Innovations in Medical Education (1)Vector-borne infectious diseases (1)Food Allergy and Anaphylaxis Research (1)Allergic Rhinitis and Sensitization (1)Hospital Admissions and Outcomes (1)
Alpha-gal syndrome (AGS) is an emerging tick-borne allergic condition associated with bites from the lone star tick (Amblyomma americanum). Unlike typical tick-borne diseases caused by bacteria or viruses, in AGS there is a delayed allergic reaction to galactose-α-1,3-galactose, a sugar referred to as alpha-gal, which is present in tick saliva; most mammalian meat, such as beef, pork, and lamb; animal-derived products, such as gelatin and dairy (including cow's milk); and certain medications containing animal products. AGS was first identified in the early part of this century, with a notable rise in reported cases in recent years. Contributing factors include climate change, altered wildlife migration, and other ecological shifts that have allowed the lone star tick to expand its range north and west across the United States. Clinically, AGS is characterized by an atypical, delayed allergic response that can occur hours after consumption of red meat. Sensitivity to alpha-gal is delayed for weeks to months after the tick bite, and the allergic reaction after ingesting something that contains the antigen is delayed by hours. Gastrointestinal manifestations are common, and patients may also develop urticaria, bronchospasm, or potentially life-threatening anaphylaxis. The condition is underdiagnosed, owing to its unusual presentation and limited awareness among clinicians. With the continued expansion of the lone star tick's habitat, the incidence of AGS is expected to rise. Enhanced awareness, targeted research, and improved education for both health care practitioners and the public are crucial to reducing misdiagnosis and improving management. Strengthening public health initiatives will be key in addressing this complex and evolving allergic condition. This article aims to describe the epidemiology; pathophysiology, including the role of A. americanum in transmission; and clinical presentation of AGS and highlight its link to tick bites; common barriers to accurate diagnosis; and current strategies for prevention.
Della Marta N, Yuile A, Mok C, Wei J, Oatley M, et al.
Cancer treatment and research communications •
Cetuximab improves survival in KRAS wildtype metastatic colorectal cancer. However, high rates of hypersensitivity reactions (HSRs) limit its use, with HSR rates up to 10-20 %. A major driver of cetuximab HSR is from pre-formed IgE antibody response to galactose-1,3-alpha-galactose (alpha-gal). Evidence from retrospective studies supports alpha-gal pre-screening in this setting. This study reports the impact of prospective alpha-gal antibody screening on cetuximab HSR. Records were reviewed across three medical oncology centres that have adopted alpha-gal antibody screening measures. Data for patients with metastatic colorectal cancer treated with cetuximab were retrieved. All centres assessed alpha-gal levels using the ImmunoCAP® immunoassay. Due to variability in alpha-gal screening practices across study sites, a standardised protocol was applied to all cases. This protocol allowed cetuximab administration if alpha-gal levels were ≤0.10 kUA/L, but prohibited it if alpha-gal levels were >0.10 kUA/L in favour of panitumumab administration. Patients were allocated to either the Alpha-gal Pre-screening Applied ('Pre-screening') or Alpha-gal Pre-screening Not Applied ('Reference') cohorts based on protocol requirements being met. The primary outcome between these patient groups was the incidence of cetuximab HSRs. Of 254 assessable patients, 39 underwent the pre-treatment screening protocol. Of the Pre-screening group, 3% (n=1/39) experienced a cetuximab HSR compared to 16% (n=35/215) in the Reference group (Odds ratio (OR) 0.14; 95% CI 0.0033-0.86, p= 0.02). Patients with alpha-gal antibody titres >0.10 kUA/L were more likely to experience a cetuximab HSR (OR 69.71; 95% CI 5.18-4296.81, p=0.0001). Pre-treatment screening for alpha-gal antibodies significantly reduces the incidence of cetuximab HSRs. A testing threshold of 0.10 kUA/L is effective in identifying patients at risk. Implementing this protocol can improve the safety of cetuximab therapy in high-risk populations. Hypersensitivity reactions (HSRs) limit cetuximab use in KRAS wildtype advanced colorectal cancer, with a significant driver being pre-formed IgE antibodies against galactose-1,3-alpha-galactose (alpha-gal). Our multicentric retrospective study assessed the impact of prospective alpha-gal antibody screening on HSR incidence following cetuximab administration. Of 254 assessable patients, pre-treatment alpha-gal antibody screening significantly reduced the incidence of cetuximab HSRs (3% vs 16%; OR 0.14, p=0.02). Our findings support pre-treatment alpha-gal screening to improve safety of cetuximab therapy in high-risk populations.