The prevalence of allergic diseases has dramatically increased among children in recent decades. These conditions significantly impact the quality of life of allergic children and their families. Lactoferrin, a multifunctional glycoprotein found in various biological fluids, is emerging as a promising immunomodulatory agent that can potentially alleviate allergic diseases in children. Lactoferrin’s multifaceted properties make it a compelling candidate for managing these conditions. Firstly, lactoferrin exhibits potent anti-inflammatory and antioxidant activities, which can mitigate the chronic inflammation characteristic of allergic diseases. Secondly, its iron-binding capabilities may help regulate the iron balance in allergic children, potentially influencing the severity of their symptoms. Lactoferrin also demonstrates antimicrobial properties, making it beneficial in preventing secondary infections often associated with respiratory allergies. Furthermore, its ability to modulate the immune response and regulate inflammatory pathways suggests its potential as an immune-balancing agent. This review of the current literature emphasises the need for further research to elucidate the precise roles of lactoferrin in allergic diseases. Harnessing the immunomodulatory potential of lactoferrin could provide a novel add-on approach to managing allergic diseases in children, offering hope for improved outcomes and an enhanced quality of life for paediatric patients and their families. As lactoferrin continues to capture the attention of researchers, its properties and diverse applications make it an intriguing subject of study with a rich history and a promising future.

Neurofibromatosis Type 1 (NF1) is an autosomal dominant tumor-predisposition disorder that is caused by a heterozygous loss of function variant in the NF1 gene, which encodes a protein called neurofibromin. The absence of neurofibromin causes increased activity in the Rat sarcoma protein (RAS) signalling pathway, which results in an increased growth and cell proliferation. As a result, both oncological and non-oncological comorbidities contribute to a high morbidity and mortality in these patients. Optic pathways gliomas, plexiform neurofibromas and malignant peripheral nerve sheath tumor (MPNST) are the most frequent NF1-associated tumors. The treatment of these complications is often challenging, since surgery may not be feasible due to the location, size, and infiltrative nature of these tumors, and standard chemotherapy or radiotherapy are burdened by significant toxicity and risk for secondary malignancies. For these reasons, following the novel discoveries of the pathophysiological mechanisms that lead to cell proliferation and tumorigenesis in NF1 patients, emerging drugs targeting specific signalling pathways (i.e. the MEK/ERK cascade), have been developed with promising results. (www.actabiomedica.it)

Selective Immunoglobulin M deficiency (SIgMD) has been recently included in the inborn errors of immunity (IEI) classification by the International Union of Immunological Societies Expert Committee. The understanding of SIgMD is still extremely limited, especially so in cases of SIgMD in the pediatric population. The epidemiology of SIgMD in the pediatric population is still unknown. The pathogenesis of SIgMD remains elusive, and thus far no genetic nor molecular basis has been clearly established as a definitive cause of this primary immunodeficiency. Recurrent respiratory infections represent the main clinical manifestations in children, followed by allergic and autoimmune diseases. No conclusive data on the correct therapeutic management of SIgMD are available. Although, for most SIgMD patients, Ig replacement therapy is not required, it may be recommended for patients with significantly associated antibody deficiency and recurrent or severe infections. Prophylactic antibiotics and the prompt treatment of febrile illness are crucial. There is insufficient evidence on the prognosis of this condition. Therefore, further studies are required to define the disease trajectories and to increase our understanding of the molecular mechanisms underlying SIgMD in order to facilitate a better clinical, immunological, and prognostic characterization of the condition and develop tailored therapeutic management strategies.

Quercetin, a natural flavonoid, present in various vegetables and fruits, has garnered increasing attraction for its potential antiallergic properties. Its broad-spectrum activity depends on its anti-inflammatory, immunomodulatory, and antioxidant effects, which target the critical pathways involved in type 2-driven allergic inflammation. Quercetin inhibits mast cell degranulation, reduces the production of histamine and pro-inflammatory cytokines, and restores homeostasis of the immune system by modulating the Th1/Th2 and Treg/Th17 balances. Additionally, its antioxidant properties help to dampen oxidative stress, a critical factor in the pathophysiology of allergic diseases. In vitro studies have consistently demonstrated quercetin’s ability to suppress allergic reactions. In contrast, in vivo studies, particularly in murine models of allergic rhinitis, have confirmed its efficacy in relieving symptoms (such as nasal itching, sneezing, rhinorrhea, and congestion) and dampening type 2 mucosal inflammation. Preclinical evidence also supports its therapeutic potential in asthma, conjunctivitis, atopic dermatitis, and food allergies. However, human studies are still scarce, as only two clinical trials investigated quercetin as a monotherapy. Both studies reported promising results, including symptom reduction and improved quality of life, though larger, randomized trials are needed to validate these findings. Some other studies have investigated multicomponent products that also contain quercetin. This review aimed to report and discuss the most recent in vitro and in vivo evidence on quercetin’s application in allergic models. It also provides a comprehensive overview of human studies, highlighting its potential as an agent in food supplements to manage patients with allergic diseases. Moreover, this review introduces a new quercetin phospholipids formulation that may represent a keystone in clinical use. The literature search was based on a PubMed consultation considering the most recent (last five years) publications using the keywords “quercetin and allergic disease” and “quercetin and immune system”.

Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic rhinitis and asthma. Sublingual immunotherapy (SLIT) is commonly used in clinical practice. Although its effectiveness has been proven in randomized controlled trials and real-world studies, poor or no responses may occur in some cases. The present review aims to summarize the main possible factors involved in ineffective SLIT treatment, including immunological mechanisms, molecular and diagnostic errors, non-purified extracts, inadequate dosage, and patients' intrinsic and extrinsic characteristics. Possible remedies are also reported to predict and overcome poor patient response to guarantee optimal treatment efficacy. Identifying the reason for SLIT ineffectiveness is clinically relevant. Allergologists should carefully investigate the possible cause of poor or no response to SLIT. Identification is important as the potential removal of the interfering problems might allow SLIT to continue. The most common causes of poor SLIT efficacy include diagnostic errors, incorrect allergen dosage and schedule, poor quality extract, comorbidity, impaired immune system function, and inadequate adherence.

Inborn errors of immunity (IEI) are disorders mostly caused by mutations in genes involved in host defense and immune regulation. Different degrees of gastrointestinal (GI) involvement have been described in IEI, and for some IEI the GI manifestations represent the main and characteristic clinical feature. IEI also carry an increased risk for atopic manifestations. Eosinophilic gastrointestinal diseases (EGIDs) are emerging disorders characterized by a chronic/remittent and prevalent eosinophilic inflammation affecting the GI tract from the esophagus to the anus in the absence of secondary causes of intestinal eosinophilia. Data from the U.S. Immunodeficiency Network (USIDNET) reported that EGIDs are more commonly found in patients with IEI. Considering this element, it is reasonable to highlight the importance of an accurate differential diagnosis in patients with IEI associated with mucosal eosinophilia to avoid potential misdiagnosis. For this reason, we provide a potential algorithm to suspect an EGID in patients with IEI or an IEI in individuals with a diagnosis of primary EGID. The early diagnosis and detection of suspicious symptoms of both conditions are fundamental to prevent clinically relevant complications.