Delayed-type hypersensitivity to subcutaneous enoxaparin

Background Enoxaparin and other low-molecular-weight heparins are widely used to prevent and treat thromboembolic disorders. Cutaneous reactions secondary to enoxaparin injections include delayed hypersensitivity skin reactions described as erythematous, infiltrated plaques at injection sites. We studied three cases of erythematous infiltrated plaques after enoxaparin injection in order to establish the allergenic importance of this low-molecular-weight heparin.
Methods Patch tests were performed with sodium heparin, calcium heparin, calcium enoxaparin, and calcium nadroparin, A subcutaneous test with calcium heparin and an intravenous challenge test with sodium heparin were done, A punch biopsy was obtained from an erythematous plaque in one patient.
Results Patch tests were negative to calcium heparin in all patients, positive t o enoxaparin and nadroparin in two patients, and positive to sodium heparin i n one patient. In two patients, the subcutaneous challenge test was positive, the intravenous challenge test was negative, and the histopathologic appearance of the biopsy resembled a delayed-type hypersensitivity reaction. Conclusions TTiese cases provide evidence of type IV hypersensitivity and the possibility of crossed-allergenicity among unfractionated heparin and low-molecular-weight heparins. We show that the subcutaneous challenge test is the most reliable diagnostic measure.     

Association of heparin‐induced skin lesions, intracutaneous tests, and heparin‐induced IgG

BACKGROUND: Cutaneous heparin-induced allergic reactions to subcutaneous heparin may begin 2-5 days after administration. The relation of the delayed-type hypersensitivity and a systemic immunologic response is controversial. The present investigation aimed to analyze the occurrence of thromboembolic complication, pathologic heparin-induced platelet activation (HIPA), and the presence of circulating heparin-induced IgG in patients with heparin-induced skin reactions. METHODS: Intracutaneous tests, HIPA assay, and heparin-heparin IgG antibodies were performed in nine patients with heparin-induced skin lesions. RESULTS: Six of eight patients showed positive intracutaneous tests to heparin and to four low-molecular-weight heparins. Three of six heparin-positive patients presented hypersensitivity to a heparinoid, too. Two of three patients had a positive HIPA test and elevated heparin-induced IgG antibodies. Both patients developed complications presenting as heparin-induced skin necrosis or arterial thrombosis. Two of nine patients were treated with danaparoid, 4/9 patients received r-hirudin, and 1/9 received oral coumarin. In 2/9 patients, anticoagulant therapy was stopped, but these patients will receive r-hirudin if indicated. CONCLUSIONS: On the basis of the coincidence of local and systemic hyperreactivity to heparin and danaparoid, patients with heparin-induced skin lesions should receive r-hirudin, a nonheparin compound, for anticoagulant treatment.     

Late-onset anaphylaxis to fermented soybeans: the first confirmation of food-induced, late-onset anaphylaxis by provocation test.

BACKGROUND: Late-onset anaphylactic reactions without early-phase reactions are rarely reported. The hypothesized mechanism of late-onset anaphylaxis to fermented soybeans is delayed absorption or release into the bowel rather than an immunologic phenomenon. OBJECTIVES: To investigate the mechanisms of late-onset anaphylaxis to fermented soybeans in 2 patients and to characterize the allergens involved in anaphylaxis caused by fermented soybeans. METHODS: Two patients underwent skin prick-by-prick tests with fermented soybeans as is. We used an open challenge for the provocation test of anaphylaxis and measured changes in plasma histamine, plasma tryptase, serum eosinophil cationic protein, and plasma leukotriene B4 levels in 1 patient. In addition, specific IgE against fermented soybeans and the allergens of fermented soybeans were detected by enzyme-linked immunosorbent assay and immunoblotting, respectively. RESULTS: The results of the prick-by-prick tests with fermented soybeans as is were positive in both patients and negative in control subjects. The challenge with 50 g of fermented soybeans caused generalized urticaria and dyspnea 13 hours after ingestion of fermented soybeans in 1 patient. In addition, his plasma histamine and tryptase levels transiently elevated during the anaphylactic event. In enzyme-linked immunosorbent assay, the patients showed elevated IgE levels to the proteins of fermented soybeans. Serum IgE antibodies of patients 1 and 2 were bound to approximately 5- and 26-kDa proteins in immunoblotting of fermented soybeans, respectively. CONCLUSION: To our knowledge, this is the first report of late-onset anaphylaxis provoked by the challenge test half a day after ingestion of fermented soybeans.     

The Utility of Serum Tryptase in the Diagnosis of Food-Induced Anaphylaxis

Purpose

This study investigates the utility of serum tryptase for the confirmation of shrimp-induced anaphylaxis.

Methods

Patients with a history of shrimp allergy and positive skin prick tests (SPT) to commercial shrimp extract were recruited for shrimp challenges. Serum total tryptase was obtained at baseline and 60 min (peak) after the onset of symptoms.

Results

Thirty-nine patients were challenged. There were 12 patients with anaphylaxis, 20 with mild reactions and 7 without symptoms (control group). Characteristic features and baseline tryptase were not different among the 3 groups. The peak tryptase levels were higher than the baseline in anaphylaxis and mild reaction groups (P<0.05). The delta-tryptase (peak minus baseline) and the tryptase ratio (peak divided by baseline) in the anaphylaxis group were higher than the mild reaction and control groups (P<0.01). The optimum cut-off for peak tryptase to confirm anaphylaxis was 2.99 µg/L with 50% sensitivity, 85% specificity, 3.33 positive likelihood ratio (LR) and 0.59 negative LR. The manufacturer''s cut-off for peak tryptase was >11.4 µg/L with 17% sensitivity, 100% specificity, infinity positive LR and 0.83 negative LR. The best cut-off for delta-tryptase was ≥0.8 µg/L with 83% sensitivity, 93% specificity, 11.86 positive LR and 0.18 negative LR. The best cut-off for tryptase ratio was ≥1.5 with 92% sensitivity, 96% specificity, 23 positive LR and 0.08 negative LR.

Conclusions

The peak tryptase level should be compared with the baseline value to confirm anaphylaxis. The tryptase ratio provide the best sensitivity, specificity, positive and negative LR than a single peak serum tryptase for the confirmation of shrimp-induced anaphylaxis.     

Successful desensitization with un-fractionated heparin in a patient with heparin allergy and tolerance to fondaparinux

Immediate hypersensitivity to low molecular weight heparin (LMWH) is rare, and we present here a case with an anaphylaxis-like symptoms to enoxaparin. The diagnosis of hypersensitivity to enoxaparin was confirmed by the clinical picture and positive skin tests. In this case, palmo-plantal itching after application of heparin was an early sign of immediate type hypersensitivity. His skin and provocation tests showed cross-reactivity with other types of LMWHs and un-fractionated heparin (UFH). Fondaparinux and desensitization with UFH were found to be safe alternative treatment options in this patient with heparin allergy.     

Intraoperative anaphylaxis to bacitracin during pacemaker change and laser lead extraction.

BACKGROUND: Bacitracin is widely used in operating rooms to soak implants, irrigate compound fractures, and apply to surgical incisions. However, bacitracin is a known sensitizer and causes not only allergic contact dermatitis but also anaphylaxis. OBJECTIVE: To describe a 72-year-old woman with anaphylaxis after irrigation and packing of an infected pacemaker pocket with a bacitracin solution. METHODS: Skin prick testing to bacitracin and latex; serum tryptase, serum histamine, serum IgE to latex, and serial cardiac enzyme measurements; blood cultures, transthoracic echocardiograms, and venograms were performed to characterize the reaction. RESULTS: Six hours after the anaphylactic event, the patient had an elevated serum tryptase level of 49 ng/mL (reference range, 2-10 ng/mL), which normalized the next morning. She had immediate-type skin prick test reactions to full-strength bacitracin ointment (500 U/g) and bacitracin solution (150 U/mL). Serum IgE level to latex was undetectable, and results of skin testing to latex were negative. CONCLUSIONS: To our knowledge, this is the first case report of anaphylaxis to bacitracin during pacemaker surgery. This case illustrates that intraoperative anaphylaxis to bacitracin can be life-threatening.     

Anaphylaxis to Patent Blue V. I. Clinical aspects

Background:  The dye Patent Blue V (PBV) is increasingly used for staging procedures in operable breast cancer, but is reported to cause adverse reactions. The aim of this study was to present the clinical features and the results of follow-up examinations in patients with such reactions.
Methods:  We studied nine patients with hypersensitivity reactions to PBV between 1999 and 2006 who were identified through the Norwegian network for reporting and investigating allergic reactions during anesthesia.
Results:  We observed incidences of 0.5% (7/1418) for all kinds of PBV reactions and 0.4% (5/1418) for anaphylaxis. Typical clinical features included: (i) cardiovascular and/or cutaneous symptoms, (ii) a delay in symptoms, compared to the time of dye injection, (iii) poor response to ephedrine and intravenous fluid, and (iv) need for adrenaline administration, sometimes prolonged, for circulatory stabilization. Cutaneous manifestations were noted in five of the seven patients with anaphylaxis and two additional patients without circulatory instability. During anaphylactic reactions, serum tryptase was increased in six patients and normal in one. Serum tryptase was normal in one patient with skin symptoms only. Skin prick tests to PBV were positive in all eight patients tested, including the two with skin manifestations only.
Conclusion:  The clinical features and the results of follow-up studies strongly suggest that these reactions are IgE mediated.     

Clinical presentation and time course in hypersensitivity reactions to beta-lactams

Background:  β-lactam hypersensitivity reactions are classified as immediate or nonimmediate. Diagnosis is usually based upon skin tests and provocation challenges.
Objective:  The time course of the reactions in proven β-lactam hypersensitivities was studied and then correlated with the symptoms to determine the relationship between the clinical presentations and the time course.
Method:  All of the patients who consulted between 1996 and 2004 for a suspected β-lactam hypersensitivity reaction were studied. Two hundred and ten patients with a proven hypersensitivity reaction diagnosed according to the European Network on Drug Allergy were included in the present study.
Results:  Of the patients, 36.7% had urticaria as a single symptom, 19.1% anaphylaxis without shock, 17.6% anaphylactic shock and 19.1% maculopapular exanthema. Anaphylactic shock and anaphylaxis mostly occurred within 1 h after drug administration. Exanthema mainly occurred after 24 h. Urticaria as a single symptom occurred at any time. A firm diagnosis was determined using immediate-reading skin prick (10.0%) and intradermal tests (38.1%), late-reading skin tests (19.1%) or provocation tests (32.9%).
Conclusion and clinical implication:  Depending on the time course of the reaction, three clinical groups were identified: anaphylaxis and anaphylactic shock (immediate reaction); maculopapular exanthema (late reaction) as well as urticaria (immediate and late reaction).     

Cutaneous manifestations in Hymenoptera and Diptera anaphylaxis: relationship with basal serum tryptase

Objectives To compare the clinical presentation of systemic anaphylaxis to Hymenoptera and Diptera with regard to basal serum tryptase (BT) and to evaluate mastocytosis in patients with elevated tryptase.
Patients and Methods The medical records of 140 patients with a history of a systemic reaction to venom were retrospectively reviewed. Symptoms and severity of anaphylaxis and BT were recorded. Most patients with elevated tryptase were screened for mastocytosis: a dermatological examination with a skin biopsy was performed in 19 cases and a bone marrow biopsy in 14 cases.
Results Tryptase was elevated in 23 patients. These patients reported fewer usual skin reactions (urticaria in 26.1% of cases with raised tryptase vs. 76.1% of cases with normal tryptase), more flushing (52.2% vs. 4.3%) and frequently did not present skin reaction (26.1% vs. 9.4%). They presented a more severe reaction (mean grade of severity: 3.48 vs. 2.69). Mastocytosis was diagnosed in seven patients with elevated tryptase: indolent systemic mastocytosis in six cases and cutaneous mastocytosis without systemic involvement in one case. In five cases, mastocytosis was previously undiagnosed. Lesions of cutaneous mastocytosis, diagnosed in five patients, consisted of urticaria pigmentosa in all cases and were often inconspicuous.
Conclusion These results demonstrate particular clinical features of the allergic reaction in patients with elevated BT and the higher frequency of mastocytosis in this population. In patients with a severe anaphylactic reaction without urticaria, but with flushing, tryptase should be assayed and an underlying mastocytosis should be considered.     

A Case of Levofloxacin-Induced Anaphylaxis With Elevated Serum Tryptase Levels

Levofloxacin, a fluoroquinolone and L-isomer of the racemate ofloxacin, has been approved for the treatment of acute and chronic bacterial infections. Gastrointestinal complaints are the most frequently reported adverse drug reactions to fluoroquinolones. Other adverse events include headache, dizziness, increased liver enzyme levels, photosensitivity, tachycardia, QT prolongation, and eruptions. Anaphylaxis has been documented as a rare adverse drug reaction to levofloxacin; however, diagnostic tests are needed to evaluate whether these reactions are the result of levofloxacin treatment. While the results of skin tests are considered unreliable due to false-positive responses, the oral provocation test is currently considered to be the most reliable test. Tryptase, a neutral protease, is the dominant protein component of secretory granules in human mast cells, and an increased serum concentration of tryptase is a highly sensitive indicator of anaphylaxis. Herein, we report a case of levofloxacin-induced anaphylaxis in which the patient exhibited elevated serum tryptase levels and a positive oral levofloxacin challenge test result. As anaphylaxis is potentially life-threatening, the administration of fluoroquinolones to patients who have experienced a prior reaction to this type of agent should be avoided.     

Elevated basal serum tryptase and hymenoptera venom allergy: relation to severity of sting reactions and to safety and efficacy of venom immunotherapy

BACKGROUND: Mastocytosis and/or elevated basal serum tryptase may be associated with severe anaphylaxis. OBJECTIVE: To analyse Hymenoptera venom-allergic patients with regard to basal tryptase in relation to the severity of sting reactions and the safety and efficacy of venom immunotherapy. METHODS: Basal serum tryptase was measured in 259 Hymenoptera venom-allergic patients (158 honey bee, 101 Vespula). In 161 of these (104 honey bee, 57 Vespula), a sting challenge was performed during venom immunotherapy. RESULTS: Nineteen of the 259 patients had an elevated basal serum tryptase. Evidence of cutaneous mastocytosis as documented by skin biopsy was present in 3 of 16 patients (18.8%). There was a clear correlation of basal serum tryptase to the grade of the initial allergic reaction (P<0.0005). Forty-one of the 161 sting challenged patients reacted to the challenge, 34 to a bee sting and 7 to a Vespula sting. Thereof, 10 had an elevated basal serum tryptase, i.e. 1 (2.9%) of the reacting and 2 (2.9%) of the non-reacting bee venom (BV) allergic individuals, as compared to 3 (42.9%) of the reacting and 4 (8%) of the non-reacting Vespula venom-allergic patients. Thus, there was a significant association between a reaction to the sting challenge and an elevated basal serum tryptase in Vespula (chi2=6.926, P<0.01), but not in BV-allergic patients. Systemic allergic side-effects to venom immunotherapy were observed in 13.9% of patients with normal and in 10% of those with elevated basal serum tryptase. CONCLUSIONS: An elevated basal serum tryptase as well as mastocytosis are risk factors for severe or even fatal shock reactions to Hymenoptera stings. Although the efficacy of venom immunotherapy in these patients is slightly reduced, most of them can be treated successfully. Based on currently available data, lifelong treatment has to be discussed in this situation.     

Serum tryptase levels in adverse drug reactions

We evaluated the usefulness of individual tryptase levels and variations after adverse drug reactions in 64 patients. Our aim was to find a tool for the diagnosis of drug allergy. Thirty-seven subjects were confirmed to have drug allergy, 12 had nonsteroidal anti-inflammatory drug (NSAID) reactions, five had negative controlled drug challenges (NAAR), and 10 had symptoms after placebo intake (PLA). Serum tryptase levels greatly increased after anaphylactic shocks (2242%) and anaphylaxis (710.5%). Patients with allergic urticaria and those with idiosyncratic responses to acetylsalicylic acid (ASA) exhibited a small increase in serum tryptase (49.5% and 38.2%, respectively). In the other two groups (NAAR and PLA), no variation in this serum protease was observed. The time of appearance of the serum tryptase peak differed considerably among patients with similar clinical reactions (from 30 min to 6 h) and was independent of the latent period, severity of symptoms, or the amount of tryptase released. We conclude that serum tryptase determinations are helpful in the diagnosis of anaphylactic shock and anaphylaxis, but serial measurements may be needed to confirm mast-cell participation in milder reactions.     

Cardiovascular disease and anaphylaxis

PURPOSE OF REVIEW: In severe anaphylaxis, the cardiovascular system is often heavily involved. Preexisting cardiovascular disease may therefore influence the course of anaphylaxis in a negative way. RECENT FINDINGS: Systemic mastocytosis and elevated baseline serum tryptase are associated with severe and fatal anaphylaxis to hymenoptera stings. This is due to an increased number of cardiac mast cells resulting in high concentrations of cardiotoxic mast cell mediators in cardiac tissue during anaphylaxis. Severe anaphylaxis in coronary heart disease, in particular, is explained by an increased load of cardiac mast cells together with coronary stenosis favouring myocardial hypoxia. Contraindications for the use of medications for cardiac disease in patients with anaphylaxis, especially beta-blockers, have been questioned by epidemiologic studies considering the positive effects of these drugs on much more prevalent cardiac diseases. SUMMARY: Preexisting cardiovascular disease, mastocytosis and elevated baseline serum tryptase are risk factors for fatal anaphylactic reactions or lasting morbidity due to myocardial or cerebrovascular infarction induced by anaphylaxis. Life-saving cardiac medications like beta-blockers may increase the severity of anaphylaxis. Since life-threatening cardiovascular diseases are much more frequent than anaphylaxis, the relative risk of either disease with and without these drugs must be analyzed carefully together with the cardiologist.     

Is unrecognized anaphylaxis a cause of sudden unexpected death?

Background: Serum tryptase levels reflect mast cell activation and correlate with anaphylactic reactions. Elevated post-mortem serum tryptase levels have been found in witnessed fatal anaphylaxis. Objective: This study was designed to examine whether or not unwitnessed anaphylaxis may be a hitherto unrecognized cause of sudden unexplained death. Methods: Mast cell tryptase was measured by immunoassay in 68 post-mortem sera remaining from a previous study which reported elevated venom-specific IgE antibodies in 22 (23%) of 94 victims of sudden unexpected death. Autopsies were performed in all cases. The cause of death was independently reported by pathologists unfamiliar with the nature of this study. Results: Serum tryptase levels were elevated (> 10ng/mL) in nine of 68 cases. The levels could not be predicted from the clinical circumstances surrounding death. Sera from four individuals contained both elevated tryptase and previously reported elevated venom-specific IgE. Conlusions: We conclude that mast cell activation may accompany up to 13% of sudden unexpected deaths in adults. Measurement of both tryptase and specific IgE antibody levels in post-mortem sera from persons experiencing sudden, unexpected death may identify a small subset of cases due to clinically unrecognized fatal anaphylaxis, including those due to insect stings.     

Effects of unfractionated heparin, low-molecular-weight heparin, and heparinoid on thromboelastographic assay of blood coagulation

Thromboelastography (TEG) has been used increasingly as an intraoperative hemostasis monitoring device. Low-molecular-weight heparins are given increasingly to reduce the development of antibodies against the heparin-platelet factor 4 complex, and heparinoids are given to patients who have developed the antibody. We studied the effect of unfractionated heparin, a low-molecular-weight heparin (enoxaparin sodium [Lovenox]), and a heparinoid (danaparoid sodium [Orgaran]) on blood clotting assayed with TEG (TEG clotting) in vitro and the efficacy of protamine sulfate and heparinase for reversing the effect. Heparin, enoxaparin, and danaparoid all caused a dose-dependent inhibition of TEG clotting of normal blood. Concentrations of enoxaparin and danaparoid that totally inhibited TEG clotting only minimally prolonged the activated partial thromboplastin time. While inhibition of TEG clotting by heparin and enoxaparin was reversed by protamine sulfate and heparinase, inhibition by danaparoid was reversed only by heparinase. Abnormal TEG clotting was observed in patients receiving enoxaparin whose plasma level of the drug was more than 0.1 antiXa U/mL. However, the degree of TEG abnormality did not always coincide with plasma levels of the drug.     

An anaphylactic reaction to intra-articular triamcinolone: a case report and review of the literature.

OBJECTIVE: The primary objective was to report a case of triamcinolone-induced anaphylaxis and review the proposed mechanisms of corticosteroid-associated hypersensitivity reactions. DATA SOURCES: Articles in French and English were identified from references in relevant articles and from articles retrieved from the PubMed web site. Indexing terms consisted of corticosteroids in conjunction with the terms anaphylaxis, hypersensitivity reactions, asthma, urticaria, and angioedema. STUDY SELECTION: We reviewed all articles that described a case or cases of allergic-type reaction in association with corticosteroid use and for which we could obtain the full text of the article (>95%). RESULTS: We report an anaphylactic reaction occurring after an intraarticular injection of triamcinolone in a 75-year-old man who had positive prick skin tests to triamcinolone and negative tests to lidocaine, methylprednisolone, and hydrocortisone. CONCLUSIONS: To date, there have been approximately 100 published reports of immediate hypersensitivity reactions occurring after oral and parenteral administration of corticosteroids. Both immunologic and nonimmunologic mechanisms are proposed, but there is no definitive evidence in favor of either hypothesis. Our patient demonstrated positive prick skin tests to triamcinolone in a dose-response manner, suggesting the likelihood that an immunoglobulin E-mediated hypersensitivity mechanism may play a role.     

Anaphylaxis to diclofenac: nine cases reported to the Allergy Vigilance Network in France

Nine cases of diclofenac hypersensitivity recorded by the Allergy Vigilance Network in France from 2002 to 2012 were studied. Data from history, symptoms, skin tests, basophil activation tests, and oral challenge (OC) were recorded. Grade 3 severe anaphylactic reactions occurred in seven cases of nine. IgE‐dependent anaphylaxis was confirmed in six cases: positive intradermal tests (n = 4), a syndromic reaction during skin tests (n = 1), and one case with grade 1 reaction and negative skin tests had an anaphylactic shock to the OC. A nonimmune reaction was suspected in one case. An IgE‐dependent mechanism may be the predominant cause of adverse reactions to diclofenac. Allergy skin tests must be carried out sequentially at the recommended concentrations. BATs may be helpful because they can support the diagnosis of anaphylaxis. Given the risks of a direct challenge to diclofenac, OC to aspirin should be performed first to exclude a nonimmunologic hypersensitivity to NSAIDs. Tests for specific IgEs to most frequently used NSAIDs such as diclofenac and ibuprofen are urgently needed.     

Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI position paper

Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells (MC) in different tissues, with a preferential localization in skin and bone marrow (BM). The excess of MC in mastocytosis as well as the increased releasability of MC may lead to a higher frequency and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22–49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti‐inflammatory drugs, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC disorders using MEDLINE, EMBASE, and Cochrane Library, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation.     

Plasma histamine and tryptase during anaphylactoid reactions

We have compared the diagnostic value of plasma histamine and mast cell tryptase to evaluatein vivo histamine-release during anaphylactoid reactions. In 17 patients, plasma histamine was measured within one hour after the reaction, and the result was compared with skin testing performed 8 weeks later. Each subject with a high histamine level had a positive skin test to one of the administered drugs. The plasma histamine level was compared to tryptase in 33 patients. In 13 cases, both were elevated and, in 15 others, both were negative. Two patients had normal histamine but high tryptase: this was due to delayed sampling. Three had high histamine but low tryptase. In one, muscle relaxant allergy was proved by positive skin tests and IgE determination. Mast cell tryptase is an efficient alternative to histamine measurement when blood withdrawing is done late. However, a few anaphylactic reactions may not be associated with high levels of tryptase.     

Plasma histamine and tryptase during anaphylactoid reactions

We have compared the diagnostic value of plasma histamine and mast cell tryptase to evaluatein vivo histamine-release during anaphylactoid reactions. In 17 patients, plasma histamine was measured within one hour after the reaction, and the result was compared with skin testing performed 8 weeks later. Each subject with a high histamine level had a positive skin test to one of the administered drugs. The plasma histamine level was compared to tryptase in 33 patients. In 13 cases, both were elevated and, in 15 others, both were negative. Two patients had normal histamine but high tryptase: this was due to delayed sampling. Three had high histamine but low tryptase. In one, muscle relaxant allergy was proved by positive skin tests and IgE determination. Mast cell tryptase is an efficient alternative to histamine measurement when blood withdrawing is done late. However, a few anaphylactic reactions may not be associated with high levels of tryptase.