Anaphylactic Death Research Articles

Mad, bad and dangerous to know: the biochemistry, ecology and evolution of slow loris venom.

Only seven types of mammals are known to be venomous, including slow lorises (Nycticebus spp.). Despite the evolutionary significance of this unique adaptation amongst Nycticebus, the structure and function of slow loris venom is only just beginning to be understood. Here we review what is known about the chemical structure of slow loris venom. Research on a handful of captive samples from three of eight slow loris species reveals that the protein within slow loris venom resembles the disulphide-bridged heterodimeric structure of Fel-d1, more commonly known as cat allergen. In a comparison of N. pygmaeus and N. coucang, 212 and 68 compounds were found, respectively. Venom is activated by combining the oil from the brachial arm gland with saliva, and can cause death in small mammals and anaphylactic shock and death in humans. We examine four hypotheses for the function of slow loris venom. The least evidence is found for the hypothesis that loris venom evolved to kill prey. Although the venom’s primary function in nature seems to be as a defense against parasites and conspecifics, it may also serve to thwart olfactory-orientated predators. Combined with numerous other serpentine features of slow lorises, including extra vertebra in the spine leading to snake-like movement, serpentine aggressive vocalisations, a long dark dorsal stripe and the venom itself, we propose that venom may have evolved to mimic cobras (Naja sp.). During the Miocene when both slow lorises and cobras migrated throughout Southeast Asia, the evolution of venom may have been an adaptive strategy against predators used by slow lorises as a form of Müllerian mimicry with spectacled cobras.

Current and emerging immunotherapeutic approaches to treat and prevent peanut allergy

Peanut-allergen hypersensitivity reactions, which can result in anaphylactic episodes and death, affect approximately 1% of the general population. Currently, strict avoidance of allergenic food is the only available treatment for this food-induced allergic reaction; however, the innocuous presence of trace amounts of peanut protein contaminating food products makes avoidance extremely difficult, especially in children. Therefore, safe and inexpensive therapeutic strategies aimed at prevention and treatment of peanut allergies is urgently required. This review summarizes the current state of knowledge of adaptive immune recognition and responsiveness to peanut allergens and how this can be integrated and subverted into new therapeutic treatment regimens for these dangerous allergic responses. The potential for new strategic vaccination-based interventions to either moderate or prevent these types of responses from occurring is also discussed.

Tropical dermatology: Venomous arthropods and human skin

Although many tropical insects carry infectious diseases, cutaneous injury can occur by other mechanisms, for example erucism (envenomation by caterpillars) or lepidopterism (dermatitis from moths). Pararama is a unique form of erucism seen in workers in contact with rubber trees in the Amazon, and it is caused by Premolis larvae, resulting in progressive periarticular fibrosis, ankylosis, and the loss of articulation. Ants and aquatic insects of the Belostomatidae family can cause painful bites and stings. Anaphylactic shock and death can result from the venom of bees and wasps. Beetles can cause vesicular dermatitis via cantharidin or paederin. Myiasis results from fly larvae (maggots) feeding on live or necrotic tissue of humans or other hosts, while New World screwworm fly larvae feed only on living tissue and burrow (ie, screw) more deeply when attempts are made to remove them. Tungiasis is characterized by very pruritic and painful papules and ulcers resulting from a Tunga flea penetrating the host's skin. Dermatologists should be able to diagnose and treat the cutaneous manifestations of these tropical insects and educate their patients on prevention.

Histopathological markers for the diagnosis of anaphylactic death

The postmortem diagnosis of anaphylactic death may be frustrating when victims are not hospital patients, even more so when they are recovered dead. The frequent lack of specific morphological findings in such cases means that diagnosis by the forensic pathologist must rely solely on exclusion criteria or circumstantial evidence. However, a diagnostic approach based on case history, analysis of circumstances, available clinical and necropsy findings, as well as toxicology, histopathology and biohumoral data, often allows demonstration of the cause of death. Some useful reflections on microscopic morphological data have come from two recent cases, where thorough data collection provided a reasonably certain diagnosis of anaphylactic death and systemic inflammatory response syndrome-related cardiac arrest, respectively. In both cases tissue histopathology proved crucial, since histochemical (GIEMSA) and immunohistochemical analysis (CD117 and tryptase) documented a large number of mast cells in tissues, particularly the laryngeal wall, and a discrepancy between cells positive for GIEMSA and tryptase and those positive for CD117. Staining for CD117 was also detected in cells with dendrite morphology and in a subpopulation of small lymphocytes with incised nuclei. The morphological findings of these cases are discussed, especially those obtained with immunohistochemistry, and the need for the latter data to be interpreted by experienced medical staff in the framework of a thorough analysis of all the data collected is highlighted.

Animals, autopsies and artefacts

In the last issue of Forensic Science, Medicine and Pathology Buschmann et al. [1] described decapitation associated with postmortem dog attacks. While drawing attention to a specific form of craniocerebral trauma, the paper also raises the issue of difficulties that may arise in assessing the significance of injuries inflicted by animals, as not infrequently autopsies are conducted on bodies with features that have been modified by animal activity. While the sequence of events leading up to, and following, the fatal episode is usually not difficult to establish, on occasion the precise role played by the injuries may be difficult to determine. Ascertaining whether injuries from animal attacks occurred before or after death, contributed to the death, were incidental to the death, or merely modified underlying diseases or other injuries are issues that may need to be addressed [2]. Deaths from animal attacks may be caused by a wide variety of mechanisms involving blunt and sharp trauma, crushing, envenomation, anaphylaxis or sepsis [3–5]. Blunt trauma from animals has been confused with homicide [6] and careful scene evaluations may need to be conducted to exclude human activity. However, attacks may either have been witnessed, or the proximity of offending animals to victims and previous behaviour may be clues to their involvement. Difficulties may arise when there is no evidence at autopsy of significant trauma as may occur, for example, with an anaphylactic death. The absence of stings does not exclude bee or wasp attack and ancillary studies, including serum tryptase and specific IgE levels, will need to be undertaken. Similarly, victims of snake bite may not have readily apparent bite marks at autopsy [4]. Those who are immunocompromised may also succumb to unusual infections following apparently innocuous animal bites [7]. Antemortem dog attacks may produce similar injuries to those arising from postmortem feeding and in the event of a suspected fatal attack examination and/or necropsy of the animal may be required. Specific guidelines on the handling of such cases have been published [8, 9]. Postmortem injuries may be species-specific related to animal size and morphology. For example sea lice tend to burrow through soft tissues under the skin creating oval defects in the overlying epidermis whereas sharks will remove large pieces of tissue, organs or entire limbs. Animals will also concentrate on body orifices or defects, and so wound characteristics may be extensively modified by many animals ranging from fly larvae (maggots) to cats and dogs. Trauma to the genitalia or anogenital region by carnivores may raise the suspicion of a sadistic sexual assault and homicide with mutilation. Given the predilection of carnivores, such as domestic dogs, for wound sites, the possibility of ingestion of projectiles from shooting deaths must be considered, with examination and X-ray of the animal and/or feces collected from the scene. Certain individuals have an increased likelihood of postmortem animal mutilation and this applies particularly to elderly recluses who may share their homes with a variety of domestic (e.g. dogs and cats) and feral animals (e.g. rats and mice). Referred to as the Diogenes syndrome, there may be great difficulties for the police and pathologist in evaluating cases as underlying alcoholism or significant illnesses may have resulted in falls with bruising. This, added to the general state of disarray of such households, may suggest assault with robbery [10]. Individuals who may have been unconscious for some time may have been R. W. Byard (&) Discipline of Anatomy and Pathology, Level 3 Medical School North Building, The University of Adelaide, Frome Rd, Adelaide, SA 5005, Australia e-mail: roger.byard@sa.gov.au

Safety profiles of total dose infusion of low-molecular-weight iron dextran and high-dose iron sucrose in renal patients

Iron sucrose and low-molecular-weight iron dextran (LMW-ID), two commonly used iron solutions, have been compared in terms of allergic adverse event profiles to date. However, the safety of total dose infusion of LMW-ID has been investigated by only one study in chronic kidney disease (CKD) (not dialysis) patients. Thus, we aimed to compare adverse event profiles of total and high-dose LMW-ID and iron sucrose infusions in a heterogenous renal patient group comprising CKD, hemodialysis, and peritoneal dialysis. In this retrospective chart review study, we included 110 predialysis CKD, 101 peritoneal dialysis, and 118 hemodialysis patients. We included a total of 329 patients who were administered parenteral iron sucrose or LMW-ID between September 2006 and April 2010. Adverse events were determined both by medical and nursing follow-up notes. Laboratory data and clinical characteristics were collected from patient charts. Adverse event rates were compared between iron sucrose and LMW-ID infusions. In a total of 329 patients, 530 infusions (3470 ampules) were administered. We detected adverse reaction in only 1 patient. This adverse reaction, which manifested as generalized pruritus, occurred in a patient who received 500 mg of iron sucrose infusion. There were neither anaphylactic reactions nor deaths associated with infusion of either preparation. We did not observe any other adverse event related to administration of 500 and 1000 mg of iron sucrose at single infusion. The results of this study showed comparable safety of total dose LMW-ID and high-dose iron sucrose in a heterogenous group of renal patients.

Cutaneous lepidopterism: dermatitis from contact with moths of Hylesia metabus (Cramer 1775) (Lepidoptera: Saturniidae), the causative agent of caripito itch

Lepidopterism derived from contact with arthropods and/or their products can result in adverse reactions that vary in severity from mild irritation to severe reactions including anaphylactic shock and death. Lepidopterism includes cutaneous and/or mucosal manifestations, systemic symptoms, or both mucocutaneous and systemic manifestations. Epidemic outbreaks of dermatitis due to Hylesia sp. have been recorded in several countries of Latin America. The impact of climatic changes occurring presently on migrational and reproductive cycles of Hylesia metabus is also discussed in this study. In Venezuela, swarms of migrating H. metabus moths are historically recognized as the causative agents of "Caripito itch," a disease that has become an important public health problem. In this review, we present a series of four case reports reflecting the wide clinical pleomorphism exhibited in lepidopterism by H. metabus. Although dermatitis caused by these moths is usually resistant to all therapeutic treatment, individualization of therapy based on symptoms led to successful treatment in all four cases.

Peanut allergy and allergic airways inflammation

Asthma is a major risk cofactor for anaphylactic deaths in children with peanut allergy. Peanut allergy is generally thought to be a lifelong condition, but some children outgrow their coexistent asthma. It has recently been shown that children who have 'outgrown' their asthma symptoms may have ongoing eosinophilic airways inflammation. The need for regular inhaled corticosteroid treatment in peanut allergic children and adolescents who have outgrown their asthma is however unclear. The aims of our study were to look at fractional exhaled nitric oxide levels (FeNO), as a non-invasive marker of eosinophilic airways inflammation, in peanut allergic children and assess whether children with outgrown asthma had elevated levels. Children with peanut allergy were recruited at two pediatric allergy clinics in Belfast, UK. Exhaled nitric oxide levels (FeNO) were measured using the Niox Mino in all children. Of the 101 peanut allergic children who consented for enrollment in the study, 94 were successfully able to use the NIOX Mino. Age range was 4-15 yr (median 10 yr); 61% were boys. Thirty (32%) had never wheezed, 37 (39%) had current treated asthma, 20 (21%) had at least 1 wheezing episode within the last year but were not taking any regular asthma medication (wheeze no treatment), and 7 (7%) had outgrown asthma. All children with outgrown asthma had elevated levels of FeNO (> 35 ppb), and 75% of children defined as 'wheeze no treatment' had elevated FeNO levels (> 35 ppb). Outgrown asthma and children defined as 'wheeze no treatment' had higher levels of FeNO than those with no history of wheeze or current treated asthma (p = 0.003). In children with peanut allergy, we found that those who had outgrown asthma had elevated FeNO levels in keeping with ongoing eosinophilic airways inflammation.

Heparin and Oversulfated Heparin Byproduct Induce Thrombin Generation Through Contact System Activation in Plasma of Patients With HIT

Heparin-induced thrombocytopenia with thrombosis (HITT) is the most severe side effect of heparin administration. Patients with HITT may die or have permanent sequelae such as stroke or limb amputation. Contaminated heparin is associated with anaphylactic reactions and deaths by activating the contact system. It is also associated with high incidence of HIT via a yet unknown mechanism. This study showed that although oversulfated heparin byproduct induced thrombin activities in both normal and HIT patient plasmas through the contact system activation, authentic heparin induced thrombin activities only in HIT patient plasmas containing autoantibodies against protein/ heparin complex. These data suggest that the negatively charged immunoglobulin G (IgG)/platelet factor 4 (PF4)/heparin complex activate the contact system and produce thrombin in human plasma, and thrombin partially activates the platelets allowing subsequent platelet activation through IgG/Fc receptor II signaling. The newly discovered mechanism of heparin-induced thrombin activity could explain the increased incidence of HIT in patients exposed to contaminated heparin. Furthermore, the assays used in these studies would be valuable for HIT diagnosis, prevention, and treatment.

Postmortem Findings After Anaphylactic Reactions to Drugs in Turkey

To determine the frequency of anaphylactic deaths at autopsies performed in Turkey between January 2001 and June 2006 and to review the circumstances of death and autopsy findings. The Council of Forensic Medicine database in Istanbul was searched for anaphylactic deaths. Postmortem reports and medical records were reviewed to determine the circumstances of death. Data about basic demographics, medical history, drugs responsible for allergic reactions, and pathologic findings at autopsy were collected. A total of 36 anaphylactic deaths from drugs were identified for the study period. Death was due to antibiotics in 26 cases, analgesics in 7 cases, an intraoperative drug in 1 case, an H2 receptor in 1 case, and intravenous contrast medium in 1 case. Out of 36 cases, 19 were male and 17 female. They were aged between 1 and 74 years with the median age of 26.7 years. Death occurred within 1 hour of the onset of anaphylaxis in 27 cases. Findings at autopsy included nonspecific pulmonary edema and congestion, upper airway edema, cerebral hypoxia, and cutaneous edema. Serum tryptase levels were not measured in all cases. Anaphylactic reaction is an uncommon cause of sudden death. In many cases, no specific macroscopic or microscopic findings were detected at autopsy. When serum tryptase levels cannot be determined, in the presence of typical clinical records, eye witness reports and autopsy findings can be useful diagnostic aids.

Anaphylactic deaths in Maryland (United States) and Shanghai (China): A review of forensic autopsy cases from 2004 to 2006

Anaphylaxis is a life threatening allergic reaction that is rapid in onset and may cause sudden death. A retrospective study was performed using the database from the Office of the Chief Medical Examiner (OCME) in the State of Maryland and the Department of Forensic Medicine in Shanghai Medical College (DFM-SMC) to examine the etiology and forensic investigation findings of anaphylactic deaths from 2004 to 2006. Details of the medical history, agent responsible for the allergic reaction, death scene investigation and postmortem examination findings were reviewed for all cases. A total of 28 cases of anaphylactic death were identified for the study period, 17 from Maryland and 11 from Shanghai. Of the 17 Maryland cases, 6 (35%) involved allergic reaction to food, 5 (25%) to drugs, 2 to bee stings, 1 to hair dye, and 3 to unknown allergens. Investigation revealed that 9 of 17 cases had a history of asthma and 8 had previous allergic reactions to certain foods and / or drugs. In Shanghai, all 11 deaths resulted from anaphylactic reaction to antibiotics, 10 of which occurred in clinics illegally operated by unlicensed physicians. The interval between the onset of symptoms and death ranged from less than 1 min to 3 days after initially contacting the allergen. In the majority (68%) of cases, death occurred within 8 h after the onset of symptoms. Postmortem findings were relatively non-specific, and included pharyngeal/laryngeal edema 14/28 (50%), mucus plugging in the airways 11/28 (39%), and pulmonary congestion and edema 28/28 (100%). Serum tryptase concentrations were measured in 14 cases in Maryland and the concentration ranged from 3.3 ng/ml to 200 ng/ml. There were significant differences with regards to allergen type and the circumstances of death between these two regions. Inappropriate use of antibiotics and illegal medical practices were the main causes of identified anaphylactic death in Shanghai. In Maryland anaphylactic deaths were mainly caused by food reactions. This study indicates that the postmortem diagnosis of anaphylactic death is usually based on exclusion and circumstantial evidence. Knowledge of the patient's history and circumstances of death is of major importance for the forensic pathologist when investigating suspected anaphylactic death.

A giant liver mass: hydatid cyst of the liver

A 20-year-old man was admitted to our clinic after complaining of right upper abdominal pain and gradually increasing visible upper abdominal lump for a month. His clinical examination revealed remarkable epigastric tenderness and right upper abdominal enlargement. His body temperature was 37.8 °C. On admission, his laboratory findings were as follows: WBC count 7800/mm3, HGB 13.1 g/dl, HTC 39.7%, eosinophils 5% (320/mm3), ESR 58 mm/h, CRP 84 mg/dl(0-5). Liver function tests were within normal range. Ultrasonography of the right upper quadrant revealed a 13 × 13 cm cystic lesion in the liver, surrounded by septated liquid 1 cm in diameter (Figure 1). A CT scan of the liver also revealed a 13 × 13 cm cystic lesion, compressing the inferior vena cava, right kidney and pancreas (Figure 2). A serological test for echinococcus was positive. Thus, the cyst and the septated liquid were diagnosed as hydatid cyst complicated by infection. The patient was treated with albendazole (10 mg/kg/day) for the hydatid cyst, and ciprofloxacin (2 × 500 mg orally) and amoxicillin/clavulanic acid (2 × 1 g orally) for the complicating infection. One week after medical intervention, his body temperature was normal, the CRP level had decreased to 28 mg/dl and ESR to 40 mm/h, and the patient underwent surgery. After surgery, the patient was prescribed albendazole for two months, and ciprofloxacin and amoxicillin/clavulanic acid for one week; during this period, the patient had regular follow-ups, with no recurrence of the hydatid cyst.Figure 2CT scan of the liver revealed a 13 × 13 cm cystic lesion, compressing the inferior vena cava, right kidney and pancreas.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Hydatid cyst is endemic in regions such as South America, the Near East, Southern Europe, Africa and Australia1Sahin D.A. Kusaslan R. Sahin O. Dilek O.N. Huge hydatid cysts that arise from the liver, growing exophytically.Can J Surg. 2007; 50: 301-303PubMed Google Scholar. The liver is the organ most likely to be affected. Although surgery is the treatment of choice for all patients with symptomatic disease, albendazole is given both pre-operatively and postoperatively to soften the cysts and to prevent recurrence after the operation2Mehra B.R. Thawait A.P. Gupta D.O. Narang R.R. Giant abdominal hydatid cyst masquerading as ovarian malignancy.Singapore Med. 2007; 48: e284-e286PubMed Google Scholar. Giant hydatid cysts can cause anaphylactic shock and death upon rupture. It is important to remain aware that trauma might lead to perforation and anaphylaxis in such patients. Conflict of interest: No conflict of interest to declare.

Immediate anaphylactic death following antibiotics injection: Splenic eosinophilia easily revealed by pagoda red stain

The comparison of 4 cases of immediate anaphylactic death following the intramuscular injection of antibiotics (different types of penicillin or cephalosporins) with 4 cases of immediate non-anaphylactic death (induced by different causes) recognized splenic eosinophilia, as the main feature for the differential diagnosis, in agreement with isolated previous studies. The use of a stain (pagoda red) little known and seldom employed in Pathology and in Forensic Medicine, showed the concomitant massive presence (immunohistochemically confirmed) of mast cells and degranulated mast cells, the latter mainly located in splenic sinuses. The whole of our findings led us to consider the spleen as the possible shock organ in man. Waiting for further judgment on our hypothesis, we seized the opportunity to remark the employment of the pagoda red stain when the contemporary demonstration of eosinophils, mast cells and degranulated mast cells is required.

Human alpha 1-antitrypsin therapy induces fatal anaphylaxis in non-obese diabetic mice

Previous studies have shown that human alpha-1 antitrypsin (hAAT) gene delivery prevents type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. Furthermore, hAAT protein administration prolongs acceptance of islet allografts. Therefore, we evaluated the use of purified hAAT protein therapy to prevent T1D in NOD mice. Female NOD, non-obese resistant (NOR), Balb/c and C57BL/6 mice were injected intraperitoneally with vehicle alone or vehicle containing hAAT, human albumin or mouse albumin (or mg/injection/mouse; 2x/week). Preparations of clinical-grade hAAT included API(R), Aralast, Prolastin and Zemaira. Surprisingly, hAAT administration was associated with a high rate of fatal anaphylaxis. In studies seeking T1D prevention at 4 weeks of age, 100% mice died after six injections of hAAT. When administrated at 8-10 weeks of age, most (80-100%) NOD mice died following the fourth injection of hAAT, while 0% of Balb/c and C57BL/6 mice and 10% of NOR mice died. Interestingly, repeated injections of human albumin, but not mouse albumin, also induced sudden death in NOD mice. Antibodies to hAAT were induced 2-3 weeks after hAAT administration and death was prevented by treatment with anti-platelet-activating factor along with anti-histamine. In studies of disease reversal in NOD mice, using the four pharmaceutical grade formulations of hAAT, anaphylactic deaths were observed with all hAAT preparations. The propensity for fatal anaphylaxis following antigenic administration appears to be NOD- but not hAAT-specific. The susceptibility of NOD mice to hypersensitivity provides a significant limitation for testing of hAAT. Development of strategies to avoid this unwanted response is required to use this promising therapeutic agent for T1D.

A population‐based epidemiologic analysis of deaths from anaphylaxis in Florida

Previous US population-based epidemiologic studies of anaphylactic deaths have been limited by small populations and/or few deaths. The objective of this study was to determine the 10-year incidence of death from anaphylaxis in Florida and its descriptive epidemiology. Patients who died from anaphylaxis from 1996 to 2005 were identified from ICD-9 and ICD-10 codes on death certificates statewide. Age, race and gender-specific anaphylactic death rates were calculated. There were 89 deaths among Florida residents. The individuals with autopsy confirmed diagnoses, and those with clinical diagnoses only, did not differ with regard to race, anaphylactic triggers or the clinical variables of lung and heart disease. Annual death rate for anaphylaxis in Florida was 5.02/10 000 000. The relative risk of death from anaphylaxis was 14.09 for individuals > or =65 years old (P = 0.0000002) and 6.38 for individuals 35-64 years old (P = 0.0019) compared with those who were 5-14 years of age. Deaths among Florida residents that occurred in emergency rooms or outpatient settings were 2.11 times as likely to be anaphylactic deaths than deaths that occurred in inpatient settings (P = 0.0026). The ratios of anaphylactic deaths to total deaths in March and April and in July and August were greater than the ratios for the other bimonthly periods (P = 0.02). Death from anaphylaxis in Florida was more likely to occur in older individuals, in an emergency department, and in the months of March and April and July and August.

Su.81. Development of a Penicillin-reactive IgE Screening Platform

Penicillins are effective for treating bacterial infections in many clinical situations, but in certain cases, they cause allergic reactions varying from mild skin rashes to anaphylactic shock and death. These symptoms often resemble those seen in immediate or delayed hypersensitivity reactions, and may be associated with drug specific IgE and/or drug specific T cells. Currently, the laboratory tests include isotope based serum IgE antibody measurement as well as skin test. However, radioisotope allergen specific tests (RAST) are not convenient, and the standardized skin-testing reagents and protocol do not usually exist. In fact, the skin test is often avoided because of the high risks. Therefore, in the current study, we have developed a non-isotope based penicillin-reactive IgE screening platform with high sensitivity and specificity. Using this screening platform to detect IgE of a mouse model sensitized with penicillin reveals that high levels of penicillin specific IgE were found in the penicillin sensitized animals but not in OVA sensitized or untreated control animals. Penicillin specific T cells produce relatively higher levels of IL-4 and IL-5 in the penicillin sensitized group, indicating a Th2-cytokine dominated response of T-cell dependent IgE production against penicillin. This observation and the development of such convenient platform to measure penicillin specific IgE may benefit further study of penicillin allergy.

Safety and pharmacokinetics of daclizumab in pediatric renal transplant recipients

This study examined the safety and pharmacokinetics/pharmacodynamics of daclizumab in combination with mycophenolate mofetil (or azathioprine), corticosteroids, and cyclosporine or tacrolimus, in 61 pediatric renal allograft recipients in three age groups: less than or equal to five yr (n = 18), 6-12 yr (n = 18), and 13-17 yr (n = 25). The dosing regimen was daclizumab 1.0 mg/kg before transplantation, followed by four biweekly doses. The pharmacokinetics of daclizumab were described using NONMEM software. Median (range) estimated trough daclizumab levels achieved on day 56 (before dose 5) were 3.88 microg/mL (2.48-8.78), 4.54 microg/mL (1.79-18.7), and 4.94 microg/mL (0.05-10.6) in the less than or equal to five yr (n = 15), 6-12 yr (n = 17), and 13-17 yr (n = 22) age groups, respectively. Steady-state median (range) daclizumab exposures were 2040 mg x h/mL (1585-3778), 2757 mg x h/mL (1873-3494) and 3297 mg x h/mL (1705-6453), respectively. Saturation of the IL-2R occurred rapidly and was maintained for greater than or equal to three months after transplantation. Daclizumab was generally well-tolerated with no acute allergic or anaphylactic reactions, deaths or malignancies during the study. The proportion of patients who developed acute rejection at six and 12 months was 8.5% and 16.7%, respectively. This study shows that adding daclizumab at 1 mg/kg to standard immunosuppressive therapy provides safe and effective IL-2R blockade.

Fatal anaphylaxis: postmortem findings and associated comorbid diseases

Anaphylaxis is an infrequent cause of sudden death. Death often results from circulatory collapse, respiratory arrest, or both. To investigate the causes of death, anatomical findings, and comorbid diseases in cases of fatal anaphylaxis. This is a retrospective case review of 25 unselected cases of documented fatal anaphylaxis. Each case report contained details of the fatal reaction, a review of the medical record, and laboratory and autopsy findings. Serum tryptase concentrations were measured in 7 cases. The anaphylactic deaths included 7 reactions to medications, 6 to radiocontrast material, 6 to Hymenoptera stings, and 4 to foods. The mean age was 59 years. The anaphylactic reaction began within 30 minutes of exposure in 21 of 25 cases, with death occurring within 60 minutes in 13 of 25 cases. Urticaria occurred in only 1 of 25 cases. Anatomical findings consistent with anaphylaxis were present in 18 of 23 patients undergoing autopsy. At least 1 significant comorbid disease was identified in 22 of 25 cases. (1) Elderly patients with substantial comorbid conditions constituted a significant number of the anaphylactic fatalities; (2) the onset of severe anaphylaxis occurred in less than 30 minutes in nearly every case; (3) 18 of 23 cases were associated with specific anatomical findings of anaphylaxis; (4) self-administered epinephrine was used in just 1 of 5 cases; and (5) serum total tryptase concentrations were elevated markedly in 4 of 7 cases tested.

Differential accumulation of pulmonary and cardiac mast cell-subsets and eosinophils between fatal anaphylaxis and asthma death: A postmortem comparative study

The distribution profile of infiltrated mast cell-subpopulations and eosinophils in the lung and heart sections of the patients who died of severe allergic hyperresponsiveness, was investigated. Four study groups were designed comprising 9 cases who died in systemic anaphylaxis (Group I), 10 asthmatic individuals whose death were assigned to acute and severe bronchial asthma (Group II), 10 asthmatic cases who died from non-immunological diseases (Group III). Twenty consecutive autopsies of non-allergic subjects who died of unnatural causes (Group IV) served as control group in this study. Utilizing antibodies against human tryptase and chymase and a double immunohistochemical staining method, we distinguished successfully all three subsets of mast cells (MC), MC-TC (containing both tryptase and chymase), MC-T (containing only tryptase) and MC-C (containing only chymase) types, subdivided on the basis of the protease compositions of their secretory granules. In order to immunostaining eosinophils, we used antibody to major basic protein as a marker. We also measured postmortem blood tryptase, specific and total serum IgE. The intriguing finding of this study was the marked differences of cellular composition in the lung between fatal anaphylaxis and asthma death. Significant augmentation of MCs infiltrated in lung and heart sections of anaphylaxis patients and drastic infiltration of bronchial eosinophils in asthmatic death and consequent release of their related inflammatory mediators might explain the differential expression of the associated symptoms in these two groups. The anaphylactic deaths did show neither emphysema nor significant mucous bronchial secretions whereas all asthmatic deaths did. The degree of pulmonary congestion and edema was also more severe in anaphylaxis. This corresponded with the histological findings and the location and number of mast cell-subsets and eosinophils in the different compartments of the lungs. We have demonstrated that the third type of mast cell MC-C is only found in the lungs in anaphylactic deaths. The practical consequence of our study will be that it is now possible to confirm a suspicion of anaphylaxis death not only by measurements of serum mast cell tryptase, but also by immunohistochemical methods.

Anaphylactic deaths in Auckland, New Zealand: a review of coronial autopsies from 1985 to 2005

To determine the frequency of anaphylactic deaths amongst coronial autopsy cases performed in the greater Auckland region from 1985 to 2005, and review the circumstances of death and autopsy findings. A computerised search for anaphylactic deaths was performed using the Forensic Pathology Department database at Auckland City Hospital. Postmortem reports and police reports were reviewed to determine the circumstances of death. Details recorded included basic demographic data, medical history, agent responsible for the allergic reaction, and pathologic findings at autopsy. A total of 18 cases of anaphylactic deaths were identified for the study period, including nine males and nine females, age range 33-76 years, mean 51.9 years. There were 10 reactions to drugs or contrast media (4 anaesthetic agents, 3 antibiotic, 2 IV contrast media, 1 streptokinase), four to bee/wasp venom, two to seafood, and two undetermined. Death occurred within 1 hour of onset of anaphylaxis in 12 cases. Findings at autopsy included non-specific pulmonary oedema and congestion (n = 13), laryngeal oedema (n = 5), cerebral hypoxia (n = 4) and cutaneous oedema (n = 1). Serum tryptase levels were measured in 15 cases, and were significantly elevated (>20 microg/L) in eight cases. Anaphylactic reaction is an uncommon cause of sudden death. In many cases, no specific macroscopic or microscopic findings were detected at autopsy. In the presence of a typical clinical history, postmortem measurement of serum tryptase levels can be a useful diagnostic aid.