Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part II diagnosis and management.

Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an exanthem, fever, and hematologic and visceral organ involvement. The differential diagnosis includes other cutaneous adverse reactions, infections, inflammatory and autoimmune diseases, and neoplastic disorders. Three sets of diagnostic criteria have been proposed; however, consensus is lacking. The cornerstone of management is immediate discontinuation of the suspected drug culprit. Systemic corticosteroids remain first-line therapy, but the literature on steroid-sparing agents is expanding. Longitudinal evaluation for sequelae is recommended. Adjunctive tests for risk stratification and drug culprit identification remain under investigation. Part II of this continuing medical education activity begins by exploring the differential diagnosis and diagnosis of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms and concludes with an evidence-based overview of evaluation and treatment.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis.

Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR) characterized by an exanthem, fever, and hematologic and visceral organ involvement. Anticonvulsants, antibiotics, and allopurinol are the most common triggers. The pathogenesis involves a complex interplay between drugs, viruses, and the immune system primarily mediated by T-cells. DiHS/DRESS typically presents with a morbilliform eruption 2-6 weeks after drug exposure, and is associated with significant morbidity, mortality, and risk of relapse. Long-term sequelae primarily relate to organ dysfunction and autoimmune diseases. Part I of this continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis.

Evaluating the PEN-FAST Clinical Decision-making Tool to Enhance Penicillin Allergy Delabeling.

This cohort study evaluated the diagnostic accuracy of PEN-FAST as a clinical decision-making tool to enhance penicillin allergy evaluation.

Antibiotic choice for Group B Streptococcus prophylaxis in mothers with reported penicillin allergy and associated newborn outcomes.

OBJECTIVE: To evaluate the choice of antibiotic used for intrapartum Group B Streptococcus (GBS) prophylaxis in pregnant individuals with reported penicillin allergies compared to those without reported penicillin allergies and investigate whether there are associated differences in neonatal outcomes. STUDY DESIGN: This retrospective cohort study included mother-infant dyads of GBS positive pregnant individuals who labored and delivered newborns ≥ 35 weeks of gestation at a high-volume urban hospital (2005-2018). The type of antibiotic administered to the mothers for GBS prophylaxis (beta-lactam prophylaxis defined as penicillin-class drug or cefazolin; alternative prophylaxis defined as vancomycin or clindamycin) was compared between those with a penicillin allergy documented in their medical record versus those who did not. Neonatal outcomes included number of postnatal blood draws, antibiotic administration, neonatal intensive care unit (NICU) admission, bacteremia, and hospital length of stay and were compared between groups. Bivariable and multivariable analyses were performed. RESULTS: Of 11,334 mother-infant pairs, 1170 (10.3%) mothers had a penicillin allergy documented in their medical record. Of them, 49 (4.2%) received a penicillin, 259 (22.1%) received cefazolin, 449 (38.4%) received clindamycin, and 413 (35.3%) received vancomycin. Patients with a reported penicillin allergy were significantly more likely to receive alternative GBS prophylaxis compared to those without penicillin allergy (73.7% vs. 0.2%, p < 0.01). Neonates of patients who received alternative GBS prophylaxis were significantly more likely to undergo a postnatal lab draw compared to neonates of patients who received beta-lactam antibiotics (20.8% vs. 17.3%, OR 1.25 (95% CI 1.08-1.46)). This significant association persisted after adjusting for potential confounders (aOR 1.23, 95% CI 1.06-1.43). There were no other significant differences seen in other newborn outcomes. CONCLUSION: Pregnant individuals who report a penicillin allergy were more likely to receive alternative antibiotics for GBS prophylaxis compared to those without a penicillin allergy. This was associated with an increased frequency of postnatal blood draws among neonates of mothers with a reported penicillin allergy. Administration of alternative intrapartum antibiotic prophylaxis with vancomycin or clindamycin is common in individuals with self-reported penicillin allergy, and maternal alternative antibiotic administration may impact neonatal care, particularly via increased lab draws.

Clinical Phenotypes of Immediate First-Dose Reactions to mRNA COVID-19: A Multicenter Latent Class Analysis.

BACKGROUND: Although immediate potentially allergic reactions have been reported after dose 1 of mRNA coronavirus disease 2019 (COVID-19) vaccines, comprehensively defined subtypes have not been clearly distinguished. OBJECTIVE: To define distinct clinical phenotypes of immediate reactions after dose 1 of mRNA COVID-19 vaccination, and to assess the relation of clinical phenotype to mRNA COVID-19 vaccine second dose tolerance. METHODS: This retrospective study included patients with 1 or more potentially allergic symptoms or signs within 4 hours of receiving dose 1 of an mRNA COVID-19 vaccine and assessed by allergy/immunology specialists from 5 U.S. academic medical centers (January-June 2021). We used latent class analysis-an unbiased, machine-learning modeling method-to define novel clinical phenotypes. We assessed demographic, clinical, and reaction characteristics associated with phenotype membership. Using log-binomial regression, we assessed the relation between phenotype membership and second dose tolerance, defined as either no symptoms or mild, self-limited symptoms resolving with antihistamines alone. A sensitivity analysis considered second dose tolerance as objective signs only. RESULTS: We identified 265 patients with dose-1 immediate reactions with 3 phenotype clusters: (1) Limited or Predominantly Cutaneous, (2) Sensory, and (3) Systemic. A total of 223 patients (84%) received a second dose and 200 (90%) tolerated their second dose. Sensory cluster (all patients had the symptom of numbness or tingling) was associated with a higher likelihood of second dose intolerance, but this finding did not persist when accounting for objective signs. CONCLUSIONS: Three novel clinical phenotypes of immediate-onset reactions after dose 1 of mRNA COVID-19 vaccines were identified using latent class analysis: (1) Limited or Predominantly Cutaneous, (2) Sensory, and (3) Systemic. Whereas these clinical phenotypes may indicate differential mechanistic etiologies or associations with subsequent dose tolerance, most individuals proceeding to their second dose tolerated it.

Outpatient penicillin allergy evaluation during pregnancy and associated clinical outcomes.

BACKGROUND: Beta-lactam antibiotics are often clinically indicated in the peripartum period, posing a challenge for pregnant women who report a penicillin allergy. Allergy verification testing is rarely performed during pregnancy, even though most women do not have a true allergy. OBJECTIVE: This study aimed to evaluate a hospital-wide multidisciplinary program introduced in August 2020 to identify, refer, evaluate, and test pregnant women with unverified penicillin allergies and assess its association with maternal and neonatal outcomes. STUDY DESIGN: We conducted a retrospective cohort study at a large academic hospital of all pregnant women with a penicillin allergy documented in the electronic medical record who delivered from September 2020 to October 2021. Data were abstracted by medical record review. Women referred for penicillin allergy evaluation were compared with those who were not. Maternal outcomes were alternative antibiotic (clindamycin or vancomycin) use, postpartum infection, and maternal length of postpartum hospital stay. Neonatal outcomes were intensive care unit admission, postnatal blood draw, antibiotic treatment, and birth hospitalization length of hospital stay. Bivariate and multivariable analyses were performed. RESULTS: Of 689 women with a documented penicillin allergy, 232 (33.7%) were referred for allergy evaluation during the study period. Of those referred, 175 (75.4%) underwent allergy consultation, and of these patients, 167 (95.4%) were considered appropriate for allergy verification testing. Of note, 117 women (70.1%) underwent skin testing with or without graded oral amoxicillin drug challenge, and all but 1 woman (99.1%) were found to be penicillin tolerant. Moreover, 5 additional women were delabeled of their penicillin allergy based on history and pharmacy confirmation of penicillin tolerance subsequent to index reaction. Referred women had a 62% lower likelihood of receiving an alternative antibiotic than those who were not referred, and this significance persisted even after adjusting for potential confounders (adjusted odds ratio, 0.49; 95% confidence interval, 0.27-0.89). Other maternal and neonatal adverse outcomes were less frequent in those referred, but these associations did not reach statistical significance. CONCLUSION: This study documented the feasibility, safety, and clinical benefit of an outpatient penicillin allergy referral program for pregnant women. Referred patients were significantly less likely to receive alternative antibiotics; however, more patients are needed to assess whether there are additional clinical benefits.

Clinical factors associated with acute exacerbations of chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is complicated by frequent acute exacerbations leading to significant health care burden and impaired quality of life. OBJECTIVE: The objective of this study was to identify clinical factors associated with frequent acute exacerbation of CRS (AECRS). METHODS: This is a retrospective cohort study of patients with CRS from January 1, 2014, to May 31, 2016. Frequent AECRS was defined as at least 4 episodes over a 12-month period in which an antibiotic was prescribed for worsening sinus symptoms, and infrequent AECRS was defined as 0 to 3 episodes. Clinical factors, including asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease, were evaluated for associations between the 2 groups. RESULTS: Of the 3109 patients with CRS who were identified, 600 (19.3%) were classified as having frequent exacerbation. Asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease were associated with frequent AECRS with statistically significant adjusted odds ratios (aORs) after controlling for age, race, and sex in multivariate analysis (asthma aOR = 2.61 [95% CI = 2.14-3.18]; allergic rhinitis aOR = 1.96 [95% CI = 1.58-2.42]; eosinophil count of at least 150 cells per microliter aOR = 1.54 [95% CI = 1.21-1.97]; and autoimmune disease aOR = 1.68 [95% CI = 1.36-2.07]). Antibody deficiency, antibiotic allergy, lower FEV1, radiographic sinus disease severity, nasal polyposis, and systemic corticosteroid use were also associated with frequent AECRS. CONCLUSION: Patients with frequent episodes of AECRS were characterized by a higher prevalence of asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, autoimmune disease, and other allergic and immunologic diseases. These findings identify a high-risk phenotype of patients with CRS for preventive interventions to reduce exacerbation frequency.

Nasal polyps and rhinosinusitis.

Rhinosinusitis is defined as inflammation of one or more of the paranasal sinuses and affects approximately 12% of the population. Acute rhinosinusitis is defined as symptoms that last < 12 weeks, and chronic rhinosinusitis (CRS) is defined as symptoms that last > 12 weeks. CRS is divided into three groups: CRS with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and allergic fungal rhinosinusitis. Nasal polyps are inflammatory outgrowths of paranasal sinus mucosa caused by chronic mucosal inflammation and are present in 20% of patients with CRS. Nasal polyps typically present with nasal congestion, nasal obstruction, and anosmia or hyposmia, and occur more frequently in patients with persistent asthma, aspirin-exacerbated respiratory disease (AERD), CRS, and cystic fibrosis. The sinus cavities are lined with pseudostratified ciliated columnar epithelial cells interspersed with mucous goblet cells. Cilia continuously sweep the mucous toward the ostial openings and are important in maintaining the proper environment of the sinus cavities. The frontal, maxillary, and anterior ethmoid sinuses drain into the ostiomeatal unit of the middle meatus. The posterior ethmoid sinuses and superior sphenoid sinuses drain into the sphenoethmoid recess of the superior meatus. Most acute sinus infections are caused by viruses, and, therefore, it is not surprising that the majority of patients improve within 2 weeks without antibiotic treatment. A bacterial infection should be considered if symptoms worsen or fail to improve within 7-10 days. Combining an intranasal corticosteroid with an antibiotic reduces symptoms more effectively than antibiotics alone. Topical nasal steroids are the treatment of choice for nasal polyps. They significantly decrease polyp size, nasal congestion, and rhinorrhea, and increase nasal airflow. Short courses of oral steroids may be needed to reduce polyp size, followed by maintenance therapy with topical steroids. Surgery is reserved for patients in which polyps cause severe obstruction or recurrent sinusitis and for patients for whom medical therapy has failed. Aspirin desensitization may decrease the requirement for polypectomies and sinus surgery in patients with AERD.

Asthma in adults: Principles of treatment.

The goals of treatment are prevention of fatalities, hospitalizations, and emergency department visits, along with achieving good long-term control of asthma, with reduction of symptoms, maintenance of normal activity level, prevention of exacerbations and accelerated loss of pulmonary function (forced expiratory volume in the first second of expiration [FEV1]), and avoidance of harm from therapies. Treatment is often initiated based on the severity of symptoms, physical examination findings, and, for some patients, the FEV1 or peak expiratory flow rates. Comorbidities such as gastroesophageal reflux disease and laryngopharyngeal reflux, rhinitis or rhinosinusitis, sleep apnea, recurrent infections, smoking, and substance abuse should be addressed. Two treatment modalities are indicated only for individuals with allergic asthma: allergen-specific immunotherapy (commonly known as allergy shots), and biologic therapies that target type-2 (T2) inflammation. Allergen immunotherapy is effective in decreasing symptoms and medication use in select patients with mild-to-moderate allergic asthma. In addition, patients who receive allergen immunotherapy for allergic rhinitis may have a decreased risk of developing asthma. Omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab are monoclonal antibodies that target T2 inflammation and are indicated for either moderate-to-severe or severe asthma. These have been well studied to improve asthma symptoms and have specific characteristics unique to each individual medication. A focus on adherence can be considered in choosing therapy because it is not clear which biologic to choose in T2 high asthma at this time.

Asthma and allergies in pregnancy.

Asthma is the most common respiratory disease observed in pregnancy and is estimated to occur in approximately 5-8% of pregnant women. The course of asthma during gestation may be affected by normal physiologic changes associated with the pregnancy, environmental exposures, and adherence to medical therapy. Uncontrolled asthma poses serious risks not only to the mother but also to the fetus. However, if asthma is controlled, then most women have outcomes at or near that of the general population. Appropriate management of asthma during pregnancy includes evaluation of symptoms, regular monitoring of pulmonary function, and patient education with regard to the risks and benefits of medications. Overall, the advantages of treating asthma in pregnancy markedly outweigh any potential risks of standard medical therapies. Comorbid conditions, including allergic rhinitis or vasomotor rhinitis of pregnancy, should also be managed during pregnancy.

Prevalence and characterization of chronic rhinosinusitis in patients with non-cystic fibrosis bronchiectasis at a tertiary care center in the United States.

BACKGROUND: Chronic rhinosinusitis (CRS) is associated with bronchiectasis; however, this relationship has not been well studied in the United States (US) population. In this work we aimed to determine the prevalence of CRS among patients with bronchiectasis affiliated with a US tertiary medical center and identify which comorbid diseases are associated with the presence of CRS in patients with bronchiectasis. METHODS: This was a retrospective cohort study in which data were obtained from a large database warehouse at a tertiary care center. Patients with bronchiectasis were identified from 2007 to 2017 using diagnosis codes from the the ninth and tenth revisions of the International Classification of Diseases (ICD-9/10) and confirmed by radiographic evidence of bronchiectasis on chest computed tomography (CT) scans. Patients were divided into cohorts based on presence or absence of concomitant CRS. Characteristics analyzed included demographics, comorbidities, peripheral eosinophil counts, and pulmonary function testing. RESULTS: CRS was present in 45% (408 of 900) of patients with bronchiectasis. Females represented a majority of bronchiectasis patients, both with and without CRS (69% and 64%, respectively, p = 0.09). After controlling for demographic factors, asthma (p < 0.01), allergic rhinitis (p < 0.01), gastroesophageal reflux disease (p < 0.01), and antibody deficiency (p < 0.01) were associated with the presence of CRS in patients with bronchiectasis. CONCLUSION: CRS had a high prevalence and was associated with numerous comorbid conditions in patients with bronchiectasis. These findings have clinical implications for the treatment of patients with bronchiectasis and future research.