A new pediatric protocol for rapid desensitization to monoclonal antibodies.

Monoclonal antibodies are important therapeutic tools, but their usefulness may be limited when patients experience acute hypersensitivity reactions. Patients reporting a history of adverse allergic reaction are likely to discontinue their therapeutic protocol or be switched to an alternative drug, which is sometimes less effective than that originally prescribed. Drug desensitization has proven to be a highly effective strategy to readminister a drug in a patient who has experienced a hypersensitivity reaction. It involves forcing the patient's immune system to accept and tolerate the allergen. Nevertheless, such a procedure is still empiric for monoclonal antibodies and not common in the pediatric population. The aim of our study is to demonstrate the clinical success of a new protocol of rapid desensitization to infliximab in a pediatric patient affected by ulcerative colitis, who developed an anaphylaxis to the drug. We used a protocol of rapid desensitization consisting of 13 steps, with the first being 1/1,000,000 of the cumulative and total dose. Such a protocol has proven to be able to induce a temporary tolerance to infliximab, allowing the patient to achieve complete control of his disease.

Risk factors for drug hypersensitivity reactions in children.

Drug hypersensitivity reactions are common in children. Risk factors predisposing to IgE-mediated drug allergies and delayed drug reactions are a matter of debate. Gender, age, previous reactions to the same drug or to another drug, reduced drug metabolism, chronic diseases, polypharmacy, drug doses are linked with the onset of hypersensitivity reactions in some children. Novel advances in genetic polymorphisms can rapidly change the approach to the prevention of reactions since gene testing can be a useful screening test for severe cutaneous adverse reactions. Viral infections may act as cofactors in susceptible individuals. Polypharmacy, high doses, repeated doses and parental route of administration are also risk factors. Clinicians should take into account risk factors to allow the risk-benefit balance to be maintained.

Drug-Induced Anaphylaxis in Children.

Drug-induced anaphylaxis in children is less common than in adults and primarily involves beta-lactams and nonsteroidal anti-inflammatory drugs. Epidemiological studies show variable prevalence, influenced by age, gender, and atopic diseases. The pathophysiology includes IgE-mediated reactions and non-IgE mechanisms, like cytokine release reactions. We address drug-induced anaphylaxis in children, focusing on antibiotics, nonsteroidal anti-inflammatory drugs, neuromuscular blocking agents, and monoclonal antibodies. Diagnosis combines clinical criteria with in vitro, in vivo, and drug provocation tests. The immediate management of acute anaphylaxis primarily involves the use of adrenaline, coupled with long-term strategies, such as allergen avoidance and patient education. Desensitization protocols are crucial for children allergic to essential medications, particularly antibiotics and chemotherapy agents.

Local Anesthetic Hypersensitivity Reactions in Pediatric Patients: Recognition and Management.

Local anesthetics (LAs) are commonly used in all medical specialties, particularly in association with surgery, obstetrics, dentistry, and emergency departments. Most individuals, starting from young children, are exposed to LAs during life. LA hardly induces adverse events when used in recommended doses and with proper injection techniques. However, immediate anaphylactic reactions to LA injections may be a rare but life-threatening manifestation. A comprehensive report of the event and performing a specialist examination are crucial to prevent further episodes. The diagnosis should be based on history, medical records, skin and challenge tests.

Silent Sinus Syndrome and Williams Syndrome: Two Rare Diseases Found in a Pediatric Patient.

Silent sinus syndrome (SSS) is a rare disease process characterized by progressive enophthalmos and hypoglobus due to ipsilateral maxillary sinus hypoplasia and orbital floor resorption. Patients may also present with eye asymmetry, unilateral ptosis, or diplopia. Most reported cases in the literature describe its occurrence in adults, but it can also affect children. The etiology remains speculative, even though the most accepted theory is that during the first or second decade of life, occlusion of the maxillary ostium causes an interruption in normal sinus development. Williams syndrome (WS) is a rare genetic, multisystem disorder characterized by a constellation of distinctive phenotypic features, including psychomotor delay and cardiovascular abnormalities. We report a case of a 7-year-old female diagnosed at 1 year old with WS and who gradually developed SSS. This last condition was diagnosed at 7 years of age, when she started showing progressive facial asymmetry in addition to typical facial features of WS; subsequent neuroimaging definitively supported the diagnosis. This case report describes for the first time in the literature an uncommon situation in which SSS and WS, both rare syndromes, are present in the same pediatric patient. We speculate that the particular facial features typical of WS could either be the basis of the development of SSS in our patient or make the SSS clinical course more severe, with signs presenting at the age of 7 years. This case report shows for the first time that facial asymmetry in WS can be caused by SSS and highlights the need for early identification of this complication in patients with syndromes characterized by dysmorphic facial features. Further studies are needed to understand whether there is a link between the two syndromes as well as to evaluate the prevalence of SSS in patients with facial dysmorphisms and define the best management.

First Case of Typhoid Fever due to Extensively Drug-resistant Salmonella enterica serovar Typhi in Italy.

Typhoid fever is a potentially severe and occasionally life-threatening bacteraemic illness caused by Salmonella enterica serovar Typhi (S. Typhi). In Pakistan, an outbreak of extensively drug-resistant (XDR) S. Typhi cases began in November 2016. We report on a five-year-old boy who contracted enteric fever while travelling in Pakistan and was diagnosed after returning to Italy in September 2019. Blood culture isolated Salmonella enterica serovar Typhi that was XDR to all first-line antibiotics, including ceftriaxone and fluoroquinolones. Empiric therapy was switched to meropenem, and the patient recovered completely. Whole-genome sequencing showed that this isolate was of haplotype H58. The XDR S. Typhi clone encoded a chromosomally located resistance region and harbored a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum ß-lactamase and the qnrS fluoroquinolone resistance gene. This is the first case of typhoid fever due to XDR S. Typhi detected in Italy and one of the first paediatric cases reported outside Pakistan, highlighting the need to be vigilant for future cases. While new vaccines against typhoid are in development, clinicians should consider adapting their empiric approach for patients returning from regions at risk of XDR S. Typhi outbreak with typhoid symptoms.