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1.
Immunol Res ; 70(4): 419-431, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1956007

ABSTRACT

Ehlers-Danlos syndrome (EDS) is a group of related connective tissue disorders consisting of 13 subtypes, each with its own unique phenotypic and genetic variation. The overlap of symptoms and multitude of EDS variations makes it difficult for patients to achieve a diagnosis early in the course of their disease. The most common form, hypermobile type EDS (hEDS) and its variant, hypermobile spectrum disorder (HSD), are correlated with rheumatologic and inflammatory conditions. Evidence is still needed to determine the pathophysiology of hEDS; however, the association among these conditions and their prevalence in hEDS/HSD may be explained through consideration of persistent chronic inflammation contributing to a disruption of the connective tissue. Aberrant mast cell activation has been shown to play a role in disruption of connective tissue integrity through activity of its mediators including histamine and tryptase which affects multiple organ systems resulting in mast cell activation disorders (MCAD). The overlap of findings associated with MCAD and the immune-mediated and rheumatologic conditions in patients with hEDS/HSD may provide an explanation for the relationship among these conditions and the presence of chronic inflammatory processes in these patients. It is clear that a multidisciplinary approach is required for the treatment of patients with EDS. However, it is also important for clinicians to consider the summarized symptoms and MCAD-associated characteristics in patients with multiple complaints as possible manifestations of connective tissue disorders, in order to potentially aid in establishing an early diagnosis of EDS.


Subject(s)
Arthritis, Rheumatoid , Ehlers-Danlos Syndrome , Joint Instability , Muscular Diseases , Ehlers-Danlos Syndrome/diagnosis , Ehlers-Danlos Syndrome/epidemiology , Ehlers-Danlos Syndrome/genetics , Humans , Joint Instability/diagnosis , Mast Cells , Syndrome
2.
Modern Pathology ; 35(SUPPL 2):1342-1344, 2022.
Article in English | EMBASE | ID: covidwho-1857710

ABSTRACT

Background: SARS-CoV-2 infection results in acute respiratory distress and multiple organ failure, but the pathogenesis of the disease is poorly understood. Recent data suggest that viral RNA may be found in mast cells, but patients with asthma who have hyperplasia of mucosal mast cells do not experience asthma exacerbations during infection and do not suffer from increased mortality due to COVID-19-associated lung damage. Mast cells from bone marrow do not express the ACE2 receptor used for SARS-CoV-2 entry into human cells, and patients with mast cell activation disorders such as systemic mastocytosis do not show mast cell activation during infection. Because activated mast cells can release potent inflammatory mediators including IL-6 and have been implicated in fibrotic lung damage, the purpose of this study was to investigate the role of mast cells in COVID-19 fatal lung disease. Design: We evaluated 19 autopsies and post-mortem biopsies performed on patients who died of COVID-19 in April and May 2020. Representative sections of lung tissue with typical histological changes of diffuse alveolar damage (DAD;both acute and organizing) were selected. Mast cells were identified by immunohistochemistry for KIT (CD117), tryptase, and chymase. Mean values for mast cells were obtained by counting 3 different areas each with the highest and lowest density of CD117/tryptasepositive cells with 40x magnification. Results: Patients in this cohort were mostly obese with systemic hypertension or diabetes and had elevated CRP and IL-6. All mast cells in COVID-19 lung autopsies were positive for tryptase and chymase, indicating a connective tissue phenotype (Figure 1). While both acute and organizing forms of non-COVID-19-related lung injury showed a 3-5-fold increase in mast cell numbers between low and high-density areas, acute COVID-19 showed a <2-fold increase. In contrast, organizing DAD in COVID-19 showed a 3-fold increase in mast cells between low and high-density areas (Figure 2). Few mast cells were co-localized with SARS-CoV-2 mRNA. Conclusions: During the early phase of DAD in SARS-CoV-2 infection, mast cells are suppressed, potentially due to an interferon surge, which is reversed during the organizing DAD phase of infection. Viral RNA is rarely present in mast cells, consistent with the reported lack of ACE2 receptors in bone marrow mast cells.

4.
Internal Medicine Journal ; 51(SUPPL 4):14, 2021.
Article in English | EMBASE | ID: covidwho-1583535

ABSTRACT

Introduction: Mechanisms underlying allergic reactions to the new BNT162b2 (Pfizer) and AZD1222 (AstraZeneca) COVID-19 vaccinations are poorly understood. Polyethylene glycol (PEG) is implicated for BNT162b2;and polysorbate 80 (PS80) and disodium edetate (EDTA) for AZD1222. Methods: Patients referred to our service were investigated with standardised vaccine skin-prick testing (SPT) and intradermal testing (IDT) protocols. Basophil activation testing (BAT) was performed in patients with history highly suggestive of excipient or vaccine allergy. Results: Reason for referral was suspected excipient allergy in 16/23 (70%), previous other vaccine reaction in 4/23 (17%), and reaction to the BNT162b2 vaccine in 3/23 (13%). In patients with suspected excipient allergy, SPT was only positive in 1/16 (6%). In 12/16 patients with suspected PEG allergy, IDT and BAT were positive in 5 (42%) for the BNT162b2 vaccine but not PEG. 3/5 have subsequently undergone successful vaccination with AZD1222, while 1/5 had cross-reactivity with AZD1222 on BAT and has not been vaccinated. 2/16 patients with suspected PS80 allergy were negative on SPT, IDT, and BAT, and have undergone successful AZD1222 vaccination. In the 2/16 patients with EDTA allergy IDT was positive to EDTA but neither vaccine, correlating with BAT. 1 has been successfully vaccinated with the EDTA-containing AZD1222 vaccine. 2 patients (1 reaction to BNT162b2, 1 other vaccine reaction) developed systemic reactions during testing without tryptase elevation. Both were associated with local flare response to the BNT162b2 vaccine, both have undergone successful vaccination with the AZD1222 vaccine. All other patients with negative SPT, IDT, and BAT results have subsequently tolerated vaccination. Conclusion: Most patients can be successfully vaccinated with available COVID-19 vaccines. SPT has low sensitivity and a combined protocol of SPT, IDT, and BAT provides confidence in allergy delabelling. Not all excipient allergies correlate to vaccination allergy and BAT provides a powerful diagnostic tool in these cases.

5.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):468-469, 2021.
Article in English | EMBASE | ID: covidwho-1570395

ABSTRACT

In 2012 a 25-year-old man presented to our outpatient clinic for severe atopic dermatitis (AD) and severe allergic eosinophilic asthma in polisensitivity (house dust mite, cat, gramineous plants, birch, milk protein and, in particular, Alternaria). His clinical history was also characterized by gastro-esophageal reflux disease and chronic rhinitis without polyposis, with septal deviation and turbinate hypertrophy, worthy of surgical intervention. History taking revealed egg and cow milk protein allergy and severe asthma since the first months of life, with frequent hospital admissions due to exacerbations. AD was severe and diffuse, involving especially face, neck, back and superior limbs, often complicated by impetigo. The esthetic, social and psychological impact led him to quit his job as a barman. At presentation, the Eczema Area and Severity Index (EASI) score was 72/72. Laboratory tests showed eosinophilic count ranging between 1.060 and 2.140/mm3, and high serum levels of total Immunoglobulin E (5.939 kUI/L). Tryptase levels were normal and autoantibody analysis was negative. Parasite stool examination was negative. Nasal swab tested positive for Staphylococcus aureus, which was treated with Sulfamethoxazole-Trimethoprim. Asthma Control Test was 15/25, pulmonary function tests (PFTs) showed mild obstruction (FEV1 4.43 L, 103%, FEV1/FVC 69%), with positive bronchodilator testing (FEV1 5.12 L, + 670 mL, + 16%). Firstly, he was treated with topical steroids and sometimes with oral corticosteroids, with poor response. Then, in July 2019, he initiated therapy with cyclosporine 3-5 mg/kg. Soon, the drug had to be discontinued due to adverse effects (gastrointestinal symptoms and infections). In November 2019, at the age of 32 years, he started therapy with monoclonal antibody anti-IL-5 receptor alpha (benralizumab 30 mg 1 subcutaneous vial every 4 weeks for the first three administrations and then every 8 weeks), with a terrific clinical improvement of AD since the first administrations and with benefit on asthma control (ACT after the first administration increased up to 25/25;PFTs could not be performed, due to SARS-CoV-2 pandemic). This therapy has always been well tolerated. The eosinophilic count decreased to 0/mm3 after the first administration. At the moment, after one year of therapy, AD is almost fully disappeared (EASI SCORE 4/72), despite being in free diet, and the quality of life of the patient has definitely improved.

6.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):480, 2021.
Article in English | EMBASE | ID: covidwho-1570384

ABSTRACT

Background: During the ongoing pandemic of Coronavirus Disease 2019 (COVID-19) allergic patients need to continue their constant and proper treatment, including allergen-specific immunotherapy. These patients are expected to be at a higher risk for exacerbation of lung inflammation during viral infection. We investigated the putative interplay existing between allergen-specific immunotherapy and COVID-19 infection in Hymenoptera venom-allergic population. Method: We evaluated the frequency and severity of COVID-19 infection in a cohort of 211 Hymenoptera venom-allergic patients referring to our Center from the end of February till May 20th 2020 for the regular administration of venom immunotherapy (VIT). Each patient completed a form with information regarding symptoms (fever, cough, dyspnoea, sore throat, anosmia and/or ageusia) and eventual close COVID-19 contacts in the previous 14 days. Results: Our result showed that the median age of our cohort is similar to the one that in our region has been associated with a high incidence of COVID-19 infection, increased hospitalization and mortality rates. We reported only an isolated positivity of COVID-19 in the overall group, whereas none suffered from upper airway symptoms associated with COVID-19 (fever, cough, dyspnoea, sore throat, anosmia and/or ageusia). In our cohort 24 patients were in monotherapy with ACE-i, but none of these patients developed COVID-19 disease. In our cohort the median serum tryptase level at baseline was 8.13 ± 11.49: no correlations were found between tryptase levels and COVID-19 infection. Conclusion: Even though the demographic characteristics pose a substantial risk for such a population, we suggest that a regular administration of VIT may help to the development of an immunological milieu able to down modulate the Th1/Th17 environment that has been linked to inflammatory manifestations of COVID-19. To the best of our knowledge, this is the first description of the incidence of COVID-19 infection in Hymenoptera venom allergic patients treated with VIT, suggesting indirectly that venom immune tolerance-inducing treatment may be capable of reducing the aberrant inflammatory response induced by the virus in this specific population. (Table Presented).

7.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):495, 2021.
Article in English | EMBASE | ID: covidwho-1570380

ABSTRACT

Background: First approved anti-COVID vaccines brought a new experience of hypersensitivity reactions into clinical practice. This experience and knowledge of mechanisms are important for further safer and wider use of these immunizations. Methods: Clinical and laboratory data collected in immunoallergology outpatient evaluation and consultation of informatic process. Written consent was obtained. Results: We report a case of a 33-year-old woman, a laboratory worker, who received the first dose of mRNA-based anti-COVID-19 vaccine. After 48-72h she presented with extensive generalized urticaria lesions and pruritus. She was admitted to the emergency department, treated with endovenous corticosteroid and antihistaminic, attenuating skin lesions. However, 12-24h later, urticaria exacerbated, with labial and bilateral ear swelling. She was medicated with oral prednisolone, gradually resolving symptoms. She had no concomitant alcohol/ drug consumption nor practiced physical exercise. She had antecedents of persistent allergic rhinitis and allergic bronchial asthma in the first step of treatment. She had no prior history of drug allergy nor adverse reactions to vaccines. Skin prick tests performed with commercial extracts of aeroallergens were positive for D. pteronyssinus, D. farinae, lepidoglyphus, olive tree pollen, grass pollen, and cat and dog dander. Skin prick test with latex was negative. Basal tryptase was 6.4 and total IgE 154.0 UI/mL. Spirometry was normal at basal condition. Prick test with anti-COVID-19 vaccine was negative. Intradermal test with 1/100 and 1/10 dilutions of anti-COVID-19 vaccine was also negative at 20-30 minutes. However, after 4h she showed hyperemia and swelling of about 7-8cm, localized at the place of both dilutions of intradermal test vaccine administration. PATCH tests performed with anti-COVID-19 vaccine were negative at 48h and 72h readings. She was diagnosed with anti-COVID-19 vaccine late hypersensitivity and, therefore, was not able to take the second dose. Discussion: We report a clinical case of late hypersensitivity to mRNA-based anti-COVID-19 vaccine in a patient without prior history of drug allergy. The reaction was documented with positive intradermal tests performed with 1/100 and 1/10 vaccine dilutions. According to EAACI indications, she did not receive the second dose of the vaccine. Extracts of vaccine components will help to understand adverse reactions and choosing an alternative vaccine, when available.

8.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):491-492, 2021.
Article in English | EMBASE | ID: covidwho-1570370

ABSTRACT

Background: To describe anaphylactic/anaphylactoid reactions induced by mRNA-vaccines against SARS-CoV-2 and immune-allergic studies carried out. Method: Twenty two patients were referred prior to the administration of the second dose of vaccine. Skin tests were performed to both mRNA vaccines (Pfizer and Moderna1/1), different sources of poliethylenglycol (PEG), Polysorbate 80 and Trometamol. Total IgE, specific IgE to ethylene oxide, tryptase and Basophile activation test (BAT) were performed to the same reactives including both Pfizer and Moderna vaccines adding PEG2000. Results: Four anaphylaxis/anaphylactoid reactions are documented. One of them with the entire study negative. The remaining three cases were non-severe anaphylaxis. PEG 1.500 0,1%, 1% and 10%, Polysorbate 80 (0,04mg/ml) and Trometamol (1 mg/ml) were negative in all cases. TAB was positive only to Pfizer and Moderna vaccines but not to PEG or other excipients. Four additional woman with positive skin test were observed in the same period of time related to the first exposition to vaccines and only positive test were obtained with vaccines but not to PEG or other excipients studied. All of them sanitary workers affected by urticaria and/or angioedema and adenitis associated with cutaneous delayed reaction. More than 20 skin tests were negative as the same concentrations in other patients with suspected adverse reactions to vaccines or other drugs containing PEG. All negative patients were encouraged to receive the second dose and 10 did not have a recurrence of reaction. More than 10 BAT were also performed in cases and controls with negative results to PEG. A positive specific IgE to ethylene oxide was obtained. Conclusion: Different mechanisms of anaphylactic/anaphylactoid reaction are inferred from the results. In the most severe case, it was not possible to demonstrate an IgE mechanism involved. Skin test to vaccines involved were the most useful tool to diagnose hypersensitivity reactions. PEG was positive in one case, Ethylene oxide was positive in other case (associated with positive ID test to vaccines) and BAT in other two patients.

9.
Vaccine ; 39(44): 6464-6469, 2021 10 22.
Article in English | MEDLINE | ID: covidwho-1440395

ABSTRACT

Among 6146 hospital employees, 118 subjects with severe allergic background were identified through a screening questionnaire and stratified into 3 groups (Low-risk (LR), Intermediate (IR) and High-risk (HR) group), based on their allergic anamnesis. Data reports on hypersensitivity reactions (HypR) have been collected in both allergic and non-allergic subjects. Seventeen patients (14%) in the allergic population had a HypR after the first, the second or both doses. Skin manifestations were the most frequent ones. Allergic events were more frequent in HR (35%) than IR (10%; p = 0.005) or LR (0%; p = 0.074) subjects. No patient had anaphylaxis. All patients completed the vaccination schedule. 13 HypR occurred in patients without severe allergic background (13/6028, 0,2%) including one (1/6148, 0.016% of total population) WAO grade-4 anaphylaxis. Our data suggest that BNT162b2 mRNA Covid-19 vaccine is relatively safe also in patients with severe allergic background; however, some precautions are required for high-risk patients.


Subject(s)
Anaphylaxis , COVID-19 , Vaccines , Algorithms , Anaphylaxis/chemically induced , Anaphylaxis/diagnosis , Anaphylaxis/epidemiology , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccines/adverse effects
10.
J Allergy Clin Immunol ; 146(2): 300-306, 2020 08.
Article in English | MEDLINE | ID: covidwho-599332

ABSTRACT

The coronavirus disease 2019 (COVID-19) (caused by severe acute respiratory syndrome coronavirus 2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase, and patients at risk can only be protected to a degree, because the virulent state may be asymptomatic. Risk factors concerning COVID-19-induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. Because no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Although the overall risk to acquire the severe acute respiratory syndrome coronavirus 2 may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain comorbidities, mast cell activation-related events affecting the cardiovascular or bronchopulmonary system, and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. In contrast, other therapies, such as anti-mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Disease Management , Mastocytosis, Cutaneous/drug therapy , Mastocytosis, Systemic/drug therapy , Pandemics , Pneumonia, Viral/epidemiology , Betacoronavirus/immunology , COVID-19 , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Diphosphonates/therapeutic use , Expert Testimony , Glucocorticoids/adverse effects , Histamine Antagonists/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , Mast Cells/drug effects , Mast Cells/immunology , Mast Cells/pathology , Mastocytosis, Cutaneous/diagnosis , Mastocytosis, Cutaneous/epidemiology , Mastocytosis, Cutaneous/pathology , Mastocytosis, Systemic/diagnosis , Mastocytosis, Systemic/epidemiology , Mastocytosis, Systemic/pathology , Myeloablative Agonists/adverse effects , Pneumonia, Viral/diagnosis , Pneumonia, Viral/pathology , Precision Medicine/methods , Risk Factors , SARS-CoV-2 , Vitamin D/therapeutic use
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