Ethylene oxide allergy in children with spina bifida.

BACKGROUND: Allergic reactions to ethylene oxide (EtO-treated products have occurred in several children with myelomeningoceles. OBJECTIVE: The object of this study was to define the prevalence and significance of EtO-specific IgE among the children in our myelomeningocele clinic. METHODS: The study population comprised three groups: children clinic. METHODS: The study population comprised three groups: children with myelomeningoceles, chronically ill controls (defined as children who had undergone at least three major operations), and well-child controls. Serum specimens were collected from each child, and a commercially available ELISA designed to identify IgE directed against both EtO and latex was performed on the specimens. RESULTS: Seventeen of 75 (23%) children with myelomeningoceles had antibodies directed against EtO, as did 1 of 26 (4%) chronically ill controls. None of the 25 well controls had detectable levels of anti-EtO IgE. Children with antibodies directed against EtO were more likely to be atopic (p = 0.007) and to have a shunt (p = 0.021) and were markedly more likely to have antibodies directed against latex (p = 0.001). On average they had undergone more shunt revisions and other operations than had children without anti-EtO antibodies. CONCLUSION: During the period of study no child had anaphylaxis thought to have been due to EtO exposure.

The role of ethylene oxide allergy in sterile shunt malfunctions.

Failure of an intact ventriculoperitoneal shunt, in the absence of an overt infection, is often due to its occlusion by cellular debris and/or an abdominal pseudocyst. This failure is thought to be caused by an infection by an organism which is difficult to culture or by some poorly defined allergic response to the shunt materials. Little attention has been directed to the treatment that the shunts receive prior to implantation: specifically, their exposure to ethylene oxide as a means of sterilization. We have found ethylene oxide metabolites in the spinal fluid of children with shunt malfunction months after their systems were implanted. Many of these patients had coincident CSF eosinophilia. In addition, two of the children had detectable serum IgE antibody directed against an albumin-ethylene oxide conjugated protein. Both of these children had several shunt malfunctions within a short period, yet neither child could be shown to have a shunt infection despite multiple cultures. We therefore suggest that in some patients proteins altered by ethylene oxide incite an IgE mediated response which may lead to shunt malfunction.

[IgE-mediated allergy to ethylene oxide in hemodialyzed patients]. / Allergia IgE-mediata verso l'ossido di etilene nei pazienti emodializzati.

Ethylene oxide (ETO) is widely employed in sterilization of hemodialysis materials. Many studies have shown that ETO may act as an antigenic compound when bound to human albumin, therefore eliciting allergic reactions during hemodialysis. In the present study, we investigated in 93 patients undergoing long-term hemodialysis the prevalence of sensitization to ETO. All the patients were investigated for the presence of allergic or pseudo allergic reactions during the treatment. Specific IgE to ETO were found in sera of 3 patients: 1 suffered from urticaria and 1 from glottic edema and hypotension during the dialysis. The third one had non symptoms. The employ of a gamma-rays sterilized filter determined the disappearance of clinical manifestations in the two symptomatic patients, therefore suggesting a pathogenetic role of the specific IgE to ETO in determining the clinical manifestations.

[Sensitization to ethylene oxide: a possible cause of reactions in hemodialysis patients]. / Sensibilizzazione verso l'ossido di etilene: una possibile causa di reazioni nei pazienti in emodialisi.

147 hemodialyzed patient were studied for the presence of allergic reactions related to the dialytic treatment. Total IgE and specific IgE to common inhalants, ethylene oxide and phthalic anhydride were determined in all patients. The same determinations were also performed in two control groups. Specific IgE to ethylene oxide were detected in 7 sera. Among these 6 had a high total IgE level and 2 had a positive Phadiatop. Only 3 among the 7 positive patients had adverse reactions related to the hemodialysis (one suffered from itching, one from urticaria and the third from angioedema and hypotension). The resolution of the symptoms was obtained utilizing a gamma-rays sterilized filter. Therefore ethylene oxide sensitization may be a cause of some problems during hemodialysis. We couldn't find a relationship between atopic status and sensitization to ethylene oxide in as much in only 2 out of 7 patients sensitized to ethylene oxide, specific IgE to common inhalants were detected.

Hypersensitivity reactions during haemodialysis: role of complement fragments and ethylene oxide antibodies.

IgE-antibodies against ethylene oxide (EtO) and activation of the complement system have been suspected as causative factors for acute hypersensitivity reactions at the onset of haemodialysis. The present study was conducted to determine which of the two mechanisms is mainly responsible for the occurrence of reactions. According to clinical criteria, 13 of the 129 patients studied were identified as having suffered from at least one episode of acute hypersensitivity. Seven of them experienced severe symptoms, including five with elevated circulating serum EtO antibodies. Of the remaining six patients who experienced moderate symptoms, only one had elevated serum EtO antibodies, and of the 114 patients not exhibiting symptoms, two had enhanced serum concentrations of EtO antibodies. In-vivo complement activation was determined during haemodialysis by measurement of both C3adesarg and C5adesarg fragments. No differences in the onset levels and the degree of complement activation were found between patients suffering from severe, moderate, or no hypersensitivity reactions. In-vitro activation of the complement cascade by zymosan, measured in plasma samples obtained from patients prior to dialysis, revealed no differences in the extent of C3adesarg generation. Finally, we determined the activity of the C3a- and C5a-inactivating enzyme, carboxypeptidase N1 (CN1), in plasma samples of patients both with and without hypersensitivity reactions. No difference in the CN1 activity between the two groups of patients was found. These data lead us to conclude that sensitisation to ethylene oxide is responsible for the majority of severe hypersensitivity reactions in haemodialysis patients. However, a small subgroup of patients having anaphylactoid reactions displayed neither elevated serum EtO antibodies with excessive complement activation nor a tendency towards reduced inactivation of anaphylatoxins.

Longitudinal study of specific IgE and IgG antibodies in a patient sensitized to ethylene oxide through dialysis.

IgE and IgG antibodies to ethylene oxide (EO) were monitored by RAST and by ELISA in serum from a patient with hypersensitivity reactions during hemodialysis. Serum samples from the patient covering a 7-year period were analyzed. The changes in titers of IgE and IgG antibodies correlated to the time of EO exposure as well as to clinical symptoms. EO-specific IgG antibodies were, however, also found in sera from hemodialysis patients without any hypersensitivity symptoms. Assay of specific IgG antibodies will only indicate whether a patient has been exposed to, and immunostimulated by, EO, whereas specific IgE antibodies appear to be clearly related to hypersensitivity symptoms. The hapten and carrier specificity of EO-induced IgE antibodies was studied. The antibodies were found to be solely hapten specific because carriers of different types could be used in RAST without changing the outcome of the test. The existence of new antigenic determinants related to the carrier could not be demonstrated.

[Ethylene oxide-induced antibodies and hypersensitivity reactions in hemodialysis]. / Athylenoxidinduzierte Antikörper und Hypersensitivitätsreaktionen während Hämodialyse.

The presence of antibodies against ethylene oxide, which is used for sterilization of dialyzers, was evaluated in 52 hemodialysis patients (30 male, 22 female). The aim of the prospective study was to evaluate a possible correlation of these antibodies with hypersensitivity reactions during hemodialysis. By means of a radio-allergo-sorbent-test (RAST) only 3.9% (2 patients) were detected to have ethylene oxide antibodies. There was no significant correlation between antibodies on the one hand, and symptoms, eosinophilia and IgE-elevation on the other hand. We could not find ETO-induced hypersensitivity reactions in our study population. Thorough rinsing and sufficient storage time of the dialyzers might be the reasons for these findings.

Ethylene oxide sensitivity in hemodialysis patients.

Sera from 138 patients who had experienced hypersensitivity-type reactions while on hemodialysis (reactors) were examined retrospectively by the radioallergosorbent test (RAST) for specific IgE antibody to ethylene oxide (ETO). Seventy-eight hemodialysis patients without a history of reaction were also evaluated as controls. Elevated serum RAST values (greater than 2.0) were more common in reactors (63%) than in controls (11%, p less than 0.001). In a second study, RAST assays were performed using human serum albumin conjugated to ETO (HSA-ETO) as antigen and also using a concentrate of fluid used to rinse ETO-sterilized dialyzers ("dialyzer extract") as antigen. The RAST ratios obtained with HSA-ETO were similar to those obtained using the dialyzer extract (rank order correlation coefficient = 0.829, p less than 0.001). In a third study, RAST inhibition was demonstrated both by HSA-ETO and dialyzer extract. Our results, extending previously published reports, suggest that hypersensitivity to ETO might play an important role in hemodialysis-associated hypersensitivity-type reactions.

IgE against ethylene oxide-altered human serum albumin (ETO-HSA) as an etiologic agent in allergic reactions of hemodialysis patients.

Ethylene oxide (ETO) is used to sterilize hemodialyzers and other medical equipment. In an attempt to confirm a link between ETO and hypersensitivity reactions during hemodialysis (HD) we quantitated IgE and total antibody directed against ETO-altered human serum albumin (ETO-HSA) in the sera of 65 hemodialysis patients. In 24 patients who had experienced anaphylaxis during HD, the levels of IgE and total antibody against ETO-HSA were significantly higher than the corresponding levels in 41 patients who had not. Our data demonstrate an association between the presence of IgE and total antibody against ETO-HSA and immediate anaphylactic reactions to HD. In further studies we characterized the ETO-HSA antigen by immunoelectrophoresis, gel filtration chromatography, and cross-inhibition immunoassay. Our results suggested that ETO gas can alter HSA and induce new antigenic determinants on the molecule. Recently, we encountered a peritoneal dialysis patient with rash and eosinophilia. Suspecting ETO allergy, we measured serum IgE and total antibody to ETO-HSA and found both to be present. The data suggest that, in addition to the familiar HD reactions, ETO sensitization might cause other allergic diseases as well.

Ethylene oxide (ETO) as a major cause of anaphylactoid reactions in dialysis (a review).

Ethylene oxide (ETO), an alkylating compound of high chemical reactivity, is widely used for gas sterilization, but recently serious ETO side reactions have been recognized. With chronic ETO exposure, increased spontaneous abortion, sister chromatid exchange, and leukemia are observed. After medical use of ETO outside nephrology, contact dermatitis, cardiopulmonary shock (during cardiopulmonary surgery), allergic local reactions to ETO sterilized lenses, and anaphylactoid reactions to ETO sterilized catheters have been described. In numerous dialysis patients widespread hypersensitivity to ETO has been documented by skin prick test and ETO radioallergosorbent test (RAST). Furthermore an anaphylactoid "first-use reaction" was described in dialyzed patients, most of whom were using hollow-fiber dialyzers. After long discussions whether complement activation versus hypersensitivity is the cause of such acute anaphylactoid reactions, more recent studies using either ETO RAST or basophil degranulation tests implicate ETO hypersensitivity as their major cause. The high prevalence of sensitization to ETO and the frequency, unpredictability, and potential danger of anaphylactoid reactions to ETO lead to the conclusion that ETO sterilization of dialyzers should be discontinued, since alternative modalities of sterilization are currently available.

Mediation of hypersensitivity reactions during hemodialysis by IgE antibodies against ethylene oxide.

Sera from 329 hemodialysis patients, 46 of whom had experienced a hypersensitivity-type reaction during hemodialysis, were screened by an enzyme-allergosorbent test (EAST) for IgE antibodies specific for ethylene oxide (ETO). In seven of nine patients who had experienced a severe hypersensitivity reaction (type II or type III), high titers of IgE antibodies against ETO (greater than 3.0 PRU/mL) were found. However, plasma levels of IgE specific for ETO were in the normal range (less than 0.35 PRU/mL) in most (30/37) patients who had experienced a mild (type I) reaction. Selected sera from patients who had experienced severe reactions were further examined for IgE directed against isopropyl myristate (IPM), 2-chloroethanol, and extracts from unsterilized dialyzers. Importantly elevated serum levels of specific IgE against these substances could not be documented. Extracts of an ETO-sterilized, hollow-fiber dialyzer were positive, whereas extracts of an ETO-sterilized dialyzer containing a flat membrane were negative in the EAST. This difference can be explained by the different amounts of ETO present in the dialyzers. We conclude that ETO causes most severe hypersensitivity reactions by an IgE-mediated mechanism. On the other hand, the pathogenesis of mild (type I) reactions is less clearly associated with ETO allergy. Our results also suggest that other potentially allergenic substances in dialyzers (e.g., IPM, 2-chloroethanol) rarely induce specific IgE antibodies in dialysis patients.

Sensitization of repeat plasmapheresis donors to ethylene oxide gas.

Repeat plasma donors were studied to determine whether there was a relationship between allergic-type reactions during plasmapheresis and IgE-dependent sensitization to ethylene oxide gas used for sterilization of disposable fluid administration sets. Serums from 32 donors with allergic-type reactions and 84 donors who had no reactions but were exposed to the same materials and served as controls were tested for IgE-antibodies to ethylene oxide. The results, expressed as an IgE ethylene oxide index, were greater than 2 in 78 percent of serums from donors with allergic reactions and 12 percent of serums from controls. This association was significant (p less than 0.0001). Reactivity of the antibodies was directed against an ethylene oxide-human serum albumin conjugate and not against human serum albumin carrier protein. IgG antibodies with ethylene oxide specificity also were present in the serums of repeat plasmapheresis donors. Each of seven rabbits immunized with an ethylene oxide-protein conjugate responded with a high serum level of antibody with ethylene oxide specificity. It was concluded that the residual ethylene oxide in fluid administration sets is immunogenic and may cause allergic reactions in plasma donors.