International archives of allergy and immunology •
Given the significant rise in the incidence of alpha-gal syndrome alongside the geographical expansion of ticks in recent years, it is crucial to conduct studies aimed at raising awareness particularly among patients with a history of, or current diagnosis of, Lyme disease, to improve their quality of life. Our study is unique in addressing this important intersection. Two groups composed of 200 residuals de-identified samples originally collected during the peak of tick activity season in Northeast Ohio were tested for alpha-gal IgE. The first group (n = 100) was from patients with Lyme IgG Western blot positive results, and the remainder were from healthy subjects only tested for immune status. Of the 200 samples, 17 tested positive for α-Gal IgE: 15 from the Lyme-positive group and 2 from the control group. A Fisher's exact test showed strong statistical significance between the two groups (p = 0.0015). Although alpha-gal syndrome had been previously associated with a history of American lone start tick bite, this study for the first time in North America shows a possible association between α-Gal IgE positivity and exposure to Ixodes ticks. This is of paramount importance given the vast prevalence of Ixodes ticks especially in areas where the American lone start ticks are scarce.
Alpha-gal syndrome is an emerging condition characterized by an immunoglobulin (Ig) E-mediated reaction to galactose-alpha-1,3-galactose (alpha-gal) after consumption of mammalian-derived food products. Identified in the early 2000s, the syndrome is linked to sensitization through tick bites; in the United States, the lone star tick () is the main vector. Symptoms range from pruritus and hives to severe systemic reactions like anaphylaxis, and typically occur 3 to 8 hours after eating meat. Diagnosis involves a history of consistent symptoms, positive alpha-gal IgE serology, and dietary exclusion trials. Management focuses on avoiding foods and products that contain alpha-gal and preventing tick bites.
Patel R, Jaglan A, Aguileraserna C, Pandya K, Goldstein L
Cureus •
Allergies are a very common pathology and their manifestations consist of a spectrum of presentations, ranging from minimal discomfort like a runny nose to lethal reactions like anaphylaxis and death. Meat allergy is not a very common form of allergy, even though there is a relatively high level of meat consumption. One of the rare forms of non-primate mammalian meat allergy is alpha-gal syndrome (AGS). It is related to IgE antibodies specific for galactose-α-1,3-galactose (α-Gal). It is triggered in sensitized individuals due to multiple bites of lone star tick bites (). Here we present a 63-year-old male with a complaint of recurrent hives and tongue swelling, developed recently after traveling to Twinsburg, OH. There is no significant history of any allergic conditions. Vital signs were stable with a normal physical examination. The patient had normal routine labs including eosinophil count, thyroid-stimulating hormone (TSH), iron panel, and negative HIV. Allergy testing showed normal total IgE but increased levels of IgE for allergens like beef, lamb, and pork (18.4, 6.71, and 7.62 respectively) and greatly increased levels of IgE for alpha-gal (42.7). Sensitization to alpha-gal can cause delayed allergic symptoms upon consuming various non-primate mammalian types of meat, particularly beef, pork, and lamb. Conditions like AGS are rare and can be missed as an initial diagnosis in many patients. A high degree of vigilance is required to diagnose such conditions.
Farley J, Sill MW, Birrer M, Walker J, Schilder RJ, et al.
Gynecologic oncology •
The purpose of this study was to evaluate the safety and efficacy of cetuximab (C225), an antibody that inhibits epidermal growth factor receptor (EGFR) activity, with cisplatin and to explore associations between EGFR protein expression with patient demographics or clinical outcome. Women with advanced, persistent, or recurrent carcinoma of the cervix were eligible. The women received cisplatin at 30mg/m(2) on days 1 and 8 with a loading dose of cetuximab at 400mg/m(2) followed by 250mg/m(2) on days 1, 8, and 15 in a 21day cycle. Adverse events were assessed with CTCAE v 3.0. Primary measure of efficacy was tumor response by RECIST. The study was stratified by prior chemotherapy (CT). EGFR protein expression in pre-treatment tumor was analyzed by immunohistochemistry. Between September 2004 and March 2008, 76 patients were enrolled. Of these, 69 were eligible and evaluable; 44 (64%) received prior chemotherapy. There were 4 responses in each group, prior chemotherapy and no chemotherapy, 9% and 16%, respectively. Grade 4 toxicities included anemia (1), allergy (1), metabolic (1), and vascular (1). The most common grade 3 toxicities were metabolic (15), dermatologic (8), fatigue (6), and gastrointestinal (6). EGFR protein was expressed in 47/48 (98%) of tumors analyzed with a median cellular expression of 81%. Exploratory analyses revealed a trend between the percentage of cells expressing EGFR protein and PFS (hazard ratio=1.76, 95% confidence interval=0.96-3.21). The combination of cetuximab with cisplatin was adequately tolerated but did not indicate additional benefit beyond cisplatin therapy.
Cetuximab is a human/mouse chimeric monoclonal antibody that binds to the EGF receptor, competitively inhibiting ligand binding, and inducing receptor dimerization and downregulation. Cetuximab has been active in multiple tumors, including colorectal cancer (CRC), head and neck, pancreatic and lung cancers. Cetuximab has been approved by the FDA, in combination with irinotecan, for the treatment of metastatic CRC in patients refractory to irinotecan, and for use as a single agent in the treatment of recurrent metastatic CRC in patients intolerant of irinotecan-based chemotherapy. Most common toxicities are rash, diarrhea, fever, headache, nausea, hypomagnesemia and hypersensitivity reactions. Data from several clinical trials with cetuximab show a positive correlation between rash and response and/or survival. Rash occurred on 90% of patients treated with cetuximab monotherapy and grade 3 or 4 skin reactions occurred on as many as 16% of patients in the trials using cetuximab. A rash usually presents as pustular or maculopapular follicular eruption, often referred to as acneiform. Cetuximab will engage in productive dimerization complexes in human skin causing significant disruption of the normal development and maintenance of the hair follicle, which leads to follicular response and inflammatory response. At this time there are no standard or evidence-based treatment plans for the rash. Most of the evidence is based on institutional or personal experiences. The most commonly used agents are topical antibiotics, oral antibiotics, topical steroids, systemic immunomodulatory agents, topical immunomodulatory agents and anti-inflammatory preparations. As cetuximab is becoming widely used in general oncology practice, it is important to understand the toxicity of rash to develop practice guidelines for their management. This review addresses recommendations for toxicity management of rash caused by cetuximab in treatment of metatstatic CRC.
