Background. Lymphocyte transformation test (LTT) has been widely used to evaluate non-immediate drug hypersensitivity reactions (NIDHRs). However, the lack of standardisation and the low sensitivity have limited its routine diagnostic use. The drug presentation by dendritic cells (DCs) and the assessment of proliferation on effector cells have shown promising results. Flow-cytometry-based methods can help apply these improvements. We aimed to assess the added value of using drug-primed-DCs and the determination of the proliferative response of different lymphocyte subpopulations in NIDHRs. Methods. Patients with confirmed NIDHR were evaluated by both conventional (C-LTT) and with drug-primed-DCs LTT (dDC-LTT) analysing the proliferative response in T-cells and other effector cell subpopulations by using the fluorescent molecule, carboxyfluorescein diacetate succinimidyl ester. Results. The C-LTT showed a significantly lower sensitivity (33.3%) compared with dDC-LTT (65.2%), which was confirmed analysing each particular clinical entity: SJS-TEN (62.5% vs 87.5%), MPE (14.3% vs 41.7%), and AGEP (33% vs 80%). When including the effector cell subpopulations involved in each clinical entity, CD3++CD4+Th1 cells in SJS-TEN, CD3++CD4+Th1+NK cells in MPE, and CD3++NK cells in AGEP, we could significantly increase the sensitivity of the in vitro test to 100%, 66.6%, and 100%, respectively. With an overall sensitivity of 87% and 85% of specificity in NIDHR. Conclusions. The use of a flow-cytometry-based test, DCs as drug presenting cells, and focussing on effector cell subpopulations for each clinical entity significantly improved the drug-specific proliferative response in NIDHRs with a unique cellular in vitro test.

Background: Although ibuprofen and other arylpropionic acid derivatives (APs) are among the non-steroidal anti-inflammatory drugs (NSAIDs) most consumed worldwide at all age ranges, little is known about hypersensitivity to this group of drugs. Our aim was to characterise in detail patients reporting hypersensitivity reactions induced by APs. Methods: We prospectively evaluated patients with symptoms suggestive of hypersensitivity to APs and analysed their clinical characteristics, the reported reactions, and the diagnosis approach. Results: A total of 662 patients confirmed as hypersensitive to APs were included: 489 as cross-reactive (CR) hypersensitivity type (73.86%) and 173 as selective responders (26.13%) (SR). The percentage of subjects reporting reactions induced by ibuprofen and dexketoprofen was higher in CRs (p=0.005 and p=0.01, respectively), whereas reactions induced by naproxen and ketoprofen were more frequent in SRs (p=0.0002 and p=0.00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria combined or not with angioedema in both NIUA and SNIUAA. NPT-LASA was positive in 156 cases (77.14% of NERD and 68.18% of blended) and DPT to ASA was needed in 246 (50.3%) CR patients. In 28 SR cases (25 SNIUAA and 3 SNIDR), DPT with the culprit AP was required. Conclusions: Skin is the most common organ involved in hypersensitivity to APs, in both CR and SR, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are needed to clarify the underlying mechanism in DHR induced by APs.

Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.