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Results of allergen-specific immunotherapy in 117 dogs with atopic dermatitis.

The success of the treatment of 117 dogs with atopic dermatitis with allergen-specific immunotherapy for up to 48 months was assessed. An excellent response (remission with exclusive immunotherapy) was recorded in 18 of the dogs, a good response (more than 50 per cent reduction in medication and improvement of clinical signs) was recorded in 57, a moderate response was recorded in 24 and a poor response in 18. The mould antigens in the allergen extract were stored in a separate vial before administration and the success rate of the immunotherapy including mould antigens was much higher than in an earlier study in which mould and pollen antigens had been stored in one vial. The success rate was not affected significantly by the age of the dogs when the disease developed, or by their age or the period for which they had shown clinical signs when the treatment began; it was also unaffected by whether pollens, moulds or dust mites were used as antigens, or by whether the offending allergens had been identified by intradermal testing or by serum testing for allergen-specific immunoglobulin E.

Age Factors↗

Peripheral cholangiocarcinoma and clonorchiasis: CT findings.

Sixteen patients with peripheral cholangiocarcinoma of the liver were examined with computed tomography (CT). None of the 16 patients presented with jaundice or had documented cirrhosis. On scans obtained both before and after the injection of contrast material, the tumors were depicted as low-attenuation masses in all cases, with wide variations in homogeneity. The tumor margin was irregular in 12 cases, and there was minimal contrast enhancement of the tumor in 14 cases. In 11 (69%) patients, CT demonstrated masses of markedly low attenuation, which corresponded to areas of diffuse microcystic change seen at histologic examination of resected specimens. In ten (63%) patients, the results of stool or intradermal tests for Clonorchis sinensis were positive. In all ten cases of clonorchiasis, mild, diffuse dilatation of the intrahepatic bile ducts was seen in addition to the low-attenuation masses, but there was no dilatation of the extrahepatic biliary tree. In five of the ten patients with clonorchiasis, stippled or aggregated, powderlike areas of high attenuation were seen on precontrast CT scans; at pathologic examination, those areas were found to be mucin. Extrahepatic metastases were demonstrated in ten (63%) patients. Peripheral cholangiocarcinoma should be the primary diagnostic consideration when these characteristic CT findings are detected in a noncirrhotic patient.

Adenoma, Bile Duct↗

A baboon syndrome induced by intravenous human immunoglobulins: report of a case and immunological analysis.

Following the second series of intravenous human immunoglobulins (IVIg; 0.4 g/kg) prescribed to treat a sensorimotor polyneuritis, a 28-year-old woman developed pompholyx that recurred after each of the following monthly treatments with IVIg. During the administration of the 10th series, the patient developed a typical baboon syndrome. Immunohistochemical studies of a skin biopsy revealed an unexpected epidermal expression of P-selectin, usually expressed by endothelial cells. Patch, prick and intradermal tests performed with IVIg on the back, arms and buttocks gave negative results on immediate and delayed readings. IVIg were re-administered, with the informed consent of the patient, and induced a generalized maculopapular rash. This is the first reported case of baboon syndrome induced by IVIg. Although extensive skin testing was performed, all test sites remained negative. We wonder whether IVIg could reproduce immunological mechanisms involved in the 3 types of systemic contact dermatitis (pompholyx, baboon syndrome and maculopapular rash), including the epidermal expression of P-selectin.

Adult↗

A mouse model of mosquito allergy for study of antigen-specific IgE and IgG subclass responses, lymphocyte proliferation, and IL-4 and IFN-gamma production.

To date, there are no ideal animal models for study of natural sensitization leading to IgE- and lymphocyte-mediated hypersensitivities. We established such a model in which four BALB/c mice were each sensitized by exposure to at least 16 mosquito Aedes aegypti bites, twice a week for 4 weeks. Four non-exposed control mice were also studied. Mosquito A. aegypti head and thorax extract, saliva, and two recombinant salivary allergens (rAed a 1 and rAed a 2) were used in vitro as antigens. Intradermal tests were performed. Serum mosquito antigen-specific IgG, IgG1, IgG2a, and total IgE were measured by ELISA; specific IgE was measured by passive cutaneous anaphylaxis (PCA). IgE responses to each antigen in the saliva were analyzed using Western blotting. Spleen lymphocyte proliferation assays were performed to determine the cell-mediated hypersensitivity response. Antigen-induced IL-4 and IFN-gamma production in the spleen lymphocytes were evaluated using ELISA. After 4 weeks, all 4 mosquito-sensitized mice developed a positive immediate wheal 20 min after skin tests with mosquito antigens, and a positive delayed papule 24 h later, while control mice did not. Also, the sensitized mice had a positive PCA response, which correlated significantly with total IgE levels (r = 0.84, p<0.05), confirming the presence of antigen-specific IgE, while none of control mice had a positive response. Antigen-specific IgG1, but not IgG2a, was increased in the sensitized mice (p<0.01). Western blotting showed that 5 of the 8 antigens which elicited mouse IgE responses, including 2 major antigens, also elicited human IgE responses. The mean lymphocyte proliferation response to mosquito antigens also elicited human IgE responses. The mean lymphocyte proliferation response to mosquito antigens was significantly increased in the sensitized mice (p<0.05). IL-4 production was significantly increased and IFN-gamma production was decreased, further suggesting that a Th2 immune response predominates despite the development of the delayed skin reaction. This new model of natural sensitization without using an adjuvant is potentially useful for the study of other allergic disorders as well as mosquito allergy.

Allergens↗

Characterization of cogon grass (Imperata cylindrica) pollen extract and preliminary analysis of grass group 1, 4 and 5 homologues using monoclonal antibodies to Phleum pratense.

BACKGROUND: Previous studies have established the role of Imperata cylindrica (Ic) pollen in type I allergic disorders. However, no systematic information is available on the allergen composition of Ic pollen extract. OBJECTIVES: To characterize the IgE-binding proteins of Ic pollen extract and to detect the presence of grass group 1, 4 and 5 allergen homologues, if any. METHODS: Pollen extract of Ic was analyzed by in vivo and in vitro procedures such as intradermal tests (ID), enzyme-linked immunosorbent assay (ELISA), ELISA-inhibition, thin-layer isoelectric focusing (TLIEF), sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Dot blot assay was carried out to check the presence of well-known group 1, 4, and 5 allergen homologues in Ic pollen extract. RESULTS: Out of 303 respiratory allergies patients skin-tested, 27 showed sensitivity to Ic pollen extract. Specific IgE levels were elevated in all 15 serum samples tested. The extract prepared for this study was found to be highly potent since it required only 400 ng of homologous proteins for 50% inhibition of binding in ELISA inhibition assays. TLIEF of Ic pollen extract showed 44 silver-stained bands (pI 3.5-7.0) while SDS-PAGE resolved it into 24 Coomassie-Brilliant-Blue-stained bands (MW 100-10 kD). Immunoblotting with individual patient sera recognized 7 major IgE-binding bands (MW 85, 62, 57, 43, 40, 28 and 16 kD) in Ic pollen extract. A panel of monoclonal antibodies, specific to group 1, 4 and 5 allergens from Phleum pratense pollen extract identified group 5 and group 4 homologues in Ic pollen extract. CONCLUSION: Ic pollen extract was characterized for the protein profile by TLIEF and SDS-PAGE. IgE reactivity was determined by ELISA and immunoblot. Monoclonal antibodies to group 5 and group 4 allergens reacted weakly showing that this pollen contains group 5 and group 4 homologous allergens.

Adolescent↗

Induction of IgE responses using a recombinant mosquito salivary allergen rAed a 2 without adjuvant in mice.

BACKGROUND: Reactions to mosquito bites are a global problem. Several salivary proteins from Aedes (Ae.) aegypti, the most common mosquito species, have been cloned and expressed. Plasmid DNA vaccination has been shown to be effective in the downregulation of IgE responses. To investigate the in vivo antigenicity of these recombinant proteins and to study the mechanisms underlying plasmid DNA vaccination, a mouse model sensitized with a recombinant antigen has been developed. METHODS: BALB/c and C57BL/6 mice were injected intradermally with a 37-kD recombinant Ae. aegypti salivary allergen (rAed a 2) in the absence of adjuvant twice weekly for 8 weeks and then challenged twice with rAed a 2 at weeks 10 and 12. Serum rAed a 2-specific IgE, IgG1 and IgG2a were measured by ELISA. Intradermal tests were performed every 4 weeks. The binding capacity of rAed a 2-specific IgE to the native Aed a 2 was examined by immunoblotting. RESULTS: In both strains, sensitization with rAed a 2 induced a significant increase in IgE and IgG1, but not IgG2a. In all sensitized mice, a positive immediate skin reaction was apparent, while delayed-type hypersensitivity reactions were not observed. BALB/c mice produced significantly higher levels of IgE and IgG1 and larger wheals than C57BL/6 mice. The IgE antibodies elicited by rAed a 2 bound to not only rAed a 2 but also its natural form in mosquito saliva. CONCLUSION: (1) Repeated injections of rAed a 2 without adjuvant induce predominant Th2-type responses in mice. (2) BALB/c mice are better responders for IgE production than C57BL/6 mice. (3) rAed a 2 has identical allergenicity to its natural form.

Adjuvants, Immunologic↗

A study comparing the inhibitory effects of single and repeated oral doses of ebastine and fexofenadine against histamine-induced skin reactivity.

OBJECTIVE: The aim of this double-blind, randomized, crossover, placebo-controlled clinical trial was to compare the inhibition of the histamine-induced skin reaction induced by ebastine 20 mg with respect to that induced by fexofenadine 120 mg or placebo. METHODS: Eighteen volunteers (10 males, 8 females) received the three treatments once daily for 5 days, with a mean 7-day washout period between treatments. Intradermal tests, using 0.05 ml from a solution containing 100 microg/ml of histamine, were performed at baseline and at 1, 1.5, 2, 3, 10 and 24 h after a single dose and repeated 5-day dose, and in addition after 34, 48, 58 and 72 h after repeated 5-day dose. RESULTS: After 24 h of acute administration, ebastine 20 mg was significantly more effective than fexofenadine 120 mg in reducing the wheal and flare induced by histamine challenge (p<0.001). Although fexofenadine 120 mg had the shortest onset of action (1.5 vs. 3 h in ebastine 20 mg), the duration of its antihistamine effect was the shortest (24 vs. 58 h in ebastine 20 mg) and wheal reduction after 24 h was not significantly different from placebo. The overall effect after single and repeated 5-day dose, expressed as the AUC of reduction of wheal and flare area (%/h), showed the following order of magnitude: ebastine 20 mg>fexofenadine 120 mg>placebo. No significant differences in the incidence of adverse events were found between the three treatments. CONCLUSIONS: The present results clearly show a superior and long-acting effect of ebastine 20 mg compared with fexofenadine 120 mg on the skin response to histamine 24 h after dosing.

Administration, Oral↗

Delayed allergic reaction to suxamethonium driven by oligoclonal Th1-skewed CD4+CCR4+IFN-gamma+ memory T cells.

BACKGROUND: Muscle relaxants represent the drugs most frequently involved in intraoperative anaphylaxis during surgical procedures. Our aim was to report the case of a delayed reaction to suxamethonium and analyze specific T cell lines with regard to their specificity, phenotype and cytokine profile. METHODS: We generated a drug-specific T cell line from a biopsy at the site of positive intradermal reactions and analyzed the immunophenotype, T cell receptor Vbeta domain expression and cytokine profile. RESULTS: T cells isolated from positive intradermal test reactions to suxamethonium showed a strict dose-dependent proliferation in response to drug-pulsed autologous antigen-presenting cells. The drug-specific CD4+ T cells were oligoclonal memory CD3+CD4+ T cells and expressed the skin homing receptors cutaneous lymphocyte antigen (CLA) and CCR4. Furthermore CD4+ suxamethonium-reactive T cell lines were IFN-gamma-positive and synthesized high levels of IFN-gamma and TNF-alpha. CONCLUSION: The study describes a delayed hypersensitivity to suxamethonium, driven by an oligoclonal T helper cell 1-skewed CD4+ memory T cell population, expressing the skin homing receptors CLA and CCR4.

Adjuvants, Anesthesia↗

Responses of monkeys with pollinosis to two major allergens of Japanese cedar pollen.

We examined the responses of two Japanese monkeys with pollinosis to two major allergens (Cry j 1 and Cry j 2) of Japanese cedar pollen. The two monkeys (A and B) had specific IgE antibodies to the allergens and showed a strong positive reaction to both of them in the intradermal test. In the histamine release test with peripheral blood mononuclear cells (PBMC), monkey A showed a typical pattern similar to that seen in human patients, while monkey B released a low level of histamine. The proliferative response of PBMC to both allergens in monkey A was weak, but was typical in monkey B. From clinical as well as immunological points of view, these monkeys may be a suitable animal model for Japanese cedar pollinosis in humans.

Allergens↗

Cutaneous late-phase reaction to environmental antigen in patients with atopic dermatitis.

Intradermal testing with 7 environmental allergens was performed on 71 patients with atopic dermatitis (AD) with respiratory atopy (RAT) and 30 pure AD patients, and the cutaneous late-phase reaction (CLPR) was observed several to 48 h after challenge. CLPR was not seen in pure AD. In AD patients with RAT, CLPR was positive in 29 of 71 patients. No macroscopic eczematous lesions appeared. All CLPR-positive patients showed RAST scores of 2 or more. We assume that CLPR can be an exacerbating factor in AD with RAT, while it is not directly involved in pure AD.

Adolescent↗

Cell-mediated immunity after bacterial infection of the lower respiratory tract.

Lower respiratory tract and systemic cell-mediated immunity have been studied in rabbits after infection with Listeria monocytogenes or Diplococcus pneumoniae. Respiratory tract cell-mediated immunity was evaluated by direct and indirect assays of migration inhibitory factor (MIF) production. Systemic delayed hypersensitivity was determined by means of intradermal testing with appropriate antigens. Aerosol exposure to listeria was followed by markedly increased numbers of free lower respiratory tract cells. These cells manifested antigen-stimulated inhibition of migration (mean inhibition of migration = 30.4%). Pneumococcal pneumonia was associated with similar but less dramatic changes. Intravenous administration of organisms was uncommonly followed by inhibition of lower respiratory tract cells in direct migration assays. Fractionated MIF, as well as crude supernates of antigen-stimulated lower respiratory tract and lymph node lymphocytes from animals exposed to listeria aerosols, caused inhibition of normal alveolar macrophage migration. MIF, produced by lymph node lymphocytes, has a molecular weight of approximately 65,000 and is inactivated by chymotrypsin or neuraminidase. Delayed dermal hypersensitivity to listeria antigen was observed in 54 of 55 animals exposed to listeria aerosols and in all 9 animals infected by the intravenous route. Delayed dermal reactions to pneumococcal sonicate antigen (but not capsular polysaccharide) followed D. pneumoniae respiratory tract infection in 19 of 28 animals, and was elicited in 5 of 6 animals after intravenous infection. Both local (macrophage migration inhibition) and systemic delayed hypersensitivity followed bacterial infection of the lower respiratory tract. MIF activity was shown to be one mechanism for inhibition of alveolar macrophage migration.

Animals↗

Anaphylaxis to suxamethonium--a case report.

A case history is presented of a woman who developed very severe bronchospasm, hypotension, "lobster-red" erythema and later angio edema of the head and neck after induction of anaesthesia for caesarean section. Intradermal testing at a later date, showed immediate-type sensitivity to suxamethonium. Reference is made to the other few reactions to suxamethonium reported in the world literature.

Adult↗

Anaphylaxis to alcuronium.

Five cases of severe anaphylactic reactions to alcuronium are described. Investigation suggested that these are probably true anaphylaxis to the drug. The cases illustrate the value of intradermal testing in detecting the drug involved and the necessity of using colloidal solutions and adrenaline in the management of hypotension due to anaphylaxis.

Adolescent↗

Alleged allergy to local anaesthetics.

The aim of this study was to determine the incidence of true local anaesthetic allergy in patients with an alleged history of local anaesthetic allergy and whether subsequent exposure to local anaesthetics is safe. Two hundred and eight patients with a history of allergy to local anaesthesia were referred over a twenty-year period to our Anaesthetic Allergy Clinic. In this open study, intradermal testing was performed in three patients and progressive challenge in 202 patients. Four patients had immediate allergy and four patients delayed allergic reactions. One hundred and ninety-seven patients were not allergic to local anaesthetics. In 39 patients an adverse response to additives in local anaesthetic solutions could not be excluded. In all but one patient local anaesthesia has been given uneventfully subsequently. A history of allergy to local anaesthesia is unlikely to be genuine and local anaesthetic allergy is rare. In most instances LA allergy can be excluded from the history and the safety of LA verified by progressive challenge.

Adolescent↗

Cisatracurium and atracurium as antigens.

Seventy-five consecutive patients referred to an anaesthetic allergy clinic were intradermally tested with atracurium and cisatracurium. With the exception of one patient the results were identical, suggesting that allergy to either drug is associated with allergy to the stereoisomer. For skin testing for allergy to neuromuscular blocking drugs it is only necessary to use either atracurium or cisatracurium and cisatracurium is the preferred drug.

Allergens↗

Insulin allergy and resistance successfully treated by desensitisation with Aspart insulin.

A 25-year-old, with type I Diabetes Mellitus with a previous diagnosis of Protamine Allergy but not to human Insulin, started to notice anaphylactic reactions immediately after bolus with Insulin. Skin prick and intradermal test were positive to all insulins. Skin tests to other potential allergens resulted negative. Examination after bolus of Human Insulin revealed urticaria. Daily insulin requirement were around 2-2,4 U/Kg/day. Slow desensitisation with Aspart insulin, the insulin with lowest size of skin test, was performed using subcutaneous insulin pump. Six months after the end of desensitisation his daily insulin requirement decreased to 0.8 U/Kg/day and oral corticosteroids are being reduced with no symptoms.

Journal Article↗

Insulin allergy: reaginic antibodies to insulin and proinsulin.

To investigate the involvement of proinsulin (one of the contaminant proteins of therapeutic insulin) in systemic insulin allergy, we studied seven diabetic patients who presented with generalized insulin allergy. Commercial and highly purified (single component) insulins produced almost identical responses on the intradermal tests. In all cases, [125I]bovine insulin and [125I]bovine proinsulin bound to the circulating reaginic immunoglobulins. The binding of [125A]proinsulin was blocked completely by unlabeled insulin and was uneffected by bovine C-peptide, indicating a cross-reaction of proinsulin with antinsulin reaginic immunoglobulins and the absence of proinsulin-specific reaginic antibodies. These observations suggest insulin, but not proinsulin, as the mediator of the immediate insulin allergic reaction.

Adult↗

Anaphylaxis during the perioperative period.

Anesthesiologists use a myriad of drugs during the provision of an anesthetic. Many of these drugs have side effects that are dose related, and some lead to severe immune-mediated adverse reactions. Anaphylaxis is the most severe immune-mediated reaction; it generally occurs on reexposure to a specific antigen and requires the release of proinflammatory mediators. Anaphylactoid reactions occur through a direct non-immunoglobulin E-mediated release of mediators from mast cells or from complement activation. Muscle relaxants and latex account for most cases of anaphylaxis during the perioperative period. Symptoms may include all organ systems and present with bronchospasm and cardiovascular collapse in the most severe cases. Management of anaphylaxis includes discontinuation of the presumptive drug (or latex) and anesthetic, aggressive pulmonary and cardiovascular support, and epinephrine. Although a serum tryptase confirms the diagnosis of an anaphylactic reaction, the offending drug can be identified by skin-prick, intradermal testing, or serologic testing. Prevention of recurrences is critical to avoid mortality and morbidity.

Anaphylaxis↗