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Gianenrico Senna,1,2 Maria Aliani,3 Elena Altieri,4 Pietro Bracciale,5 Luisa Brussino,6 Maria Filomena Caiaffa,7 Paolo Cameli,8 Giorgio Walter Canonica,9,10 Cristiano Caruso,11 Maria D’Amato,12 Fausto De Michele,13 Stefano Del Giacco,14 Fabiano Di Marco,15 Francesco Menzella,16 Girolamo Pelaia,17 Paola Rogliani,18,19 Micaela Romagnoli,20 Pietro Schino,21 Jan Walter Schroeder,22 Alessandra Vultaggio,23 Sara Rizzoli,24 Alessandro Zullo,24 Silvia Boarino,25 Marilena Palmisano,26 Alessandra Rossi,26 Gianfranco Vitiello,26 Stefano Centanni27 1Department of Medicine, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 3UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 4Reparto di Pneumologia, P.O., Garbagnate Milanese, Italy; 5Reparto di Pneumologia, Ospedale Ostuni, Ostuni, BR, Italy; 6Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I, Torino, Italy; 7Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 8Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy; 9Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy; 10Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano, MI, Italy; 11Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 12UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 13UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 14Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 15Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 16UOC Pneumologia, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna, TV, Italy; 17Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 18Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 19Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 20UOC Pneumologia, ULSS 2 Marca Trevigiana, Treviso, Italy; 21Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti, BA, Italy; 22Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 23Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 24Medineos Observational Research - An IQVIA Company, Modena, Italy; 25Medical Evidence R&I, AstraZeneca, Milano, Italy; 26Medical Affairs R&I, AstraZeneca, Milano, Italy; 27Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, ItalyCorrespondence: Marilena Palmisano, Medical Affairs R&I, AstraZeneca, Milano, Italy, Email marilena.palmisano@astrazeneca.comPurpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300– 450 cells/mm3 subset of patients.Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300– 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected.Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300– 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300– 450 subset showed similar reductions in AER (− 94.8% vs − 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered.Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300– 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300– 450 patients as in the total population.Keywords: severe eosinophilic asthma, blood eosinophil count, benralizumab, observational, real-world evidence, real-life

At the end of December 2020, the anti-SARS-CoV2 vaccination campaign began in Italy. As the number of vaccinated subjects in the general population has increased, several adverse reactions have been observed and reported. Severe cutaneous adverse reactions (SCARs) induced by drugs or vaccines are rare but distinguished by high mortality and include DRESS syndrome or drug induced hypersensitivity syndrome (DiHS), a condition characterized by skin rash, eosinophilia, fever, lymphadenopathy, and involvement of one or more internal organs. Here we present a definite case of DRESS that occured following the administration of Pfizer/BioNTech COVID 19 vaccine. He required hospitalization and was managed with supportive care, antihistamines, and intravenous steroid.

Airborne anaphylaxis is a rare disorder defined by the occurrence of anaphylactic reactions to inhaled allergens, which may arise not only in occupational exposure but also in common settings. Foods are the most common cause of airborne anaphylaxis, even organic mixtures scents. The other important cause is represented by drugs, while in the wide range of other causes, there are often reports on unique cases. This review aims to make an overview about the potential causes of airborne anaphylaxis, by analysing what is described in literature on this topic.Concerning epidemiology, no data on specific prevalence of airborne allergy in adults are available. To date, only one study evaluated the specific prevalence of airborne allergy with anaphylaxis to foods in children, resulting in 5.9% of reactions due to exposure to aerosolized foods, compared with 78% of reactions caused by food ingestion. In addition to anaphylaxis, airborne-related reactions may also present with symptoms such as rhino-conjunctivitis, wheezing, dyspnoea and asthma.A detailed anamnesis facilitates a correct diagnosis, which allows appropriate therapeutic and preventive interventions, but, similarly to rare diseases in general, only specialized doctors are able to implement it. The assumption of the approach used in emergency medicine for other causes of anaphylaxis, that is referring the patient at discharge to an allergist who will teach the basic notions to recognize symptoms and access the appropriate therapy, would allow the patient to avoid situations of serious danger.

Chronic spontaneous urticaria (CSU) is a benign skin disorder usually responsive to treatment; however, at times it can be difficult to control and become very debilitating. We discuss the case of a woman with CSU that was unresponsive to H1-antihistamines who was treated with omalizumab and became pregnant during omalizumab treatment. We also considered the follow-up of the mother and newborn for 4 years after delivery. Our case report confirms that omalizumab is a safe and effective therapeutic option, after careful evaluations in terms of cost-effectiveness, in pregnant and lactating women with severe chronic urticaria. Assessment throughout follow-up confirmed a regular progression of pregnancy parameters and no adverse reaction was documented in the child from birth to 4 years of age.

Purpose: In the era of precision medicine, target-therapy with monoclonal antibodies (mAb) has enabled new treatment options in patients affected by eosinophilic granulomatosis with polyangiitis (EGPA). Nevertheless, sometimes unsatisfactory results at a nasal level may be observed. The aim of this study is to describe reboot surgery as a potential adjuvant strategy in multi-operated, yet uncontrolled EGPA patients treated with Mepolizumab. Methods: We performed reboot surgery on EGPA patients with refractory CRSwNP. We obtained clinical data, nasal endoscopy, nasal biopsy, and symptom severity scores two months before surgery and 12 months after it. Computed tomography (CT) prior to surgery was also obtained. Results: Two patients were included in the study. Baseline sinonasal disease was severe. Systemic EGPA manifestations were under control, and the patients received previous mepolizumab treatment and previous surgery with no permanent benefits on sinonasal symptoms. Twelve months after surgery, nasal symptoms were markedly improved; endoscopy showed an absence of nasal polyps and there were fewer eosinophils at histology. Conclusions: We presented the first experience of two EGPA patients with refractory CRSwNP who underwent non-mucosa sparing (reboot) sinus surgery; our results support the possible adjuvant role of reboot surgery in this particular subset of patients.

DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its severity by analyzing the clinical conditions and therapies preceding the reaction. We conducted a retrospective analysis on patients admitted to our center between 2010 and 2020 who were discharged with a diagnosis of DRESS. We used the RegiSCAR diagnostic criteria. We defined the severity of DRESS using the criteria of Mizukawa et al. We included 25 patients (15 females) with a median age of 66 years. Skin involvement, eosinophilia, and liver injury were the most important aspects. Allopurinol was found to be the most involved drug. Reaction severity was significantly associated with the number of daily medications (p = 0.0067) and an age of at least 68 years (p = 0.013). In addition, 75% of severe cases had at least three comorbidities in history, and most of the severe cases were female. In our study the advanced age, the high number of comorbidities and home therapies, and the inflammatory state were found to be predisposing elements to the development of the disease and its severity.

Biointerphases 16(1), 011004 (1-8) (2021). doi:10.1116/6.0000593, X-ray fluorescence analysis enables the study of trace element distributions in biological specimens. When this analysis is done under cryogenic conditions, cells are cryofixed as closely as possible to their natural physiological state, and the corresponding intracellular elemental densities can be analyzed. Details about the experimental setup used for analysis at the P06 beamline at Petra III, DESY and the used cryo-transfer system are described in this work. The system was applied to analyze the elemental distribution in single HeLa cells, a cell line frequently used in a wide range of biological applications. Cells adhered to silicon nitride substrates were cryoprotected within an amorphous ice matrix. Using a continuous scanning scheme and a KB x-ray focus, the distribution of elements in the cells was studied. We were able to image the intracellular potassium and zinc levels in HeLa cells as two key elements relevant for the physiology of cells., Published by AVS, New York, NY

Background: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen–hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen–allergic patients. Patients: A total of 835 cypress pollen–hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. Results: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein–allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. Conclusion: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Introduction: Allergy to Hymenoptera venom (HV) may lead to life-threatening anaphylaxis. Some of the factors influencing the symptom’s severity are still undetermined. The aim of this study was to identify the clinical aspects associated with the most severe reactions in a population with HV allergy, by comparing clinical and immunochemical biomarkers between patients with previous local large reactions (LLRs) and systemic reactions (SRs). Methods: We selected adult patients with a history of HV allergy, with positive diagnostic tests and a correlation with one single Hymenoptera species. Age, gender, atopy, serum basal tryptase (sBT) value, total IgE, venom-specific IgE, history of hypertension, cardiovascular diseases, and hypercholesterolemia were compared between patients with previous LLRs and SRs. Results: 460 adult patients (381 SRs, 79 LLRs) were included. Age (p = 0.0097), male gender (p < 0.0001), arterial hypertension (p = 0.046), hypercholesterolemia (p = 0.009), and higher sBT levels (p = 0.0004) were significantly associated with severe reactions as independent variables. Moreover, considering the previous variables as risk factors, there was a significant and progressive increase in the odds of being Mueller III + IV as the number of positive variables increased. Patients with sBT ≥6.4 ng/mL adjusted for any of the positive variables had increased the risk of Mueller grade IV reaction (p < 0.0001). Conclusion: According to our results, older age, male gender, arterial hypertension, hypercholesterolemia, and increased levels of sBT ≥6.4 ng/mL are risk factors for severe anaphylaxis to HV in adults. Atopy and allergic asthma do not increase the risk of HV-induced SRs.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis associated with asthma, anti-neutrophil cytoplasmic antibodies (ANCA) positivity, and tissue eosinophilia. Objective: To describe the presenting clinical features, significant biochemical alterations, and also potential pathogenic factors in adult patients diagnosed in our Center over a period of >20 years. Method: A retrospective study of EGPA patients diagnosed from 1994 to 2019 at ASST Grande Ospedale Metropolitano Niguarda Ca’ Granda, Milan (Italy), which was performed according to the 1990 American College of Rheumatology criteria and Chapel Hill Consensus Conference definition. A dataset was compiled, registering demographic and clinical features, biochemical analysis at onset, and also the therapies received 3 months prior to EGPA diagnose. Statistical analyses were subsequently conducted dividing patients in 2 groups based on ANCA positivity and comparing them. Results: Two groups were clearly identified by ANCA serology and specific organ involvement in accordance with literature reports; however, our data underline for the first time the association between anti-leukotriene receptor antagonists (LTRAs) and ANCA positivity. The group of previously treated patients presents an OR of 6.42 to be ANCA positive. This finding could be attributed to an imbalanced stimulation of leukotriene receptors, inducing both mast cells activation and an increased neutrophil extracellular traps release from neutrophils. Conclusion: Despite the limitations of this retrospective study, the association between LTRAs and ANCA antibodies elucidates the mechanism by which innate immunity is directly involved in tolerance breakdown and autoantibodies production. Validation of our results with targeted studies could clarify the differences between ANCA-positive and ANCA-negative patients with important consequences on the use of some drug classes in the treatment of EGPA and asthmatic subjects.

Necrotizing eosinophilic myocarditis (NEM) is a life-threatening condition that needs rapid diagnosis by endomyocardial biopsy and hemodynamic support usually by mechanical circulatory systems. We present the case of a 25-year-old Caucasian man who developed a refractory cardiogenic shock due to a NEM that was supported with a peripheral veno-arterial extracorporeal membrane oxygenation associated with intravenous steroids and recovered after 2 weeks. Further instrumental investigations lead to the final diagnosis of NEM as first presentation of eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), remarking the importance of identifying the systemic disorder that usually triggers the eosinophilic damage of the myocardium.

Background Anticonvulsant hypersensitivity syndrome represents a rare but potentially fatal kind of adverse drug reaction. This clinical picture often hampers the flexibility with which alternative anticonvulsants or even other classes of drugs are prescribed in these patients, negatively affecting the efficacy of treatment and the course of the disease. The aim of this study was to analyse a group of six patients with severe cutaneous drug reactions induced by anticonvulsants and to report which alternative antiepileptic drugs and which drugs of other classes were tolerated. Case presentation A total of six patients (2 males and 4 females, age 11–73 years) are described in this study. In all the patients the onset of the severe cutaneous drug reactions was 2–4 weeks after initiating the anticonvulsant therapy: 2 out of 6 patients presented with a drug reaction with eosinophilia and systemic symptoms under therapy with phenytoin; 2 out of 6 presented with Stevens–Johnson syndrome under therapy with lamotrigine; and 2 out of 6 presented with a toxic epidermal necrolysis, one of them under therapy with valproic acid, and the other one under therapy with lamotrigine. Alternative anticonvulsants tolerated after the reaction were: clonazepam, levetiracetam, diazepam, delorazepam and lormetazepam. Conclusions In our cases we observed that non aromatic anticonvulsants and benzodiazepines were well tolerated as alternative treatments in six patients with reactions to aromatic anticonvulsivants and that the risk of hypersensitivity reactions to other drug classes was not increased as compared to general population.

An electrotactile feedback system (EFS) is a specific form of biofeedback using electrocutaneous stimulation and can help people with problems of pressure estimation caused by a sensation loss in their feet to maintain their balance and reduce the risk of falls. In this research project embedded software has been designed and tested on a wearable EFS that tackles the problem of improving balance control for impaired individuals. The program has several inventive features. An intelligent agent was implemented to process information from the sensor system and taking an action in the form of electrocutaneous stimulation. In a training routine the force sensor system is calibrated and COP information obtained. Furthermore the software detects individual parameters of the wearer by testing the sensation threshold for electrocutaneous stimulation. The system uses artificial intelligence (AI), in form of a simple reflex agent (SRA) to prevent harmful or unwanted feedback. A preliminary test was performed to test the repeatability of the sensory threshold detection and showed a high repeatability. The developed software has several novel components and can be integrated in innovative wearable EFS that can be used by people with sensory impairment to improve their ability of controlling their balance and thus preventing falls.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are represented by rare but life-threatening cutaneous adverse reactions to different drugs. Previous studies have found that in a Han Chinese population from Taiwan and other Asian Countries, a strong genetic association between HLA-class I alleles (B*15:02, B*58:01) and SJS and TEN was induced by carbamazepine and allopurinol, respectively. To identify genetic markers that covered the MHC region, we carried out a case-control association enrolling 20 Caucasian patients with SJS/TEN. Our patient series included 10 cases related to paracetamol, 7 to allopurinol and 3 to different drugs (plaquenil, itraconazol, nabumetone). Healthy controls were represented by 115 Caucasian bone marrow or stem cell donors. The HLA-A*, B*, C*, DRB1*, DQB1*, DQA1* and DPB1* genotyping were determined. The frequencies of HLA-A*33:03 as well as C*03:02 and C*08:01 were significantly higher in SJS/TEN patient subgroup showing allopurinol drug-induced severe cutaneous adverse reactions (SCAR) as compared to controls (28.6% vs 0%, P=0.00002, Pc=0.0011; 28.6% vs 0%, P=0.00002, Pc=0.001; 28.6% vs 0%, P=0.00002, Pc=0.001, respectively). In the same subgroup the frequencies of B*58:01, DRB1*15:02 and DRB1*13:02 alleles, although considerably higher than in control group (42.8% vs 5.2%, P=0.003; 28.6% vs 1.7%, P=0.005; 28.6% vs 3.5%, P=0.037, respectively), appeared no more statistically different after P correction (Pc=0.248; Pc=0.29; Pc=1.00, respectively). In addition, in 10 of the 20 SJS/TEN patient subgroup with paracetamol-induced SCAR no statistically significant association with HLA alleles could be found. However, in the same SJS/TEN patient subgroup showing allopurinol drug-induced SCAR, haplotype analysis indicated that B*58:01, DRB1*13:02 and DRB1*15:02 alleles, that in a single allele analysis lost statistical significance after P correction, may still confer susceptibility, because the B*58:01-DRB1*13:02 and DRB1*15:02-DQB1*05:02 are positively associated with the disease (14.2% vs 0.43%, P= 0.00001, Pc=0.00028; 14.2% vs 0.43%, P=0.00001, Pc=0.00028, respectively). Our results show that in contrast to SCAR-related to paracetamol, where HLA alleles do not appear to be involved, HLA molecules behave as a strong risk factor for SCAR-related to allopurinol even when a limited number of patients are considered.

Human skin deformation occurs due to external loading. As a result, blood flow in soft tissue becomes low and also the oxygenation decreases. Tissue under continuous loading results in tissue necrosis and leads to pressure ulcer (PU), also known as bedsore, decubitus ulcer, and ischemia. The amount of external load applied to the body support surface is associated with a subject's BMI (body mass index). Therefore interface pressure (IP) at the skin and the surface is the result of a subject's physical and support surface properties. Interface pressure increases, the blood flow decreases and a subject starts developing stage-1 pressure ulcer. Previous research suggests that interface pressure of 32 mmHg (4.26 kPa) can cause PU, but there is no strong evidence to show at what time that pressure is reached. Also interface pressure changes from subject to subject due to their body compositions. Three risk assessment scales are available to predict overall risk of PU formation. But none of these scales take interaction of body support surface materials into account. Also these do not provide any information at which area a subject is at risk of PU formation. In this work a study is presented where external load at different bony areas are measured using 11 volunteers. By measuring the external load for 11 subjects (age:33 ± 7 yrs and BMI:25.04 ± 3.01 kg/m2) at different bony areas, the relationship with the total body weight was identified. A mathematical model is proposed to predict the risk of PU formation combining the Waterlow risk assessment scales for bony areas and a graphic user interface to predict this is discussed.

Background Hypersensitivity reactions to anaesthetic agents are rare but often severe, with a mortality ranging from 4 to 9% in IgE-mediated events. Identification of the risk factors may contribute to limit the incidence of these reactions. The aim of our study was to search for possible risk factors of severe perioperative hypersensitivity reactions in our study population. Methods For this study we retrospectively reviewed data from 193 patients who experienced drug hypersensitivity reactions during general anaesthesia. The diagnostic protocol consisted of 1) history of the reaction, 2) measurement of serum baseline tryptase and specific IgE-assays for latex, beta-lactams and succinylcholine, 3) skin tests for the agents listed in the anaesthesia chart and for others likely to be safe for future use, latex, and others medications administered during the perioperative period (i.e. antibiotics), 4) subdivision of our patients on the basis of two criteria: a) grade of severity of clinical reactions according to the Ring and Messmer classification; b) results of skin tests and/or serum specific IgE-assays. Results One hundred of 193 patients had reactions of grade I, 32/193 patients had reactions of grade II, 55/193 patients had reactions of grade III and 6/193 patients had reactions of grade IV. A diagnosis of IgE-mediated reaction was established in 55 cases (28.50%); the most common causes were neuromuscular blocking agents, followed by latex and beta-lactams. Severe reactions were associated with older age (p = 0.025), asthma (p = 0.042), history of hypertension (p = 0.001), intake of serum angiotensin converting enzyme inhibitor medication (p = 0.012) or serum angiotensin II antagonist (p = 0.033), higher levels of basal tryptase (p = 0.0211). Cardiovascular symptoms (p = 0.006) and history of hypersensitivity to antibiotics (p = 0.029) were more frequently reported in IgE-mediated reactions. Conclusions We confirmed the relevance of several clinical features as risk factors for anaphylactic reactions induced by anaesthetic agents: older age, asthma, hypertension and antihypertensive drugs. We observed increased levels of serum basal tryptase in severe reactions: this finding may signify that this biomarker is useful for the identification of patients at risk. Electronic supplementary material The online version of this article (doi:10.1186/s12948-015-0017-9) contains supplementary material, which is available to authorized users.

Background One of the greatest challenges in cardiovascular medicine is to define the best tools for performing an accurate risk stratification for the recurrence of ischemic events in acute coronary syndrome (ACS) patients. Methods We followed 65 ACS patients enrolled in a previous pilot study for 2 years after being discharged, focusing on the occurrence of major adverse cardiovascular events (MACE). The relationship between serum tryptase levels on admission, SYNergy between percutaneous coronary intervention with the TAXUS drug-eluting stent and the cardiac surgery score (SX-score), cardiovascular complexity and MACE at 2 years follow-up were analyzed. Results The ACS population was divided in two groups: patients with MACE (n = 23) and patients without MACE (n = 42). The tryptase measurement at admission (T0) and at discharge (T3) and SX-score were higher in patients who experienced MACE than in those without (p = 0.0001, p

A 46 year old woman from Sri Lanka, underwent blood examination after her return to Italy and found high titers of uric acid (8.2 mg/dl), thus her family physician prescribed allopurinol 300 mg once daily. After 3 weeks she presented to the ER with fever and esantematic rash on the thorax and limbs, therefore allopurinol was stopped and began prednisone 25 mg/day. A week later she returned to the ER for a worsening of the cutaneous eruption, high fever and marked weakness. The admitting physician excluded an adverse drug reaction and was admitted to the Infectious diseases ward with altered liver function tests, high inflammation indices and eosinophilia. All the tests for infectious disease workup resulted negative, but her general condition worsened with high fever, anasarcatic status and neurological weakness. The total body CT scan showed lung and abdominal lymphadenopathy and pleural effusion. The bone marrow biopsy excluded a lympho myeloproliferative disorder and revealed two microgranulomas and 34% eosinophils. The hepatic biopsy showed a diffuse acute hepatitis with marked infiltrate of T-lymphocytes (CD3+) and eosinophils. Cardiac examination with EKG and echocardiography was normal but the cardiac MNR dimostrated a severe pericardial inflammation with effusion. Only when the eosinophilic blood concentration raised to 52% the diagnosis of DRESS was made. The patient also resulted positive for HLA-B*58:01. She began treatment with high glucocorticoid i.v. (1 mg/kg/day) and obtained rapid improvement of the general condition of weakness, skin healing by desquamation and normalization of eosinophilia and hepatic function. She was discharged after one month of hospital stay. Conclusion This is a particular case of DRESS with extensive histological, blood, and radiological examination. It is important to employ elevated levels of glucocorticoids in the treatment of DRESS. The normal cardiac screening by EKG and echocardiography may sometimes prove inadequate for identifying real cardiac injury. We believe that it’s important to undergo cardiac MR imaging since appropriate therapy may prevent progression of cardiac disease.

Fluoroquinolones are widely used because of their broad spectrum of activity. Their benefit-risk profile needs careful evaluation as they can induce T cell-dependent reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Here we present two rare cases of SJS/TEN overlap syndrome and SJS caused by levofloxacin. Case 1. A 70-year-old woman with a history of chronic obstructive pulmonary disease was treated with levofloxacin for acute bronchitis. After taking medications for 10 days she complained of generalized skin eruptions and mucosal erosions. On the day of admission in the burn intensive care department 28 % of her body surface was covered by rash, blistering and epidermal peeling; 65 % of body surface presented dusky red skin. Levofloxacin was stopped and our patient was treated with topical solution to keep the wounds moist, fluid replacement, well balanced nutrition, systemic corticosteroids and intravenous immune globulin (IVIG). We also administrated teicoplanin because of S. aureus infection of central i.v. catheter confirmed by a positive culture. She was subsequently treated with meropenem because of a Klebsiella pneumoniae urinary tract infection. The main laboratory findings were: anemia, leukocytosis and increased CRP levels. The diagnosis was performed on the basis of clinical and histological features. Gradually her symptoms improved and the epidermal peeling also subsided. Case 2. A 72-year-old woman was referred to our department with multiple skin lesions involving more than 50 % of the total body surface area occurred after 2 weeks of starting levofloxacin treatment for pneumonia. She developed high fever and had the appearance of a severe burn patient. Laboratory analysis showed anaemia, leukocytosis, hypoalbuminaemia and elevated procalcitonin and CRP. The levofloxacin treatment was stopped immediately and replaced with teicoplanin and meropenem. Subsequently because of A. baumanii complex infection of the central i.v. catheter she was treated also with colistin. Our management included IVIG treatment, intravenous glucocorticoids, proper fluid balance, attention to nutritional status and pain relief. The skin lesions healed within 3 weeks and the patient left our department in good general condition.

Background: Mast cell tryptase has recently been reported to be involved in atherosclerotic plaque destabilization. However, the results of these reports are conflicting. Methods: The aim of this study was to characterize the role of tryptase as a prognostic marker of patient cardiovascular complexity in acute coronary syndrome (ACS). Furthermore, its association with an angiographic scoring system [defined by the SYNergy between percutaneous coronary intervention (PCI) with the TAXUS drug-eluting stent and the cardiac surgery (SYNTAX) score] was examined. The serum tryptase was measured at admission in 65 consecutive ACS patients and in 35 healthy controls. In the patients with ACS, a composite measure of clinical and angiographic patient cardiovascular complexity was indicated by two of the following: clinical adverse events at hospitalization, at least 2 epicardial coronary arteries involved in the atherosclerotic disease, more than 1 stent implanted or more than 2 coronary artery disease risk factors. Results: The tryptase measurements were lower in patients without the composite measure (p < 0.0005). Linear regression showed a significant relationship between tryptase levels and the SYNTAX score (SX-score). Conversely, high-sensitivity troponin values did not correlate with either the composite outcome or the SX-score. The predictive accuracy of serum tryptase for the composite outcome was set at the cut-off point of 5.22 ng/ml (sensitivity 81% and specificity 95.7%). Conclusion: In ACS patients, serum tryptase levels at admission may predict patient cardiovascular complexity more reliably than currently known biomarkers. Further studies are needed to demonstrate the long-term prognostic role of this biomarker in ACS.

Background: The roles played by different peach allergens with respect to symptom severity have not been completely ascertained. We have evaluated the diagnostic efficacy of peach recombinant allergens ImmunoCAP compared to peach in the identification of subjects at an increased risk for severe reactions to peaches. Methods: 148 peach-allergic patients were divided based on their symptom severity into 2 groups: mild oral allergy syndrome (OAS) and severe OAS. Anti-rPru p 1, 3 and 4 IgE levels were measured. Statistical analyses were carried out using parametric and non-parametric tests. Results: anti-rPru p 1 and anti-rPru p 4 IgE levels were significantly higher in patients with mild OAS than in patients with severe OAS (p = 0.0001); in contrast, anti-rPru p 3 IgE levels were significantly higher in patients with severe OAS than in patients with mild OAS (p < 0.00005). Moreover, we found that any unitary increase in anti-rPru p 1 IgE values corresponded to a 2.48% reduction in the odds of having severe OAS (p = 0.048), whereas any unitary increase in anti-rPru p 3 IgE values corresponded to a 9.02% increase in the probability of having severe OAS (p = 0.001). Unexpectedly, we found that patients positive to rPru p 3 as well as rPru p 1 and 4 demonstrated a significant reduction of the odds of developing severe symptoms than those positive to rPru p 3 alone. Anti-rPru p 3 IgE levels were a significantly better indicator than anti-peach IgE values (p = 0.016) of patients with the highest risk for severe OAS. A cutoff of 2.69 kUA/l for anti-rPru p 3 IgE values better discriminated peach-allergic patients at a higher risk for symptoms. Conclusions: Italian patients with positive anti-rPru p 1, 4 and 3 IgE levels seemed less likely to experience the clinical effects of high anti-rPru p 3 IgE values.

Three-dimensional (3D) body surface reconstruction is an important field in health care. A popular method for this purpose is laser scanning. However, using Photometric Stereo (PS) to record lumbar lordosis and the surface contour of the back poses a viable alternative due to its lower costs and higher flexibility compared to laser techniques and other methods of three-dimensional body surface reconstruction. In this work, we extended the traditional PS method and proposed a new method for obtaining surface and volume data of a moving object. The principle of traditional Photometric Stereo uses at least three images of a static object taken under different light sources to obtain 3D information of the object. Instead of using normal light, the light sources in the proposed method consist of the RGBColor-Model's three colors: red, green and blue. A series of pictures taken with a video camera can now be separated into the different color channels. Each set of the three images can then be used to calculate the surface normals as a traditional PS. This method waives the requirement that the object imaged must be kept still as in almost all the other body surface reconstruction methods. By putting two cameras opposite to a moving object and lighting the object with the colored light, the time-varying surface (4D) data can easily be calculated. The obtained information can be used in many medical fields such as rehabilitation, diabetes screening or orthopedics.

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening cutaneous severe adverse reactions (SCAR) most frequently induced by a drug hypersensitivity. The clinical manifestations seem to be related either to a particular group of drugs, such as antibacterial sulfonamides, anticonvulsant agents, allopurinol, non-steroidal anti-inflammatory drugs (NSAIDs), aminopenicillins and quinolones, as well as to the ethnic/genetic background of the affected individual. A relevant problem in these subjects is the selection of a potentially tolerated drug that is less likely to induce a relapse of the reaction on the basis of cross-reactivity. Aim of the present study was to analyse a population of 16 patients that were treated in the burn/intensive care department for a SJS/TEN reaction, and determine the drugs that were tolerated after the reaction with respect to the culprit substances. The diagnosis was performed on the basis of the clinical and histological features according to the RegiSCAR classification and the first step was withdrawal of the offending drug. Among the 16 cases, we found 5 cases of SJS, 8 cases of TEN, and 3 cases of SJS/ TEN overlap. Of the 16, 4 patients were male and 12 were female, age 14-92 years (average 57.1 years; median 63.5 years). A total of 12 drugs were found as suspected causative agents. In 3 cases multiple drugs were suspected, whereas in 13 cases a single drug was implicated. Antimicrobials including amoxicillin, levofloxacin, trimethoprimsulfamethoxazole, vancomycin (8/16; 50 %) were the most commonly associated agents followed by antiseizure drugs (4/16; 25 %), NSAIDs (3/16; 18.75 %), benzodiazepines (2/16; 12.5 %) and allopurinol (1/16; 6.25 %). The most common complications noted were secondary infections (15/16; 93.75 %) and septicemia (11/16; 68.75 %). Mortality rate was 18,75 % (3/16). Interestingly patients with reactions to quinolones tolerated glycopeptides and carbapenems. Also, a patient with reaction to amoxicillin tolerated carbapenems. One of the 4 patients with reaction to anticonvulsant tolerated levetiracetam, 4/4 benzodiazepines, and 1/4 haloperidol. A patient with suspected reaction to acetaminophen (amoxicillin was the other involved drug) tolerated nimesulide and carbapenems. A patient with reaction to oxcarbazepine tolerated diazepam. We conclude that a competent burn centre staff can guarantee the successful management of the patients.

A small girl of 2 years-6-months was admitted to our hospital for widespread rash on the face, trunk and limbs that had begun 24 hours previously; she also complained arthralgia of small and large joints and fever. She had received acetaminophen at home for 3 days because of febrile gastroenteritis. Family history was positive for allergy (mother had allergic rhinitis and beta-lactam drug allergy). The rash was widespread and included confluent purpuric macules on the trunk, limbs and on the face. There was no mucosal involvement and no skin detachment. Blood work up showed a slight increase of CRP (1.1 mg/dl) and ESR (34 mm/1h), as well as elevated tryptase (19.2 ng/ml – nv 0-5) and total IgE (178 KU/I). Liver and kidney function was normal as well as electrolytes and coagulation; screening for autoimmunity (ANA, ENA, AMA, antiDNA, ASMA, ANCA, C3, C4, rheumatoid factor) and the infectious valutation (Ab anti CMV, EBV, HHV6 and 8, Mycoplasma, postnasal swab for virus) were negative. Skin biopsy was compatible with vasculitis from possible adverse drug reaction (slight oedema in the upper dermis associated with perivascular lymphohistiocytic infiltrate, without a relevant presence of eosinophils). The patient was treated with methylprednisolone with rapid alleviation of symptoms and a complete resolution within 10 days. The pediatric literature reports numerous hypersensitivity reactions with vascular involvement, caused by NSAIDs and beta-lactam agents (1), while cases regarding the assumption of acetaminophen are rare. Although adverse cutaneous reactions to acetaminophen are rare, considering the widespread use of this drug in pediatric age, we believe that the description of this case is useful inasmuch as a prompt diagnosis and an early treatment as well as drug suspension are crucial for improving the prognosis. Authors’ details Allergy and Immunology Unit, Niguarda Hospital, Italy. Niguarda Hospital, Pediatric Ward, Italy. Niguarda Hospital, Burn Unit, Italy.

Methods within a population of patients with peach allergic symptoms of variable severity we investigated which patients also had documented allergy to fresh fennel (Clinical Trials.gov, protocol ID NCT00715156). We examined the type of allergic reaction to fennel by means of a clinical questionnaire, skin prick test, prickprick with fresh fennel, open challenge and IgE-specific levels to fennel and to the following recombinant allergens: anti-rPru p 1, 3, 4, anti-rBet v 1, 2 and 4. We compared the different clinical reactions to fennel between patients with mild symptoms to peach (group A, 21pts) and patients with severe systemic symptoms to peach (group B, 16 pts). SDS-Page and IgE immunoblotting were performed with fennel extract and the Nterminal sequences of the allergenic molecules were determined analyzing the proteins eluted by SDS-gel on a protein sequencer. Immunoblotting inhibition was performed to evaluate the cross-reactivity between fennel and peach extract.

Target cells were predominant in the blood smear of a 53-year-old negro man admitted for a perforated duodenal ulcer. Hemoglobin was 100% fetal by alkali denaturation, cellulose acetate an...

Background Churg-Strauss syndrome (CSS) is a rare systemic necrotizing vasculitis characterized by asthma, hypereosinophilia, cardiac failure, renal damage and peripheral neuropathy. CSS typically develops in three clinical phases, beginning with asthma, followed by tissue eosinophilia and finally in a systemic small-vessel vasculitis. During the late phase, coronary vessels and myocardium are interested leading to a variety of clinical manifestations such as myocarditis, heart failure, pericarditis and coronary vasculitis. Heart involvement is found in over 50% of autopsied CSS patients with evidence of an extremely high mortality in those with cardiac disease left untreated. Cardiac MR has emerged as a promising technique not only for the early diagnosis of cardiac involvement in the setting of this insidious and complex condition, but also for a better risk stratification and tailoring of immunosuppressive therapy. Methods

Background allergy to tomato is very common in the Mediterranean area, where tomato consumption has increased in the last years: fresh in salads, cooked in household sauces or industrially processed foods. Many patients allergic to tomato present severe reactions and have symptoms also with commercial tomato products. Objective to examine the possibility of a relationship between severe allergic symptoms to tomatoes and peach; and, in the event of such a relationship, examine the correlation between severe tomato allergy and IgE positivity to peach allergens, i.e. Pru p 3 and Pru p 1. Methods within a population of patients with different grades of OAS for peach (mild-OAS, group A; and severe systemic symptoms to peach, group B) we selected patients with documented allergic reactions to tomato. We investigated the type of reaction to tomato by means of a clinical questionnaire, skin prick tests, prick + prick with fresh tomato and anti-rPru p 1, 3, 4, anti-rBet v 1, 2 and 4 IgE specific measurements. We compared the kind of clinical reactions to tomato between group A and group B patients. Statistical analyses were carried out with parametric and non parametric tests to examine the relationship between anti-rPru p 1 and 3 IgE levels and symptom severity. Results