Outcomes of eosinophilic esophagitis in patients managed in a multidisciplinary clinic.

Background: Eosinophilic esophagitis is a complex disease with an increasing prevalence. Multidisciplinary teams are often needed to manage this difficult-to-treat condition. Objective: To observe the clinical and histologic outcomes of patients with eosinophilic esophagitis after management in a multidisciplinary clinic. Methods: An observational, retrospective chart review was conducted to include all patients referred to the Walter Reed National Military Medical Center multidisciplinary eosinophilic esophagitis clinic between August 2012 and February 2021. Only patients who had at least one esophagogastroduodenoscopy before referral, one or more visits and endoscopy after multidisciplinary management, and documented clinical symptoms were included. Statistical analysis was performed by using McNemar and Wilcoxon tests. Results: A total of 103 patients were included in the study, with a mean age at diagnosis of 17.9 years. Management in the multidisciplinary clinic was associated with a reduction in solid-food dysphagia by 70.9%, poor growth by 70.8%, and emesis or regurgitation by 87.5%. We observed that 48.5% and 62.1% had histologic remission (<15 eosinophils/hpf) on the initial and any post-multidisciplinary endoscopy, respectively. Only seven patients (5.8%) with two or more visits and endoscopies did not achieve histologic remission. More than two-thirds of the patients (68.9%) required combination therapy to achieve remission. Conclusion: Although an observational study, these findings may suggest that the management of patients with eosinophilic esophagitis in a multidisciplinary clinic may improve the likelihood of clinical and histologic remission. Targeted management with a multidisciplinary approach may reduce overall morbidity and slow disease progression; however, more research is needed.

Combining Discordant Serum IgE and Skin Testing Improves Diagnostic and Therapeutic Accuracy for Hymenoptera Venom Hypersensitivity Immunotherapy.

BACKGROUND: Diagnosis of patients with hymenoptera venom hypersensitivity consists of elucidating clinical symptoms suggestive of systemic reaction (SR) and then confirmation of sensitization via intradermal skin testing (IDST) first and serum IgE assays such as ImmunoCAP (ICAP) as a complementary modality of diagnosis. OBJECTIVE: Determine the concordance between ICAP and IDST in patients with a clinical history suggestive of hymenoptera venom SR. Determine whether venom immunotherapy would change on the basis of IDST versus ICAP results. METHODS: A prospective diagnostic study was designed to test the concordance between IDST and ICAP venom testing in the diagnosis of hymenoptera venom hypersensitivity. This study entailed testing both IDST and ICAP for 5 hymenoptera venoms (honey bee, wasp, yellow jacket, yellow hornet, and white-faced hornet) in both a case group with SR to hymenoptera venom (N = 70) and a control group without SR (N = 51). RESULTS: Significant discordance was observed between positive IDST and ICAP results for any of the 5 hymenoptera venoms (McNemar test, P = .001). In the case group, there was significant discordance for wasp (P < .0001), yellow jacket (P = .002), and white-faced hornet (P = .02). More than 47% of the case patients would have different venom immunotherapy prescriptions if ICAP and IDST had been performed during initial diagnosis versus IDST alone. CONCLUSIONS: Our study shows significant discordance between IDST and ICAP; however, they are complementary. On the basis of our data, we propose ICAP testing first followed by IDST for ICAP-negative venoms as an alternative and efficient diagnostic strategy.

Multisystem Inflammatory Syndrome in Children during the COVID-19 Pandemic: A Case Report on Managing the Hyperinflammation.

The novel human coronavirus of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly swept throughout the entire world. As the ongoing pandemic has spread, recent studies have described children presenting with a multisystem inflammatory disorder sharing the features of Kawasaki disease (KD) and toxic shock syndrome, now named Multisystem Inflammatory Syndrome in Children (MIS-C). These cases report a similar phenotype of prolonged fever, multisystem involvement, and biomarkers demonstrating marked hyperinflammation that occurs temporally in association with local community spread of SARS-CoV-2. Herein, we describe the presentation, clinical characteristics, and management of an 11-year-old boy with prolonged fever, strikingly elevated inflammatory markers, and profound, early coronary artery aneurysm consistent with a hyperinflammatory, multisystem disease temporally associated with coronavirus disease 2019. We highlight our multidisciplinary team's management with intravenous immunoglobulin, methylprednisolone, and an interleukin-1 receptor antagonist, anakinra, as a strategy to manage this multisystem, hyperinflammatory disease process.

Birt-Hogg-Dubé Syndrome: Another Battle for a Retired Navy Seal.

Birt-Hogg-Dubé syndrome is an autosomal dominant cancer syndrome characterized by upper torso and facial fibrofolliculomas, acrochordons, pneumothorax, and renal cell carcinoma. Although a rare syndrome, its prevalence is likely underestimated. Additionally, since it presents in patients' 20s or 30s, otherwise healthy members of the military may be affected, as with the index patient discussed in this case report.

Can we find a possible structural explanation for antibody-dependent enhancement of dengue virus infection resulting in hemorrhagic fever?

Dengue virus infection is one of the most prevalent mosquito-borne illnesses worldwide, affecting as many as 400 million persons annually. Most people experience a self-limited viral illness, but some experience life-threatening disease. Subsequent infection with other dengue virus serotypes increases the risk of development of severe dengue disease with plasma leakage with or without hemorrhage and end organ impairment. Antibody-dependent enhancement of dengue virus infection has been implicated in the development of severe dengue disease, previously referred to as dengue hemorrhagic fever and dengue shock syndrome. We propose a structural explanation for the role of non-neutralizing antibodies in the development of antibody-dependent enhancement of dengue virus infection via complement fixation or binding to Fcγ receptors facilitating entry into target cells.

Can we use DNA triple helices as treatment for systemic lupus erythematosus?

Systemic lupus erythematosus (SLE) is a chronic disease characterized by a variable clinical course and is associated with the presence of numerous autoantibodies. Autoantibodies against double-stranded DNA are highly specific for SLE and are directly associated with distinct clinical manifestations of the disease, specifically lupus nephritis. Examination of the sequences and the three-dimensional structures of autoantibodies specific for nucleic acids, confirms the presence of positively charged amino acids which could interact with the phosphate groups of self DNA. We hypothesize that DNA triple-helices, which can be constructed using short DNA sequences, may be useful in decreasing the clinical manifestations of SLE by inhibiting anti-dsDNA autoantibodies.

Allergen immunotherapy extract treatment set preparation: making a safer and higher quality product for patients.

The best possible allergen immunotherapy clinical outcomes require the provision of high quality and safe allergen immunotherapy extract preparations. Evolving national guidelines and regulatory bodies have devoted special attention to the safe compounding of sterile products, including allergen extracts. It is incumbent upon allergists preparing extract treatment sets for patients to be familiar with and adopt training, procedures and safety measures that lead to standardized high quality products. Preparers and supervisors must maintain ongoing competency in aseptic technique and prescribing principles, such as probable effective dose ranges, allergen cross-reactivity, and separation of high protease-containing extracts from susceptible extracts. Accordingly, knowledge and application of vial labeling, diluent selection, standard operating procedures, mixing log documentation, and mixing condition principles are a necessity. Although there have been no instances of infectious complications from allergen immunotherapy in a century of clinical practice, continued vigilance in the use of measures that ensure extract sterility is paramount. A review of allergen immunotherapy preparation recommendations and best practices based on published national guidelines is presented. Further study of preparation measures and prescribing principles will continue to advance the practice of allergen immunotherapy and offer opportunities for refinement of current recommendations.

Can we explain the allergenicity of peanuts on the basis of the three-dimensional structure of its allergens and use the information to devise means of eliminating peanut allergy?

Helical bundles are found in all the known structures of peanut allergens. The peptide fragments, which survive gastrointestinal digestion of the allergens and are absorbed intact, are hypothesized to reassociate and form stable helical bundles in the circulation, which could elicit a specific IgE response resulting in peanut allergy. The hypothesis is supported by the finding of a diminished allergenicity of an isoform of the peanut allergen, Ara h 3, which has a major deletion. A very probable consequence of this deletion is the reduced tendency to form a stable helix bundle. The discovery of structurally disrupted isoforms of the other peanut allergens and the breeding of plants that contain only those isoforms could lead to the elimination of peanut allergy.

Solar urticaria.

A case of solar urticaria is presented, followed by a discussion of the clinical characteristics, pathophysiology, diagnosis, and management of this disease. Special emphasis is given to clinical pearls and pitfalls for the practicing allergist. Solar urticaria is a physical urticaria that can be difficult to diagnose and distinguish from other photodermatoses. There are some characteristic features that are important to remember when evaluating a patient with suspected solar urticaria. Testing can be difficult without the assistance of an experienced dermatologist because there are several different wavelengths of light that can lead to a patient's symptoms. Solar urticaria tends to be a chronic disease with a low 5-year resolution rate but can usually be effectively managed with multiple antihistamines.

Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: a meta-analysis.

BACKGROUND: Patients who have angioedema after taking angiotensin-converting enzyme inhibitors (ACE-Is) have been reported to develop angioedema when taking an angiotensin receptor blocker (ARB), but few studies quantify the risk. OBJECTIVE: To perform a systematic review of the literature. METHODS: A literature search was performed in MEDLINE, EMBASE, BIOSIS, and Current Contents, with no limitations from January 1990 to May 2007. Any article that described a cohort of patients who had angioedema after taking an ACE-I, were subsequently exposed to an ARB, and were followed for a least 1 month were included. The percentage of patients who had angioedema was abstracted from each article, and confidence intervals were calculated using the exact binomial method. The pooled percentage was calculated with the inverse variance method. RESULTS: Two-hundred fifty-four unique articles were identified, and 3 articles met inclusion criteria, which described 71 patients with the outcome of interest. One was a randomized controlled trial and 2 were retrospective cohorts. These articles described both confirmed and possible cases of angioedema. The risk of angioedema was 9.4% (95% confidence interval, 1.6%-17%) for possible cases and 3.5% (95% confidence interval, 0.0%-9.2%) for confirmed cases. No fatal events were reported. No statistical heterogeneity was reported between trials (P > .3). CONCLUSIONS: Limited evidence suggests that for patients who develop angioedema when taking an ACE-I, the risk of development of any subsequent angioedema when taking an ARB is between 2% and 17%; for confirmed angioedema, the risk is 0% to 9.2%. This information will aid clinicians in counseling patients regarding therapy options after development of angioedema due to ACE-Is.

Common variable immune deficiency (CVID) presenting as an autoimmune disease: role of memory B cells.

Common variable immunodeficiency (CVID) is a clinically heterogeneous disorder. Most often patients present with recurrent sinopulmonary infections, although it may present with autoimmune manifestations. Immune cytopenias, particularly thrombocytopenia and hemolytic anemia, are the most commonly observed. While the pathophysiology of CVID remains elusive, in many patients it may be due to an intrinsic B cell defect. Memory B cells (CD27+) in particular, have been noted to correlate with certain aspects of the disease. High numbers of IgM+ memory B cells appear to correlate with the presence of infections, whereas decreased numbers of switched memory B cells correlate with lower serum IgG levels and increased rates of autoimmune features. Because of these defects in the memory B cell compartment, there is a greater potential risk for infection and related complications. Review of the literature suggests that splenectomy should be avoided in patients with immune cytopenia and CVID and that serum immunoglobulins should be obtained in patients presenting with immune cytopenias to screen for CVID.

Why is there a greater incidence of allergy to the tropomyosin of certain animals than to that of others?

Tropomyosin is a major allergen in various foods, implicated in a spectrum of mild to life threatening systemic reactions. The incidence of allergy to tropomyosin varies greatly by species, with sensitivity to crab, shrimp, cockroach, and dust mite tropomyosins, among others, being the highest, while tropomyosins in vertebrate species are considered non-allergenic. We have analyzed the possible fragments which may result from Pepsin A digestion of tropomyosins from various species and find that larger fragments of the tropomyosins from crab, shrimp, cockroach, and especially, dust mites will probably survive gastric digestion, compared to those from, for example, chicken, cattle, rabbit, or fish. These larger peptide fragments may enter the bloodstream and assume a three-dimensional structure whose stability approaches that of the intact molecule. Antibodies, including IgE, would be expected to be produced specifically against stable regions of the tertiary structure. We propose that this is a plausible explanation for the greater ability of the larger molecules derived from invertebrate tropomyosins to trigger an immediate hypersensitivity response.

Vocal cord dysfunction.

A case of vocal cord dysfunction (VCD) is presented, followed by a discussion of the clinical characteristics, pathogenesis, diagnosis, and management of this disorder. Special emphasis is given to clinical pearls and pitfalls for the practicing allergist. VCD is a common condition that mimics asthma. Dyspnea, cough, and chest tightness are frequent manifestations of the disease. A high degree of clinical suspicion is required to recognize VCD and diagnosis is made most confidently by laryngoscopy. The mainstay of treatment for VCD is reassurance, speech therapy, and treatment of associated comorbidities including gastroesophageal reflux disease, postnasal drip syndrome, and psychiatric conditions.

Allergic bronchopulmonary aspergillosis.

A case of allergic bronchopulmonary aspergillosis (ABPA) is presented, followed by a discussion of the clinical characteristics, pathogenesis, diagnosis, and management of this disease. Special emphasis is given to clinical pearls and pitfalls for the practicing allergist. ABPA is a hypersensitivity response to Aspergillus antigens in the lung and is distinct from other forms of Aspergillus pulmonary disease. Episodic bronchospasm, expectoration of mucous plugs, and fleeting pulmonary infiltrates are common manifestations of the disease. Several diagnostic schemes for ABPA have been described with varying criteria, which uniformly includes asthma and positive immediate skin-prick test to Aspergillus fumigatus. The mainstay of treatment for ABPA is corticosteroids, which are normally effective.

Nosocomial transmission of methicillin-resistant Staphylococcus aureus: a blinded study to establish baseline acquisition rates.

OBJECTIVE: To define the extent of nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to a tertiary-care hospital. DESIGN: A blinded, prospective surveillance culture study of patients admitted to the hospital to determine the transmission (acquisition) rate of MRSA. Risk factors associated with the likelihood of MRSA colonization on admission were investigated. SETTING: Tertiary-care military medical facility. PARTICIPANTS: All patients admitted to the medicine, surgery, and pediatric wards, and to the medical, surgical, and pediatric intensive care units were eligible for inclusion. RESULTS: Five hundred thirty-five admission and 374 discharge samples were collected during the study period. One hundred forty-one patients were colonized with methicillin-susceptible S. aureus (MSSA) and 20 patients (3.7%) were colonized with MRSA on admission. Of the 354 susceptible patients, 6 acquired MRSA during the study for a transmission rate of 1.7%. Patients colonized with MRSA on admission were more likely to be older than non-colonized or MSSA-colonized patients, to have received antibiotics within the past year, to have been hospitalized within the prior 3 years, or to have a known history of MRSA. Patients acquiring MRSA had an average hospital stay of 17.7 days compared with 5.3 days for those who did not acquire MRSA. Pulsed-field gel electrophoresis of the 6 MRSA isolates from patients who acquired MRSA revealed 4 distinct band patterns. CONCLUSIONS: Most patients colonized with MRSA were identified on admission samples. Surveillance cultures of patients admitted may help to prevent MRSA transmission and infection.

Sedation for pediatric diagnostic imaging: use of pediatric and nursing resources as an alternative to a radiology department sedation team.

OBJECTIVE: To develop a pathway to provide safe, effective, and efficient sedation for pediatric diagnostic imaging studies using non-radiology personnel. MATERIALS AND METHODS: A multidisciplinary team considered manpower and training requirements and national sedation standards before designing a sedation pathway, which included scheduling, pre-sedation history and physical, medication protocols, and monitoring. Oral and IV medication protocols were developed based on patient age and weight. Sedation delays were defined as >15 min (IV) or >30 min (PO) from start of sedation to start of imaging. A sedation failure resulted in an incomplete diagnostic imaging study. Failure rates of 124 sedations before and 388 sedations after the pathway were compared. RESULTS: The sedation failure rate for 7 months prior to pathway initiation was 15% (19/124). In the first 25 months after pathway initiation, failures were significantly reduced to 1.5% (6/388) ( P<0.0001). Three (50%) of the six failures after pathway initiation were long examinations (>55 min). Deviation from the recommended medication protocol accounted for most of the 115 delays. Only minor adverse events were seen (12/388, 3.1%). CONCLUSION: Implementing a pediatric sedation pathway significantly decreases the sedation failure rate. Pediatric residents and nurses can safely, effectively and efficiently sedate pediatric patients for routine diagnostic imaging procedures without the need for a radiology department sedation team in a department with a small-to-moderate volume of pediatric patients.