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Frontiers in Medicine 2023Bullous pemphigoid (BP) is one of the most common autoimmune bullous diseases and mainly affects an elderly population with multi-morbidity. Due to the frailty of many... (Review)
Review
Bullous pemphigoid (BP) is one of the most common autoimmune bullous diseases and mainly affects an elderly population with multi-morbidity. Due to the frailty of many BP patients, existing treatment options are limited. The blisters associated with BP result from IgG and IgE autoantibodies binding to the central components of hemidesmosome, BP180, and BP230, stimulating a destructive inflammatory process. The known characteristic features of BP, such as intense pruritus, urticarial prodrome, peripheral eosinophilia, elevated IgE, as well as recent expanding evidence from and studies implicate type 2 inflammation as an important driver of BP pathogenesis. Type 2 inflammation is an inflammatory pathway involving a subset of CD4+ T cells that secrete IL-4, IL-5, and IL-13, IgE-secreting B cells, and granulocytes, such as eosinophils, mast cells, and basophils. It is believed that effectors in type 2 inflammation may serve as novel and effective treatment targets for BP. This review focuses on recent understandings of BP pathogenesis with a particular emphasis on the role of type 2 inflammation. We summarize current clinical evidence of using rituximab (B-cell depletion), omalizumab (anti-IgE antibody), and dupilumab (anti-IL-4/13 antibody) in the treatment of BP. The latest advances in emerging targeted therapeutic approaches for BP treatment are also discussed.
PubMed: 37614956
DOI: 10.3389/fmed.2023.1196946 -
The Journal of Allergy and Clinical... Nov 2023To improve β-lactam delabeling outcomes, we need to understand current practice and the evidence base regarding its outcomes, safety, and impact.
BACKGROUND
To improve β-lactam delabeling outcomes, we need to understand current practice and the evidence base regarding its outcomes, safety, and impact.
OBJECTIVES
We sought to assess the existing published evidence reporting on the effectiveness of penicillin allergy testing and delabeling.
METHODS
We conducted a systematic review of studies reporting β-lactam delabeling practices and outcomes after testing, including β-lactam use and patient understanding of the delabeling result. Searches of the PubMed, Scopus, and Embase databases; clinical trial registries; and websites of professional organizations were conducted. Data were extracted from the included studies in duplicate, with a third extraction if discrepancies remained.
RESULTS
We included 284 publications (covering 98,316 participants); 173 were prospective studies, with no randomized controlled trials. The overall study quality was low. In all, 95.6% of individuals who underwent provocation testing were delabeled. Factors associated with successful delabeling could not be determined because of significant heterogeneity between studies. Anaphylaxis due to testing occurred in 0.3% of participants (95 of 31,667). Subjects who did not undergo skin testing (6,980 patients in 31 studies) before challenge had higher rates of provocation test positivity (8.8% vs 4.1% [ < .0001]) and anaphylaxis (15.9% vs 2.7% [ < .0001]) than those subjects who underwent skin testing (51,607 patients in 177 studies). Six studies (2.1%) followed patients after testing to assess their adherence to prescribing recommendations. In all, 136 participants (20.6%) were actively avoiding β-lactams despite delabeling.
CONCLUSIONS
The available data suggest that penicillin allergy testing is safe and effective in delabeling most individuals, but the evidence base is incomplete and more work is required to assess the role of skin testing and the impact that delabeling is having on prescribing habits.
PubMed: 37781667
DOI: 10.1016/j.jacig.2023.100160 -
Antimicrobial Stewardship & Healthcare... 2023The Beta-lactam Comprehensive Allergy Management Program (CAMP) was implemented to facilitate complete beta-lactam allergy history documentation in the electronic...
OBJECTIVE
The Beta-lactam Comprehensive Allergy Management Program (CAMP) was implemented to facilitate complete beta-lactam allergy history documentation in the electronic medical record (EMR) and increase beta-lactam utilization. The study objective was to assess the rate of complete allergy histories and days of antimicrobial therapy (DOT) before versus after CAMP implementation.
DESIGN
Quasi-experimental study with interrupted time-series analysis.
SETTING
Non-teaching, urban, and community medical center within a multi-hospital health system.
PATIENTS
Adult inpatients with a beta-lactam allergy receiving antimicrobial therapy.
METHODS
The multidisciplinary CAMP team screened, interviewed, and collected allergy history details of adult inpatients with a beta-lactam allergy receiving antimicrobial therapy starting January 4, 2021. Patients were stratified as high, moderate, or low risk of IgE-mediated allergy and referred to an allergist for skin testing or drug challenge. The EMR was updated with interview details and drug challenge or skin test results. The primary endpoint was rate of complete allergy history documentation before (12/1/18-4/1/19) compared to after (1/4/21-5/1/21) program implementation. The secondary endpoint was days of inpatient beta-lactam therapy. Implementation logistics, de-labeling rate, and antimicrobial therapy changes were evaluated.
RESULTS
The program evaluated 392 individuals, with 184 and 208 patients comprising the pre- and post-intervention groups, respectively. The post-intervention period was associated with an increase of 19.8% in complete allergy histories (0.359 PPc; 0.26; = 0.002) and 9.34 beta-lactam DOT per 1,000-days-present (1.106 PPc; 0.194; = 0.009).
CONCLUSION
Implementation of a comprehensive beta-lactam allergy management program was associated with higher rates of complete beta-lactam allergy history and beta-lactam use.
PubMed: 38028889
DOI: 10.1017/ash.2023.461 -
Drug Safety Oct 2023Biosimilar CT-P13 was approved with limited data from clinical trials compared to the originator infliximab in biologic-naïve patients with rheumatoid arthritis. Three... (Observational Study)
Observational Study
Real-World Safety and Efficacy of Biosimilar CT-P13 in Patients with Immune-Mediated Inflammatory Diseases: Integrated Analysis of Three Japanese Prospective Observational Studies.
INTRODUCTION
Biosimilar CT-P13 was approved with limited data from clinical trials compared to the originator infliximab in biologic-naïve patients with rheumatoid arthritis. Three prospective post-marketing surveillance studies have been conducted in Japanese biologic-naïve patients and switched patients from biologics including the originator infliximab.
OBJECTIVE
We performed an integrated analysis of final data from three post-marketing studies to provide long-term safety and efficacy data of CT-P13 in a real-world clinical setting.
METHODS
A total of 1816 patients consisting of 987 patients with rheumatoid arthritis, 342 patients with Crohn's disease, 322 patients with ulcerative colitis, and 165 patients with psoriasis were evaluated for safety. Efficacy was assessed in 1150 patients whose disease parameter values were serially collected.
RESULTS
Adverse drug reactions were reported in 24.2% of all patients. The incidence of adverse drug reactions differed by the prior treatment status with biologics: 30.5% in patients naïve to biologics, 17.0% in patients switched from the originator infliximab, and 33.5% in patients switched from other biologics. Infusion reactions were the most frequent adverse drug reactions (8.2%), and its incidence was significantly higher in patients with ulcerative colitis and an allergy history in a multivariable Cox regression analysis. Infection was the second most frequent (6.1%), but tuberculosis only occurred in four patients (0.2%). The incidence of infection was low in patients with Crohn's disease and psoriasis, and significant risk factors were an allergy history, comorbidities, and concomitant steroid use. Interstitial lung disease occurred in 16 patients (0.9%), including 11 patients with rheumatoid arthritis. With CT-P13 therapy, disease activity parameters decreased similarly in all four diseases, although long-term drug discontinuation rates because of inefficacy varied by disease. In naïve patients, the disease activity parameters decreased rapidly and the proportion of patients in remission increased. Patients switched from infliximab maintained lowered parameter levels with infliximab pretreatment. Decreases were also observed in patients switched from other biologics, but discontinuations were most often because of insufficient efficacy.
CONCLUSIONS
The integrated analysis of a large number of patients detected no new safety signals with long-term CT-P13 treatment. Efficacy in rheumatoid arthritis, psoriasis, Crohn's disease, and ulcerative colitis cases was confirmed in biologic-naïve patients and switched patients from the originator infliximab or other biologics.
Topics: Humans; Infliximab; Colitis, Ulcerative; Crohn Disease; Biosimilar Pharmaceuticals; Prospective Studies; East Asian People; Treatment Outcome; Arthritis, Rheumatoid; Psoriasis; Drug-Related Side Effects and Adverse Reactions; Hypersensitivity; Inflammatory Bowel Diseases
PubMed: 37700154
DOI: 10.1007/s40264-023-01340-1 -
The World Allergy Organization Journal Mar 2024The majority of viral rashes occurring during an antibiotic therapy are considered as a drug hypersensitivity reaction (DHR). Differentiating a viral rash versus a DHR... (Review)
Review
The majority of viral rashes occurring during an antibiotic therapy are considered as a drug hypersensitivity reaction (DHR). Differentiating a viral rash versus a DHR is difficult or even impossible. In delayed DHRs the interplay between viruses and drugs is summarized according to the recent literature. The question is if the same reaction will again occur in case of drug re-exposure in absence of the concomitant viral infection because of persistent immune reactivity. Epstein Barr Virus (EBV) and Human Herpes virus 6 (HHV-6) models are analyzed in case of maculopapular exanthemas (MPEs) and drug reaction with eosinophilia and systemic symptoms (DRESS) over a course of drug therapy. MPEs are the most common skin manifestation during a viral infection and a concomitant drug therapy. In type IVb reactions to drugs a hapten/pro-hapten mechanism and a pharmacological interaction (p-i mechanism) are described as the 2 major ways to make T cells response functional. Rarely the altered repertoire model is involved. The Human Leukocyte Antigen (HLA) predisposition is an additional essential factor that can facilitate DHR. In MPEs rarely a DHR is confirmed by allergy testing. Severity and duration of MPEs, the presence of eosinophilia and systemic symptoms make more reliable the persistent nature of the reaction. Research on this topic is needed in order to provide the clinicians with instruments to decide when to suspect future reactions upon drug re-exposure even in the absence of a viral infection, because those patients should be investigated by a complete drug allergy work up.
PubMed: 38361746
DOI: 10.1016/j.waojou.2024.100877 -
Annals of Medicine and Surgery (2012) Oct 2023Ketorolac is a commonly used non-steroidal anti-inflammatory drug for reducing pain and inflammation. Anaphylaxis is a medical emergency that occurs after exposure to an...
BACKGROUND
Ketorolac is a commonly used non-steroidal anti-inflammatory drug for reducing pain and inflammation. Anaphylaxis is a medical emergency that occurs after exposure to an allergen, with a varied clinical presentation requiring prompt and appropriate measures to prevent or manage it. Although uncommon, ketorolac can cause anaphylaxis requiring immediate medical care. The authors present two cases of anaphylaxis in females induced after oral intake of ketorolac with successful outcomes.
CASE PRESENTATIONS
The cases involve two adult women who experienced an allergic reaction to ketorolac. The first woman, aged 36, and the second woman, aged 26, on her second postpartum day, both developed similar types of symptoms like periorbital swelling, itching, and difficulty breathing after taking oral ketorolac. The second woman had a history of allergic rashes. They received immediate treatment with epinephrine, oxygen therapy, intravenous fluids, and other medications. They showed a rapid improvement and were discharged after observation.
CLINICAL DISCUSSION
Anaphylactic reactions to ketorolac, a commonly used pain management drug, have been reported. Symptoms include swelling, difficulty breathing, and hypotension. Treatment involves medications like epinephrine, hydrocortisone, and pheniramine. A detailed medical history, laboratory investigations, appropriate medication, oxygen therapy, and follow-up care are important in managing anaphylactic reactions, which can be life-threatening.
CONCLUSION
Although rare, ketorolac can cause anaphylactic reactions in patients with or without a history of drug allergy. Immediate recognition and management are essential, along with a detailed medical history and follow-up care.
PubMed: 37811072
DOI: 10.1097/MS9.0000000000001156 -
Acta Dermato-venereologica Dec 2023
Topics: Humans; Everolimus; Drug Eruptions; Exanthema
PubMed: 38112207
DOI: 10.2340/actadv.v103.12197 -
BMC Genomics May 2024While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in...
BACKGROUND
While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework.
METHODS
Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications.
RESULTS
Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR.
CONCLUSION
Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets.
Topics: Humans; Mendelian Randomization Analysis; Proteomics; Biomarkers; Blood Proteins; Hypersensitivity; Bayes Theorem; Genome-Wide Association Study
PubMed: 38773393
DOI: 10.1186/s12864-024-10412-0 -
Translational Pediatrics Nov 2023Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. While cutaneous adverse drug reactions associated with TMP-SMX are commonly recognized, lung...
BACKGROUND
Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. While cutaneous adverse drug reactions associated with TMP-SMX are commonly recognized, lung toxicity induced by TMP-SMX is an unusual condition, with scattered reports of hypersensitivity pneumonitis, acute fibrinous organizing pneumonia, interstitial lung disease and acute respiratory distress syndrome. Reports of TMP-SMX-associated drug-induced lung injury (DLI) are rare in the pediatric population and its pathogenesis is not well understood. Diagnosis of DLI remains a challenge, given the wide range of clinical presentations that overlap with other conditions and the lack of diagnostic tests. In this report, we describe a case of TMP-SMX-induced lung injury in an eight-year-old child.
CASE DESCRIPTION
An eight-year-old girl presented in respiratory failure with acute symptoms of shortness of breath, fever, maculopapular rash and vomiting. This was associated with pneumonitis, pneumothorax, pneumomediastinum and subcutaneous emphysema on imaging. She had been on 25 days of TMP-SMX for treatment of Group D bacteremia and osteomyelitis that was diagnosed prior to this current presentation. TMP-SMX was discontinued on admission due to concerns of possible drug reaction. Extensive infective, autoimmune and immunologic workup did not reveal the cause of the respiratory failure. Considering the absence of an alternative explanation for her clinical presentation and similarities in clinical courses to other reported cases, she was eventually diagnosed with TMP-SMX-associated DLI. She received a course of corticosteroids with subsequent clinical improvement and was weaned off home oxygen therapy a few months after her discharge from the hospital.
CONCLUSIONS
Diagnosis of DLI can be challenging. The early identification of DLI and discontinuation of culprit drug is essential in its management. Further understanding of the underlying pathophysiology and risk factors for TMP-SMX-associated DLI is required.
PubMed: 38130590
DOI: 10.21037/tp-23-383 -
Journal of Investigational Allergology... Dec 2023Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are... (Review)
Review
Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.
Topics: Humans; Conjunctivitis, Allergic; Histamine Antagonists; Histamine H1 Antagonists; Ophthalmic Solutions
PubMed: 38095492
DOI: 10.18176/jiaci.0963