (8). A study in a large population of patients with CU revealed a higher prevalence of CU in first-degree relatives than in the general population (8, 9). As for the CU presented by the twins, possible causes were investigated. They were both euthyroids with negative antithyroid antibodies. They had negative serology for Mycoplasma and Helicobacter Pylori infection. Their parents did not refer a history of CU. We also searched for the presence of autoantibodies directed towards the alpha subunit of the
high-affinity IgE receptor (FceRI) of mast cells and basophils which resulted negative in both twins. These autoantibodies were found in approximately 40% of subjects with CU in a study conducted by Saini (10). Although they are not specific for CU and the assays used for their detection are not specific for them, their presence is thought to be pathogenic for CU. Specific differences in the expression of FceRI-signaling molecules in the basophils or mast cells of CU patients may also lead to the onset of urticaria eruptions (10). In conclusion, the international literature reports that CU predisposes to hypersensitivity reactions to NSAIDs and is genetically inherited principally in first-degree relatives. On the other hand, NSAIDs hypersensitivity may lead to the onset of CU and is genetically determined. With our report we support the existence of a familial inheritance of the genetic mechanism causing NSAIDs hypersensitivity for which further investigations are needed. Silvia Maria Elena Caimmi1; Enrica Manca1; Davide Caimmi2; Gian Luigi Marseglia1 & Pascal Demoly3,4 1 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, opital Arnaud University of Pavia, Pavia, Italy; 2Department of Pediatrics, H^ de Villeneuve, University Hospital of Montpellier, Montpellier; 3Allergy Unit, D epartement de Pneumologie et Addictologie, H^ opital Arnaud Villeneuve, University Hospital of Montpellier, Montpellier; 4Sorbonne Universit es, UPMC Paris 06, UMR-S 1136, IPLESP, Equipe EPAR, Paris, France E-mail: [email protected] DOI:10.1111/pai.12300
References 1. Kim YJ, Lim KH, Kim MY, et al. Cross-reactivity to Acetaminophen and Celecoxib according to the type of nonsteroidal anti-inflammatory drug hypersensitivity. Allergy Asthma Immunol Res 2014: 6: 156–62. 2. Cornejo-Garcia JA, Blanca-L opez N, Do~ na I, et al. Hypersensitivity reactions to non steroidal anti-inflammatory drugs. Curr Drug Metab 2009: 10: 971–80. 3. Ag undez JA, Ayuso P, Cornejo-Garcıa JA, et al. The diamine oxidase gene is associated with hypersensitivity response to nonsteroidal anti-inflammatory drugs. PLoS ONE 2013: 7: e47571.
4. Kim SH, Sanak M, Park HS. Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs. Immunol Allergy Clin North Am 2013: 33: 177–94. € Aydın O, € Demirel 5. C ß elik GE, Erkekol FO, YS, Mısırlıgil Z. Are drug provocation tests still necessary to test the safety of COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity? Allergol Immunopathol 2013: 41: 181–8. 6. Caimmi S, Caimmi D, Bousquet PJ, Demoly P. How can we better classify NSAID hypersensitivity reactions?–validation from a large database. Int Arch Allergy Immunol 2012: 159: 306–12.
7. Asero R. Intolerance to nonsteroidal anti-inflammatory drugs might precede by years the onset of chronic urticaria. J Allergy Clin Immunol 2003: 111: 1095–8. 8. Losol P, Yoo HS, Park HS. Molecular genetic mechanisms of chronic urticaria. Allergy Asthma Immunol Res 2014: 6: 13–21. 9. Asero R. Chronic idiopathic urticaria: a family study. Ann Allergy Asthma Immunol 2002: 89: 195–6. 10. Saini SS. Basophil responsiveness in chronic urticaria. Curr Allergy Asthma Rep 2009: 9: 286–90.
Pre-treatment by omalizumab allows allergen immunotherapy in children and young adults with severe allergic asthma To the Editor, Subcutaneous allergen immunotherapy (SCIT) is a valuable treatment option for patients with controlled mild to
moderate allergic asthma (1). However, SCIT is contraindicated for patients with severe persistent asthma due to a potential systemic allergic reaction: in a cluster protocol,
Pediatric Allergy and Immunology 25 (2015) 817–837 ª 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
829
Letters to the Editor
the risk of serious adverse reactions, including anaphylaxis, was found to increase from 36% in patients treated by conventional immunotherapy and SCIT, respectively (2). Several studies in adolescents and adults with persistent allergic rhinitis and moderate persistent allergic asthma have shown that SCIT is better tolerated when combined with omalizumab, an anti-IgE antibody that blocks an early step in the allergic cascade (3–5). Nevertheless, no previous studies have been conducted in children and adolescents with severe asthma to assess the safety and efficacy of a combination treatment of SCIT and omalizumab, especially when SCIT is continued after stopping omalizumab. We report here the observations of six patients, aged 11–21 years, with severe persistent asthma controlled by omalizumab as add-on therapy who received SCIT under a cluster protocol during omalizumab treatment and then SCIT maintenance alone after discontinuation of omalizumab. Asthma severity in these patients was evidenced by severe and frequent exacerbations despite a high level of maintenance treatment: exacerbations were experienced once every 2 months (n = 1), once a month (n = 4) and once a week (n = 1) requiring hospitalization in an intensive care unit (n = 2) and needing systemic corticosteroids once a month (n = 2), 8 times a year (n = 1), 6 times a year (n = 1) and three times a year (n = 2). FEV1 for all the patients was normal, as frequently encountered in children with severe asthma. All the patients presented dyspnoea on exercise. All the patients were treated with a high dose of inhaled corticosteroid (>500 lg/day of equivalent of beclomethasone dipropionate) (Table 1) in combination with montelukast (n = 6), long-acting theophylline (n = 4) and/or long-acting b2-adrenoceptor agonists (LABA) (n = 6). House dust mite (HDM) allergy was defined by a positive skin prick test with concordant positive specific IgE and allergic symptoms during exposure to this inhaled allergen. After a median time of 8 months of omalizumab treatment (median dosage = 351 mg per month), asthma control was significantly improved in all the patients according to GINA asthma guidelines (6), and there was a significant decrease in exacerbations despite reduction of maintenance treatment (Table 1 and Fig. 1). After achieving asthma control, SCIT to HDM (ALK laboratory, France) was performed by the cluster method. Over 4 days, we were able to increase the SCIT dose to a monthly maintenance dose of 10 lg of Derp1 allergen. Although SCIT had to be discontinued for patient n°6 due to uncontrolled asthma, continued treatment by omalizumab resulted in regaining asthma control and pharmacologic treatment could be decreased. For the five remaining patients, asthma control continued to improve during the combined treatment with SCIT and omalizumab (median time duration = 8 months) despite a decrease in maintenance treatment for all of them (Table 1 and Fig. 1). Omalizumab was stopped after less than 1 year (n = 2), 2 years (n = 1). 3 years (n = 1) and 4 years (n = 1). SCIT was continued alone for a median time of 25.5 months and was well tolerated. For these patients,
830
asthma was totally controlled and therapeutic levels of maintenance treatment could be further reduced (Table 1 and Fig. 1). Discussion Our experience with these six children with severe allergic asthma indicates that pre-treatment with omalizumab seems to improve tolerability (during and after discontinuation of omalizumab) and efficacy of SCIT in this setting. Omalizumab decreases side effects of SCIT and improves efficacy Five of the six patients pre-treated with omalizumab presented no severe side effects of SCIT. This result is in accordance with the literature. Kuehr et al. (4) showed a reduction of 48% in symptom load in children with allergic rhinitis over the pollen seasons with a combination of SCIT with omalizumab compared to SCIT alone. More recently, Kopp et al. (7) reported in a review that omalizumab reduces systemic side effects and amplifies the therapeutic effect of SCIT for inhaled allergen in pollen-induced allergic rhinitis, mild–moderate allergic asthma and venom allergy. Furthermore, Massanari et al. (5) showed that omalizumab use in adult patients with moderate persistent allergic asthma was associated with fewer systemic allergic reaction to SCIT and enabled more patients to achieve the target. SCIT had to be stopped for one of our patients due to uncontrolled asthma. To better understand why SCIT failed in this patient despite pre-treatment with omalizumab, it would have been interesting to assess the patient’s HDM specific IgE-antibody fraction (specific IgE-ab/Total IgE) (8, 9) and CD-sens to HDM (10). Closer monitoring and a possible increase in the omalizumab dosage might have allowed SCIT to be continued. SCIT alone was well tolerated after discontinuation of omalizumab and asthma control continued despite reduction of maintenance treatment In an editorial, Casale et al. (11) noted that there are no data to date about the risks of continuing SCIT after discontinuation of omalizumab or about resulting asthma control. Our observations are a step towards completing this information void and indicate that SCIT is well tolerated after discontinuation of omalizumab despite a high dosage of injected allergen over a long follow-up. This could be the result of a possible induction of a tolerogenic mechanism by SCIT under omalizumab treatment. The persistence of asthma control under SCIT treatment alone could be explained by the remaining effect of omalizumab. However, this effect remains debatable when considering the duration of omalizumab treatment before cessation. Slavin et al. (12) have shown that asthmatic symptoms reappeared 16 weeks after stopping omalizumab. In the same manner, it has been shown that while one remaining effect of omalizumab exists, it does not last for more than a few months after treatment cessation. Furthermore, a longer duration of omalizumab
Pediatric Allergy and Immunology 25 (2015) 817–837 ª 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
400 200 400 200 700 200
6
400 200 400 200 700 200
Asthma control
5 4
Uncontrolled asthma
3
ParƟally controlled asthma
2
Totally controlled asthma
1 0
Decrease of maintenance treatment
400 400 700 400 700 400
Omalizumab and SCIT Omalizumab alone
7
Before Omalizumab SCIT and SCIT alone omalizumab alone omalizumab Montelukast n = 6, LAT n = 5
BDP 300 mcg/day
Figure 1 Asthma control and therapeutic level for the four periods. SCIT, Subcutaneous allergen-specific immunotherapy; BDP, Equivalent of beclomethasone dipropionate; LAT, Long-acting theophylline.
F, Female; M, Male; HDM, House dust mite allergen; SCIT, Subcutaneous allergen-specific immunotherapy.
1000 800 1000 800 1000 1000 300 750 235 300 300 225 >100 >100 50 25 10 >100 493 1796 288 101 529 288 99 100 118 97 58 100 11 21 15 16 15 16 1 2 3 4 5 6
F F M M M M
45 105 89 76 10 7
OmalizumabDoses (mg per month) Total IgE kU/l Gender Patients
FEV1% predictive value
FeNO at baseline (ppb)
IgE HDM (KU/l)
Before omalizumab
BDP 1000 mcg/day
Age (years)
Table 1 Characteristics of the population
Equivalent of beclomethasone dipropionate lg per day
SCIT alone
Letters to the Editor
treatment seems to induce a longer remaining effect. Nopp et al. (13) show a persistence of asthma control and the reduction of basophil allergen sensitivity during 3 years of follow-up after a discontinuation of 6 years of treatment with omalizumab. The duration of omalizumab treatment in the study we report here was short (10% between both values; 165 (71.1%) with higher Alt a 1; 67 (28.9%) with higher Alternaria. Table 1 shows the results of the two patients with negative Alternaria and positive Alt a 1, and of the ten patients with negative Alt a 1 and positive Alternaria. Component-resolved diagnosis permits a more accurate diagnosis of sensitization with potential impact on therapeutic approaches in the case of pollen, food, or even animal dander allergy (1, 2, 6–8). There is, however, scarce information on the potential impact of CRD on mold allergy (3–5). Most of our patients were sensitized to Alt a 1, and levels of specific IgE to this allergen were higher than to Alternaria (Fig. 1). On the other hand, there were some patients, with long distances plotted under the diagonal, who had much higher values with Alternaria than with Alt a 1, meaning that sensitization to other allergens might be relevant. Overall, the number of positive cases was higher, not significantly, with Alternaria (84.7% vs. 81.6%), so this would
Pediatric Allergy and Immunology 25 (2015) 817–837 ª 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
