ペニシリンアレルギーのレビュー
N Engl J Med 2019;381:2338-51.
また、秀逸なレビューがNEJMからです。途中病態生理などわからないことが多かったけどまとめると
・ペニシリンアレルギーがあると個人にも社会にも損失がある
ってところが臨床的に大事かと思いました。
○以下本文抜粋
・1928年にsir Alexander Flemingがpenicillinを発見
→1945年にノーベル賞
・On the basis of a nationwide survey in 1957, covering 827 hospitals in the United States, it was estimated that a total of 1000 penicillin-related deaths occurred during the first 10 years of penicillin use.
・In addition, the increased use of penicillin since 1950 led to estimates that from 1965 to 1968 there had been 300 deaths annually from anaphylactic shock due to penicillin use in the United States, but these data were not verifiable.
・The mean interval between the administration of penicillin and the onset of symptoms was less than 15 minutes in 85% of cases, and most patients died within 1 hour after administration.
Current Epidemiology and Geographic Relevance
・Penicillin is the most common drug allergy identified in medical records, with a prevalence ranging from 6 to 25% across various regions and treatment populations.
・ The incidence of new reports of penicillin allergy in 2007 in the United States was 1.4% for females and 1.1% for males in a study that extracted data from the electronic health records of 411,534 patients who had received care from Kaiser Permanente.
Penicillin and Beta-Lactams
・他のbeta-lactamsと違い、penicillinsはthiazolidine ringをもち、cephalosporins and carbapenemsと違い、R2 or additional side-chain structuresを持たない
・早期のstudiesではpenicillinsとcephalosporinsのcross-reactivityが5%以上と言われてきたが、contamination of the early cephalosporin prepa- rations with penicillins was suspected→現在はpenicillin skin-testに陽性の患者の2%以下がcephalosporinsとcross-reactionがある。
・In 99% of patients with a history of penicillin allergy, a skin test and a challenge with carbapenems are associated with an accept- able side-effects profile
Mechanisms of Penicillin Allergy
・penicillinsがproteins in plasmaと結合してhapten-carrier complexesを形成→アレルギー
Diagnosis of IgE-Mediated Penicillin Allergy
・penicillin reagentsが同定→ the major determinant (penicilloyl polyly- sine), which is penicilloyl coupled to lysine for stabilization as a diagnostic agent; use of a minor- determinant mixture
・the positive predictive value for penicillin skin testing with these reagents was established at 50 to 75%, and the negative predictive value at more than 93%.
Penicillin Skin Testing for IgE-Mediated Reactions
・drug challenges with penicillinがreference standard
・The current negative predictive value with the use of a complete set of major and minor deter- minants is estimated at approximately 98%, with a 2 to 3% rate of false negative reactions after penicillin challenge and generally mild cutaneous reactions
Direct Challenge without Skin Testing for Children
・Penicillin skin testing is safe and effective in the evaluation of children with a history of penicillin allergy.
・These and other studies suggest that a direct penicillin challenge without skin testing is probably appropriate for children with a history of a benign rash but without a history of anaphylaxis
・Other indications for direct challenges include a recorded history of penicillin allergy involving symptoms that are not suggestive of allergy (e.g., nausea or headache), a family history of penicil- lin allergy, unknown reactions, and pruritus without rash.
・A direct penicillin challenge as a general approach is not recommended until larger studies can confirm its safety and effectiveness
Testing for Delayed Penicillin Allergy
・Skin-testing procedures for delayed reactions to penicillins include patch, delayed prick, and intradermal testing
Genetic Risk
Natural History of Penicillin Allergy
Clinical Implications of a Penicillin-Allergy Label
・お金もかかる→A label of penicillin allergy is also costly. Several studies from North America and Europe have documented higher costs of inpatient and outpatient care for patients with penicillin aller- gy,51,52 and it is estimated that penicillin-allergy testing and delabeling lead to cost savings, with the largest study showing a reduction in total health care expenses of $1,915 (in U.S. dollars) per patient per year
Penicillin-Allergy Assessment in Antibiotic Stewardship Programs
・In contemporary clinical practice, more than 90% of patients labeled as allergic to penicillin can safely receive the drug.
・Since the majority of adults with a penicillin-allergy label acquired it in childhood and since more than 90% of patients labeled as allergic to penicillin can have the label removed
Best Clinical Practices for Removing the Penicillin-Allergy Label
Penicillin Desensitization
・Patients with IgE-dependent penicillin allergy, including anaphylaxis, who require penicillin as first-line therapy are candidates for rapid desensitization
