Search

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.

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.

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic.Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.

Acute food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by the onset of delayed repetitive and projectile vomiting accompanied by other clinical manifestations such as pallor, hypotonia, lethargy, hypothermia and/or diarrhea (1). Acute FPIES can be classified as classic or atypical based on the absence or presence of sensitization to the trigger food (2).

Anaphylaxis represents one of the most frequent medical emergencies in childhood. However, as compared to adults, drugs are less common triggers of anaphylaxis in children, with a frequency which is increasing from infancy to adolescence. Deaths seldom occur, maybe because of the paucity of comorbidities in children. Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) are the main elicitors in drug-induced anaphylaxis in children. Both immune-mediated (mainly IgE-mediated) and non immune-mediated may be involved. IgG-mediated and complement-mediated mechanisms has been also hypothesized. Correct management relies on a right diagnosis and prompt therapy. A proper work-up is also important to prevent further potentially fatal re-exposures to the same drug or other structurally similar molecules but also unnecessary avoidance of medications not representing the culprit of the episode. (www.actabiomedica.it)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe reaction to drugs. Incidence of DRESS in children is not well known and the mortality rate seems to be lower than 10%. Anticonvulsants are the main drugs involved both in adults and in children. The treatment of choice is intravenous immunoglobulins and corticosteroids used in synergy. Today there are not controlled clinical trials regarding DRESS treatment in children. Anyway, the prompt withdrawn of the offending drug is of paramount importance for a better prognosis. DRESS sequels may occur, consequently, follow-up visits are required at least until the first year after the reaction. (www.actabiomedica.it)

Along with the anamnesis and clinical evaluation, diagnostic tests are one of the mainstream key points in the evaluation and management of drug hypersensitivity reactions (DHR). A wide knowledge gap, both in diagnosis and management of pediatric DHR, must be filled. Only a few published studies evaluated sensitivity and specificity of skin and in vitro tests in children. However, selected case series show that diagnostic work-up for adults could be useful, with some limitations, in pediatric age. Indeed, despite improvement in in vivo and in vitro diagnosis, drug provocation test remains the gold standard in pediatric age, too. Unmet needs in children include multi-centric studies on incidence of DHR, utility and feasibility of in vivo and in vitro diagnostic tests and specifically dedicated guidelines for the diagnosis and management of DHR in children. (www.actabiomedica.it)

The cause of chronic urticaria remains often elusive. The association between chronic urticaria and intake of medications have been reported in children. However, the causative role of drugs has been rarely ascertained by onset of symptoms on drug provocation test. Chronic urticaria can be mediated by immunologic and nonimmunologic mechanisms. The diagnostic work-up of chronic urticaria includes a comprehensive evaluation of triggering factors such as drugs. A diagnosis is necessary in order to permit a safely administration of drugs in children with chronic urticaria. (www.actabiomedica.it)

Drug hypersensitivity reactions (DHRs) in childhood are mainly caused by betalactam or non-betalactam antibiotics, and non-steroidal anti-inflammatory drugs (NSAIDs). Laboratory tests for identifying children who are allergic to drugs have low diagnostic accuracy and predictive value. The gold standard to diagnose DHR is represented by the drug provocation test (DPT), that aims of ascertaining the causative role of an allergen and evaluating the tolerance to the suspected drug. Different protocols through the administration of divided increasing doses have been postulated according to the type of drug and the onset of the reaction (immediate or non immediate reactions). DPT protocols differ in doses and time interval between doses. In this position paper, the Italian Pediatric Society for Allergy and Immunology provides a practical guide for provocation test to antibiotics and NSAIDs in children and adolescents.

The prevalence of food allergy has increased in recent years, especially in children. Allergen avoidance, and drugs in case of an allergic reaction, remains the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanut, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization through the consumption of an increasing amount of a food allergen, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current pediatric OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, pediatric OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes. post-print 6382 KB

Biologic drugs are widely used in pediatric medicine. Monoclonal antibodies (mAbs) in particular are a therapeutic option for rheumatic, autoinflammatory and oncologic diseases. Adverse drug reactions and hypersensitivity reactions (HSR) to mAbs may occur in children. Clinical presentation of HSRs to mAbs can be classified according to phenotypes in infusion-related reactions, cytokine release syndrome, both alpha type reactions and type I (IgE/non-IgE), type III, and type IV reactions, all beta-type reactions. The aim of this review is to focus on HSRs associated with the most frequent mAbs in childhood, with particular attention to beta-type reactions. When a reaction to mAbs is suspected a diagnostic work-up including in-vivo and in-vitro testing should be performed. A drug provocation test is recommended only when no alternative drugs are available. In selected patients with immediate IgE-mediated drug allergy a desensitization protocol is indicated. Despite the heavy use of mAbs in childhood, studies evaluating the reliability of diagnostic test are lacking. Although desensitization may be effective in reducing the risk of reactions in children, standardized pediatric protocols are still not available.

Allergic diseases have different frequencies. In particular, allergic rhinitis and asthma have high frequencies of about 20% and 10%, respectively. Other allergic diseases have lower frequencies; for example, food allergy has a frequency of 1%-4%. There are also rare allergic diseases, with a prevalence of 5 cases per 10 000 people in the general population, and they are included in Orphanet. However, other extremely rare allergic diseases still need to be properly known in order to be possibly recognized as rare diseases and cataloged in Orphanet.

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.

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)

Background Few studies on the age of resolution of Food Protein Induced Enterocolitis Syndrome (FPIES) induced by solid foods are available. In particular, for FPIES induced by egg, the mean age of tolerance acquisition reported in the literature ranges from 42 to 63 months. Objective We have assessed whether the age of tolerance acquisition in acute egg FPIES varies depending on whether the egg is cooked or raw. Methods We conducted a retrospective and multicentric study of children with diagnosis of acute egg FPIES seen in 10 Italian allergy units between July 2003 and October 2017. The collected data regarded sex, presence of other allergic diseases, age of onset of symptoms, kind and severity of symptoms, cooking technique of the ingested egg, outcome of the allergy test, age of tolerance acquisition. Results Sixty-one children with acute egg FPIES were enrolled, 34 (56%) males and 27 (44%) females. Tolerance to cooked egg has been demonstrated by 47/61 (77%) children at a mean age of 30.2 months. For 32 of them, tolerance to raw egg has been demonstrated at a mean age of 43.9 months. No episodes of severe adverse reaction after baked egg ingestion have been recorded. Conclusions It is possible to perform an OFC with baked egg, to verify the possible acquisition of tolerance, at about 30 months of life in children with acute egg FPIES.

Introduction and objectives The reproducibility of the adverse reaction increases the suggestiveness of a history of food allergy. However, the positive predictive value (PPV) of multiple adverse reaction episodes for the diagnosis of IgE-mediated food allergy is not known. This evaluation was the objective of our study. Patients and methods We retrospectively studied 180 children with a history of non-anaphylactic adverse reactions after the ingestion of a food. All children had the prick test positive for the offending food and performed the oral food challenge (OFC) within 12 months after the last adverse reaction episode (ARE). We have evaluated whether increasing the number of ARE increased the probability that the OFC would be positive (failed). Results 93 patients (52%) presented one ARE, 49 (27%) presented two ARE, 24 (13%) presented three ARE, 14 (8%) patients presented ≥ four ARE. The OFC was positive in 94/180 (52%). The outcome of the OFC was found to be positively correlated with the number of ARE (OR = 1.56; 95% CI = 1.16–2.09; p = 0.003). A PPV = 100% was observed with a number of ARE ≥ five. Conclusions The number of ARE is an important predictor of the diagnosis of food allergy, although less than we would have imagined. The number of ARE could be used to increase the predictability of the diagnostic tests currently in use, to define clinical prediction rules alternative to OFC and easy to use in clinical practice.

Background Vaccines often contain potentially allergenic material in addition to pathogen-specific immunogens that may induce allergic reactions. Parents and physicians often suspect that adverse reactions to vaccines are allergic in etiology. The concern that some of the substances contained in vaccines may trigger an anaphylactic reaction may lead to a low vaccination adherence with emergence of infectious disease epidemics. Objective To provide practical suggestions for managing children suspected to have an allergic reaction to a vaccine. Methods Information was obtained from a search of guidelines and relevant studies on allergic reactions to vaccines for infectious diseases. Results True allergic reactions elicited by a vaccine are rare. Skin testing to the vaccine and to its components may identify the triggering agent. Graded dosing desensitization is helpful in children sensitized to the offending vaccine. Conclusion All children with a suspected allergic reaction to a vaccine should be carefully evaluated by routine allergy tests. When it is necessary, further immunization should be given under strict medical surveillance, which ensures that every child can safely complete the vaccination schedule.

Background Children with IgE-mediated cow's milk allergy (IgE-CMA) often tolerate baked milk within a wheat matrix. In our study we evaluated the impact of wheat matrix and of little standardised cooking procedures on tolerance of baked milk. We also tested tolerance versus parmigiano reggiano (PR) and whey-based partially hydrolysed formula (pHF). Methods Forty-eight children with IgE-CMA were enrolled. They underwent prick-by-prick (PbP) and open oral food challenge (OFC) with baked cow's milk (CM), both within a wheat matrix (an Italian cake named ciambellone) and without (in a liquid form), with PR and with pHF. After a passed OFC, children continued to eat the food tolerated. In particular, after passed OFC with ciambellone, children were allowed to eat any food containing CM within a wheat matrix, with the only condition that it was baked at 180 °C for at least 30 min. Three months after, parents were asked to answer a survey. Results 81% of children tolerated ciambellone, 56% liquid baked CM, 78% PR and 82% pHF. Negative predictive value of PbP performed with tested foods was 100%. No IgE-mediated adverse reactions were detected at follow-up carried out by the survey. Conclusions Wheat matrix effect on tolerance of baked milk was relevant in slightly less than half of cases. If our results are confirmed by larger studies, a negative PbP will allow patients to eat processed CM without undergoing OFC. Moreover, in order to guarantee tolerance towards baked milk, strict standardised cooking procedures do not seem to be necessary.

Background Children with IgE-mediated hen's egg allergy (IgE-HEA) often tolerate baked egg within a wheat matrix. Objective To evaluate the influence of wheat matrix and the effects of little standardized cooking procedures on baked egg tolerance. Methods Fifty-four children with IgE-HEA were enrolled. They underwent prick-by-prick (PbP) tests and open oral food challenges (OFC) performed with baked HE within a wheat matrix (a home-made cake, locally called ciambellone), baked HE without a wheat matrix (in the form of an omelet, locally named frittata) and boiled HE. Three months after passing ciambellone OFC, parents were asked to answer a survey. Results About 88% of children tolerated ciambellone, 74% frittata, and 56% boiled HE. Negative predictive value of PbP performed with ciambellone, frittata, and boiled HE was 100%. No IgE-mediated adverse reactions were detected at follow-up carried out by the survey. Conclusions Wheat matrix seemed to be relevant only in few cases. If our results will be confirmed by larger studies, a negative PbP with ciambellone, frittata, or boiled HE will allow patients with IgE-HEA to eat these foods without undergoing OFC. Moreover, our study showed that very strict standardized cooking procedures do not seem to be essential, to guarantee tolerance toward baked HE.

Kikuchi-Fujimoto disease (KFD) is a rare and benign disease that typically affects the cervical lymph nodes. Its aetiology is unknown and a role of the autoimmune system in the pathogenesis is hypothesized. This self-limiting disease is often confused with malignancies. No specific management is generally required but long-term follow-up should be planned despite the low risk of recurrence, as recurrences have been described many years after the first episode and there is a high risk of development of an autoimmune disease or even lymphoma. We review the clinical and histological features of KFD and report an unusual case presenting with cervical and supraclavicular lymphadenopathy, and persistent fever.

The aim of this study was to evaluate longitudinally functional and neuro-radiologic findings in childhood optic gliomas (OG), by comparing flicker visual evoked potentials (F-VEPs) with brain magnetic resonance imaging (MRI) changes. Fourteen children (age range: 1-13 years) with OGs underwent serial F-VEP, MRI and neuro-ophthalmic examinations over a 38 month (median, range: 6-76) follow-up. F-VEPs were elicited by 8 Hz sine-wave flicker stimuli presented in a mini-Ganzfeld. Contrast-enhanced MRI examinations were performed. Results of both tests were blindly assessed by independent evaluators. F-VEPs were judged to be improved, stable or worsened if changes in the amplitude and/or phase angle of the response exceeded the limits of test-retest variability (+/-90th percentile) established for the same patients. MRI results were judged to show regression, stabilization or progression of OG based on its changes in size (+/-20%) or extension. Two to seven pairs of F-VEP/MRI examinations per patient (median: 4) were collected. Based on a total of 38 pairs of F-VEP/MRI examinations, both tests agreed in showing worsening (progression), stabilization and improvement (regression) in 5, 15 and 10 cases, respectively. In 3 cases, F-VEPs showed a worsening and MRI a stabilization, while in 5 cases F-VEPs showed an improvement and MRI a stabilization. Agreement between F-VEP and MRI changes was 78.9% (95% CI: +/- 37%, K statistics = 0.67, P0.001). The results indicate that longitudinal F-VEP changes can predict changes in MRI-assessed OG size and extension, providing a non-invasive functional assay, complementary to neuro-imaging, for OG follow-up.

Pain is the most common discomfort experienced by children with cancer and occurs in almost 89% of patients in an advanced stage of the disease. It is most often not adequately treated because of inexperience and unfounded fears of analgesic treatment. In adults, patient controlled analgesia (PCA) is widely administered, while in children with moderate to severe cancer pain its use is still under evaluation for safety and efficacy.To evaluate the efficacy and safety of fentanyl administered by PCA in children with cancer pain.Eighteen children (range 6 to 15 years) with moderate to severe pain were enrolled and treated with fentanyl by PCA plus background infusion (BI) (BI of 1 microg/kg/h with booster doses of 1 microg/kg by intravenous route). To evaluate efficacy and safety of the analgesic treatment, different subjective and objective parameters were monitored at 4-h intervals. In addition, patients' satisfaction was assessed by a questionnaire at the end of the treatment.All children experienced a good degree of analgesia and did not require any other analgesic drug during the treatment. Both subjective and objective parameters improved after starting pain-relieving treatment and no major side effects occurred. The questionnaire administered to the children showed a high grade of satisfaction.PCA plus BI with fentanyl administered by intravenous route is a safe and efficacious method for analgesia in children with moderate to severe cancer pain. Our policy of fentanyl-treatment did not show any major side effects.