Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.

All named authors were involved consensus group meetings, retrival of information of drug allergy documentation in different countries and in the discussion and approval of the final manuscript.

Controversies exist with regards to in vivo approaches to delayed immunologically mediated adverse drug reactions (ADR) such as exanthem (maculopapular eruption), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruption. In particular, widespread differences exist between regions and practice on the availability and use of intradermal testing (IDT) and patch testing, the standard drug concentrations used, the use of additional drugs in IDT and patch testing to help determine cross-reactivity, the timing of testing in relation to the occurrence of the adverse drug reaction, the use of testing in specific phenotypes, and the use of oral challenge in conjunction with delayed intradermal and patch testing to ascertain drug tolerance. It was noted that there have been advances in the science of delayed T-cell mediated reactions that have shed light on immunopathogenesis and provided a mechanism of pre-prescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine SJS/TEN in Southeast Asians. Future directions should include the collaboration of large international networks to develop and standardize in vivo diagnostic approaches such as skin testing and patch testing combined with ex vivo and in vitro laboratory approaches.

Dermatological complications involve one of five patients treated with anti-TNF therapy after a 14-year follow-up. Association of cutaneous infections with higher anti-TNF dosing suggests a dose-dependent effect. Discontinuation of anti-TNF therapy due to dermatological complications is required in one out of five patients with psoriasiform lesions, but specific dermatological treatment allows to continue anti-TNF therapy in half of them.

Drug skin tests can reproduce delayed hypersensitivity to drugs and entail a moderate reexposure of patients to offending drugs. Drug patch tests (DPTs) and prick tests can be done with any commercialized form of a drug. In non-severe delayed non-IgE-mediated reactions to drugs, intradermal tests (IDT) with delayed readings have a greater value, but their techniques lack standardization. A negative drug skin test does not exclude the responsibility of a drug, and the drug must be rechallenged in non-severe cases. DPTs are useful in maculopapular rashes, flexural exanthemas, and if done in situ, also in fixed drug eruption. Their best indication is in acute generalized exanthematous pustulosis or drug reaction with eosinophilia and systemic symptoms (DRESS). They should be carried out cautiously, following strict guidelines. Prick tests have a low value but they can sometimes be positive on delayed readings. In non-severe delayed reactions to drugs, intradermal tests with delayed readings are the most sensitive skin tests especially for beta-lactam antibiotics, radiocontrast media, heparins but also some biological agents. The value of patch testing varies according to the implicated drug and the non-immediate adverse drug reaction. In DRESS, DPTs have a good value in testing carbamazepine or proton pump inhibitors but remain negative in testing with allopurinol or salazopyrin. In toxic epidermal necrolysis, DPTs are safe but positive in only 9 to 23 % of the reported cases.

This is the largest population-based study aiming to estimate the prevalence of five chronic skin inflammatory diseases.

Epidermal necrolysis (EN) encompasses Stevens-Johnson syndrome (SJS, < 10% of the skin affected), Lyell syndrome (toxic epidermal necrolysis, TEN, with ≥30% of the skin affected) and an overlap syndrome (10 to 29% of the skin affected). These rare diseases are caused, in 85% of cases, by pharmacological treatments, with symptoms occurring 4 to 28 days after treatment initiation. Mortality is 20 to 25% during the acute phase, and almost all patients display disabling sequelae (mostly ocular impairment and psychological distress).The objective of this French national diagnosis and care protocol (protocole national de diagnostic et de soins; PNDS), based on a critical literature review and on a multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with EN. This PNDS, written by the French National Reference Center for Toxic Bullous Dermatoses was updated in 2017 (https://www.has-sante.fr/portail/jcms/c_1012735/fr/necrolyse-epidermique-syndromes-de-stevens-johnson-et-de-lyell). The cornerstone of the management of these patients during the acute phase is an immediate withdrawal of the responsible drug, patient management in a dermatology department, intensive care or burn units used to dealing with this disease, supportive care and close monitoring, the prevention and treatment of infections, and a multidisciplinary approach to sequelae. Based on published data, it is not currently possible to recommend any specific immunomodulatory treatment. Only the culprit drug and chemically similar molecules must be lifelong contraindicated.

Drug hypersensitivity reactions (DHRs) affect an unknown proportion of the general population, and are an important public health problem due to their potential to cause life-threatening anaphylaxis and rare severe cutaneous allergic reactions. DHR evaluations are frequently needed in both ambulatory and hospital settings and have a complex diagnosis that requires a detailed clinical history and other tests that may include in vitro tests and in vivo procedures such as skin tests and drug provocation tests. Although over the years both European and U.S. experts have published statements on general procedures for evaluating DHRs, a substantial discordance in their daily management exists. In this review, we highlight both the differences and the similarities between the European and U.S. perspectives. While a general consensus exists on the importance of skin tests for evaluating DHRs, concordance between Americans and Europeans exists solely regarding their use in immediate reactions and the fact that a confirmation of a presumptive diagnosis by drug provocation tests is often the only reliable way to establish a diagnosis. Finally, great heterogeneity exists in the application of in vitro tests, which require further study to be well validated.