Serum sickness-like reaction to D-supplement: a case report.

BACKGROUND: Serum Sickness-Like Reaction (SSLR) is an immune response characterized by rash, polyarthralgias, inflammation, and fever. Serum sickness-like reaction is commonly attributed to antibiotics, anticonvulsants, and anti-inflammatory agents. CASE PRESENTATION: A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. She was evaluated by her pediatrician and started on a 7-day course of prednisone, as well as antihistamines. Her CBC, basic metabolic panel, liver function panel, Lyme titers, and urinalysis were all within normal limits. With concern for hypersensitivity reaction to medication, all medications were discontinued. Nine days after symptom onset, the patient was evaluated by an allergist, who confirmed her presentation was consistent with serum sickness-like reaction. Her symptoms resolved, and her medications were re-introduced sequentially over several months. Restarting UQora, however, triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free. CONCLUSIONS: This case report describes the first documented case of serum sickness-like reaction caused by UQora (active ingredient D-mannose). D-mannose is a monosaccharide, and it is frequently promoted to prevent urinary tract infections. While the clinical features and timeline in this case were typical of serum sickness-like reaction, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of serum sickness-like reaction and the importance of prompt identification and management to enhance patient safety. Further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.

Update on indoor allergens and their impact on pediatric asthma.

OBJECTIVE: In recent decades, many indoor allergens have been identified, including dust mite, cat, dog, mouse, cockroach, and indoor molds, which have important health effects particularly in sensitized individuals with asthma. This review aims to update our understanding regarding the extent of these exposures in the indoor environment, review strategies for reducing their levels in the environment, and highlight innovative recent trials targeting these exposures and their impact on pediatric asthma morbidity. DATA SOURCES: Recent practice parameter updates on indoor allergen exposures, seminal studies, and recent peer-reviewed journal articles are referenced. STUDY SELECTIONS: This review cites recent cohort studies of well-characterized pediatric patients with asthma and innovative randomized controlled trials evaluating exposure to environmental allergens, interventions to limit these exposures, and their outcomes. RESULTS: Links between indoor aeroallergen exposures and health outcomes have been well established. However, only some allergen reduction interventions have been successful in improving health outcomes. CONCLUSION: There are many complicating factors involved in allergic exposures and health outcomes. The interplay between patient genetic factors, indoor allergic triggers, airborne irritants and pollutants, and microbial exposures complicates the study of indoor allergen exposures and their impact on asthma morbidity.

Impact of Prenatal Exposure to Smoking on Child Health.

Prenatal exposure to tobacco smoke remains common, through active smoking and/or passive environmental exposure, and is linked to adverse childhood outcomes. Not only have high-quality studies and meta-analyses demonstrated increased risks of prenatal as well as postnatal complications, but adverse child outcomes are well described. In utero exposure to tobacco smoke has been associated with congenital anomalies, infant and teenager overweight and obesity, and neuropsychiatric sequelae. In addition, certain childhood malignancies have been linked to paternal smoking during pregnancy. In this chapter, adverse childhood outcomes related to intrauterine exposure to electronic cigarettes and marijuana are described.

Hypersensitivity to tetracyclines: Skin testing, graded challenge, and desensitization regimens.

BACKGROUND: Hypersensitivity reactions (HSRs) to tetracyclines and the related compound, tigecycline, can limit the use of these medications and compromise optimal patient care. Despite this, there is little discussion in the literature describing the presentation of these reactions or guiding clinicians on the management of these reactions in adult and pediatric patients. OBJECTIVE: To describe the clinical features, optimal diagnostic approach, and management of HSRs to tetracyclines. METHODS: Patients with reactions to tetracyclines at our institution from 2011 to 2019 were identified by retrospective chart review. Skin testing protocols were designed for each antibiotic. Graded challenge and desensitization procedures were devised based on medical history, skin testing results when available, and need for readministration. RESULTS: The HSRs to tetracyclines, their workup, and management are described for 10 patients, aged 7 to 68 years. Our skin testing protocols for doxycycline, minocycline, and tigecycline described herein had good negative predictive value. When skin testing was negative and the initial reaction was not severe, graded challenge to the culprit drug was performed. Using the included procedures, 3 patients were desensitized to oral doxycycline, 3 to oral minocycline, and 2 to intravenous tigecycline. All the desensitizations were successful. CONCLUSION: Once identified, HSRs to tetracyclines can be further evaluated with skin testing and graded challenge and managed in appropriate cases with desensitization. These procedures can facilitate first-line therapy for patients who require tetracyclines but developed hypersensitivity reactions.

Human inherited complete STAT2 deficiency underlies inflammatory viral diseases.

STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients' cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival.

Standards for practical intravenous rapid drug desensitization & delabeling: A WAO committee statement.

Drug hypersensitivity reactions (DHRs) to intravenous drugs can be severe and might leave patients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics, and antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients. Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first-choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally. The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe. This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy).

Successful Rapid Desensitization to Micafungin in a Pediatric Patient.

Introduction: Echinocandin antifungal medications including micafungin are being used more commonly in the treatment of invasive fungal infections in both pediatric and adult patients. Micafungin is also a first-line therapeutic option for candidemia and antifungal prophylaxis in a variety of clinical settings. Hypersensitivity reactions have not been well described; however, isolated cases have been reported. No cases of desensitization to echinocandins have been previously described. Case Presentation: In this report, we described a 14-year-old female with high-risk pre-B cell acute lymphoblastic leukemia diagnosed with pulmonary aspergillosis. She developed a hypersensitivity reaction to micafungin, which was deemed first-line therapy for the infection. A rapid intravenous desensitization protocol was successfully completed without reactions. The patient completed the remaining 2 months of therapy without reactions. Conclusion: This report outlines the first report of a successful desensitization to micafungin or any echinocandin. This is a safe method of completing antifungal therapy in a patient with echinocandin hypersensitivity and may be considered for other patients with micafungin hypersensitivities.

Detection of Food Allergens in School and Home Environments of Elementary Students.

BACKGROUND: Little is known about environmental food allergen exposure on school surfaces. OBJECTIVE: To compare the distribution of major food allergens in floor dust and table wipe samples from elementary schools and dust samples from students' homes. METHODS: In this substudy of the School Inner-City Asthma Study-II, 103 table wipe samples and 98 floor dust samples from cafeterias and classrooms in 18 elementary schools were analyzed for milk, peanut, cashew, hazelnut, and egg using a multiplex array. Home kitchen floor and bed dust samples from 90 students were also analyzed. RESULTS: Food allergens were detectable in schools, but at significantly lower levels than in homes (P < .001). In schools, milk and peanut were detected in all table wipe samples; milk and egg were detected in all floor dust samples. Cafeteria table wipe samples contained significantly higher levels of milk, peanut, hazelnut, and egg, compared with classrooms. Cafeteria floor dust samples contained higher levels milk than classrooms. Peanut-restrictive policies did not consistently reduce environmental peanut exposure in schools. Peanut allergen was lower in dust from homes of students with peanut allergy (n = 5) compared with those without peanut allergy (n = 85) (P < .001). Reassuringly, peanut allergen in the schools of peanut-allergic students was not significantly different than in their homes. CONCLUSION: Food allergens were readily detectable on tables and floors in elementary schools, but at levels lower than in students' homes. For peanut-allergic students, the levels of detectable peanut in their schools were not higher than their homes. The low levels of detectable food allergens in school environments are unlikely to result in severe allergic reactions.

Prevention of Asthma: Targets for Intervention.

Approximately 300 million people worldwide are estimated to be affected by asthma, and the number of patients affected is growing exponentially-with potential for an additional 100 million people affected by the condition by 2025. With this increasing burden of disease, there is high motivation to discover effective prevention strategies. Strategies aimed at stalling the atopic progression, modifying the microbiome, preventing respiratory viral infections, and reducing the impact of toxin/pollutant exposure through dietary supplements have had limited success in the prevention of asthma. This is likely because asthma is heterogenous and is influenced by different genetic and environmental factors. Genes underlie a predisposition to asthma and allergic sensitization, whereas exposure to allergens, respiratory infections, and pollution may modify asthma pathogenesis and the variation in severity seen among individuals. Future advances in asthma prevention may include a more personalized approach: genetic variations among susceptible individuals with distinct asthma phenotypes or different biomarkers of disease may help individualize prevention strategies and render them more . In this article, we summarize interventions that have been studied for the prevention of asthma and identify some of the clinical trials that are actively underway in asthma prevention.

A Slice of Food Protein-Induced Enterocolitis Syndrome (FPIES): Insights from 441 Children with FPIES as Provided by Caregivers in the International FPIES Association.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy. There is little known about the demographic characteristics, food triggers, and risk factors for FPIES. OBJECTIVE: To characterize the demographic characteristics, food triggers, risk factors, and management in children with FPIES. METHODS: We retrospectively analyzed surveys completed by 410 caregiver-members of the International FPIES Association, both at a conference for families affected by FPIES and online. RESULTS: Most of the children were female (50.7%), white (86.2%), and atopic (54.8%), with a median age of 2 years (ranging from 2 months to 19 years). The most common food groups avoided were grains (60.0%), cow's milk (52.4%), vegetables (42.7%), and fruits (38.0%). Avocado was the most commonly avoided fruit. Avoiding avocado was associated with increased likelihood of avoiding banana (P < .001). Of these children, 69.4% avoided at least 2 food groups because of FPIES, and 20.3% had a first-degree relative with FPIES. Having a first-degree relative with FPIES was associated with increased likelihood of avoiding multiple food groups (P = .035). CONCLUSIONS: The most common food group avoided was grains, consistent with recent literature. Avocado avoidance was higher than previously reported, and this is the first report of an association between avocado and banana avoidance in FPIES. Avoiding multiple food groups because of FPIES was more common than previously reported. A large proportion of children in our cohort had first-degree relatives with FPIES, and, furthermore, having a first-degree relative with FPIES was significantly associated with the affected child avoiding multiple food groups.

The Psychosocial Impact of Food Protein-Induced Enterocolitis Syndrome.

BACKGROUND: Little is known about the psychosocial impact of food protein-induced enterocolitis syndrome (FPIES). OBJECTIVE: To characterize quality of life, stress, worry, anxiety, and self-efficacy in caregivers of children with FPIES and affected children, and determine risk factors for increased psychosocial burden. METHODS: Surveys completed by caregiver-members of the International FPIES Association at a conference (n = 42) and online (n = 368) were analyzed. RESULTS: There was significant burden, stress, worry, and anxiety among caregivers. There was a positive correlation among Food Allergy Quality of Life-Parental Burden, Perceived Stress Scale-10, Penn State Worry Questionnaire, and Beck Anxiety Inventory scores, and these were negatively associated with Food Allergy Self-Efficacy for Parents (FASE-P) scores. Lower income was associated with poorer caregiver health-related quality of life (HRQoL) (P = .039) and lower FASE-P (P = .028). Greater number of food groups avoided correlated moderately with poorer HRQoL (r = 0.386; P < .001), higher anxiety among preschoolers (r = 0.262; P = .013) and parents (r = 0.594, P = .025). Avoiding cow's milk due to FPIES was associated with poorer caregiver HRQoL (P < .001), higher stress (P = .001), and lower FASE-P (P = .013). Caregivers whose child was not attending daycare/school due to FPIES had poorer HRQoL (P < .001), higher stress (P < .014), and worry (P = .004). Compared with published cohorts of caregivers of children with IgE-mediated food allergy, the burden of FPIES on caregivers was significantly higher (mean = 3.4 vs 3.0; P < .001) and self-efficacy was significantly lower (mean = 63.9 vs 76.1; P < .001). CONCLUSIONS: There is increased stress, worry, anxiety, and reduced HRQoL and self-efficacy among caregivers of children with FPIES and increased general anxiety among preschoolers. Additional research is needed to inform effective psychosocial interventions.

Preventing the development of asthma: stopping the allergic march.

PURPOSE OF REVIEW: To describe important precipitants of asthma and allergic disease, to highlight the links between these triggers and modifications within the immune system, and to examine innovative research regarding asthma prevention with focus on attenuating the atopic march. RECENT FINDINGS: Allergen avoidance, allergen immunotherapy, IgE antagonists, prevention and treatment of respiratory infections, as well as management of gastrointestinal and respiratory dysbiosis have been considered as strategies in asthma prevention. Antenatal vitamin D supplementation in expectant mothers and aggressive control of atopic dermatitis to prevent the development of other allergic conditions were carefully studied as well. SUMMARY: Asthma is a major cause of morbidity and lost productivity. Despite the tremendous burden of this disease, the scientific community is still struggling to find an effective means of prevention. The contribution of genetics to the development of atopy cannot be altered, but environmental changes as well as pharmacotherapy have been studied as modifiable risk factors. Many trials to date have been effective only for subjects with certain characteristics. This is likely because asthma is a heterogenous condition, with a variety of triggers and clinical phenotypes. Thus far, a universally effective prevention strategy has eluded us. However, if an intervention can be found to prevent asthma and the allergic march, it will greatly improve quality of life for millions of sufferers and decrease healthcare expenditures.