Management of hypersensitivity reactions to contrast media

As imaging technologies have become essential for diagnosing various diseases, the use of contrast agents is rapidly expanding. As a result, hypersensitivity reactions (HSRs) to contrast agents have also increased. However, protocols for managing, diagnosing, and preventing these reactions are not fully established yet. Since the guidelines for contrast agent hypersensitivity suggested by domestic and international academic societies are not standardized and sometimes difficult to follow in medical facilities, there is a need for practical recommendations in a real-world setting. This review introduces the strategy to manage, diagnose, and prevent HSRs to contrast agents, which have been successfully implemented at Seoul National University Hospital for a decade. First, every single HSRs should be documented in the medical records because a previous history of hypersensitivity to contrast agents is the most significant risk factor for developing HSR to iodinated contrast media. Secondly, avoidance of culprit agents is the main strategy for preventing recurrences of HSRs to contrast agents. Thirdly, it is important to identify nonsensitized contrast agents using skin tests for future exposure to contrast media. In addition to skin testing, side chains of iodinated contrast media may provide a clue to reactive contrast agents. Fourthly, provocation tests can be performed in selected cases with a nonreactive agent based on the skin testing and side chain commonness. Prior to performing imaging studies, premedication can be applied stratified to the severity of the index HSR. All of these procedures are safe and prove to be executable in the medical facilities.

Desensitization for the prevention of drug hypersensitivity

Drug desensitization is a treatment strategy for patients with hypersensitivity to essential drugs without alternatives. The gradual increase in the drug dosage from low doses to therapeutic levels induces a transient immune tolerance to the culprit drug. Although desensitization has traditionally been recommended for IgE-mediated immediate hypersensitivity, this indication has recently been expanded to include non-IgE-mediated immediate responses, nonimmunological responses, and T-cell-mediated delayed hypersensitivity reactions. Although the exact mechanism behind desensitization remains unclear, the process is thought to attenuate various intracellular signals in target cells through Fcɛ receptor 1 internalization, alteration in signaling pathways in mast cells and basophils, reduction in Ca 2+ influx, and production of anti-drug IgG4 blocking antibody. Desensitization can be used for the safe administration of anti-neoplastic agents, antibiotics, aspirin, and nonsteroidal anti-inflammatory drugs. Various desensitization protocols have been proposed for each drug. The optimization of drug concentration, target dosage, administration interval, and route of administration is key to successful desensitization. In addition, the desensitization protocol should be individualized for each patient with consideration of the severity of the initial hypersensitivity response, the characteristics of the culprit drug, and the nature of the breakthrough reactions.

A Case of Schnitzler's Syndrome without Monoclonal Gammopathy-Associated Chronic Urticaria Treated with Anakinra

Chronic urticaria may often be associated with interleukin (IL)-1-mediated autoinflammatory disease, which should be suspected if systemic inflammation signs are present. Here, we report a case of Schnitzler's syndrome without monoclonal gammopathy treated successfully with the IL-1 receptor antagonist anakinra. A 69-year-old man suffered from a pruritic urticarial rash for 12 years. It became aggravated episodically and was accompanied by high fever, arthralgia, leukocytosis, and an elevated C-reactive protein and erythrocyte sedimentation rate. The episodes each lasted for over one week. Neutrophilic and eosinophilic inflammation was found on skin biopsy. However, serum and urine electrophoresis showed no evidence of monoclonal gammopathy. The cutaneous lesions were unresponsive to various kinds of anti-histamines, systemic glucocorticoids, colchicine, cyclosporine, dapsone, and methotrexate, which were administered over a span of 3 years immediately preceding successful treatment. A dramatic response, however, was observed after a daily administration of anakinra. This observation suggests that the correct diagnosis of this case is Schnitzler's syndrome without monoclonal gammopathy. For an adult patient with refractory chronic urticaria and systemic inflammation, Schnitzler's syndrome could be considered as a possible differential diagnosis. Although the typical form of Schnitzler's syndrome exhibits the presence of monoclonal gammopathy as a diagnostic criterion, monoclonal gammopathy may be absent in an atypical form. In such a situation, an IL-1 antagonist should be effective for the management of chronic urticaria.

Long-term Clinical Outcomes in Acute Myocardial Infarction Patients with Left Ventricular Dysfunction

OBJECTIVE: The purpose of this study was to define the effect of the changes of left ventricular ejection fraction (LVEF) on long-term major adverse cardiac events (MACEs) in patients with acute myocardial infarction (AMI). METHODS: Clinical analysis was performed on 1,188 AMI patients who completed follow- up 2-dimensional (2D) echocardiography after one year and clinical follow-up for 5 years. These patients were divided into three groups according to the LVEF change ratio: group A [increased LVEF change ratio, N=626], group B [decreased LVEF change ratio<20%, N=414], group C [decreased LVEF change ratio≥20%, N=148]. RESULTS: Initial low LVEF group and normal LVEF group showed no differences in MACEs. The mean initial and follow-up LVEF were 54.4±12.2% and 60.4±12.3% in the group A, 54.6±13.0% and 47.9±12.1% in the group B, and 56.5±12.6% and 39.9±11.6% in the group C (p=0.71). Total MACEs occurred in 62 (9.9%) patients in the group A, 83 (20.0%) patients in the group B, 44 (29.7%) patients in the group C during 5-year clinical follow-up (p=0.01). Initial low EF (<45%) was not a risk factor for long-term MACEs (Odd ratio (OR), 1.686; 95% confidence index (CI), 0.861-2.862, p=0.065), but the LVEF change ratio was a strong risk factor for long-term MACEs (OR, 3.731; 95% CI, 2.039-6.828, p=0.001). MACE-free survivals of patients with initial low LVEF and patients with low LVEF during follow-up period showed no significant differences (p=0.731). CONCLUSION: Initial low LVEF is not a predictor of long-term MACEs, but the decreased LVEF ratio during follow-up period is a strong predictor of long-term MACEs.

Pravastatin-induced Stevens-Johnson syndrome

Stevens-Johnson syndrome (SJS) manifests with severe cutaneous reactions, most commonly triggered by medications, which are characterized by fever and mucocutaneous lesions leading to necrosis and sloughing of the epidermis. To our knowledge, pravastatin-induced SJS has not yet been reported. Here, we describe a case of SJS due to pravastatin, which was diagnosed by a patch test. A 70-year-old woman presented with maculopapular skin rashes, which developed 2 weeks after medication of bisoprolol, amlodipine, pravastatin, spironolactone, and indobufene for cardiac problems. Various bullous-erosive mucocutaneous lesions occupied less than 10% of the total body surface area. Painful oropharyngeal mucous membrane lesions were observed. The vermilion border of the lips became denuded and developed serosanguinous crusts. With the drug withdrawal and the use of systemic corticosteroids, her manifestations resolved. Drug patch tests with bisoprolol, amlodipine, pravastatin, spironolactone, and indobufene were performed, resulting in a positive reaction to pravastatin, but not to the other drugs. To the best of our knowledge, this is the first case of pravastatin-induced SJS.