Kawasaki disease, multisystem inflammatory syndrome in children, and adenoviral infection: a scoring system to guide differential diagnosis.

Children with Kawasaki disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), and Adenovirus infections (AI) of the upper respiratory tract show overlapping features. This study aims to develop a scoring system based on clinical or laboratory parameters to differentiate KD or MIS-C from AI patients. Ninety pediatric patients diagnosed with KD (n = 30), MIS-C (n = 26), and AI (n = 34) admitted to the Pediatric Emergency Unit of S.Orsola University Hospital in Bologna, Italy, from April 2018 to December 2021 were enrolled. Demographic, clinical, and laboratory data were recorded. A multivariable logistic regression analysis was performed, and a scoring system was subsequently developed. A simple model (clinical score), including five clinical parameters, and a complex model (clinic-lab score), resulting from the addition of one laboratory parameter, were developed and yielded 100% sensitivity and 80% specificity with a score ≥2 and 98.3% sensitivity and 83.3% specificity with a score ≥3, respectively, for MIS-C and KD diagnosis, as compared to AI. CONCLUSION: This scoring system, intended for both outpatients and inpatients, might limit overtesting, contribute to a more effective use of resources, and help the clinician not underestimate the true risk of KD or MIS-C among patients with an incidental Adenovirus detection. WHAT IS KNOWN: • Kawasaki Disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C) and adenoviral infections share overlapping clinical presentation in persistently febrile children, making differential diagnosis challenging. • Scoring systems have been developed to identify high-risk KD patients and discriminate KD from MIS-C patients. WHAT IS NEW: • This is the first scoring model based on clinical criteria to distinguish adenoviral infection from KD and MIS-C. • The score might be used by general pediatricians before referring febrile children to the emergency department.

Outdoor Air Pollution and Childhood Respiratory Disease: The Role of Oxidative Stress.

The leading mechanisms through which air pollutants exert their damaging effects are the promotion of oxidative stress, the induction of an inflammatory response, and the deregulation of the immune system by reducing its ability to limit infectious agents' spreading. This influence starts in the prenatal age and continues during childhood, the most susceptible period of life, due to a lower efficiency of oxidative damage detoxification, a higher metabolic and breathing rate, and enhanced oxygen consumption per unit of body mass. Air pollution is involved in acute disorders like asthma exacerbations and upper and lower respiratory infections, including bronchiolitis, tuberculosis, and pneumoniae. Pollutants can also contribute to the onset of chronic asthma, and they can lead to a deficit in lung function and growth, long-term respiratory damage, and eventually chronic respiratory illness. Air pollution abatement policies, applied in the last decades, are contributing to mitigating air quality issues, but more efforts should be encouraged to improve acute childhood respiratory disease with possible positive long-term effects on lung function. This narrative review aims to summarize the most recent studies on the links between air pollution and childhood respiratory illness.

Epidemiology and clinical evolution of non-multisystem inflammatory syndrome (MIS-C) dermatological lesions in pediatric patients affected by SARS-CoV-2 infection: A systematic review of the literature.

COVID-19 can present with a range of skin manifestations, some of which specific of the pediatric age. The aim of this systematic literature review was to determine the type, prevalence, time of onset, and evolution of cutaneous manifestations associated with COVID-19 in newborns, children, and adolescents, after excluding multisystem inflammatory syndrome in children (MIS-C). PubMed, Tripdatabase, ClinicalTrials, and Cochrane Library databases were searched using an ad hoc string for case reports/series and observational studies, published between December 2019 and February 2022. Study quality was assessed using the STROBE and CARE tools. Seventy-three (49 case reports/series and 24 studies) out of 26,545 identified articles were included in the analysis. Dermatological lesions were highly heterogeneous for clinical presentation, time of onset, and association with other COVID-19 manifestations. Overall, they mainly affected the acral portions, and typically presented a favorable outcome. Pseudo-chilblains were the most common. CONCLUSIONS: Mucocutaneous manifestations could be the only/predominant and early manifestation of COVID-19 that could precede other more severe manifestations by days or weeks. Therefore, physicians of all disciplines should be familiar with them. WHAT IS KNOWN: • A variety of cutaneous manifestations have been reported in association with COVID-19. • Urticaria, maculopapular, or vesicular rashes can occur at any age, while chilblains and erythema multiforme are more common in children and young patients. WHAT IS NEW: • Skin lesions related to SARS-CoV-2 infection often show a peculiar acral distribution. • Mucocutaneous lesions of various type may be the only/predominant manifestation of COVID-19; they could present in paucisymptomatic and severely ill patients and occur at different stages of the disease.

Multicentre study revealed significant gaps between evidence-based recommendations for using corticosteroids for croup and clinical practice.

AIM: Adherence to croup management recommendations has been poorly investigated. This study aimed to describe the treatment patterns in two paediatric emergency departments and analyse the adherence to recommendations. METHODS: We conducted a retrospective chart review of children diagnosed with croup in two Italian paediatric emergency departments in 2017. Data on clinical presentation, corticosteroid administration and home therapy were collected. Length of stay, hospitalisation and re-access rates were compared among different corticosteroid treatment groups. RESULTS: We enrolled 632 patients (61.1% males) with a mean age of 42.8 ± 55.1 months. Corticosteroids were administered to 403 (63.8%) children in the emergency departments. Dexamethasone was administered to 1 (0.4%) patient. Inhaled and oral corticosteroids were given to 342 (54.1%) and 226 (35.8%) patients, respectively. Home therapy was prescribed for 603 (95.4%) patients, either with inhaled (86.2%) and/or oral (43.8%) corticosteroids. The re-access rate was 2.8%. The actual pharmaceutical costs were an estimated 10 times higher than they would have been if the recommendations had been followed. CONCLUSION: A significant gap between the evidence and clinical practice for croup treatment was observed. Improving adherence to the recommendations could lead to clinical and economic benefits.

Viral rashes mimicking drug reaction with eosinophilia and systemic symptoms syndrome in children after ß-lactams intake: a diagnostic challenge.

In cases of skin eruptions over the course of antibiotic therapy and concomitant viral infection, differential diagnosis is often challenging. Confirming or ruling out drug hypersensitivity is not always a clear-cut question. Drug reaction with eosinophilia and systemic symptoms (DRESS) cases, for example, is classified as severe cutaneous adverse reactions due to drugs, but frequently the clinical manifestations do not completely fit into the diagnosis of DRESS. The aim of the present paper is to highlight similarities and differences among DRESS syndrome and DRESS-like rashes during viral infections and amoxicillin intake in children, in order to highlight those aspects that can help clinicians in early detection. We describe the dermatological, clinical, and laboratory characteristics of five patients hospitalized for DRESS-like skin rashes appearing roughly 1 week since the start of an amoxicillina course for upper respiratory tract infection (URTI) symptoms. The data are compared with those of 3 patients with early-onset DRESS syndrome. The absence of eosinophilia might be an initial marker to help identifying DRESS-like rashes; a quick clinical improvement and the confirmation of a viral infection able to explain the symptoms can help to finally rule out DRESS syndrome. Conclusion: A rapid, correct diagnosis of such DRESS-like rashes during viral infections allows more appropriate management and avoids unnecessary, life-long exclusion of useful and effective antibiotics because of a falsely "amoxicillin-allergy" labelling. What is Known: • Viral infections are common causes of skin rashes in children during antibiotic intake and may require differential diagnosis with drug reactions. • Early-onset DRESS syndrome is usually induced by antibiotics and appears ≤15 days after drug intake. What is New: • Prominent midface edema, maculopapular rash, and mild-to-moderate systemic symptoms may appear in children during viral illnesses treated with amoxicillin few days after drug intake, and may require differential diagnosis with early-onset DRESS. • In such cases, absence of eosinophilia, low (2-3) RegiSCAR score, confirmation of viral etiology, and a rapid resolution of the rash (2-5 days) might help to rule out DRESS; conversely, at an early stage, the presence of eosinophilia should suggest a diagnosis of DRESS.

Passive Immunoprophylaxis against Respiratory Syncytial Virus in Children: Where Are We Now?

Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab's usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio.

Early molecular biomarkers predicting the evolution of allergic rhinitis and its comorbidities: A longitudinal multicenter study of a patient cohort.

BACKGROUND: Pollen-related seasonal allergic rhinoconjunctivitis (SAR) is a very frequent pediatric disease in Westernized countries. Risk factors and disease phenotypes have been thoroughly examined in several cross-sectional studies. By contrast, only a few studies have examined disease evolution in patient cohorts. We investigated predictive biomarkers of disease evolution in a large cohort of children with SAR. METHODS: During 2015-2017 (follow-up), we re-examined 401 patients from those enrolled in 2009-2011 (baseline) by the "Panallergens in Pediatrics" study, a large multicenter survey of Italian children with SAR. Information on clinical history (standard questionnaire, AllergyCARD®; TPS, Italy) and skin prick tests for inhalant and foods extracts (ALK-Abelló, Hørsholm, Denmark) was acquired as at baseline visit. Evolution in clinical and sensitization data of patients was analyzed over time, as well as their association with the main baseline characteristics and atopy risk factors. RESULTS: The average age of participants was 10.4 ± 3.4 years at baseline and 16.2 ± 3.6 years at follow-up. SAR persisted in 93.3% of patients at follow-up and became more frequently associated with asthma (from 36.7% at baseline to 48.6% at follow-up) and oral allergy syndrome (OAS, from 23.4% to 37.7%). Compared to baseline, the prevalence of skin sensitization to some pollens (Phleum pratense, Corylus avellana, Platanus acerifolia, Artemisia vulgaris) and vegetables (hazelnut, wheat, and apple) significantly decreased at follow-up. Earlier onset of SAR and polysensitization at baseline were associated with incident asthma at follow-up. The presence at baseline of serum IgE to the following allergen molecules was identified as biomarkers of clinical evolution: (a) Phl p 1, for persistence of SAR; (b) Phl p 5, for persistence of both rhinitis and asthma; (c) Pru p 3, for new onset of asthma; (d) Bet v 1, for persistence of OAS. CONCLUSIONS: Seasonal allergic rhinoconjunctivitis is clinically heterogeneous in its evolution from childhood to adolescence. The detection of serum IgE to specific molecules (Phl p 1, Phl p 5, Bet v 1, Pru p 3) may be useful as biomarkers to predict SAR persistence and future onset of comorbidities, such as asthma and/or OAS.

Lung ultrasound for the diagnosis of pneumonia in children with acute bronchiolitis.

BACKGROUND: Guidelines currently do not recommend the routine use of chest x-ray (CXR) in bronchiolitis. However, CXR is still performed in a high percentage of cases, mainly to diagnose or rule out pneumonia. The inappropriate use of CXR results in children exposure to ionizing radiations and increased medical costs. Lung Ultrasound (LUS) has become an emerging diagnostic tool for diagnosing pneumonia in the last decades. The purpose of this study was to assess the diagnostic accuracy and reliability of LUS for the detection of pneumonia in hospitalized children with bronchiolitis and to evaluate the agreement between LUS and CXR in diagnosing pneumonia in these patients. METHODS: We enrolled children admitted to our hospital in 2016-2017 with a diagnosis of bronchiolitis and undergone CXR because of clinical suspicion of concomitant pneumonia. LUS was performed in each child by a pediatrician blinded to the patient's clinical, laboratory and CXR findings. An exploratory analysis was done in the first 30 patients to evaluate the inter-observer agreement between a pediatrician and a radiologist who independently performed LUS. The diagnosis of pneumonia was established by an expert clinician based on the recommendations of the British Thoracic Society guidelines. RESULTS: Eighty seven children with bronchiolitis were investigated. A final diagnosis of concomitant pneumonia was made in 25 patients. Sensitivity and specificity of LUS for the diagnosis of pneumonia were 100% and 83.9% respectively, with an area under-the-curve of 0.92, while CXR showed a sensitivity of 96% and specificity of 87.1%. When only consolidation > 1 cm was considered consistent with pneumonia, the specificity of LUS increased to 98.4% and the sensitivity decreased to 80.0%, with an area under-the-curve of 0.89. Cohen's kappa between pediatrician and radiologist sonologists in the first 30 patients showed an almost perfect agreement in diagnosing pneumonia by LUS (K 0.93). CONCLUSIONS: This study shows the good accuracy of LUS in diagnosing pneumonia in children with clinical bronchiolitis. When including only consolidation size > 1 cm, specificity of LUS was higher than CXR, avoiding the need to perform CXR in these patients. Added benefit of LUS included high inter-observer agreement. TRIAL REGISTRATION: Identifier: NCT03280732 . Registered 12 September 2017 (retrospectively registered).

Atypical Forms of Hand, Foot, and Mouth Disease: A Prospective Study of 47 Italian Children.

BACKGROUND: Atypical forms of hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 have been reported in recent years. High fever and severe cutaneous lesions are common, whereas neurologic complications are rare. Eczematous areas of patients with atopic dermatitis show more lesions. The goal of the current study was to describe the clinical characteristics of children with atypical HFMD and to investigate the involvement of the different enterovirus serotypes associated. METHODS: All patients referred to our service for atypical HFMD from January 2012 to February 2014 were enrolled and classified as having the diffuse form (lesions extended to the trunk), the acral form (lesions with a mainly acral distribution), or eczema coxsackium (lesions on preexisting eczematous areas). RESULTS: Data from 47 patients were analyzed (median age 22 months [range 4-84 mos]); viral genotyping was performed in 11 cases. Sixty-two percent of the subjects developed the acral form, 23% eczema coxsackium, and 15% the diffuse form. Most patients had a nonclassical vesicular eruption and moderate to severe extent of cutaneous involvement. Approximately 80% of patients had palmoplantar purpuric macules. Most children younger than 2 years old had the acral form, most patients with eczema coxsackium were age 2 years and older, and the diffuse form was similarly distributed between the two age groups. Coxsackievirus A6 was detected in 9 of 11 genotyped cases. CONCLUSION: Our prospective study allowed the identification of three HFMD phenotypes differing from the classical form. Clinical care of these patients should include symptomatic treatment of extracutaneous features and, if necessary, hospitalization for complications.

Prevalence and Clinical Relevance of IgE Sensitization to Profilin in Childhood: A Multicenter Study.

BACKGROUND: Little is known about the prevalence and clinical relevance of hypersensitivity to the plant panallergen profilin in children. OBJECTIVES: The present study aimed to investigate prevalence, risk factors and clinical relevance of profilin sensitization in a large cohort of Italian children of different ages living in different geographic areas. METHODS: Children with pollen allergy enrolled by 16 pediatric outpatient clinics sited in three main geographic areas of Italy were studied. SPT were carried out with commercial pollen extracts and a commercial purified date palm pollen profilin. IgE specific for allergenic pollen molecules, Phl p 12 (grass profilin) and Pru p 3 (peach lipid transfer protein) were tested by ImmunoCAP FEIA. RESULTS: IgE to Phl p 12 (≥0.35 kU/l) was observed in 296 of the 1,271 participants (23%), including 17 of the 108 (16%) preschool children. Profilin SPT was positive (≥3 mm) in 320/1,271 (25%) participants. The two diagnostic methods were concordant in 1,151 (91%, p < 0.0001) cases. Phl p 12 IgE prevalence declined from northern to southern Italy and was directly associated with IgE to Phl p 1 and/or Phl p 5 and Ole e 1. Among children with IgE to Phl p 12, OAS was provoked by kiwi, melon, watermelon, banana, apricot and cucumber. CONCLUSIONS: Profilin sensitization is very frequent among pollen-allergic children, occurs at a very young age and contributes to the development of childhood OAS with a typical pattern of offending foods. Pediatricians should always consider IgE sensitization to profilin while examining pollen-allergic children, even if they are at preschool age.

Is it possible to make a diagnosis of raw, heated, and baked egg allergy in children using cutoffs? A systematic review.

The diagnosis of IgE-mediated egg allergy lies both on a compatible clinical history and on the results of skin prick tests (SPTs) and IgEs levels. Both tests have good sensitivity but low specificity. For this reason, oral food challenge (OFC) is the ultimate gold standard for the diagnosis. The aim of this study was to systematically review the literature in order to identify, analyze, and synthesize the predictive value of SPT and specific IgEs both to egg white and to main egg allergens and to review the cutoffs suggested in the literature. A total of 37 articles were included in this systematic review. Studies were grouped according to the degree of cooking of the egg used for OFC, age, and type of allergen used to perform the allergy workup. In children <2 years, raw egg allergy seems very likely when SPTs with egg white extract are ≥4 mm or specific IgEs are ≥1.7 kUA /l. In children ≥2 years, OFC could be avoided when SPTs with egg white extract are ≥10 mm or prick by prick with egg white is ≥14 mm or specific IgE is ≥7.3 kUA /l. Likewise, heated egg allergy can be diagnosed if SPTs with egg white extract are >5 and >11 mm in children <2 and ≥2 years, respectively. Further and better-designed studies are needed to determine the remaining diagnostic cutoff of specific IgE and SPT for heated and baked egg allergy.

The effect of component-resolved diagnosis on specific immunotherapy prescription in children with hay fever.

BACKGROUND: Sensitization to profilins and other cross-reacting molecules might hinder proper specific immunotherapy (SIT) prescription in polysensitized patients with pollen-related allergic rhinitis (AR). In these patients, component-resolved diagnosis (CRD) might modify SIT prescription by improving the identification of the disease-eliciting pollen sources. OBJECTIVES: We sought to measure the effect of CRD on SIT prescription in children with pollen-related AR. METHODS: Children (n = 651) with moderate-to-severe pollen-related AR were recruited between May 2009 and June 2011 in 16 Italian outpatient clinics. Skin prick test (SPT) reactivity to grass, cypress, olive, mugwort, pellitory, and/or Betulaceae pollen was considered clinically relevant if symptoms occurred during the corresponding peak pollen season. IgE sensitization to Phl p 1, Phl p 5, Bet v 1, Cup a 1, Art v 1, Ole e 1, Par j 2, and Phl p 12 (profilin) was measured by using ImmunoCAP. SIT prescription was modeled on SPT responses first and then remodeled considering also CRD according to GA(2)LEN-European Academy of Allergology and Clinical Immunology guidelines and the opinions of 14 pediatric allergists. RESULTS: No IgE to the respective major allergens was detected in significant proportions of patients with supposed clinically relevant sensitization to mugwort (45/65 [69%]), Betulaceae (146/252 [60%]), pellitory (78/257 [30%]), olive (111/390 [28%]), cypress (28/184 [15%]), and grass (56/568 [10%]). IgE to profilins, polcalcins, or both could justify 173 (37%) of 464 of these SPT reactions. After CRD, the SPT-based decision on SIT prescription or composition was changed in 277 (42%) of 651 or 315 (48%) of 651 children according to the European or American approach, respectively, and in 305 (47%) of 651 children according to the opinion of the 14 local pediatric allergists. CONCLUSIONS: In children with pollen-related AR, applying CRD leads to changes in a large proportion of SIT prescriptions as opposed to relying on clinical history and SPT alone. The hypothesis that CRD-guided prescription improves SIT efficacy deserves to be tested.

Recent advances in epidemiology and prevention of atopic eczema.

Atopic dermatitis (AD), named also atopic eczema, is a chronic relapsing inflammatory skin disease with a considerable social and economic burden. The primum movens of AD is in most cases a genetic and/or immune-supported defect of the skin barrier, facilitating penetration and sensitization to food or airborne allergens, as well as infections by Staphylococcus aureus, herpes simplex virus, or other microbes. New pathogenetic concepts have generated new approaches to prevention and therapy of AD. In particular, the daily use of emollients in newborns at high risk of AD has shown interesting results, with a reduction in the cumulative incidence of AD ranging from 32% to 50% of the treated infants. On the other hand, the AD preventive efficacy of food and/or inhalant allergen avoidance has been questioned, and supplementation strategies (vitamin D, probiotics, or other compounds) need to be further investigated.

Baboon-like syndrome in children.

Baboon syndrome is a combination of diffuse symmetrical erythema on the major flexural areas and V-shaped erythema on both upper anteromedial thighs. Infectious agents have been described as possible triggers. We describe for the first time baboon syndrome in a child induced by a coinfection with Epstein-Barr virus and cytomegalovirus.

Pollen-induced allergic rhinitis in 1360 Italian children: comorbidities and determinants of severity.

BACKGROUND: Pollen-induced allergic rhinoconjunctivitis (AR) is highly prevalent and rapidly evolving during childhood. General practitioners may not be fully aware of the nature and severity of symptoms experienced by patients and might underestimate the prevalence of moderate or severe disease. Thus, the relevance of early diagnosis and intervention may be overlooked. OBJECTIVES: To investigate the severity of pollen-induced AR and its determinants in Italian children referred to allergy specialists and who had never received specific immunotherapy (SIT). METHODS: Children (age 4-18 yr) affected by pollen-induced AR who had never undergone SIT were recruited between May 2009 and June 2011 in 16 pediatric outpatient clinics in 14 Italian cities. Recruited children's parents answered standardized questionnaires on atopic diseases (International Study of Allergy and Asthma in Childhood, Allergic Rhinitis and its Impact on Asthma, Global Initiative for Asthma). The children underwent skin-prick test (SPT) with several airborne allergens and six food allergens. Information on socio-demographic factors, parental history of allergic diseases, education, perinatal events, breastfeeding, nutrition and environmental exposure in early life was collected through an informatics platform shared by the whole network of clinical centers (AllergyCARD™). RESULTS: Among the 1360 recruited patients (68% males, age 10.5 ± 3.4 yr), 695 (51%) had moderate-to-severe AR, 533 (39%) asthma, and 325 (23.9%) oral allergy syndrome (OAS). Reported onset of pollen-induced AR was on average at 5.3 ± 2.8 yr, and its mean duration from onset was 5.2 ± 3.3 yr. Only 6.2% of the patients were pollen-monosensitized, and 84.9% were sensitized to ≥3 pollens. A longer AR duration was significantly associated with moderate-to-severe AR symptoms (p 0.004), asthma (p 0.030), and OAS comorbidities (p < 0.001). CONCLUSIONS: This nationwide study may raise awareness of the severity of pollen-induced AR among Italian children who have never received pollen SIT. The strong association between pollen-induced AR duration and several markers of disease severity needs replication in longitudinal studies, while suggesting that countrywide initiatives for earlier diagnosis and intervention should be planned.

Should idiopathic facial aseptic granuloma be considered granulomatous rosacea? Report of three pediatric cases.

Idiopathic facial aseptic granuloma (IFAG), or pyodermite froide du visage, is a skin disease reported only in children and characterized by painless red nodules usually located on the cheeks. Its etiology is still unclear, but some authors considered the possibility that IFAG might be included in the spectrum of granulomatous rosacea (GR). The histopathological features of IFAG and GR are quite similar, showing perifolliculitis, granulomas, folliculitis, and lymphocytes and plasmacells around epithelioid histiocytes. In the present article, we discuss three cases in which an association between a facial nodule, compatible with both IFAG and GR, and recurrent chalazia make us support the hypothesis that IFAG should be considered as GR.

Molecular profiles of IgE to Phleum pratense in children with grass pollen allergy: implications for specific immunotherapy.

BACKGROUND: The so-called component-resolved immunotherapy of allergies proposes an immunization tailored to the molecular sensitization profiles of individual patients. OBJECTIVES: We sought (1) to investigate the profiles of IgE sensitization to Phleum pratense in children with grass pollen allergy and (2) to define the compatibility of these profiles with a mixture of recombinant allergenic molecules of P pratense previously proposed for specific immunotherapy. METHODS: We examined 200 children (age, 4-18 years; 126 boys) with allergic rhinitis, asthma, or both ascertained through validated questionnaires. Each child underwent skin prick testing (ALK-Abelló) and serum IgE assays (ImmunoCAP, Phadia) with 9 pollen extracts. Sera reacting against P pratense were tested for the individual molecules (rPhl p 1, rPhl p 2, rPhl p 4, nPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, and Phl p 12). Through a combinatorial approach, the IgE individual sensitization profiles were matched against an experimental allergen-specific immunotherapy (SIT) preparation containing Phl p 1, Phl p 2, Phl p 5, and Phl p 6. RESULTS: Among the 176 of 200 children with IgE sensitization to P pratense extract, 39 profiles of sensitization to the 8 allergenic molecules tested (cutoff, 0.35 kU/L) were identified. This high heterogeneity was reduced by considering only 6 or 4 P pratense molecules but not by increasing the cutoff levels of IgE positivity. The molecular profile of the experimental SIT preparation matched that of 7 (4%) of 176 patients only; the remaining 169 patients were classified in 4 mismatch categories: underpowered (29%), overpowered (32%), underpowered/overpowered (32%), and unrelated (3%). CONCLUSIONS: IgE sensitization profiles to P pratense are highly heterogeneous. Molecularly designed SIT preparations tailored to patients' needs should consider this high heterogeneity and be driven by locally performed population studies.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome in childhood: a narrative review.

Despite being rare, the Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a serious, possibly fatal condition that may affect both adults and children who may be also burdened by delayed sequelae. It is an adverse drug reaction characterized by widespread skin involvement, fever, lymphadenopathy, visceral involvement, and laboratory abnormalities (eosinophilia, mononucleosis-like atypical lymphocytes). It is more frequently triggered by anticonvulsants, sulphonamides, or antibiotics, the latter being responsible for up to 30% of pediatric cases. The disease typically develops 2-8 weeks after exposure to the culprit medication, with fever and widespread skin eruption; mild viral prodromes are possible. Unfortunately, diagnosis is challenging due to the absence of a reliable test; however, a score by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) allows to classify suspect patients into no, possible, probable, or definite DRESS cases. Moreover, rapid-onset DRESS syndrome has been described in recent years. It affects children more often than adults and differs from the most common form because it appears ≤15 days vs. >15 days after starting the drug, it is usually triggered by antibiotics or iodinated contrast media rather than by anticonvulsants and has a higher presence of lymphadenopathy. Differential diagnosis between rapid-onset antibiotic-driven DRESS syndrome, viral exanthems, or other drug eruptions may be challenging, but it is mandatory to define it as early as possible to start adequate treatment and monitor possible complications. The present review reports the latest evidence about the diagnosis and treatment of pediatric DRESS syndrome.