Anne Liu, MD

Abstract

There is no accepted grading system classifying the severity of immediate reactions to drugs.The purpose of this article is to present a proposed grading system developed through the consensus of drug allergy experts from the US Drug Allergy Registry (USDAR) Consortium.The USDAR investigators sought to develop a consensus severity grading system for immediate drug reactions that is applicable to clinical care and research.The USDAR grading scale scores severity levels on a scale of 0 to 4. A grade of no reaction (NR) is used for patients who undergo challenge without any symptoms or signs, and it would confirm a negative challenge result. A grade 0 reaction is indicative of primarily subjective complaints that are commonly seen with both historical drug reactions and during drug challenges, and it would suggest a low likelihood of a true drug allergic reaction. Grades 1 to 4 could meet the criteria for a positive challenge result and be considered indicative of a drug allergy. Grade 1 reactions are suggestive of a potential immediate drug reaction with mild symptoms. Grade 2 reactions are more likely to be immediate drug reactions of moderate severity. Grade 3 reactions have features suggestive of a severe allergic reaction, whereas grade 4 reactions are life-threatening reactions such as anaphylactic shock and fatal anaphylaxis.This proposed grading schema for immediate drug reactions improves on prior schemata by being developed specifically for immediate drug reactions and being user-friendly and easy to implement in clinical and research practice.

View details for DOI 10.1016/j.jaci.2023.08.018

View details for PubMedID 37652140

View details for DOI 10.1513/AnnalsATS.202212-994RL

View details for PubMedID 37233740

Abstract

Allergists have been at the forefront of addressing the burden of unverified penicillin allergy labels. Coordinated national efforts with infectious diseases, antimicrobial stewardship experts, and pharmacy societies to advocate for formal evaluation of patient-reported penicillin allergy have resulted in improvements in delabeling efforts. Given the poorer health outcomes associated with the penicillin allergy label and the potential health benefits that can be gained with delabeling, improving access to penicillin allergy evaluation is of the utmost importance. Health disparities are widely recognized to impact all aspects of healthcare, and multilevel interventions at the patient, clinician and systems level are required to ensure equitable care delivery. Structural racism underpins many social determinants of health and is a key driver of racial and ethnic health disparities. In this Rostrum, we use a conceptual framework from the 2015 National Academy of Medicine report Improving Diagnosis in Health Care to explore how inequities are related to the evaluation of penicillin allergy. We use the National Institute on Minority Health and Health Disparities Strategies to Advance Health Disparities to elucidate areas of important study. Building upon existing efforts to address disparities in Allergy/Immunology, we highlight the urgent importance of understanding and eliminating health disparities in penicillin allergy evaluation and delabeling.

View details for DOI 10.1016/j.jaip.2022.12.001

View details for PubMedID 36521831

View details for DOI 10.1016/j.jaip.2022.01.031

View details for PubMedID 35397816

View details for Web of Science ID 000778999300453

View details for Web of Science ID 000778999300264

View details for Web of Science ID 000778999300512

Abstract

While fluoroquinolones, vancomycin, macrolides, and tetracyclines are generally safe antibiotics, they can induce both immediate and delayed hypersensitivity reactions (HSRs). Historically, less has been published on allergies to these antibiotics compared to beta lactams, but the prevalence of non-beta lactam HSRs is increasing. To fluoroquinolones, immediate HSRs are more common than delayed reactions. Both IgE and non-IgE mechanisms, such as the mast cell receptor Mas-related G protein-coupled receptor X2 (MRGPRX2), have been implicated in fluoroquinolone-induced anaphylaxis. Skin testing for fluoroquinolones is controversial, and the gold standard for diagnosis is a graded dose challenge. To vancomycin, the most common reaction is vancomycin infusion reaction (previously called "red man syndrome"), which is caused by infusion rate-dependent direct mast cell degranulation. Severity can range from flushing and pruritis to angioedema, bronchospasm, and hypotension that mimic type I HSRs. MRGPRX2 has been implicated in vancomycin infusion reactions. IgE-mediated HSRs to vancomycin are rare. Vancomycin skin testing yields high false positive rates. Thus, direct provocation challenge with slower infusion rate and/or antihistamine pre-treatment is preferred if symptoms are mild to moderate, and desensitization can be considered if symptoms are severe. To tetracyclines, non-IgE-mediated and delayed HSRs predominate with cutaneous reactions being the most common. There is no standardized skin testing for tetracyclines, and avoidance is generally recommended after a severe reaction because of the paucity of data for testing. Graded dose challenges and desensitizations can be considered for alternative or index tetracyclines if there are no alternatives. With macrolides, urticaria/angioedema is the most common immediate HSR, and rash is the most common delayed HSR. The predictive value for skin testing to macrolides is similarly poorly defined. In general, HSRs to fluroquinolones, vancomycin, macrolides, and tetracyclines are challenging to diagnose given the lack of validated skin testing and in vitro testing. Direct provocation challenge remains the gold standard for diagnosis, but the benefits of confirming an allergy may not outweigh the risk of a severe reaction. Skin testing, direct provocation challenge, and/or desensitization to the index non-beta lactam antibiotic or alternatives in its class may be reasonable approaches depending on the clinical context and patient preferences.

View details for DOI 10.1007/s12016-021-08919-5

View details for PubMedID 35092578

View details for Web of Science ID 000729864400020

View details for DOI 10.1016/j.anai.2021.08.010

View details for PubMedID 34391901

View details for DOI 10.1016/j.jdcr.2021.04.033

View details for PubMedID 34195327

View details for DOI 10.1016/j.jaip.2021.02.061

View details for PubMedID 34112480

View details for Web of Science ID 000629158000021

Abstract

We describe the case of a 44-year-old female on Rituximab for treatment of multiple sclerosiswith undetectableSARS-CoV-2 IgG specific antibodies eighteen days after second dose ofSARS-CoV-2 vaccine. Interferon-gamma release assay testing for SARS-CoV-2 was positive on day nineteen, demonstrating robust T-cell mediated responsedespite lack of antibody-mediated response.

View details for DOI 10.1016/j.ijid.2021.06.054

View details for PubMedID 34216738

View details for Web of Science ID 000580645300029

View details for DOI 10.1016/j.anai.2020.07.014

View details for PubMedID 32707161

Abstract

Targeting interleukins that drive innate inflammation has expanded treatments of autoinflammatory and autoimmune disorders. Interleukin (IL)-1 inhibition has proven useful for monogenic autoinflammatory syndromes, and IL-6 inhibition for autoimmune arthritides. Biological therapies impeding these pathways impair detection and containment of pathogens, particularly invasive bacteria, reflecting the importance of IL-1 and IL-6 in communicating danger throughout the immune system. Biologics targeting T helper type 2 inflammation are used to treat specific allergic, atopic, and eosinophilic diseases. They may impair protections against local herpesvirus reactivations while augmenting antiviral responses to respiratory viruses. Their risks with helminth exposures have yet to be defined.

View details for DOI 10.1016/j.idc.2020.02.003

View details for PubMedID 32334983

View details for Web of Science ID 000540191100107

View details for DOI 10.1007/s10875-020-00748-z

View details for PubMedID 31955317

View details for DOI 10.1016/j.jaip.2020.08.006

View details for PubMedID 33039007

View details for DOI 10.1016/j.diagmicrobio.2019.03.011

View details for Web of Science ID 000483427000016

View details for DOI 10.1016/j.jaip.2019.03.027

View details for Web of Science ID 000484456300050

Abstract

Allergic immune-mediated hypersensitivity reactions are known potential complications of enzyme replacement therapy. Sebelipase alfa, recombinant lysosomal acid lipase (LAL), is a potentially life-altering treatment for patients with LAL deficiency. There is very little information on the diagnosis and management of immediate hypersensitivity reactions to this drug. Here we present three unique cases of hypersensitivity reactions to sebelipase alfa, spanning a broad age spectrum from infancy to adulthood, each managed with successful rapid desensitization.

View details for DOI 10.1002/jmd2.12066

View details for PubMedID 31497479

Abstract

Treatment of symptomatic candiduria is notoriously challenging because of the limited repository of antifungals that achieve adequate urinary concentrations. Fluconazole, amphotericin B-based products, and flucytosine are established treatment options for most Candida species. Candida krusei exhibits intrinsic resistance to fluconazole and decreased susceptibility to amphotericin B and flucytosine. In transplant patients, both amphotericin B-based products and flucytosine are less desirable due to their toxicities. Other triazole antifungals are unappealing because they do not achieve adequate urinary concentrations, have multiple toxicities, and interact with transplant-related immunosuppressive medications. Echinocandins are well-tolerated but have been traditionally deferred in the treatment of symptomatic funguria because of their poor urinary concentrations but there is a small but emerging body of literature supporting their use. Here, we present a case of successful eradication of chronic symptomatic Candida krusei urinary tract infection with micafungin 150 milligrams daily in a liver and kidney transplant recipient, and we review the literature on treatment of symptomatic candiduria. This article is protected by copyright. All rights reserved.

View details for DOI 10.1111/tid.13118

View details for PubMedID 31111613

View details for Web of Science ID 000463709600114

View details for DOI 10.1016/j.jaci.2018.12.856

View details for Web of Science ID 000457771200843

View details for DOI 10.1186/s13223-019-0321-x

View details for Web of Science ID 000457080900001

View details for PubMedID 30946976

Abstract

Eremothecium coryli is a dimorphic fungus of the Saccharomycetes class. While species within this class are known to cause human infection, Eremothecium species have previously only been known as phytopathogens and never been isolated from a human sample. Here, we report the first known case of human E. coryli infection.

View details for PubMedID 31005402

Abstract

We report a male with longstanding warts who presented with severe West Nile virus encephalitis (WNVE) and recovered after interferon alfa-2b and intravenous immunoglobulin. He was later found to have GATA2 deficiency and underwent successful hematopoietic stem cell transplant.

View details for PubMedID 30697248

Abstract

Recombinant human erythropoietin, such as epoetin alfa and darbepoetin alfa, is an important therapy for anemia due to chronic renal failure. Allergy to recombinant human erythropoietin and the need for desensitization are rare.We report here a novel epoetin alfa outpatient desensitization protocol in a girl who developed delayed cutaneous hypersensitivity to subcutaneous epoetin alfa and intravenous darbepoetin alfa. An initial attempt at traditional epoetin alfa desensitization failed, so we created a slower 17-day outpatient desensitization that succeeded and allowed treatment continuation.This case highlights the notion that delayed-type hypersensitivity to recombinant human erythropoietin can occur as evident by reproducible reactions after repeated exposures and slow outpatient desensitization can be considered when a trial of more rapid induction of tolerance is unsuccessful.

View details for PubMedID 29545827

View details for PubMedCentralID PMC5846227

Abstract

Infection with Scedosporium species is associated with a significant morbidity and mortality and is becoming increasingly common, especially in immunocompromised patients. We describe the presentation and successful management of an immunocompromised patient with Scedosporium apiospermum infection of the upper urinary tract system, a rare disease manifestation. The current literature on urinary tract scedosporiosis is further reviewed with emphasis on treatment options and limitations of current antifungal therapy.

View details for PubMedID 29111602

View details for PubMedCentralID PMC5871223

Abstract

The FilmArray meningitis/encephalitis (ME) panel is a novel syndromic, nucleic acid amplification test for diagnosis of acute meningitis and encephalitis. Emerging data on its performance are concerning for false-positive results. We present a case of tuberculous meningitis misdiagnosed as herpes simplex virus-1 encephalitis with the FilmArray ME panel. Strategies to mitigate erroneous results are discussed.

View details for DOI 10.1093/ofid/ofw245

View details for PubMedID 28540320

Abstract

Rapid drug desensitization (RDD) is used to address hypersensitivity reactions to chemotherapeutics and monoclonal antibodies, allowing patients to be treated with optimal pharmacological agents. RDD protocols are tailored to each individual patient's reaction and needs, and protect against anaphylaxis, but overall risks, costs, and benefits have not been determined.We investigated the safety, efficacy, costs, and life expectancy of patients in a large population undergoing RDD.We analyzed 2177 RDD procedures performed in 370 patients with cancer, vasculitis, and hematological and connective tissue diseases who presented 402 reactions. A subgroup of carboplatin allergic patients with ovarian cancer treated with RDD was analyzed for costs and life expectancy and compared with a nonallergic control group.RDD allowed all patients to receive safely the full dose of the medication to which they were reactive. A gradual increase in the fraction of outpatient desensitizations from 81% to 98% was achieved through risk stratification. Of the 2177 desensitizations, 93% had no or mild reactions whereas 7% had moderate to severe reactions, which did not preclude the completion of the treatment, and there were no deaths. Overall health costs in the carboplatin allergic group were not higher than those in the nonallergic group treated with standard of care. Administration of carboplatin through RDD was as effective as standard administration with a nonsignificant increase in life expectancy in desensitized patients as compared with nonallergic, nondesensitized controls.RDD is cost effective and safe for allergic patients with cancer and chronic disease to remain on first line therapy.

View details for DOI 10.1016/j.jaip.2015.12.019

View details for PubMedID 26895621

Abstract

The FilmArray meningitis/encephalitis (ME) panel is a novel syndromic, nucleic acid amplification test for diagnosis of acute meningitis and encephalitis. Emerging data on its performance are concerning for false-positive results. We present a case of tuberculous meningitis misdiagnosed as herpes simplex virus-1 encephalitis with the FilmArray ME panel. Strategies to mitigate erroneous results are discussed.

View details for DOI 10.1093/ofid/ofw245

View details for PubMedCentralID PMC5437853

Abstract

In contrast to resident constitutive mast cells (CMCs), mucosal MCs (MMCs) appear in the lung and trachea of sensitized mice only following inhalation challenge. We monitored the influx and maturation of MCs by their expression of Kit, FcRI, 7-integrin and side scatter (SSC) by flow cytometry. Influx of MC progenitors (MCps) (FcRI(lo), Kit(int), 7(hi), and SSC(lo)) peaks 1 day after challenges and subsides to baseline by day 7 after challenge. The mature MMCs appear as a distinct population on day 7 and peak at day 14 with higher SSC and FcRI expression, but lower 7 and Kit expression. A distinct transitional population is present between 1 and 7 days after challenge. Maturation occurs more rapidly in the trachea. The resident tracheal CMCs had higher SSC, FcRI, and Kit and lower 7-integrin expression than the MMCs. By histology, the MMCs follow similar kinetics to the flow cytometry-identified mature MMCs and are notably persistent for >42 days. Steroid treatment reduced inflammation and MCp influx but had no effect on established MMCs. Thus, changes in SSC, FcRI, and Kit together with the expression of E/4:7-integrins characterizes the development of induced MMCs from MCps and distinguishes them from resident CMCs in the trachea and large airways.

View details for DOI 10.1038/mi.2014.91

View details for PubMedID 25291985

View details for DOI 10.1016/j.jaci.2013.12.532

View details for Web of Science ID 000330241300505

Abstract

Mast cells (MC) and basophils share expression of the high-affinity receptor for IgE (FcRI) but can be distinguished by their divergent expression of KIT and CD49b. In BALB/c mice, MC lineage cells expressing high levels of FcRI by flow cytometry were seen only in bone marrow whereas those expressing intermediate levels of FcRI were present in bone marrow and spleen of naive mice and in mesenteric lymph nodes (mLN) of Trichinella spiralis-infected mice. These FcRI(+)KIT(+)CD49b(-) cells had a membrane phenotype similar to i.p. connective tissue-type MC, but were smaller and hypogranular by flow cytometry forward and side scatter profiles, respectively. Consistent with this, they lacked the prominent secretory granules identified by histochemistry and immunodetection for the MC-specific granule proteases that are readily seen in mature jejunal mucosal MC that also are induced by the infection and present at the same time. The concentration of these MC lineage cells in mLN determined by flow cytometry was comparable to that of MC progenitors (MCp) measured by limiting dilution and clonal expansion with maturation. We observed upregulation of IL-4 transcription by MCp in mLN and spleens of helminth-infected 4get mice, and we demonstrated by intracellular cytokine staining production of IL-4 and IL-6 by the mLN MCp in helminth-infected mice. Furthermore, treatment of helminth-infected mice with anti-FcRI mAb, a protocol known to deplete basophils, also depleted mLN MCp. Thus, this study identifies a hypogranular subset of MCp recruited to mLN by helminth infection that may be an important unrecognized source of cytokines.

View details for DOI 10.4049/jimmunol.1202567

View details for Web of Science ID 000314825400039

View details for PubMedID 23319739

Abstract

Adverse reactions to drugs are increasingly being recognized as important contributions to disease in their own right as well as impediments to the best treatment of various conditions, including infectious, autoimmune, and neoplastic maladies. Rapid drug desensitization (RDD) is an effective mechanism for safely administering important medications while minimizing or entirely circumventing such adverse reactions in sensitized patients. We reviewed the literature on RDD in the last 10 years, including our experience from the Brigham and Women's Hospital Desensitization Program with hundreds of patients desensitized to a broad variety of drugs. RDD in our programme has been uniformly successful in patients with hypersensitivity reactions to antibiotics, chemotherapeutics, and monoclonal antibodies. Any reactions that occur during desensitization are generally much less severe than the initial hypersensitivity reaction to the drug, and patients have received the full dose of the desired medication 99.9% of the time out of (796) desensitizations. To date, there have been no fatalities. RDD is a safe and highly effective method for treating sensitized patients with the optimal pharmacologic agents. Its use should be expanded, but because patient safety is paramount, protocols must be created, reviewed, and overseen by allergist-immunologists with special training and experience in modern techniques of desensitization.

View details for DOI 10.1111/j.1365-2222.2011.03825.x

View details for Web of Science ID 000297283800005

View details for PubMedID 21883538

Abstract

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

View details for DOI 10.1126/science.1195271

View details for Web of Science ID 000285153500069

View details for PubMedID 21051598

View details for DOI 10.1056/NEJMcps0708369

View details for PubMedID 20592300

View details for DOI 10.1056/NEJMimc0903117

View details for PubMedID 20560180

Abstract

Infection and malignancy often have common characteristics which render the differential diagnosis for a prolonged fever difficult. Imaging and tissue biopsy are crucial in making a correct diagnosis, though differentiating between chronic osteomyelitis and malignancy is not always straightforward as they possess many overlapping features.A 52-year-old Caucasian man was treated with antibiotics for his diabetic foot infection after a superficial culture showed Staphylococcus aureus. He had persistent fevers for several weeks and later developed acute onset of back pain which was treated with several courses of antibiotics. Radiographic and pathological findings were atypical, and a diagnosis of Hodgkin's lymphoma was made 12 weeks later.Clinicians should maintain a suspicion for Hodgkin's lymphoma or other occult malignancy when features of presumed osteomyelitis are atypical. Chronic vertebral osteomyelitis in particular often lacks features common to acute infectious disease processes, and the chronic lymphocytic infiltrates seen on histopathology have very similar features to Hodgkin's lymphoma, highlighting a similar inflammatory microenvironment sustained by both processes.

View details for DOI 10.1186/1752-1947-4-102

View details for PubMedID 20370895

Abstract

Parasite Ag-specific T cell unresponsiveness and diminished IFN-gamma production are immunologic hallmarks of patent infection with lymph-dwelling filarial nematodes. Although this diminished responsiveness is directed primarily against the intravascular microfilarial (MF) parasite stage and mediated in part by reduced APC function, the mechanisms involved are not fully understood. In this report, we demonstrate that human dendritic cells (DC) exposed to live MF up-regulate both the cell surface and gene expression of CD54 (ICAM-1). Moreover, live MF result in a 3-fold increase in DC death compared with MF-unexposed DC, primarily due to apoptosis. Notably, microarray and real-time RT-PCR data indicate that live MF concurrently up-regulate mRNA expression of proinflammatory molecules such as IL-8, RANTES, IL-1alpha, TNF-alpha, and IL-beta in DC, the presence of which is also detected at the protein level, while inhibiting the production of IL-12 (p40 and p70) and IL-10. Soluble excretory-secretory products from live MF diminished IL-12 and IL-10 production and induced DC death, although to a lesser degree. Moreover, exposure of DC to live MF resulted in a decrease in the ability of DC to promote CD4(+) T cell production of IFN-gamma and IL-5. Our findings clearly suggest that the interaction between live MF and DC is complex but contributes to the hyporesponsiveness and parasite persistence associated with the MF(+) state in the infected human. These data further suggest that MF induce an orchestrated response in APC that leads to a diminished capacity to function appropriately, which in turn has significant consequences for CD4(+) T cells.

View details for Web of Science ID 000184667400044

View details for PubMedID 12902498