Drug reaction with eosinophilia and systemic symptoms (DRESS) is a heterogeneous, multiorgan and potentially life-threatening drug-hypersensitivity reaction (DHR) that occurs several days or weeks after drug initiation or discontinuation. DHRs constitute an emerging issue for public health, due to population aging, growing multi-organ morbidity, and subsequent enhanced drug prescriptions. DRESS has more consistently been associated with anticonvulsants, allopurinol and antibiotics, such as sulphonamides and vancomycin, although new drugs are increasingly reported as culprit agents. Reactivation of latent infectious agents such as viruses (especially Herpesviridae) plays a key role in prompting and sustaining aberrant T-cell and eosinophil responses to drugs and pathogens, ultimately causing organ damage. However, the boundaries of the impact of viral agents in the pathophysiology of DRESS are still ill-defined. Along with growing awareness of the multifaceted aspects of immune perturbation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the ongoing SARS-CoV-2-related disease (COVID-19) pandemic, novel interest has been sparked towards DRESS and the potential interactions among antiviral and anti-drug inflammatory responses. In this review, we summarised the most recent evidence on pathophysiological mechanisms, diagnostic approaches, and clinical management of DRESS with the aim of increasing awareness on this syndrome and possibly suggesting clues for future research in this field.

Severe drug allergy affects patient hesitancy to new treatments, posing unprecedented challenges to anti-SARS-CoV-2 vaccination campaigns. We aimed to analyze the psychological profile of vaccinees with a history of severe allergy in comparison to subjects with a milder allergy history. Patients attending a dedicated vaccination setting were administered an anonymized questionnaire including clinical data and the State-Trait Anxiety Inventory (STAI) scale (score range 20–80). Patients were also asked whether being in a protected setting affected their attitude toward vaccination. Data are expressed as median (interquartile range). We enrolled 116 patients (78% women), of whom 79% had a history of drug anaphylaxis. The median state anxiety score was 36.5 (30–47.2), while the trait anxiety score was 37 (32–48). State anxiety was higher in those with severe than mild allergy [39 (32–50) vs. 30 (25–37); p < 0.001], with the highest score found in a patient with previous drug anaphylaxis (42.5 [32–51.7]). More than 50% of patients reported that being in a protected setting had lowered their anxiety. Severe allergy is associated with a higher burden of situational anxiety in the setting of vaccination without affecting patient constitutional (trait) levels of anxiety. Vaccination in dedicated facilities might overcome issues related to hesitancy and improve patients’ quality of life.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination is the world’s most important strategy for stopping the pandemic. Vaccination challenges the body’s immune response and can be complicated by hypersensitivity reactions. The autonomic nervous system can modulate the inflammatory immune response, therefore constituting a potential marker to characterize individuals at high risk of hypersensitivity reactions. Autonomic nervous system functionality was assessed through measurement of the heart rate variability (HRV) in subjects with a history of severe allergic reactions and 12 control subjects. HRV parameters included the mean electrocardiograph RR interval and the standard deviation of all normal R–R intervals (SDNN). All measurements were performed immediately before the anti-SARS-CoV-2 vaccination. The median RR variability was lower in the study than in the control group: 687 ms (645–759) vs. 821 ms (759–902); p = 0.02. The SDNN was lower in the study group than in the control group: 32 ms (23–36) vs. 50 ms (43–55); p < 0.01. No correlation was found between age and the SDNN. Autonomic nervous system activity is unbalanced in people with a severe allergy background.

Background: Hypersensitivity reactions to antineoplastic agents are an increasing clinical challenge due to their rising incidence and potential severity. Early allergological assessment and tailored drug re-exposure strategies may allow continuation of essential therapies, although real-world data remain limited. Methods: We conducted a monocentric retrospective observational study including adult oncologic patients with suspected chemotherapy-induced hypersensitivity reactions. Clinical features, allergological work-up, and management strategies were analyzed. The primary outcome was the success rate of drug reintroduction using desensitization or enhanced premedication. Secondary outcomes included skin test positivity rates and the association between cumulative chemotherapy exposure and anaphylaxis. Results: Forty-two patients were included (95% female; median age 57.5 years). Re-exposure was required in 18 patients, and was successful in all patients undergoing desensitization and in 92% of those managed with enhanced premedication. Skin testing was positive in 71% of suspected platinum reactions, 30% of taxanes, and 40% of biologic agent reactions. Anaphylaxis occurred in 26.2% of patients, and a trend toward an association with cumulative chemotherapy exposure was observed; each additional cycle was associated with a 28% increase in the odds of anaphylaxis (adjusted OR 1.28; 95% CI, 1.00–1.63). Conclusions: Desensitization and enhanced premedication allow safe reintroduction of antineoplastic agents. Cumulative chemotherapy exposure is associated with an increased risk of anaphylaxis.

“Leishmaniasis” represents a group of infectious diseases provoked by protozoan parasites belonging to the Leishmania genus. The inoculation of Leishmania into skin may result in 3 different clinical entities (cutaneous, mucosal, or visceral leishmaniasis), and severity depends on both parasite and host factors.¹ Few studies demonstrating Leishmania establishment in the spleen and subsequent splenic marginal zone lymphoma, as a conceivable result of chronic antigenic stimulation, are available.² Nevertheless, very little is known about protozoa persistence into aerodigestive mucosal tissues and its possible long-term sequelae. We present a case of an extranodal natural killer/T-cell lymphoma (ENKTL) of the oropharynx arising in a patient with a previous history of mucosal leishmaniasis (ML).

The present national observational cohort study investigated in patients followed for long COVID—mostly hospitalized during acute infection—the presence, severity and evolution of dyspnea and its functional correlates. Dyspnea was assessed with the modified Medical Research Council (mMRC) dyspnea scale and its functional correlates via six-minutes walking distance (6MWD). A total of 217 individuals were evaluated. The mean difference in 6MWD between patients with and without dyspnea (mMRC score ≥ 1) was 87 m (95%CI 56–117, p < 0.001). Significant declines were observed between four and eight months from COVID-19 in prevalence of dyspnea (from 56.7% to 36.4%, p < 0.001), mean mMRC score (from 0.95 to 0.63, p < 0.001), and proportion of patients with 6MWD ˂ 65% of predicted value (from 15.5% to 9.4%, p = 0.035). Each additional point in mMRC score corresponded to −56.3 m walked at first assessment and to −47.7 m walked at second assessment. In the longitudinal analysis, each unitary mMRC score increase between the two assessments corresponded to a concurrent 6MWD reduction of 22.5 m (95%CI −40.1 to −4.8 m, p = 0.013). Although the prevalence of dyspnea reduced significantly over time, roughly one-third of patients remained affected eight months after COVID-19. The 6MWD was a sensitive measure in capturing the functional correlates of presence, severity and evolution of dyspnea.