Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction

Abstract Background Allergic, especially anaphylactic, reactions during immunoglobulin replacement therapy are rare, but their pathophysiology and classification remain ambiguous. Recent findings show positive results of skin tests with commercially available immunoglobulins, but target antigens and...

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Main Authors: Przemyslaw Zdziarski, Andrzej Gamian, Jacek Majda, Agnieszka Korzeniowska-Kowal
Format: Article
Language:English
Published: BMC 2017-09-01
Series:Allergy, Asthma & Clinical Immunology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13223-017-0213-x
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author Przemyslaw Zdziarski
Andrzej Gamian
Jacek Majda
Agnieszka Korzeniowska-Kowal
author_facet Przemyslaw Zdziarski
Andrzej Gamian
Jacek Majda
Agnieszka Korzeniowska-Kowal
author_sort Przemyslaw Zdziarski
collection DOAJ
description Abstract Background Allergic, especially anaphylactic, reactions during immunoglobulin replacement therapy are rare, but their pathophysiology and classification remain ambiguous. Recent findings show positive results of skin tests with commercially available immunoglobulins, but target antigens and responsible compounds of the tested immunoglobulins have not been strictly identified. Case description and findings Four adult patients with recently diagnosed common variable immunodeficiency qualified for standard subcutaneous immunoglobulin replacement therapy regimen. They had no history of receiving immunoglobulins, blood or blood product transfusions. Edema, confluent wheals and erythema were observed at the site of subcutaneous immunoglobulin infusion: typical early and late phase reaction. A transient increase in various passively transferred IgG and IgE antibodies was responsible for misleading positive outcome of the serological testing for active humoral response such as type I allergy, anti-Rh, isohemagglutinins and rheumatoid factor (RF). Although the clinical presentation was very unusual and severe, the retrospective analysis showed no isohemagglutinins, RF and IgE in the patients’ serum before but it was positive after the infusion (median IgE = 18 IU/ml, RF = 8 IU/ml). Type I allergic reaction (laryngeal edema, rhinoconjuctivitis) came out at +14 days of replacement therapy when the patient visited countryside. In the second patient anaphylactic reaction was observed 5 days after ScIg administration, and only when the patient consumed peanuts. Therefore, IgE concentration was measured retrospectively in a series of commercial preparations used in the initial subcutaneous immunoglobulin replacement therapy that caused the adverse event (AE) and it was determined between 138 and 232 IU/ml (kU/l), i.e. 690–2100 IU per g of protein. Specific IgE was within a wide range from 198 (mix of food) to 2809 kUA/l (mix of grass) but many of the tested allergen-specific IgE were class 2 or 3 (i.e. 0.71–17.5 kUA/l). Conclusions The case resembles passive cutaneous anaphylaxis and Prausnitz–Küstner reaction but clinical significance of the classical phenomena has not yet been described. This observation indicates that anaphylactic reactions during immunoglobulin replacement therapy may result from IgE or pathological IgG content. Such IgE presence was sporadically reported (34.5–105 IU/ml, i.e. 862.5–1450 IU/g of protein) in intravenous immunoglobulins that are used and monitored by healthcare professionals. In clinical practice the definition of adverse events is inadequate since individual batches of immunoglobulins come with different specificity therefore, they should be classified as transfusion products (not bioequivalents). Such new approach implies establishing (1) new control methods and strategies to ensure introduction of the safety regulations for subcutaneous home self-administration of immunoglobulins as well as (2) guidelines for the prevention of anaphylaxis in patients receiving immunoglobulins (for example peanut).
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spelling doaj.art-8a7e36ac142d42e8bcef709591de79882022-12-22T01:56:13ZengBMCAllergy, Asthma & Clinical Immunology1710-14922017-09-011311910.1186/s13223-017-0213-xPassive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reactionPrzemyslaw Zdziarski0Andrzej Gamian1Jacek Majda2Agnieszka Korzeniowska-Kowal3Department of Clinical Immunology, Lower Silesian Center for Cellular TransplantationDepartment of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesDepartment Laboratory, 4th Military Teaching HospitalDepartment of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesAbstract Background Allergic, especially anaphylactic, reactions during immunoglobulin replacement therapy are rare, but their pathophysiology and classification remain ambiguous. Recent findings show positive results of skin tests with commercially available immunoglobulins, but target antigens and responsible compounds of the tested immunoglobulins have not been strictly identified. Case description and findings Four adult patients with recently diagnosed common variable immunodeficiency qualified for standard subcutaneous immunoglobulin replacement therapy regimen. They had no history of receiving immunoglobulins, blood or blood product transfusions. Edema, confluent wheals and erythema were observed at the site of subcutaneous immunoglobulin infusion: typical early and late phase reaction. A transient increase in various passively transferred IgG and IgE antibodies was responsible for misleading positive outcome of the serological testing for active humoral response such as type I allergy, anti-Rh, isohemagglutinins and rheumatoid factor (RF). Although the clinical presentation was very unusual and severe, the retrospective analysis showed no isohemagglutinins, RF and IgE in the patients’ serum before but it was positive after the infusion (median IgE = 18 IU/ml, RF = 8 IU/ml). Type I allergic reaction (laryngeal edema, rhinoconjuctivitis) came out at +14 days of replacement therapy when the patient visited countryside. In the second patient anaphylactic reaction was observed 5 days after ScIg administration, and only when the patient consumed peanuts. Therefore, IgE concentration was measured retrospectively in a series of commercial preparations used in the initial subcutaneous immunoglobulin replacement therapy that caused the adverse event (AE) and it was determined between 138 and 232 IU/ml (kU/l), i.e. 690–2100 IU per g of protein. Specific IgE was within a wide range from 198 (mix of food) to 2809 kUA/l (mix of grass) but many of the tested allergen-specific IgE were class 2 or 3 (i.e. 0.71–17.5 kUA/l). Conclusions The case resembles passive cutaneous anaphylaxis and Prausnitz–Küstner reaction but clinical significance of the classical phenomena has not yet been described. This observation indicates that anaphylactic reactions during immunoglobulin replacement therapy may result from IgE or pathological IgG content. Such IgE presence was sporadically reported (34.5–105 IU/ml, i.e. 862.5–1450 IU/g of protein) in intravenous immunoglobulins that are used and monitored by healthcare professionals. In clinical practice the definition of adverse events is inadequate since individual batches of immunoglobulins come with different specificity therefore, they should be classified as transfusion products (not bioequivalents). Such new approach implies establishing (1) new control methods and strategies to ensure introduction of the safety regulations for subcutaneous home self-administration of immunoglobulins as well as (2) guidelines for the prevention of anaphylaxis in patients receiving immunoglobulins (for example peanut).http://link.springer.com/article/10.1186/s13223-017-0213-xSubcutaneous immunoglobulins (ScIg)IgEIgGSerum half-lifeAnaphylaxisHypersensitivity
spellingShingle Przemyslaw Zdziarski
Andrzej Gamian
Jacek Majda
Agnieszka Korzeniowska-Kowal
Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction
Allergy, Asthma & Clinical Immunology
Subcutaneous immunoglobulins (ScIg)
IgE
IgG
Serum half-life
Anaphylaxis
Hypersensitivity
title Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction
title_full Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction
title_fullStr Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction
title_full_unstemmed Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction
title_short Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction
title_sort passive blood anaphylaxis subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction
topic Subcutaneous immunoglobulins (ScIg)
IgE
IgG
Serum half-life
Anaphylaxis
Hypersensitivity
url http://link.springer.com/article/10.1186/s13223-017-0213-x
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AT jacekmajda passivebloodanaphylaxissubcutaneousimmunoglobulinsareacauseofongoingpassiveanaphylacticreaction
AT agnieszkakorzeniowskakowal passivebloodanaphylaxissubcutaneousimmunoglobulinsareacauseofongoingpassiveanaphylacticreaction