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Background: This study aimed to evaluate the impact of severe asthma (SA) treatments after 12 months in achieving clinical remission (CR) within the context of the Severe Asthma Network in Italy (SANI) using the recent SANI definition of CR on treatment. Methods: CR has been defined by SANI as complete, partial, and no CR. Complete CR is defined by the absence of oral corticosteroids (OCS), no symptoms, no exacerbations, and stable lung function, and partial CR requires the absence of OCS and the fulfillment of 2 out of the other 3 criteria. Patients who do not meet the previous criteria do not reach CR. Results: After 12 months of treatment, 283 patients were selected to evaluate the effectiveness of biologics (225 patients) and inhaled therapy (58 patients) in achieving CR. Among patients treated with biologic agents, 45.8% reached complete CR, 23.1% partial CR, and 31.1% no CR. Differences in CR achievement according to type of biologic agent administered were observed. Interesting results were found when assessing the inhaled therapy (ICS/LABA/LAMA and no biologics) effectiveness: 34.5% patients reached complete CR, 34.5% partial CR, and 31.0% did not reach CR. This finding is noteworthy since it further supports the efficacy of inhaled treatment in certain SA patients and highlights the relevance of using CR as a modern outcome of SA treatments. Chronic rhinosinusitis with nasal polyps (CRSwNP) comorbidity was associated, though not significantly, with CR achievement in patients treated with biologics. Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores significantly impacted CR (p = 0.003 and p = 0.027, respectively), while biomarkers, namely IgE, blood eosinophils, or fractional exhaled nitric oxide (FeNO), were not associated with CR achievement. Conclusions: This study confirmed the effectiveness of biologics in reaching CR and demonstrated also inhaled therapies able to achieve CR. These innovative findings should encourage post hoc analysis of randomized clinical trials or even retrospective analysis of SA patient cohorts to evaluate CR with different inhaled treatments and further define the populations eligible for each treatment. Trial registration: ClinicalTrials.gov ID: NCT06625216; Central Ethics Committee: Comitato Etico Area Vasta Nord-Ovest Toscana (study number 1245/2016, protocol number:73714).

BackgroundGrowing evidence reveals the important role of clinical psychological factors in chronic-immune diseases. The aim of this study was to investigate Health-Related Quality of Life (HR-QoL), depression, anxiety, and alexithymia in patients with severe hypersensitivity reactions such as Severe Allergic Asthma (SAA) and Hymenoptera Venom Anaphylaxis (HVA).MethodsThe Short-Form Health Survey-36 (SF-36), the Beck Depression Inventory Questionnaire (BDI-II), the Hamilton Anxiety Rating Scale (HAM-A) and the Toronto Alexithymia Scale (TAS-20) were used to assess HR-QoL and clinical psychological features of patients with SAA and HVA.ResultsOverall, 78 patients were recruited. Patients with SAA (n = 35) reported lower scores for physical functioning [65 (58–75) vs. 90 (85–95); p =

Background: Aging implies changes in terms of lung function, immune system, and respiratory and extra-respiratory comorbidities. Few studies have specifically addressed the relevance of age on severe asthma burden and control. We aimed to evaluate whether age acts as an independent determinant of asthma severity, in terms of clinical, functional, and inflammatory profile, and to explore potential cofactors that contribute to a more difficult disease control in different age groups. Methods: Patients from Severe Asthma Network Italy (SANI) registry were retrospectively divided in subgroups according to their age. Cutoffs for age were established according to quartiles in order to obtain a comparable number of patients for each group, and then rounded for the sake of simplicity. Results: Overall, 1805 severe asthma patients were analyzed. Lung function represented the most important age-related variable. On the opposite the level of asthma control was not differently distributed among age ranges. In young people the presence of atopy-related comorbidities (allergic rhinitis, atopic dermatitis) predominated, whilst systemic-metabolic and degenerative comorbidities such as diabetes, cardiovascular diseases, anxious-depressive syndrome, and osteoporosis prevailed in elderly. Bronchiectasis and sleep disturbances were significantly associated with age. Conclusions: Despite that it cannot be considered a treatable trait, our study suggests that age should be evaluated within a personalized approach to severe asthma patients, in order to provide a better clinical profiling and a more tailored treatment strategy.

BackgroundTo date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.AimTo elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.MethodsThis was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.ResultsOverall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and

Growing evidence from scientific research elucidates the important role of alexithymia in chronic immune diseases. This Review aims to explore the presence of alexithymia in patients affected by asthma and clarify its associations with other involved psychological and physical factors. In January 2023, according to PRISMA guidelines, a systematic search using PubMed and Scopus was conducted. Twenty-six studies were eligible based on inclusion criteria. Alexithymia was significantly present in asthma patients, with most studies reporting a higher prevalence (from 9 to 62.8%) than in control groups (approximately 10%). The coexistence of asthma and alexithymia was associated with a worse quality of life, psychiatric comorbidity, poor symptom control, and difficulty in recognizing exacerbations of the disease. These results suggest that alexithymia can negatively impact the management of asthma. For this reason, we recommend an accuracy assessment in clinical settings and the implementation of psychological interventions to promote the emotional and physical wellbeing of asthmatic patients.

Background: Severe asthma patients are those suffering from asthma exacerbations despite adherence to maximal optimized asthma treatment such as high dose inhalant corticosteroids and long-acting beta2 agonists (ICS-LABA). It is estimated that about 300 million people in the world are affected from asthma and among them a percentage between 3-10% suffer from severe asthma. The prevalence of Alexithymia in chronic illness is notably high and it is strictly related to clinical severity of chronic diseases. Methods: Pub Med and Google Scholar databases were consulted using the terms “severe asthma” AND “alexithymia” to search English-language articles. According to inclusion criteria 37 articles were finally included and analyzed. Alexithymia may interfere with the perception of the disease and the patients’ awareness of the need of a strict follow-up, to adhere to the physicians’ treatment plans. Results: Alexithymia and related psychological distress as anxiety and depression may compromise the patient’s compliance and adherence, leading to a severe clinical presentation and pathologies’ course. This review highlights a potential relationship between alexithymia and severe asthma as a chronic inflammatory disease and the ways this correlation can be assessed and managed in the Outpatient Asthma Clinic to ensure a global approach to SA patients. Findings reported in literature suggest that, among severe asthma patients, alexithymia is present even if the prevalence of this disorder has not yet been defined. Conclusions: It is likely that the introduction of a gold standard clinical psychological evaluation in medical settings, such as clinical allergy and immunology, may allow to support suffering patients helping them to adequately elaborate their particular condition developing useful strategies to control and to manage with their severe asthma.

BackgroundThe efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation.ObjectiveTo assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence.MethodsClinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP.ResultsAmong the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p < 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p < 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p < 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p < 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p < 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p < 0.01).ConclusionOur results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation.

Abstract Background Processionary caterpillar (PC), also named Thaumatopea pityocampa, has been reported to cause hypersensitivity reactions after contact with a toxin contained in hair-like bristles which cover this insect. Occupational exposure to PC is underestimated in outdoor workers and especially in forestry workers (FW) and is globally diffusing because of rising temperatures. Cases presentation We present the first three cases of FW from Sicily, a Southern Italy (SI) region, which reported hypersensitivity reactions due to exposure to PC infested trees. These cases were identified by the occupational health physician during the annual screening of FW working in the Mountains of north-eastern Sicily. Interviewing a population of 630 FW, 1 male and 2 females reported direct contact skin reactions together with airborne contact reactions to PC hairs causing mild respiratory symptoms in two cases and ocular symptoms in one case, which needed treatment with systemic corticosteroids and antihistamines. Conclusions This is the first report of hypersensitivity reactions in SI FW due to occupational exposure to PC. Further screenings not only in FW but also in other populations of outdoor workers are needed in order to assess the real incidence of contact and airborne reactions due to occupational exposure to PC. Though so far no correlation has been found with atopy, it seems apparent that the reactions occur in susceptible subjects; further research is needed for a correct diagnosis and to identify possible desensitization procedures.

Chronic inflammation represents the cornerstone of the raised cardiovascular (CV) risk in patients with inflammatory rheumatic diseases (IRD), including vasculitis. Standardized mortality ratios in these patients are higher as compared to the general population, and the excess of premature mortality is due to early atherosclerotic events. Thus, IRD patients need appropriate CV risk assessment and management according to this CV disease (CVD) burden. Adequate control of CV risk is still lacking in usual care, but early diagnosis of silent and subclinical CVD is crucial to improve the long-term prognosis of these patients. Increased arterial stiffness may provide a pathophysiological link between inflammation and increased cardiovascular risk. Several noninvasive methods are now available to estimate artery stiffness in the clinical setting, including pulse wave velocity assessment. The independent predictive value of arterial stiffness for cardiovascular events has been demonstrated in general as well as in selected populations, and reference values adjusted for age and blood pressure have been suggested. Thus, arterial stiffness is an interesting biomarker for cardiovascular risk stratification. This systematic review summarizes the additional value that PWV measurement can provide in the setting of vasculitis, with a focus in the different clinical stages and CV risk prevention. This systematic review is registered with registration number: Prospero CRD42021259603.

Background: Traditionally, Eosinophilic Granulomatosis with Polyangiitis (EGPA) has been treated with systemic corticosteroids and immunosuppressants. In recent years, therapeutic efforts have been directed towards targeting eosinophils which represent a major player in the pathogenesis of EGPA. In 2017 the Food and Drug Administration (FDA) approved mepolizumab, a humanized monoclonal antibody targeting interleukin 5 (IL-5) which reduces the production and survival of eosinophils, already used to treat severe eosinophilic asthma, for the management of EGPA. Benralizumab is a humanized monoclonal antibody that targets the IL-5 receptor and is indicated in the treatment of severe eosinophilic asthma.Case description: We describe the case of a young female with a positive history of severe eosinophilic asthma associated with EGPA, treated successfully with benralizumab.

Background: Clinical psychological dynamics are known as effective in the onset of medical conditions. In this regard, alexithymia represents a well-recognized and studied phenomenon, whose study is attracting academic attention. Its relations with several conditions have found consistent resonance in the clinical fields, so that the application of clinical models to disregarded populations represents a relevant clinical opportunity. The current study was aimed at extending alexithymia study to a population consisting of State Forestry officers, including significant variables as age and years of tenure. Methods: The observation group consisted of 59 State Forestry officers, aged between 48 and 67 years old (SD=3.436). All subjects fully completed the protocol, consisting of the Toronto Alexithymia Scale (TAS-20) and a sociodemographic questionnaire. Descriptive statistics, correlational analyses, dependencies and statistical differences were performed in order to let significant relations emerge. Statistical analyses were performed using SPSS 24.0 for the Window package. Results: Descriptive statistics highlighted high scores related to all alexithymia factors (Difficulty Identifying Feelings, Difficulty Describing Feelings, Externally Oriented Thinking, TAS-20 Total score) in the considered individuals. Correlational analyses provided significant relations with reference to age, years of tenure and the whole set of alexithymic variables. Significant dependencies emerged among the selected predictors (age and years of tenure) and Tas-20 variables (including total score), as well as significant differences between two selected groups (38 and 38 years of tenure). Conclusion: Alexithymia emerged as particularly present in the considered population of State Forestry officers, demonstrating its sensibility with reference to age and years of tenure variables. The study of psychological phenomena affecting general subjects’ condition represent an extension of a present research field of high innovativeness, considering the lack of knowledge referred to the selected sample. Furter studies should increase the number of included individuals in order to favor the extension of the emerged results.

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods: Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results: 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions: The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

Chronic spontaneous urticaria (CSU) is defined as the almost daily occurrence of widespread wheals, angioedema, or both, for more than 6 weeks. It affects 1–2% of the general population, with a higher prevalence in female patients, and is more frequent patients over 20 years of age. More than half of all cases of chronic idiopathic urticaria are thought to occur due to an autoimmune mechanism, specifically the production of autoantibodies against the high-affinity immunoglobulin E (IgE) receptor (FcεRI). The quality of life in these patients is often greatly compromised, also due to the onset of comorbidities represented by other autoimmune diseases, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, celiac disease, and type 1 diabetes, among others. This review aimed to analyze the close correlation between CSU and some autoimmune and autoinflammatory diseases, in order to encourage a multidisciplinary and multimorbid approach to the patient affected by CSU, which allows not only control of the natural course of the disease, but also any associated comorbidities.

The immune system is made up by an extremely composite group of cells, whose regulated and harmonious activity is fundamental to maintain health. The mast cells are an essential effector of inflammatory response which is characterized by a massive release of mediators accumulated in cytoplasmic secretory granules. However, beyond the effects on immune response, mast cells can modify bone metabolism and are capable of intervening in the genesis of pathologies such as osteoporosis and osteopenia. Vitamin D is recognized to induce changes in bone metabolism, but it is also able to influence immune response, suppressing mast cell activation and IgE synthesis from B cells and increasing the number of dendritic cells and IL-10-generating regulatory T cells. Vitamin D deficit has been reported to worsen sensitization and allergic manifestations in several different experimental models. However, in clinical situations, contradictory findings have been described concerning the correlation between allergy and vitamin D deficit. The aim of this review was to analyze the close relationships between mast cells and vitamin D, which contribute, through the activation of different molecular or cellular activation pathways, to the determination of bone pathologies and the onset of allergic diseases.

Background and aims: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods: Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. Results: 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24). Conclusions: Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics.

Background: Adherence to medications is crucial in patients with severe asthma in light of the negative clinical impact and costs of non-adherence. Adherence to omalizumab has not been well studied in real-world settings. The aim of this study was to assess adherence to omalizumab and evaluate treatment effectiveness in relation to adherence. Methods: This was a retrospective, observational, and multicenter real-world study. Omalizumab dose, timing of administration, and duration of treatment ( 4 years) were analyzed. Adherence was evaluated by examining rates of expected and missing doses. Good adherence (10% doses missed) were determined. For effectiveness in relation to adherence of omalizumab we considered asthma exacerbations, hospitalizations, asthma control test (ACT), and Forced Expiratory Volume in 1 s (FEV1). Results: A total of 196 patients were evaluated, and 161 were suitable for data analyses. Good adherence was shown in 90.7% of patients and poor adherence in 9.3%. Considering adherence in relation to treatment duration: 4 years, 100% were adherent (expected doses, 6120; missed doses, none). Indices of efficacy between pre- and post-treatment showed significant improvement (p

Abstract Background Kounis syndrome (KS) has been described as the coincidental occurrence of acute coronary syndromes during an allergic reaction with cardiac anaphylaxis. It is caused by inflammatory mediators released after exposure to drugs, food, environmental and other triggers. Oxidative stress occurring in various inflammatory disorders causes molecular damage with the production of advanced oxidation products (AOPPs) and advanced glycation end products (AGEs). Case presentation Markers of oxidative stress were evaluated in a patient who had experienced KS after antibiotic administration in order to investigate the possible role of these molecules in KS. No data, up to now, are available on biomarkers of oxidative stress in patients with drug-induced KS. Conclusions AOPPs, but not AGEs, were significantly increased in the KS affected patient compared to controls as already reported in mastocytosis affected patients.

Abstract Background Hymenoptera sting reactions are among life-threatening causes of allergy. Several epidemiology studies have assessed the risk of these kind of reactions, among the general population, around 3% of adults. This incidence increases among highly at risk populations such as outdoor workers. Hymenoptera stings among forestry workers (FW) are occupational triggers but it has not yet been well defined which is the real incidence of anaphylaxis in these workers, not even in Italy. Two Italian studies reported on the risk of hymenoptera stings (HS) in northern Italy (NI) and central Italy (CI) FW while no data is available on the prevalence in southern Italy (SI) ones. Methods A population of 341 SI FW (301 males and 40 females, mean age 51 years, range 43–63 years), who worked in Sicily, was investigated submitting a standardized questionnaire dealing with reactions to Hymenoptera stings, such as large local reactions (LLR) and systemic reactions (SR). Results HS occurred in 203 FW (59%) and caused reactions in 77 (22%); LLR occurred in 46 (13%) and SR in 31 (9%); SR were life threatening in 9/341 (3%) FW and were treated with epinephrine at the emergency unit as workers did not carry an epinephrine auto-injector. A SR at a subsequent HS followed a LLR in 21/46 FW (46%). Conclusions FW in SI have a generic risk of HS anaphylaxis as in the general population but a higher risk of SR and LLR respect to forestry populations from different Italian geographical areas.SR among SI FW occurred in 9% of them, while published data report the incidence of SR around 2 and 4%, respectively, in the Centre and North Italy FW. The incidence of LLR in SI FW was also higher (13%) than in CI (2%) and NI (10%) ones. Previous LLR in our SI population represented a high risk factor for developing a SR and therefore a red flag for future anaphylaxis and prescription of an epinephrine auto-injector.

Background: Cross-reactivity between pollens and plant food has been widely described. Pollen extract subcutaneous immunotherapy in patients with pollens and plant food allergy has been shown to improve tolerance not only to inhalant allergens but also to reduce symptoms in patients with various food allergies. Methods: We retrospectively report our experience with 15 female patients with a positive history for moderate, persistent allergic rhinitis due to grass pollen and oropharyngeal symptoms after ingestion of different plant food. These patients followed a five-grass pollen sublingual tablet immunotherapy for three years in a discontinuous pre-co-seasonal scheme. Results: All 15 patients treated with the 5-grass pollen sublingual tablet immunotherapy, taken once daily for 3 years on a 7-month course, showed improved ocular/nasal symptoms, with a reduction in the use of symptomatic drugs (e.g., nasal corticosteroids and H1 antihistamines). After the first seven-month course of immunotherapy, all patients declared a good tolerance to the intake of fruits and vegetables, and in particular, good tolerance to the offending foods. Conclusions: In conclusion, we have observed improvement of both respiratory and plant food allergies after sublingual immunotherapy (SLIT) with a five-grass pollen tablet.

Common variable immunodeficiency (CVID) is a primary immunodeficiency due to a disorder of the adaptive immune system which causes hypogammaglobulinemia and therefore an increased susceptibility to infection; noninfectious, inflammatory conditions including systemic autoimmunity and lymphoproliferative complications are also commonly associated with CVID. Castleman disease (CD) is a systemic disease clinically characterized by diffuse lymphadenopathy, splenomegaly, anemia, and systemic inflammatory symptoms. This makes CD a great mimicker of more common benign and malignant masses in the neck, chest, abdomen, and pelvis. A novel case of primary immunodeficiency (CVID) in a middle-aged woman, who developed multicentric CD (MDC) with splenomegaly, is described. The authors suggest that the onset of MCD and of the correlated splenomegaly was due to incorrect management of the hypogammaglobulinemia as immunoglobulin G (IgG) levels were not kept within normal ranges. Correct management of the hypogammaglobulinemia allowed splenectomy to be performed without any infectious surgical complications. MCD is reported for the first time in association with an adult case of CVID. The above reported case highlights the need for a timely correct diagnosis and treatment of CVID to avoid complications, which could cause recourse to splenectomy, such as in our case or development of malignancies.