Evaluation of respiratory allergies burden and management in primary care and comparative analysis of health care data from Romania, Poland, Czech Republic and Bulgaria - preliminary study.

BACKGROUND: Respiratory allergies mostly allergic rhinitis and asthma represent an important and increasing public health problem and one of the priorities for the European health systems. There is an increasing public concern regarding the persistence and severity of allergic diseases and many difficulties of health systems in providing prompt specialized medical assistance. Our study aims to highlight the main results of the Alliance 4Life project focused on the evaluation of the burden and management of respiratory allergies in primary care from Romania and comparative health-related data from four Central and Eastern European countries. METHOD: We developed a questionnaire focused on patients with allergic rhinitis and asthma directly addressed to general practitioner (GP) specialists from Romania who attended the annual national conference in Bucharest. RESULTS: The main results showed that patients with respiratory allergies are frequently encountered in primary care practice, only a few patients are evaluated by allergists and there is a clear need for education in this field. CONCLUSIONS: This preliminary study confirms that respiratory allergies represent a considerable burden in primary care and the questionnaire may be a useful tool in further studies considering the experience of other healthcare systems. More advanced studies integrating epidemiology with data on air pollution and environmental conditions should be envisaged.

COVID-19-Associated Rhino-Orbital Mucormycosis: Histological and Electron Microscopy Characteristics.

COVID-19-associated rhino-orbital mucormycosis has become a new clinical entity. This study's aim was to evaluate the histopathological and ultramicroscopic morphological aspects of this fungal infection. This was an observational retrospective study on eight patients from three tertiary centers in Romania. The tissue samples collected during functional endoscopic sinus surgery were studied through histopathological examination, scanning electron microscopy, and transmission electron microscopy. In the histopathological examination, the morphological aspects characteristic of mucormycosis in all cases were identified: wide aseptate hyphae with right-angle ramifications, which invade blood vessels. One case presented perineural invasion into the perineural lymphatics. And in another case, mucormycosis-aspergillosis fungal coinfection was identified. Through scanning electron microscopy, long hyphae on the surface of the mucosa surrounded by cells belonging to the local immune system were identified in all samples, and bacterial biofilms were identified in half of the samples. Through transmission electron microscopy, aseptate hyphae and bacterial elements were identified in the majority of the samples. Rhino-orbital-cerebral mucormycosis associated with COVID-19 produces nasal sinus dysbiosis, which favors the appearance of bacterial biofilms. The way in which the infection develops depends on the interaction of the fungi with cells of the immune system.

Histopathological Lung Findings in COVID-19 B.1.617.2 SARS-CoV-2 Delta Variant.

BACKGROUND: The Delta variant (Pango lineage B.1.617.2) is one of the most significant and aggressive variants of SARS-CoV-2. To the best of our knowledge, this is the first paper specifically studying pulmonary morphopathology in COVID-19 caused by the B.1.617.2 Delta variant. METHODS: The study included 10 deceased patients (40-83 years) with the COVID-19 Delta variant. The necrotic lung fragments were obtained either by biopsy (six cases) or autopsy (four cases). Tissue samples were subjected to virology analysis for identification of the SARS-CoV-2 variant, histopathology, and immunohistochemistry (anti-SARS coronavirus mouse anti-virus antibody). RESULTS: Virology analysis identified B.1.617.2 through genetic sequencing in eight cases, and in two cases, specific mutations of B.1.617.2 were identified. Macroscopically, in all autopsied cases, the lung had a particular appearance, purple in color, with increased consistency on palpation and abolished crepitations. Histopathologically, the most frequently observed lesions were acute pulmonary edema (70%) and diffuse alveolar damage at different stages. The immunohistochemical examination was positive for proteins of SARS-CoV-2 in 60% of cases on alveolocytes and in endothelial cells. CONCLUSIONS: The histopathological lung findings in the B.1.617.2 Delta variant are similar to those previously described in COVID-19. Spike protein-binding antibodies were identified immunohistochemically both on alveolocytes and in the endothelial cells, showing the potential of indirect damage from thrombosis.

Asymptomatic Esophageal Necrosis in a Patient with Recent COVID-19: The First Case Diagnosed through Autopsy.

Acute esophageal necrosis is a rare condition, characterized by a distinctive endoscopic/necropsic image-circumferential black area of the esophagus. This paper presents a case of a 78-year-old patient with recent history of a severe form of COVID-19 (2 months previously), with multiple comorbidities, which presents sudden death in hospital. Anatomic-pathological autopsy showed extensive esophageal necrosis, pulmonary thromboses, and coronarian and aortic atherosclerosis. The histopathological examination revealed necrosis of the esophageal mucosa and phlegmonous inflammation extended to the mediastinum, chronic pneumonia with pulmonary fibrosis, viral myocarditis, papillary muscle necrosis, and pericoronary neuritis. Thromboses and necroses were identified also in the liver, pancreas, and adrenal glands. Post-COVID-19 thromboses can manifest late, affecting various vascular territories, including esophageal ones. Their clinical picture may be diminished or absent in elderly and/or diabetic patients.

Fatal Form of COVID-19 in a Young Male Bodybuilder Anabolic Steroid Using: The First Autopsied Case.

We report the case of a 34-year-old male patient, a bodybuilding trainer and user of anabolic androgenic steroids (AASs) for 16 years. He was found in cardio-respiratory arrest in his home. By performing a medico-legal autopsy, a severe form of COVID-19, aortic atherosclerotic plaques, and an old myocardial infarction was found. The SARS-CoV-2 RT-PCR test on necroptic lung fragments was positive, with a B.1.258 genetic line. The histopathological examinations showed microthrombi with endothelitis in the cerebral tissue, massive pulmonary edema, diffuse alveolar damage grade 1, pulmonary thromboembolism, hepatic peliosis, and severe nesidioblastosis. The immunohistochemical examinations showed SARS-CoV-2 positive in the myocardium, lung, kidneys, and pancreas. ACE-2 receptor was positive in the same organs, but also in the spleen and liver. HLA alleles A*03, A*25, B*18, B*35, C*04, C*12, DRB1*04, DRB1*15, DQB1*03, DQB1*06 were also identified. In conclusion, death was due to a genetic predisposition, a long-term abuse of AASs that favored the development of a pluriorganic pathological tissue terrain, and recent consumption of AASs, which influenced the immune system at the time of infection.

Biologic Pollution Due to Ambrosia (Ragweed) Pollen in Urban Environment of Bucharest.

Ragweed pollen is an important component of biological pollution in the urban environment, responsible for increasing respiratory allergies and significant contribution to the health impact of air pollution in the Bucharest area. The aim of this paper is to present the eight-year ragweed pollen monitoring data from Bucharest, to place them in the context of local air pollution, public health regulations and available data on the health impact of ragweed pollen in the urban environment. Our pollen data were correlated with major air pollutant concentrations and with meteorological factors in a recently published local paper and the clinical data of patients with ragweed-induced respiratory symptoms were collected and published in 2019. The ragweed pollen monitoring data, correlated with field data reported by patients and plant specialists confirm the rapid spread of Ambrosia in the Bucharest city area, in addition to some stringent environmental local problems due to air pollution. The number of patients addressed to allergists almost doubled from one year to another, confirming the real alarming health impact of this environmental hazard. Our study confirms the need for more coherent strategies to control ragweed spread, based on application of existing local and international regulations, air pollution control and evaluation of consequences on human health.

Follow-Up of a Rare Case of Eosinophilic Gastroenteritis Associated with Persistent Blood Eosinophilia and Multiple Food Allergies.

Eosinophilic gastroenteritis (EGE) is a subgroup of the eosinophilic gastro-intestinal disorders (EGIDs), characterized by eosinophilic infiltration and chronic inflammation of the gastrointestinal tract. These are rare diseases with still incompletely elucidated causes and mechanisms, with frequently delayed diagnosis and variable outcome. Despite increased interest in eosinophilic diseases in recent years, fewer data have been published on EGE and no standardized diagnostic and therapeutic approach exists. This paper reports the case of a young male patient diagnosed with EGE in 2017 based on clinical and histopathological criteria and constantly monitored during five years. Besides gastrointestinal eosinophilic infiltration, biopsies also revealed eosinophilic infiltration of the oesophagus, despite no declared characteristic oesophageal symptoms. We found increased specific IgE to multiple foods and progressive blood hypereosinophilia which preceded EGE diagnosis by three years. The EGE management included selective dietary restrictions and pharmacologic therapy based on daily budesonide non-enteric coated tablets, proton pumps inhibitors, antihistamines, cromoglycate, correction of iron, calcium and vitamin D deficiencies. The clinical outcome was good, while blood eosinophilia and endoscopic appearance remained almost unchanged. After one year the patient complained of respiratory symptoms suggesting asthma, needing continuous combined inhaled therapy. The reported case is illustrative for complex presentation, diagnosis and outcome of a rare case of mucosal chronic EGE associated with oesophageal involvement, peripheral eosinophilia, multiple food allergies and asthma.

Role of Allergist Advice in Determining Personal Decisions for COVID-19 Vaccination of People With a History of Allergies.

Introduction Vaccination is the most important confirmed tool that can stop the ongoing coronavirus disease 2019 (COVID-19) pandemic, but the vaccination rate remains low in some countries, including Romania, despite consistent and undoubtedly scientific proof of this disease-prevention method. The risk of allergic reactions after COVID-19 vaccines may be a reasonable cause for the antivaccination attitude of people with a history of allergies or who consider themselves at risk for having severe allergic reactions after vaccination. Objective Our paper aims to analyze the role of allergist advice in getting people with a history of allergies to trust and accept COVID-19 vaccines and to evaluate the real risk of allergic reactions to these vaccines in this population. Method We performed a retrospective study of patients who asked for allergist advice from our hospital before getting one of the COVID-19 vaccines and who received a consultation either through phone call or online or have been admitted for hospital evaluation in 2021. Results More than 300 calls and 100 online consultations for COVID-19 vaccination-related allergist advice were done in our center within one year. From the total number of 210 people who were evaluated based on a one-day hospital stay in the Allergology department, 64 patients (30.47%) have been scheduled for evaluation before vaccination because of their past or recent medical history of allergies. Nine patients had documented post-vaccination adverse events, which occurred after the first dose in seven cases, after the second dose in one case, and after the booster in one case. The reactions were mild but one was moderate. No patient was considered to have a contraindication or special precaution for COVID-19 vaccination, and all patients with reactions after the first dose could safely complete the vaccination scheme. Conclusion In conclusion, allergist advice and evaluation can significantly influence the decision to vaccinate in patients with a history of allergies.

Real-Life Benefit of Omalizumab in Improving Control of Bronchial Asthma During COVID-19 Pandemic.

Biologic therapy is recommended by Global Initiative for Asthma (GINA) guidelines in asthma patients not controlled with maximal inhaled therapy corresponding to GINA step 4. Omalizumab is an anti- immunoglobulin E (IgE) monoclonal antibody and the first biological available for the add-on treatment of severe allergic asthma, approved by Food and Drug Administration (FDA) in 2003. Diagnosing and managing asthma patients during coronavirus disease 2019 (COVID-19) pandemic since early 2020 has been challenging, mainly due to the risk of contracting COVID-19 disease and to the limited access to hospital care and pulmonary function tests. We report a case of a 52-year-old female patient, diagnosed with adult-onset asthma in 2018, who was first referred to the Allergy Department of our hospital in January 2019 for dyspnea, wheezing, and worsening cough. Despite continuous inhaled therapy and good inhalation technique, she had frequent asthma symptoms, requiring short courses of oral corticosteroids (CS). Physical examination and pulmonary function tests on admission revealed broncho-obstructive syndrome and laboratory tests showed mild inflammation and high total serum IgE. She continued to have two moderate-severe exacerbations after stepping up to maximal inhaled therapy plus oral montelukast and theophylline, according to GINA step 4. By the end of 2019, we additionally started omalizumab, which resulted in prompt clinical benefits and resolution of asthma symptoms. Given the ongoing COVID-19 pandemic limiting in-person visits, virtual follow-ups indicated adequate control of his symptoms, as proved by asthma control test and no need for hospital presentation.

Mast cell activation syndromes - evaluation of current diagnostic criteria and laboratory tools in clinical practice (Review).

Mast cell activation syndromes (MCAS) represent a heterogeneous clinical entity caused by episodic and severe mast cell activation, including primary and secondary mast cell disorders (MCDs). The group of primary or clonal MCDs refers to systemic mastocytosis, other clonal MCAS and hereditary hypertryptasemia, while the secondary MCAS is characterized by normal mast cells (MCs) which are activated by external triggers, such as allergens or physical stimuli. Another category of MCAS is the idiopathic form, when no trigger or genetic mutation can be identified. Symptoms of mast cell activation are due to release of specific mediators and can be seen in many diseases, such as allergies, with localized or systemic clinical manifestations. Confirmation of MCAS is based on diagnostic criteria proposed by an international group of experts and the best available evidence in this field. It is generally accepted that the clinical picture of MCAS is non-specific and there are few available laboratory tools, making it difficult for clinicians to identify and confirm this entity. The diagnosis is established after exclusion of other possible clinical entities in most of the cases. Therefore, the actual diagnostic criteria of MCASs, some relevant clinical aspects and laboratory tools used in clinical practice were reviewed.

Acquired angioedema induced by angiotensin-converting enzyme inhibitors - experience of a hospital-based allergy center.

Angiotensin-converting enzyme inhibitors (ACEIs) represent an important group of pharmacological compounds, largely prescribed for more than 30 years. They have been extensively evaluated in clinical trials, demonstrating significant reduction of morbidity and mortality of patients with cardiovascular diseases, mainly high blood pressure, myocardial infarction, heart failure and stroke. Besides their beneficial effects and a general good safety profile, it was proven that ACEIs might also induce adverse effects in some patients, most notably angioedema (AE) and chronic cough. The occurrence rate of adverse events induced by ACEIs is low, but the number of suffering patients is relatively high, since ACEIs is one of the most frequently prescribed medication worldwide. The aim of our study was to evaluate clinical pattern, risk factors and general management of ACEI-induced angioedema in a cohort of patients addressed for allergist evaluation in one university hospital in Romania, during a period of 32 months. It was found that ACEI-induced angioedema (ACEI-AE) represented more than half of the total number of patients addressed for angioedema without urticaria, with variable clinical and time-patterns. Most of the patients were referred by general practitioners (GPs) with diagnosis of urticaria or other skin allergy and continued to take ACEIs for months and years after onset of angioedema. We concluded that the awareness of acquired, non-allergic angioedema induced by ACEI therapy in medical practice is still low and there is a need for improved knowledge and interdisciplinary collaboration in this field.

Five-Year Data on Pollen Monitoring, Distribution and Health Impact of Allergenic Plants in Bucharest and the Southeastern Region of Romania.

Background and objectives: Respiratory allergies induced by allergenic pollen represent an important public health problem with increasing prevalence and severity in Europe. Romania has no aerobiology network and pollen measurements have been done for about ten years in the west region only. Materials and Methods: We established the first pollen monitoring center in the capital of Bucharest in 2013, based on collaboration with the Réseau National de Surveillance Aérobiologique (RNSA) from France. The aim of our paper is to present results from five years of pollen monitoring in the city center of Bucharest and preliminary data on distribution and health impact of some allergenic plants, mainly Ambrosia artemisiifolia, which is considered a real danger for the public health. Results: Our data show a significant atmospheric amount and a longer season than previously considered of grass (Gramineae) pollen and short period with a high level of Ambrosia pollen, while tree pollen looks less important in this area. The plant distribution data provided by specialists and information from affected persons showed the wide and increasing spread of Ambrosia in Bucharest and other cities from the south region. Preliminary health data from allergists confirmed that the number of patients with allergies to Ambrosia pollen is increasing from one year to another and almost all patients describe a high urban exposure from their living or working place. Conclusions: We consider that the recently implemented Law 62/2018 against Ambrosia may help reduce weed distribution and the atmospheric pollen load, but a more complex and coordinated strategy for controlling urban vegetation and reducing biologic pollution is needed.

Nine year follow-up of a rare case of angioedema due to acquired C1-inhibitor deficiency with late onset and good response to attenuated androgen.

BACKGROUND: Angioedema due to acquired deficiency of C1-inhibitor (C1-INH-AAE) is a rare disease sharing some clinical and laboratory similarities with hereditary angioedema, but with late onset and no positive family history. The underlining cause may be malignant or due to autoimmune diseases, but some cases remain idiopathic. CASE PRESENTATION: We report a case of a 75 year old woman suffering from recurrent episodes of angioedema since the age of 66, considered first induced by treatment with angiotensin-converting-enzyme inhibitors (ACEI). She continued to have angioedema attacks during 6 years after discontinuation of ACEI, until evaluation in our clinic in 2014, when C1 inhibitor esterase (C1-INH) deficiency was confirmed. The extended medical evaluation for inflammatory, allergic, autoimmune and neoplasic diseases was negative. C1-INH and complement fraction C4 plasma levels were significantly decreased at all measurements, but no diagnostic criteria for diseases known to induce C1-INH deficiency could be found. We first initiated daily prophylactic treatment with tranexamic acid, with no amelioration after 3 months. During the last and most severe attack, with the first facial and laryngeal edema, we have switched to attenuated androgen danazol. The evolution was very good, with prompt remission of angioedema and significant increase of C1-INH and C4 plasma levels after 2 weeks of daily danazol use. She completed 3 years of continuous treatment with low daily maintenance dose of danazol (ongoing), with no angioedema attack. We closely monitored C1-INH and C4 plasma levels, possible danazol side effects and any signs suggesting late onset of C1-INH deficiency causal disease. CONCLUSION: We reported a particular case of rare angioedema due to acquired deficiency of C1-inhibitor, which has no clear cause after long follow-up, but good response to attenuated androgen. We concluded that the awareness of angioedema due to C1-INH deficiency should be increased within medical community and therapeutic options should be more clearly indicated and available for all diagnosed cases.