Intradermal skin tests in the diagnostic evaluation of food allergy.
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Although bovine tuberculosis is widespread throughout Africa, very little is known about risk factors for Mycobacterium bovis infection in either human or cattle populations. A human case-control study was conducted in northern Tanzania, comparing risk factors and prevalence of cattle interdermal test positives of cases (cervical adenitis cases from which M. bovis was isolated) with age- and sex-matched controls (selected at random from potential hospital attendees within the community). A cattle cross-sectional study was also set-up involving 27 villages selected at random in four districts, with 10,549 cattle and 622 herds tested, and questionnaire surveys conducted in 239 households. M. bovis was confirmed in seven of 65 (10.8%) human cervical adenitis cases, of which only one came from a household owning infected cattle. M. bovis in human patients was associated with families in which a confirmed diagnosis of tuberculosis had previously been made (p<0.001) and with households far (>100m) from neighbours (p=0.003). In cattle, overall prevalence of intradermal test positives was low at 0.9% (0.70-1.06%), but widespread, with 11.8% (8.44-13.17%) herds containing at least one reactor. Prevalence of intradermal test positives increased significantly with cattle age (p<0.001). Herds with the following risk factors had a significantly greater prevalence of intradermal test positives: >50 cattle in the herd (p=0.024); herds housed inside at night (p=0.021) and herds in contact with wildlife (p=0.041). Furthermore, villages that experienced annual flooding had a higher prevalence of infection (p=0.043).
A 68-year-old man who was treated for febrile angina with gentamicin, doxycycline, phenoxymethylpenicillin K, and minocycline developed a generalized pustular exanthema favoring the predilected areas (hands, feet). Apart from a subepidermal pustule, the most noteworthy histological finding was a pronounced leukocytoclastic vasculitis. After disappearance of the skin lesions an intradermal test using cilligen (penicilloyl-polylysin) was conducted. The test gave a strongly positive early reaction, and 48 h after this an acute pustular outbreak developed analogous to the original manifestation. Doxycycline tested late, produced no exacerbation even though it was positive in the intradermal test. This pustular allergical drug rash can be classified as a vasculitis leucocytoclastica allergica which, as we know, appears in various clinical forms. It does not form a new disease entity. Terms used so far, such as "pustular necrotizing angiitis", "generalized pustular drug rash", "acute generalized pustular bacterid", "pustulosis acuta generalisata", only partially correspond to the actual pathoetiology.
BACKGROUND: In the last few years, adverse reactions to mydriatic eyedrops have been investigated. However, is not still available a standardized protocol, capable of identify the pathogenetic mechanism. In the light of these findings we have evaluated the reliability of a protocol with well established concentration of specific allergens. METHODS: The diagnostic method includes the application of patch test series Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali (GIRDCA), medicaments, corticosteroids, local anesthetics, main eyedrops' excipients, pure active principles and extemporaneous preparations with mydriatic eyewashes. At the same time, skin prick test with a solution of atropine sulfate at 1 per thousand and an intradermal test with injection of atropine at 0.01 per thousand were carried out. RESULTS: After patch tests were removed, we detected seven positiveness to the phenylephrine, two to the benzalkonium chloride, one to thiomersal, one to the ethylendiamine and one to the atropine sulfate 1 per thousand. With intradermal tests we obtained three positiveness in patients who reported adverse reactions to atropine. CONCLUSIONS: Our results show that phenylephrine is frequently responsible for allergic conjunctivitis (53.8%). In the case of atropine, even though the limited number of patients suggests to perform more extensive studies, it emerges that our diagnostic protocol is safe and might be able to screen allergic reactions in the field of ophthalmopathies.
A 71-year-old woman was seen for cutaneous lesions that appeared on her abdomen 15 days after the beginning of subcutaneous injection of nadroparin calcium (Fraxiparina), a low molecular-weight heparin (LMWH). The lesions were very pruriginous, measured 0.5-3 cm, and appeared at and around the point of Fraxiparina injection. Fraxiparina treatment was stopped and the lesions subsided spontaneously in one week. The patient had been treated with intravenous heparin (H) one year before. A 6 mm punch biopsy showed spongiosis and a mild dermal superficial perivascular infiltrate composed of lymphocytes and eosinophils. A challenge test with a therapeutic dose of Fraxiparina produced a lesion similar to those described above. Epicutaneous, prick and intradermal tests with undiluted samples of different H (both preservative-containing and preservative-free) were performed. Patch tests produced a mild erythematous reaction to all H at 48 hours and a (++) reaction at 96 hours. These reactions persisted for one week. Prick tests showed neither an immediate nor a delayed reaction. Intradermal tests with H did not produce an immediate reaction, but induced an infiltrated erythematous reaction at 48 hours that enlarged during the next 2 days and was transformed into pruritic plaques with vesicles. The lesions cleared in two weeks. Our findings confirm a delayed-type hypersensitivity to H and cross-reactivity between unfractioned and LMWH.
A 29 year-old female patient suffered vascular collapse which became apparent immediately after general anaesthesia. Resuscitation was prolonged and difficult, and complicated by the need for reoperation. Based on the time history, fentanyl was suspected as the causative agent. Fentanyl allergy was confirmed by skin testing one month later. The case is discussed, and the possible reasons for the delay in appearance of symptoms and signs are considered.
BACKGROUND: Although hyaluronan has been acknowledged as being free of species and organ specificity, for 4 years I have encountered a variety of adverse reactions to injectable hyaluronic acid as used in aesthetic medicine. OBJECTIVE: I have tried to prove that some of those side effects may be allergic reactions to the commercial preparations of injectable hyaluronic acid. METHODS: I began with intradermal tests to the reactive patients and to 2 witnesses; then lymphocyte transforming tests were performed at the University of Geneva (Switzerland). Histology was performed on the skin tests and on reactive treated areas of the face of different patients. A serum analysis was then done by Pr. Sainte Laudy of Laboratoire Pasteur--Cerba (France). RESULTS: The skin tests were positive for one or the other or both of the injectable hyaluronic acid preparations used in aesthetic medicine. The different biopsies have shown for some a chronic inflammatory reaction, even 11 months after the treatment or a severe granulamatous reaction to foreign bodies. Serum analysis revealed positive antibodies against Restylane and/or Hylaform and even IgG and E anti-hyaluronic acid. CONCLUSION: Since 1995, I have 8 patients with adverse reactions to injectable hyaluronic acid, which after several tests, may be allergic to those products. Isn't it time to introduce intradermal tests before any injection of this type, as done with injectable bovine collagen?
The prick method of skin testing is advantageous for young children because of the decreased risk of anaphylaxis and less patient discomfort. Some would argue, however, that the necessity of keeping extract drops at the skin-test sites makes prick testing impractical compared with intradermal testing for squirming youngsters. Since the literature is not clear concerning the length of time extract must be present at the prick site, we performed duplicate sets of prick tests with five concentrations of ragweed extract on 16 ragweed-sensitive adults. For one set of tests, the drops were removed immediately after the skin had been pricked; for the other set, extracts remained at the site for 15 min. After 15 min we recorded the size of the wheal and flare response for each test. On the basis of analysis of these paired observations, we concluded that there is no significant difference between these two methods of administering prick skin tests.
BACKGROUND: Allergy skin testing is a cornerstone in the evaluation of the allergic patient. This seemingly simple test is subject to multiple variables that can affect the result. OBJECTIVE: To evaluate the degree of variability among board-certified/board-eligible allergists in the scoring and interpretation of allergen skin tests. MATERIALS AND METHODS: A series of allergen prick skin tests were digitally photographed and a questionnaire generated. Approximately 70 board-certified/board-eligible allergists were asked to grade each test item and to interpret them as positive, negative, or indeterminate or if they desired a followup intradermal test. RESULTS: Thirty-three interpretable responses were obtained. The majority of respondents (24) used a grading scale of 0 to 4. Agreement among physicians using a 0 to 4+ scale ranged from a standard deviation of 0.26 to 1.35, with greatest agreement on items with median/mode scores of 4+. The largest standard deviations were found on test items with median/mode scores of 1+ to 2+. Interpretation of the test items also showed greatest variation for those items with median/mode scores of 1+ to 2+. The number of intradermal tests requested ranged from 0 to 11 (of 22 test items). CONCLUSIONS: The results demonstrate interphysician variation in the scoring and interpretation of epicutaneous skin tests. A questionnaire such as the one used here may serve a useful quality control instrument to ensure reproducible scoring of skin tests. In addition, the results highlight the need for greater study on the clinical utility of intradermal skin testing when epicutaneous tests are negative or equivocal.
The frequency and class of immediate-type hypersensitivity manifestations were studied in 494 snakebitten and scorpion stung patients who were treated with intravenous injections of antivenom sera. These patients were admitted to HC-FMRPUSP from 1983 to 1988. The effectiveness of a hypersensitivity skin test was also investigated. Eighty two out of 320 patients admitted following snake bites (25.6%) had immediate-type reactions consisting of isolated skin lesions (40%), skin lesions plus respiratory manifestations (19%) and gastrointestinal involvement (17%). Anaphylactic shock occurred in ten patients (12%). Thirteen out of 174 patients admitted following scorpion stings had immediate-type reactions (7.5%). There was also a preponderance of skin reactions. Anaphylactic shock was observed in one patient. The positive predictive value of hypersensitivity skin test was 31.8% and its sensibility was 54.8%. These data show that a hypersensitivity skin test is ineffective in predicting immediate-type hypersensitivity manifestations in patients given snake and scorpion antivenom. Considering these results, this test should be eliminated as a routine procedure when treating victims of poisonous animals. These studies indicate that prior to the administration of antivenom anti-histamine (H1- and H2-antagonists) as well corticosteroids should be given by i.v. route in order to prevent or reduce hypersensitivity reactions. Antivenom sera must always be given under continuous medical surveillance by an intravenous route, without dilution, drop by drop for 15-30 minutes.
BACKGROUND: Despite enormous efforts toward the standardization of fungal extracts, only a few extracts have been characterized that are relevant for the diagnosis and immunotherapy of allergy-associated disorders. OBJECTIVE: The goal of this study was to determine the optimum growth condition of Curvularia lunata, an important fungal allergen for quality raw material, and to analyze the C lunata extract for IgE- and IgG-binding proteins. METHODS: C lunata was grown in synthetic (Czapeck Dox medium), semisynthetic (Sabouraud's broth [SB]), and natural media (potato dextrose [PD]) for different periods of time. The extracts were probed for allergenic and antigenic activity, with pooled patient sera and polyclonal antibodies raised against C lunata by means of ELISAs, immunoblots (in vitro), and intradermal tests (in vivo). RESULTS: The growth of C lunata was better in semisynthetic media (ie, SB) compared with other types of media. Dry weight and protein content was maximum in the 7-day culture of SB. ELISA with pooled sera from C lunata-sensitive patients exhibited that cultures grown in SB for 11 to 13 days and PD plus 1.0% agar for 5 days were the most potent. Intradermal tests with 11- to 13-day SB culture extract showed maximum skin reactivity in allergy patients. Immunoblots with patient sera showed 10 to 14 IgE-binding proteins in 5- to 15-day SB cultures. Analysis of 5- to 15-day SB extract with rabbit sera showed 10 to 16 IgG-binding proteins. CONCLUSIONS: The extract from 11- to 13-day SB cultures were most biologically potent (intradermal tests) and showed high antigenic and allergenic reactivity (ELISA and immunoblot). The addition of yeast extract did not affect the dry weight and protein content of the C lunata extract. Furthermore, addition of agar in PD medium increases the dry weight and protein content of the fungal mat. Synthetic media was not suitable for mass cultivation of C lunata.
Malassezia pachydermatis is considered to be a contributing factor to canine atopic dermatitis (AD). The purpose of this study was to investigate the humoral response to a commercially produced M. pachydermatis extract. Fifteen atopic dogs with Malassezia overgrowth on the skin (MD), 16 atopic dogs without MD, three atopic dogs with overgrowth of Malassezia in the ears only (MO), and 12 normal dogs were intradermally tested with M. pachydermatis extract at 50, 100, 250, 500, 1000, 2000 and 4000 PNU mL(-1). All dogs were evaluated cytologically by cutaneous tape strip and bilateral ear exudate sampling to determine presence of MD or MO. Each had serum evaluated for anti-Malassezia IgE using three Malassezia extracts with an ELISA assay. The irritant threshold concentration at which healthy nonatopic dogs ceased to react was 1000 PNU mL(-1). There was a significant difference in intradermal test reactivity between the atopic groups. At this dilution, 93% (14/15) of the atopic MD group, 31% (5/16) of the atopic group without MD or MO, and 100% (3/3) of the atopic MO only group reacted. There were no significant differences in the serum IgE levels as measured by the Greer ELISA assay, between any groups using any of the three extracts. These results support that Greer's M. pachydermatis extract is useful for intradermal testing of dogs with an allergic phenotype, and that atopics with MD are more likely to have a type-1 Malassezia hypersensitivity than those without. The ELISA assay may require further development in order to be useful for the diagnosis of Malassezia hypersensitivity.
Cell mediated immune response in vitro to a number of antigens has been reported in patients with Type 1 diabetes. The aim of the present study was to develop an in vivo intradermal (delayed type hypersensitivity) skin test using antigens known to be recognized by lymphocytes of patients with Type 1 diabetes and to compare, where possible, the in vivo response to the in vitro T cell proliferation to the same antigens. The skin test was performed in the following group of patients: 55 with recent onset Type 1 diabetes; 16 patients with Type 1 diabetes of longer duration; 10 patients with autoimmune thyroid disease and 20 patients with Latent Autoimmune Diabetes in Adults (LADA). Type 1 diabetes specific antigens for the skin test included glutamic acid decarboxilase (GAD65), insulin and beta casein, whereas diabetes non specific antigens included tetanus toxoid, diphteria, proteus, tubercolin, streptococcus, and glycerol as control. A multitest device consisting of heads delivering intradermally 10 microl of solution containing the antigens was applied to the forearms; the specific antigens were injected in one forearm whereas the non specific antigens were injected in the other forearm. Reading of the reaction, which was considered positive in the presence of a nodule of 2 mm diameter was performed 48 h after the multitest application. The in vitro T cell response to diabetes specific antigens used in the multitest was studied using conventional proliferation assays in patients with recent onset Type 1 diabetes and in age matched normal subjects. Only recent onset Type 1 diabetes patients showed an in vivo positive response to GAD65, such response being detectable in 10 patients (18%). Two patients reacted also to beta casein and insulin, all other patient groups resulted negative but 2 patients with longer duration of Type 1 diabetes. There was no apparent link between the in vivo skin test and in vitro T cell proliferation to GAD65. We conclude that in vivo cell mediated immune reaction to GAD65, insulin and beta casein can be visualized in a minority of patients with recent onset Type 1 diabetes. Further studies are required to determine specificity and whether altering the dose can improve the sensitivity of the test.
BACKGROUND: Although skin reactions have been reported during use of diclofenac, a nonsteroidal anti-inflammatory drug, immunopathogenic mechanisms have been demonstrated in only a few cases. METHODS: We administered skin and patch tests to two subjects who had developed maculopapular rashes respectively 48 and 72 hours after initiation of treatment with diclofenac. RESULTS: In both cases, prick and intradermal tests with the drug were negative at 20 minutes, but 24 hours later an erythematous infiltrate had appeared at the intradermal test site. Patch tests with diclofenac were also positive at 48 and 72 hours. CONCLUSIONS: The features of both these cases are suggestive of delayed hypersensitivity to diclofenac. Delayed-reading intradermal and patch tests may be a simple and effective means of diagnosing reactions of this type.
The case of a 39-year-old female with generalized eczema following sodium nadroparin administration was referred to us. Positive patch-tests for several low molecular weight heparins (LMWH), but negative for unfractionated heparins (UFH) and tinzaparin were obtained. Furthermore, intradermal tests gave positive results to sodium and calcium heparin, while only subcutaneous challenge showed tinzaparin sensitivity. In summary, in heparin type IV hypersensitivity diagnosis, the intradermal test seems to be an eligible tool, rather than patch-test.
Fifty-one patients with surgically proven hydatid disease were examined with the intradermal (ID) (Casoni) and latex-agglutination (LA) tests. Before surgery, results of the former test were 80.4% positive and of the latter were 82.3%. For 105 persons who were diagnosed free of hydatid cysts by surgical, clinical and serological observations, 6.7% were positive with the ID test and 4.8% with the LA test. The close agreement between results obtained with the LA and ID tests in this selected group of patients suggests that the LA test merits further evaluation as a diagnostic tool.
BACKGROUND: Anaphylaxis to the bite of Diptera and specifically the bite of the Tabanidae family (horsefly) have been sparsely documented. The coexistent hypersensitivity to both the order Diptera and Hymenoptera has not been documented. METHODS: We present a patient who experienced anaphylaxis to both insect species. Venom skin testing and RAST revealed sensitivity to several members of the Hymenoptera order. Prick, intradermal and RAST with whole body extracts of Tabanidae species is also documented in this patient. Twenty patients who are sensitive to Hymenoptera and have been bitten by horseflies but have had no reaction to the horsefly bite were used as controls. RESULTS: An anaphylactic reaction to horsefly bite has been documented in a 56-year-old white male. This patient also demonstrated evidence of anaphylactic reaction to Hymenoptera envenomation. In controls consisting of 20 patients with Hymenoptera sensitivity, there was no clinical history of reaction to horsefly bite despite the presence of positive prick and/or positive intradermal tests and/or positive RAST to mixed Tabanidae species extract. CONCLUSIONS: Skin testing to horsefly by prick and/or intradermal testing using whole body insect extract is not useful in making a diagnosis of Tabanidae hypersensitivity. RAST using Tabanidae species as antigen is similarly useless in making a diagnosis of Tabanidae hypersensitivity. In vivo and in vitro diagnosis of horsefly hypersensitivity may be achieved when the salivary gland antigen of the horsefly becomes available.
We report a patient with recurrent generalized itching and urticaria due to inhalation of nicotine in tobacco smoke. A skin prick test with nicotine base (1:10 w/v) was negative but an intradermal test with nicotine base (1:100 w/v) was strongly positive. Intradermal tests with nicotine base (1:100 w/v) performed on 10 healthy controls were negative. A provocation test with a nicotine patch showed the same symptoms and signs including generalized itching, weals and flares, and mild dyspnoea, which occurred when he was exposed to tobacco smoke. Nicotine in tobacco smoke can act as an inhalant allergen and induce urticaria in hypersensitive persons.