Delayed Hyperpigmented Injection Site Reactions Due to Chronic Dupilumab Use.

Dupilumab is a humanized monoclonal antibody approved for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, atopic dermatitis, eosinophilic esophagitis, and prurigo nodularis. The most common adverse reactions from dupilumab use are temporary injection site reactions and ocular surface reactions; however, a variety of both acute and delayed cutaneous reactions have also been described. We present a case of delayed hyperpigmented injection site reactions following chronic dupilumab use.

Long-term adherence to imported fire ant subcutaneous immunotherapy.

BACKGROUND: Imported fire ant (IFA) whole-body extract subcutaneous immunotherapy (IT) is a safe and effective treatment for IFA hypersensitivity, with a recommended length of treatment of 3 to 5 years. OBJECTIVE: To evaluate long-term IFA IT adherence in patients with IFA allergy living in an endemic area. METHODS: During 2007 to 2014, patients with IFA-sting systemic reactions and a recommendation to start IFA IT were prospectively enrolled in this study. Subjects were contacted annually for interval IT adherence. Institutional review board approval was obtained. RESULTS: A total of 87 subjects, ages 2 to 64 years, with a recommendation to initiate IFA IT, were enrolled. Subjects were predominantly adult (76%) and female (55%), and 30% had asthma. Of these patients, 77 (89%) initiated treatment within 1 year of recommendation; 18 (23%) adhered to a 3-year course; and 10 (13%) adhered to a 5-year course. At 3 years, there were no significant differences in adherence between male and female subjects (28% vs 19%, P = .33), children and adults (25% vs 22%, P = .79), or those with or without asthma (30% vs 20%, P = .31). Adherence in subjects with mild initial reactions was lower than in subjects with moderate-to-severe reactions (0% vs 25%, P = .05) at 3 years only. Conventional buildup and concurrent flying Hymenoptera venom immunotherapy were predictive of adherence. Reasons for discontinuation were relocation to a nonendemic area (29%) and inconvenience (27%). CONCLUSION: This study showed poor long-term adherence to IFA IT at 3 and 5 years. Initial sting severity, buildup protocol, and concurrent flying Hymenoptera venom immunotherapy were predictors for long-term IT adherence.

Successful Long-Term Aspirin Desensitization in a Pilot With Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is a triad of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and adverse respiratory reactions to the ingestion of aspirin/non-steroidal anti-inflammatory drugs.1 Patients with AERD are frequently plagued with CRSwNP that is difficult to manage with systemic steroids, nasal steroids, and surgical polypectomy, often requiring multiple endoscopic sinus surgeries and frequent otolaryngology follow-up.2,3 There are an abundance of therapies to treat CRSwNP in the setting of AERD, all with varying costs, efficacies, and indications for treatment.4 While limited by side effect profile, aspirin desensitization remains an effective, low-cost treatment for patients with CRSwNP and non-steroidal anti-inflammatory drug sensitivity.5 We describe a case of an active duty U.S. Air Force pilot with AERD whose CRSwNP was successfully treated with aspirin desensitization without detrimental effect on his flying status.

Quantification of COVID-19 Vaccine Needle and Syringe Dead Space Volumes.

INTRODUCTION:  The COVID-19 pandemic taught many lessons regarding vaccine manufacturing, transportation, and delivery. Throughout the vaccination campaign, different vaccination sites reported that six or seven doses of the Pfizer/BioNTech COVID-19 vaccine could be reliably withdrawn from each multidose vial. This discrepancy was hypothesized to be caused by the differences in needle and syringe dead space volumes with differing supplies utilized at each site, but independent data regarding these volumes are lacking; therefore, we sought to objectively evaluate the volume of dead space for supplies commonly used for immunizations. MATERIALS AND METHODS: Available needles and syringes of different brands and specifications that could be used for administering vaccines were gathered. Each needle and/or syringe was weighed with a scientific, calibrated scale upon removal from the manufacturer's packaging and then filled with distilled water to simulate standard vaccine preparation. The water was then expelled, simulating vaccination, and then reweighed on the same scientific scale. The difference between the two weights was secondary to the water remaining within the needle or syringe after the simulated use, which was equivalent to the dead space volume. RESULTS: Manufacturer design, gauge, needle length, and syringe volume separately correlate with volume differences. Intuitively, the needles and syringes with the most dead space were consistently the 1.5-inch needles and the larger volume syringes, regardless of the manufacturer. CONCLUSION: The withdrawal of individual vaccine doses from a multidose vial inevitably results in vaccine volume loss due to the dead space of needles and syringes. As such, reliably obtaining seven doses of the Pfizer/BioNTech COVID-19 vaccine is improbable without utilizing specialized low dead space supplies.

Randomized Prospective Study Evaluating Single-Injection Paravertebral Block, Paravertebral Catheter, and Thoracic Epidural Catheter for Postoperative Regional Analgesia After Video-Assisted Thoracoscopic Surgery.

OBJECTIVE: Video-assisted thoracoscopic surgery (VATS) has improved patient outcomes; however, postoperative pain remains potentially severe. The objective of this study was to compare adjunct analgesic modalities for VATS, including paravertebral nerve blockade (PVB) and thoracic epidural anesthesia (TEA). DESIGN: Prospective, randomized trial. SETTING: Large academic hospital, single institution. PARTICIPANTS: Adult patients undergoing VATS. INTERVENTIONS: Ultrasound-guided PVB catheter, ultrasound-guided single-injection PVB, or TEA. MEASUREMENTS AND MAIN RESULTS: Postoperative visual analog scale pain scores (at rest and with knee flexion) and opioid usage were recorded. Pain scores (with movement) for the TEA group were lower than those for either PVB group at 24 hours (p ≤ 0.008) and for the PVB catheter group at 48 hours (p = 0.002). Opioid use in TEA group was lower than that for either PVB group at 24 and 48 hours (p < 0.001) and 72 hours (p < 0.05). Single-injection PVB was faster compared with PVB catheter placement (6 min v 12 min; p < 0.001) but similar to TEA (5 min). Patient satisfaction, nausea, sedation, and 6-month postsurgical pain did not differ between groups. CONCLUSIONS: TEA led to lower pain scores and opioid requirement for VATS procedures compared with PVB techniques. Single-injection PVB was faster and equally as effective as PVB catheter, and it led to similar patient satisfaction as TEA; therefore, it should be considered in patients who are not ideal candidates for TEA.

Characteristics of venom allergy at initial evaluation: Is fire ant hypersensitivity similar to flying Hymenoptera?

BACKGROUND: Hymenoptera venom allergy (HVA) is a well-established cause of anaphylaxis; however, studies comparing patients with imported fire ant (IFA) to flying hymenoptera (FH) allergies are lacking. OBJECTIVE: This study sought to characterize the initial presentation and examine differences between patients with IFA and FH reactions. METHODS: A multiyear (2007-2014), observational, single-institution analysis of patients referred for evaluation of HVA was performed. Data was obtained via physician interview, chart review and specific IgE results. RESULTS: 175 patients were enrolled with no difference between FH and IFA patients when analyzing mean age, sex or likelihood to seek emergency department (ED) care. Asthma was similar in all groups at 21%. ED treatments were also similar (epinephrine: 32/150, 21%; antihistamines: 141/155, 91%; corticosteroids: 67/148, 45%). Reaction severity correlated with likelihood of ED visit (P <.001), use of epinephrine (P <.001) and corticosteroid use (P <.05). Patients presenting to the ED with anaphylaxis received epinephrine in 27/73 (37%) of cases. Overall, 149/175 (85%) patients in our cohort were confirmed to be sensitized to hymenoptera. Of those with positive testing 127/149 (85%) chose to pursue VIT. CONCLUSION: IFA and FH patients have many similarities at presentation. Asthma occurred 2.5 times more frequently our cohort compared to the general US population. Epinephrine administration in our cohort was suboptimal. Children have initial reactions and are treated in the ED similarly to adults, with a notable (although not statistically significant) reduced use of epinephrine. The majority of patients seen in the ED and subsequently followed up in an allergy clinic had their venom allergy confirmed and initiated life-saving immunotherapy.

Proposal of a Global Training Load Measure Predicting Match Performance in an Elite Team Sport.

Aim: The use of external and internal load is an important aspect of monitoring systems in team sport. The aim of this study was to validate a novel measure of training load by quantifying the training-performance relationship of elite Australian footballers. Methods: The primary training measure of each of 36 players was weekly load derived from a weighted combination of Global Positioning System (GPS) data and perceived wellness over a 24-week season. Smoothed loads representing an exponentially weighted rolling average were derived with decay time constants of 1.5, 2, 3, and 4 weeks. Differential loads representing rate of change in load were generated in similar fashion. Other derived measures of training included monotony, strain and acute:chronic ratio. Performance was a proprietary score derived from match performance indicators. Effects of a 1 SD within-player change below and above the mean of each training measure were quantified with a quadratic mixed model for each position (defenders, forwards, midfielders, and rucks). Effects were interpreted using standardization and magnitude-based inferences. Results: Performance was generally highest near the mean or ~1 SD below the mean of each training measure, and 1 SD increases in the following measures produced small impairments: weekly load (defenders, forwards, and midfielders); 1.5-week smoothed load (midfielders); 4-week differential load (defenders, forwards, and midfielders); and acute:chronic ratio (defenders and forwards). Effects of other measures in other positions were either trivial or unclear. Conclusion: The innovative combination of load was sensitive to performance in this elite Australian football cohort. Periods of high acute load and sustained increases in load impaired match performance. Positional differences should be taken into account for individual training prescription.

Impact of Immunoglobulin Therapy in Pediatric Disease: a Review of Immune Mechanisms.

Intravenous immunoglobulin (IVIG) provides replacement therapy in immunodeficiency and immunomodulatory therapy in inflammatory and autoimmune diseases. This paper describes the immune mechanisms underlying six major non-primary immunodeficiency pediatric diseases and the diverse immunomodulatory functions of IVIG therapy. In Kawasaki disease, IVIG plays a major, proven, and effective role in decreasing aneurysm formation, which represents an aberrant inflammatory response to an infectious trigger in a genetically predisposed individual. In immune thrombocytopenia, IVIG targets the underlying increased platelet destruction and decreased platelet production. Although theoretically promising, IVIG shows no clear clinical benefit in the prophylaxis and treatment of neonatal sepsis. Limitations in research design combined with the unique neonatal immunologic environment offer explanations for this finding. Inflammation from aberrant immune activation underlies the myelinotoxic effects of Guillain-Barré syndrome. HIV-1 exerts a broad range of immunologic effects and was found to decrease serious bacterial infections in the pre-highly active anti-retroviral therapy (HAART) era, although its practical relevance in the post-HAART era has waned. Clinical and experimental data support the role of immune mechanisms in the pathogenesis of childhood epilepsy. IVIG exerts anti-epileptic effects through targeting upregulated cytokine pathways and antibodies thought to contribute to epilepsy. Applications in six additional pediatric diseases including pediatric asthma, atopic dermatitis, cystic fibrosis, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), autism, and transplantation will also be briefly reviewed. From autoimmunity to immunodeficiency, a dynamic immunologic basis underlies major pediatric diseases and highlights the broad potential of IVIG therapy.

Trimethoprim-sulfamethoxazole-induced aseptic meningitis-not just another sulfa allergy.

OBJECTIVE: To review the literature on trimethoprim-sulfamethoxazole (TMP-SMX)-induced aseptic meningitis (TSIAM) and discuss the features, possible mechanisms, evaluation, and treatment options relevant for the allergist. DATA SOURCES: A MEDLINE search was performed using the terms aseptic meningitis, trimethoprim-sulfamethoxazole, trimethoprim, and sulfamethoxazole. STUDY SELECTIONS: Cases were included that fit the case definition of headache, neck pain, or change in mental status with elevated cerebrospinal fluid white blood cell count or protein attributable to TMP-SMX or either medication alone. RESULTS: Forty-one patient cases were reviewed. There was a predominance of female patients and patients with autoimmune disease reported. Fever, headache, neck pain, and altered mental status were the most common findings reported in TSIAM reactions. Severe reactions ranged from hypotension to seizure and unconsciousness or coma. Typical cerebrospinal fluid findings included elevated white blood cell count with neutrophil predominance, elevated protein, and normal glucose. Symptoms quickly remitted with withdrawal of TMP-SMX, typically over 48 to 72 hours. Full recovery was typically experienced, although permanent paraplegia was reported in 1 case. The mechanism of reaction is unknown, although an IgE-mediated reaction is unlikely. Many patients experienced multiple TSIAM reactions before the diagnosis was made. Diagnosis can be confirmed with drug challenge or graded test dosing when necessary. Patients with TSIAM subsequently reacted to TMP and SMX alone and therefore should be advised to avoid these 2 classes of medication after diagnosis. CONCLUSION: TMP-SMX is the most common antibiotic to cause drug-induced aseptic meningitis. By being aware of this reaction, allergists are well poised to diagnose TSIAM and prevent future reoccurrences for the patient.

Genetic susceptibility to interstitial pulmonary fibrosis in mice induced by vanadium pentoxide (V2O5).

Interstitial lung diseases (ILDs) are characterized by injury, inflammation, and scarring of alveoli, leading to impaired function. The etiology of idiopathic forms of ILD is not understood, making them particularly difficult to study due to the lack of appropriate animal models. Consequently, few effective therapies have emerged. We developed an inbred mouse model of ILD using vanadium pentoxide (V2O5), the most common form of a transition metal found in cigarette smoke, fuel ash, mineral ores, and steel alloys. Pulmonary responses to V2O5, including dose-dependent increases in lung permeability, inflammation, collagen content, and dysfunction, were significantly greater in DBA/2J mice compared to C57BL/6J mice. Inflammatory and fibrotic responses persisted for 4 mo in DBA/2J mice, while limited responses in C57BL/6J mice resolved. We investigated the genetic basis for differential responses through genetic mapping of V2O5-induced lung collagen content in BXD recombinant inbred (RI) strains and identified significant linkage on chromosome 4 with candidate genes that associate with V2O5-induced collagen content across the RI strains. Results suggest that V2O5 may induce pulmonary fibrosis through mechanisms distinct from those in other models of pulmonary fibrosis. These findings should further advance our understanding of mechanisms involved in ILD and thereby aid in identification of new therapeutic targets.

A side-by-side comparison of Rotorod and Burkard pollen and spore collections.

BACKGROUND: The Rotorod sampler and Burkard spore trap are 2 devices commonly used to quantify airborne particles. OBJECTIVE: To evaluate the differences in collections between the 2 devices for a wide range of plant pollens and fungal spores. METHODS: Pollens and spores were collected simultaneously with each device on 167 days during a 1-year period. RESULTS: The Burkard yielded significantly higher total and individual mold spore counts. It yielded statistically higher total grass, total weed, and Urticaceae daily pollen counts, although the absolute differences were small. Daily counts were positively correlated between the 2 devices for the most abundant pollens and mold spores. CONCLUSION: The Burkard spore trap collects many more mold spores than the Rotorod over a wide variety of species. The Burkard also yielded higher total grass, total weed, and Urticaceae daily pollen counts. Despite these differences, however, either device can be used to follow trends in the most abundant pollen and mold spores.

Adherence to imported fire ant subcutaneous immunotherapy.

BACKGROUND: Imported fire ant (IFA) subcutaneous immunotherapy (SCIT) is safe and effective. For optimal protection, SCIT is given monthly for 3 to 5 years. Successful outcomes require patient adherence. OBJECTIVE: To evaluate SCIT adherence in IFA allergic patients in an endemic area. METHODS: Patients with systemic reactions to an IFA sting, with detectable specific IgE, who received a recommendation to start IFA SCIT were included. Initial reaction severity and demographic data were collected. Patients were contacted at 1 year regarding interval reactions to stings, SCIT adherence, and reason for nonadherence. Adherence rates were analyzed for association with age, sex, and severity of initial reaction. RESULTS: Seventy-six patients were enrolled, and 71% adhered to the recommendation to start IFA SCIT. Subgroup analysis did not find significant differences. At 1 year, 97% completed follow-up for analysis, and only 35% remained adherent. Subgroup analysis did not find significant differences. Inconvenience and fear were reported as reasons for not following the recommendation to start or continue with IFA SCIT. CONCLUSION: IFA SCIT is a life-saving therapy that is safe and effective. Despite this, only 71% followed the recommendation to start, and at 1 year only 35% remained adherent. Adherence was not statistically related to age, sex, or severity of initial reaction. Logistical constraints and fear were significant impediments.

Safety of angiotensin-converting enzyme inhibitors while receiving venom immunotherapy.

BACKGROUND: Case reports have raised concern about concurrent use of angiotensin-converting enzyme inhibitors (ACE-Is) in patients receiving venom immunotherapy (VIT). No surveys have been performed on the number of venom allergic patients who take ACE-Is and their outcomes. OBJECTIVE: To survey the use of ACE-Is and systemic reaction (SR) characteristics in patients receiving VIT. METHODS: A retrospective medical record review was performed on all patients evaluated for Hymenoptera venom allergy at a single center from 2000 to 2005. Patient records were evaluated for presenting symptoms, specific IgE testing, VIT treatment course, ACE-I use during VIT, and the presence of any SRs to field stings or VIT. RESULTS: Of 288 patients evaluated from 2000 to 2005 for Hymenoptera venom allergy, 157 were found to have venom specific IgE. Of these 157 patients, 79 (50%) of those with Hymenoptera venom allergy underwent VIT. Seventeen of these 79 patients (21%) were taking an ACE-I during VIT. The mean overlap of a patient taking an ACE-I with the time they were receiving VIT was 30.9 months (range, 3-114 months). Patients taking ACE-Is were older (mean age, 56.2 vs 36.4 years; P < .001) and received VIT for a longer period (mean, 72.3 vs 29.9 months; P < .04). Thirteen of 62 patients not taking an ACE-I (21%) experienced an SR during their VIT. No patients taking an ACE-I experienced an SR to VIT while taking an ACE-I (P = .03). CONCLUSIONS: This study suggests that there is not an association between ACE-I use and increased frequency of SRs to venom immunotherapy.