- Email: [email protected]
Selective allergy to the salmonidae fish family: a selective parvalbumin epitope?
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Letters / Ann Allergy Asthma Immunol 108 (2012) 60 – 67
results and the failure of C1-INH, antihistamines, steroids, and epinephrine to treat or prevent episodes of angioedema are diagnostic of type III HAE. Recently, the patient presented to the emergency department of a children’s hospital with marked facial, tongue, and lip angioedema, which developed after mild facial trauma. He was not treated with antihistamines, steroids, or epinephrine. Forty-five minutes after subcutaneous administration of 30 mg of ecallantide, his angioedema had significantly improved, and by 90 minutes it had completely resolved. Ecallantide ameliorated the patient’s attack because it potently inhibited kallikrein and halted bradykinin production. His response to ecallantide proves that even though his laboratory test results are normal, his HAE is bradykinin mediated, similar to type I and type II HAE. Spontaneous resolution, although possible, is unlikely given the severity and duration of his prior episodes and the rapid resolution of symptoms after receiving ecallantide. Although much progress has been made in diagnosing and treating HAE, there are still limited effective treatment options for patients with type III HAE. This case report describes a patient with type III HAE whose angioedema responded quickly and successfully to treatment with ecallantide, proving that his HAE attacks are due to overproduction of bradykinin. To our knowledge, this is the first documented report of efficacy of a plasma kallikrein inhibitor for
treatment of an acute type III HAE attack. Further studies should be undertaken to explore the efficacy of kallikrein inhibitors for acute attacks in patients with type III HAE. Julia A. Cronin, MD*† Kelly M. Maples, MD*† *Eastern Virginia Medical School † Children’s Hospital of the King’s Daughters Norfolk, Virginia Reference [1] Bowen B, Hawk JJ, Sibunka S, Hovick S, Weiler JM. A review of the reported defects in the human C1 esterase inhibitor gene producing hereditary angioedema including four new mutations. Clin Immunol. 2001;98:157–163. [2] Bork K, Gu¨l D, Dewald G. Hereditary angio-oedema with normal C1 inhibitor in a family with affected women and men. Br J Dermatol. 2006;154:542–545. [3] Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun. 2006;343:1286 –1289. [4] Bowen T, Cicardi M, Farkas H, et al. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6:24. [5] Kaplan AP, Joseph K. The bradykinin-forming cascade and its role in hereditary angioedema. Ann Allergy Asthma Immunol. 2010;104:193–204. [6] Cicardi M, Levy RJ, McNeil DL, et al. Ecallantide for the treatment of acute attacks of hereditary angioedema. N Engl J Med. 2010;363:523–531. [7] Levy RJ, Lumry WR, McNeil DL, et al. EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema. Ann Allergy Asthma Immunol. 2010;104:523–529.
Selective allergy to the salmonidae fish family: a selective parvalbumin epitope? Parvalbumins are the major fish allergens and share sequence identities of 61% to 93%, which support cross-reactivity among fish species.1-4 We report an unusual case of selective allergy to fish of the Salmonidae family in which salmon- and trout-specific parvalbumins seem to be the only allergens involved. A 62-year-old, nonatopic woman presented to our clinic with oropharyngeal itching, angioedema, dysphagia, dysphonia, and generalized exanthema with palmar pruritus after having eaten half a trout (approximately 100 g). In the emergency department, the woman had an oxygen saturation of 91%, blood pressure of 70/40 mm Hg, dizziness, and emesis. She had previously tolerated all kinds of fish, but after the reaction she stopped eating fish. The results of skin prick tests with extracts of tuna, sardine, whiff, hake, cod, sole, sea bream, and the fish parasite Anisakis (Leti Alergia, Barcelona, Spain) were negative. The results of prick to prick tests with boiled fish were positive for salmon (6 mm), trout (6 mm), and whiff (3.5 mm) and negative for tuna, cod, and gilthead. The total IgE level (ImmunoCAP; Phadia, Uppsala, Sweden) was 179 kU/L, and specific IgE tested positive for trout (1.44 kU/L), salmon (1.31 kU/L), hake (0.8 kU/L), and cod (0.45 kU/L) and negative (⬍0.35 kU/L) for Anisakis, whiff, tuna, mackerel, anchovy, herring, cod (rGad c 1). and carp (rCyp c1) parvalbumins. In summary, the patient reported anaphylaxis to trout and had positive skin test results and ImmunoCAP results for trout and salmon, 2 Salmonidae species, but sensitization to other fish was absent or discordant. With the suspicion of a selective reactivity to Salmonidae fish, double-blind, placebo-controlled food challenges (DBPCFCs) with cod, gilthead bream, salmon, and trout were performed to provide adequate dietary advice. In both the trout and salmon DBPCFCs, the patient presented 15 minutes after the intake of 10 g of oropharyngeal pruritus and tightness of the throat. Cod and gilthead bream challenge results were negative. She was advised to avoid trout and salmon, but other fish species were al-
Disclosures: Dr VÂzquez-CortÊs was the holder of a Contrato Post-FormaciÔn Sanitaria Especializada from the Spanish Ministry of Health. Dr Jimeno-Nogales and Dr Ledesma are employed by ALK-AbellÔ SA, Spain. The remaining authors have nothing to disclose.
lowed. In a follow-up visit 1 year later she reported a good tolerance of different fish (gilthead, sea bass, sole, cod, hake, whiting, whiff, sardine, tuna, swordfish, and anchovy) that she had eaten regularly. For the in vitro studies, salmon, trout, whiff, and cod were extracted at 10% (wt/vol) and stored at ⫺20⬚C. Salmon, trout, cod, and whiff extracts (5 g of protein per well in 50mM sodium bicarbonate, pH 9.6) were coated on microtiter plates overnight at 4⬚C and incubated with sera (1:4 dilution) overnight. The patient’s serum showed IgE binding to salmon (0.57 optical density [OD]; pooled negative serum, 0.1 OD) and trout (0.71 OD; pooled negative serum, 0.1 OD), without recognition of cod and whiff. The IgE immunoblotting was performed under nonreducing conditions. Separated proteins were transferred onto a nitrocellulose membrane and incubated with the patient’s serum (1:5 dilution). Bound IgE was detected by peroxidase-conjugated antihuman IgE antibody (1: 3,000) with an enhanced chemiluminescence blotting kit (GE Healthcare, Buckinghamshire, United Kingdom). The patient’s serum showed specific recognition of a 12-kDa band in salmon and trout (Fig 1). A pooled serum sample of 15 negative controls did not show any reactivity. By mass spectrometry (matrix-assisted laser desorption/ionization tandem time-of-flight) the following peptide sequences were obtained: AADTFNFK, VIDQDASGFIEVEELK, and AGDADGDGMIGIDEFAVLVKQ for the salmon band and TFFHTIGFASK, VIDQDASGFIEVEELK, and AGDADGDGMIGIDEFAVLVKQ for the trout band. Protein identification performed by searching a nonredundant protein sequence database (National Center for Biotechnology Information) using the Mascot program showed results highly consistent with salmon parvalbumin (confidence ⬎95%). Most fish allergic patients report clinical reactivity to several fish species due to cross-reactivity of parvalbumins. However, a few cases of selective fish allergy have been reported.5-8 The selective reactivity has never been confirmed by oral challenges,5-8 and the allergens involved are different than parvalbumin,5-7 with the exception of a recent report of a selective allergy to salmon and trout.8 In our patient, the results of skin tests, CAP, and enzyme-linked immunosorbent assay pointed to a selective IgE-mediated response to trout and salmon. Their clinical relevance was confirmed for the first
Letters / Ann Allergy Asthma Immunol 108 (2012) 60 – 67
63
tive reactions to fish species may be caused by the fish panallergen parvalbumin. Acknowledgments We thank the Universidad Complutense de Madrid-Proteomica Campus Moncloa Proteomic facility, a member of the ProteoRed network, for performing the proteomic matrix-assisted laser desorption/ionization tandem time-of-flight analysis. Sonia VÂzquez-CortÊs, MD* Beatriz NuÒez-Acevedo, MD* LucÎa Jimeno-Nogales, PhD† Amalia Ledesma, PhD† Montserrat FernÂndez-Rivas, MD, PhD* *Servicio de Alergia Hospital Clìnico San Carlos Instituto de Investigaciòn Sanitaria del Hospital Clìnico San Carlos (IdISSC) Madrid, Spain † Department I+D ALK-Abellò SA Madrid, Spain [email protected] Reference
Figure 1. Salmon and trout IgE immunoblot. T indicates trout extract; S, salmon extract; C, pooled control serum; and P, patient’s serum. Trout (lane 1) and salmon (lane 2) extracts were incubated with a pooled serum of 15 nonallergic controls. Trout (lane 3) and salmon (lane 4) extracts were incubated with the patient’s serum.
time by DBPCFC and further supported by the subsequent good tolerance of more than 10 fish species not belonging to the Salmonidae family. Our IgE immunoblotting and mass spectrometry results suggest a specific epitope recognition pattern of Salmonidae parvalbumins, which is supported by the fact that the sequence identity between salmon and trout parvalbumins is higher than with the counterparts of cod, hake, sole, tuna, and whiting,1-4 fish species tolerated by our patient. In summary, this case report shows that selec-
[1] Swoboda I, Bugajska-Schretter A, Valenta R, Spitzauer S. Recombinant fish parvalbumins: candidates for diagnosis and treatment of fish allergy. Allergy. 2002;57:S94 –S96. [2] Van Do T, Elsayed S, Florvaag E, Hordvik I, Endresen C. Allergy to fish parvalbumins: studies on the cross-reactivity of allergens from 9 commonly consumed fish. J Allergy Clin Immunol. 2005;116:1314 –1320. [3] Griesmeier U, VÂzquez-CortÊs S, Bublin M, et al. Expression levels of parvalbumins determine allergenicity of fish species. Allergy. 2010;65:191–198. [4] Perez-Gordo M, Cuesta-Herranz J, Maroto AS, et al. Identification of sole parvalbumin as a major allergen: study of cross-reactivity between parvalbumins in a Spanish fish-allergic population. Clin Exp Allergy. 2011;41:750 –758. [5] Kelso JM, Jones RT, Yunginger JW. Monospecific allergy to swordfish. Ann Allergy Asthma Immunol. 1996;77:227–228. [6] Asero R, Mistrello G, Roncarolo D, Casarini M, Falagiani P. True monosensitivity to a tropical sole. Allergy. 1999;54:1228 –1229. [7] Ebo DG, Kuehn A, Bridts CH, Hilger C, Hentges F, Stevens WJ. Monosensitivity to pangasius and tilapia caused by allergens other than parvalbumin. J Investig Allergol Clin Immunol. 2010;20:84 – 88. [8] Kuehn A, Hutt-Kempf E, Hilger C, Hentges F. Clinical monosensitivity to salmonid fish linked to specific IgE-epitopes on salmon and trout beta-parvalbumins. Allergy. 2011;66:299 –301.
Allergy to local anesthetics: specific IgE demonstration to both amides and esters in a single patient IgE-mediated reactions to local anesthetics (LAs) are rare. Case series have demonstrated that IgE-mediated reactions comprise only 0.6% of all adverse reactions to these medications.1⫺4 Only 2 cases of specific IgE have been demonstrated via in vitro methods.5,6 Immediate reactions have been reported to additives (eg, sulfites, parabens derivatives, and latex) found in LAs, but most non–IgE-mediated adverse reactions are due to sympathetic stimulation, vasovagal reaction, or hyperventilation. There are 2 classes of LAs. Amides (eg, lidocaine, bupivacaine, mepivacaine) are most frequently used and usually do not crossreact.7 Esters (eg, procaine, tetracaine) have a higher risk of IgEmediated reactions and cross-reactivity has been reported. The LA articaine is considered an amide, but its unique structure consists
Disclosures: Authors have nothing to disclose. Funding Sources: This study was funded by the US Air Force. Disclaimer: The opinions or assertions herein are the private views of the authors and are not to be construed as reflecting the views of the US Department of the Air Force or the US Department of Defense.
of both an amide and an ester group. We report a case in which a patient demonstrated a clinical history, skin test result, and in vitro evidence consistent with a dual IgE reaction to both amide and ester LAs. In 2009, a 44-year-old atopic woman was referred to our clinic after 2 reactions to an LA at the dental office. Her initial reaction consisted of generalized pruritus and urticaria 5 minutes after a lidocaine injection, with symptoms resolving after oral antihistamines. She returned to the dentist 1 week later and was given a different, unknown LA, which resulted in similar symptoms, including facial angioedema. Her symptoms resolved within 24 hours. No antibiotics were given before either visit. She had her wisdom teeth extracted 25 years previously without reaction, and she had no history of adverse reactions to antibiotics, latex, or food. The patient underwent skin testing to lidocaine, articaine, and tetracaine with a positive 1:10 intradermal test result to tetracaine and positive incremental injection challenge results to lidocaine (pruritic rash at 0.5 mL) and articaine (pruritus and hives at 0.1 mL).
Letters / Ann Allergy Asthma Immunol 108 (2012) 60 – 67
results and the failure of C1-INH, antihistamines, steroids, and epinephrine to treat or prevent episodes of angioedema are diagnostic of type III HAE. Recently, the patient presented to the emergency department of a children’s hospital with marked facial, tongue, and lip angioedema, which developed after mild facial trauma. He was not treated with antihistamines, steroids, or epinephrine. Forty-five minutes after subcutaneous administration of 30 mg of ecallantide, his angioedema had significantly improved, and by 90 minutes it had completely resolved. Ecallantide ameliorated the patient’s attack because it potently inhibited kallikrein and halted bradykinin production. His response to ecallantide proves that even though his laboratory test results are normal, his HAE is bradykinin mediated, similar to type I and type II HAE. Spontaneous resolution, although possible, is unlikely given the severity and duration of his prior episodes and the rapid resolution of symptoms after receiving ecallantide. Although much progress has been made in diagnosing and treating HAE, there are still limited effective treatment options for patients with type III HAE. This case report describes a patient with type III HAE whose angioedema responded quickly and successfully to treatment with ecallantide, proving that his HAE attacks are due to overproduction of bradykinin. To our knowledge, this is the first documented report of efficacy of a plasma kallikrein inhibitor for
treatment of an acute type III HAE attack. Further studies should be undertaken to explore the efficacy of kallikrein inhibitors for acute attacks in patients with type III HAE. Julia A. Cronin, MD*† Kelly M. Maples, MD*† *Eastern Virginia Medical School † Children’s Hospital of the King’s Daughters Norfolk, Virginia Reference [1] Bowen B, Hawk JJ, Sibunka S, Hovick S, Weiler JM. A review of the reported defects in the human C1 esterase inhibitor gene producing hereditary angioedema including four new mutations. Clin Immunol. 2001;98:157–163. [2] Bork K, Gu¨l D, Dewald G. Hereditary angio-oedema with normal C1 inhibitor in a family with affected women and men. Br J Dermatol. 2006;154:542–545. [3] Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun. 2006;343:1286 –1289. [4] Bowen T, Cicardi M, Farkas H, et al. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6:24. [5] Kaplan AP, Joseph K. The bradykinin-forming cascade and its role in hereditary angioedema. Ann Allergy Asthma Immunol. 2010;104:193–204. [6] Cicardi M, Levy RJ, McNeil DL, et al. Ecallantide for the treatment of acute attacks of hereditary angioedema. N Engl J Med. 2010;363:523–531. [7] Levy RJ, Lumry WR, McNeil DL, et al. EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema. Ann Allergy Asthma Immunol. 2010;104:523–529.
Selective allergy to the salmonidae fish family: a selective parvalbumin epitope? Parvalbumins are the major fish allergens and share sequence identities of 61% to 93%, which support cross-reactivity among fish species.1-4 We report an unusual case of selective allergy to fish of the Salmonidae family in which salmon- and trout-specific parvalbumins seem to be the only allergens involved. A 62-year-old, nonatopic woman presented to our clinic with oropharyngeal itching, angioedema, dysphagia, dysphonia, and generalized exanthema with palmar pruritus after having eaten half a trout (approximately 100 g). In the emergency department, the woman had an oxygen saturation of 91%, blood pressure of 70/40 mm Hg, dizziness, and emesis. She had previously tolerated all kinds of fish, but after the reaction she stopped eating fish. The results of skin prick tests with extracts of tuna, sardine, whiff, hake, cod, sole, sea bream, and the fish parasite Anisakis (Leti Alergia, Barcelona, Spain) were negative. The results of prick to prick tests with boiled fish were positive for salmon (6 mm), trout (6 mm), and whiff (3.5 mm) and negative for tuna, cod, and gilthead. The total IgE level (ImmunoCAP; Phadia, Uppsala, Sweden) was 179 kU/L, and specific IgE tested positive for trout (1.44 kU/L), salmon (1.31 kU/L), hake (0.8 kU/L), and cod (0.45 kU/L) and negative (⬍0.35 kU/L) for Anisakis, whiff, tuna, mackerel, anchovy, herring, cod (rGad c 1). and carp (rCyp c1) parvalbumins. In summary, the patient reported anaphylaxis to trout and had positive skin test results and ImmunoCAP results for trout and salmon, 2 Salmonidae species, but sensitization to other fish was absent or discordant. With the suspicion of a selective reactivity to Salmonidae fish, double-blind, placebo-controlled food challenges (DBPCFCs) with cod, gilthead bream, salmon, and trout were performed to provide adequate dietary advice. In both the trout and salmon DBPCFCs, the patient presented 15 minutes after the intake of 10 g of oropharyngeal pruritus and tightness of the throat. Cod and gilthead bream challenge results were negative. She was advised to avoid trout and salmon, but other fish species were al-
Disclosures: Dr VÂzquez-CortÊs was the holder of a Contrato Post-FormaciÔn Sanitaria Especializada from the Spanish Ministry of Health. Dr Jimeno-Nogales and Dr Ledesma are employed by ALK-AbellÔ SA, Spain. The remaining authors have nothing to disclose.
lowed. In a follow-up visit 1 year later she reported a good tolerance of different fish (gilthead, sea bass, sole, cod, hake, whiting, whiff, sardine, tuna, swordfish, and anchovy) that she had eaten regularly. For the in vitro studies, salmon, trout, whiff, and cod were extracted at 10% (wt/vol) and stored at ⫺20⬚C. Salmon, trout, cod, and whiff extracts (5 g of protein per well in 50mM sodium bicarbonate, pH 9.6) were coated on microtiter plates overnight at 4⬚C and incubated with sera (1:4 dilution) overnight. The patient’s serum showed IgE binding to salmon (0.57 optical density [OD]; pooled negative serum, 0.1 OD) and trout (0.71 OD; pooled negative serum, 0.1 OD), without recognition of cod and whiff. The IgE immunoblotting was performed under nonreducing conditions. Separated proteins were transferred onto a nitrocellulose membrane and incubated with the patient’s serum (1:5 dilution). Bound IgE was detected by peroxidase-conjugated antihuman IgE antibody (1: 3,000) with an enhanced chemiluminescence blotting kit (GE Healthcare, Buckinghamshire, United Kingdom). The patient’s serum showed specific recognition of a 12-kDa band in salmon and trout (Fig 1). A pooled serum sample of 15 negative controls did not show any reactivity. By mass spectrometry (matrix-assisted laser desorption/ionization tandem time-of-flight) the following peptide sequences were obtained: AADTFNFK, VIDQDASGFIEVEELK, and AGDADGDGMIGIDEFAVLVKQ for the salmon band and TFFHTIGFASK, VIDQDASGFIEVEELK, and AGDADGDGMIGIDEFAVLVKQ for the trout band. Protein identification performed by searching a nonredundant protein sequence database (National Center for Biotechnology Information) using the Mascot program showed results highly consistent with salmon parvalbumin (confidence ⬎95%). Most fish allergic patients report clinical reactivity to several fish species due to cross-reactivity of parvalbumins. However, a few cases of selective fish allergy have been reported.5-8 The selective reactivity has never been confirmed by oral challenges,5-8 and the allergens involved are different than parvalbumin,5-7 with the exception of a recent report of a selective allergy to salmon and trout.8 In our patient, the results of skin tests, CAP, and enzyme-linked immunosorbent assay pointed to a selective IgE-mediated response to trout and salmon. Their clinical relevance was confirmed for the first
Letters / Ann Allergy Asthma Immunol 108 (2012) 60 – 67
63
tive reactions to fish species may be caused by the fish panallergen parvalbumin. Acknowledgments We thank the Universidad Complutense de Madrid-Proteomica Campus Moncloa Proteomic facility, a member of the ProteoRed network, for performing the proteomic matrix-assisted laser desorption/ionization tandem time-of-flight analysis. Sonia VÂzquez-CortÊs, MD* Beatriz NuÒez-Acevedo, MD* LucÎa Jimeno-Nogales, PhD† Amalia Ledesma, PhD† Montserrat FernÂndez-Rivas, MD, PhD* *Servicio de Alergia Hospital Clìnico San Carlos Instituto de Investigaciòn Sanitaria del Hospital Clìnico San Carlos (IdISSC) Madrid, Spain † Department I+D ALK-Abellò SA Madrid, Spain [email protected] Reference
Figure 1. Salmon and trout IgE immunoblot. T indicates trout extract; S, salmon extract; C, pooled control serum; and P, patient’s serum. Trout (lane 1) and salmon (lane 2) extracts were incubated with a pooled serum of 15 nonallergic controls. Trout (lane 3) and salmon (lane 4) extracts were incubated with the patient’s serum.
time by DBPCFC and further supported by the subsequent good tolerance of more than 10 fish species not belonging to the Salmonidae family. Our IgE immunoblotting and mass spectrometry results suggest a specific epitope recognition pattern of Salmonidae parvalbumins, which is supported by the fact that the sequence identity between salmon and trout parvalbumins is higher than with the counterparts of cod, hake, sole, tuna, and whiting,1-4 fish species tolerated by our patient. In summary, this case report shows that selec-
[1] Swoboda I, Bugajska-Schretter A, Valenta R, Spitzauer S. Recombinant fish parvalbumins: candidates for diagnosis and treatment of fish allergy. Allergy. 2002;57:S94 –S96. [2] Van Do T, Elsayed S, Florvaag E, Hordvik I, Endresen C. Allergy to fish parvalbumins: studies on the cross-reactivity of allergens from 9 commonly consumed fish. J Allergy Clin Immunol. 2005;116:1314 –1320. [3] Griesmeier U, VÂzquez-CortÊs S, Bublin M, et al. Expression levels of parvalbumins determine allergenicity of fish species. Allergy. 2010;65:191–198. [4] Perez-Gordo M, Cuesta-Herranz J, Maroto AS, et al. Identification of sole parvalbumin as a major allergen: study of cross-reactivity between parvalbumins in a Spanish fish-allergic population. Clin Exp Allergy. 2011;41:750 –758. [5] Kelso JM, Jones RT, Yunginger JW. Monospecific allergy to swordfish. Ann Allergy Asthma Immunol. 1996;77:227–228. [6] Asero R, Mistrello G, Roncarolo D, Casarini M, Falagiani P. True monosensitivity to a tropical sole. Allergy. 1999;54:1228 –1229. [7] Ebo DG, Kuehn A, Bridts CH, Hilger C, Hentges F, Stevens WJ. Monosensitivity to pangasius and tilapia caused by allergens other than parvalbumin. J Investig Allergol Clin Immunol. 2010;20:84 – 88. [8] Kuehn A, Hutt-Kempf E, Hilger C, Hentges F. Clinical monosensitivity to salmonid fish linked to specific IgE-epitopes on salmon and trout beta-parvalbumins. Allergy. 2011;66:299 –301.
Allergy to local anesthetics: specific IgE demonstration to both amides and esters in a single patient IgE-mediated reactions to local anesthetics (LAs) are rare. Case series have demonstrated that IgE-mediated reactions comprise only 0.6% of all adverse reactions to these medications.1⫺4 Only 2 cases of specific IgE have been demonstrated via in vitro methods.5,6 Immediate reactions have been reported to additives (eg, sulfites, parabens derivatives, and latex) found in LAs, but most non–IgE-mediated adverse reactions are due to sympathetic stimulation, vasovagal reaction, or hyperventilation. There are 2 classes of LAs. Amides (eg, lidocaine, bupivacaine, mepivacaine) are most frequently used and usually do not crossreact.7 Esters (eg, procaine, tetracaine) have a higher risk of IgEmediated reactions and cross-reactivity has been reported. The LA articaine is considered an amide, but its unique structure consists
Disclosures: Authors have nothing to disclose. Funding Sources: This study was funded by the US Air Force. Disclaimer: The opinions or assertions herein are the private views of the authors and are not to be construed as reflecting the views of the US Department of the Air Force or the US Department of Defense.
of both an amide and an ester group. We report a case in which a patient demonstrated a clinical history, skin test result, and in vitro evidence consistent with a dual IgE reaction to both amide and ester LAs. In 2009, a 44-year-old atopic woman was referred to our clinic after 2 reactions to an LA at the dental office. Her initial reaction consisted of generalized pruritus and urticaria 5 minutes after a lidocaine injection, with symptoms resolving after oral antihistamines. She returned to the dentist 1 week later and was given a different, unknown LA, which resulted in similar symptoms, including facial angioedema. Her symptoms resolved within 24 hours. No antibiotics were given before either visit. She had her wisdom teeth extracted 25 years previously without reaction, and she had no history of adverse reactions to antibiotics, latex, or food. The patient underwent skin testing to lidocaine, articaine, and tetracaine with a positive 1:10 intradermal test result to tetracaine and positive incremental injection challenge results to lidocaine (pruritic rash at 0.5 mL) and articaine (pruritus and hives at 0.1 mL).