Leslie C. Grammer

Provocative challenge with local anesthetics in patients with a prior history of reaction

Possible allergic sensitivity to local anesthetic agents remains problematic for some patients who could benefit from their use. We retrospectively reviewed all our consultations for evaluation of local anesthetic allergy from 1965 to 1985 to assess the safety and efficacy of skin testing and provocative test dosing with a variety of local anesthetic agents. Fifty-nine patients reported 70 reactions from the administration of six different local anesthetics. Fifty-four patients could name one or more local anesthetic agents they believed were responsible, and five patients named only caine drugs. Multiple reactions of the same type to the same agent were considered as one reaction. On the basis of their history of reaction, the patients were categorized as follows: anaphylactoid reactions (urticaria, angioedema, wheezing, or hypotension within 1 to 2 hours of exposure), possible anaphylactoid reactions (tachycardia, dizziness, syncope, breathlessness, or pruritus occurring within 1 to 2 hours of exposure), contact dermatitis (a typical eczematous skin eruption after appropriate cutaneous sensitization), and other reactions (nonanaphylactoid reactions other than those already described or those occurring more than 2 hours after exposure). Fifty-nine patients were administered local anesthetics after skin testing and provocative test dosing, including two patients who required intravenous lidocaine (Xylocaine; Astra Pharmaceutical Products, Inc., Westboro, Mass.) acutely to control cardiac arrhythmias. These two patients had reported anaphylactoid reactions to oral antiarrhythmic drugs of the local anesthetic class. Despite the history of previous reactions, there were no positive skin tests or positive provocative drug challenges in any patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind histamine placebo—controlled trial of polymerized whole grass for immunotherapy of grass allergy

Twenty-six patients were recruited for a study of the safety and efficacy of immunotherapy with IPG. They were randomly assigned to two groups based on skin test titrations to grass allergens. One group was treated in a double-blind fashion before the 1982 grass season with 12 weekly injections totaling approximately 48,000 PNU, and the other group was treated with 12 weekly injections of caramelized glucose histamine placebo. Daily symptom and medication score sheets were completed by all patients each day of the grass season. Blocking antibody rose ninefold in the IPG group (p less than 0.007) but was unchanged in the placebo group. There was no significant change in IgE against rye grass group I in either the IPG or the placebo group. Symptom-score mean in the IPG group was 217 +/- 71 (S.E.M.), statistically lower (p less than 0.02) than the mean in the placebo group 496 +/- 117 (S.E.M.). There were no systemic reactions and only minor local reactions. There was no change in routine laboratory tests in either group. Although two prior studies with grass allergen immunotherapy reported efficacy, these studies did not use symptom-score analysis. This is the first double-blind, histamine placebo-controlled study of grass immunotherapy that demonstrates efficacy by symptom-score index evaluation. IPG is a safe, clinically effective, and potentially cost-effective therapy for grass pollinosis.

Persistence of efficacy after a brief course of polymerized ragweed allergen: A controlled study☆

Immunotherapy with PRW has been demonstrated to be safe and effective. To determine whether the efficacy would remain in successive ragweed seasons without further therapy, a trial was conducted comparing PRW to histamine placebo therapy in patients that had received courses of PRW previously. Those patients were also compared to previously untreated ragweed-sensitive patients. In a double-blind fashion, 21 previously treated patients were treated before the 1982 ragweed season with four injections of PRW therapy, whereas 21 previously treated patients were treated with four injections of placebo therapy. An additional control group of 21 previously untreated ragweed-sensitive patients received no injections. Daily symptom and medication score sheets were completed by patients each day of the ragweed season. Blocking antibody rose elevenfold with treatment (p less than 0.0001) in the PRW group. There was a statistically significant difference in symptom score mean between untreated patients (1007 +/- 174) and previously treated patients whether they received supplemental injections (554 +/- 180) (p less than 0.01) or whether they did not (650 +/- 168) (p less than 0.03). In summary the efficacy of 15 injections of PRW immunotherapy persists at least several years without need for supplemental immunotherapy.

Human antibodies against formaldehyde-human serum albumin conjugates or human serum albumin in individuals exposed to formaldehyde

Sera from patients undergoing hemodialysis with formaldehyde (F)-sterilized dialyzers were studied to determine if antibodies against F conjugated to human serum albumin (HSA) could be detected. F-human serum albumin (F-HSA) conjugates were prepared using ratios of F to HSA that did not precipitate the HSA. The F-HSA conjugates migrate differently electrophoretically than HSA with an increased negative charge of F-HSA as compared with HSA. The F-HSA was used in an ELISA. The results demonstrated that in certain sera, IgG, IgM, IgA and IgE antibodies against F-HSA could be measured. In the highest titered sera, it was shown that the IgG antibody was not directed against F alone or F-lysine but against an antigenic grouping of F-HSA. No correlation of either IgG or IgE antibodies with immune complex or allergic reactions was found in this series of dialysis patients. Some sera from dialysis patients had antibody activity against HSA. Sera from 2 physicians with rhinitis after F exposure had no antibody activity against F-HSA or HSA. Two nurses with a history of F-induced asthma had no IgG antibodies but did have IgE antibodies against F-HSA and HSA. This spectrum of immunologic responses is analogous to responses in dogs immunized with F or F dog albumin. We have not been able to identify anti HSA antibodies in patients reactive to other hapten-HSA compounds and it is suggested that anti HSA antibodies in F-exposed humans may relate to the F exposure.

IgE against ethylene oxide-altered human serum albumin in patients with anaphylactic reactions to dialysis☆

We have measured total antibody and IgE directed against ethylene oxide-altered human serum albumin (ETO-HSA) in the sera of 24 patients who have experienced anaphylaxis during hemodialysis and of 41 patients who have not had such episodes during hemodialysis. ETO is used to sterilize dialyzers and other medical equipment. The geometric mean level of IgE to ETO-HSA in patients with reactions (0.9 ng ETO-HSA bound to IgE per milliliter of serum) is significantly higher than in nonreacting patients (0.1 ng/ml, p less than 0.0001). Sixteen of 24 patients with reactions had detectable levels of IgE to ETO-HSA, whereas only three of 41 nonreacting patients had detectable levels (p less than 0.0001 chi-square). The geometric mean level of total antibody to ETO-HSA is also significantly higher in patients with reactions (270 ng ETO-HSA bound per milliliter) than in nonreacting patients (31 ng/ml, p less than 0.0001). Fourteen of 24 patients with reactions but only four of 39 nonreacting patients had total antibody binding of ETO-HSA (p less than 0.0001 chi-square). These data extend our previous observations on a small group of 13 patients receiving hemodialysis (seven patients with reactions, and six nonreacting patients) and clearly demonstrate an association between the presence of IgE or total antibody to ETO-HSA and immediate anaphylactic reactions in this group of 65 patients receiving hemodialysis.

IgE against ethylene oxide-altered human serum albumin patients who have had acute dialysis reactions

Serum samples obtained from seven hemodialysis patients with immediate-type allergic reactions, from six hemodialysis patients without reactions, and from three nonatopic control subjects were analyzed for IgE against human serum albumin exposed to ethylene oxide (ETO-HSA). ETO is used to sterilize medical equipment like dialyzers that cannot withstand heat sterilization. IgE to ETO-HSA, measured by a polystyrene tube technique was found in six of seven dialysis reactor patients but in only one of six nonreactor patients (p less than 0.05 two-tailed Fishers exact test). No control sera from three nonatopic individuals had antibody. The reactor patients had 2.0 +/- 8.0 ng (SD) of ETO-HSA bound per milliliter of serum, whereas nonreactor patients had 0.2 +/- 8.0 ng per milliliter bound (p less than 0.05 one-tailed Students t test on log transformed values). We suggest that there is an association between the presence of IgE to ETO-HSA and immediate-type allergic reactions to dialysis in this group of patients.

A double-blind placebo-controlled trial of polymerized whole grass administered in an accelerated dosage schedule for immunotherapy of grass pollinosis☆

Forty-four patients were entered into a study of the efficacy and safety of individually polymerized grass (IPG) immunotherapy with an accelerated dosage schedule. Patients were paired on the basis of cutaneous end point titrations to timothy, orchard, and Bermuda grass-pollen extracts. In a double-blind manner, one patient in each pair was treated in nine weekly visits with 13 injections that totaled 24,000 PNU of each grass to which the patient had cutaneous reactivity. The other patient in each pair received caramelized glucose histamine placebo. Symptom and medication score sheets were completed by 33 patients each day of the grass season. Blocking antibody rose significantly in the IPG-treated group but was unchanged in the placebo-treated group. By Wilcoxon paired signed-rank test, the symptom medication scores in the IPG-treated group were significantly lower than those in the placebo-treated group. There were no systemic reactions and no clinically significant changes in routine laboratory tests in either group. In summation, this study demonstrates the safety, immunogenicity, and efficacy of IPG therapy in an accelerated dosage schedule for treatment of grass pollinosis.

Drugs that may exacerbate myasthenia gravis.

Myasthenia gravis is an uncommon disease. The emergency physician should be cautious when prescribing medications to myasthenics for problems not related to myasthenia gravis. We have discussed some of those agents (Figure 3) that are recognized to cause exacerbation of MG or that may have the potential to exacerbate MG. We recommend that management of any medical or surgical problem of the myasthenic be done in consultation with a managing neurologist, and that either early follow-up or admission is necessary when these agents are used in the patient with myasthenia gravis.

Toluene diisocyanate respiratory reactions. I. Reassessment of the problem.

A series of workers with exposure to and respiratory symptoms from toluene diisocyanate (TDI) was compared with a group of exposed, asymptomatic workers and with normal controls using immunologic and clinical evaluations. Improved understanding of TDI-induced respiratory disease may best be achieved by categorizing the symptomatic workers into at least 3 and possibly 4 groups: immunologic TDI asthma; pre-existing chronic respiratory disease exacerbated or unaffected by TDI; asthma coincidental with TDI exposure, and possibly TDI respiratory disease secondary to toxic or inflammatory mechanisms.

Characterization of an antigen in acute anaphylactic dialysis reactions: ethylene oxide-altered human serum albumin.

Anaphylactic reactions to dialysis have been associated with antibody to human serum albumin (HSA) that has been reacted with ethylene oxide (ETO). ETO, an agent used to sterilize dialyzers, is a potent alkylator of proteins. We have studied the antigenic characteristics of ETO-HSA. By use of immunoelectrophoresis we have demonstrated differences in electrophoretic mobility between HSA and ETO-HSA. By gel chromatography we have observed an apparent increase in the molecular weight of ETO-HSA as compared to HSA. Antigenic activity of ETO-HSA as determined by the technique of Lidd and Farr is found in all molecular weight fractions. Cutaneous reactivity to ETO-HSA can be transferred to subhuman primates. That reactivity is lost if the sera are heated to 56 degrees C for 4 hours. Antibody activity to ETO-HSA cannot be inhibited by ETO-glycine or HSA but can partially be inhibited by ETO-polylysine or ETO-ovalbumin. This suggests that antibody is directed against a new antigenic determinant on the ETO-protein moiety, probably an ETO-amino acid determinant like lysine.