Non-immediate Cutaneous Reactions to Beta-Lactams: Approach to Diagnosis

  • Antonino Romano
  • Rocco Luigi Valluzzi
  • Cristiano Caruso
  • Michela Maggioletti
  • Francesco Gaeta
Allergic Skin Diseases (L Fonacier, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Allergic Skin Diseases


Non-immediate cutaneous reactions (i.e., occurring at least 1 h after the initial drug administration), particularly maculopapular exanthemas and urticarial eruptions, are common during beta-lactam treatments. A T cell-mediated pathogenic mechanism has been demonstrated in some cutaneous reactions, such as maculopapular exanthema, fixed drug eruption, acute generalized exanthematous pustulosis, and drug-induced hypersensitivity syndrome. In the diagnostic work-up, patch testing is useful, together with delayed-reading intradermal testing. Patch tests are a simple and safe diagnostic tool, which in the case of severe reactions should be used as the first line of investigation. However, patch tests are less sensitive than intradermal tests, which are preferable in subjects with mild reactions. Lymphocyte transformation or activation tests and enzyme-linked immunosorbent spot assays can be used as complementary tests. In selected cases of mild or moderate reactions, displaying negative results in the aforesaid allergy tests, a graded challenge with the implicated beta-lactam can be performed.


Beta-lactam allergy Challenges Cross-reactivity Non-immediate reactions Skin tests Tolerability 



Acute generalized exanthematous pustulosis


Amoxicillin plus clavulanic acid




Cutaneous adverse drug reaction(s)


Drug-induced hypersensitivity syndrome


Drug provocation test(s)


Drug reaction with eosinophilia and systemic symptoms


Enzyme-linked immunosorbent spot


European network for drug allergy


Fixed drug eruption(s)


Intradermal test(s)


Lymphocyte transformation test(s)


Minor determinant


Minor determinant mixture


Maculopapular exanthema(s)




Patch test(s)


Symmetrical drug-related intertriginous and flexural exanthema


Stevens-Johnson syndrome


Skin prick test(s)


Skin test(s)


Toxic epidermal necrolysis


Compliance with Ethical Standards

Conflict of Interest

Drs. Romano, Valluzzi, Caruso, Maggioletti, and Gaeta declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance•• Of major importance

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Antonino Romano
    • 1
    • 2
  • Rocco Luigi Valluzzi
    • 1
    • 3
  • Cristiano Caruso
    • 1
  • Michela Maggioletti
    • 1
  • Francesco Gaeta
    • 1
  1. 1.Allergy Unit, Presidio ColumbusRomeItaly
  2. 2.IRCCS Oasi Maria S.STroinaItaly
  3. 3.Department of Pediatrics, Division of AllergyPediatric Hospital Bambino GesùRomeItaly

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