Exercise-induced anaphylaxis: an update

Exercise-induced anaphylaxis (EIAn) is a rare and potentially fatal syndrome associated with exercise. It is the most serious and potentially life-threatening hypersensitivity phenomenon for athletes of all sports. Food-dependent EIAn (FDEIAn) shares the same symptoms, but ingestion of foods 2–3 h prior to exercise is crucial for its presentation. Attacks may seldom occur also if food ingestion is made 2–3 hours after exercise. Concomitant use of drugs, particularly aspirin and non-steroidal anti-inflammatory drugs, can worsen the clinical presentation. Clinical manifestations cover a wide range of symptoms, from pruritus to dyspnoea to vascular collapse. Differential diagnoses must be investigated when symptoms are unusual. Several pathogenetic theories have been formulated but the rarity of EIAn has not facilitated the efforts of scientists to find pathophysiological and immunological mechanisms that may account for these conditions. Diagnosis is mainly clinical and can be difficult. Validated protocols including skin prick testing together with food–exercise challenges, laboratory investigations looking for specific immunoglobulin E or through allergy molecular diagnostics are often required. Preventative measures are of fundamental importance, in particular regarding education of patients, family/ carers, trainers and teammates. Use of adrenaline autoinjectors is also fundamental and their correct use must be taught to patients, doctors and nurses. Pharmacological preventative measures are not supported by sufficiently powered studies. Further research will be needed to investigate deeper the complexities of EIAn

A Strategy analysis for genetic association studies with known inbreeding

Background: Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results: We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the betathalassemia, which is a well known Mendelian disease, and also to the common asthma where we have identified candidate genes that underlie to the susceptibility of the asthma. Some of such candidate genes have been also found related to common asthma in the current literature. Conclusions: The data analysis approach, based on selecting the most related cases and controls along with the Random Forest model, is a powerful tool for detecting genetic variants associated to a disease in isolated populations. Moreover, this method provides also a prediction model that has accuracy in estimating the unknown disease status and that can be generally used to build kit tests for a wide class of Mendelian diseases

Clinical pitfalls of leishmaniasis and Whipple’s disease hidden behind systemic lupus erythematosus: A case series

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that can affect major organs possibly leading to life-threatening complications and appears with heterogeneous clinical picture. SLE could present with broad spectrum of clinical and laboratory features that can resemble those of other diseases, such as hemopoietic malignancies, infections, or immune-mediated disorders. Its complexity and protean features overlap with many other diseases, hindering the differential diagnosis. Rarely, true overlap with other diseases may occur. Herein, we report a case series of two patients affected by infectious diseases, namely visceral leishmaniasis and Whipple’s disease (WD), intertwined with clinical or serological features of SLE. In both cases, several confounding factors have led to a delay in the diagnosis. Moreover, we first describe the persistent elevation of autoantibodies and a monoclonal gammopathy in a patient with WD. Awareness of unusual presentations of infections or other rare disorders, which may be encountered in clinical practice when taking care of SLE patients, is essential for timely diagnosis and treatment of potentially lethal diseases

Fungal allergy in asthma-state of the art and research needs

Sensitization to fungi and long term or uncontrolled fungal infection are associated with poor control of asthma, the likelihood of more severe disease and complications such as bronchiectasis and chronic pulmonary aspergillosis. Modelling suggests that >6.5 million people have severe asthma with fungal sensitizations (SAFS), up to 50% of adult asthmatics attending secondary care have fungal sensitization, and an estimated 4.8 million adults have allergic bronchopulmonary aspergillosis (ABPA). There is much uncertainty about which fungi and fungal allergens are relevant to asthma, the natural history of sensitisation to fungi, if there is an exposure response relationship for fungal allergy, and the pathogenesis and frequency of exacerbations and complications. Genetic associations have been described but only weakly linked to phenotypes. The evidence base for most management strategies in ABPA, SAFS and related conditions is weak. Yet straightforward clinical practice guidelines for management are required. The role of environmental monitoring and optimal means of controlling disease to prevent disability and complications are not yet clear. In this paper we set out the key evidence supporting the role of fungal exposure, sensitisation and infection in asthmatics, what is understood about pathogenesis and natural history and identify the numerous areas for research studies

A Traditional Diet Is Associated with a Reduced Risk of Eczema and Wheeze in Colombian Children

Background: Diet might influence the risk of allergic diseases. Evidence from developing countries with high prevalence of childhood asthma is scant. Methods: Information on wheeze, rhinitis, and eczema was collected from 3209 children aged 6–7 years in 2005, who were taking part in the International Study on Asthma and Allergy in Children (ISAAC) in Colombia. Intake frequency of twelve food groups was assessed. Associations between each food group and current wheeze, rhino-conjunctivitis, and eczema were investigated with multiple logistic regressions, adjusting for potential confounders. Simes’ procedure was used to test for multiple comparisons. Results: 14.9% of children reported wheeze in the last 12 months, 16% rhino-conjunctivitis, and 22% eczema. Eczema was negatively associated with consumption of fresh fruits and pulses three or more times per week (adjusted Odds ratio (aOR): 0.64; 95% Confidence Interval (CI): 0.49 to 0.83; p value = 0.004; and aOR: 0.62, 95% CI: 0.47 to 0.80; p value < 0.001, respectively). Current wheeze was negatively associated with intake of potatoes (aOR: 0.44, 95% CI: 0.31 to 0.62, p value = 0.005), whilst this outcome was positively associated with consumption of fast food (aOR: 1.76, 95% CI: 1.32 to 2.35, p value = 0.001). These associations remained statistically significant after controlling for multiple comparisons. Conclusions: A traditional diet might have a protective effect against eczema and wheeze in Colombian children, whilst intake of fast foods increases this risk

HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections

One of the mechanisms by which viruses can evade the host's immune system is to modify the host's DNA methylation pattern. This work aims to investigate the DNA methylation and gene expression profile of COVID-19 patients, divided into symptomatic and asymptomatic, and healthy controls, focusing on genes involved in the immune response. In this study, changes in the methylome of COVID-19 patients' upper airways cells, the first barrier against respiratory infections and the first cells presenting viral antigens, are shown for the first time. Our results showed alterations in the methylation pattern of genes encoding proteins implicated in the response against pathogens, in particular the HLA-C gene, also important for the T-cell mediated memory response. HLA-C expression significantly decreases in COVID-19 patients, especially in those with a more severe prognosis and without other possibly confounding co-morbidities. Moreover, our bionformatic analysis revealed that the identified methylation alteration overlaps with enhancers regulating HLA-C expression, suggesting an additional mechanism exploited by SARS-CoV-2 to inhibit this fundamental player in the host's immune response. HLA-C could therefore represent both a prognostic marker and an excellent therapeutic target, also suggesting a preventive intervention that conjugate a virus-specific antigenic stimulation with an adjuvant increasing the T-cell mediated memory response