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Background: Italy was one of the first affected countries by coronavirus disease 2019 (COVID-19) pandemic. Public health measures like quarantine or national lockdown were adopted, with negative psychological and clinical effects on patients with chronic diseases. To investigate the impact of lockdown on patients with multiple sclerosis (MS), we developed a 36 items self-report questionnaire. Methods: Questionnaires were emailed to 120 patients with MS and 100 with chronic migraine (CM) as a control group, matched for age, sex, and education. The questionnaire was divided into five domains, evaluating concerns about 1) MS and therapy during COVID-19 pandemic, 2) personal and family caregiving, 3) working activities, 4) general and disease-related emotions during the lockdown, 5) future expectations concerning health status, social life, and working activity. Results: patients with MS had higher scores than those with CM in domains 4 and 5, investigating respectively general and disease-related emotions and future expectations (p= 0.05 and 0.02 respectively). About half of the patients with MS expressed some concern about the need to continue their therapy during the pandemic compared to people with CM (p= 0.0002). Conclusions: Covid-19 pandemic had a more negative impact on psychological status of patients with MS compared with those with CM

In recent years, the prevalence of large spectrum of gluten-related disorders (GRDs) has increased. Gluten is one of the most widely distributed components of food in both industrialized and developing countries. The main structural protein complex of wheat and its proteins are classified into albumins, salt-soluble globulins, and insoluble prolamins (gliadins and glutenins). Gluten is also included in other cereals, including rye and barley. GRDs can be classified, based on their pathogenic mechanism, into (i) Autoimmune disorders, (ii) Allergic disorders, (iii) No autoimmune, not allergic disorders. Coeliac disease (CD) is an autoimmune disorder that occurs in genetically predisposed individuals who develop an immune reaction to gluten. It affects about 1% of people in most populations. The disease primarily interests the small intestine, but it is characterized by a wide range of clinical presentations, with both intestinal and extra-intestinal symptoms. Wheat allergy (WA) is an adverse immunologic reaction to wheat proteins. In the large field of WA a further classification can be made, distinguishing IgE-dependent WA, triggered by ingestion, inhalation or cutaneous and/or mucosal contact of wheat, and IgE-non-dependent WA. Its prevalence varies depending on the age and region, from 0.4% to 4%. Urticaria and/or angioedema, and anaphylaxis with or without exercise as a trigger, appear typically during childhood, asthma and/or rhinitis (Baker’s asthma) are more common during adulthood. Non-coeliac gluten sensitivity (NCGS) is a condition in which gluten ingestion leads to one or more of a variety of immunological, morphological or symptomatic (both gastrointestinal or extra gastrointestinal) manifestations in people in whom CD has been excluded. It is supposed it’s due to an activated innate immune response.

Allergic individuals at risk for hypersensitivity reactions to measles vaccine marketed for a long time are well established. On the other hand, risk factors for hypersensitivity reactions to the new mRNA COVID-19 vaccines currently include a history of allergy, allergy to excipient of the vaccine, or hypersensitivity reactions to the first dose of COVID-19 vaccine. In the last two cases, the recipient should be assessed by an allergist before vaccination to share a decision on the choice of vaccination. Studies on skin testing accuracy and desensitization protocols to the COVID-19 vaccines and the efficacy of potential alternatives in patients with confirmed hypersensitivity reactions to the first COVID-19 vaccine are necessary to improve the safety of COVID-19 vaccines.

To highlight the current evidence on food desensitization in children with food allergy.Food Allergen Specific Immunotherapy (FA-AIT) is currently recognised as a treatment option for treating children with allergy at least to the main common foods (i.e. milk, egg and peanut). The oral route of administration has been proven to be the most effective in achieving desensitisation. Efforts are devoted to overcome the current unmet needs mainly related to safety issues and long-term efficacy, as well as adherence to the treatment and improvement of health-related quality of life. In this perspective, alternative routes of administration and adjunctive treatments are under investigation.The future of food allergy management is a personalised approach based on a shared decision-making that takes into account the needs of patients and families. Health professionals will be able to offer multiple treatment options, including FA-AIT with adjunctive or alternative therapies. Thus, patients should be correctly identified, using validated predictive factors, in order to select appropriate candidates for these therapies.

Objective Motor surround inhibition (mSI) is a physiological mechanism that contributes to hand movement control by focusing voluntary movement. Growing evidence suggests that hand movement control is impaired in multiple sclerosis. The aim of the study was to evaluate mSI in MS and to investigate the brain structures involved in mSI in multiple sclerosis. Methods We recruited 33 patients and 23 controls. To investigate mSI, we delivered transcranial magnetic single pulses during index finger flexion. Motor evoked potentials were recorded and first dorsal interosseous (“active muscle”) and from the abductor digiti minimi (“surround muscle”). mSI was expressed as the ratio between Motor evoked potentials recorded from the surround muscle during movement and at rest. Participants underwent a magnetic resonance study. Results Patients had impaired mSI as compared with controls. Magnetic resonance showed that basal ganglia had smaller volumes and higher mean diffusivity than controls. Impaired mSI correlated with primary motor cortex and basal ganglia involvement in multiple sclerosis. Conclusion Altered mSI in multiple sclerosis is related to cortical and subcortical grey matter involvement. Significance Our study provides the first demonstration of a pathophysiological mechanism underlying hand movement control dysfunction in multiple sclerosis. mSI represents a new therapeutic target of multiple sclerosis rehabilitative approaches.

Introduction: In recent years, the advent of immunotherapy has remarkably improved the management of IgE-mediated food allergy. However, some barriers still exist. Therefore, the effort of researchers aims to investigate new perspectives in the field of non-allergen specific therapy, also based on the current knowledge of the pathogenesis of this disease.Areas covered: This review aims to focus on the role of biologics as a treatment option in patients with IgE-mediated food allergy. These agents are characterized by their ability to inactivate the Th2 pro-inflammatory pathways. Biologics can be used both alone and in association with immunotherapy. Monoclonal antibodies targeting IgE, the IL-4/IL-13 axis, IL-5, and alarmins have been proposed and investigated for treating food allergy.Expert opinion: The clinical efficacy and safety of biologics have been demonstrated in several preclinical studies and randomized controlled trials. Future studies are still required to address current unmet needs, including the identification of the optimal dose to be used by ensuring the effectiveness of therapy.

In the "parallel studies" project led by Carl Rogers at the Counseling Center of the University of Chicago over 70 years ago, measures of personality organization and other clinical ratings were applied to 10 recorded and transcribed cases. This paper applied computerized measures of the referential process to the treatment by Rogers of the client known as Miss Vib. The treatment was considered successful and used by Rogers to illustrate his theory of personality, and his view of the therapeutic process. Using the DAAP system, the measures were applied to therapist and client speech at embedded levels of magnification, including measures for the treatment as a whole to be compared to other treatments in the referential process data base; measures for individual sessions to show progression across the trajectory of a treatment for comparison with the clinical ratings; and measures representing word by word variation within a session to enable close examination of the process. The initial prediction concerning the relation of the referential process measures to the clinical measures was not confirmed. Close examination of pivotal sessions provided an account of the results beyond that emphasized in the client-centered approach.

Mastocytosis, a heterogeneous mastcell disease, include three different entities: cutaneous mastocytosis, systemic mastocytosis (SM) and mast-cell sarcoma. Tryptase levels can differentiate cutaneous mastocytosis from SM. In mastocytosis, quick onset drug hypersensitivity reactions (DHRs) that are facilitated by mastcell mediators, are investigated in adults. Due to the limited number of children with mastcell disease and increased serum tryptase levels, the role of drugs in this age group is less studied. In this review, we critically assessed relevant papers related with immediate DHRs in children with mastocytosis and discuss practical issues of the management. In childhood mastocytosis, anaphylaxis is frequently idiopathic, and elevated level of basal tryptase, and high burden of disease may increase the risk. Among drugs, antibiotics, NSAIDs and opioids can potentially induce anaphylaxis, anyway avoidance should be recommended only in case of previous reactions. Moreover, vaccinations are not contraindicated in patients with mastocytosis. The risk of severe systemic reactions after drugs intake seems to be extremely low and in general lower in children than in adults. Anyway, studies on this topic especially focusing on children, are missing to state final recommendations.

IntroductionThe Health Assessment Questionnaire (HAQ) has been translated into many languages and it has been classified as the predictor of disability and medical costs, however, the psychometric properties of the HAQ have never been studied in a population with neurological disease. The purpose of this study was the evaluation of the psychometric properties of HAQ in a population of individuals with multiple sclerosis (MS).Materials and MethodsThis cross-sectional study was conducted with patients diagnosed with MS. The evaluation tools administered were the 36-item short form health survey (SF–36) to evaluate the health state of the patients and HAQ and to evaluate the limitations of the activities of daily living (ADL).ResultsA total of 34 patients were included in this study. Cronbach's alpha assessed the internal consistency of the HAQ, and it is equal to 0.94. The study revealed some significant correlations between the dimensions of the SF-36 and the sub-categories of the HAQ using Pearson's Correlation Coefficient. Significant correlations emerged between the demographic and clinical characteristics of patients and the subcategories of HAQ.DiscussionThe HAQ is a valid and reliable tool to assess the limitations of the activities of daily living, and it could provide for the healthcare and rehabilitation sector with an additional evaluation tool.

Food allergy is a potentially life-threatening medical condition and a significant public health concern worldwide. The current management consists of strict avoidance of the culprit food and treating any adverse reactions from unintended food ingestion. The increasing prevalence of food allergy encouraged research and clinical trials in the field of specific allergen immunotherapy (AIT) which represents an appealing approach, especially in pediatric age. AIT consists of the gradual administration of growing amounts of the offending allergen in order to induce food desensitization, which is an increase in the threshold for reactivity while continuing on regular exposure to the allergen. AIT can be administered through oral, sublingual, epicutaneous, and subcutaneous routes. Reports on oral immunotherapy (OIT) thus far have been more extensive. The desirable goal is to achieve "post desensitization effectiveness", that is the ability to introduce food without reaction even after a period of discontinuation of the offending food. Other therapeutic approaches are being studied alongside immunotherapy such as modified proteins, probiotics, Chinese herbal supplements, biologic therapies, and DNA vaccines.

Hypersensitivity reactions to radiocontrast media seem to be rare in children. Furthermore, the use of radiocontrast media in children remains quite safe in terms of the severity of reactions. Since pediatric guidelines are lacking, the diagnostic workup employed in adults could be adapted to children, taking into account that results have not yet been validated in this age group. Specific protocols for risk stratification and management of severe reactions have been proposed so far.

Secondary progressive multiple sclerosis (SPMS) subtype is retrospectively diagnosed, and biomarkers of the SPMS are not available. We aimed to identify possible neurophysiological markers exploring grey matter structures that could be used in clinical practice to better identify SPMS. Fifty-five people with MS and 31 healthy controls underwent a transcranial magnetic stimulation protocol to test intracortical interneuron excitability in the primary motor cortex and somatosensory temporal discrimination threshold (STDT) to test sensory function encoded in cortical and deep grey matter nuclei. A logistic regression model was used to identify a combined neurophysiological index associated with the SP subtype. We observed that short intracortical inhibition (SICI) and STDT were the only variables that differentiated the RR from the SP subtype. The logistic regression model provided a formula to compute the probability of a subject being assigned to an SP subtype based on age and combined SICI and STDT values. While only STDT correlated with disability level at baseline evaluation, both SICI and STDT were associated with disability at follow-up. SICI and STDT abnormalities reflect age-dependent grey matter neurodegenerative processes that likely play a role in SPMS pathophysiology and may represent easily accessible neurophysiological biomarkers for the SPMS subtype.

Intravenous iron is widely used for the treatment of iron deficiency anemia when adherence to oral iron replacement is poor. Acute hypersensitivity reactions during iron infusions are very rare but can be life threatening. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, atopic diseases, high serum tryptase levels, asthma, and urticaria. The management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff. Avoidance of IV iron products in patients with iron hypersensitivity reactions may not be considered as a standard practice.

Food allergy is a potentially life-threatening condition and a significant public health concern worldwide. The current management includes food avoidance and use of emergency medications. The growing prevalence of food allergy drives research towards specific allergen immunotherapy (AIT), which represents a potential disease-modifying approach. AIT consists of the progressive administration of amounts of the offending allergen in order to induce food desensitisation, creating an increase in reaction threshold with regular exposure to the allergen. AIT can be performed through oral, sublingual, epicutaneous, and subcutaneous routes. The target is to achieve post desensitisation effectiveness: a long-lasting condition allowing patients to introduce food without reactions, even after a period of discontinuation of the offending food.

Background: Immunoglobulin E (IgE) mediated food allergy is a potentially life-threatening condition and represents a heavy burden for patients and their families. Identification of the most suitable way for management of each patient has currently become the primary goal for physicians. Methods: This study reviewed the current literature related to IgE-mediated food allergy. Results: The use of innovative diagnostic tools, such as allergen-specific IgG4 determination, basophil activation test, and component-resolved diagnostics, is currently available to facilitate a proper diagnosis of food allergy. After several decades of “passive clinical management” of the disease, which was based only on avoidance of the allergenic food and the use of epinephrine in the event of anaphylaxis, there has been a switch to active treatment. The most recent evidence-practice guidelines strongly recommend the use of immunotherapy as an effective therapeutic option, particularly in cases of allergy to cow's milk, egg, or peanut. The use of omalizumab, in association with immunotherapy or alone, has been tested in several studies, and results on its effectiveness seemed to be encouraging. Other biologics, such as dupilumab, reslizumab, mepolizumab, and other anticytokines therapies, are being investigated. Another interesting future treatment strategy could be the use of DNA vaccines. Conclusion: In recent years, the management of IgE-mediated food allergy has greatly improved. Knowledge of pathogenetic mechanisms, understanding of the disease course, and the introduction of novel biomarkers led to more accurate diagnoses along with the active treatment of patients.

Background: Frailty is an age-related status of increased vulnerability to stressors caused by the accumulation of multiple health deficits. This construct may allow to capture the clinical complexity of patients with multiple sclerosis (MS). Objective: To investigate the relationship between frailty and the clinical manifestations of MS. Methods: Patients with MS were consecutively enrolled at five tertiary dedicated services. Disability and fatigue were assessed. The phenotypes of MS were also identified. Frailty was measured using a frailty index (FI), computed by cumulatively considering 42 age-related multidimensional health deficits. Results: Overall, 745 MS patients (mean age = 48.2 years, standard deviation = 11.7 years; women 68%) were considered. The median FI value was 0.12 (interquartile range = 0.05–0.19) and the 99th percentile was 0.40. FI scores were associated with MS disease duration, disability, fatigue, as well as with the number of previous disease-modifying treatments and current symptomatic therapies. A logistic regression analysis model showed that FI score was independently associated with the secondary progressive phenotype. Conclusion: Frailty is significantly associated with major characteristics of MS. The findings of the present cross-sectional investigation should be explored in future longitudinal studies.

Introduction Bowel dysfunction (BD) is reported as a common and disabling symptom in multiple sclerosis (MS) patients. To date, no studies have explored the prevalence of these symptoms in a large multicenter outpatient setting. The aims of the present study are to assess: (i) the prevalence of BD in a large multicenter Italian MS population, and (ii) the correlation between clinico-demographic variables and the severity of BD. Methods Each of the nine participating center screened MS patients prospectively: 1100 subjects were enrolled. All patients underwent the Expanded Disability Status Scale (EDSS) and completed the Neurogenic Bowel Dysfunction score (NBDs). Multivariable linear and logistic regression models were used to assess the association between NBDs and several clinico-demographic variables. Results Fourteen percent of MS patients showed a moderate/severe BD (NBDs > 10); this percentage increased in patients with high disability, ranging from 26 to 32%. Moderate/severe BD was more frequent in MS patients with: progressive phenotypes, higher disability, older age, and longer disease duration. NBDs severity was predicted by female sex, ambulation impairment and bladder symptoms. Conclusion This study confirms the relatively high prevalence of moderate/severe BD in a large, multicenter, unselected, outpatient MS population. BD appears to be mainly associated to female sex and MS-related disability.

In the "parallel studies" project led by Carl Rogers at the Counseling Center of the University of Chicago over 70 years ago, measures of personality organization and other clinical ratings were applied to 10 recorded and transcribed cases. This paper applied computerized measures of the referential process to the treatment by Rogers of the client known as Miss Vib. The treatment was considered successful and used by Rogers to illustrate his theory of personality, and his view of the therapeutic process. Using the DAAP system, the measures were applied to therapist and client speech at embedded levels of magnification, including measures for the treatment as a whole to be compared to other treatments in the referential process data base; measures for individual sessions to show progression across the trajectory of a treatment for comparison with the clinical ratings; and measures representing word by word variation within a session to enable close examination of the process. The initial prediction concerning the relation of the referential process measures to the clinical measures was not confirmed. Close examination of pivotal sessions provided an account of the results beyond that emphasized in the client-centered approach.

The recent EAACI/GA2 LEN/EDF/WAO guidelines recommend omalizumab (anti-IgE) for the management of patients aged ≥12 years with chronic urticaria unresponsive to high-doses second-generation H1 -antihistamines (antiH1 ). However, there is little published information on the success of omalizumab for such a treatment in children. We reported our experience of six patients with chronic spontaneous urticaria (CSU) treated with omalizumab. Mean age of our case series was 14.7 years (range 11-16 years) with a prevalence of male gender (66.7%). All six patients were treated with at least one 6-months course of omalizumab. The average follow-up period was 13 ± 6 months. Only one patient was no responder to omalizumab therapy. Thus far, two patients have experienced a complete CSU regression over 12 months after the final omalizumab administration. The remaining three patients needed a second course of treatment. Our experience demonstrates that omalizumab is effective and safe as treatment option for CSU unresponsive to antiH1 , even in adolescent age.

The COVID-19 pandemic is the most challenging global health crisis of our times. Vaccination against COVID-19 plays a key role to control the current pandemic situation. The risk of allergic reactions to new COVID-19 vaccines is low. However, there is a debate on the safety in allergic patients following post marketing findings by different agencies. Our aim is to understand from current experiences whether children with cow’s milk or food allergy are at higher risk than a general population for allergic reactions to COVID-19 vaccines. Current data indicate that patients with a history of allergy to cow’s milk or other foods, even if severe, should receive COVID-19 vaccine in a setting with availability of treatments for anaphylactic reactions and under medical supervision. Recipients should be discharged after a protracted observation period of 30 min if no reaction developed.

Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by the progressive loss of cortical, bulbar, and spinal motor neurons (MNs). The cardinal manifestation of ALS is a progressive paralysis which leads to death within a time span of 3 to 5 years after disease onset. Despite similar final output of neuronal death, the underlying pathogenic causes are various and no common cause of neuronal damage has been identified to date. Inflammation-mediated neuronal injury is increasingly recognized as a major factor that promotes disease progression and amplifies the MN death-inducing processes. The neuroimmune activation is not only a physiological reaction to cell-autonomous death but is an active component of nonautonomous cell death. Such injury-perpetuating phenomenon is now proved to be a common mechanism in many human disorders characterized by progressive neurodegeneration. Therefore, it represents an interesting therapeutic target. To date, no single cell population has been proved to play a major role. The existing evidence points to a complex cross talk between resident immune cells and nonresident cells, like monocytes and T lymphocytes, and to a dysregulation in cytokine profile and in phenotype commitment. After a summary of the most important mechanisms involved in the inflammatory reaction in ALS, this review will focus on novel therapeutic tools that rely on tackling inflammation to improve motor function and survival. Herein, completed, ongoing, or planned clinical trials, which aim to modify the rapidly fatal course of this disease, are discussed. Anti-inflammatory compounds that are currently undergoing preclinical study and novel suitable molecular targets are also mentioned.

The aim of this guidance is to provide recommendations to clinicians and other interested parties on chronic urticaria in children. The Italian Society for Pediatrics (SIP), the Italian Society for Allergy and Immunology (SIAIP), the Italian Society for Pediatric dermatology (SIDerP) convened a multidisciplinary panel that prepared clinical guidelines for diagnosis and management of chronic urticaria in childhood. Key questions on epidemiology, natural history, diagnosis, and management were developed. The literature was systematically searched and evaluated, recommendations were rated and algorithms for diagnosis and treatment were developed. The recommendations focus on identification of diseases and comorbidities, strategies to recognize triggering factors, improvement of treatment by individualized care.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be considered a late-onset allergic reaction, can cause serious long-term sequelae. SJS/TEN are considered a spectrum of life-threatening adverse drug reactions. They have the same clinical manifestations and the only difference is in the extent of epidermal detachment. These conditions are associated with high mortality, although incidence of SJS/TEN is rare in children. SJS/TEN is an adverse drug reaction influenced by genes that involve pharmacokinetics, pharmacodynamics and immune response. Infective agents are additional influencing factors. Anticonvulsants and antibiotics, and especially sulphonamides and non-steroidal anti-inflammatory drugs, are among the drugs that were predominantly suspected of triggering SJS/TEN. No evidence-based standardized treatment guidelines for SJS or TEN are currently available. The usual treatment is mainly founded on the withdrawal of the suspected causative agent and supportive therapy. In pediatric patients, the specific therapeutic strategies are controversial and comprise systemic corticosteroids and the use of intravenous immunoglobulin (IVIG). More recently, new therapeutic approaches have been used, such as immunosuppressive therapies, including cyclosporine and TNF-α inhibitors. (www.actabiomedica.it)

About 10% of the parents reported that their children are allergic to one drug and the betalactam antibiotics are the most frequently suspected. Even if most of the adverse events following antibiotic prescriptions to children are considered allergic, after a full allergy work-up only a few of the suspected reactions are confirmed. For this reason, many children are incorrectly labelled as “allergic” and this represents an important challenge for the choice of the antibiotic therapy in these “labelled” children, who are frequently improperly deprived of narrow-spectrum antibiotics because considered as allergic. When an allergic reaction is suspected a precise diagnosis and a choice of a safe and effective alternative is essential for the future antibiotic option. In the light of this, the main aim of this paper is to try to provide a practical approach to managing the individuals who have reported adverse reactions to antibiotics. (www.actabiomedica.it)

Drug allergy is an increasing problem worldwide, affecting all populations and races, children and adults, and for which diagnosis and treatment are not well standardized yet. Besides classical treatments, new drugs have been developed, especially for patients suffering from malignancies and chronic inflammatory diseases, that specifically target the cause of the disease. For those patients requiring such molecules, it is sometimes difficult to find an alternative drug when hypersensitivity reactions occur. Desensitization is therefore the best option whenever no alternative therapy is available but also when alternative treatments are considered therapeutically inferior and or more toxic. Despite its clinical success, little is known about the mechanisms and molecular targets of drug desensitization. Desensitization protocols use a gradual dose escalation to allow the safe administration of a treatment to which a patient previously presented a hypersensitivity reaction. The procedure requires special training and coordination of an allergy team, including physicians, nurses, and pharmacists, working together to safely and successfully implement desensitization protocols when appropriate. There is no difference in desensitization protocol between adults and children, except for the final cumulative dose of the administered drug. (www.actabiomedica.it)

Non-steroidal anti-inflammatory drugs, perioperative drugs, radio contrast media and chemotherapeutics drugs are, after the non-antibiotic drugs, the drugs most commonly responsible for allergic reactions in children. Management is different depending on the drug involved. (www.actabiomedica.it)

Children who are highly sensitive to milk may also have severe allergic reactions after exposure to cow's milk proteins(CMP) through a different administration route than the oral one. We describe the case of a 16-year-old Caucasian boy with a clinical history of persistent cow's milk allergy (CMA), who developed one episode of anaphylaxis following cutaneous application of a bovine colostrum containing cream to a surgical wound. UniCAP testing showed a significant elevation in specific IgE antibodies to whey milk proteins. Until now, only three cases of anaphylaxis following cutaneous application of products containing milk proteins were available in the scientific literature.

Allergen immunotherapy (AIT) is currently the only available disease-modifying and aetiological treatment of IgE-mediated diseases. Sublingual allergen immunotherapy (SLIT) constitutes the preferred route of administration of AIT for respiratory allergies in Europe. Recently it has also been approved in the US. Further applications are currently under evaluation, such as IgE-mediated food allergy and IgE-mediated atopic dermatitis. The SLIT safety profile is overall favourable, although local adverse events, usually mild, are described. Most of the meta-analyses confirmed the efficacy of SLIT in reducing symptoms and medication intake in children with allergic diseases. AIT, as an immune-modulating treatment, can modify the natural history of the allergic diseases: reduction of the risk of development of asthma and bronchial hyperreactivity in patients with allergic rhinitis, and reduction of the onset of new sensitizations. A great interest is now devoted to the preventive effects of AIT and, consequently, to the optimal time of initiation.

Background Cow's milk allergy is common in infancy, and total avoidance of this food is the only effective approach. In alternative, oral immunotherapy has been proposed to achieve tolerance. Once desensitization is achieved, daily intake of milk is recommended to maintain it, but this may be impractical for children/parents. We assessed whether a twice weekly maintenance regimen is effective. Methods Children who were successfully desensitized with oral immunotherapy were randomized to two maintenance regimens for 1 year: group A had to eat 150–200 ml milk daily, group B had to eat 150–200 ml milk twice weekly. Both regimens were associated to a totally free diet. Maintenance of tolerance and adverse events were recorded during 1 year. Specific IgE, IgG4 and prick-by-prick test to milk were carried out before immunotherapy (T0), before maintenance (T1), and after 1 year (T2). Results Recorded episodes included asthma, oral itching, urticaria, rhinitis, abdominal pain variously combined, usually associated with concomitant illness or exercise. The episodes were 8 in group A and 9 in group B, with no difference. None of the children discontinued the feeding maintenance. Specific IgG4 increased at T1 and remained high at T2. Specific IgE and skin reactivity significantly decreased at T2. There was no difference in those parameters between the groups. Conclusion After achieving desensitization to cow milk with oral immunotherapy, a maintenance regimen with milk given twice weekly is as effective as the daily maintenance.

To cite this article: Pajno GB, Caminiti L, Crisafulli G, Vita D, Valenzise M, De Luca R, Passalacqua G. Direct comparison between continuous and coseasonal regimen for sublingual immunotherapy in children with grass allergy: A randomized controlled study. Pediatr Allergy Immunol 2011: 22: 803–807. Abstract Background: Pre-seasonal, pre-coseasonal and continuous regimens of immunotherapy have been proposed, but their efficacy was never compared. This phase IV open study was designed to compare the clinical efficacy of a continuous and a coseasonal sublingual immunotherapy (SLIT) for grass allergy over 3 years. Methods: Children with rhinitis/asthma because of grass were randomized to SLIT given continuously (all year long) or coseasonally. The treatment started in October 2005 in the continuous SLIT group and in March 2006 in the coseasonal group Diary cards for clinical symptoms (from 0 = none to 3 = severe), and drug intake were recorded form March to June in 2005 (baseline), 2006 2007, and 2008. Specific IgE and IgG4 were evaluated every year. Results: Eighty children (age range 8–16) were randomized and 72 completed the study. In the first year, the symptom + medication score improved by 44% in the continuous group and by 20% in the coseasonal group (p = 0.04). Symptoms, chest symptoms, and drug intake separately showed a greater decrease vs. baseline in the continuous group. In the second year, the global score decreased in both groups with no significant difference, whereas symptom score decreased more in the continuous group. In the 3rd year, there was no difference in clinical parameters between the two groups. Specific IgG4 were significantly higher vs. baseline since the 1st year in the continuous group and since the 2nd in the coseasonal group. Conclusion: In grass pollen allergy, the continuous regimen performs better than the coseasonal in the first season, whereas in the subsequent years, the two regimens are nearly equivalent.

Cow milk allergy is a common disease of infancy, often associated with atopic dermatitis (AD). Avoidance of cow milk (CM) implies the use of alternative dietary supports such as mammalian milks. In this study, we assessed the tolerability and clinical effect of ass's milk (AM), when compared with the largely used goat's milk (GM) in a single-blind, controlled, randomized crossover. Twenty-eight children with AD and ascertained allergy to CM were enrolled. The children were randomized to AM or GM for 6 months, then switched to the other milk for further 3 months. The SCORAD index (SI) and a visual analog scale (VAS) were evaluated blindly. After termination of the study, food challenges with GM and AM were performed. An SDS-PAGE analysis of different milks was performed. Two children from the GM group dropped out after randomization and 26 completed the study. Ass milk invariantly led to a significant improvement of SI and VAS of symptoms (p < 0.03 vs. baseline and inter-group), whereas GM had no measurable clinical effect. At the end of the study 23 of 26 children had a positive food challenge with GM and one of 26 with AM. Ass's milk had a protein profile closer to human milk than GM. Ass milk is better tolerated and more effective than GM in reducing symptoms of AD. It may represent a better substitute of CM than the currently used GM.

OBJECTIVE: In order to ascertain the advantages of early GH treatment in Turner syndrome (TS), we started a prospective study aimed at evaluating prepubertal height gain in a cohort of 29 girls who were treated with the same pro-kilo GH dose (1.0 IU/kg per week) since they were less than 6 years old and for at least 5 years before entering puberty. PATIENTS AND DESIGN: Following a minimum of 6 months of baseline observations, 29 girls with TS were enrolled for this prospective study provided that they (a) were less than 6 years old, (b) were below -1.0 standard deviation score (SDS) for height, (c) had a projected adult height (PAH) lower than the respective target height (TH) and (d) had a height velocity (HV) lower than -1.0 SDS. All the selected girls underwent a 5-year treatment with biosynthetic GH at a stable dose of 1.0 IU/kg per week and were periodically measured during the treatment period in order to evaluate height, HV and PAH. RESULTS: After a dramatic acceleration during the 1st year, HV was attenuated during the subsequent years, reaching its nadir at the 5th year. Height deficiency under therapy progressively decreased from entry onwards, shifting from -2.4+/-0.7 to -1.0+/-1.2 SDS. In the same period, mean PAH progressively increased, although after 5 years it remained lower than the average TH. CONCLUSIONS: (a) An effective growth-promoting strategy in TS should be based on early GH treatment, as suggested by our results. (b) This strategy could result in a prepubertal normalization of height, thus allowing the appropriate timing for the induction of puberty. (c) An initial GH dose of 1.0 IU/kg per week may be suitable during the first years of therapy, as shown by our data documenting an important waning effect of GH therapy only after the 4th year of treatment. (d) No acceleration of bone maturation was observed under this treatment regimen.

OBJECTIVE: The loss of pancreatic beta-cells is thought to be one of the principal causes of diabetes mellitus (DM) in cystic fibrosis (CF), but the role of peripheral insulin resistance (IR) in the pathogenesis of DM in CF remains unclear. The aim of this study was to evaluate whether eventual changes of glucose tolerance (GT) over time were associated with modifications of insulin secretion or sensitivity. METHODS: Plasma glucose and insulin responses to an oral GT test (OGTT) were investigated and reinvestigated 13 Years later in 14 CF patients with initial and persistent fasting euglycemia and no history of insulin treatment. Insulin sensitivity (IS) at both tests was assessed on the basis of insulin and glucose levels both in the fasting state and during OGTTs. RESULTS: From the 1st to the 2nd OGTT: (a) the prevalence of DM responses significantly increased; (b) the areas beneath the respective glucose and insulin curves significantly increased and decreased respectively; (c) IR and IS indices decreased and increased respectively, even in the patients who developed DM; (d) pulmonary function significantly worsened in the entire series, especially in the patients who developed DM. CONCLUSIONS: (i) the natural history of glyco-metabolic status in CF is characterized by deteriorating GT over time; (ii) insulinopenia plays a prominent role in the pathogenesis of GT worsening; (iii) IR does not play any significant part in the pathogenesis of DM development; (iv) deterioration of lung function tests is more severe in the subjects who develop DM over time.

Background Oral immunotherapy (OIT) may be an effective treatment for food allergy in children. It is not clear if the OIT-induced effect is achieved by desensitization (transient state dependent on regular antigen exposure), or by tolerance (persistent condition where the ability to consume the food is retained even after a period of withdrawal). Objective The aim of this study was to investigate the efficacy of OIT-egg desensitization in a double-blind placebo-controlled study, and to evaluate if, after desensitization, tolerance can be maintained. Methods Children with egg allergy were randomized to OIT or placebo for 4 months. At the end of the controlled phase, a double-blind food challenge was repeated to confirm the achieved desensitization. Those subjects found to be desensitized were placed on an egg-containing diet for 6 months, followed by an egg avoidance phase for 3 months, when the food challenge was repeated to determine the maintained tolerance. Results A total of 31 children were randomized to OIT with dehydrated egg white (n = 17) or placebo (n = 14). Of the 17 active patients (1 dropout), 16 achieved desensitization and started the 6-month egg-containing diet. After 3-month of egg avoidance, 31% remained tolerant. In the control group, only 1 passed the final food challenge. Egg-specific IgG4 increased only in the active group. Five active OIT patients had side effects. Conclusion Egg OIT results in desensitization in almost all subjects, although tolerance was maintained in only 1/3 of them after a 3-month period of withdrawal. Side effects were encountered, but the procedure appeared safe. In hen egg allergy, OIT is effective for desensitization.

Resume Les donnees de la litterature mettent en evidence des resultats decevants du traitement par l'hormone de croissance recombinante (GHr) des enfants avec deficit en GH lorsque le traitement est debute tardivement. Cela incite a debuter le traitement par GHr le plus tot possible avec pour corollaire un diagnostic precoce. Cette etude a ete entreprise: 1) pour definir les principales caracteristiques cliniques du deficit en GH (DGH) au cours de la premiere annee de vie, dans le but de preciser les signes devant attirer l'attention du clinicien; 2) pour evaluer l'effet sur la croissance du traitement de GHr debute avant l'âge de l an. Seize enfants avec DGH diagnostique avant l'âge de l an, et traites par GHr des la premiere annee et pendant une duree minimale de 5 ans, ont ete etudies; quatre avaient un DGH isole secondaire a une deletion du gene de la GH (DGH de type 1A). Les principales caracteristiques anamnestiques et cliniques du DGH a revelation precoce dans cette serie sont les suivantes: pathologie perinatale frequente, petite taille a la naissance dans plus de la moitie des cas, poids de naissance relativement eleve dans tous les cas, cassure de la croissance staturale des la naissance, signes associes particuliers (hypoglycemie, dysmorphie faciale, micropenis, cryptorchidie, atteinte hepatique). L'effet du traitement de GHr (≥ 5 ans) sur la croissance: 1) a ete limite et transitoire chez les enfants avec DGH de type 1A; 2) a permis de reduire le retard statural chez les enfants avec DGH sporadique, mais leur taille moyenne est restee significativement inferieure a la taille projetee.

Food protein-induced enterocolitis syndrome (FPIES) is an uncommon and potentially severe non IgE-mediated gastrointestinal food allergy. It is usually caused by cow’s milk or soy proteins, but may also be triggered by ingestion of solid foods. The diagnosis is made on the basis of clinical history and symptoms. Management of acute phase requires fluid resuscitation and intravenous steroids administration, but avoidance of offending foods is the only effective therapeutic option. Infant with FPIES presented to our emergency department with vomiting, watery stools, hypothension and metabolic acidosis after ingestion of rice beverage. Intravenous fluids and steroids were administered with good clinical response. Subsequently, a double blind placebo control food challenge (DBPCFC) was performed using rice beverage and hydrolyzed formula (eHF) as placebo. The “rice based formula” induced emesis, diarrhoea and lethargy. Laboratory investigations reveal an increase of absolute count of neutrophils and the presence of faecal eosinophils. The patient was treated with both intravenous hydration and steroids. According to Powell criteria, oral food challenge was considered positive and diagnosis of FPIES induced by rice beverage was made. Patient was discharged at home with the indication to avoid rice and any rice beverage as well as to reintroduce hydrolyzed formula. A case of FPIES induced by rice beverage has never been reported. The present case clearly shows that also beverage containing rice proteins can be responsible of FPIES. For this reason, the use of rice beverage as cow’s milk substitute for the treatment of non IgE-mediated food allergy should be avoided.

The most common agents that are responsible for intraoperative anaphylaxis are muscle relaxants. In fact, neuromuscular blocking agents (NMBAs) contribute to 50-70 percent of allergic reactions during anaesthesia. The main mechanism of hypersensitivity reactions to NMBAs is represented by acute type I allergic reactions and the most severe form is anaphylaxis. The rate of non IgE mediated immediate hypersensitivity reactions usually varies between 20 percent and 35 percent of the reported cases in most large series. In a recent report, non allergic suspected reactions to NMBAs occurred with almost the same frequency as did those with an allergic component. Although the precise mechanisms of these reactions remain difficult to ascertain, they usually result from direct non specific mast cell and basophil activation. After diagnostic procedures, regardless of the specific IgE results, NMBAs are contraindicated if the skin tests were positive. In view of the constantly evolving anesthesiologic practices, and of the complexity of allergy investigation, an active policy to identify patients at risk and to provide any necessary support to anaesthetists and allergologists should be promoted. The high frequency of IgE anaphylactic reactions and the feasibility of skin tests in children justify systematic allergy testing whenever hypersensitivity reaction occurs during general anaesthesia.

Background: GH-IGF-I axis is mainly involved in the complex process of somatic growth but emerging evidence suggests that it also influences hypothalamic-pituitary-gonadal (HPG) function. Subjects: We report some data regarding long-term auxological and pubertal outcome of five female patients with hereditary forms of GH-IGF-I deficiency (Laron and GH-gene deletion syndrome) and a mean age of 23.4±5.3 yr (range 19–32). Methods: All the patients received recombinant human IGF-I (rhIGF-I, Pharmacia and Upjohn, Stockholm, Sweden, and rhIGF-I, Genentech, San Francisco, CA, USA) from a mean age of 8.6 yr (range 3.2–14.2) up to the final height. Results: Final height was very disappointing (≤ − 5.0 SD scores) and lower than target height in all the patients. Pubertal onset was delayed in most of them but menarche occurred spontaneously in all the patients. Median age at menarche was 15.1 yr. Menstrual cycles were regular for several years. Median duration of gynecological follow-up was 8.3 yr with the longest span of 17.2 yr. Conclusion: We can assert that GH-IGF-I axis has an essential role in promoting linear growth in humans and its physiological action cannot be replaced by pharmacological treatment in most patients with hereditary forms of IGF-I insufficiency as demonstrated by their subnormal final height. Our clinical observations can also support an essential role of IGF-I in genitalia growth but not in the function of HPG axis as demonstrated by the maintenance of regular menstrual cycles in the presence of subnormal levels of IGF-I after treatment discontinuation.

Here we report for the first time the results of the molecular study of 17 unrelated patients with salt-wasting (SW) congenital adrenal hyperplasia (CAH) belonging to a Sicilian ethnic group, as corroborated by patients’ pedigree taken to include 2 generations in the paternal and maternal lineage. The aim of this report was to confirm that genetic basis of CAH may be characterized by population differences. In our series, the overall predominant mutation was IVS2A/C>G, that was detected in 50% of alleles and in 58.8% of patients. The allelic and homozygous frequencies of IVS2A/C>G, Del8bpE3, and R356W mutations were significantly higher in our series than in other populations. Our study population included 2 cases with 2 different mutations that have been recently reported for the first time, 3 cases with a double mutation on the same allele, and 1 case with homozygous de novo mutation. We concluded that: a) in a Sicilian ethnic group the most frequent genotype in SW CAH is IVS2A/C>G homozygocity; b) surprisingly Del8bpE3 and R256W homozygocity are also well represented.

The aim of the present study was to retrospectively re-evaluate a population of selected infants with congenital hypothyroidism (CH), in order to investigate whether sexual dimorphism affects: a) CH etiology; b) its biochemical severity at the time of screening and recall; c) patients’ biochemical response to replacement treatment during the 1st yr of life; d) their bone maturation (BM) at birth; e) their psychomotor status at 1 yr. This retrospective study covers 192 infants (116 females) with persistent CH who were selected from a larger population of CH patients identified during a 10-yr period (1990–1999) by the screening programs of 5 northern, central, and southern regions of Italy. Thirty boys (39.5%) and 66 girls (56.9%) were found to have ectopia, whereas the remaining 46 boys and 50 girls exhibited the other causes of CH. When compared with the prevalence of the remaining causes that of ectopia was significantly higher in girls than in boys (66/116 vs 30/76; χ2=5.57, p

varicocele ligation in adults with the laparoscopic approach in children in whom the artery and vein were ligated. The laparoscopic approach resulted in shorter operative times and there were fewer recurrent varicoceles but the postoperative hydrocele rate (3 of 36) was high. Pediatric urologists have commonly favored high ligation of the internal spermatic vein over the subinguinal approach. As we become more facile with the laparoscope, I suspect that the majority will continue with high ligation but will perform it laparoscopically. The risk of hydrocele is greater when the artery and vein and presumably lymphatics are taken than when lymphatics are spared, as is routinely the case in the subinguinal approach. Success rates in varicocele repair are high and complications are low using both approaches. Some laparoscopists are sparing the artery (and presumably with it the vasa vasorum). In these cases as long as the vasa vasorum is not dissected free of the artery, there is theoretically a higher risk of recurrence of the varicocele. It is less clear, despite the currently accepted indications for varicocele ligation in the adolescent (testicular size discrepancy or decreased relative growth of the left testis), that ligating the varicocele by either approach in the vast majority of adolescents who are asymptomatic actually decreases the risk of infertility in these boys.

The Short Form 36 Health Survey (SF-36) is a self-administered scoring system that has been widely used and validated as a quality of life (QOL) assessment tool. In our study, a cluster analysis of SF-36 scores was performed in 50 healthy volunteers (controls) and 50 neurobiologically asymptomatic patients on maintenance hemodialysis (MHD). Firstly, we assayed the tendency to form clusters from each of the investigated dimensions. Statistic analysis was performed using the Student's t-test for independent measurements and multiple regression analysis. Secondly, we attempted to evaluate if the MHD to apply to both groups a general psychobiological personality model developed by Cloninger in 1987. Cloninger describes three independent personality dimensions: novelty seeking (NS), harm avoidance (HA)and reward dependence (RD). Each personality dimension would be the expression of hereditary variations integrating the three main brain systems, respectively: dopaminergic, serotoninergic and noradrenergic. Finally, we then aimed to investigate possible interferences among the seric concentrations of the neuromodulators and SF-36 scores, in the attempt to identify, using a simple approach, the complex personality structure of MHD patients. QOL self-assessment and seric neuromodulators were measured in both groups, choosing an interdialytic day for MHD patients. We found that MHD patients perceived a significant worsening in their QOL in all investigated dimensions with respect to the controls. In addition, they showed significantly lower dopamine and serotonine concentrations and significantly higher noradrenaline concentrations. Therefore, our study, confirmed data reported previously in the literature, that cluster analysis of SF-36 scores provides different results in the MHD population in comparison to normal subjects. In fact, comparing the hierarchical trees of both groups, it appeared evident that in MHD patients, cluster dimensions were greater than in the controls. In cluster compositions showed differences between the two groups. In fact, in MHD patients there were only a few of the clusters that were observed in the controls (mental health and social functioning, vitality and general health), while role-physical and role-emotional dimensions aligned outside the hierarchical tree, with a considerable linkage distance. In our opinion, it is fascinating that the three Cloninger neuromodulators could suggest that HD patient personalities are potentially cyclothymiac, altering the disposition of the two role functions inside the hierarchical tree.

Parvovirus B19, a DNA virus, is the etiologic agent of erythema infectiosum. This virus is also responsible for less common presentations as the papular-purpuric syndrome, a nosologic entity characterized by pruritic and painful edema and erythema localized to the hands and feet. We describe the case of a young girl with serologically documented B19 infection in whom the dermatologic lesions occurred with severe and unusual hematologic alterations.