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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.

Acute Disease↗

Allergic reactions to 6-mercaptopurine during treatment of inflammatory bowel disease.

Hypersensitivity reactions to 6-mercaptopurine (6-MP) or azathioprine occur during the treatment of inflammatory bowel disease (IBD), raising significant diagnostic and therapeutic challenges. Charts of 591 patient with IBD treated with 6-MP in a single center were retrospectively reviewed. All allergic reactions were recorded along with results of rechallenge, desensitization, and subsequent course of IBD. Sixteen (2.7%) allergic reactions to 6-MP were noted, with fever being the most common (14 cases). Nine of these were rechallenged with 6-MP with recurrence of the same symptoms. Azathioprine was tried in six patients and in five the same symptoms recurred. Four patients underwent successful desensitization to either 6-MP or azathioprine; all four plus another patient who tolerated direct switch to azathioprine entered long-term remission. Among the remaining 11, 5 required surgery, 2 are well on methotrexate, and 4 have chronic symptoms while being treated with other medications. If an allergic reaction to 6-MP occurs during the treatment of IBD, direct switching to azathioprine is probably not justified. Instead, desensitization to either 6-MP or azathioprine should be attempted. Patients who can tolerate these medications after previous allergic reactions have improved outcomes compared with patients who resort to other forms of treatment.

Adolescent↗

Patterns of anaphylaxis: acute and late phase features of allergic reactions.

Anaphylaxis is usually defined as a multi-system allergic reaction, but includes isolated shock or airway obstruction. Hives do not occur in 20-30% of cases. Gastrointestinal (GI) symptoms are more common with foods. Cardiac anaphylaxis can cause arrhythmias, bradycardia or chest pain with ECG changes. Plasma histamine level correlates with hives and GI symptoms. Serum tryptase is elevated less often in food allergy, and correlates poorly with plasma histamine level. Anaphylaxis occurs in 30/100,000 population/year (mortality 1-2%) and is caused by foods (35%), drugs/ biologicals (25%), insect stings (15%), exercise (5%) or is idiopathic (20%). Onset of anaphylaxis to stings or allergen injections is usually rapid: 70% begin in < 20 minutes and 90% in < 40 minutes. Food/ingestant anaphylaxis may have slower onset or slow progression. Rapid onset is associated with greater severity. Prolonged anaphylaxis can be resistant to epinephrine and i.v. fluids. Biphasic allergic reactions which recur some hours after the early phase of the reaction were reported in 25% of cases of fatal and near-fatal food reactions, and in 23% of drug/biological reactions. But they occurred in only 6% of anaphylaxis of mixed causes and are uncommon with insect stings. Late phase (biphasic) reactions rarely occur without initial hypotension or airway obstruction.

Allergens↗

Clinical features of acute allergic reactions to peanut and tree nuts in children.

BACKGROUND: Peanut (PN) and tree nut (TN) allergies are potentially life-threatening, rarely outgrown, and appear to be increasing in prevalence. However, there is relatively little reported about the clinical features of acute reactions to these foods and their potential association. OBJECTIVE: To describe the clinical features of acute reactions during initial and subsequent accidental ingestions of PN and TN among children with a history of at least one acute allergic reaction to these foods. DESIGN: Questionnaire survey, examination, and serologic testing for specific IgE antibody of patients with convincing histories of acute reactions (at least one organ system involved within 60 minutes of ingestion) to PN or TN. RESULTS: A total of 122 patients (63% males; median age, 8 years at time of study) had acute reactions; 68 had reactions only to PN, 20 only to TN, and 34 to both PN and TN. Of those reacting to TN, 34 had reactions to one, 12 to two, and 8 to three or more different TN, the most common being walnut, almond, and pecan. Initial reactions usually occurred at home (median age, 24 months for PN and 62 months for TN) and were considered to result from a first exposure in 72% of cases. Eighty-nine percent of the reactions involved the skin (urticaria, angioedema), 52% the respiratory tract (wheezing, throat tightness, repetitive coughing, dyspnea), and 32% the gastrointestinal tract (vomiting, diarrhea). Two organ systems were affected in 31% of initial reactions, and all three in 21% of reactions. Thirty-eight of 190 first reactions to PN or TN were treated with epinephrine. Accidental ingestions occurred in 55% of PN-allergic children (average of two accidents per patient with an accidental ingestion) and in 30% of TN-allergic children over a median period of 5.5 years. On average, symptoms after accidental exposure were generally similar to those at initial exposure. Accidents occurred commonly in school but also at home and in restaurants. Modes of accidental ingestion included sharing food, hidden ingredients, cross-contamination, and school craft projects using peanut butter. Eighty-three percent of the children were breastfed, with >90% of the mothers ingesting PN and at least one TN during lactation. Among patients reporting no history of exposure (>60% of patients for each TN), IgE antibodies were found to a particular TN in 50% to 82% of patients and to PN in 100% of patients. CONCLUSIONS: Acute allergic reactions to PN occur early in life. PN and TN allergic reactions coexist in one third of PN-allergic patients, frequently occur on first known exposure, and may be life-threatening, requiring emergency treatment. Accidental ingestions are common, occur frequently outside of the home, and often require emergency treatment. Consequently, early diagnosis followed by education on avoidance and treatment measures (including self-administered epinephrine) is imperative.

Arachis↗

Allergic reactions to teniposide in patients with neuroblastoma and lymphoid malignancies.

Acute allergic reactions have been reported in 1%-5% of patients receiving teniposide. In a patient population of 82 children with leukemia and lymphoma, we observed only two acute reactions during the infusion of 1707 doses of teniposide. In contrast, 14 of 105 children with neuroblastoma developed acute allergic reactions during the infusion of 665 doses of teniposide. Four rechallenge doses of the drug were given to patients with neuroblastoma after premedication with antiallergic agents. All four doses resulted in repeat reactions. Our data suggest that children with neuroblastoma have a significantly higher incidence of acute reactions to teniposide than patients with other malignancies (P = 0.008), and that these reactions cannot be prevented by premedication with antiallergic drugs.

Child↗

[Clinical significance of allergic reactions in glucocorticoid therapy].

BACKGROUND: Glucocorticoids are widely used in medicine. Within the last few years, however, patients have become very suspicious of corticoids. The attending physicians frequently has to use a great deal of persuasion prior to applying this very effective and often indispensable group of medication. PATIENTS: We report on four patients who developed allergic reactions (i.e. erythema in face and on body, itching, flushing, drop in blood pressure, respiratory distress, cold sweats, etc.) immediately after intravenous administration of prednisolone-21 hydrogen succinate (Solu-Decortin H, SDH). RESULTS: Three out of four patients had a positive reaction to an intracutaneous test with SDH, but no reaction to the additive sodium succinate. The prick test was negative in all patients. No specific IgE antibodies were detected in the serum of these patients. However allergic reaction to SDH must be presumed in at least three cases as it is difficult to detect glucocorticoid antibodies in serum and standardizes techniques are lacking. One female patient had a cross-reaction to prednisolon and dexamethasone. A renewed application of SDH was tolerated well by all patients when H1- and H2-receptors were blocked and calcium was administered to stabilize membranes. CONCLUSIONS: Allergic reactions after glucocorticosteroid therapy are only occasionally mentioned in literature, appear more often when the agent is applied topically, and may lead to dangerous complications in patients if administered intravenously. Therefore, when allergic reactions result from glucocorticoid therapy (immediate reactions should be suspect), corticosteroid allergy should be considered as a differential diagnosis.

Administration, Topical↗

[Allergic reactions in treatment with L-asparaginase. Significance of specific IgE antibodies].

The formation of specific IgE antibodies to L-Asp was studied in 27 children with ALL. Increased titers of specific IgE antibodies were significantly more frequent (p less than 0.001) prior to L-Asp infusions followed by allergic reactions than in those without reactions. After passive sensitization of basophile granulocytes of a healthy volunteer using patient's serum with the highest titers of specific IgE antibodies to L-Asp a significant release of histamine was observed after exposure of cells to L-Asp. In 1 of 8 patients with allergic reactions titers of specific IgE antibodies were elevated, while there was not detectable activation of the complement system. In conclusion, elevated titers of specific IgE antibodies to L-Asp are frequently detectable prior to L-Asp infusions which are associated with allergic reactions. In addition to activation of the classical complement pathway specific IgE antibodies and mediator release from mast cells may contribute to clinical symptoms. In a small number of patients this mechanism alone may be responsible for the allergic reaction.

Adolescent↗

Orgotein in radiation treatment of bladder cancer. A report on allergic reactions and lack of radioprotective effect.

The possible protective effect of orgotein (a superoxide dismutase) on radiation cystitis and proctitis was studied in patients with carcinoma of the urinary bladder. A double-blind study in 60 patients was planned but due to unacceptable side effects only 30 patients were included. Radiation treatment was given with curative intent at a dose of 63 Gy in 30 fractions. Orgotein was injected 15 min after each daily radiation treatment at a dose of 4 or 8 mg. No effect of orgotein on tumour radiation response or on the acute radiation reactions in the bladder and rectum was detected. Marked subcutaneous infiltration and redness was seen at the local injection site in 5 patients. No general symptoms were observed. Intradermal tests and antibody titration tests showed that the local reactions were due to allergic reactions to the drug itself. The lack of radioprotective effect and the high frequency of unacceptable side effects makes orgotein an unsuitable drug in clinical radiation therapy.

Actuarial Analysis↗

Are allergic reactions to skin clips associated with delayed wound healing?

BACKGROUND: Metal skin clips are used in surgery. They may contain metals that might cause allergic reactions and delayed wound healing. METHODS: The metal composition of 18 different surgical clamps was examined. The allergy status of 184 patients was determined by patch tests and was correlated with the clinical outcome of wound healing after application of skin clips. RESULTS: Skin clips contained chromium, nickel, molybdenum, cobalt, and titanium in concentrations high enough to cause allergic reactions. Eighteen percent of the men and 23% of the women were sensitive to nickel and 16% of the men to chromium. We found a positive correlation between the grade of nickel allergy and the reaction to the skin clips. CONCLUSIONS: Our study suggests that allergic reactions and delayed wound healing can be caused by the use of surgical skin clips. Therefore skin clips are not recommended for patients with a history of contact dermatitis to metals and/or atopy.

Adolescent↗

[The efficacy of using enzymes in treating toxic-allergic reactions after cataract extraction with intraocular lens implantation].

Physiotherapy was administered to 84 patients aged 59-78 years with toxic allergic reaction in the eye after extracapsular cataract extraction with implantation of intraocular lenses (IOL). The patients were divided into 4 groups. Group 1 (n = 15) were treated by fibrinolysin magnetophoresis, group 2 (n = 17) lidase magnetophoresis, group 3 (n = 28) lecozyme magnetophoresis, and group 4 (n = 24) collalysin magnetophoresis. Treatment started on days 3-5 after surgery. Magnetophoresis was carried out using Russian Gradient-1 device, generating a low-frequency magnetic field of 10-12 mT, 10-12 min exposure. For patients with pronounced iridocyclitis and uveitis, enzyme magnetophoresis was supplemented with atropine, adrenalin, and calcium chloride electrophoresis (with monitoring the pupil size). Comprehensive treatment resulted in complete resolution of exudation in the anterior and posterior segments of the eye, hypopyon, loosening and resorption of anterior and posterior synechiae, the vitreous body grew more transparent, visual acuity improved in 91.1% patients (coarse dystrophic changes in the central zone of the fundus oculi were detected in 8.9%). Magnetophoresis with fibrinolysin and lidase is most effective in patients with toxic allergic reaction during the early periods after cataract extraction with IOL implantation, while in later periods magnetophoresis with lecozyme and collalysin should be preferred. The efficacy of collalysin is not inferior to that of lecozyme, but its effect is more mild and the drug causes no allergic reactions. Magnetophoresis with mydriatics (with monitoring the pupil size) and calcium chloride is recommended for all cases.

Aged↗

Inhibition of immediate-type allergic reactions by the aqueous extract of Salvia plebeia.

The effect of aqueous extract of Salvia plebeia R. Brown (Labiatae) (SPAE) on the mast cell mediated immediate-type allergic reactions in rats was studied. SPAE (0.05 to 1 g/kg) inhibited systemic allergic reaction induced by compound 48/80. SPAE (0.001 and 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis (PCA) when intraperitoneally, intraveneously or orally administered. When SPAE was pretreated at the same concentrations with systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. SPAE (0.001 to 1 mg/mL) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, when SPAE (0.1 and 1 mg/mL) was added, significantly increased compared with that of basal cells. Moreover, SPAE (0.01 to 1 mg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) production. These results indicate that SPAE may possess strong antiallergic activity and suggest that differences in bioavailability may cause differential activity following different administration routes.

Animals↗

Allergic reactions associated with airborne fish particles in IgE-mediated fish hypersensitive patients.

We evaluated the clinical characteristics found in 21 children who showed allergic reactions upon incidental inhalation of fish odors or fumes, from 197 diagnosed with IgE-mediated fish hypersensitivity. Allergic reactions to fish via ingestion began in most patients (86%) within the first 24 months of life. The vast majority (19/21) of patients showed cutaneous symptoms, either alone or, less frequently, associated with other clinical manifestations. Hake and flounder were the species of fish most frequently implicated in eliciting clinical manifestations upon ingestion. After diagnosis, all these patients were placed on a strict fish-avoidance diet. During this period of avoidance, patients reported allergic reactions (mean age 7 years) after incidental exposure to airborne fish odors or fumes. Clinical manifestations through inhalation were respiratory (mainly wheezing) in 12 patients and cutaneous (mainly urticaria) in nine patients. Nineteen of 21 patients reported three or more episodes upon exposure to fish aerosols; in most cases, these episodes occurred at home when other people were eating fish. In conclusion, incidental inhalation of fish odors or fumes could play an important role in accidental and unknown encounters with fish in children on fish-avoidance diets for fish IgE-mediated hypersensitivity. Such exposures could elicit clinical symptoms and could have some effect in delaying the development of tolerance.

Air Pollutants↗

Systemic allergic reaction and diffuse bone pain after exposure to a preparation of betamethasone.

Allergic reactions to corticosteroids are unexpected as they seem to contradict their pharmacodynamic action. Nevertheless, they are not infrequent, with an estimated incidence of up to 4% for cutaneous reactions. Systemic reactions are rarely reported, but their incidence might be underestimated. We report here an unusual allergic reaction to betamethasone presenting with diffuse bone pain, erythema, and bronchoconstriction, which was confirmed by a positive rechallenge in a double-blind procedure. This is the first case report of a systemic reaction to betamethasone confirmed by a positive rechallenge. An impurity in betamethasone diproprionate cannot be excluded. As this substance is frequently used in rheumatologic soft-tissue injections, it is important to recognize this potentially life-threatening side effect.

Journal Article↗

Significance of soluble Fc epsilon receptor II (sFc epsilon RII/CD23) in serum and possible application of sFc epsilon RII for the prevention of allergic reactions.

The significance of sFc epsilon RII in IgE-mediated allergic disease was examined. sFc epsilon RII in serum was found to decrease following clinical improvement, suggesting sFc epsilon RII in serum may be an indicator of allergic diseases. Significant proportions of sFc epsilon RII in serum were present as complexes with IgE in normals as well as in atopic patients, and these complexes were more prominent in the former than in the latter group. From these observations, attempts were made to inhibit IgE-mediated allergic reactions in vitro employing recombinant sFc epsilon RII. sFc epsilon RII inhibited IgE-binding as well as IgE-mediated release of chemical mediators from Fc epsilon RI and Fc epsilon RII expressing cells. These results show the functional significance of sFc epsilon RII in the negative regulation of IgE-mediated allergic reactions.

Antigens, CD↗

Allergic reactions to polidocanol for vein sclerosis. Two case reports.

BACKGROUND: Polidocanol is a sclerosing solution that is highly valued by clinicians and patients for its painlessness, high efficacy, excellent safety profile, low incidence of side effects, and for the rarity of its allergic reactions. Previous estimates of the incidence of allergic reactions have ranged from 0 to 0.06%. OBJECTIVE: Improved recognition of systemic allergy to polidocanol is desirable for both clinicians and for patients. We have attempted to describe two cases recently observed in our population and to provide an improved upper-bounds estimate for the true population incidence of allergy to polidocanol. RESULTS: We report two recent cases of mild systemic allergic reaction to polidocanol in a population of 689 exposed patients, for an observed incidence of 0.3% in our patient population. We have calculated a 95% confidence upper-bound estimate of 0.91% for the incidence of polidocanol allergy in the general population. CONCLUSION: Allergy to polidocanol may be more common than previously recognized. Careful questioning of previously treated patients and more prolonged observation of patients after treatment may yield a larger number of recognized cases.

Adult↗

[Effect of KC-404 on allergic reactions types I-IV].

The effects of 3-isobutyryl-2-isopropylpyrazolo [1,5-a] pyridine (KC-404), a new anti-allergic agent, on type I to IV allergic reactions were investigated. KC-404 administered orally inhibited heterologous and homologous passive cutaneous anaphylaxis (PCA) reactions in guinea pigs and homologous PCA in rats; the minimum effective doses were 50, 12.5 and 3 mg/kg, respectively. However, the inhibition of PCAs by KC-404 was incomplete so that only 50 to 60% inhibitions were obtainable even at the highest doses used. KC-404 had no effect on increased vascular permeability by chemical mediators other than SRS-A and hardly affected antigen-induced degranulation of the sensitized mesenteric mast cells in vitro. These results suggest that KC-404 exerts its effect conceivably through inhibition of the SRS-A-mediated component of PCA. KC-404 had no effect on type II allergic reaction as estimated by its failure to inhibit reversed cutaneous anaphylaxis in rats and the Forssman systemic reaction in guinea pigs. Also, no influence on complement activity was observed in vitro and in vivo. KC-404 (100 approximately 200 mg/kg, p.o.) produced a marked inhibition of passive and active Arthus reactions in guinea pigs and rabbits, respectively. The tuberculin reaction in guinea pigs was not affected by KC-404. These results suggest that KC-404 inhibits PCAs mediated by IgE as well as IgG antibodies probably through a unique mechanism of action. KC-404 was shown to be effective also on type III allergic reaction.

Anaphylaxis↗

Participation of T lymphocytes in cutaneous allergic reactions to drugs.

Immunological mechanisms implicated in drug allergic reactions are not yet well understood, but there is 'in vivo' and 'in vitro' evidence that T lymphocytes are involved in these hypersensitivity reactions. The cutaneous lymphocyte-associated antigen (CLA) is the skin homing receptor and is involved in targeting a skin-selective memory T lymphocyte to cutaneous sites of chronic inflammation. We have seen that CLA expression is increased in circulating T lymphocytes of patients who develop a drug allergic cutaneous reaction, these cells are activated and their CLA values tend to become normal in parallel with the disappearance of skin symptoms, demonstrating that CD3+ CLA+ cells are involved in the immunological mechanisms responsible for the pathogenesis of the chronic inflammation process in cutaneous drug reactions.

Antigens, Differentiation, T-Lymphocyte↗