Role of minor determinants of amoxicillin in the diagnosis of immediate allergic reactions to amoxicillin

• Published in: Allergy (Copenhagen) 2010-05, Vol.65 (5), p.590-596
• Main Authors: Torres, M.J, Ariza, A, Fernández, J, Moreno, E, Laguna, J.J, Montañez, M.I, Ruiz-Sanchez, A.J, Blanca, M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Allergies; amoxicillin; Amoxicillin - adverse effects; Amoxicillin - immunology; amoxicilloic; Anti-Bacterial Agents - immunology; Antibiotics; Basophil Degranulation Test; Biological and medical sciences; Cell Separation; Chromatography, High Pressure Liquid; Dermatology; Diagnostic tests; diketopiperazine; Diketopiperazines - immunology; Drug Hypersensitivity - diagnosis; Epitopes - immunology; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; IgE; Male; Medical sciences; Middle Aged; minor determinants; Radioallergosorbent Test; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sensitivity and Specificity; Skin Tests - methods; Young Adult
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2009.02245.x

To cite this article: Torres MJ, Ariza A, Fernández J, Moreno E, Laguna JJ, Montañez MI, Ruiz-Sanchez AJ, Blanca M. Role of minor determinants of amoxicillin in the diagnosis of immediate allergic reactions to amoxicillin. Allergy 2010; 65: 590-596. Skin testing of subjects with immediate hypersensitivity to amoxicillin is performed using major and minor determinants of benzylpenicillin plus amoxicillin. However, sensitivity is not optimal, and other determinants need to be considered. We assessed the sensitivity of stable, well-characterized minor determinants of amoxicillin in subjects with immediate allergic reactions to amoxicillin to improve skin test sensitivity. Amoxicillin, amoxicilloic acid, and diketopiperazine were prepared and characterized by reverse-phase HPLC, tested in vivo by skin testing and in vitro by basophil activation test and RAST inhibition assay. Patients with immediate hypersensitivity to amoxicillin were selected: Group A (n = 32), skin test positive just to amoxicillin; Group B (n = 19), skin test positive to benzylpenicillin determinants; Group C (n = 10), skin test negative and amoxicillin drug provocation test positive. In Group A, 27 subjects (81.8%) were skin test positive to amoxicillin, ten (30.3%) to amoxicilloic acid, two (6.1%) to diketopiperacine, and six (18.2%) negative. In Group B, nine (50%) were positive to amoxicillin, eight (42.1%) to amoxicilloic acid, none to diketopiperacine, and nine (50%) negative. In Group C, skin tests were negative. BAT was positive to amoxicillin in 26 patients (50.9%), to amoxicilloic acid in 15 (29.1%), and diketopiperazine in four (7.8%). RAST inhibition studies showed > 50% inhibition in all sera, with the highest concentration of amoxicillin and amoxicilloic acid. The combination of minor determinants of amoxicillin, amoxicilloic acid, and diketopiperazine seems to be of no greater value than the use of amoxicillin alone. Further efforts are needed to find new structures to improve sensitivity in the diagnosis of immediate hypersensitivity to betalactams.