Penicillin minor determinants: History and relevance for current diagnosis.

OBJECTIVE: To review the history of the penicillin minor determinants and evaluate their relevance for current diagnosis. DATA SOURCES: Skin testing to detect immunoglobulin E (IgE) sensitivity to penicillins in patients with a history of penicillin allergy has been the subject of more than 55 years of published research involving tens of thousands of patients. STUDY SELECTIONS: Selection of data was based on its relevance to the objective of this article. RESULTS: It was established early on that testing with the major penicilloyl determinant using the polyvalent penicilloyl-polylysine (PPL) is negative in a substantial portion (10% to 64%, including recent increases) of those at risk for immediate hypersensitivity reactions. A variety of minor penicillin determinants are clinically significant in that their use in skin testing is essential to detect all those at risk. In particular, a minor determinant mixture of benzylpenicillin, benzylpenicilloate, and benzylpenilloate, used in conjunction with PPL, has been shown in numerous studies to achieve an average negative predictive value (NPV) of 97.9% in history-positive patients. Benzylpenicillin alone, as the sole minor determinant, leaves many skin test-positive patients undiscovered. Use of amoxicillin as an additional minor determinant reagent appears to identify another 2% to 8% of skin test-positive patients in some populations. CONCLUSION: IgE skin testing, using both the major and appropriate minor determinants of penicillin, can identify, with a high degree of reliability (NPV ∼97%), penicillin allergy history-positive patients who can receive beta-lactam antibiotics without concern for serious acute allergy, including anaphylaxis. The few false-negative skin tests reported globally are largely confined to minor, self-limited cutaneous reactions.

Community Private Practice Clinical Experience with Peanut Oral Immunotherapy.

BACKGROUND: Peanut oral immunotherapy is an effective treatment for desensitizing peanut-allergic patients, but the frequency of adverse reactions has limited its widespread use. OBJECTIVE: To review the frequency of adverse reactions that patients on peanut oral immunotherapy experience during build-up and maintenance phases and explore factors that may contribute to adverse events. METHODS: A retrospective chart review of children and adults with peanut allergy undergoing peanut oral immunotherapy at the New England Food Allergy Treatment Center in West Hartford, Conn was performed. Data on patient demographics, allergic profile, peanut allergy testing, and details of reactions in build-up and maintenance phases were collected. A systemic reaction was defined as one of the following: (1) severe reaction involving 1 system, such as generalized hives and/or angioedema; (2) 2 or more of the following symptoms: cutaneous or oral, respiratory, or gastrointestinal symptoms; (3) drop in blood pressure; or (4) need for epinephrine. RESULTS: Data were available on 783 patients aged 3.5 to 48.3 years. During buildup, 78 patients (10%) experienced at least 1 systemic reaction, 660 (84%) at least 1 gastrointestinal adverse event, 369 (47%) at least 1 cutaneous adverse event, and 157 (20%) at least 1 respiratory adverse event. Thirty-four patients (4%) required epinephrine during buildup. Six hundred ninety-seven patients (89%) completed buildup and progressed to maintenance. During maintenance, 131 patients (19%) experienced at least 1 systemic reaction, 190 (27%) at least 1 gastrointestinal adverse event, 104 (15%) at least 1 cutaneous adverse event, and 50 (7%) at least 1 respiratory adverse event. Seventy-four patients (11%) required epinephrine during maintenance. None of the adverse events required hospitalizations, and there were no mortalities. Nine patients (1%) were diagnosed with eosinophilic esophagitis during buildup or maintenance. Increasing pretreatment peanut specific IgE levels were associated with increased odds of a systemic reaction during buildup. Increasing age, pretreatment peanut specific IgE level, and a systemic reaction in buildup were associated with increased odds of a systemic reaction during maintenance. CONCLUSIONS: Peanut oral immunotherapy may be an effective and safe treatment for carefully selected peanut-allergic patients under the guidance of experienced providers. Specific patient characteristics and immunologic factors may help predict adverse events.

Penicillin Allergy Evaluation: A Prospective, Multicenter, Open-Label Evaluation of a Comprehensive Penicillin Skin Test Kit.

BACKGROUND: Ten percent of the population claims an allergy to penicillin, but 90% of these individuals are not allergic. Patients labeled as penicillin-allergic have higher medical costs, longer hospital stays, are more likely to be treated with broad-spectrum antibiotics, and develop drug-resistant bacterial infections. Most penicillin skin test reagents are not approved by the Food and drug Administration or readily available to evaluate patients labeled penicillin-allergic. OBJECTIVE: To determine the negative predictive value (NPV) of the Penicillin Skin Test Kit containing the major allergenic determinant (penicilloyl polylysine), a minor determinant mixture (penicillin G, penicilloate, penilloate), and amoxicillin, produced according to Food and Drug Administration standards. METHODS: This was a prospective, multicenter, open-label investigation of penicillin skin testing using the Penicillin Skin Test Kit. Skin test-negative subjects were challenged with 250 mg amoxicillin, whereas skin test-positive patients were not challenged. The primary end point was NPV of the Penicillin Skin Test Kit, defined as the percentage of subjects with negative skin test results who did not experience an IgE-dependent reaction within 72 hours of amoxicillin challenge. RESULTS: In total, 455 patients with a history of penicillin allergy underwent skin testing and 63 (13.8%) had 1 or more positive test results; 65% of the positive test results were to the minor determinant mixture and/or amoxicillin alone. In the per protocol group of 373 skin test-negative subjects, 8 developed potential IgE-dependent reactions following oral amoxicillin challenge, translating to an NPV of 97.9% (95% CI, 95.8-99.1; P < .0001). All but 1 of the reactions was mild or moderate, and most subjects who required treatment received only antihistamines. CONCLUSIONS: The Penicillin Skin Test Kit, containing all relevant penicillin allergenic determinants, demonstrated very high NPV. Removal of a penicillin allergy label in a large majority of currently mislabeled patients has substantial personal and public health implications.

Oral immunotherapy for peanut allergy: multipractice experience with epinephrine-treated reactions.

BACKGROUND: Peanut allergy creates the risk of life-threatening anaphylaxis that can disrupt psychosocial development and family life. The avoidance management strategy often fails to prevent anaphylaxis and may contribute to social dysfunction. Peanut oral immunotherapy may address these problems, but there are safety concerns regarding implementation in clinical practice. OBJECTIVE: The purpose of this report is to communicate observations about the frequency of epinephrine-treated reactions during peanut oral immunotherapy in 5 different allergy/immunology practices. METHODS: Retrospective chart review of peanut oral immunotherapy performed in 5 clinical allergy practices. RESULTS: A total of 352 treated patients received 240,351 doses of peanut, peanut butter, or peanut flour, and experienced 95 reactions that were treated with epinephrine. Only 3 patients received 2 doses of epinephrine, and no patient required more intensive treatment. A total of 298 patients achieved the target maintenance dose for a success rate of 85%. CONCLUSION: Peanut oral immunotherapy carries a risk of systemic reactions. In the context of oral immunotherapy, those reactions were recognized and treated promptly. Peanut oral immunotherapy may be a suitable therapy for patients managed by qualified allergists/immunologists.