The influence of nutritional habits, body mass index and intestinal microbiota in mastocytosis on clinical symptoms using conventional culture and next generation sequencing.

BACKGROUND: Mastocytosis is a rare neoplastic disease of the bone marrow associated with the proliferation and accumulation of mast cells in various internal organs, including the gastrointestinal tract. There are few studies describing the gut microbiome of patients with mastocytosis using next generation sequencing supported using traditional culture methods. The aims of the study were, firstly, the determination of nutrition habits, composition of the intestinal microflora and BMI in mastocytosis, and secondly, analysis of mastocytosis severity and symptoms depending on the composition of the intestinal microflora. METHODS: The study included 47 patients with indolent systemic mastocytosis and 18 healthy controls. All participants gave their informed consent to participate in the study. The study consisted of 3 parts: I-clinical assessment, II - examination of the intestinal microflora using the biochemical method, III - 16S rRNA sequencing. RESULTS: The nutrition habits and BMI of mastocytosis patients were similar to controls; however, most patients with mastocytosis had a low dietary vitamin and mineral content. As many as 94.5% of patients had too little fiber intake and mineral content. The most common cause of the abnormal stool test result with traditional culture was a titer of E. coli <106 . The low richness of microbiota species indicated by the Simpson index was observed in mastocytosis, p = 0.04. There were no significant differences in the composition of the intestinal microflora depending on the type of mastocytosis; however, the tryptase level correlated with the amount of Suterella, Barnesiellaceae, Eubacterium, Odoribacter, and Anaerostipes. CONCLUSIONS: The nutritional habits and BMI of mastocytosis patients are similar to the general population, except for too little fiber intake and mineral content. The gastrointestinal symptoms of mastocytosis patients may be related to the low richness of microbiota species and the amount of Suterella, Barnesiellaceae, Eubacterium, Odoribacter, Anaerostipes, which correlated with tryptase levels.

Hypersensitivity of azo dyes in urticaria patients based on a single-blind, placebo-controlled oral challenge.

Introduction: The role of azo dyes in urticaria is not fully understood. Aim: To assess the incidence rate of hypersensitivity reactions to food azo dyes based on a placebo-controlled oral challenge in a group of patients with suspected urticaria exacerbation after consuming food additives. Material and methods: The study included patients over 18 years of age with chronic urticaria, in whom hypersensitivity to food additives was suspected based on a questionnaire and medical history. Patients suspected of urticaria exacerbations after ingestion of azo dyes were enrolled in a placebo-controlled single-blind oral challenge (OC) with a mixture of azo food dyes: tartrazine, Quinoline Yellow, Sunset Yellow, Cochineal Red, Allura Red, and azorubine. Results: Out of 110 patients (76 women and 34 men, mean age 46.1 (20-76 years), 39 patients were qualified for the oral challenge. We observed two subjects (5.1%) with a positive result. Conclusions: Azo dyes ingested in food or medications incidentally cause urticaria but may exacerbate its course. Oral challenge-confirmed hypersensitivity to azo dyes is much less common than reported by patients.

The role of the clinical and psychological symptoms of mastocytosis in the patient's quality of life.

Introduction: Patients with mastocytosis have various clinical and psychological symptoms, for example, life-threatening anaphylactic reactions or anxiety, resulting in decreased quality of life (QoL). Aim: To assess the clinical and psychological symptoms (such as depression, anxiety) as well as the quality of life and satisfaction with life in patients with mastocytosis. Material and methods: The study group included 85 patients with mastocytosis (57 women and 28 men) treated at the Department of Allergology, Medical University of Gdansk, Poland. The measures employed in the study were the following: HADS-M, QLMS, and Cantril ladder. Results: Among clinical symptoms that occurred in the studied group, only allergy differentiated between the patients in terms of their QoL. Patients experiencing allergy symptoms presented lower QoL in the area of leisure time. The study findings indicate that 27.1% of participants experience anxiety, 12.9% experience depression, 15.3% present low satisfaction with the current life, and 10.6% express low satisfaction with life in the next 4 weeks. General QoL in mastocytosis, as well as the four areas of QoL in mastocytosis, remain positively correlated with anxiety, depression, and irritability, as well as negatively correlated with the satisfaction with current life and life in 4 weeks' time. Conclusions: Patients who experience allergy symptoms have a lower level of QoL in the area of leisure time. Having more obstacles in various areas of life is associated with anxiety, depression, irritability, and low satisfaction with life. Learning how to overcome them can potentially improve the patients' QoL.

Protocol of safe vaccination against COVID-19 in patients with high risk of allergic reactions.

Background: Sars-CoV-2 infections are hazardous, especially to the elderly and patients with comorbidities. With no efficient treatment available, newly developed vaccines are the only way to change the course of the pandemic. However, reports of allergic reactions resulted in some patients and practicing physicians being concerned about the safety of vaccine administration, particularly in people with severe anaphylactic reactions to multiple or unknown factors in their medical history.This study aimed to develop an allergic work-up protocol based on skin prick tests (SPT), intradermal testing (IDT) and intramuscular provocations, and desensitisation which may contribute to diagnosis and management of anti-COVID-19 vaccine allergy. Methods: Two hundred and eighty-five patients were enrolled. Two hundred and five of them entered the study based on severe anaphylactic reaction to unknown or multiple factors in their medical history which disqualified them for standard treatment. Another 80 patients were enrolled after developing an allergic reaction to the first dose of one such vaccine. In all subjects, SPT and IDT were performed. Serum tryptase was assessed in 79 patients randomly chosen from the study group. Results: Two hundred and seventy-seven patients with negative tests were given a vaccine without complications. Seven patients had positive skin tests. In two cases, tests confirmed Comirnaty allergy, while the other five confirmed solely skin sensitisation with no exposure prior to the study. Six patients with positive tests received titrated challenge using desensitisation protocol with a reasonable tolerance. One patient did not consent to desensitisation and one patient resigned despite negative tests. Overall, 283 (99%) patients were vaccinated using this newly developed protocol. Patients with adverse reactions to the first dose of the vaccine before the study had a significantly lower basal serum tryptase concentration (p = 0.001). Conclusion: Skin tests with anti-COVID-19 vaccines are a useful tool in the vaccination protocol. This protocol enables safe immunisation of high-allergy-risk patients even in cases of positive skin tests.

Carmine allergy in urticaria patients.

Introduction: Carmine, a commonly used natural red dye, can cause immediate and delayed allergic reactions, which are frequently overlooked. Aim: To assess the incidence of carmine allergy and its clinical significance based on the placebo-controlled oral challenge in urticaria patients and suspected hypersensitivity to food additives. Material and methods: Patients' histories were recorded by means of a standardized questionnaire. The subjects underwent skin prick tests and patch tests for carmine, while the level of specific IgE was measured in 52 patients. The patients with at least one positive carmine test or with suspected hypersensitivity to carmine were suggested to undergo a placebo-controlled oral challenge test. Results: One hundred and ten patients were enrolled in the study. Carmine skin testing was positive in 22 patients: skin prick tests were positive in 17% (n = 19), while patch tests were doubtful in 6% (n = 6). In 25/52 patients, the level of specific IgE was min. 0.01 kU/l. Oral challenge was performed in 33 subjects. Allergy to carmine was diagnosed in 9 (8%) patients; all of them suffered from chronic inducible urticaria. Conclusions: Carmine is a potential allergen in patients with chronic inducible urticaria especially with concomitant systemic symptoms. Skin tests and specific IgE level measurement may be helpful tools to diagnose E120 hypersensitivity.

IFNG, FCER1A, PCDHB10 expression as a new potential marker of efficacy in grass pollen allergen-specific immunotherapy.

INTRODUCTION: Allergen-specific immunotherapy (AIT) is the core treatment in allergic rhinitis and asthma. Although widely used, some patients do not benefit from treatment and there is no efficacy objective marker. AIM: To define the profile of gene transcripts during the build-up phase of AIT and their comparison to the control group and then search for a viable efficacy marker in relation to patient symptoms. MATERIAL AND METHODS: AIT was administered in 22 patients allergic to grass pollen. Analysis of 15 selected transcript expression was performed in whole blood samples taken before AIT (sample A) and after reaching the maintenance dose (sample B). The control group included 25 healthy volunteers (sample C). The primary endpoint was Relative Quantification. The gene expression analysis was followed by clinical evaluation with the use of Allergy Control Score (ACS). RESULTS: Comparison between samples A and B of gene expression showed a significant increase in IFNG expression (p = 0.03). In relation to the control group, pretreatment samples from patients showed higher levels of AFAP1L1 (p = 0.006), COMMD8 (p = 0.001), PIK3CD (p = 0.027) and TWIST2 (p = 0.0003) in univariate analysis. A generalized linear regression model was built according to the Bayesian Information Criterion based on the IFNG, FCER1A and PCDHB10 expression pattern for prediction of the AIT outcome. The model showed a correlation in predicted and observed changes in ACS. CONCLUSIONS: There is a significant change in the expression of IFNG during the build-up phase of AIT. The authors propose an in vitro model of AIT efficacy prediction for further validation.

ß-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy.

BACKGROUND: There is controversy whether taking ß-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). METHODS: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking ß-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. RESULTS: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took ß-blockers, 11.9% ACEI, 5.0% ß-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of ß-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took ß-blockers, none an ACEI. CONCLUSIONS: This trial provides robust evidence that taking ß-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).

Assessing quality of life in patients with mastocytosis: development of the disease-specific questionnaire.

INTRODUCTION: Appropriate and targeted psychological care, as well as psychoeducation covering the disease causes, symptoms, and their management are crucial elements of the therapeutic process in patients with mastocytosis. This care is based on the identification of problematic areas that are of the greatest importance for patients. The quality of life questionnaires available in Poland are designed for the general population; therefore, they do not encompass the specificity of difficulties experienced by people suffering from mastocytosis. AIM: To develop a questionnaire measuring the quality of life in patients with mastocytosis, and including the issues and symptoms typical for this group. MATERIAL AND METHODS: The study involved 85 patients (57 women and 28 men) suffering from mastocytosis. RESULTS: The analyses revealed that the Quality of Life in Mastocytosis Scale (QLMS) is a reliable and valid tool for measuring the quality of life, and it takes into account the specific difficulties experienced by patients with mastocytosis. Apart from the measurement of the global quality of life, QLMS offers a deeper assessment of the quality of patient's lives, including the difficulties in professional life, everyday life, leisure time, or those associated with protective behaviours. CONCLUSIONS: The presented questionnaire completes a gap in quality-of-life studies by allowing to plan psychoeducation and offering a tool for a precise diagnosis of the quality of life in patients with mastocytosis.

Oral premedication in patients with a history suggesting hypersensitivity to iodinated contrast media.

INTRODUCTION: Iodinated contrast media (ICM) are pharmaceuticals widely used in diagnostic procedures. Adverse effects associated with their administration are quite frequent and mostly mild. However, they raise concerns in patients and doctors in the context of their future use. AIM: To determine efficacy of premedication before medical procedures with the use of iodinated contrast media in patients with a history suggesting a hypersensitivity reaction after their past use. MATERIAL AND METHODS: Out of 152 patients consulted due to adverse reactions after ICM (85 women and 67 men, aged 43-90), 101 were selected with the history suggesting a mild hypersensitivity reaction (urticaria, itching, skin redness, malaise etc.). All the patients had health problems requiring a procedure with ICMadministration in the near future. The premedication was given with cetirizine (10 mg) and prednisone (20 mg or 50 mg, randomly assigned) 13, 7 and 1 h before the ICM administration. Presence of adverse events was compared between the subgroups with χ 2 test and efficacy of premedication - with Wilcoxon test. RESULTS: Seventy-six patients underwent the radiologic procedure with premedication with antihistamine and a lower (40 patients) or higher dose (36 patients) of prednisone. Four of them reported a cutaneous hypersensitivity reaction (urticaria, itching, redness) and one - dyspnoea. There was no statistically significant difference in relation to the premedication protocol (p = 0.1306). CONCLUSIONS: Premedication with cetirizine and prednisone before radiologic procedures proved to be efficient in patients with a history suggesting hypersensitivity to iodinated contrast media. There was no significant difference in efficacy related to the dose of prednisone (20 mg vs. 50 mg).

COMMD8 changes expression during initial phase of wasp venom immunotherapy.

BACKGROUND: Hymenoptera venom allergy (HVA) is of great concern because of the possibility of anaphylaxis, which may be fatal. Venom immunotherapy (VIT) is the only disease-modifying treatment in HVA and, although efficient, its mechanism remains partially unknown. Gene expression analysis may be helpful for establishing a proper model of tolerance induction during the build-up phase of VIT. The present study aimed to analyze how the start of VIT changes the expression of 15 selected genes. METHODS: Forty-five patients starting VIT with a wasp venom allergy were enrolled. The diagnosis was established based on anaphylaxis history (third or fourth grade on the Mueller scale) and positive soluble immunoglobulin E and/or skin tests. Two blood collections were performed in the patient group: before and after 3 months of VIT. One sample was taken in the control group. Gene expression analysis was performed using a reverse transcriptase-polymerase chain reaction with microfluidic cards and normalized to the 18S housekeeping gene. RESULTS: Commd8 was the only gene that changed expression significantly after the start of VIT (p = 0.012). Its expression decreased towards the levels observed in the healthy controls. Twelve out of 15 genes (commd8, cldn1, cngb3, fads1, hes6, hla-drb5, htr3b, prlr, slc16a4, snx33, socs3 and twist2) revealed a significantly different expression compared to the healthy controls. CONCLUSIONS: The present study shows that commd8 changes significantly its expression during initial phase of VIT. This gene might be a candidate for VIT biomarker in future studies.

Evaluation of asthma course in pregnancy.

The prevalence of asthma has been rising in recent decades. It is the most common disease among pregnant women andaffects ca. 12% of this population. The course of asthma in pregnancy may change. In 1/3 of patients, it worsens; in 1/3 ofpatients, the symptoms are milder; in 1/3 of patients, it remains unchanged. Well-controlled asthma decreases the risk ofpregnancy complications. Uncontrolled and severe asthma increases the risk of congenital malformations and obstetricalcomplications for both mother and baby. Exacerbations may also contribute to poor pregnancy outcomes. These occur mostlyeither in the first or in the second trimester. The most common triggers are viral infections and treatment non-compliance.The key to maintaining and gaining control of asthma is active treatment of asthma and its exacerbations.

Histoplasmosis in an elderly polish tourist - a case report.

BACKGROUND: Histoplasmosis is a mycosis caused by soil-based fungus Histoplasma capsulatum endemic in the USA, Latin America, Africa and South-East Asia. The disease is usually self-resolving, but exposure to a large inoculum or accompanying immune deficiencies may result in severe illness. Symptoms are unspecific with fever, cough and malaise as the most common. Thus, this is a case of disease which is difficult to diagnose and very rare in Europe. As a result, it is usually not suspected in elderly patients with cough and dyspnea. CASE PRESENTATION: This is a case of a 78-year-old patient, admitted to our department due to respiratory failure, cough, shortness of breath, fever and weight loss with no response to antibiotics administered before the admission. Chest CT revealed numerous reticular and nodular infiltrations with distribution in all lobes. The cytopathology of BAL showed small parts of mycelium and numerous oval spores. Considering clinical presentation and history of travel to Mexico before onset of disease, pulmonary histoplasmosis was diagnosed. After introduction of antifungal treatment rapid improvement was achieved in terms of both clinical picture and respiratory function. CONCLUSIONS: Since the risk of Histoplasma exposure in Europe is minimal, patients, who present with dyspnea, fever and malaise are not primarily considered for diagnosis of histoplasmosis. However, taking into account increasing popularity of travelling, also by elderly or patients with impaired immunity, histoplasmosis should be included into differential diagnosis.

Smoking history is negatively associated with allergen specific immunotherapy efficacy: a retrospective analysis.

INTRODUCTION: Allergen specific immunotherapy (AIT) is the only treatment modifying the course of the disease in patients allergic to airborne allergens. It has been proven to be effective in allergic populations, however individual patients vary in terms of response to the therapy. AIM: To assess the factors that might affect the efficacy of AIT. MATERIAL AND METHODS: Patients treated with AIT for grass pollen or house dust mites were included. The efficacy of AIT was assessed with the use of Allergy Control Score (ACS), performed before and at least 1 year after AIT. The following variables were assessed as potential risk factors for a worse response to AIT: age, gender, type of allergy, type of allergen, type of vaccine, type of AIT and smoking history. RESULTS: The study group consisted of 145 subjects.AIT was effective in the entire group; the mean ACS results decreased from 21.14 to 14.41 points (p< 0.0001). No differences in efficacy in terms of assessed risk factors were found, except for smoking history (ACS change in the smoking group was smaller: from 21.8 to 18.1 points; p = 0.09, OR = 0.323; 95% CI: 0.11-0.88; p = 0.02). CONCLUSIONS: Smoking history may affect AIT outcomes.

Changes in the Expression of MicroRNA in the Buildup Phase of Wasp Venom Immunotherapy: A Pilot Study.

BACKGROUND: Allergen-specific immunotherapy is the most effective method of treatment in allergy to wasp venom. However, its mechanism of action is still not fully understood. The aim of this study is to describe changes in microRNA (miRNA) expression in patients undergoing the buildup phase of venom immunotherapy. METHODS: The study group comprised 7 adult patients with a history of severe systemic reactions after stinging by a wasp. In all patients, sensitization to wasp venom had been confirmed by skin tests and serum IgE. The buildup phase of wasp venom immunotherapy (VIT) was conducted according to an ultrarush protocol. In blood samples collected before and 24 h after completing the VIT buildup phase, 740 miRNAs were assessed. RESULTS: Of the 740 miRNAs, 440 were detected in the study group, and in 5 expression was significantly changed after the buildup phase of VIT: miR-370, miR-539, miR-502-3p, miR-299, and miR-29c. Another 62 miRNAs changed 2-fold in some patients (nonsignificant), including increases in miR-143 (stimulating FOXp3 expression) and let-7d (reducing expression of IL-13, IL-6, and TLR4), and decreases in proinflammatory miR-301, miR-146b, miR-106, and miR-485. CONCLUSIONS: Several changes in miRNA expression have been found as a result of the buildup phase of wasp VIT, with lower expression of some miRNAs involved in allergic inflammation and higher expression of those possibly involved in tolerance induction. However, the role of the most significant changes is uncertain.

Differentiating of cross-reactions in patients with latex allergy with the use of ISAC test.

INTRODUCTION: Differentiating between cross-reactivity and double sensitization is still a challenging issue in allergology. AIM: To differentiate cross-reactions accompanying latex allergy with the use of the ISAC test. MATERIAL AND METHODS: Thirty-nine patients reporting immediate allergic reactions to latex were enrolled into the study (group A). The control group was comprised of 41 patients with allergic diseases not associated with latex (group B) and 20 healthy individuals (group C). Their history was recorded and skin prick tests were performed with latex, airborne and food allergens. Specific IgE against food allergens, latex (k82) and recombined latex allergens were determined. ImmunoCAP ISAC test was performed with 103 molecules. RESULTS: Sensitization to latex was found by means of skin tests in 16 cases and sIgE against latex was revealed in 12 cases (including 10 positive in both SPT and sIgE). In the ISAC test antibodies against recombined latex allergens were found in 8 patients with rHev b 6 as the most common. All the patients positive for rHev b 1, 5, 6, 8 had allergy or asymptomatic sensitization to food allergens cross-reacting with latex. Some reactions could not have been differentiated due to the lack of allergens in the ISAC test. Others, not related to latex-fruits syndrome were explained by cross-reactivity with other profilins or PR-10 proteins. CONCLUSIONS: ImmunoCAP ISAC test could be useful in differentiating between cross-reactions and double sensitizations. However, in the case of latex its advantages are limited due to a small panel of allergens.

The Role of TRAF4 and B3GAT1 Gene Expression in the Food Hypersensitivity and Insect Venom Allergy in Mastocytosis.

Mastocytosis is an uncommon disease classified as a myeloproliferative neoplasm, however, its symptoms are broad and place patients at crossroads between dermatology, hematology and allergology. Patients with mastocytosis often suffer from symptoms resulting from the activation and release of mediators from the mast cells, such as generalized itching, redness, headache, abdominal cramps, diarrhea, bone pain or arthritis, hypotension and shock. The possible severe, fatal or near fatal reactions caused by food hypersensitivity are reasons for the research focused on marker identification. The aim of the study was to analyse the gene expression differences in mastocytosis patients with and without food and drug hypersensitivity and insect venom allergy (IVA). A total of 57 Caucasian patients with mastocytosis were studied [median age 41.8; range 18-77 years; 15 (26.3 %) males and 42 (73.7 %) females]. Quantitative RT-PCRs of 11 genes plus ribosomal 18S RNA were run. Symptoms of food hypersensitivity were found in 12 patients (21 %), including 3 patients (13 %) with cutaneous mastocytosis (CM), and 9 (28 %) with indolent systemic mastocytosis (ISM). IVA was confirmed in 13 patients (22.8 %) including 6 patients (10.5 %) with CM, and 7 patients (12.3 %) with ISM. Drug hypersensitivity was diagnosed in 10 patients (17.5 %). Significant differences in the gene expression were found for TRAF4 (p = 0.008) in the comparison of the mastocytosis patients with and without concomitant food hypersensitivity. Furthermore significant differences were found in gene expression for B3GAT1 (p = 0.003) in patients with IVA compared to patients without insect sting anaphylaxis in the medical history. The expression of studied genes did not differ according to the presence of drug hypersensitivity. The TRAF4 expression was higher in mastocytosis patients with food hypersensitivity in their medical history, the B3GAT1 expression was lower in mastocytosis patients with IVA in history.

Typing safe antibiotics in amoxicillin hypersensitive patients--development of a stepwise protocol.

INTRODUCTION: A history of an adverse reaction to amoxicillin, irrespective of the mechanism involved, significantly elevates patients' anxiety and affects therapeutic decisions in the future, leading to unnecessary avoidance of antibiotics. As a consequence, it would be useful to find a safe and reliable protocol for typing safe alternative antibiotics. The aim of the study was to determine negative predictive value of typing safe antibiotic in patients with a history of hypersensitivity reaction to amoxicillin. MATERIAL AND METHODS: 71 patients, aged 20-83, with a history of an adverse reaction to amoxicillin were retrospectively analysed. On the basis of the reaction type they were divided into three groups: A - symptoms not typical for hypersensitivity reactions, B - allergy manifested by urticaria and/or angioedema, C - anaphylaxis. In group A amoxicillin was tested, in group B - cefuroxime, and in group C - macrolide: azithromycin or clarithromycin. Telephone follow-up visits were performed twice: 6-12 months and 3-5 years after the clinical assessment to evaluate tolerance of antibiotics. On the basis of the follow-up results, the negative predictive value (NPV) of the protocol was calculated. RESULTS: The full diagnostic protocol was applied in 62 participants. Amoxicillin was found safe in 22, cefuroxime - in 21 and macrolide - in 19 patients. No anaphylactic reactions were observed during the tests. On the basis of the telephone follow-up, the NPV of the protocol was 96% in the first follow-up and 97% in the second one. CONCLUSION: A stepwise approach including SPTs, ICTs and provocations with amoxicillin / cefuroxime/macrolide - depending on a patient's history - is safe and allows typing an antibiotic in the vast majority of patients.