Observations on the cellular response to filarial skin test antigen using the "skin window" technique: a preliminary report.
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Although anergy testing is commonly used to help interpret negative tuberculin skin test results, the validity of this approach has not been demonstrated. Specific issues include lack of a standardized protocol for antigen selection, number needed to reliably evaluate inability to respond, and uniform criteria for defining cutaneous reactivity, as well as regional variation in skin test reactivity. Tuberculin skin testing is used to screen for latent infection and to evaluate the need for isoniazid prophylaxis. The presence or absence of reactivity to control antigens does not affect this decision. The results of anergy testing also do not predict the risk for progression to active disease in either HIV-negative or HIV-positive patients. In HIV-negative patients with active tuberculosis, 10% to 20% have negative tuberculin test results, and 5% to 10% have a negative tuberculin result but have a positive reaction to another antigen. A negative tuberculin skin test result does not exclude either latent infection or active disease, even in the presence of a reaction to other antigens. Neither anergy testing nor tuberculin testing obviates the need for microbiologic evaluation when there is suspicion for active tuberculosis infection. Therefore, anergy testing is not useful in screening for asymptomatic tuberculous infection or for diagnosing active tuberculosis.
One hundred twenty five allergic patients ranging in age from 0 to 36 years old (mean age 9 years) were tested. Intradermal skin tests were performed on the volar surface of the forearm by injection of a five-fold dilution of histamine dihydrochloride (from 1 x 5(-5) mg/ml to 1 x 5(-2) mg/ml). The wheal diameters increased incrementally with histamine concentration. The whealing capacity of the skin to histamine was found to be significantly lower in patients 0 to 5 years of age. There was no difference in the mean wheal size between patients 6 to 10 and 11 to 15 years of age. The wheal size in patients 16 to 36 years of age were significantly larger than those in the other age groups. The flare diameters also increased incrementally with histamine concentration. The mean diameter of flares was significantly lower in patients 0 to 5 years of age. Concentrations between 1 x 5(-3) mg/ml and 1 x 5(-2) mg/ml of histamine dihydrochloride should be taken for a positive control in intradermal allergen skin tests.
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Delayed hypersensitivity skin testing with multiple antigens is frequently used to evaluate immunopotentiation therapy in man. Since serial skin testing with a single antigen has been shown to augment the skin test response, the present study was undertaken to assess the effect of serial delayed hypersensitivity skin testing on skin test reactivity with multiple antigens. Each of twelve healthy volunteers received 0.1 ml of five antigens on two occassion, 6 weeks apart. The antigens used were streptokinase-streptodornase, Candida, Trichophyton, mumps and Mycobacterium tuberculosis (PPD). The results demonstrated enhancement of skin test reactivity in the majority of tests. Indeed, 38.9% of the tests which were negative with the first skin test ( less than 10 mm induration) converted to positive. Enhancement in reactivity was observed in the majority of test subjects with all antigens except PPD. Similar enhanced skin test reactivity was observed in fifteen additional subjects tested serially with Candida only. The observations in this study suggest that uncontrolled studies of immunopotentiation must be interpreted with caution since serial delayed hypersensitivity skin testing with single or multiple antigens results in enhanced skin test reactivity.
Skin testing for penicillin allergy is an imperfect predictor of severe allergic reactions. We used decision analysis to identify the types of allergy history for which skin testing should alter management. The treatment threshold, the probability of a serious allergic reaction at which point one should switch from penicillin to another antibiotic, depends on the quality of life associated with the clinical outcomes. We measured 12 physicians' attitudes toward the outcomes of treatment with penicillin or vancomycin for Streptococcus viridans endocarditis in patients with a history of penicillin allergy. The clinicians' threshold probabilities ranged from .00010 to .00210 (median, .00013). Given the sensitivity (89% to 96%) and specificity (89% to 96%) of skin testing and our clinicians' median threshold, test results could alter the choice of antibiotic when the probability of a severe allergic reaction is between .00001 and .001. This range corresponds to a weak history of penicillin allergy. Although the decision should be individualized, our study suggests that skin testing is unnecessary when the patient has a convincing history of a severe allergic reaction to penicillin.
Routine tuberculin skin testing (intradermal PPD test) at a university health service is carried out to fulfill requirements for students in healthcare and teaching programs. Currently, students must have the test done and return to the clinic 2 days later for a reading by a health professional. We performed a study to determine whether students could reliably interpret their own PPD tests. We found that student readings (based on written instructions) reflected reliable interpretations of their PPD skin tests.
The whole blood interferon-gamma (IFN-gamma) test has proven to be a practical ancillary test for re-testing cattle for bovine tuberculosis 8-28 days following tuberculin skin testing. An improvement in the specificity of the IFN-gamma test could further reduce culling of false positive animals. The primary aim of this study was to evaluate a single mycobacterial antigen, ESAT-6 in the IFN-gamma test for use in skin test-positive cattle. These skin test-positive cattle comprised 51 Mycobacterium bovis-infected animals from tuberculosis-infected herds and 85 non-infected animals from tuberculosis-free herds. The test based on ESAT-6 had a higher specificity than the test based on purified protein derivative (PPD) tuberculin, but this was offset by a small decrease in sensitivity. Use of a lower cut-off in the ESAT-6-based test improved the sensitivity, while still maintaining a very high specificity. A secondary aim in the study was to assess the ESAT-6 and PPD-based tests for detecting bovine tuberculosis in skin test-negative animals from a persistently infected herd. The PPD-based test detected the majority of the lesioned or M. bovis-culture positive animals, while the ESAT-6-based test detected a smaller proportion. The false negatives in the IFN-gamma test from both the skin test-negative and positive groups were predominantly M. bovis-culture positive animals with no visible lesions. The current study has shown that a defined specific antigen such as ESAT-6 can markedly improve the specificity of the IFN-gamma test for re-testing skin test-positive animals. An ESAT-6-based IFN-gamma test could be particularly useful to reduce the false positive rate, yet still maintain an acceptable level of sensitivity.
Twenty volunteers underwent intradermal skin testing with tetanus toxoid (TT) and varicella-zoster (VZ) antigens weekly for 7 weeks. In addition to measurements of delayed hypersensitivity skin test responses, in vitro antigen specific lymphocyte stimulation and antibody levels were monitored. Data for TT exhibited more variability than VZ, demonstrating a marked boost in antibody titers after the first skin test and a shift in the kinetics of the skin test reaction to later maximum responses after the first 3 weeks. In contrast, serial skin testing with VZ was not associated with changes in cellular immune assays. Following the initial VZ skin test there was a slight rise in antibody levels for one-third of studied individuals. These observations suggest that VZ skin test antigen is ideal for monitoring immune function and that repeated testing should not significantly influence in vitro assays.
The results of skin tests with two antigens of the yeast phase of Histoplasma capsulatum are presented. Both antigens were able to fix complement and form precipitating bands in the presence of sera from patients with active histoplasmosis. Their sensitivity was lower than the metabolic antigen usually employed in serology. Results of skin tests obtained with both yeast phase antigens and a standard histoplasmin coincided in animals infected with H. capsulatum. Only one cross reaction was observed in animals inoculated with Paracoccidioides brasiliensis. Skin tests in humans were conducted on patients with and without mycotic disease. The percentages of positive reactions in patients with histoplasmosis were not significantly different between control histoplasmin and whole cell extracts. In the patients with non mycotic diseases the frequency of positive tests varied between 28.8% and 32%, which agrees with previous statistical data for the general population of the area. Equally the positive percentage of 55% and 68% in patients with paracoccidioidomycosis coincided with the results of previous studies. The histological patterns of these skin tests showed that they were produced by cell mediated hypersensitivity. The sensitivity of a whole yeast cell extract was similar to histoplasmin L48, but its preparation was quicker and easier to perform and it had no foreign substances from the culture medium, so we think that it would be easier to standardize it chemically.
BACKGROUND: Skin prick testing is a major tool for diagnosing food allergy. Food allergen extracts have not been standardized; this may lead to great variability in the predictive accuracy of skin prick tests. METHODS: Six commercial peanut skin test extracts were compared in vitro with RAST inhibition assays, ELISA, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting with sera from peanut-allergic adults and in vivo by skin prick testing. RESULTS: ELISA showed that the content of peanut allergens Ara h I and Ara h II in the extracts ranged from 0.0015 to 0.0236 and 0.0001 to 0.0164 mg Eq/ml, respectively. RAST inhibition studies showed that the extracts produced curves of similar slope, suggesting conservation of allergenic epitopes. SDS-PAGE revealed differences in protein profiles because roasted extracts generally possessed the same number and proportion of major protein bands but raw extracts varied more in both respects. SDS-PAGE and immunoblotting showed that two of the extracts contained major IgE-binding protein bands that did not appear in the others. One roasted extract gave little protein banding and consequently little IgE binding. CONCLUSIONS: Skin testing results showed no differences in the ability of the extracts to provoke a positive skin test response in peanut-sensitive subjects.
BACKGROUND: Latex allergy is mediated by residual IgE-binding proteins found on latex products. While most reported reactions involve latex gloves, the allergenic potential of other latex containing devices is unknown. OBJECTIVE: To assess the allergenic potential of latex urologic catheters. METHODS: Two identical lots of urologic catheters were extracted in sterile saline and analyzed for latex protein content using sensitive ELISA and Western blot assays. The extracts were tested by skin prick testing in a population of 47 latex-allergic patients. RESULTS: Latex proteins were detected by ELISA assay, however, the Western Blot method was not sensitive enough to measure latex proteins in these catheter extracts. Skin prick testing using a standard latex reagent (Bencard) demonstrated the test population to be extremely sensitive to latex as 68% of the population reacted to a 1/100,000 dilution. Using undiluted catheter extracts, only 11% of these latex-allergic patients reacted to catheter lot A and 2% to catheter lot C, by prick skin test. Eight percent of the control patients had a positive latex prick skin test and none reacted to the catheter extract. CONCLUSIONS: The data suggest that processing and leaching of these specific latex urologic catheters resulted in a very low latex allergen content. The low prevalence of skin test reactivity in a population of latex-allergic patients suggests that these catheters would be an unusual cause of allergic reactions. It is not possible, however, to determine whether latex-allergic patients could safely use latex urologic catheters.
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Two hundred and ten (210) patients attending the Allergy Clinic of King Fahd Hospital, KFU, with a history of allergy related problems were tested for skin sensitivity. A total of 52 allergens were used. Only 55 patients were found to be positive to one or more of the allergens. House dust and inhalants were the most common allergens. Sixty percent (60%) of the patients had elevated IgE levels though all had evidence of allergy-related clinical disease. Clinical history appeared to be the most sensitive indicator of allergic problems. Skin testing and IgE levels were less sensitive.
Skin reactions have been produced in normal subjects by the injection of highly purified influenza A and B viruses. The reactions reached a maximum at 24-48 hr. and the histological pattern was compatible with a delayed hypersensitivity reaction. There was no close relation between skin test results and circulating antibodies. Twenty-seven subjects were challenged intranasally with attenuated influenza A (H3N2): 5 of 14 skin-test-negative subjects were infected, but none of 13 skin-test-positive subjects.
OBJECTIVE: We sought to assess skin whealing with glycerin-containing control injections for intradermal skin tests. DESIGN: Observational. METHODS: Wheal sizes were measured at 0, 10, and 15 minutes after intradermal injection of 0.01 and 0.02 mL of phenolated normal saline and 0.5% and 5% concentrations of glycerin in the same quantity of phenolated saline. RESULTS: Intradermal injection of 0.01 mL of phenolated saline produced an average 4.9-mm wheal, which expanded to 5.2 mm at 10 minutes and to 6.0 mm at 15 minutes. Intradermal injection of 0.02 mL of phenolated saline produced a 6.4-mm wheal, which expanded to 7.0 mm at 10 minutes and 8.0 mm at 15 minutes. The addition of glycerin produced proportionally larger wheals. CONCLUSIONS: Because glycerin increases whealing beyond that with phenolated saline, skin tests containing glycerin must be compared with glycerin-containing negative controls. Intradermal skin tests that fail to compare findings in this manner contain an inherent methodologic flaw and are uninterpretable.
OBJECTIVE: To provide the reader with a relevant review of the literature regarding skin testing in the allergist's office. DATA SOURCES: A PubMed search for the years 1970 through 2005 was performed using the following keywords: allergy skin testing, skin prick testing, and intradermal skin testing. STUDY SELECTION: Articles that highlighted aspects of sentinel to clinical allergists' use of skin testing in the office, such as methods of skin testing, intradermal vs skin prick testing, skin test devices, and methods of expressing skin test results, were selected for further review. RESULTS: Skin testing remains the central test to confirm an allergic response. It is minimally invasive and when performed correctly has good reproducibility. Results are easily quantifiable and correlate well with end organ challenge. It is imperative however that technicians who perform the skin tests and the clinicians who order or interpret these tests understand the characteristics of the specific tests they are administering. It is also important that the clinician express skin test results in a manner that allows easy interpretation by another physician. CONCLUSIONS: Allergists must consider controllable variables that affect skin test results and their interpretation. When not considered, they may be responsible for some of the inaccuracies associated with allergy skin testing.