Serum Anaphylaxis Research Articles

Platelet-activating factor acetylhydrolase is a biomarker of severe anaphylaxis in children.

There is limited ability to predict the severity of allergic reactions in children. Data derived predominantly from adults have implicated the platelet-activating factor pathway as a potential contributor to severe anaphylaxis. In this study, we sought to prospectively assess involvement of key components of the platelet-activating factor pathway in pediatric patients with anaphylaxis. Forty-six pediatric patients (<18years) presenting with acute anaphylaxis were assessed. Anaphylaxis severity was graded and serum anaphylaxis markers were measured acutely and in 36 children who returned for follow-up >4weeks after their acute presentation. These markers were compared with pediatric laboratory reference sera. Severe anaphylaxis was experienced by 12/46 (26%) and mild-moderate anaphylaxis in 34/46 (74%) children. Platelet-activating factor acetylhydrolase (PAF-AH) activity was inversely associated with severe anaphylaxis: 9/12 children with severe anaphylaxis had reduced PAF-AH activity as compared with 14/34 with mild-moderate anaphylaxis (p < .05). Furthermore, 3/3 children who required intensive care had markedly reduced mean PAF-AH (nmol/ml/min) (13.73, 95%CI: 7.42-20.03) versus 20/23 who required ward/emergency department care (17.81, 95%CI: 16.80-18.83; p < .05). In children with anaphylaxis, PAF-AH during acute anaphylaxis was unchanged relative to the child's basal levels (mean, 17.26, 95%CI: 16.10-18.42 vs 17.50, 95%CI: 16.21-18.78, p = .63) and was lower than healthy pediatric controls (mean 19.21; 95%CI:18.21-20.21; p < .05). Decreased serum PAF-AH activity is a biomarker of severe anaphylaxis. Levels of this enzyme do not change from basal levels during acute anaphylaxis. Our results show that PAF-AH is a biomarker of anaphylaxis severity in children. This key regulatory enzyme may modulate susceptibility to severe anaphylaxis.

Alternative anti-CD20 antibody versus desensitization for lymphoma patients with drug hypersensitivity reactions requiring discontinuation of rituximab, obinutuzumab, or ofatumumab.

8062 Background: Immunotherapy with anti CD20 is often associated with mild easily manageable infusion reactions. In rare cases, patients experience severe drug hypersensitivity reactions (DHR) serum sickness or anaphylaxis. These in turn may lead to discontinuation of the drug. In our experience, switching to a different anti-CD20 agent is a feasible alternative to discontinuation or desensitization protocols. Methods: From our pharmacology database we identified all the patients that received rituximab and/or obinutuzumab, and/or ofatumumab, and/or all the patients who received a flat dose of less than 50 mL of the same drugs and were followed at our institution. From the medical record, we identified all the cases where the anti-CD20 antibody was changed due to allergy, serum sickness or other types of DHR, and all those who received minimal doses of anti-CD20 in the context of a desensitization protocol. DHRs were evaluated either by an allergist, or by retrospective review following the World Allergy Organization guidelines. Our primary comparison, was to assess the proportion of pts able to completed planned infusion of abs using either approach (Fisher’s exact Test). Results: Among 343 patients receiving at least two different anti-CD20 antibodies or a flat dose of &lt; 50 mL, we identified 44 patients experiencing severe DHRs needing intervention. At the time of the reaction, 16 (36%) received the anti-CD20 as single agent, 24 (54%) in combination with chemotherapy, 4 (9%) in combination with ibrutinib or lenalidomide. In 9 (20%) patients the reaction was defined as anaphylactoid (8 rituximab; 1 obinutuzumab) and in 8 (18%) patients, all receiving rituximab, as serum sickness. Episodes of DHR were addressed with either desensitization (n = 29) or change of anti-CD20 agent (n = 25), 9 patients received both of these approaches, one patient switched anti-CD20 antibodies twice. Overall, 21 desensitizations were successful (72.4%), 8 failed; 23 changes of anti-CD20 were successful (92%) and 2 failed (p = 0.09). Conclusions: In patients with DHR use of an alternative anti-CD20 antibody is safe and is an alternative or complementary approach to anti-CD20 desensitization.

Prevention of tetanus during the First World War

The emergence of tetanus in wounded soldiers during the first months of the First World War (WWI) resulted from combat on richly manured fields in Belgium and Northern France, the...

The Three Ps: Unabridged

The circumstances and coincidences of life often lead us down strange and circuitous routes as we travel on this journey. How well I remember, as a fledgling first year medical student, having a Schick test placed on my arm as part of a laboratory exercise in an immunology course. The results, a large slough on my forearm, indicated that I was susceptible to diphtheria. Little did I realize then the importance of that name, nor was I aware of his contributions to the definition of serum sickness and anaphylaxis. But even more removed from the realm of possibility was to have imagined that I would one day have the privilege of standing before this distinguished body to honor the memory of Dr. Bela Schick. As I began searching for information about Dr. Schick, my secretary pulled from the shelf in our own office library a volume, published by Schering, that contains the first five Bela Schick lectures. Dr. Murray Peshkin delivered the first Bela Schick lecture to this body in 1968, followed by Howard Rapaport, John McGovern, Jerome Glaser, and Susan Dees. Most of them knew Bela Schick and had worked under him or had been inspired by him. Dr. John McGovern who spoke in 1970 began with these words of Dr. Schick: “First, the patient, second, the patient, third, the patient, fourth the patient, fifth the patient, and then maybe comes science. We first do everything for the patient; science can wait, research can wait.”1 Dr. McGovern noted that these are strange words for a great scientist. They become much less strange when we recognize the fact that Dr. Schick was also a great humanitarian with a particular genius to combine these two cultures in medicine in perfect harmony. The title of this presentation is “The three Ps: Unabridged.” These Ps could represent pollens, pets, and pests or providers, payors, and politicians, but instead they represent the three most important elements in our lives and work: PATIENTS, PHYSICIANS, AND PROFESSION. The word unabridged, which means to be whole, complete, uncut, leaving nothing out, suggests to us the way in which we should approach the three Ps. I hope to develop this theme as it pertains to us and our acknowledgment of these most important areas.

Effects of lead acetate on sensitivity to shock, intravascular carbon and endotoxin clearances, and hepatic endotoxin detoxification.

SummaryLead acetate iv at 5 mg/300 g to male rats of the Holtzman strain sensitized to the lethal shock induced by endotoxin, Noble-Collip tumbling trauma, hind limb ischemia, bowel ischemia, and horse serum anaphylaxis. Lead treatment depressed the intravascular phagocytic clearance of colloidal carbon as evaluated at 15, 30, 60, 120 and 240 min. By use of an endotoxin bioassay based on lethality in lead-treated assay rats, the intravascular removal of a test dose of 0.5 mg of endotoxin was not altered by lead treatment as compared to normal and sodium acetate treated controls. The ability of liver homogenates to detoxify endotoxin was not altered by lead administration at 0.5, 1, 2, 3, or 8 hr prior to sacrifice. The in vitro addition of lead to homogenates incubated with endotoxin did not alter detoxification. It is suggested that the mechanism of lead sensitization to endotoxin probably does not reflect alteration in its rate of clearance or detoxification but rather may relate to lead's ability to al...

Protection by histamine and metabolites in anaphylaxis, scalds, and endotoxin shock.

The release of toxic factors has been implicated in the mechanism of shock from various forms of trauma. If histamine (H) released after anaphylaxis, endotoxin shock, or thermal burns is a lethal factor in mice, priming with (H) before injury would presumably enhance mortality. Mice were pretreated with (H) or certain metabolites prior to inducing shock via horse serum anaphylaxis, scald injury, or lethal dose of E. coli endotoxin. Large doses of (H) did not enhance mortality; actually, mortality from these three forms of shock was lowered by pretreatment with (H) or imidazoleacetic acid, but not by other metabolites tested. The data, while unexplained, do not appear to support hypotheses assigning an active role to (H) release in these three forms of shock in mice.

Influences of epinephrine on the blood picture and the bone marrow in the experimental serum anaphylaxis

Influences of epinephrine on the blood picture and the bone marrow in the experimental serum anaphylaxis

FATAL ANAPHYLACTIC SHOCK

Deaths related to the injection of foreign protein in man are fortunately few. The exact number of such occurrences is difficult to estimate from the available literature. By 1942 Kojis1was able to find 61 such deaths, and he added 4 more from the Willard Parker Hospital. The most complete and most recent study of necropsies was made by Vance and Strassmann,2who added 7 autopsy studies from the Office of the Chief Medical Examiner to 19 taken from the literature. Park3in 1932 recorded the mortality from serum anaphylaxis as 0.002 per cent. Kojis1in 1942 found it to be just under 0.1 per cent in a series of 6,211 subjects treated for various infections. Rutstein and his associates,4in their analysis of pneumonia cases treated with antipneumococcus horse serum, found the mortality to be 0.45 per cent. In only 1 or possibly 2

血清過敏症に及ぼすHistotoxinの影響

The Histotoxin which has been already demonstrated by Miura, Yasuno and Uehara, is not only a significant substance in Pharmacology and Toxicology, but also is being used as drug in the Therapeutics, as it has been justified by a number of authors.The author observed the influence of Histotoxin upon the serum anaphylaxis and found the following experimental results.Guinea pig weighing 200g was used as the experimental animal. For the sensitization, fresh normal horse serum was injected subcutaneously, using 0, 25 cc per 100g of body weight, and reinjections were made intravenously 2 weeks later the same horse serum was injected, using 0, 5cc per 100g of body weight, and the anaphylatic shock was observed. 1) When the reinjection of the serum was performed, a typical anaphylatic shock followed and the mortality of the animals showed 100%. 2) After the sensitization, when Histotoxin-Ringer solution was injected subcutaneously daily, using 4 cc per 100g of body weight before the reinjection, the anaphylactic shock was inhibited. Especially, when Histotoxin-Ringer solution was injected 2 hours before the reinjection, using 8cc per 100g of body weight, the anaphylatic symptoms were definitely inhibited and the mortality was reduced markedly. 3) Normal Ringer solution which was injected daily or once 2 hours before reinjection, had no effect on the serum anaphylactic symptoms. 4) After the sensititization, Histamin chloride or Histidin chloride was injected daily or once 2 hours before the reinjection, it has no influence on the serum anaphylactic symptoms. The results of the above experiments lead to a conclusion that the Histotoxin inhibits definitely on the serum anaphylactic symptoms.

Acute edema of the pancreas, gall bladder, and stomach in serum anaphylaxis: Auer, J., and Krueger, H.: Proc. Soc. Exper. Biol. & Med. 46: 74, 1941

Acute edema of the pancreas, gall bladder, and stomach in serum anaphylaxis: Auer, J., and Krueger, H.: Proc. Soc. Exper. Biol. & Med. 46: 74, 1941

Acute Edema of the Pancreas, Gallbladder and Stomach After Histamine Injections

Since acute serum anaphylaxis produced well marked edema of some abdominal organs in the dog, it became desirable to test the effect of histamine in this direction, especially as a search of the literature gave no information on this question. Incidence. In 14 dogs, edema of the pancreas occurred 6 times; edema of the gallbladder 14 times; of the stomach 7 times. Degree of Edema. This varied as has been described in serum anaphylaxis; on the whole, it seemed not as strong as in the serum dogs, yet it must be noted that occasionally degrees of edema were seen in the pancreas, gallbladder and stomach that were equal to those observed in serum anaphylaxis. The location of edema was the same as in serum anaphylaxis. The edema fluid in all instances was clear and not bloody. The lymph glands between the pancreas and duodenum were brown red in color, and showed red areas on section; they were never black and hard as in serum anaphylaxis. The dogs were males and weighed between 6 and 8 kg; the histamine hydrochloride was infused into a jugular vein in a 0.1% solution using a Mariotte burette; the dose ranged between 2 and 6 mg per kg. Biopsy was performed within 30 minutes after the fall of blood pressure. Ether was discontinued as soon as the blood pressure had reached a low level.

Acute Edema of the Pancreas, Gallbladder and Stomach in Serum Anaphylaxis

As far as we are aware, the occurrence of acute edema of the gallbladder, pancreas and stomach has not been described as a consequence of serum anaphylaxis in the dog.Incidence. In 21 dogs, we observed edema of the pancreas 8 times; edema of the gallbladder-mucosa and adventitia 15 times; and edema of the stomach-submucosa 8 times.Degree of Edema. This varied considerably; in the pancreas the entire gland could be involved so that the lobules were separated by a clear, watery fluid; or the edema was largely limited to that portion closely adherent to the duodenum and antrum.The lymph glands between the pancreas and stomach were generally black, hard and gorged with blood. Other lymph glands of the viscera appeared normal.In the gallbladder the edema of the mucosa and adventitia varied between 1 and 3 mm in thickness; the fundus was chiefly involved and the edema was less on the body and apparently absent on the neck of the bladder.In the stomach, the edema was found chiefly in the submucosa of the antrum ...

THE PREVENTION OF ANAPHYLACTIC SHOCK

An analysis of anaphylactic reactions following pollen injections revealed that their principal cause is a too sudden absorption of larger amounts of pollen extract than the individual can tolerate. 1 It has been pointed out that, clinically, such reactions are identical with anaphylaxis which arises following injections of horse serum. Some investigators do not fully accept this view, principally because it is said that complete desensitization, which is possible in horse serum anaphylaxis, cannot be achieved in pollen sensitiveness. Since, however, the present conceptions on desensitization are vague, and, on the other hand, the mechanism arising in the two phenomena parallel each other so strikingly, I feel that experience gained from the study of pollen reactions will aid in the prevention of serum shock and vice versa. A brief review of what produces anaphylactic shock with pollen extracts is therefore given in table 1. A study of eight patients who

Encephalitic lesions in a case of serum anaphylaxis in a child of eight years: Bertoye, P., and Dechaume, J.: Lyon Méd. 144: 762, 1929

Encephalitic lesions in a case of serum anaphylaxis in a child of eight years: Bertoye, P., and Dechaume, J.: Lyon Méd. 144: 762, 1929

Erythrocyte Anaphylaxis in Dogs.

Dogs injected intraperitoneally with 0.5 cc. 50 per cent horse erythrocyte suspension per kilogram of body weight followed 24 hours later by an intravenous injection with the same dose, are almost invariably hypersensitive if tested after an incubation period of about 20 days. The shock thus produced, however, differs materially from the shock in canine serum anaphylaxis. In serum anaphylaxis, the characteristic precipitous fall in arterial blood pressure and the characteristic contraction of the urinary bladder do not begin till at least 45 to 60 seconds after commencing the intravenous protein injection. This is the time necessary for the formation or liberation of histamine-like depressor substances by the hypersensitive liver and their transmission to other parts of the body. In erythrocyte anaphylaxis (Fig. 1) both reactions begin within 15 to 20 seconds after commencing the intravenous corpuscle injection, the same time relations as those observed on intravenous injection with histamine. It is evident, therefore, that the characteristic reactions in erythrocyte anaphylaxis do not depend upon hepatic function, but are presumably due to immediate humoral or vaso-motor reactions. The above tracing represents the maximum reaction we have thus far obtained in canine erythrocyte anaphylaxis, corresponding roughly with the transcent clinical symptoms reported by Kritschewsky and Friede.

Specificity of Hepatic Anaphylatoxins.

In previous papers, it was shown (a) that normal canine organs transplanted by blood vessel anastomosis into horse serum hypersensitive dogs are thrown into typical histamine-like reactions by the toxic products (anaphylatoxins) explosively formed or liberated by the hypersensitive liver during acute anaphylactic shock in the recipient. (b) That immune organs similarly transplanted are completely resistant to the histamine-like action of these hepatic products. And (c) that this acquired anaphylatoxin insusceptibility is not due to circulating antibodies, since it can not be transferred from one animal to another by even massive immune blood transfusion. We have thought to throw light on the nature of hepatic anaphylatoxins by a study of the specificity of this acquired fixed tissue anaphylatoxin resistance. To do this, tissue transplantations have been made between dogs immunized and sensitized with different antigens. The following is a summary of our results to date: (1) Urinary bladders of goat serum immune dogs, transplanted into horse serum hypersensitive dogs, show no suggestion of an acquired immunity to the hepatic anaphylatoxins explosively formed or liberated during acute horse serum shock in the recipient. (2) Horse serum immune urinary bladders, transplanted into goat serum hypersensitive dogs, show no suggestion of an acquired immunity to the hepatic anaphylatoxins explosively formed or liberated during acute goat serum shock in the recipient. From this it is evident that the hepatic anaphylatoxins are of different chemical nature in goat serum and horse serum anaphylaxis. This finding is in accord with our working hypothesis, that hepatic anaphylatoxins are specific secondary antigens of complex protein nature, presumably denaturization products of the primary antigens used in sensitization and immunization.

ALLERGIC REACTIONS OF THE UPPER RESPIRATORY TRACT

It has become a common observation that a large percentage of people can be injured by contact with substances that are absolutely innocuous to others. Minute doses of an essentially inert substance have been known to produce violent reactions in a susceptible person. This peculiar reactivity has been referred to as idiosyncrasy, hypersensitiveness, anaphylaxis or allergy. The primary reactions of an allergic individual after contact with an exciting agent are manifested by local symptoms. When the contact is a very intimate one, general reactions result, and death may follow the entrance of a relatively small amount of the allergic substance. The studies of Walker, Goodale, Cooke, Duke, Kessler, Scheppegrell and others have demonstrated the allergic nature of hay-fever, as well as of many cases of asthma, urticaria and eczema. The present conception of the nature of allergic reactions is a development from the observations on serum anaphylaxis in lower animals.

The specificity of the desensitized state in serum anaphylaxis

Aside from the academic questions involved, there is an important practical problem which concerns the specificity of the desensitized state in anaphylaxis. If the occasional hypersensitiveness of man to serums which contain specific immune substances could be reduced or elimirtated, the safety of employment of such serums would be much enhanced. The danger of specific desensitization lies largely in the possibility of severe or even fatal shock during desensitization. Nonspecific desensitization might eliminate this danger. Although there are certain hypersensitive states to pure or relatively pure proteins, as for example, those of the vegetable pollens, the fatalities in man have so far resulted from injections of serum. We have therefore confined this study to serum anaphylaxis in the hope that ultimately a practical method may be devised for employment in man. It does not necessarily follow that results in animals, which have been artificially sensitized, are entirely applicable to natural hypersensitiveness in man, but there are instances of the acquired state in man which seem to be identical with that of animals and it has yet to be proved that natural hypersusceptibility differs materially. If, therefore, nonspecific desensitization in the acquired serum hypersusceptibility of animals can be demonstrated satisfactorily it is worthy of further trial in human experiments.

The mechanism of corpuscle and serum anaphylaxis in the rabbit

1. In rabbits dying acutely after a reinjection of corpuscles or after a primary injection of pig's corpuscles, the pulmonary circulation is found to be impermeable to saline solution under pressures so much greater than the maximal normal blood pressure in the pulmonary artery of that animal (over four times as great in some instances) that a sufficient immediate cause of death under these circumstances is seen in this physiologically complete interruption of the pulmonary circulation. 2. This obstruction of the pulmonary circulation is not due to an agglutination of the corpuscles and it may reasonably be referred to an effect on the muscular coat of the arterioles because the same phenomenon is produced by the injection of dissolved corpuscles and by the reaction of acute serum anaphylaxis—active and passive—and also by the introduction of the antigen into the pulmonary circulation after the latter has been perfused for five minutes with saline solution. 3. In the light of these observations, the local effect of Arthus would seem reasonably explicable as an area of infarction due to the interference with the blood supply to the area. 4. The cachexia and late death of rabbits in serum anaphylaxis offered, in the one instance of this kind, examined, a pathological picture consonant with the findings in acute anaphylaxis in the rabbit-the usual picture of a chronic interference with the circulation; namely, anasarca and greatly dilated right heart. 5. In the guinea-pig dying in acute anaphylaxis, the pulmonary circulation offers no increased resistance to the passage of fluid through it.

STUDIES ON BACTERIAL ANAPHYLAXIS AND INFECTION

STUDIES ON BACTERIAL ANAPHYLAXIS AND INFECTION