Contact allergy from Frullania and respiratory allergy from Thuja

Occupational allergic contact dermatitis in 52 forest-workers was caused by sesquiterpene lactones from liverworts (Frullania) and by usnic acid from lichens which grow on various trees including cedar (Thuja). Occupational asthma and rhinitis in 35 wood-workers was caused by wood dust of western red cedar (Thuja plicata). Characteristically, the respiratory symptoms occurred in the evening and at night and not during working hours; inhalation challenge with plicatic acid from the wood provoked immediate, late or dual (combined immediate and late) asthmatic reactions. Another class of compounds, tropolones, derived from Thuja plicata wood, was responsible for dermatitis in a wood-worker. These distinct industrial hazards in two groups of workers at the tree-felling and wood-working levels in the forest-products industry can be identified by clinical history and examination supplemented by specific cutaneous or respiratory clinical investigation.     

II. The late asthmatic responses

Immediate asthmatic responses have been regarded as the characteristic type of asthmatic response to follow exposure to inhaled allergens in patients with extrinsic asthma. They begin within minutes, clear within one to three hours and are inhibited by disodium cromoglycate but not by corticosteroids. They involve the reaction of antigen with antibodies usually of the IgE class. In recent years allergen inhalation tests have demonstrated the frequent occurrence of late asthmatic responses, either following immediate responses (dual responses) or occurring in isolation. The late asthmatic responses begin two to six hours after the allergen challenge, are prolonged and often severe, and are inhibited by both disodium cromoglycate and corticosteroids. The mechanisms involved in their provocation are not clearly understood but from the allergic viewpoint they may involve the participation of IgG ± IgM antibodies and/or IgE antibodies. Late asthmatic responses explain the frequent occurrence of allergen-induced prolonged asthma. Their features suggest that they are more important than immediate responses in the pathophysiology of asthma.     

A novel Candida albicans skin test antigen: efficacy and safety in man

Yeast phase Candida albicans (ATCC No. 10231) was grown in a nonantigenic medium, harvested and lyophilized. Ammonium sulfate fractions of an aqueous extract of the lyophilized cells were evaluated and the fraction yielding the highest specific delayed cutaneous reactivity in sensitized guinea-pigs was used to prepare a C. albicans skin test antigen (CASTA). The safety of the antigen was evaluated by measuring immediate and delayed (0.25, 6, 24, 48 and 72 h) cutaneous reactions in atopic and nonatopic human subjects. The outcome of three repetitive monthly Mantoux skin tests with 0.01-1 microgram antigen doses was used to test for booster effects in 14 subjects and to estimate a safe initial test antigen dose. The utility of a single skin test as a measure of cell-mediated immunity was evaluated in 40 healthy subjects. Reactor rates (greater than or equal to 2 mm, 48 h) of 40% and 85% were detected, respectively, with doses of 0.0316 and 1 microgram. Using a skin test reaction diameter greater than or equal to 5 mm at 48 h, the reactor rate was 50% for the 1-microgram dose. The only adverse reaction (45 mm, 0.25 h) was detected with the 1-microgram dose in an atopic subject who also exhibited exquisite scratch test reaginic hypersensitivity to C. albicans allergen. The prevalence of other adverse reactions to this antigen compared favorably with that to other antigens used for recall antigen testing. These studies suggest the 1-microgram CASTA dose can be used for effective, safe recall antigen skin tests.     

Diagnosis of penicillin allergy by skin testing: the Manitoba experience.

The reliability of skin testing in the diagnosis of penicillin allergy was studied in 86 adults and 167 children with a history of possible hypersensitivity reactions to penicillin. Skin testing was done with the major antigenic determinant of benzylpenicillin and minor determinants of benzylpenicillin, ampicillin, cloxacillin, methicillin and cephalothin. The overall frequency of positive skin reactions was 11.5%. Among the patients with positive skin reactions about half had a history of immediate or accelerated reactions to penicillins, but 2 of 11 adults and 50% of the children in this group had a history of maculopapular rash of delayed onset. There was a low frequency of positive skin reactions when there was a long interval between the times of clinical reaction and skin testing. Of 169 patients reacting negatively to skin testing who received a specific drug challenge only 2 manifested mild urticaria; this indicates the reliability of the skin tests in predicting penicillin allergy. The major and minor determinants of benzylpenicillin were the most useful reagents. One fifth of the patients with penicillin hypersensitivity would have been missed if the major determinant of benzylpenicillin alone had been used for skin testing. The additional use of the minor determinants of other penicillin derivatives, however, did not increase substantially the clinical reliability of the skin testing procedure.     

Leukotriene B4 and late asthmatic reactions induced by toluene diisocyanate

We investigated whether leukotriene B4 (LTB4) is released from the lungs of sensitized subjects during asthmatic reactions induced by toluene diisocyanate (TDI). We examined three groups of TDI-sensitized subjects, one after no exposure to TDI, the second 8 h after an exposure to TDI that caused an early asthmatic reaction, and the third 8 h after an exposure to TDI that caused a late asthmatic reaction. We analyzed bronchoalveolar lavage (BAL) fluid by reverse-phase high-performance liquid chromatography and by specific radioimmunoassay. The mean concentration of LTB4 was higher [0.31 +/- 0.09 (SE) ng/ml, range 0.15-0.51] in BAL fluid of sensitized subjects who developed a late asthmatic reaction than in BAL fluid of subjects who developed an early asthmatic reaction (0.05 +/- 0.04 ng/ml, range 0-0.224), and no LTB4 was detectable in the control subjects. We also performed BAL 8 h after TDI exposure on four TDI-sensitized late-dual reactors who were on steroid treatment. In this group of subjects no LTB4 was detectable. These results suggest that LTB4 may be involved in late asthmatic reactions induced by TDI.     

REACTIONS TO INSECT ALLERGENS—The Incidence of Response to Testing Among Allergic and Nonallergic Persons

Positive reactions to skin tests with extracts of various insects were found to be significantly higher in 200 patients with allergic disease than in 150 nonallergic controls.Forty-seven per cent of the allergic group had positive reaction to bee, 46 per cent to house fly, 39.5 per cent to moth, 29.5 to ant and 28.5 to aphid. Ant and house fly extract caused the greatest number of severe reactions (4+), with moth second and bee third.Because extracts of nonstinging insects caused reaction almost as often and as strong as stinging insects, it may be inferred that sensitization is due to inhaled insect particles. There appeared to be no necessary connection between a history of having been stung and a strong skin test reaction to bee protein.Testing for insect sensitivity appears a good way to get diagnostic information that can enhance the effectiveness of treatment.     

Clinical Significance of Skin Reactions to Mite Extracts in Children with Asthma

The mite Dermatophagoides pteronyssinus has been identified in dust from the houses of children in Birmingham suffering from asthma. Skin tests were carried out on 150 asthmatic children with extracts of D. pteronyssinus, of the related species D. farinae, of other mites found in house dust, and of crude house dust. Though positive reactions to D. pteronyssinus were obtained more frequently and were of greater size than those to the other extracts, it was considered that D. farinae is a suitable substitute for D. pteronyssinus for skin testing.In further tests on 302 asthmatic children with mite extracts and with extracts of allergens obtained commercially reactions to the former extracts were much more common than reactions to the latter.Major skin reactions (weals with diameter of 5 mm. or more) were present in 77% of children with a history of perennial asthma and house-dust sensitivity. Hence allergy to house-dust mites, particularly D. pteronyssinus, is of considerable importance in childhood asthma, and further study of the ecology and control of the mites in dust is desirable.     

Nonmutated self-antigen-derived cancer vaccine peptides elicit an IgE-independent but mast cell-dependent immediate-type skin reaction without systemic anaphylaxis

We previously reported an unexpected phenomenon, i.e., several cancer vaccine peptides, including a cyclophilin B-derived peptide (CypB-84), elicited an immediate-type skin reaction in prevaccination skin tests. These peptides were prohibited in the subsequent vaccinations because of a possible induction of systemic anaphylaxis. In this study, we investigated mechanisms involved in the peptide-elicited inflammatory reactions in BALB/c mice whose MHC class I molecule (Kd) shared similar binding motifs with the human HLA-A24 molecule. Among 11 peptides tested, all of which had been scheduled for use in clinical trials with HLA-A24+ cancer patients, three peptides (CypB-84, ART1-170, and ART4-13) elicited immediate footpad reactions in BALB/c mice similar to the skin reactions in humans. The footpad reaction was also observed in C57BL/6, athymic nu/nu, and CB17-SCID mice, but not in mast cell-deficient WBB6F1w/wv mice, indicating the reaction was not mediated by specific immunity, but was mast cell-dependent. Furthermore, the reactions were not correlated to in vivo antitumor effects of the peptides. An anaphylaxis was not elicited when the peptides were systemically injected due to a very rapid clearance of the peptides from the plasma by in vivo degradation. These results suggest that certain peptides of cancer vaccine candidates exhibit an IgE-independent but mast cell-dependent inflammatory response with no elicitation of systemic anaphylaxis, and may provide new insights for further development of peptide-based vaccinations for cancer patients.     

Isolation and characterization of an asthma-inducing sea-squirt antigen

An antigen capable of inducing asthmatic attack in patients with sea-squirt allergy has been isolated from body fluid of sea-squirt, Styela plicata, and designated as DIIIa. The chemical composition and the behavior in anion-exchange chromatography showed that the antigen was a weakly acidic glycoprotein. The weight-average molecular weight of DIIIa was estimated to be 9,880 by the sedimentation equilibrium method. This antigen was apparently discriminated from the previously isolated sea-squirt antigens, Gi-rep and Ei-M, by its activity to induce asthmatic attack and conjunctival congestion, though it gave a strongly positive reaction in skin tests against allergic patients, similarly to the previous antigens. From the cross-reaction of DIIIa to rabbit anti-Gi-rep and anti-Ei-M sera in vitro, it was confirmed that the antigen carried essentially the same antigenic determinant as Gi-rep and Ei-M, and this was termed type alpha determinant. Furthermore, the allergenic activities detectable in vivo and the reactivity to the rabbit antisera in vitro were simultaneously absorbed by immobilized immunoglobulin from anti-Gi-rep serum. Thus, it was suggested that the antigenic determinant responsible for the allergic reactions in vivo corresponded to that specified as type alpha in vitro on the basis of the reactivity against the rabbit anti-Gi-rep serum.     

The relationship between infiltrating CD4+ lymphocytes, activated eosinophils, and the magnitude of the allergen-induced late phase cutaneous reaction in man

The phenotype and activation status of leukocytes infiltrating human late phase allergic skin reactions were investigated by immunocytochemistry using a panel of mAb. Late phase skin reactions were induced in atopic individuals by intradermal challenge with allergen extract (grass pollen or house dust mite) and skin biopsies were obtained 6, 24, or 48 h after challenge. Cryostat sections were examined for evidence of infiltration and activation of T cells and eosinophils. Biopsies from saline-challenged control sites were used for comparison. A substantial number of CD3+ cells were observed close to the dermal capillaries. The number of CD4+ cells showed a similar pattern but few CD8+ cells were seen. The ratio of CD4 and CD8 subsets in tissue did not relate to the CD4/CD8 ratio in the peripheral blood. Two observations suggested that T cells had become activated: first, a small number of infiltrating cells bore receptors for IL-2, and second, there was indirect evidence of IFN-gamma secretion, demonstrated by increased expression of HLA-DR on endothelial cells and de novo expression of CD4 Ag on epidermal Langerhans cells. Activated eosinophils were detected in most of the allergen-challenged biopsies. The late phase reaction diameter at 6 h correlated with the number of activated eosinophils at 48 h (r = 0.61, p = 0.05), but not with infiltration by T cells. There was a strong correlation between the numbers of CD4+ cells and activated eosinophils at 24 h (r = 0.94, p less than 0.001). These findings suggest that interactions between T lymphocytes and eosinophils in reactions to airborne allergens may be more important than has previously been recognized.     

Detection of hypersensitivity toLegionella pneumophila in guinea pigs by skin test

Cross-reacting antigens of three serogroups ofLegionella pneumophila differed serologically and immunologically from the serogroup-specific antigens. Intradermal injection of cross-reacting antigens into sensitized guinea pigs evoked skin hypersensitivity. Animals were sensitized either by injection of inactivatedL. pneumophila in adjuvant or by infection with live organisms. Skin reactions were measurable about 2–4 h after injection and continued to increase in intensity for the first 24 h, followed by a gradual decline over the next 48 h. Histological examination of skin reactions taken from test sites at 48 h revealed infiltration of mononuclear cells in and about the small subcutaneous blood vessels and throughout the dermis, compatible with a delayed-type reaction. The overall appearance and time course of the reaction resembled a combination of immediate and delayed types of hypersensitivity. Each cross-reacting antigen of the three serogroups evoked skin reactions in animals which had been sensitized to any of those serogroups, but was not reactive in nonsensitized animals. These observations indicate the possibility of detecting present or past infection ofL. pneumophila by skin tests.     

Evaluation of The Safety and Efficacy of Newly Developed Domestic Allergenic Extracts for Skin Prick Testing

Background:Allergic disorders are common health problems worldwide with significant socio-economic impacts. The best diagnostic method using allergenic extract is the skin prick test. Regarding the effects of geo-climatic factors and allergenic extract source material quality, the aim of study was to determine the safety and efficacy of some in-house-developed allergenic extracts.Methods:Forty-five different allergenic extracts, including common regional pollen, foods, and dog and cat hair, as well as positive and negative extracts, were prepared from domestic sources using optimum extraction methods. All extracts passed stability and sterility testing, and sterile final products containing 50% glycerin in 10 and 20 w/v concentrations were used. Skin prick testing was performed on volunteers and immediate or late side effects were recorded. Results:In total, 56 students (mean age: 21.2±2.3y, M/F ratio: 1.07) participated in this study. For inhalant allergens, all extracts except dog hair extract caused positive responses. Salsola kali (Russian thistle) and Fraxinus velutina (ash tree) were the most common grass and tree pollen extracts, respectively. Of 18 different food extracts, five, including egg white, tomato, fig, melon, and green pepper caused skin reactivity in only one person. No participant reported any immediate or late side effects, including large local reaction or systemic response.Conclusion:The result of the current study confirmed the safety of all our in-house-developed allergenic extracts. Regarding efficacy, almost all inhalant and five food allergens caused positive skin responses.Key Words: Allergenic extract, In-house extract, Skin prick test     

Reduction in skin test reactions to inhaled allergens during a 12 weeks stay in the alpine climate

Fiftyfour allergic patients with bronchial asthma or obstructive lung disease were investigated at admission and discharge after a 3 months hospitalization period in the alpine valley Davos. An intracutaneous skin test procedure was carried out with 16 common inhalant allergens. Histamine 0.01 mg/ml was used as a positive control and a phosphate buffered saline with 0.03% HSA and 0.5% phenol were used as negative controls. A liophylized control for house dust mite was used for every patient on admission and discharge, in order to control loss of allergen potency of the vial. Furthermore, an additional freshly prepared vial of house dust mite allergen was analyzed after it was opened and stored at 4°C after 3 months. The wheal and flare reactions were calculated separately for the early reaction (at 15 minutes) and the late reaction (at 6 hours). The sum of wheal/histamine index and fare/histamine index were calculated for the early phase reactions and analyzed according two-tailed paired student's t tests. Using RAST inhibition, the liophylized house dust mite showed the same allergen concentration as in the fluid form. The 3 months old vial was analyzed and showed the same allergen concentration as was expected. Results for histamine reactions on admission and discharge showed no significant difference. Patients showed no reactions on the negative controls. Differences were found between skin test reactions on admission and discharge for the sum of early wheal reactions (p = 0.0001), and to certain allergen wheal such as house dust mite and some other common allergens. We conclude that during a 12 weeks stay in the alpine climate Davos, intracutaneous early wheal reactions to certain allergens are decreasing possibly reflecting a decreased exposure. The late reaction showed no significant change.     

Echinococcus granulosus: host lymphocyte transformation by parasite antigens.

Lymphocyte transformation, measured by in vitro tritiated thymidine incorporation, and indirect hemagglutination tests were carried out on hydatid patients and normal individuals using sheep and human hydatid fluid or scolex antigens. The hydatid patients showed statistically significant lymphocyte transformation with human and sheep hydatid fluid or scolex antigens when compared to normal individuals. The indirect hemagglutination tests resulted in high titers of antibody with sheep or human hydatid fluid antigens, while very low titers were obtained with scolex antigens. Unlike in the indirect hemagglutination test, the source of the antigen, scolex or fluid, was not of consequence in the lymphocyte transformation test. Furthermore, there was no correlation between the results of the serologic and lymphocyte transformation tests, since some patients with very high lymphocyte stimulation indices produced low indirect hemagglutination titers and vice versa. Similar results were obtained from rabbits which were immunized with sheep hydatid fluid or scolex extracts. The skin tests were of the immediate type of hypersensitivity reactions. Delayed skin reactions did not occur in spite of the presence of sensitized lymphocytes in the blood of the immunized rabbits.     

Schistosoma japonicum: Immediate hypersensitivity reactions to egg antigen in humans and rodents

Immediate hypersensitivity reactions in schistosoma japonicum infections were examined in both man and experimental animals. In man higher reaction to soluble egg antigen than to adult worm antigen was detected by the use of the radioallergosorbent test (RAST). Blood-collecting filter paper can be used in RAST for seroepidemiological study in place of a skin test. Reaginic antibody formation against egg antigen was detected at the approximate time of egg deposition in strains of mice, Mongolian gerbils, cotton rats, and laboratory rats by the use of passive cutaneous anaphylaxis or Prausnitz-Küstner-type skin tests. At the same time circumoval precipitin tests were positive. Results with athymic nude mice suggest that these reactions are T-cell dependent. No detectable reagin synthesis against adult worm antigen was found in the animals so far examined, confirming stronger allergenic reaction to egg antigen than to that of adult worms in S. japonicum infections in man and animals.     

The effects of eastern red cedar (Juniperus virginiana) invasion and removal on a dry bluff prairie ecosystem

Eastern red cedar (Juniperus virginiana) establishment increased dramatically in the tallgrass prairie biome of North America during the last 30 years. Since many of the remaining remnant prairies occur on steep, dry, and nutrient poor sites, threatened by the invasion of native and non-native woody species, it is important to understand how an invasive species such as eastern red cedar influences key environmental factors that may determine the future trajectory of these systems and whether abiotic and biotic components of the system are resilient following cedar removal. To address these issues we: (1) investigated the influence of eastern red cedar on micro-environmental factors; (2) evaluated how these micro-environmental factors responded to eastern red cedar removal; and (3) assessed the effect of eastern red cedar on herbaceous species germination and distribution. The invasion of eastern red cedar was associated with lower surface light availability and soil temperature, as seen in prior studies, but otherwise had effects distinct from those observed in prior studies. There was no effect of cedar on soil pH, and unlike prior studies, cedar patches had higher soil moisture compared to native C₄ prairie grass plots. Moreover, these effects had strong spatial signatures, with impacts of invasion on micro-environment and native vegetation differing dramatically with slope position and aspect. Three years after eastern red cedar was removed, micro-environmental factors and species composition became similar to the tree-free grass-dominated plots, indicating a significant capacity for recovery following possible cedar control. In a broader context, this study sheds light on the pathways and mechanisms driving the impacts of this biological invasion on dry, steep, nutrient poor systems and illustrates the capability of these systems to recover once the invading species is removed.     

Hypersensitivity to Some Nematode Antigens

Immediate and delayed skin reactions to antigens derived from Ascaris suum, Necator americanus, and Toxocara canis are described in three subjects and related to eosinophil counts and serum IgE levels. One, who had laboratory contact with ascarides but no known infection, gave positive immediate reactions to all three antigens. Another, following repeated experimental infection with necator, gave positive immediate reactions to all three antigens and a delayed reaction to necator alone. The third, following a single recent infection with necator, gave no immediate or delayed reaction.     

Occurrence of early and late asthmatic reaction after provocation with antigen and the status of pulmonary ventilation in patients with hay fever after the pollination season]

Pulmonary ventilation and asthmatic reaction under laboratory conditions have been investigated in 23 patients with allergic rhinitis hypersensitive to grass pollen. Pulmonary ventilation has been assessed with the aid of VCin, FVC, FEV1, FEV1/VCin, PEF, MEF50, and MTT. Asthmatic reaction has been produced by an inhalation of allergens mixture with dose-response technique. An early reaction has been diagnosed, when FEV1 decreased by at least 20% or MEF50 by 30% within 10 minutes, and late reaction when the same parameters decreased after 6 or 24 hours. An early asthmatic reaction has been noted in 2 patients (8.7%), late--in 4 patients (17.4%), and double (both early and late) reaction in 2 patients (8.7%). Pulmonary ventilation has been normal in all examined patients, except two of them with peripheral airways obstruction (MEF50 less than 70% of the normal value). Results suggest, that asthmatic reaction may be provoked in the laboratory in patients with pollinosis and normal pulmonary ventilation after pollen season. Such a reaction may also be expected during a natural exposition to pollens.     

Food hypersensitivity; correlation of intradermal skin tests with clinical allergenicity

A study was made to determine how well the results of skin tests for sensitivity to various foods agreed with observation of clinical reactions to those foods. Test reactions were divided into several categories-negative, and 1, 2, 3 or 4 plus. Then the strong reactions, that is the 3 and 4 plus reactions, the milder reactions and the negative results were studied separately to determine the agreement of results, in each category, with the clinical response. Wide variations were noted. For some foods the agreement was high, for others low. For some foods, the agreement was high in some categories of reaction, low in others. For example, negative results of skin test might match with nonreaction to the food clinically in a high proportion of cases, and 3 or 4 plus reaction to skin test might be in close agreement with the incidence of distress upon ingestion of the food, yet for the same food there might be very poor correlation between mild reaction to skin test and clinical response. This being the case, accuracy of skin tests cannot be determined simply by combining all data on reactions, of whatever degree, and taking the aggregate of agreement in all categories as an index of the validity of the test. Each category of reaction must be considered separately.Combined data and categorized data on accuracy of skin tests for sensitivity to 26 foods were tabulated in the present study.     

Comparative study of the basic immunological reactions for assessing tularemia immunity in inoculated persons or those who have had the disease

In the comparative study of immunological tests used for the determination of immunity to tularemia in vaccinees the greatest number of persons with the positive reaction was detected by means of the tularine skin test. Former tularemia patients retained allergic skin reaction to this test irrespective of the time of the disease.