Management of patients at risk of anaphylaxis after COVID 19 vaccination.

The success of a vaccination campaign depends on the possibility of guaranteeing not only a wide distribution of effective vaccines, but also on their safety and acceptance by the population. Vaccine safety questions should be answered by correct, unbiased and evidence-based reports, and by addressing all possible problems including allergic reactions. Despite the fact that many COVID-19 vaccines are free from the majority of potentially sensitizing components, an allergic reaction can occur even in the form of a severe, life-threatening anaphylaxis. The frequency of allergic reactions against COVID vaccine is greater than that observed for other vaccinations. National and international allergology societies have proposed specific guidelines for individuals at risk of anaphylaxis by vaccine. Vaccines, like all the pharmaceutical preparations, are submitted to great safety and efficacy valuations, however, even the greatest pre-licensure experimentations are insufficient to evaluate the vaccine's potential to provoke anaphylaxis. Therefore, post-market surveillance is essential to analyze, record and characterize all adverse events. To this purpose, specific algorithms should be used as a monitoring strategy of adverse events in patients undergoing vaccination against COVID 19.

Urticaria and coronavirus infection: a lesson from SARS-CoV-2 pandemic.

Summary: Urticaria is a condition involving both skin and mucosal tissues characterized by the presence of wheals and/or angioedema. The acute form has been related to allergic reactions to drugs or foods, interaction with chemicals, or infections. We reviewed the association of urticaria with coronavirus infections. This review was carried out by the use of two search engines for published original articles, employing two key terms correlated to urticaria and viruses: "urticaria" and one term linked to each virus. The research of the relationships between SARS-CoV-2 and urticaria produced 18 papers (including a total of 114 cases). Surprisingly, the search for cases of urticaria in patients with SARS-CoV or MERS produced no results. We tried to interpret this discrepancy and attempted to analyze the possible pathogenesis of urticaria lesions in SARS-CoV-2.

Microbiota and microRNAs in lung diseases: mutual influence and role insights.

Trillions of microbial cells colonize human body both internally and externally. The prevalent amount of these reside in the gastrointestinal tract (gut microbiome). Gut microflora support the transformation of food nutrients. The products of this modification processes both modulate gastro-intestinal immunity, and influence other organs such as lung and brain. Recently, it was reported the role of micro-RNAs (miRNAs) as regulators in different pathways of the innate and/or adaptive immune responses. Latest studies discussed the aptitude of probiotics strains to balance the host immune response at a post-transcriptional level by controlling miRNAs expression. We speculated a model of lung immune regulation driven by the axis microbiota-microRNAs, involving asthma, acute injury, cancer and COPD. Based on this axis, we propose a novel approach based on the modification of microRNAs expression centered not exclusively on antagomiRs but also on microbiota modification in order to further potentiate their therapeutic effects.

Vitamin deficiency as risk factor for SARS-CoV-2 infection: correlation with susceptibility and prognosis.

OBJECTIVE: In 2019, an infection provoked by SARS-CoV-2 virus arose in Wuhan, China. Currently, there is still no definite and efficacious therapy for SARS-CoV-2 infection. Moreover, our understanding of the physiopathology of the infection, and risk elements for severity and mortality, is incomplete. PATIENTS AND METHODS: One largely neglected element that could affect prognosis of SARS-CoV-2 infection is the vitamin status of population. The purpose of this review is to evaluate whether a vitamin insufficiency could provoke an augmented risk of SARS-CoV-2 infection or the appearance of major complications. In particular, we evaluated the presence of studies related to the state and effects of vitamin D, C, B, and A in subjects with SARS-CoV-2 disease. RESULTS: Although, actually, the interest in a possible use for vitamin supplementation in SARS-CoV-2 patients is essentially based on indirect data, we tried to examine the evidence about a favorable effect of vitamin supplementation in the therapy of the infection and its complications. CONCLUSIONS: Supplements with vitamin A, B, C, D, and E could represent an inexpensive and sufficiently safe approach, and a useful therapeutic complement. However, solid clinical research data are expected to support such claim.

Allergic reactions to genus Morus plants: a review.

Mulberry is a plant belonging to the family Moraceae, and genus Morus. Allergic sensitization to mulberries has been reported as both food allergy or respiratory allergy, and cross-reactivity between mulberries and other pollens or fruits was described. Clinically, in the articles reporting mulberry allergy, the reactions included respiratory allergy, airborne contact urticaria, anaphylaxis, oral allergy syndrome, and food induced urticaria. As far as cross-reactivity is concerned, the allergens identified thus far in mulberries include pathogenesis-related (PR)10 proteins, with sequence identity to Bet v 1 from birch, lipid transfer (LTP)1 proteins with identity with LTPs from Rosaceae family plants, panallergens groups, and also ubiquitin-like protein and cystatin-like protein. The two latter proteins account for cross-reactions with Parietaria judaica and Olea europaea. Such large cross-reactivity warrants to pay particular attention to the risk of systemic reactions to foods, particularly in subjects sensitized to birch, parietaria or olive pollens. In fact, the increasing use of mulberry as a food product, which is encouraged by its remarkable antioxidant power, expose sensitized patients to possible reactions after ingesting foods, dietary supplements or nutraceuticals containing mulberry. Mulberry allergenicity can vary according to the processing methods used since some allergens are thermostable and other loss their reactivity during heating.

Omalizumab retreatment in patients with chronic spontaneous urticaria: a systematic review of published evidence.

Summary: A systematic review of the current literature on retreatment with omalizumab of patients with relapsing chronic spontaneous urticaria was performed. Published evidence shows that retreatment is safe and clinically effective, and that time to complete clinical response reduces as the number of retreatments increases.

Increased serum interleukin-37 (IL-37) levels correlate with oxidative stress parameters in Hashimoto's thyroiditis.

PURPOSE: Interleukin-37 (IL-37), member of the IL-1 family, is a natural suppressor of immune and inflammatory responses. Increased serum IL-37 levels were observed in several autoimmune diseases, including Graves' disease. To our knowledge, no data on Hashimoto's thyroiditis (HT) are available in the literature. METHODS: Aim of our study was to measure serum IL-37 levels and evaluate their relationship, if any, with oxidative stress markers in HT patients. We enrolled 45 euthyroid HT patients (5 M e 40 F, median age 40 years) and 50 age- and sex-matched healthy controls. None was under L-thyroxine therapy. Serum IL-37 levels were measured by ELISA. Specific serum tests, such as derived reactive oxygen metabolites (d-ROMs), and biological anti-oxidant potential (BAP) test were performed in all subjects to investigate the changes in oxidative balance, and advanced glycation end products (AGEs) were determined as a specific marker of oxidative stress. RESULTS: IL-37 levels were significantly higher in HT than in controls (median 475 vs. 268 pg/ml, P = 0.018). In the same patients, serum oxidants (d-ROMs) were increased and anti-oxidants (BAP) decreased compared with controls (P = 0.011 and < 0.0001, respectively), clearly indicating an enhanced oxidative stress. In addition, AGEs levels were higher in HT patients than in controls (210 vs. 140 AU/g prot, P < 0.0001) and directly correlated with IL-37 levels (P = 0.048). At multivariate analysis, the main independent predictors that influenced IL-37 levels were both anti-thyroid antibodies (P = 0.026) and AGEs levels (P = 0.001). CONCLUSIONS: IL-37 is up-regulated in HT and may exert a protective role by counteracting oxidative stress and inflammation.

Lack of clear and univocal genotype-phenotype correlation in familial Mediterranean fever patients: A systematic review.

Familial Mediterranean fever (FMF) is the most common autosomal recessive autoinflammatory disease. To date, following the isolation of more than 280 MEFV sequence variants, the genotype-phenotype correlation in FMF patients has been intensively investigated; however, an univocal and clear consensus has not been yet reached. Thus, the aim of this systematic review was to analyze the available literature findings in order to provide to scientific community an indirect estimation of the impact of genetic factors on the phenotypic variability of FMF. This systematic review has been conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. The p.M694V mutation was reported to have a relatively severe clinical course, similarly, patients homozygous for M694I and M680I, or carrying a combination of both at codons 694 and 680, have a severe disease. Also, patients homozygous for M694V and V726A variants experienced more severe clinical picture. Conversely, heterozygous p.V726A and p.E148Q genotypes have been correlated with a milder disease course. At present, doubts remain on the potential pathogenic role of E148Q variant. The heterogenity in clinical FMF manifestations reflects the changes occuring in repertoire of mutations. We believe that clinical criteria and gene tests, enhancing each other, could better support the diagnosis of FMF.

Interleukin 31 is involved in intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder characterized by maternal itching and altered liver function. Interleukin (IL)-31 is known to be involved in the pathogenesis of pruritic inflammatory skin diseases. In a three-year period, 13 women with a singleton pregnancy and a diagnosis of intrahepatic cholestasis (ICP) were enrolled together with 26 healthy single pregnant women who concluded an uncomplicated pregnancy. The inclusion criteria were itching and elevated levels of liver transaminases. Median serum levels of IL-31 were significantly higher in ICP patients than in the control group (p = 0.004). Furthermore, IL-31 values were directly dependent on liver transaminase levels.

Mucosal exfoliation as a selective reaction to etoricoxib.

WHAT IS KNOWN AND OBJECTIVE: Etoricoxib is a non-steroidal anti-inflammatory drug (NSAID) that inhibits the inducible cyclooxygenase (COX-2) with a good safety profile. We describe the first case of two mucosal adverse events to etoricoxib in the same patient. CASE DESCRIPTION: Our patient developed stomatitis with mucosal exfoliation after etoricoxib assumption. Some months later, after a new etoricoxib intake, she presented with vaginal burning, tongue angioedema and erosions, oral exfoliation and wheals on the hands. A provocation test with diclofenac was negative. WHAT IS NEW AND CONCLUSION: The peculiarities of our case are the rare clinical manifestation and the selective hypersensitivity to COX-2 inhibitor with tolerance to a non-selective NSAID.

Relationship between lead exposure and mild cognitive impairment.

INTRODUCTION: Since it is still controversial whether-low-to moderate long-term lead below current threshold values causes neurobehavioural deficits in adults. METHODS: Forty lead-exposed workers subjects with a mean blood lead (PbB) level of 56.4 µg/dL and 40 non-lead-exposed aged matched subjects (PbB: 15.4 µg/dL) with the same socio-economic background were investigated. Participants were administered a neuropsychological tests consisting of BAMT (Branches Alternate Movements Task), FT (Finger Tapping Speed), DS (Digit Span) POMS (Profile of Mood States). RESULTS: Authors noted a significant relationship between the exposed and the referent groups in tests mainly involving executive functions, short time memory and psycho-emotional variables. In addition, Poisson regression test performed on single psychoemotional factors (POMS), has allowed to evidence a significant influence of Pb e ZPP levels on tension, anxiety and depression. CONCLUSIONS: The present study showed that lead exposure among adults at levels previously considered safe, results in impairment of certain cognitive abilities.

IL-31 and IL-33 circulating levels in allergic contact dermatitis.

Enhanced IL-31 expression in skin biopsies is present in allergic contact dermatitis (ACD). IL-33 expression is induced in keratinocytes and in skin of ACD patients. This overexpression is present in both allergic and irritant conditions. The aim of this work was to test the systemic involvement of IL-31 and IL-33 in ACD. IL-31 levels were significantly higher in patients than in controls. IL-33 serum levels, on the contrary, were similar in patients and controls. This work shows a possible systemic involvement of IL-31 and the absence of a systemic involvement of IL-33 in ACD. IL-31 levels do not seem related to the allergen involved, and did not change on the strength of the allergen involved. More likely, IL-31 levels are related to the itch. IL-33, instead, is secreted from damaged or inflamed tissue and might function as an early warning system at the site of skin damage. In the future, IL-31 could be a possible therapeutic target of all pruritic skin diseases resistant to conventional therapies.

Lymphoproliferative disease and cancer among patients with common variable immunodeficiency.

Innate immune deficiencies are a heterogeneous group of genetically inherited diseases affecting the innate and adaptive immune systems that confer susceptibility to infection, autoimmunity, and cancer. This review discusses the latest insights into the links between common variable immunodeficiency (CVI) and malignancies. Although Ig therapy greatly reduces the number of infections and enhances survival, it does not appear to address the development of cancer, especially lymphoma. The reasons for the increased susceptibility to lymphoid malignancies are unclear. These include genetics, immune dysregulation, radiosensitivity and chronic infections such as Helicobacter pylori, EBV, human herpes virus type 8 and cytomegalovirus. Further studies will allow us to better stratify the risk for cancer in these patients, and teach us to better prevent these complications and to better treat them.

Cutaneous adverse reactions to lenalidomide

Lenalidomide is an immunomodulatory drug (IMiD) used principally in the treatment of multiple myeloma (MM), myelodysplastic syndromes (MS) and amyloidosis. Adverse reactions related to lenalidomide include myelosuppression (mainly neutropenia but also thrombocytopenia), gastrointestinal problems, skin eruption, atrial fibrillation and asthenia, decreased peripheral blood stem cell yield during stem cell collection, venous thromboembolism, and secondary malignances. In this review we focused our attention on the cutaneous adverse reactions to lenalidomide

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Oxidative stress markers are increased in patients with mastocytosis.

BACKGROUND: Mastocytosis is characterized by clonal proliferation of mast cells limited to the skin (cutaneous mastocytosis: CM and mastocytosis in the skin: MIS) and/or involving internal organs (systemic mastocytosis: SM). Oxidative stress occurring in various inflammatory and neoplastic disorders causes molecular damage with the production of advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEs). We evaluated these markers of oxidative stress in patients with CM/MIS and SM and correlated their levels with the presence of symptoms related to mast cell activation. METHODS: Serum levels of AOPPs and AGEs in 34 patients with mastocytosis (23 CM/MIS and 11 SM) and 27 healthy controls were measured by spectrofluorimetric and spectrophotometric methods. Serum tryptase levels were measured by immunofluorescence. RESULTS: Serum AOPPs, but not AGEs, were significantly higher in patients with mastocytosis as compared to healthy controls. While serum tryptase levels were higher in patients with SM as compared to those with CM/MIS, there was no difference in AOPP and AGE concentrations between these two groups of patients. Patients with recurrent mediator-related symptoms had lower AOPPs and AGEs as compared to patients without symptoms. AOPPs and AGEs were inversely correlated with the severity of symptoms, and in patients with symptoms, AOPPs correlated with tryptase levels. DISCUSSION: Our data show that mastocytosis is associated with a state of increased oxidative stress that, in patients with mediator-related symptoms, correlates with mast cell burden as assessed by tryptase. Patients with symptoms presumably have an adaptive response resulting in lower blood levels of AOPPs and AGEs.

Pityriasis rosea of Gibert: immunological aspects.

More than 200 years after first description and 150 years after complete definition by Gibert, pityriasis rosea (PR) is still a clinical entity with many obscure aspects. Although great interest was focused on aetiology, studies on immunological mechanisms associated with this disease were rather discontinuous. We present a review of the literature on immunological features of PR, aimed to outline a unified picture of currently available knowledge in this field and create a useful starting point for future research.