Anaphylaxis to Patent Blue V. II. A unique IgE-mediated reaction

Background:  Patent Blue V (PBV) is injected in order to map sentinel nodes during cancer staging procedures. Anaphylactic reactions, allegedly IgE antibody mediated, have been reported. The aim of the study was to explore the immunological mechanism of anaphylaxis to PBV.
Methods:  PBV allergen threshold basophil sensitivity, CD-sens, was performed on cells from nine patients diagnosed as having had adverse reactions to PBV. The mechanisms of the CD-sens were studied by immunological and immuno-chemical methods.
Results:  Five of the nine patients had a positive CD-sens to PBV which was completely eliminated by washing the cells in phosphate buffered saline before allergen challenge. However, the positive CD-sens was completely reconstituted by incubating the cells in plasma or serum of that patient or the other PBV-anaphylactic patients for 15 min at room temperature. In some patients the factor mediating CD-sens was completely or partially destroyed by heating at +56°C for 30 min or being exposed to the low pH used for elution from anti-Ig columns. A 1000-fold excess of monoclonal IgE blocked the reconstitution by approximately 50%.
Conclusion:  Anaphylactic reactions to PBV are mediated by IgE antibodies giving a classical CD-sens reaction. However, the allergenic configuration seems to constitute a structure completely dependent on PBV, as a hapten, linked to a, so far, unknown carrier that seems to be unique for patients having experienced a PBV-induced reaction. Further studies are needed to characterize the postulated carrier.     

Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients

Background:  Excessive mast cell mediator release may lead to anaphylaxis in patients with mastocytosis. However, the incidence, clinical features and trigger factors have not yet been analyzed.
Methods:  To identify risk factors for anaphylaxis in mastocytosis, we determined cumulative incidence, severity, clinical characteristics, and trigger factors for anaphylaxis in 120 consecutive patients (53 male; 67 female, median age and range 24 years, 1 month to 73 years), and correlated these with disease severity of mastocytosis, skin involvement, basal total serum tryptase, and diaminooxidase concentrations.
Results:  The cumulative incidence of anaphylaxis in patients with mastocytosis was higher in adults (49%; P  < 0.01) compared with that in children (9%). Only children with extensive skin involvement had experienced anaphylaxis. In adults, anaphylaxis was correlated to the absence of urticaria pigmentosa lesions ( P  < 0.03). Reactions occurred more frequently in adults with systemic (56%) when compared with cutaneous mastocytosis (13%; P  < 0.02). In adults, 48% of reactions were severe, and 38% resulted in unconsciousness. Major perceived trigger factors for adults were hymenoptera stings (19%), foods (16%), and medication (9%); however, in 26% of reactions, only a combination of different triggers preceded anaphylaxis. Trigger factors remained unidentified in 67% of reactions in children compared with 13% in adults. Patients with anaphylaxis had higher basal tryptase values (60.2 ± 55 ng/ml, P  < 0.0001) in comparison with those without (21.2 ± 33 ng/ml), but not diaminooxidase levels.
Conclusion:  Adult patients and children with extensive skin disease with mastocytosis have an increased risk to develop severe anaphylaxis; thus, an emergency set of medication including epinephrine is recommended.     

Paediatric anaphylaxis: a 5 year retrospective review

Objective:  To describe the demographic characteristics, clinical features, causative agents, settings and administered therapy in children presenting with anaphylaxis.
Methods:  This was a retrospective case note study of children presenting with anaphylaxis over a 5-year period to the Emergency Department (ED) at the Royal Children's Hospital, Melbourne.
Results:  One-hundred and twenty-three cases of anaphylaxis in 117 patients were included. There was one death. The median age of presentation was 2.4 years. Home was the most common setting (48%) and food (85%) the most common trigger. Peanut (18%) and cashew nut (13%) were the most common cause of anaphylaxis. The median time from exposure to anaphylaxis for all identifiable agents was 10 min. The median time from onset to therapy was 40 min. Respiratory features were the principal presenting symptoms (97%). Seventeen per cent of subjects had experienced anaphylaxis previously.
Conclusions:  This is the largest study of childhood anaphylaxis reported. Major findings are that most children presenting to the ED with anaphylaxis are first-time anaphylactic reactions and the time to administration of therapy is often significantly delayed. Most reactions occurred in the home. Peanut and cashew nut were the most common causes of anaphylaxis in this study population, suggesting that triggers for anaphylaxis in children have not changed significantly over the last decade.     

How much specific is the association between hymenoptera venom allergy and mastocytosis?

Background:  The preferential association of mastocytosis with hymenoptera sting reactions is well known, but there is no data on the prevalence of clonal mast cell disorders in subjects with severe systemic reactions due to foods or drugs.
Methods:  Patients with food- or drug-induced severe systemic reactions, including anaphylaxis, and increased serum tryptase were studied for the presence of mastocytosis, and compared with a population of patients with hymenoptera allergy. The aetiological role of foods or drugs was assessed according to current recommendations. Systemic reactions were graded in severity according to the procedure described by Mueller. Serum tryptase was considered increased if the level was >11.4 ng/ml. Subjects with increased tryptase had dermatological evaluation and Bone marrow(BM) aspirate-biopsy, which included histology/cytology, flow cytometry and detection of KIT mutations.
Results:  A total of 137 subjects (57 male, mean age 42 years) were studied. Of them, 86 proved positive for drugs and 51 for foods. Overall, out of 137 patients, only nine (6.6%) had a basal tryptase >11.4 ng/ml, and only two (1.5%) were diagnosed with mastocytosis. This was clearly different from patients with hymenoptera allergy, where 13.9% had elevated tryptase and 11.1% had a clonal mast cell disorder.
Conclusion:  The association of clonal mast cell disorders with hymenoptera allergy seems to be more specific than that with food- or drug-induced systemic reactions.     

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.     

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).     

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.     

IGE-mediated allergic reactions to seminal plasma

INTRODUCTION:  Human seminal plasma anaphylaxis has to be differentiated from allergic reactions to latex, spermicidal substances, local anesthetics or components of lubricants. In this study clinical findings of women with IgE-mediated (type I) allergic reactions against seminal plasma antigens are compared to those reported in the literature.
METHODS:  Medical history of the couple, andrological work-up of the male partners, specific IgE against seminal plasma, prick tests with spermatozoa and seminal plasma.
RESULTS:  Patients with human seminal plasma anaphylaxis have rarely been reported. However, it is likely that a significant number of cases remains unpublished or undiagnosed. Most patients are younger than 40 years. Human seminal plasma anaphylaxis is not always associated with female infertility. Symptoms start immediately or within one hour after exposure to the ejaculate. Local reactions include itching, burning, erythema and edema of the perivaginal region or other areas that have been exposed to seminal plasma. Systemic reactions are dyspnea, dysphagia, rhinitis, conjunctivitis, urticaria, angioedema, gastrointestinal symptoms, anaphylaxic shock or exacerbation of atopic eczema. These complaints may become manifest during the first sexual intercourse. Available data imply that seminal plasma allergens are of prostatic origin and that prostate specific-antigen is one of the clinically relevant components.
CONCLUSIONS:  The diagnostic procedure is based on medical history, evaluation of specific IgE-antibodies in the serum of patients and skin tests. Patients are advised to avoid allergen contact by proper usage of condoms. In occasional cases specific hyposensitization have been performed successfully.     

Usefulness of UniCAP‐Tryptase fluoroimmunoassay in the diagnosis of anaphylaxis

BACKGROUND: Serum tryptase level measured by RIA is the main in vitro tool to confirm the diagnosis of anaphylaxis. METHODS: Serum tryptase levels were determined by UniCAP-Tryptase fluoroimmunoassay (Pharmacia & Upjohn, Uppsala, Sweden), in 30 consecutive patients who presented at the emergency room with a clinical allergic reaction of less than 6-h duration to assess the value of this method in the diagnosis of anaphylaxis. Anaphylaxis was established by clinical criteria and by immunoallergic study. Baseline tryptase levels were determined 1 month later in 21 patients. The receiver operating curve (ROC) was used to establish the best cutoff point of tryptase levels to confirm the diagnosis of anaphylaxis. RESULTS: Seventeen patients were diagnosed with anaphylaxis. In this group, tryptase levels were higher than in the nonanaphylaxis group, composed mostly of patients with urticaria or angioedema (P<0.001). ROC established the best cutoff of tryptase levels at 8.23 ng/ml with a 94.12% sensitivity and 92.31% specificity, whereas the 13.5 ng/ml cutoff recommended by the manufacturers showed 35.29% sensitivity and 92.31% specificity. The reaction-tryptase/baseline-tryptase ratio was 2.85 in the anaphylaxis group and 1.29 in the nonanaphylaxis group. CONCLUSIONS: Serum tryptase levels of >8.23 ng/ml by UniCAP-Tryptase fluoroimmunoassay identify anaphylaxis in patients with symptoms of less than 6-h duration. The usefulness of this determination is higher if baseline tryptase levels are available.     

Fatal anaphylaxis: postmortem findings and associated comorbid diseases.

BACKGROUND: Anaphylaxis is an infrequent cause of sudden death. Death often results from circulatory collapse, respiratory arrest, or both. OBJECTIVE: To investigate the causes of death, anatomical findings, and comorbid diseases in cases of fatal anaphylaxis. METHODS: 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. RESULTS: 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. CONCLUSIONS: (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.     

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.     

Wheat allergy: clinical and laboratory findings

BACKGROUND: Food allergy affects 6-8% of infants and wheat allergy is one of the common food allergies among children. The clinical and laboratory manifestations of wheat allergy were evaluated in this study. METHODS: Thirty-two children (< or =12 years old) with suspected wheat allergy were evaluated for wheat allergy. The patients underwent wheat skin prick test (SPT), measurement of wheat-specific IgE and wheat challenge test. The patients with a convincing history of anaphylaxis following ingestion of wheat or with a positive challenge test, and those with a history of immediate hypersensitivity reaction following ingestion of wheat in addition to a positive wheat SPT and/or positive wheat-specific IgE were considered wheat allergic. Then, the laboratory and clinical manifestations of their disease were studied. RESULTS: Among patients with suspected wheat allergy, 24 patients with definite wheat allergy were identified. Anaphylaxis was a dominant clinical feature, accounting for 54.1% of acute symptoms. Chronic allergy symptoms like asthma and eczema were noted in 50% of the patients. Wheat-specific IgE was higher in patients with anaphylaxis (p<0.02) and the risk of anaphylaxis was 14.4 times more in patients with wheat-specific IgE equal to or more than 3+. CONCLUSIONS: Anaphylaxis had occurred in a remarkable number of patients repeatedly, which demonstrates the severity of the reactions, poor knowledge of the disease and probable existence of more patients with mild reactions. Regarding the higher level of wheat-specific IgE in patients with anaphylaxis, wheat-specific IgE could be used to predict the severity of symptoms.     

Epidemiologic and clinical features of anaphylaxis in Korea.

BACKGROUND: Little is known about the characteristics of anaphylaxis in Korea or even in Asia. OBJECTIVE: To evaluate the incidence of anaphylaxis and the clinical features of patients with anaphylaxis in a Korean tertiary care hospital. METHODS: We performed a retrospective review from January 1, 2000, through July 31, 2006, of 138 patients with anaphylaxis, including inpatients, outpatients, and emergency department visitors, in the Seoul National University Hospital. RESULTS: Among 978,146 patients, 138 (0.014%) had anaphylaxis. Two cardiopulmonary resuscitations were performed and 1 death occurred. The total mortality rate of anaphylactic patients was 0.0001%. The causes of anaphylaxes were drug (35.3%), food (21.3%), food-dependent exercise-induced (13.2%), idiopathic (13.2%), insect stings (11.8%), exercise induced (2.9%), blood products (1.5%), and latex (0.7%). Radiocontrast media and buckwheat were the leading causes of drug and food anaphylaxis, respectively. The organs most frequently involved in the anaphylaxis were cutaneous (95.7%), cardiovascular (76.8%), and respiratory (74.6%). The most common manifestations were dyspnea (71.3%), urticaria (81.9%), and angioedema (69.4%). Three of 138 patients (2.2%) had biphasic reactions. CONCLUSIONS: The incidence, mortality rate, and clinical features of Korean patients with anaphylaxis were similar to rates for patients from other countries, despite some differences in causative agents.     

Wheat anaphylaxis in children

Food anaphylaxis is now the leading known cause of anaphylactic reactions treated in emergency departments, and wheat is one of the most common causes of anaphylaxis. Wheat is an important source of food worldwide. Wheat anaphylaxis is increasingly observed in our clinic. The purpose of this study was to describe the clinical features of wheat-induced anaphylaxis in 19 children for better elucidation of this disease. Children with severe reactions after ingestion of small amounts of wheat were referred to our clinic during a 4-year period. A detailed clinical history was recorded for each of the patients and a skin prick test was performed with wheat allergen extracts. The wheat-specific IgE and total IgE were measured. Grading of anaphylaxis episodes was performed according to a specific grading system. We identified 36 episodes of wheat anaphylaxis in 19 patients. All of the first attacks of wheat anaphylaxis occurred in the first-time ingestion. The most frequent manifestations of the reactions were skin and respiratory symptoms. In this study 78.9% of reactions were moderate and 21.1% of them were severe. All of our patients had positive skin prick tests to wheat. Mean total IgE level was 853.4 ± 455.27 IU/ml, and mean wheat-specific IgE was 70 ± 14.61 Ucs/ml. We conclude that wheat-induced anaphylaxis is a disease that is sufficiently severe, and. prevention of first wheat-induced anaphylaxis episodes is almost impossible. It would, however, probably be good practice to educate physicians to recognize the common clinical manifestations of this disease for early management.     

Hereditary alpha-tryptasemia in 101 patients with mast cell activation–related symptomatology including anaphylaxis

BackgroundHereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait characterized by multiple copies of the alpha-tryptase gene at the TPSAB1 locus. Previously described symptomatology involves multiple organ systems and anaphylaxis. The spectrum of mast cell activation symptoms is unknown, as is its association with specific genotypes.ObjectiveTo describe clinical, laboratory, and genetic characteristics of patients referred for the evaluation of mast cell activation–related symptoms and genotype-confirmed HαT.MethodsWe retrospectively describe clinical characteristics, baseline tryptase, and tryptase genotype in 101 patients. Patients were referred for mast cell activation–related symptoms and underwent genotyping to confirm diagnosis of HαT.ResultsOf 101 patients, 80% were female with average tryptase of 17.2 ng/mL. Tryptase was less than 11.4 ng/mL in 8.9% and greater than 20 ng/mL in 22.3% (range 6.2-51.3 ng/mL). KIT D816V mutation was negative in all subjects tested. 2α:3β was the most common genotype but did not correlate with tryptase levels. Unprovoked anaphylaxis was noted in 57% of the subjects with heterogeneous genotypes. Most common symptoms include gastrointestinal, cutaneous, psychiatric, pulmonary, cardiovascular, and neurologic. A total of 85% of patients were taking H₁- or H₂-antihistamines with partial symptom relief. Omalizumab was effective at suppressing anaphylaxis or urticaria in 94% of the patients.ConclusionHαT encompasses a broad range of baseline tryptase and should be considered in patients with symptoms of mast cell activation and tryptase levels greater than 6.2 ng/mL. Patients may present with complex symptomatology including cutaneous, gastrointestinal, neurologic, and psychiatric symptoms and anaphylaxis, some of which respond to omalizumab.     

Wheat Anaphylaxis in Children

Food anaphylaxis is now the leading known cause of anaphylactic reactions treated in emergency departments, and wheat is one of the most common causes of anaphylaxis. Wheat is an important source of food worldwide. Wheat anaphylaxis is increasingly observed in our clinic. The purpose of this study was to describe the clinical features of wheat-induced anaphylaxis in 19 children for better elucidation of this disease. Children with severe reactions after ingestion of small amounts of wheat were referred to our clinic during a 4-year period. A detailed clinical history was recorded for each of the patients and a skin prick test was performed with wheat allergen extracts. The wheat-specific IgE and total IgE were measured. Grading of anaphylaxis episodes was performed according to a specific grading system. We identified 36 episodes of wheat anaphylaxis in 19 patients. All of the first attacks of wheat anaphylaxis occurred in the first-time ingestion. The most frequent manifestations of the reactions were skin and respiratory symptoms. In this study 78.9% of reactions were moderate and 21.1% of them were severe. All of our patients had positive skin prick tests to wheat. Mean total IgE level was 853.4 ± 455.27 IU/ml, and mean wheat-specific IgE was 70 ± 14.61 Ucs/ml. We conclude that wheat-induced anaphylaxis is a disease that is sufficiently severe, and. prevention of first wheat-induced anaphylaxis episodes is almost impossible. It would, however, probably be good practice to educate physicians to recognize the common clinical manifestations of this disease for early management.     

Interleukin 6 and C-reactive protein levels in patients with acute allergic reactions: an emergency department-based study.

BACKGROUND: Elevations of interleukin 6 (IL-6) have been described in drug-induced anaphylaxis. Although IL-6 is well known to stimulate an acute phase response, profiling acute phase protein levels, such as C-reactive protein (CRP), has, to our knowledge, never been performed in patients with acute allergic reactions. OBJECTIVE: To examine the pattern of IL-6 and CRP levels in patients with acute allergic reactions and to relate these to relevant clinical and laboratory parameters. METHODS: Plasma CRP and serum IL-6 levels were determined in 85 adult emergency department patients. These patients had been previously studied with questionnaires, physical examinations, and histamine/tryptase levels. Clinical and historical features were related to CRP and IL-6 levels. CRP and IL-6 levels were also examined for relationships with histamine and tryptase levels. RESULTS: CRP and IL-6 levels were significantly correlated with one another in the study patients (Spearman p = 0.36, P = 0.0008). Similar to histamine levels, IL-6 levels were significantly correlated with the extent of erythema manifested by the study patients. The extent of erythema was independently predicted by both IL-6 and histamine levels. Histamine levels were negatively correlated with CRP levels (Spearman p = -0.32, P = 0.003). Unlike histamine levels, IL-6 and CRP did not show significant relationships with the extent or presence of urticaria/angioedema or the presence of wheezing. IL-6 levels were correlated with the duration of symptoms before serologic sampling. An inverse correlation was observed between IL-6 levels and mean arterial blood pressure. Multivariate modeling showed significant independent effects from mean arterial pressure, duration of symptoms, erythema extent, and age in predicting IL-6 levels. Tryptase levels were higher in patients whose IL-6 levels were >20 pg/mL. CONCLUSIONS: CRP and IL-6 levels are not simple surrogate markers for histamine or tryptase release by mast cells or basophils in acute allergic reactions. Increasing IL-6 levels relate to greater erythema extent, lower mean arterial blood pressure, and a longer duration of symptoms. It would be interesting to speculate that CRP and IL-6 increases characterize a late-phase response in immediate hypersensitivity reactions. In this perspective, the inverse relationship between CRP and histamine levels could be explained. As histamine levels are waning, CRP levels are increasing. Timed studies for histamine and CRP/IL-6 levels in allergic reactions are necessary to confirm this hypothesis.     

Incidence of anaphylaxis in the emergency department: a 1-year study in a university hospital

The aim of this study was to estimate the incidence of anaphylaxis in an emergency department, identify rate and risk factors of recurrent anaphylaxis, and describe its clinical features and management. A retrospective study of patients who attended the emergency department at Thammasat University Hospital was conducted during 2003-2004 with anaphylactically related ICD-9 and ICD-10 terms. There were 64 patients who experienced 65 anaphylactic episodes during the 1-year period. The anaphylaxis occurrence rate was 223 per 100,000 patients per year. The most common manifestations were cutaneous symptoms and signs, followed by respiratory expression. Food allergy was the most common cause of anaphylaxis. Eighty-five percent of admitted cases had monophasic anaphylaxis. Patients with and without biphasic reactions did not differ significantly in terms of epinephrine and steroid usage. In conclusion, anaphylaxis is not rare. Epinephrine and steroid usage did not prevent biphasic reactions.     

Mastocytosis and allergy

PURPOSE OF REVIEW: To illustrate features of allergy in mastocytosis. RECENT FINDINGS: The rates of atopy in patients with mastocytosis have generally been found to be similar to those of the normal population, although the incidence of anaphylaxis is much higher in mastocytosis. Introduction of objective pathologic criteria by the WHO for the diagnosis of mastocytosis has greatly facilitated the workup of patients with suspected mastocytosis, and has led to identification of mast cell disease in a subset of patients with anaphylaxis. There is increasing evidence that an activating c-kit mutation (D816V) exists in a subset of patients with recurrent mast cell activation symptoms who have normal-appearing bone marrow biopsies in routine evaluations without skin lesions. The genetic deficiency of alpha tryptase has not been found to influence serum tryptase levels in patients with mastocytosis. SUMMARY: Pathologic mast cell activation is a key finding in both allergic diseases and mastocytosis, albeit caused by entirely different mechanisms. Mastocytosis should be suspected in patients with recurrent anaphylaxis, who present with syncopal or near-syncopal episodes without associated hives or angioedema.     

Clinical and laboratory parameters of mast cell activation as basis for the formulation of diagnostic criteria

Mast cell (MC) activation occurs in a number of different pathologic conditions. Acute activation is commonly seen in patients with allergic reactions, with consecutive massive release of vasoactive and proinflammatory mediator substances from MCs, leading to the clinical signs and symptoms of anaphylaxis. In these patients, serum tryptase concentrations usually increase subtantially above baseline levels. Chronic MC activation is more difficult to diagnose, especially when symptoms are mild or atypical, and no underlying disease is found. In these patients, serum tryptase levels usually are normal. In a smaller group of patients, tryptase levels are constantly elevated and may point to an occult form of mastocytosis. These patients have to be examined for MC monoclonality, other criteria of a primary MC disease, non-MC hematopoietic neoplasms, and reactive disorders producing chronic MC activation or MC accumulation. In most patients in whom MC activation is found, histamine-induced symptoms can be documented and usually respond to treatment with histamine receptor antagonists or MC stabilizers. If this is not the case, alternative explanations for symptoms and differential diagnoses have to be considered.