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Flea bite hypersensitivity: new aspects on the involvement of mast cells.

A study was performed to test the effect of sensitization to flea antigen, followed by exposure to fleas on mast cells (MCs), their subtypes, and IgE+ cells. Biopsies were taken from flea-sensitized dogs (n=28) and non-sensitized dogs (n=5) that had been exposed to fleas. Control groups consisted of flea-sensitized (n=12) and non-sensitized dogs (n=9) that were not exposed to fleas. Biopsies, taken before, 24 and 72 h after local flea exposure, were stained with haematoxylin and eosin (H&E), toluidine blue, a double labelling technique for MC chymase and tryptase and anti-IgE. An intradermal test for flea antigen was performed and serum titres of allergen-specific IgE and IgG were measured. Significantly higher numbers (P<0.001) of double labelled MCs compared to toluidine blue stained MCs were detectable in flea-sensitized dogs independent of flea exposure. In contrast, in non-sensitized dogs, the number of toluidine blue stained MCs and the number of double labelled MCs did not differ. In flea-sensitized dogs after flea exposure the percentage of C-MC was significantly increased at day 1 (P<0.001) and day 3 (P<0.001), whereas the percentage of TC-MCs decreased significantly at day 1 (P<0.001) and day 3 (P<0.05). The percentage of T-MCs decreased (P<0.05 day 0 versus day 1; P<0.05 day 0 versus day 3). No significant difference was detectable after toluidine blue staining and staining for IgE+ cells between the groups nor between the MC density and the number of IgE+ cells. All flea-sensitized dogs had positive skin tests to flea antigen and high serum titres of flea-specific serum IgE and IgG antibodies. In non-sensitized dogs, these results were negative. Our data provide strong evidence for an upregulation of MC proteases during the process of sensitization and a generalized selective release of mast cell tryptase after exposure to the antigen.

Animals↗

Delayed hypersensitivity responses of experimental animals to histoplasmin from the yeast and mycelial phases of Histoplasma capsulatum.

Controlled yeast lysate (CYL) and controlled mycelial lysate (CML) histoplasmins were produced from Histoplasma capsulatum grown in a nutritionally lean, chemically defined medium. The lysates were assayed for skin-test activity in guinea pigs sensitized by infection with the homologous organism. In some studies, nonliving vaccine preparations were employed also. Inter-lot biological variation was minimal, and 20 lots of the CYL reagent elicited strong dermal reactions with high specificity. Further, CYL reagents were nonreactive in guinea pigs infected with Coccidioides immitis, whereas the commercial Food and Drug Administration preparations cross-reacted to some degree. The CML histoplasmins were generally less reactive than the CYL preparations and exhibited somewhat more inter-lot variation in sensitivity and specificity. No correlation between potency and protein:polysaccharide ratios were observed with either reagent. An intradermal test with the CYL reagent did not induce significant changes in the complement-fixing titer of sensitized guinea pigs. Such changes in sensitized animals were elicited by a skin test with commercial histoplasmin.

Animals↗

Morphine alteration of histamine release in vivo.

Studies were performed to evaluate the effects of either acute or chronic morphine exposure on histamine release in vivo and supporting studies in vitro. In order to effectively assess histamine release in swine, studies were undertaken to evaluate the effectiveness of compound 48/80 as an intradermal skin test and determine its ability to release histamine in swine cells. Compound 48/80 skin testing was found to be a useful measure of histamine release in swine as evidenced by dose dependent wheal and flare reaction in vivo and histamine release from swine cells in vitro. Acute effects of morphine were determined on swine administered a single injection of morphine alkaloid. Skin tests using intradermal compound 48/80 and histamine, were performed using compound 48/80 both prior to, and 24 h following initiation of morphine treatment. Morphine tolerant swine were subjected to in vivo skin tests and the resulting wheal and flare responses measured. In select swine skin samples from the test sites were measured for mast cell numbers. Swine dermal mast cells were found to release histamine in a dose dependent manner upon compound 48/80 exposure. Both acute and chronic morphine-treated swine had significantly depressed responses to compound 48/80, however this difference was not due alteration in mast cell number or morphology, and skin responsiveness to histamine remained intact.

Animals↗

Intradermal positivity after negative prick testing for inhalants.

OBJECTIVE: Examine the incidence of positive intradermal tests after a negative skin prick test for 24 inhalant antigens. STUDY DESIGN AND SETTING: Retrospective study. Charts from patients who underwent modified quantitative testing (MQT) over a 3-year period were reviewed. Patients were initially tested with Multi-Test II. Subjects with negative wheals to a specific allergen were then tested with a 1:500 weight:volume intradermal injection of that allergen. RESULTS: One hundred thirty-three patients underwent MQT for 24 antigens. Allergens with the highest incidence of positive intradermal wheals after negative prick testing were Dermatophagoides pteronyssinus and Dermatophagoides farinae at 26.67%. Allergens with elevated incidence of positive intradermals included fusarium, cockroach, cocklebur, rough marsh elder, and ragweed, all with incidences of 16% to 19%. CONCLUSION: Positive intradermal responses after negative prick testing occur commonly. Future study is needed to determine the generalizability and clinical significance of these findings. EBM RATING: C-4.

Algorithms↗

Fatalities from immunotherapy (IT) and skin testing (ST)

The Committee on Allergen Standardization of the American Academy of Allergy and Immunology obtained information about 46 fatalities that had occurred during immunotherapy (IT) or skin testing (ST) since 1945. Sufficient information for complete analysis was provided for 30 patients (six for ST and 24 for IT). Of the 30 fatalities, there were 15 male and 15 female fatalities ranging in age from 7 to 70 years (x = 33 years). Known errors of administration accounted for three and possibly an additional three fatalities. Ten fatalities occurred during seasonal exacerbation of the patient's disease, four in patients who had been symptomatic at the time of the injection, two of whom had been receiving beta-adrenergic blockers. Of the 24 fatalities associated with IT, four had experienced previous reactions, 11 manifested a high degree of sensitivity, and four had been injected with newly prepared extracts. Fifteen of the 30 fatalities had received pollen extracts as part of the fatal injection. Of the six fatalities associated with ST, five were due to intradermal testing without prior puncture testing. The signs and symptoms were variable and did not indicate that death was imminent nor predict the cause of death. The time to onset of the reaction was less than 30 minutes in 22/30, more than 30 minutes in 3/30, and not reported in 5/30. The cause of death in 14/16 patients with asthma was respiratory. Epinephrine had been administered to 18, not administered to three, and was either not recorded or unknown in the remaining nine patients. Since seven to 10 million allergen injections are administered yearly, the risk of a fatal reaction is low and may be lessened even further as additional precautions are taken in the selection and treatment of allergic patients and in improved treatment of the anaphylactic reactions.

Adult↗

Hemolytic streptococcus preparation OK-432; beneficial adjuvant therapy in recurrent gastric carcinoma.

The administration of a hemolytic streptococcus preparation, OK-432, is thought to be of therapeutic value in the treatment of cancer patients through a stimulatory effect on the immune system. In order to evaluate any beneficial effect of such an administration, a group of patients with recurrent gastric cancer was studied. This group was randomly subdivided into 3 groups: 1) Intradermal group (ID Group), 42 patients given an intradermal injections of OK-432. 2) Intramuscular group (IM Group), 40 patients given an intramuscular injections of OK-432. 3) Control group (C Group), 39 patients not given injections. Each group was studied in regards to the length of survival, the host immune response and the incidence of side effects. When compared to the IM and C Groups, the ID Group showed improved survival. Accompanying this improved survival, the ID Group also had greater white cell and lymphocyte counts, a greater number of T cells, and a more dramatic skin reaction to the extracted cell wall polysaccharide of hemolytic streptococcus Su-strain (Su-PS). The ID Group, following OK-432 injection, had a 4.8% incidence of fever and a 52.4% incidence of local abscess formation at the injection site. 90% of the IM Group developed fever but abscess formation was absent in all patients. From these results, it was concluded that in the patients tested, intradermal injection of OK-432 appears to be clinically superior to intramuscular injection.

Adjuvants, Immunologic↗

Comparative skin testing with PPD tuberculin, Mycobacterium avium and M. scrofulaceum sensitin in schoolchildren in Saudi Arabia.

SETTING: Jizan region, Saudi Arabia. OBJECTIVE: To test methodology for studies of tuberculin sensitivity and effectiveness of BCG vaccination programme. DESIGN: School children (n = 315) aged 6-12 years simultaneously tested intradermally with PPD tuberculin RT23, 2TU and 0.1 microgram Mycobacterium avium or M. scrofulaceum sensitin. Presence of BCG scar as evidence of previous BCG vaccination. Cervical lymph nodes palpated. RESULTS: BCG coverage was 75%. The prevalences of positive reactions (induration > or = 6 mm) were higher among children with than without scar. Prevalences of positive reactions to PPD and M. scrofulaceum sensitin were higher among girls than boys. In children with scar, the mean size of positive reactions to PPD was larger among girls than boys, and the prevalence of positive reactions was smaller in this group among children with than without palpable cervical lymph nodes. The sizes of reactions both to M. avium and to M. scrofulaceum sensitin were correlated to the size of the tuberculin reactions. Previous admission to hospital was reported less often by children with than without scar. CONCLUSIONS: The technique applied and training of staff was satisfactory. In further studies, however, we will apply three simultaneous tests to each person.

Age Factors↗

Persistent cutaneous pseudolymphoma after intradermal gold injection.

After intradermal testing with goldsodiumthiomalate (GSTM), 5 out of 8 patients developed skin papules at the test sites, which persisted up to 20 months. The lesions were surgically excised. Histology revealed pseudolymphoma of B and T cell type containing follicular structures and occasional small granulomas. The amount of histiocytic cells among B and T lymphocytes was pronounced, including acid cysteine proteinase inhibitor (ACPI) positive follicular dendritic cells, CD68 positive macrophages, factor XIIIa positive dermal dendrocytes and S-100 positive cells. By electron microscopy, the macrophages contained endosomes loaded with crystalloid material which contained gold in X-ray microanalysis. Atomic absorption spectrophotometry also confirmed the presence of gold in one specimen. Thus GSTM seemed to accumulate in tissue macrophages leading to constant immunologic activation with lymphoid proliferation and histiocytic response.

Adolescent↗

Mass Chemotherapy In The Control Of Paragonimiasis.

Among 11,005 inhabitants(61% of total population) surveyed in 13 villages of Che Ju Island in 1964, were identified as paragonimiasis patients, of these 1,355 were treated with 40 mg/kg body weight of bithionol for 10~15 doses. The purpose of the study was to test whether mass chemotherapy of the human host may provie an answer for the control of paragonimiasis in an area where the human host is main source of infection to the intermediate hosts. The efficacy of the mass chemotherapy as control program was measured by the acceptance of the survey and treatment by the inhabitants, the efficacy and the toxicity of the drug applied, and the influence of the infection rates of the intermediate hosts. The acceptance of the survey and the treatment was not entirely satisfactory: an estimate based on data suggests that only fifty to sixty percent of all cases infected were detected, and 93% of detected cases were treated in the primary program. All cases detected during the follow up survey, which could not cover whole population, were treated. The efficacy of bithionol was excellent when the treatment was completed. 40 mg/kg body weight for 10~15 doses was sufficient to turn the sputum egg-negative except in a few cases infected heavily that needed 20 doses. Side reactions were generally mild; the most frequent reaction was gastrointestinal; which spontaneously subsided within a few to several days. The infection rate of intermediate hosts started to decrease from the third year of the mass treatment with a pattern of gradual drop. Follow up studies on general population in three and four years of the mass treatment also showed markedly decreased prevalence of paragonimiasis by intradermal test and sputum examination. It is concluded that a complete mass chemotherapy with bithionol in an area where human is the main source of infection to the intermediate hosts can be the answer for control of paragonimiasis.

Journal Article↗

[Current incidence of tubercular infection in children in the Dolj district].

A lot of 122459 children under the age of 14 were tested intradermally with 2 U PPD. Most of them had been vaccinated at birth and some revaccinated later during the 1966-1967 period, which does not represent interpretation of the prevalance of tuberculosis today, bearing in mind the low postvaccinal allergy of young children and the interval after the last vaccination, only the children with a reaction of more than 10 mm in diameter were taken into consideration as they represented the highest probability of the actual spread of the infection. In the age group up to 6 years 6.82% of the children were infected and 17.12% of the school children of grades II to VIII, i.e. less than the mean values recorded in the whole country. This was attributed to the intensive specific chemotherapy applied within the area. The prevalence gradually increased from 3.93% at the age of l year to 4.90% at 3 years, then sharply to 6.93% at 4 years (when the child's relations are extended) and 10.46% at 5 years. The proportion of infections was of 12--13% in grades II--IV (7-9 years), 16.63% in grade V, 20% in grade VI and 23.21% in grade VIII (13-14 years). The present values are much lower than those recorded in 1966. The present risk of infection is of 1%, with an annual decrease rate of 7%, starting in 1956. By comparison with the published data it is considered that neutralization by chemotherapy of all bacilli carriers will accelerate the rate of decrease of infection.

Adolescent↗

Cholinergic urticaria. A clinical and histologic study.

We studied the natural history, the prevalence of atopy, and the frequency of systemic symptoms during attacks in 35 patients with cholinergic urticaria, the histologic condition of the eruption in seven patients (20%), and the response to intradermal injections of acetylcholine, histamine, and methacholine in 18 patients (51%). In most patients symptoms began between the ages of 10 and 30 years, persisted for many years, and caused them to modify their activities to avoid the provoking factors of exercise, emotion, and heat. The condition usually improved with time, and five patients (14%) had a spontaneous remission. Atopy, present in about 12 (34%) of the patients, was more frequent than in the general population. Systemic symptoms were uncommon during attacks, and patients had no greater responses than controls to the intradermal tests. The histologic study revealed neutrophils in and around the walls of superficial subpapillary dermal vessels.

Adolescent↗

Drug eruptions from mesna. After cyclophosphamide treatment of patients with systemic lupus erythematosus and dermatomyositis.

BACKGROUND: Mesna is used to abolish urotoxicity of cyclophosphamide and related compounds in immunosuppressive and antineoplastic treatment schedules. Adverse reactions to this drug have been reported only rarely. OBSERVATIONS: Drug eruptions to mesna have developed in seven of 15 patients with autoimmune disorders treated with monthly pulses of intravenous cyclophosphamide. Two different types of drug eruptions were observed: five patients had development of a macular and partly papular or urticarial rash and angioedema and two patients had a generalized fixed drug eruption, primarily and predominantly at the sites of previous skin lesions of their underlying condition. The results of prick, patch, and intradermal tests were similar in both types of rash; however, the two patients with fixed drug eruption had developed a generalized eruption upon prick testing with mesna. CONCLUSIONS: Two distinct eruptions to mesna have been induced in these patients during cyclophosphamide/corticosteroid therapy; these eruptions are not thought to share a common pathogenic mechanism. The results of skin and challenge tests do not support the hypothesis that a type 1 or a type 4 immune reaction may be responsible for these eruptions. The unusually high incidence (about 50%) of these reactions and their clinical presentation make it important to distinguish them from an exacerbation of the preexistent autoimmune disorder.

Adult↗

Cytarabine-induced anaphylaxis. Demonstration of antibody and successful desensitization.

An anaphylactic episode occurred in a patient receiving cytarabine (Ara-C) for acute myeloid leukemia. Specific allergy of the patient to cytarabine was demonstrated in vivo by intradermal testing and in vitro by four-hour passive cutaneous anaphylaxis in guinea pigs. Desensitization to cytarabine was successfully performed. This case represents the first known report of both cytarabine anaphylaxis and densensitization, and provides immunologic evidence implicating an allergic reaction to cytarabine.

Aged↗

Automated serology with recombinant allergens. A feasibility study.

Diagnosis of allergic conditions is based on skin prick- and/or intradermal tests and on serology. Both methods make use of allergenic preparations and the results mainly depend on the quality of the substances applied and on the reactivity of the subjects. Recombinant allergens can be produced as highly pure proteins. They may contribute to a significant improvement of the diagnosis of allergic diseases provided that the allergens became available in a pure, fully antigenic form suitable for routine assessments. We have studied the diagnostic properties of recombinant Aspergillus fumigatus allergen I (rAsp f I/a), a major allergen recognised by about 60% of the A. fumigatus allergic individuals, to test the feasibility of using recombinant allergens for automated serology in the Pharmacia CAP System, a new solid-phase immunoassay. ImmunoCAPs carrying immobilised rAsp f I/a were produced and evaluated using sera from well characterised patients with allergic bronchopulmonary aspergillosis (ABPA), allergic asthmatics with or without A. fumigatus sensitisation, and healthy control persons. The clinical parameters used for the diagnosis of allergy to A. fumigatus were RAST and skin test reactivity to commercial A. fumigatus extracts. IgE antibodies recognising rAsp f I/a were determined by a direct antigen-specific ELISA and with the newly developed rAsp f I/a ImmunoCAPs. Quantitative results from the two rAsp f I/a detection systems correlated closely, indicating that this recombinant allergen can be incorporated in the Pharmacia CAP System with unaltered antigenic activity. The behaviour of a panel of recombinant A. fumigatus allergens in the Pharmacia CAP System will be evaluated in the near future to assess the potential of recombinant allergens for the automated diagnosis of allergic conditions.

Allergens↗

Digestion of killed Paracoccidioides brasiliensis by neutrophils.

We previously described an in vitro assay showing that neutrophils (PMNs) from patients with paracoccidioidomycosis (PARA) have a specific digestive deficiency against suspensions of live Paracoccidioides brasiliensis. We now report that this defect is equally detectable against autoclaved, but not Amphotericin B-killed P. brasiliensis. The use of autoclaved suspensions facilitates the use of our in vitro assay. It might allow the development of an in vitro intradermal test for digestion of fungi. Differential digestive ability of phagocytes against live (or autoclaved) and Amphotericin-B killed fungi is of conceptual interest. It may be relevant in understanding therapeutic effect of Amphotericin B.

Amphotericin B↗

Tuberculosis in children: a 13-year follow up of 1714 patients in a Belgian home care centre.

From May 1970 to September 1983, 1714 children with different forms of primary tuberculosis were referred to the paediatric home care centre (Enfants soignés au Foyer, E.S.F.) of the Brussels University Hospital St.-Pierre. They were subdivided in five groups: asymptomatic (33%), symptomatic (28%), dubious tuberculous infections (35%), high-risk contacts (3%) and unestablished diagnosis (1%). They were aged from 10 days to 19 years, and 82% of them were migrants of low socio-economic level. Fifty percent of the symptomatic infections, mainly pulmonary, appeared in children under 3 years of age. An adult source of contamination was identified in 33% of the cases (48% of the symptomatic children). Diagnosis was based on tuberculin screening with a 2IU intradermal test. Gastric aspirates yielded Mycobacterium tuberculosis in 15% of our patients, 11% of them showing resistance to one or more tuberculostatic drugs. Treatment was given to 1359 patients with excellent results. Therapy was shortened during the last 2 years of the study from 12 to 6 months for the asymptomatic patients and from 12 to 9 months for the symptomatic infections. Few complications were observed. Tuberculosis remains a serious cause of morbidity particularly in migrant children. Correct diagnosis and treatment of the disease is very important.

Adolescent↗