Vaccine-associated hypersensitivity
2018; Elsevier BV; Volume: 141; Issue: 2 Linguagem: Inglês
10.1016/j.jaci.2017.12.971
ISSN1097-6825
AutoresMichael M. McNeil, Frank DeStefano,
Tópico(s)Respiratory and Cough-Related Research
ResumoInformation for Category 1 CME CreditCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted.Date of Original Release: February 2018. Credit may be obtained for these courses until January 31, 2019.Copyright Statement: Copyright © 2018-2019. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Michael M. McNeil, MD, MPH, and Frank DeStefano, MD, MPH (authors); Zuhair K. Ballas, MD (editor)Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: The authors declare that they have no relevant conflicts of interest. Z. K. Ballas (editor) disclosed no relevant financial relationships.Activity Objectives:1.To be able to discuss the differences in underlying mechanisms and presentation of immediate and delayed vaccine reactions.2.To be aware of the most recent vaccine guidelines regarding patients with egg allergy and influenza vaccination.3.To understand the limited data supporting other components of vaccines that might be implicated as possible causes of anaphylaxis.4.To be able to discuss the rate and clinical risk factors for vaccine-triggered anaphylaxis.Recognition of Commercial Support: This CME activity has not received external commercial support.List of CME Exam Authors: Daniel Har, MD, Shyam Joshi, MD, Mariam Wahidi, MD, Shazia Lutfeali, MD, and David A. Khan, MD.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: The exam authors disclosed no relevant financial relationships.Vaccine-associated hypersensitivity reactions are not infrequent; however, serious acute-onset, presumably IgE-mediated or IgG and complement-mediated anaphylactic or serious delayed-onset T cell–mediated systemic reactions are considered extremely rare. Hypersensitivity can occur because of either the active vaccine component (antigen) or one of the other components. Postvaccination acute-onset hypersensitivity reactions include self-limited localized adverse events and, rarely, systemic reactions ranging from urticaria/angioedema to full-blown anaphylaxis with multisystem involvement. Risk of anaphylaxis after all vaccines is estimated to be 1.31 (95% CI, 0.90-1.84) per million vaccine doses, respectively. Serious hypersensitivity reactions after influenza vaccines are particularly important because of the large number of persons vaccinated annually. Influenza vaccines are unique in requiring annual changes in the vaccines’ antigenic composition to match the predicted circulating influenza strains. Recently, novel influenza vaccine types were introduced in the United States (recombinant vaccines, some with higher antigen content and a new adjuvanted vaccine). Providers should be aware of changing recommendations on the basis of recent published evidence for persons with a history of egg allergy to receive annual influenza vaccination. Further research is needed to elucidate the pathophysiology and risk factors for reported vaccine-associated adverse events. Further research is also needed to determine whether repeated annual inactivated influenza vaccination, the number of vaccine antigens administered at the same time, and the current timing of routine infant vaccinations are optimal for overall population well-being. Information for Category 1 CME CreditCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted.Date of Original Release: February 2018. Credit may be obtained for these courses until January 31, 2019.Copyright Statement: Copyright © 2018-2019. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Michael M. McNeil, MD, MPH, and Frank DeStefano, MD, MPH (authors); Zuhair K. Ballas, MD (editor)Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: The authors declare that they have no relevant conflicts of interest. Z. K. Ballas (editor) disclosed no relevant financial relationships.Activity Objectives:1.To be able to discuss the differences in underlying mechanisms and presentation of immediate and delayed vaccine reactions.2.To be aware of the most recent vaccine guidelines regarding patients with egg allergy and influenza vaccination.3.To understand the limited data supporting other components of vaccines that might be implicated as possible causes of anaphylaxis.4.To be able to discuss the rate and clinical risk factors for vaccine-triggered anaphylaxis.Recognition of Commercial Support: This CME activity has not received external commercial support.List of CME Exam Authors: Daniel Har, MD, Shyam Joshi, MD, Mariam Wahidi, MD, Shazia Lutfeali, MD, and David A. Khan, MD.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: The exam authors disclosed no relevant financial relationships.Vaccine-associated hypersensitivity reactions are not infrequent; however, serious acute-onset, presumably IgE-mediated or IgG and complement-mediated anaphylactic or serious delayed-onset T cell–mediated systemic reactions are considered extremely rare. Hypersensitivity can occur because of either the active vaccine component (antigen) or one of the other components. Postvaccination acute-onset hypersensitivity reactions include self-limited localized adverse events and, rarely, systemic reactions ranging from urticaria/angioedema to full-blown anaphylaxis with multisystem involvement. Risk of anaphylaxis after all vaccines is estimated to be 1.31 (95% CI, 0.90-1.84) per million vaccine doses, respectively. Serious hypersensitivity reactions after influenza vaccines are particularly important because of the large number of persons vaccinated annually. Influenza vaccines are unique in requiring annual changes in the vaccines’ antigenic composition to match the predicted circulating influenza strains. Recently, novel influenza vaccine types were introduced in the United States (recombinant vaccines, some with higher antigen content and a new adjuvanted vaccine). Providers should be aware of changing recommendations on the basis of recent published evidence for persons with a history of egg allergy to receive annual influenza vaccination. Further research is needed to elucidate the pathophysiology and risk factors for reported vaccine-associated adverse events. Further research is also needed to determine whether repeated annual inactivated influenza vaccination, the number of vaccine antigens administered at the same time, and the current timing of routine infant vaccinations are optimal for overall population well-being. Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions. Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted. Date of Original Release: February 2018. Credit may be obtained for these courses until January 31, 2019. Copyright Statement: Copyright © 2018-2019. All rights reserved. Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Michael M. McNeil, MD, MPH, and Frank DeStefano, MD, MPH (authors); Zuhair K. Ballas, MD (editor) Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: The authors declare that they have no relevant conflicts of interest. Z. K. Ballas (editor) disclosed no relevant financial relationships. Activity Objectives:1.To be able to discuss the differences in underlying mechanisms and presentation of immediate and delayed vaccine reactions.2.To be aware of the most recent vaccine guidelines regarding patients with egg allergy and influenza vaccination.3.To understand the limited data supporting other components of vaccines that might be implicated as possible causes of anaphylaxis.4.To be able to discuss the rate and clinical risk factors for vaccine-triggered anaphylaxis. Recognition of Commercial Support: This CME activity has not received external commercial support. List of CME Exam Authors: Daniel Har, MD, Shyam Joshi, MD, Mariam Wahidi, MD, Shazia Lutfeali, MD, and David A. Khan, MD. Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: The exam authors disclosed no relevant financial relationships. Vaccines have been recognized as one of the most effective public health interventions.1National Vaccine Advisory CommitteeProtecting the public's health: critical functions of the Section 317 Immunization Program—a report of the National Vaccine Advisory Committee.Public Health Rep. 2013; 128: 78-95Crossref PubMed Scopus (19) Google Scholar Routine immunization has resulted in major reductions in vaccine-preventable infectious disease and death. The Advisory Committee on Immunization Practices (ACIP) recommends an immunization schedule for the United States in which children receive 10 vaccines to protect against 16 diseases before the age of 2 years.2Robinson C.L. Romero J.R. Kempe A. Pellegrini C. Advisory Committee on Immunization Practices (ACIP) Child/Adolescent Immunization Work Group. Advisory Committee on Immunization Practices Recommended immunization schedule for children and adolescents aged 18 years or younger—United States, 2017.MMWR Morb Mortal Wkly Rep. 2017; 66: 134-135Crossref PubMed Scopus (56) Google Scholar Although vaccination programs have as their main goal the protection of the person vaccinated, in some cases the protective effect extends to nonvaccinated persons, producing herd immunity (ie, resistance to the circulation of contagious disease in a population that results if a sufficiently high proportion of subjects are immune to the disease, especially through vaccination).3Scarbrough Lefebvre C.D. Terlinden A. Standaert B. Dissecting the indirect effects caused by vaccines into the basic elements.Hum Vaccines Immunother. 2015; 11: 2142-2157Crossref PubMed Scopus (28) Google Scholar Vaccine-associated hypersensitivity reactions are not infrequent. Fortunately, most reported vaccine-associated adverse reactions are not serious, and many are not immunologically mediated or even reproducible on re-exposure.4Caubet J.C. Ponvert C. Vaccine allergy.Immunol Allergy Clin North Am. 2014; 34: 597-613Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar Serious anaphylactic or cutaneous adverse reactions do occur but are extremely rare. Evaluation of immunization-associated, potentially immunologically mediated hypersensitivity is important to help determine the mechanism or mechanisms of the reaction. If acute hypersensitivity is confirmed, it allows future exposure to the needed vaccine through desensitization or in split doses if low risk (one tenth of the dose and then nine tenths of the dose). Patients erroneously labeled as “vaccine intolerant” might be inadequately immunized and experience preventable disease. Careful review of the timing of the adverse reaction and the clinical nature of the reaction, along with appropriate testing for IgE-mediated allergy, mast cell activation, vaccine-specific IgG and complement activation, and T cell–mediated delayed-type hypersensitivity can in most cases allow safe re-exposure to the implicated vaccine when needed in the future. In this report we review the types of immunologically mediated hypersensitivity that can occur after vaccination, the components in vaccines implicated in these reactions, and the incidence of serious acute-onset and delayed-onset reactions and highlight recent important research advances. The interested reader is referred to excellent recent reviews of allergic outcomes and clinical guidance on treatment of these outcomes.5Dreskin S.C. Halsey N.A. Kelso J.M. Wood R.A. Hummell D.S. Edwards K.M. et al.International consensus (ICON): allergic reactions to vaccines.World Allergy J. 2016; 9: 32Crossref PubMed Scopus (108) Google Scholar, 6Simons F.E.R. Ebisawa M. Sanchez-Borges M. Thong B.Y. Worm M. Kase Tanno L. et al.2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines.World Allergy Organ J. 2015; 8: 32Crossref PubMed Scopus (366) Google Scholar, 7Simons F.E.R. Sampson H.A. Anaphylaxis: unique aspects of clinical diagnosis and management in infants (birth to age 2 years).J Allergy Clin Immunol. 2015; 135: 1125-1131Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 8Lieberman P. Nicklas R.A. Randolph C. Oppenheimer J. Berstein D. Bernstein J. et al.Anaphylaxis–a practice parameter update 2015.Ann Allergy Asthma Immunol. 2015; 115: 341-384Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar, 9Nilsson L. Brockow K. Alm J. Cardona V. Caubert J.C. Gomes E. et al.Vaccination and allergy: EAACI position paper, practical aspects.Pediatr Allergy Immunol. 2017; 28: 628-640Crossref PubMed Scopus (85) Google Scholar, 10Zafack J.G. De Serres G. Rouleau I. Gariépy M.C. Gagnon R. Drolet J.P. et al.Clinical approach used in medical consultations for allergic-like events following immunization: case series report in relation to practice guidelines.J Allergy Clin Immunol. 2017; 5: 718-727Abstract Full Text Full Text PDF Scopus (12) Google Scholar Immunologically mediated allergic reactions are either acute in onset or delayed.6Simons F.E.R. Ebisawa M. Sanchez-Borges M. Thong B.Y. Worm M. Kase Tanno L. et al.2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines.World Allergy Organ J. 2015; 8: 32Crossref PubMed Scopus (366) Google Scholar The majority of acute-onset reactions are type I hypersensitivity reactions mediated by preformed IgE antibodies against a vaccine component. The importance of distinguishing acute-onset IgE-mediated reactions is that they can manifest as severe life-threatening anaphylaxis in the patient and require more careful evaluation. Typically, these reactions occur within minutes of exposure to the relevant allergen, and most normally occur within 4 hours; possible exceptions might include delayed-onset reactions to rabies and Japanese encephalitis vaccines.9Nilsson L. Brockow K. Alm J. Cardona V. Caubert J.C. Gomes E. et al.Vaccination and allergy: EAACI position paper, practical aspects.Pediatr Allergy Immunol. 2017; 28: 628-640Crossref PubMed Scopus (85) Google Scholar The most common symptoms of acute-onset IgE-mediated hypersensitivity range from urticaria to angioedema to anaphylaxis. Anaphylaxis can occur after exposure to allergens from a variety of sources, including food, venom, drugs, and immunizations. Anaphylaxis is a rare, severe, life-threatening allergic reaction with a rapid onset that involves multiple organ systems and can progress rapidly. Symptoms and signs of anaphylaxis can include but are not limited to generalized urticaria; wheezing; swelling of the mouth, tongue, and throat; difficulty breathing; vomiting; diarrhea; hypotension; decreased level of consciousness; and shock.6Simons F.E.R. Ebisawa M. Sanchez-Borges M. Thong B.Y. Worm M. Kase Tanno L. et al.2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines.World Allergy Organ J. 2015; 8: 32Crossref PubMed Scopus (366) Google Scholar, 7Simons F.E.R. Sampson H.A. Anaphylaxis: unique aspects of clinical diagnosis and management in infants (birth to age 2 years).J Allergy Clin Immunol. 2015; 135: 1125-1131Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 8Lieberman P. Nicklas R.A. Randolph C. Oppenheimer J. Berstein D. Bernstein J. et al.Anaphylaxis–a practice parameter update 2015.Ann Allergy Asthma Immunol. 2015; 115: 341-384Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar, 9Nilsson L. Brockow K. Alm J. Cardona V. Caubert J.C. Gomes E. et al.Vaccination and allergy: EAACI position paper, practical aspects.Pediatr Allergy Immunol. 2017; 28: 628-640Crossref PubMed Scopus (85) Google Scholar, 10Zafack J.G. De Serres G. Rouleau I. Gariépy M.C. Gagnon R. Drolet J.P. et al.Clinical approach used in medical consultations for allergic-like events following immunization: case series report in relation to practice guidelines.J Allergy Clin Immunol. 2017; 5: 718-727Abstract Full Text Full Text PDF Scopus (12) Google Scholar Urticaria characterized by wheals (hives) accompanied by an itching or burning sensation resolves generally within 24 hours. Urticaria can result from immunologic and nonimmunologic mast cell activation. Although allergic triggers, such as stinging insects, foods, and medications (including vaccines), are commonly considered and sometimes confirmed as the cause of acute urticaria, several studies have identified infections (urinary tract and upper respiratory tract) as a cause with rates as high as 81%, whereas others have found foods, food additives, and infections also to be common, with rates of 11% to 13% each.11Radonjic-Hoesli S. Hofmeier K.S. Micaletto S. Schmid-Grendelmeier P. Bircher A. Simon D. Urticaria and angioedema: an update on classification and pathogenesis.Clin Rev Allergy Immunol. 2017; ([Epub ahead of print])Crossref PubMed Scopus (70) Google Scholar Angioedema is a potentially life-threatening adverse event with less well-circumscribed edema than urticaria and mainly involves the deeper subcutaneous tissues, often of the face, oropharynx, or both; tissue involvement is painful rather than pruritic and tends to fade more slowly, usually within 24 to 48 hours.12Jaiganesh T. Weise M. Hollingsworth J. Hughan C. Kamara M. Wood P. et al.Acute angioedema: recognition and management in the emergency department.Eur J Emerg Med. 2013; 20: 10-17Crossref PubMed Scopus (32) Google Scholar Although urticaria and angioedema are considered typical manifestations of immediate-type reactions, they can also occur with delayed reactions. In a delayed reaction these might be the result of non–IgE-mediated processes, such as complement activation, by immune complexes (type 3 hypersensitivity or an Arthus reaction) or other less-well defined mechanisms, including T cell–mediated processes or, less likely, late activation of the IgE system.5Dreskin S.C. Halsey N.A. Kelso J.M. Wood R.A. Hummell D.S. Edwards K.M. et al.International consensus (ICON): allergic reactions to vaccines.World Allergy J. 2016; 9: 32Crossref PubMed Scopus (108) Google Scholar Delayed-type reactions occur commonly within hours or days after exposure, although symptom onset can be delayed up to 2 to 3 weeks. The most common signs of delayed-type reactions are rashes (ie, various morphologic forms of maculopapular eruptions).4Caubet J.C. Ponvert C. Vaccine allergy.Immunol Allergy Clin North Am. 2014; 34: 597-613Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar Some delayed reactions might not be immunologically mediated. Persistent hard nodules at the injection site can involve nonspecific inflammation or irritant reactions usually induced by adjuvants, such as aluminum, and do not necessarily reflect immunologic hypersensitivity to vaccine constituents.13Miliauskas J.R. Mukherjee T. Dixon B. Postimmunization (vaccination) injection-site reactions. A report of four cases and review of the literature.Am J Surg Pathol. 1993; 17: 516-524Crossref PubMed Scopus (56) Google Scholar, 14Lauren C.T. Belsito D.V. Morel K.D. LaRussa P. Case report of subcutaneous nodules and sterile abscesses due to delayed hypersensitivity to aluminum-containing vaccines.Pediatrics. 2016; 138: e20141690Crossref PubMed Scopus (32) Google Scholar Large local vaccine reactions secondary to T-cell infiltration are often associated with prolonged and very effective immunity. Delayed reactions are often self-limiting conditions that do not contraindicate administration of future doses (eg, booster doses) of the same vaccine. Vaccines, similar to other drugs, have the potential to cause allergic reactions. Vaccines contain an active component (the antigen) and additional components. Vaccine antigens can comprise whole organisms or parts of organisms, inactivated toxins (toxoids), or both that induce protective immune responses. Vaccine antigens themselves rarely, if ever, are the cause of hypersensitivity reactions. Rather, hypersensitivity reactions after vaccination are usually due to individual vaccine components, such as egg protein, gelatin, and potentially other additives. The manufacturer's package insert for each of the currently available US vaccines can be found on the US Food and Drug Administration (FDA)'s Web site at http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093833.htm, and these contain a description of that vaccine's manufacturing process, including the amount and purpose of each excipient substance. Many of these components are present in small amounts that are usually insufficient to induce allergic reactions in most patients with possible hypersensitivity to the component. However, patients with unusually high levels of IgE antibody can theoretically react to very small amounts of these antigens and experience severe reactions, including anaphylaxis. Rarely, hypersensitivity to the microbial component itself has been implicated in patients with systemic allergic reactions after immunizations (eg, hypersensitivity to tetanus and diphtheria toxoids, pneumococcus, or Bordetella pertussis antigens).15Stratton K. Ford A. Rusch E. Clayton E.W. Adverse effects of vaccines; evidence and causality. Institute of Medicine, National Academies Press, Washington (DC)2001Google Scholar Delayed urticaria, angioedema, or both and nonspecific skin rashes have been reported frequently (5% to 13%) in patients receiving these vaccines.4Caubet J.C. Ponvert C. Vaccine allergy.Immunol Allergy Clin North Am. 2014; 34: 597-613Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar However, comprehensive allergy testing to confirm an immune-mediated allergic reaction was not performed in the great majority of these reports. Acute-onset hypersensitivity reactions or anaphylaxis are uncommon and occur principally among persons with histories of allergies to egg or other substances.4Caubet J.C. Ponvert C. Vaccine allergy.Immunol Allergy Clin North Am. 2014; 34: 597-613Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar Egg allergy is the most frequent food allergy among children, and sensitization reactions occur most frequently before 5 years of age. Egg allergy might be the cause of hypersensitivity reactions to vaccines.16Echeverria-Zudaire L.A. Ortigosa-del Castillo L. Alonso-Lebrero E. Álvarez-García F.J. Cortés-Álvarez N. García-Sánchez N. et al.Consensus document on the approach to children with allergic reactions after vaccination or allergy to vaccine components.Allergol Immunopathol (Madr). 2015; 43: 304-325Crossref PubMed Scopus (18) Google Scholar Certain commonly used vaccines contain small amounts of residual egg protein (ovalbumin) from the vaccine manufacturing process. Ovalbumin concentrations are not usually reported and can vary among vaccine brands and batches.17Kelso J.M. Influenza vaccine and egg allergy: nearing the end of an evidence-based journey.J Allergy Clin Immunol. 2015; 3: 140-141Abstract Full Text Full Text PDF Scopus (7) Google Scholar Concentrations are usually higher in vaccines cultured on embryonated chicken eggs (influenza, yellow fever, and rabies) and lower for vaccines cultured on fibroblasts of chicken embryos (measles, mumps, and rubella vaccine [MMR; Merck, Whitehouse Station, NJ]). Most studies to evaluate the safety of vaccines containing egg proteins in patients with egg allergy have assessed the influenza vaccines.4Caubet J.C. Ponvert C. Vaccine allergy.Immunol Allergy Clin North Am. 2014; 34: 597-613Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 17Kelso J.M. Influenza vaccine and egg allergy: nearing the end of an evidence-based journey.J Allergy Clin Immunol. 2015; 3: 140-141Abstract Full Text Full Text PDF Scopus (7) Google Scholar Until recently, propagation of the virus in embryonated eggs was integral for the preparation of influenza vaccines, resulting in small amounts of residual ovalbumin in these vaccines. After ACIP's 2010 recommendation for universal annual influenza vaccination of all persons older than 6 months, the total number of influenza vaccine doses distributed in the United States has steadily increased and reached approximately 146 million in the 2016-2017 season (https://www.cdc.gov/flu/professionals/vaccination/vaccinesupply-2016.htm). Egg allergy has been a longstanding concern with influenza vaccination. Egg allergy can be confirmed by a consistent medical history of adverse reactions to egg-containing foods plus skin and/or blood testing for IgE directed against egg proteins. Studies to date have indicated that severe allergic reactions to the currently available egg-based influenza vaccines in persons with egg allergy are rare, and consequently, ACIP has modified its recommendations for this patient group. The current 2017-2018 recommendations for vaccination of patients with egg allergies state that most can receive any licensed and recommended age-appropriate influenza vaccine and no longer have to be monitored for 30 minutes after receiving the vaccine.18Grohskopf L.A. Sokolow L.Z. Broder K.R. Walter E.B. Bresee J.S. Fry A.M. et al.Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices—United States, 2017–18 Influenza Season.MMWR Recomm Rep. 2017; 66: 1-24Crossref PubMed Scopus (252) Google Scholar Patients with severe egg allergies should be vaccinated in a medical setting and supervised by a health care provider who is able to recognize and manage severe allergic conditions. This current official US Centers for Disease Control and Prevention guidance is slightly more restrictive than 2017 season's guidance from the American Academy of Pediatrics Committee on Infectious Diseases, which states that because the rate of anaphylaxis after inactivated influenza vaccine (IIV) administration is not greater in recipients with egg allergy than those without egg allergy or from other universally recommended vaccines, all children with egg allergy of any severity can receive influenza vaccine without any additional precautions beyond those recommended for any vaccine.19Committee on Infectious DiseasesRecommendations for prevention and control of influenza in children, 2017-2018.Pediatrics. 2017; 140: e20172550Crossref PubMed Scopus (10) Google Scholar The American Academy of Pediatrics Committee on Infectious Diseases guidance also states that standard vaccination practice for all vaccines in children should include the ability to respond to rare acute hypersensitivity reactions.19Committee on Infectious DiseasesRecommendations for prevention and control of influenza in children, 2017-2018.Pediatrics. 2017; 140: e20172550Crossref PubMed Scopus (10) Google Scholar Gelatin is an animal protein used widely in foods and medications. Gelatin of either bovine or porcine origin is added to both live and inactivated vaccines as a stabilizing agent. Formerly, allergic reactions afte
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