Hoigné's syndrome, an uncommon mimicker of anaphylaxis: Systematic literature review.

The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by non-thrombotic pulmonary and systemic drug micro-embolization. It has so far been documented uniquely in case reports and small case series. Because this condition has never been systematically evaluated, we performed a structured literature review (pre-registered as CRD42023392962). The search was carried out in Excerpta Medica, National Library of Medicine, and Google Scholar. Cases with features consistent with anaphylaxis, urticaria, angioedema, asthma, syncope, anxiety, or panic attack triggered by needle phobia, and local anesthetic systemic toxicity were excluded. For the final analysis, we retained reports published between 1951 and 2021, which presented 247 patients with Hoigné's syndrome: 37 children and 211 adults with a male: female ratio of 2.1 : 1.0. The patients presented within 1 min after parenteral administration of a drug (intramuscular penicillin in 90 % of the cases) with chest discomfort, shortness of breath, fear of death, psychomotor agitation, and auditory or visual hallucinations and impairment. Recovery occurred within 30 min. The diagnosis of Hoigné's syndrome was also established in five patients 66-91 years of age with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the aforementioned symptoms. It was therefore speculated that pulmonary drug micro-embolization induced a lethal cardiovascular compromise in these individuals. Histologic investigations supporting this hypothesis were performed in only one case. The diagnosis of Hoigné's pulmonary drug micro-embolization was established also in five patients with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the afore mentioned symptoms. Histologic investigations supporting this hypothesis were performed in only one case. In conclusion, Hoigné's syndrome is an uncommon non-immune-mediated reaction. This report seeks to promote broader awareness and knowledge regarding this alarming mimicker of anaphylaxis. Diagnosis relies solely on clinical evaluation.

A case of severe anaphylactic reaction after administration of diagnostic-dose ferumoxytol in a pediatric patient.

We describe a case of anaphylaxis during administration of intravenous (IV) ferumoxytol as a magnetic resonance imaging (MRI) contrast agent in a 4-year-old patient with complicated past medical history including YARS genetic mutation with resultant liver failure and deceased donor liver transplantation, stage IV chronic kidney disease (CKD), and hypertension. The patient was noted to have labored breathing 4 min after initiation of ferumoxytol infusion and was subsequently rapidly intubated and returned to the intensive care unit (ICU) for monitoring. Anaphylactic reactions to therapeutic doses of ferumoxytol led to issuance of a black box warning by the FDA in 2015. Adverse reactions to lower-dose ferumoxytol used in diagnostic imaging, however, are rare and there has been a paucity of documented anaphylactic reactions in the literature.

Tablet allergen immunotherapy: the anaphylaxis issue.

For the first time 15 years ago, tablet allergen immunotherapy (T-AIT) formulations were approved by regulatory agencies for treating allergic rhinitis caused by grass pollen in adults and children aged >5 years. Extensive evidences existed about effectiveness and safety of AIT. However, the safety profile is particularly compelling in children. Generally, T-AIT causes local reactions, mostly in the oral cavity, that are usually mild-to-moderate and often self-resolving. However, systemic allergic reactions are also observed with T-AIT, anaphylaxis representing the most fearsome adverse event, considering that it occurs in subjects treated for allergic rhinitis. Therefore, we conducted a literature search of patients reporting anaphylaxis because of T-AIT. Nine cases of anaphylactic reactions were reported in literature. Notably, no death was reported using T-AIT. This outcome was very important as it underscored the substantial safety of T-AIT. However, T-AIT deserves careful attention, mainly in the pediatric population. In this regard, after the first report of anaphylactic reaction at the first administration of T-AIT, manufacturers recommended that the first dose should be administered in a medical facility in the presence of staff with experience in managing anaphylaxis and the patient should be observed for at least 30 min. Interestingly, reported anaphylactic reactions were due to grass pollen extracts, with no report concerning other allergen extracts. However, it is relevant to note that anaphylactic reactions because of T-AIT are not reported in recent years.

[Coronary anaphylaxis or Kounis syndrome]. / Anaphylaxie coronaire ou syndrome de Kounis.

Although not well known, Kounis syndrome represents 3.4 % of anaphylactic reactions and has a high level of mortality (7 %). Its main clinical presentation looks like an acute coronary syndrome. We report the case of a 61-year old patient who was admitted in the emergency department because of a malaise with loss of consciousness due to a Kounis syndrome that occurred after the ingestion of amoxycilline.

Le syndrome de Kounis représente une entité mal connue, bien que présent dans 3,4 % des réactions anaphylactiques avec une mortalité élevée de 7 %. Ses manifestations sont des symptômes mimant un syndrome coronarien aigu. Nous présentons ici le cas d'un patient de 61 ans admis au service des urgences pour un malaise avec perte de connaissance attribué à un syndrome de Kounis survenu dans les suites de la prise d'amoxycilline.

Suicide or not? Issues in the demonstration of anaphylaxis, a review of the literature.

The authors review the literature on the determination of post-mortem serum tryptase values and present the case of a young man who was hit by a train. However, his family believes he has no motivation to commit suicide. Collision with a train is one of the most common methods of suicide, especially among young men under 40 years of age. (1). The forensic autopsy showed that the man died due to the collision with the train, with traumatic hemorrhagic shock stated as a cause of death. Following toxicological, biochemical, and immunological tests created a supposition that the incident was not a result of suicidal action but a consequence of a possible allergic or anaphylactic reaction of the organism combined with a state of mild alcohol intoxication.

Glucagon-Like Peptide 1 Receptor Agonists and Risk of Anaphylactic Reaction Among Patients With Type 2 Diabetes: A Multisite Population-Based Cohort Study.

Case reports and a pharmacovigilance analysis have linked glucagon-like peptide 1 receptor agonists (GLP-1 RAs) with anaphylactic reactions, but real-world evidence for this possible association is lacking. Using databases from the United Kingdom (Clinical Practice Research Datalink) and the United States (Medicare, Optum (Optum, Inc., Eden Prairie, Minnesota), and IBM MarketScan (IBM, Armonk, New York)), we employed a new-user, active comparator study design wherein initiators of GLP-1 RAs were compared with 2 different active comparator groups (initiators of dipeptidyl peptidase 4 (DPP-4) inhibitors and initiators of sodium-glucose cotransporter 2 (SGLT-2) inhibitors) between 2007 and 2019. Propensity score fine stratification weighted Cox proportional hazards models were fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for an anaphylactic reaction. Database-specific HRs were pooled using random-effects models. Compared with the use of DPP-4 inhibitors (n = 1,641,520), use of GLP-1 RAs (n = 324,098) generated a modest increase in the HR for anaphylactic reaction, with a wide 95% CI (36.9 per 100,000 person-years vs. 32.1 per 100,000 person-years, respectively; HR = 1.15, 95% CI: 0.94, 1.42). Compared with SGLT-2 inhibitors (n = 366,067), GLP-1 RAs (n = 259,929) were associated with a 38% increased risk of anaphylactic reaction (40.7 per 100,000 person-years vs. 29.4 per 100,000 person-years, respectively; HR = 1.38, 95% CI: 1.02, 1.87). In this large, multisite population-based cohort study, GLP-1 RAs were associated with a modestly increased risk of anaphylactic reaction when compared with DPP-4 inhibitors and SGLT-2 inhibitors.

[ANAPHYLACTIC REACTION TO LYSOZYME CHLORIDE-INCLUDING DEODORANT SPRAY IN A CHILD WITH EGG ALLERGY].

BACKGROUND: Lysozyme chloride is a bactericidal substance that is included as an active ingredient in many medicines and quasi-drugs. We experienced a case of anaphylactic reaction caused by deodorant spray-containing lysozyme chloride. CASE: The patient was a 10-year-old girl who had an egg allergy. She visited an emergency department because of urticaria, wheezing, dyspnea, and pallor after she used deodorant spray that contained lysozyme chloride derived from hen's egg white. Results for deodorant spray and lysozyme chloride were positive in both skin prick tests and basophil activation tests. According to the medical history and the results, her condition was diagnosed as an anaphylactic reaction to lysozyme chloride in the deodorant spray. DISCUSSION: Although ingredient labelling is obligatory for lysozyme chloride in quasi-drugs, lysozyme chloride is not often described to be derived from egg white. It is important to alert patients with egg allergy to avoid lysozyme chloride-containing products.

Acute thyroid swelling after fine needle aspiration-a case report of a rare complication and a systematic review.

BACKGROUND: Thyroid fine needle aspiration (FNA) is the procedure of choice in the management of thyroid nodules. Acute thyroid swelling after FNA is a rare complication and is reported in a finite number of literatures. To the best of our knowledge, only seven reported cases exist in literatures. This study describes an addition case with an acute thyroid swelling after FNA, as well as puts forward a new hypothesis of this phenomenon. CASE PRESENTATION: The case is presented of a 30-year-old female with an acute thyroid swelling after FNA, with funicular hypoechoic lesions in thyroid gland. The size of thyroid was 1.5-fold enlarged in the unilateral thyroid gland. No complains of pain or other discomforts with her and no signs of hemorrhage were found along the passage of the fine needle. The episode was recovered spontaneously. CONCLUSIONS: An acute thyroid swelling is a rare complication of FNA. A hypothesis of anaphylactic reaction was suggested in our study. Physicians should pay more attention of this phenomenon and more information is needed to support our hypothesis.

Bee Sting to Boerhaave's Syndrome.

Boerhaave's syndrome is a rare condition defined as the spontaneous rupture of the esophagus that generally occurs due to retching, forceful vomiting and sometimes even spontaneously. Atypical presentation often misleads the diagnosis leading to a delay in early intervention, and a strong clinical suspicion is indeed required to diagnose the condition. Definitive treatment being surgical repair, endoscopic intervention can be attempted in nonseptic patients. How to cite this article: Kaladhar S, Nikilesh Kumar G, Misra KC, Hemanth C, Appasani S. Bee Sting to Boerhaave's Syndrome. Indian J Crit Care Med 2021;25(3):346-348.

Secondary prevention measures in anaphylaxis patients: Data from the anaphylaxis registry.

BACKGROUND: Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. METHODS: Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. RESULTS: The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. CONCLUSIONS: Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.

Sex Differences in Adults with Insect Venom Allergy regarding Psychological Distress, Attitudes toward the Emergency Medication, and Factual Knowledge about the Disease.

BACKGROUND: Hymenoptera venom allergy (HVA) has a prevalence of 3% in adults. Although patients have no ongoing symptoms, they often suffer from an impairment of their psychological well-being and quality of life. OBJECTIVE: The aim of this study was to analyze sex-specific differences regarding the psychological burden caused by this allergy and handling of the emergency medication. METHOD: Study participants filled out a questionnaire including sociodemographic and disease-specific characteristics, the Hospital Anxiety and Depression Score (HADS), and theoretical knowledge about the emergency medication set (EMS). Additionally, an objective structured clinical examination was used to assess practical knowledge and handling of the EMS. RESULTS: Fifty-six patients were included (55.4% females). Female patients showed higher subjective anxiety levels due to HVA compared to men (mean 7.2 vs. 4.6, p = 0.0003). Furthermore, the HADS revealed that women had a significant higher anxiety level, especially after Mueller grade I-II anaphylactic reactions (mean 6.3 vs. 2.8, p = 0.0134). This was associated with a higher theoretical but not practical knowledge about their disease. On the other hand, males were less inclined to carry the emergency medication "always" or "almost always" (56 vs. 87.1%, p = 0.0015) but showed higher self-assurance in using it (mean 7.3 vs. 6.1, p = 0.0446). CONCLUSIONS: This clinical study provides evidence for sex differences in coping with HVA. The results suggest that females should be monitored more closely for allergy-associated anxiety symptoms, while men need more encouragement to carry the emergency medication.

Drug-induced anaphylactic reactions in children: A retrospective analysis of 159 validated spontaneous reports.

PURPOSE: The main objective of this study was to analyze validated cases of drug-induced anaphylactic reactions in children with regard to incriminated drugs, clinical characteristics, and associated factors. A further objective was to compare differences in incriminated drugs and characteristics between validated cases and a reference excluding anaphylactic reaction cases (basic dataset). METHODS: Spontaneous reports of anaphylactic reactions in children (0-17 years) registered between January 2000 to December 2016 were extracted from the adverse drug reaction database of the German Federal Institute for Drugs and Medical Devices. These reports were restricted to drugs for which at least four cases were found. After case validation, 159 reports remained (validated dataset) and were compared with the basic dataset (n = 12.168 reports) using inferential statistics. RESULTS: Estimated yearly increase of reports (36.8 vs 0.1), most frequently incriminated drugs (antibiotics 30.2% vs 11%, analgesics/antipyretics 22.0% vs 5.6%; P values less than 0.001) and route of administration (38.4% vs 6.7%) differed between the validated dataset and the basic dataset. Validated cases differed in severity (higher with atracurium), reported symptoms (urticaria leading with analgesics), and associated factors (atopy/allergy rarely reported with antibiotics) depending on the incriminated drug class. In 13.8% (11.3% if excluding repeated readministration in one person) of the cases, the drug had not been tolerated before. CONCLUSIONS: A heterogeneous clinical phenotype with differences in associated factors was observed, suggesting different underlying mechanisms triggered by the different drug groups. Occurrence of serious drug-induced anaphylactic reactions in children could be reduced by carefully considering patient history.

Systemic reaction to and interference with urine protein measurements after intravenous fluorescein injection.

BACKGROUND: Fluorescein angiography is an important and frequently used diagnostic tool in ophthalmological practice. In this case report we describe a patient who experienced an anaphylactic reaction after the injection of fluorescein. Furthermore, we report an interference with laboratory testing by fluorescein in this patient and summarize the literature on this topic. CASE PRESENTATION: An 86-year old Caucasian woman undergoing fluorescein angiography due to suspected peripapillary neovascularizations collapsed after the injection of fluorescein. The patient developed an anaphylactic reaction. With fluid resuscitation and oxygen therapy, the patient regained consciousness after a few minutes. The patient was admitted to the geriatric ward for observation, and routine blood and urine tests were performed. Urine protein concentration appeared to be falsely increased as a consequence of disturbance of the laboratory analysis by the presence of fluorescein. CONCLUSIONS: Serious complications can occur with fluorescein angiography, such as an anaphylactic reaction. In the case of anaphylaxis appropriate supportive measures including the use of oxygen and epinephrine (e.g. EpiPen), should be available to prevent morbidity and mortality from this test. Furthermore, these potential complications should be taken into consideration when choosing the healthcare setting for fluorescein angiography, such as the immediate availability of an acute medical team. Several studies have demonstrated the interference of laboratory analyses by fluorescein. The majority of these studies were published 10 to 30 years ago. By presenting this case, the authors hope to bring renewed attention to this phenomenon among clinicians, as falsely increased or decreased laboratory values can result in unnecessary diagnostics and/or therapy.

A Severe Anaphylactic Reaction Associated with IgM-Class Anti-Human IgG Antibodies in a Hyper-IgM Syndrome Type 2 Patient.

PURPOSE: A 42-year-old man with hyper-IgM syndrome type 2 caused by activation-induced cytidine deaminase (AID) deficiency developed a severe anaphylactic reaction to intravenous immunoglobulin. The purpose of this study was to clarify the cause of the anaphylactic reaction of the patient. METHODS: We measured IgM-class anti-human IgG and anti-human IgA antibodies in his serum by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The sandwich ELISA assay revealed that serum from the patient, but not the controls, reacted to three different IgG products and purified human IgA. This indicated that the patient had IgM-class anti-human IgG and IgA antibodies in his serum, which associated with the anaphylactic reactions after the administration of IgG products. The anti-IgG antibody was likely to be the main cause of the reactions because an IgA-depleted IgG product also induced a severe reaction in this case and showed high absorbance in the ELISA system, similar to other IgG products containing more IgA. CONCLUSIONS: This is the first report of IgM-class anti-human IgG associated with an anaphylactic reaction to an IgG infusion. The anaphylactic reactions were very severe in this case, probably because IgM-class antibodies are potent activators of the complement pathway.

More than a drink: A rare anaphylactic reaction to sparkling water.

Anaphylaxis is a potentially life threatening, type I hypersensitivity reaction which can occur within seconds to minutes after exposure to an allergen. Sulfites have been implicated in causing such reactions with symptoms ranging from mild to potentially life threatening. Here we present a patient who had an anaphylactic reaction secondary to exposure to sulfites found in sparkling water.

Management of Acute Contrast Reactions-Understanding Radiologists' Preparedness and the Efficacy of Simulation-Based Training in Canada.

PURPOSE: Acute radiologic emergencies, primarily severe contrast reactions, are rare but life-threatening events. Given a generalized paucity of formalized or mandated training, studies have shown that radiologists and trainees perform poorly when acutely managing such events. Moreover, skill base, knowledge, and comfort levels precipitously decline over time given the infrequent occurrence of these events during one's daily practice. The primary aim of this study was to assess radiologists' preparedness for managing acute radiologic emergencies and to determine the efficacy of a high-fidelity simulation based training model in an effort to provide a rationale for similar programs to be implemented on a provincial or national level. METHODS: This was a prospective, observational study of radiology residents and attending radiologists throughout the province who were recruited to attend a full-day simulation-based course presenting various cases of acute radiologic emergencies. Participant demographics were collected at the time of commencement of the workshop. Course materials were disseminated 4 weeks prior to the workshop, and a 17-question knowledge quiz was administered before and after the workshop. Likert-type questionnaires were also distributed to survey comfort levels and equipment familiarity. The knowledge quiz and questionnaire were redistributed at 3- and 6-month intervals for acquisition of follow-up data. RESULTS: A total of 14 attending radiologists and 7 residents attended the workshop, with all participants completing the preworkshop questionnaire and 90.5% (19 of 21) completing the post-workshop questionnaire. Participants' principle locations of practice were as follows: academic institutions (50%), community hospitals (36.9%), and private clinics (13.1%). A significant increase in knowledge was demonstrated, with average scores of 10 out of 17 (59%) and 14.5 out of 17 (85%) (P < .001) before and after the workshop, respectively. A significant increase in participants' comfort levels in recognizing acute anaphylactic reactions (3.5; 4.7, P < .001), commencing initial management for acute radiologic emergencies (3.3; 5.0, P < .001), and administering the correct dose for anaphylactic reactions (2.5; 4.8, P < .001) was also demonstrated. Moreover, participants became increasingly familiar with the contents and equipment found within contrast reaction kits (2.8; 3.8, P < .01). Repeat evaluations at 3 and 6 months found an average knowledge test score of 13.8 out of 17 (81%) and 10.8 out of 17 (64%), respectively. Comfort levels were also reassessed in recognizing acute anaphylactic reactions (4.5; 4.1), commencing initial management (4.0; 3.9) and administering the correct dose of medication (4.0; 3.7) at 3- and 6-month intervals. CONCLUSIONS: Acute radiologic emergencies are rare but life-threatening events that require rapid diagnosis and treatment to mitigate associated morbidity and mortality. Simulation-based workshops are a highly efficacious training model to increase knowledge, comfort levels, and equipment familiarity for radiologists and trainees alike; however, retraining at regular intervals is required.

Basophils and mast cells are crucial for reactions due to epicutaneous sensitization to ovalbumin.

The prevalence of food allergies worldwide has increased recently. Epicutaneous sensitization to antigen could be a method to study food allergy. To clarify the mechanisms of food allergy, we established a mouse model of epicutaneous sensitization using ovalbumin (OVA). BALB/c mice were sensitized by three-time application of OVA to tape-stripped skin (1-week sensitization at 2-week intervals) and oral challenge of OVA undertaken. Rectal temperature was monitored. Blood and tissue (skin and jejunum) of challenged mice were taken. Numbers of mast cells (MCs) and basophils were counted. Serum and/or tissue levels of OVA -specific IgE and IgG antibodies and several cytokines were measured using enzyme-linked immunoassay kits. MC and basophil depletion experiments were undertaken. In OVA/epicutaneous-sensitized and orally challenged mice, systemic anaphylaxis (as evidenced by reduced rectal temperature) was observed. Levels of OVA-specific IgE and IgG antibodies were increased in these mice, as were increased number of MCs and basophils. Serum levels of MC protease 1 were increased significantly. Basophil and MC depletion experiments revealed that they both participate in reactions. Increased production of thymic stromal lymphopoietin (TSLP) at skin sites of OVA sensitization was noted. We speculate that TSLP produced from epidermal cells during antigen sensitization can enable basophils to promote a T helper (Th)2 immune reaction, leading to and systemic anaphylaxis by antigen-specific IgE-bearing MCs. This TSLP-basophils-MC axis could be a novel therapeutic target against food allergy.

Ultrasensitive and rapid immuno-detection of human IgE anti-therapeutic horse sera using an electrochemical immunosensor.

Antivenom allergy disease mediated by patient IgE is an important public health care concern. To improve detection of hypersensitive individuals prior to passive antibody therapy, an amperometric immunosensor was developed to detect reactive human IgE. Whole horse IgG3 (hoIgG3) was immobilized onto the surface of carbon or gold screen-printed electrodes through a cross-linking solution of glutaraldehyde on a chitosan film. Sera from persons with a known allergic response to hoIgG3 or non-allergic individuals was applied to the sensor. Bound human IgE (humIgE) was detected by an anti-humIgE antibody through a quantitative amperometric determination by tracking via the electrochemical reduction of the quinone generated from the hydroquinone with the application of a potential of 25 mV. The optimal immunosensor configuration detected reactive humIgE at a dilution of 1:1800 of the human sera that represent a detection limit of 0.5 pg/mL. Stability testing demonstrated that through 20 cycles of a scan, the specificity and performance remained robust. The new immunosensor successfully detected humIgE antibodies reactive against hoIgG3, which could allow the diagnosis of potential allergenic patients needing therapeutic antivenom preparations from a horse.

Anaphylactic Reaction During Implantation of the Ovation Stent-Graft System in a Patient With Abdominal Aortic Aneurysm.

PURPOSE: To describe a case of anaphylactic reaction during implantation of the Ovation Abdominal Stent Graft System in a patient treated for abdominal aortic aneurysm (AAA). CASE REPORT: An 82-year-old man with a 5.3-cm asymptomatic AAA underwent endovascular repair using an Ovation stent-graft. Polymer was infused into the inflatable rings of the aortic body under continuous angioscopy, but the rings were not filled, even though the entire amount of the polymer was administered. Simultaneously, the patient presented with a severe anaphylactic reaction resulting in cardiopulmonary arrest. He was successfully resuscitated, but the procedure was abandoned; the patient refused any further treatment. CONCLUSION: A rupture of the Ovation main body's polymer-filled rings may lead to extremely severe anaphylactic reaction.

Severe adverse drug reaction following Crotalidae Polyvalent Immune Fab (Ovine) administration for copperhead snakebite.

OBJECTIVE: To present the case of a severe anaphylactic/anaphylactoid reaction to Crotalidae Polyvalent Immune Fab (Ovine) in a patient bitten by a copperhead snake. CASE SUMMARY: A 68-year-old man presented with progressive envenomation after receiving a copperhead snakebite on each hand. Crotalinae Fab antivenom was administered. While the initial and only dose was partially infusing, the patient developed an adverse drug reaction (ADR) of urticaria and hypotension, which resolved with cessation of the infusion, recurred with resumption of the infusion, and ultimately was completed with supportive care. An additional episode of hypotension, urticaria, and angioedema occurred shortly after antivenom therapy completion. Epinephrine was administered, resolving the reaction with complete patient recovery. The event received a Naranjo score of 10, indicating a definite ADR. DISCUSSION: Treating copperhead snakebites with antivenom is a matter of debate. Concern over adverse events and cost induce some physicians to manage copperhead bites without antivenom because they are generally milder in severity. CONCLUSION: As demonstrated in this case, severe ADR can occur with Crotalinae Fab antivenom, and its efficacy for copperhead envenoming needs to be better established via placebo-controlled, randomized trials.