Mediator release in local heat urticaria

We described the sixteenth reported case of local heat urticaria, in a 59-yr-old woman with erythema and angioedema upon contact with hot water or outdoor heat exposure. Immersing her hand in 39° to 40° C heated water resulted in an erythematous, angioedematous response sharply demarcated by the line of immersion and was associated with immediate increases in histamine concentration (18 to 135 ng/ml) and high molecular weight neutrophil chemotactic activity (two to five times prechallenge levels) in venous blood draining the challenge site. We suggest that the local heat urticarial response in this woman was a form of physical urticaria associated with release of mast cell-derived mediators, akin to cold and cholinergic urticaria.     

Localized heat urticaria

The pathophysiology of localized heat urticaria was studied by performing a heat challenge on a patient with this disease. Serum levels of total hemolytic complement, C3, and factor B decreased following heat challenge, whereas levels of C4 and C5 did not. Plasma histamine levels remained unchanged. Electron microscopic studies of affected tissue revealed endothelial cell damage and neutrophilic degranulation in the affected area. Mast cells remained intact. These data imply that activation of the alternative complement pathway is involved in the pathogenesis of localized heat urticaria and that mast cell histamine release does not play a significant role in this disease.     

Stinging insect allergy: Natural history and modification with venom immunotherapy

The natural history of stinging insect allergy and its modification by venom immunotherapy was investigated by follow-up observations of patients with histories of venom anaphylaxis and detectable venom-specific IgE. The patients were divided into three categories: (1) receiving venom immunotherapy, (2) declined venom immunotherapy, and (3) terminated venom immunotherapy. One hundred twenty-seven patients were evaluated after 6 mo to 9 yr of venom immunotherapy. Most received top venom doses of 50 μg of yellow jacket and/or honeybee venoms every 4 wk. There were 87 restings in 48 patients resulting in two systemic reactions, only one of which could be considered a treatment failure (1%). Fifty-six patients never received venom immunotherapy. In this group there were 40 restings in 28 patients with 14 systemic reactions (35%). In 88 patients who stopped venom immunotherapy, 61 restings in 41 patients led to 11 systemic reactions (17%). Patients with cardiovascular/or respiratory symptoms with initial sting anaphylaxis were at risk for subsequent reactions. With one exception, patients with hives and edema only as the initial reaction either had a similar or no reaction when they were restung. These results confirm the efficacy of venom immunotherapy but also suggest that there are factors other than the presence of venom-specific IgE modulating the occurrence of clinical anaphylaxis.     

Venom skin tests in insect-allergic and insect-nonallergic populations

Intradermal skin tests with varying concentrations of honeybee, yellow jacket, white-faced hornet, yellow hornet, and Polistes venoms were done on 85 patients with histories of insect-sting anaphylaxis and on 56 insect-nonallergic subjects. Positive skin tests (wheal greater than or equal to 5 to 10 mm and flare greater than or equal to 11 to 20 mm) were present in 67 insect-allergic patients at venom concentrations ranging from 0.001 microgram/ml to 0.1 microgram/ml. Seven additional allergic patients had positive skin tests with the 1.0 microgram/ml venom concentration. Twenty-six nonallergic subjects had positive skin tests at the venom concentration of 1.0 microgram/ml, and two patients had positive skin tests at the lower venom concentrations (0.001 to 0.1 microgram/ml). These results confirm venom skin tests as a highly sensitive method of detecting venom-specific IgE in the evaluation of patients with stinging-insect hypersensitivity. Since a large percentage of insect-nonallergic subjects reacted to the 1.0 microgram/ml concentration, clinical judgment and further in vitro testing should be considered in the evaluation of patients who react only at this venom concentration.     

Insect venom allergy: a prospective case study showing lack of correlation between immunologic reactivity and clinical sensitivity

This case report demonstrates the lack of correlation between clinical sensitivity to insect venoms and immunologic reactivity as indicated by the presence of venom-specific IgE. A 20-yr-old venom collector was monitored over a 3-yr period with measurements of venom-specific IgE (skin test and RAST) and venom-specific IgG. In the first year of venom collection, multiple stings were tolerated with no reaction. In the second season, she had an anaphylactic reaction after a yellow jacket sting. Subsequently, there was a rising titer of serum yellow jacket and bee venom-specific IgE and positive skin-test reactions. In the third season, yellow jacket, hornet, and bee venom skin tests remained positive and serum IgE antibody titers remained elevated. Stings from all three insects were tolerated with no reaction. Throughout the 3-yr course, serum venom-specific IgG remained low and unchanged. The factors other than IgE-modulating clinical anaphylaxis, perhaps responsible for this clinical and immunologic dichotomy, are unknown. These observations add a further complication to the choice of patients for venom immunotherapy.     

Significance of tartrazine sensitivity in chronic urticaria of unknown etiology

Of 38 patients with chronic urticaria of unknown etiology who were evaluated for food and drug additive sensitivity, 53% (20/38) had urticaria for 1 yr or more. Total eosinophil counts ware not elevated in most patients, and the frequency of atopy was found to be similar to that in a general population. Of these 38 patients, 10 (26%) had a personal history of aspirin intolerance, but elimination of aspirin did not relieve the urticaria. In a double-blind crossover challenge with 0.22 mg of tartrazine and a control, tartrazine sensitivity was found in 8% (3/38) of patients with chronic urticaria and 20% (2/10) of patients with aspirin intolerance.     

Significance of H1 and H2 receptors in the human nose: rationale for topical use of combined antihistamine preparations

The aim of this experiment was to study the importance of histamine H1 and H2 receptors in the human nose. We therefore provoked 25 healthy human subjects with histamine after local pretreatment with the H1 receptor antagonist, chlorpheniramine maleate, the H2 receptor antagonist, ranitidine hydrochloride, and a combination of these two antihistamines. The histamine-induced increase in nasal airway resistance was 52% inhibited by combined use of the two antihistamine sprays (p less than 0.05), 22% by chlorpheniramine alone (p less than 0.05), and 29% by ranitidine. The two sprays together were significantly better than the H1 antagonists alone (p less than 0.05). These results suggest an equal importance of H1 and H2 receptors in nasal blood vessels, and an additive effect of H1 and H2 antihistamines. Although chlorpheniramine effectively blocked tickling and the reflex-mediated symptoms, sneezing and hypersecretion, ranitidine had no effect, which suggests an H1 and not an H2 effect on sensory nerve endings in the airway epithelium.     

Comparison of vespid venoms collected by electrostimulation and by venom sac extraction

Venoms of three vespid species, yellow jacket, bald-faced hornet, and yellow hornet, obtained by either electrostimulation or venom sac extraction were compared with regard to their enzymatic activity, antigenicity, and allergenicity. Phospholipase A, phospholipase B, and hyaluronidase enzymatic activities were present in all six preparations. The activity of venom sac extracts lay in the range found in different batches of venoms obtained by electrostimulation for each species. Analysis of sera from vespid-sensitive patients in the radioallergosorbent test (RAST) with discs coupled with either venom sac extracts or venoms obtained by electrostimulation showed a good correlation of the results within all three species (r = 0.95). In RAST inhibition the potency of venom sac extracts and venom obtained by electrostimulation was similar for each species. Analysis of rabbit antisera to the six preparations revealed similar patterns in immunoelectrophoresis and identity reactions between the major antigens within each species. Tissue protein contamination was detected in all venom sac extracts but not in venoms obtained by electrostimulation.     

Comparison of biochemical and immunologic properties of venoms from four hornet species

Venoms of two American hornets, Vespula maculata (bald-faced hornet) and Vespula arenaria (yellow hornet), and two Old World hornets, Vespa crabro and Vespa orientalis, were investigated for biochemical and immunologic properties. They were similar with regard to enzymatic activities (phospholipase A, phospholipase B, and hyaluronidase) and molecular composition. Analysis of radioallergosorbent test (RAST) results obtained from 30 vespid-sensitive patients suggests extensive cross-reactivity between the venoms of V. arenaria, V. maculata, and V. crabro, but the venom of V. orientalis seems to lack at least one important allergen. Rabbit antisera to each of the four venoms contain precipitating antibodies to all four venoms. Strong cross-reactivity was found between the venoms of V. maculata, V. arenaria, and V. crabro and between V. crabro and V. orientalis. V. orientalis venom cross-reacts weakly with the venoms of both V. maculata and V. arenaria. It is concluded therefore that diagnosis and immunotherapy with commercially available venoms of V. maculata and V. arenaria should be adequate for most patients sensitive to V. maculata, V. arenaria, or V. crabro but probably not for a significant proportion of those individuals primarily sensitive to V. orientalis.     

Local heat urticaria/angioedema: evidence for histamine release without complement activation

A 42-yr-old white woman reported onset in 1976 of local pruritus, burning, erythema, and edema within minutes after exposure in heat. With more extensive exposure, she occasionally had transient headaches and nausea. In order to investigate the etiology of this condition, her forearm was exposed to water at 44 degree C for 4 min. Within a few minutes, a lesion identical to her spontaneously induced ones developed only at the area exposed to heat. Samples of venous blood from this extremity demonstrated a transient rise in plasma histamine levels without any significant change in serum hemolytic complement activity or in C3, C4, or factor B. These findings suggest that this rare syndrome involves local activation of mediator release from mast cells, without participation of the complement system.     

The effect of histamine-1 and histamine-2 antagonists on airway responses to histamine in the rhesus monkey.

This study used rhesus monkeys with consistent respiratory responses to aerosolized histamine. Two systems of histamine challenge were evolved to study the effects of histamine antagonists on the histamine-induced respiratory response. One system consisted of administering increasing subreactive concentrations of histamine until an airway response (H) occurred. This threshold histamine dose was repeated (H'). The pulmonary function changes occurring with the H' challenge were less intense than those with H. M, a histamine-2 receptor antagonist, when given before the H' dose was associated with a potentiated H' response compared with the threshold H response. This provides evidence for histamine-2 receptor sites in rhesus monkey airways. A second system used duplicate histamine challenges with a known reactive dose of histamine. In this system, the pulmonary function changes occurring with the repeated challenge (H') were greater than with the first reactive challenge dose (H). This H' response was inhibited partially with diphenhydramine, a histamine-1 receptor antagonist. These two systems of histamine challenge provide an experimental model for evaluating pharmacologic alteration of histamine-induced respiratory responses. There is evidence for the existence of histamine-1 and histamine-2 receptor sites in the airways of the rhesus monkey.     

Localized heat and cold urticaria: Rare phenomena occurring in the same individual

The phenomenon of localized heat urticaria is described and illustrated by the report of a case. The patient also exhibited localized cold urticaria. No definite immunologic mechanisms were defined for the association of these 2 unusual conditions.     

Comparison of the venom immunogenicity of various species of yellow jackets (genus Vespula)

Venoms from various yellow jacket species were examined by two-dimensional thin-layer chromatography (TDTLC), double-diffusion gel precipitation (DDGP) using rabbit antisera, and the radioallergosorbent test (RAST). Comparison of representative venoms by the TDTLC showed that the venoms of V. vulgaris and V. maculifrons have a larger number of Ninhydrin (triketohydrindene hydrate)-positive substances than the venom of V. squamosa. The results of the DDGP confirmed the differences; venoms of V. vulgaris, V. maculifrons, V. flavopilosa, and V. germanica have one or more major components with immunogenic identity. The venom of V. squamosa has a species-specific major component and some minor components immunologically identical to the other venoms examined. Sera from 21 patients with a history of anaphylaxis following yellow jacket stings were examined by the RAST. Using the venoms of V. maculifrons, V. vulgaris, V. flavopilosa, and V. germanica as coupling antigens, most sera reacted similarly. The sera did not react with V. squamosa. These results suggest that the major component in venom obtained from the four yellow jacket species has immunogenic identity. Venom of V. squamosa differs from the remaining venoms. As a practical corollary, with the exception of venom from V. squamosa, common sensitivity appears to exist among the yellow jacket venoms examined.     

Effects of experimental rhinovirus 16 infection on airways and leukocyte function in normal subjects

We infected 7 normal volunteers with rhinovirus 16. In general, the symptoms and alterations in airways were minimal although all subjects had upper respiratory symptoms. Three subjects developed in addition lower respiratory and systemic symptoms accompanied by either an increase in the volume of isoflow or a positive methacholine response. Furthermore, these three had a decrease in beta adrenergic and Hz histamine receptor responses of their granulocytes. Since the peripheral airway obstruction and decreased beta adrenergic and H2 histamine responses occurred together, these two phenomenon may have a common cause. All seven subjects had a decrease in number of circulating E rosette forming lymphocytes, and in 6 of 7, there was a decrease in the antibody-dependent cellular cytotoxicity capacity of mononuclear cell preparations. It is not clear whether these changes reflect redistribution of mononuclear cells or alteration of their function.     

Aspirin and tartrazine oral challenge: Incidence of adverse response in chronic childhood asthma

Reports of adverse response to acetylsalicylic acid (ASA) and tartrazine in asthma disagree widely on the incidence of these phenomena. The present study seeks to define these incidences for asthmatic children in a statistically acceptable, standardized, and simple fashion. Fifty-four chronic asthmatic children 10 to 17 yr of age underwent blinded oral provocation challenge with ASA, tartrazine, and placebo on separate days. The pulmonary function results were expressed in percent predicted units and the absolute change from the subject's baseline to ASA and tartrazine were compared to the normal variation encountered to placebo challenge. Five children developed sustained decreases of one-second forced expiratory volume (L) (FEV₁) or forced expiratory flow rate at 25% to 75% of effort (L/sec) (FEF_0.25–0.75) exceeding 2 SD of the group mean response to placebo following oral ASA; none did following tartrazine. Two additional patients included in this population sample were considered to have adverse pulmonary response (APR) by history and were consequently not challenged. There were no clinical or laboratory findings associated with APR to ASA. Adverse response to ASA is sufficiently common among our population of children with chronic asthma to warrant ASA avoidance, unless ASA therapy is needed for another condition, such as rheumatoid arthritis, in which case careful provocation testing should be considered.     

Acute urticaria and bronchospasm following radiographic contrast media in a dog.

An immediate-type systemic reaction in a dog following intravenous radiographic contrast media (RCM) manifested by urticaria and wheezing on one occasion and urticaria alone on another occasion is described. This reactivity disappeared spontaneously and plans to study the mechanisms of such a reaction were not possible. If such reactivity is more persistent in certain other dogs, a model for study of immediate type reactivity to RCM would be available.