Filippo Fassio

Kounis syndrome (allergic acute coronary syndrome): different views in allergologic and cardiologic literature

The clinical picture of myocardial ischemia accompanying allergic reactions is defined in the cardiologic literature as Kounis syndrome (KS) or allergic angina/myocardial infarction. In PubMed, a search for “Kounis syndrome”, “allergic angina” or “allergic myocardial infarction” retrieves more than 100 results (among case reports, case series and reviews), most of which are published in cardiology/internal medicine/emergency medicine journals. In allergologic literature, heart involvement during anaphylactic reactions is well documented, but Kounis syndrome is hardly mentioned. Single case reports and small case series of angina triggered by allergic reactions have been reported for many years, and involvement of histamine and others mast cell mediators in the pathogenesis of coronary spasm has long been hypothesized, but the existence of an allergic acute coronary syndrome (ACS) is still questioned in the allergologic scientific community. Putative mechanisms of an allergic acute coronary syndrome include coronary spasm or heart tissue-resident mast cell activation (precipitating coronary spasm or inducing plaque rupture and coronary or stent thrombosis) due to systemic increase of allergic mediators, or heart tissue-resident mast cell activation by local stimuli. Indeed, the pathogenic mechanism of an ACS after an allergic insult might be related to direct effects of mast cell mediators on the myocardium and the atherosclerotic plaque, or to exacerbation of preexisting disease by the hemodynamic stress of the acute allergic/anaphylactic reaction. Which of these mechanisms is most important is still unclear, and this review outlines current views in the cardiologic and allergologic literature.

A new framework for the interpretation of IgE sensitization tests

IgE sensitization tests, such as skin prick testing and serum‐specific IgE, have been used to diagnose IgE‐mediated clinical allergy for many years. Their prime drawback is that they detect sensitization which is only loosely related to clinical allergy. Many patients therefore require provocation tests to make a definitive diagnosis; these are often expensive and potentially associated with severe reactions. The likelihood of clinical allergy can be semi‐quantified from an IgE sensitization test results. This relationship varies though according to the patients’ age, ethnicity, nature of the putative allergic reaction and coexisting clinical diseases such as eczema. The likelihood of clinical allergy can be more precisely estimated from an IgE sensitization test result, by taking into account the patients presenting features (pretest probability). The presence of each of these patient‐specific factors may mean that a patient is more or less likely to have clinical allergy with a given test result (post‐test probability). We present two approaches to include pretest probabilities in the interpretation of results. These approaches are currently limited by a lack of data to allow us to derive pretest probabilities for diverse setting, regions and allergens. Also, cofactors, such as exercise, may be necessary for exposure to an allergen to result in an allergic reaction in specific IgE‐positive patients. The diagnosis of IgE‐mediated allergy is now being aided by the introduction of allergen component testing which may identify clinically relevant sensitization. Other approaches are in development with basophil activation testing being closest to clinical application.

Natural killer cell deficiencies in a consecutive series of children with herpetic encephalitis.

Natural killer (NK) cells play a fundamental role in innate and early phases of adaptive immunity against viral infections, both in humans and in animal models. To date, NK cell deficiencies in patients with severe herpetic infections have been reported in single cases, and their role as predisposing factor is still controversial. Five children affected by herpetic encephalitis were consecutively admitted to the Anna Meyer Childrens Hospital in Florence (Italy) between 2003 and 2005. We therefore investigated the presence of NK cell deficiencies in a consecutive series of children with herpetic encephalitis. Five healthy children were included in the study as controls. Differential WBC counts, main Ig and IgE class serum analysis, cytofluorimetric analysis of circulating T, B and NK cells were performed on our study population. Sequencing of a selected region of CD16A gene transcript was carried out in two patients. All patients resulted to be affected by deficiencies related to NK cells in respect to controls. One patient was also affected by lymphopenia, while no other significant deficits of immunity were detected in the study population. To date, this is the first survey that demonstrates isolated NK cell deficiencies in a cohort of consecutive patients affected by severe herpes simplex infections. These findings suggest a role for NK cell deficiencies as a predisposing factor for increased susceptibility and severe course of disease in these patients.

Italian study on buckwheat allergy: prevalence and clinical features of buckwheat-sensitized patients in Italy

Buckwheat allergy is considered a rare food allergy outside of Asia. In Europe, buckwheat has been described mainly as a hidden allergen. Data on the prevalence of buckwheat hypersensitivity in non-Asian countries is very poor. The aim of this multicenter study was to evaluate the prevalence of buckwheat sensitization and its association with other sensitizations among patients referred to allergy clinics in different geographic areas of Italy. All patients referred to 18 Italian allergy clinics from February through April 2011 were included in the study and evaluated for sensitization to buckwheat and other allergens depending on their clinical history. A total of 1,954 patients were included in the study and 61.3% of them were atopic. Mean prevalence of buckwheat sensitization was 3.6% with significant difference between Northern (4.5%), Central (2.2%) and Southern (2.8%) regions. This is, to our knowledge, the largest epidemiological survey on buckwheat allergy reported outside of Asia. Buckwheat is an emerging allergen in Italy, being more frequently associated to sensitization in Northern regions.

Herpes Simplex Encephalitis With Occipital Localization in an Infant: A Different Route of Entry in the Brain System?

Herpes simplex encephalitis classically involves the periventricular white matter in infants and the mesial temporal lobes, inferior frontal lobes, and insula in older children and adults. However, the increasing use of polymerase chain reaction to detect viral DNA in the cerebrospinal fluid has allowed the expansion of the spectrum of radiologic findings possibly associated with herpes simplex encephalitis. This study presents a rare case of a previously healthy infant with herpes simplex encephalitis with occipital involvement and permanent visual impairment. Possible pathogenic mechanisms are discussed.

The 10th anniversary of the Junior Members and Affiliates of the European Academy of Allergy and Clinical Immunology

To cite this article: Skevaki CL, Maggina P, Santos AF, Alves RR, Antolin‐Amerigo D, Borrego LM, Bretschneider I, Butiene I, Couto M, Fassio F, Gardner J, Xatzipsalti M, 
Hovhannisyan L, Hox V, Makrinioti H, O’Neil SE, Pala G, Rudenko M, Santucci A, Seys S, Sokolowska M, Whitaker P, Heffler E. The 10th anniversary of the Junior Members and Affiliates of the European Academy of Allergy and Clinical Immunology. Pediatric Allergy Immunology 2011: 22: 754–757.

Heart as the early main target of severe anaphylactic reactions: two case reports

Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity reaction, in which mast cells and basophils play a major role through the release of mediators [1]. Patients suffering from anaphylaxis may show a broad range of cardiovascular symptoms, and mast cells are found in large amounts in heart tissue [2]. Herein we describe two cases undergoing different clinical expression of ‘‘heart anaphylaxis’’. Case 1 A 53-year-old man with no previous history of hypersensitivity reactions, developed generalized urticaria approximately 2 h after dinner and concurrent intake of ASA (500 mg). At dinner, the patient ate beef, chicken, and potatoes, and drank mineral water. Clinical manifestations rapidly evolved into a severe malaise with hypotension (90/40 mmHg), tachycardia (120 beats/min), and chest pain that led to hospitalization. The electrocardiogram (ECG) showed a diffuse ST segment elevation with normal cardiac enzymes. The patient was studied by both echocardiography and coronary arteriography, but neither of them revealed any meaningful alteration. His condition rapidly improved after intravenous corticosteroid (hydrocortisone 500 mg) and antihistamine (hydroxyzine 10 mg) with normalization of the ECG. The urticaria cleared 3 h later. Serum tryptase detection was not performed. After discharge, the patient developed three episodes of immediate urticaria/angioedema after eating lamb and beef, and was referred for allergy consultation. Food allergy was investigated by skin prick tests (Lofarma allergens, Milan, Italy) that resulted in positive reactions to beef, pork, and milk. This result was confirmed by the detection of specific serum IgE Antibodies (Pharmacia CAP FEIA), revealing a very important sensitization toward animal proteins like beef (39.1 kUA/l), pork (13.1 kUA/l), lamb (3.68 kUA/l), and milk (8.35 kUA/l). Total IgE serum level was 248 kU/l. Taking into account the severity of the reaction that occurred, the double blind placebo-controlled food challenge, as the gold standard assay indicated in the international consensus protocol for the diagnosis of food allergy, was not performed [3]. In conclusion, the patient’s symptoms were triggered by the simultaneous intake of different compounds able to synergize each other in the massive activation and degranulation of mast cells through both IgE-mediated (food allergy) and non-IgE-mediated mechanisms (ASA nonallergic drug hypersensitivity). Case 2 A 50-year-old woman underwent hysterectomy for uterine fibroma. Propofol (130 mg) and succinylcholine (75 mg)-induced anesthesia was then maintained by sevoflurane (2%), fentanyl (3 ml), and atracurium (50 mg). She developed intra-operative hypotension (70/30 mmHg), associated with urticaria, after 1 h of surgery. The clinical condition rapidly evolved, and 2 min later she experienced ventricular tachycardia and then ventricular fibrillation. She was administered i.v. lidocaine (200 mg) and was defibrillated (200 J), without effect. The patient was treated with intravenous (1 mg) and endotracheal (1 mg) epinephrine A. Matucci (&) A. Vultaggio O. Rossi Immunoallergology Unit, Department of Biomedicine, AOUC, University of Florence, VialeMorgagni, 85, 50134 Florence, Italy e-mail: a.matucci@dmi.unifi.it

Autoimmune hepatitis in a patient affected by neuromyelitis optica: a new association.

Autoimmune hepatitis (AIH) is a chronic autoimmune disease of the liver of unknown etiology associated with autoantibodies [1]. Many overlapping syndromes with other autoimmune liver and extra-hepatic diseases are being increasingly reported [1]. The term neuromyelitis optica (NMO, formerly known as Devic’s disease) identifies an idiopathic, severe, inflammatory demyelinating disease of the central nervous system that preferentially affects the spinal cord and the optic nerves and spares the brain, at least in early stages, affecting gray and white matter [2]. It has long been thought a variant of multiple sclerosis (MS); however, clinical, laboratory, immunologic and pathologic characteristics that distinguish it from MS are now well recognized [2]. Here, we report the case of a 28-year-old Italian female referred to our Department in 2005 because of abnormal liver function tests — a 24-fold rapid increase in aminotransferases — and a history of relapsing neurologic deficits represented by transverse myelitis and bilateral optic neuritis. Disease onset was in May 2004, after a period of relapsing febrile episodes, with altered sensory examination (burning paresthesia followed by hypoanesthesia to the pelvis and the limbs), without sphincter dysfunctions or limb weakness. Admitted to the Neurologic Unit of her local hospital, she underwent MRI scanning of the spine, which showed an area of abnormally increased signal with contrast media enhancement within the spinal cord involving the whole dorsal tract, and electromyogram/electroneurogram examination, which showed signs of myelitis. Laboratory tests, microbiologic tests and cerebrospinal fluid (CSF) examination were all negative. Brain MRI and EEG did not show any abnormality. A diagnosis of transverse myelitis was made. She was treated with corticosteroids (6-methylprednisolone 1 gram intravenously in bolus, followed by an oral maintenance regimen), obtaining progressive remission of her symptoms over the ensuing

Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia ― The SCELTA Trial ―

BACKGROUND The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes express low levels of CD34 (CD14+CD34lowcells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14+and CD34+cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO2. In ECEPC-treated patients, there was a positive correlation between injected CD14+CD34lowcell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients. CONCLUSIONS This study supports previous trials showing the efficacy of BM-MNC autotransplantation in CLI patients and demonstrates comparable therapeutic efficacy between BM-MNC and EPEPCs.

House dust mite-related respiratory allergies and probiotics: a narrative review

The socio-economic burden of allergic respiratory conditions on continental Europe is even higher than that of mainstream diseases, such as diabetes and cardiovascular disease, as allergic rhinitis alone accounts for billions of Euros in healthcare expenses across Europe. House dust mites (HDM) are one of the most common triggers behind allergic rhinitis and asthma. The role of probiotics in the treatment and prevention of some allergic conditions, such as atopic dermatitis, is already well recognized, whereas evidence about their efficacy in patients with respiratory allergies—while increasing—is still limited. Here the current evidence for the use of probiotics in patients with allergic rhinitis and/or asthma is discussed.