Search PubMed⌕ Search

Biomedical subjects

D P Bruynzeel

Publications and source records attributed to D P Bruynzeel.

At least 19 recordsLinked to original sources

Contact allergy and respiratory/mucosal complaints from heroin (diacetylmorphine).

After the start of heroin (diacetylmorphine)-assisted treatment to a selected group of chronic treatment-resistant heroin-dependent patients in the Netherlands, we reported about work-related eczema and positive patch tests to heroin in some nurses and nasal and respiratory complaints. To investigate the prevalence of heroin contact allergy, we started a questionnaire-based study with follow-up by allergological examinations. Of 120 questionnaires sent, 101 (84%) was returned: 67 from nurses and 34 from other employees. Of 101 workers, 38 (38%) had reported work-related complaints: 33 of 67 (49%) nurses and 5 of 34 (15%) other employees. Patch tests to heroin were performed in 24 nurses and were positive in 8 (33%). All the 8 had eyelid or facial eczema and, in 6, accompanied by mucosal or respiratory complaints. The prevalence of heroin contact allergy in this study was 8% (8/101) among all employees and 12% (8/67) among nurses. Respiratory and mucosal complaints could not be ascribed to a contact allergy, and in these cases, serum was analysed for specific immunoglobulin E to heroin. A type 1 allergy to heroin could not be shown. These complaints are possibly due to the histamine-liberating effect of heroin, to atopic constitution, to a combination of these factors or - less likely - to other non-allergic factors.

Allergens↗

[Insulin allergy: background, diagnosis and treatment].

An allergic reaction develops in 2.4% of patients that use insulin. This ranges in severity from erythema and pruritus to life-threatening anaphylaxis. llergic reactions to insulin usually occur within a few hours after an injection and are usually due to a local or systemic type I IgE-mediated hypersensitivity reaction. Despite considerable research into the immunogenicity of insulin, this has not yet been clarified completely and allergic reactions to insulin still occur. A systematic diagnostic approach is essential for an adequate treatment plan. A blood test for anti-insulin antibodies and intradermal skin tests are of great importance. There are many options available for the treatment of insulin allergy and each patient must therefore be evaluated individually.

Anaphylaxis↗

CXCL8 secretion by dendritic cells predicts contact allergens from irritants.

Monocyte-derived dendritic cell functions have been explored for identification of contact allergens in vitro. Current methods, including measurement of changes in cell surface marker expression (e.g. CD83, CD86) do not provide a sensitive method for detecting the sensitising potential of a chemical. In this study, we investigated whether chemokine production by monocyte-derived dendritic cells is increased upon maturation and whether chemokine production can provide methodology for the detection of allergens. Monocyte-derived dendritic cells were exposed to allergens (nickel sulphate, cobalt chloride, palladium chloride, copper sulphate, chrome-(III)-chloride, potassium dichromate, p-phenylenediamine and dinitrochlorobenzene) and irritants (sodium dodecyl sulphate, dimethylsulphoxide, benzalkoniumchloride and propane-1-ol). CD83 and CD86 expression was analysed by flow cytometry and chemokine production (CXCL8, CCL5, CCL17, CCL18, CCL19, CCL20, CCL22) was determined by ELISA. Significant up regulation of CD83 and CD86 expression could only be induced by three out of seven and five out of seven allergens, respectively. In contrast, CXCL8 production was significantly increased after stimulation with all allergens tested, whereas irritant exposure led to decreased CXCL8 production. All other chemokines tested, failed in identifying contact allergens. In conclusion, CXCL8 production, next to CD83 and CD86 up regulation, by monocyte-derived dendritic cells provides a promising in vitro tool for discrimination between allergens and irritants.

Allergens↗

Patch testing with methyldibromo glutaronitrile, a multicentre study within the EECDRG.

Contact allergy to and allergic contact dermatitis from methyldibromo glutaronitrile (MDBGN) have frequently been reported. As there has been no agreement on which MDBGN test preparation to use, a study was initiated to help determine the optimal patch test preparation for MDBGN. 2661 consecutively patch tested patients at 11 test clinics representing 9 European countries participated. Petrolatum preparations with MDBGN at 1.0%, 0.5%, 0.3% and 0.1% were inserted in the standard series. Contact allergy rates were noted in the range 4.4-1.1% following decreasing test concentrations. Reactions not fulfilling all criteria to be classified as allergic reactions could represent either weak allergic or irritant reactions, and such reactions were noted in the range 8.2-0.5% with decreasing concentrations. A significant number of these reactions represented weak allergic reactions, as allergic reactions were obtained to higher patch test concentrations in the same individual. Morphologically irritant reactions were noted only for the highest test concentrations. In summary, the contact allergy rates and frequencies of doubtful and irritant reactions vary with the patch test concentration. The final decision on patch test concentration for MDBGN should not only rely on these factors but also include information on patch test concentrations required to diagnose individual cases with allergic contact dermatitis from MDBGN as well as results of repeated open application tests.

Allergens↗

Repeated open application test with methyldibromo glutaronitrile, a multicentre study within the EECDRG.

Contact allergy to and allergic contact dermatitis from methyldibromo glutaronitrile (MDBGN) have frequently been reported. This study was initiated to help determine the optimal patch test preparation for MDBGN. In 51 patients with a doubtful or a positive patch test reaction to at least 1 of 4 test preparations with MDBGN in petrolatum at 1.0% w/w, 0.5%, 0.3% and 0.1%, a repeated open application test (ROAT) with moisturizers with and without MDBGN at 0.03% w/w was performed on the upper arms for 2 weeks. 18 of the 51 (35.3%) patients developed a positive ROAT. In all patients, there was a positive ROAT only to the moisturizer with MDBGN (P < 0.001). A statistically significant association was also found between the patch test reactivity (PTRL) and the outcome of the ROAT (P < 0.001). If only considering those with a PTRL above 0.3%, thus with negative or doubtful test reactions to 0.1% and 0.3%, there were still statistically significantly more patients with a positive ROAT to the moisturizer with MDBGN than to the moisturizer without MDBGN. The study demonstrates that patch testing with MDBGN at 0.3% and 0.1% will miss clinically relevant patch test reactions to MDBGN.

Adult↗

Monitoring the European standard series in 10 centres 1996-2000.

A 5-year retrospective study of the frequency of sensitization to the 25 allergens of the European standard series (ESS) was conducted in 10 centres in 8 European countries. Included were the results of 26 210 patients. The range in sensitivities differed moderately between the centres. Combining results of different centres and drawing conclusions on incidences can be done only with great care. The information on the ranking of the allergens and their sensitization incidence in the clinics are useful for decisions on the future composition of the standard series. The ESS is still a valid screening tool, and no substances should be deleted.

Allergens↗

Regulation of nickel-induced T-cell responsiveness by CD4+CD25+ cells in contact allergic patients and healthy individuals.

In this study, we investigated the capacity of CD4+CD25+ regulatory T cells to suppress nickel-specific effector T cells, both in nickel-allergic patients and healthy controls. CD4+ cells isolated from allergic patients showed an increased proliferative response to nickel, whereas CD4+ cells from negative controls did not respond to allergen. When CD4+CD25+ cells were depleted, nickel-specific responsiveness was strongly increased both in allergic and in non-allergic individuals, with the most pronounced effect in allergic patients. These regulatory T cells were anergic to nickel but inhibited nickel-specific CD4+CD25- effector T cells in coculture experiments. CD4+CD25+ cells from nickel-allergic patients showed only a limited capacity to suppress effector T-cell responsiveness, because an increased nickel reactivity could still be detected in these cocultures. None of the isolated CD4+CD25+ cells, either isolated from healthy controls or allergic patients, produced IL-10 in response to nickel. Overall, these results support the view that CD4+CD25+ cells can control the activation of nickel-specific effector T cells in non-allergic individuals, whereas this regulatory capacity is impaired in allergic patients. To investigate the presence of allergen-specific regulatory T cells in truly naïve, non-sensitized individuals, T-cell reactivity should also be studied with non-environmental contact allergens, such as para-phenylenediamine.

CD4-Positive T-Lymphocytes↗

Induction of cytokine (interleukin-1alpha and tumor necrosis factor-alpha) and chemokine (CCL20, CCL27, and CXCL8) alarm signals after allergen and irritant exposure.

The immune system is called into action by alarm signals generated from injured tissues. We examined the nature of these alarm signals after exposure of skin residential cells to contact allergens (nickel sulfate and potassium dichromate) and a contact irritant [sodium dodecyl sulfate (SDS)]. Nickel sulfate, potassium dichromate, and SDS were applied topically to the stratum corneum of human skin equivalents. A similar concentration-dependent increase in chemokine (CCL20, CCL27, and CXCL8) secretion was observed for all three chemicals. Exposure to nickel sulfate and SDS was investigated in more detail: similar to chemokine secretion, no difference was observed in the time- and concentration-dependent increase in pro-inflammatory cytokine [interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha)] secretion. Maximal increase in IL-1alpha secretion occurred within 2 h after exposure to both nickel sulfate and SDS and prior to increased chemokine secretion. TNF-alpha secretion was detectable 8 h after chemical exposure. After allergen or irritant exposure, increased CCL20 and CXCL8, but not CCL27, secretion was inhibited by neutralizing human antibodies to either IL-1alpha or TNF-alpha. Our data show that alarm signals consist of primary and secondary signals. IL-1alpha and TNF-alpha are released as primary alarm signals, which trigger the release of secondary chemokine (CCL20 and CXCL8) alarm signals. However, some chemokines, for example, CCL27 can be secreted in an IL-1alpha and TNF-alpha independent manner. Our data suggest that skin residential cells respond to both allergen and irritant exposure by releasing mediators that initiate infiltration of immune responsive cells into the skin.

Allergens↗

[Cutaneous reactions to drugs].

Exact data concerning the incidence of cutaneous drug eruptions are lacking due to underreporting. Diagnostics of cutaneous drug eruptions is hampered by the fact that one drug may induce different eruptions while the same cutaneous eruption can be caused by several drugs. Important steps in the diagnostics of cutaneous drug eruptions are: suspicion of the drugs as cause of the eruption, precise history-taking with emphasis on medication use and a complete physical examination. The 'golden standard' in the diagnostics of a drug eruption is the dechallenge-rechallenge procedure, but in severe cutaneous reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis and vasculitis, this procedure can cause severe, sometimes life-threatening reactions. Reporting suspected adverse drug reactions to pharmaco-vigilance centres is important to identify rare drug reactions.

Adverse Drug Reaction Reporting Systems↗

Nickel-responding T cells are CD4+ CLA+ CD45RO+ and express chemokine receptors CXCR3, CCR4 and CCR10.

BACKGROUND: Whereas T lymphocytes are widely accepted as effector cells determining the pathogenesis of allergic contact dermatitis, contradictory results have been found regarding the roles of different T-cell subsets. The use of various experimental models, involving long-term cultured T-cell lines or clones, may explain these contradictory results. OBJECTIVE: To investigate the involvement of distinct T-cell subsets in patients with nickel contact allergy. METHODS: Different T-cell subsets were directly isolated from peripheral blood mononuclear cells (PBMCs) of nickel-allergic patients, and their proliferative capacity, type-1 or type-2 cytokine secretion [measured by interferon (IFN)-gamma or interleukin (IL)-5 release] and phenotypical marker expression were analysed after stimulation with nickel. RESULTS: Only CD4+ CLA+ CD45RO+ and not CD8+ T cells proliferate and produce both type-1 (IFN-gamma) and type-2 (IL-5) cytokines in response to nickel. Moreover, cells expressing the marker CLA in combination with CD4, CD45RO or CD69 are increased after nickel-specific stimulation. Interestingly, in addition, CD45RA+ CLA+ cells showed an increased frequency after allergen-specific stimulation. Analysis of nickel-reactive T cells for expression of distinct chemokine receptors showed that both proliferative capacity and cytokine production are restricted to subsets expressing CXCR3, CCR4 but not CCR6. Fluorescence-activated cell sorting analysis of chemokine receptors expressed on nickel-stimulated T cells confirmed these results; a subset of T cells expressing CLA and CXCR3, CCR4 and, most importantly, CCR10 increased in response to allergen, while these CLA+ nickel-reactive T cells were all negative for CCR6. CONCLUSIONS: These findings demonstrate that freshly isolated nickel-reactive T cells can be characterized as CD4+ CLA+ memory T cells which express the chemokine receptors CXCR3, CCR4 and CCR10, but not CCR6.

Antigens, CD↗

Analysis of effector and regulatory immune reactivity to nickel.

BACKGROUND: Diagnostic patch testing in allergic contact dermatitis faces the risk of boosting existing hypersensitivities or active sensitization. Risk-free and reliable in vitro assays using peripheral blood are, therefore, wanted. OBJECTIVES: Here, we studied new approaches for in vitro monitoring of nickel-specific effector ad regulatory cell functions in allergic patients and potentially tolerized individuals. METHODS: Lymphocyte proliferation assays were carried out with the allergen and additional IL-12/IL-7 or IL-4/IL-7 cytokine supplements. Release of IFN-gamma and IL-5 were assessed as measures for type-1 and type-2 effector T cell function, respectively, and IL-10 and TGF-beta1 to monitor possible regulatory T cell function reflecting immunological tolerance. After optimization of in vitro cut-off values, potency of these parameters was evaluated as compared with conventional nickel patch testing. RESULTS: One hundred and fifty six outpatients were included in this study, 74 of whom presenting with a positive history of nickel allergy. Nickel-sulphate patch test results showed positive reactions in 43 patients, of whom 40 had a positive history (test sensitivity 54%; specificity 96%; overall accuracy 76%). Proliferation tests without cytokine supplementation showed an accuracy of 68%, which was further improved by supplementing IL-4/IL-7 (82%). IFN-gamma and IL-5 cytokine production, as revealed in IL-12/IL-7 and IL-4/IL-7 supplemented cultures, respectively, showed accuracies of 70% and 83%. As to the production of putatively immunoregulatory cytokines, IL-10 was most informative, with highest production rates in nickel-skin test negative individuals with long-lasting mucosal metal contact preceding skin piercing. CONCLUSIONS: These results indicate that measuring both T cell proliferation and cytokine secretion profiles, in particular IL-5 release using IL-4/IL-7 supplemented medium, offers a promising improvement of the in vitro diagnostic options in monitoring nickel contact sensitization. Since oral nickel contact has been shown earlier to induce active tolerization, nickel-induced in vitro IL-10 production may help identify nickel-tolerized individuals.

Adolescent↗

Identification of anti-inflammatory drugs according to their capacity to suppress type-1 and type-2 T cell profiles.

BACKGROUND: Down-regulation or modulation of T cell activity by immunosuppressive drugs is an effective treatment in diseases where exaggerated T cell responses play a role. A primary effect of the anti-inflammatory drugs (AIDs) is inhibition of the synthesis of growth factors, such as IL-2, thereby down-regulating T cell proliferation. However, it is still largely unknown to what extent these AIDs are able to down-regulate specifically type-1 or type-2 T cell cytokine production, and whether they can down-modulate chemokine receptor expression, thereby preventing migration of T cells to the site of inflammation. OBJECTIVE: We investigated the suppressive effect of dermatologically used AID (cyclosporin A (CsA), lactoferrin (LF), 1 alpha, 25-dihydroxyvitamin D(3) (VD(3)), hydrocortisone (HC), di-methyl-fumarate (DMF), diclofenac (DF)) on both type-1 and type-2 T cells. Since allergic contact dermatitis is a skin disorder in which an exaggerated T cell response of both types of T cell subsets can be observed, we used this disorder as a model to study the capacity of AID to suppress type-1 or type-2 T cell responses. METHODS: Peripheral blood mononuclear cells of nickel allergic patients were cultured in the presence of allergen and increasing concentrations of AID. Proliferation was determined by measuring (3)H thymidine incorporation; chemokine receptor (CCR10, CCR4, CXCR3) expression was studied by flow cytometric analysis and IFN-gamma or IL-5 cytokine production was measured by ELISA. RESULTS: Three major patterns can be distinguished regarding the effect of AID on T cell responses. The first group, including CsA and LF, inhibited non-selectively T cell proliferation, chemokine receptor expression and cytokine production, with CsA as the most potent drug tested. A second group of AID, which included VD(3), HC and DMF, suppressed mainly type-1 T cell responses, as revealed by strong interference with IFN-gamma production and CXCR3 expression, and limited effects on either or both IL-5 and CCR4 expression. The third pattern was displayed by DF, which down-regulated IL-5 production and CCR4 expression, whereas IFN-gamma and CXCR3 were unaltered. CONCLUSIONS: Using a contact allergy model, we have demonstrated that various AIDs show distinct pharmacological profiles in that either type-1 or type-2 or both T cell responses are suppressed. These results should contribute to a more rational selection of AID in treating inflammatory skin diseases mediated by either or both of these T cell subsets.

Anti-Inflammatory Agents↗

Photopatch testing: a consensus methodology for Europe.

A group of interested European Contact Dermatologists/Photobiologists met to produce a consensus statement on methodology, test materials and interpretation of photopatch testing. While it is recognized that a range of local variables operate throughout Europe, the underlying purpose of the work is to act as an essential preamble to a Pan European Photopatch Test Study focusing particularly on sunscreen chemicals.

Dermatitis, Photoallergic↗

Routine patch testing with frullanolide mix: an European Environmental and Contact Dermatitis Research Group multicentre study.

Contact sensitivity to plants containing 1 or more sesquiterpene lactones (SLs) is difficult to diagnose. The mixture of SLs (SL mix) has been shown to detect only about 60% of sensitized individuals. In order to improve the diagnosis of sensitization to plants containing SLs, we have tested a mixture of frullanolides contained in Frullania dilatata and Frullania tamarisci at 3 different concentrations (0.01%, 0.033% and 0.1% in petrolatum). 8605 consecutive eczema patients in 1 North American and 15 European dermatology departments were tested with this mix, and 0.35% of positive cases to the different concentrations were found. Routine use of this mix permitted detection of only a small percentage of extra cases and did not improve the SL mix score. The frullanolide mix should therefore be restricted to investigations in particular geographical zones and/or in particular occupations.

Allergens↗

Is PPD a useful screening agent?

In this study, the usefulness was assessed of para-phenylenediamine (PPD) base as a marker for contact allergy to para-compounds and disperse dyes. 59 patients with a positive reaction to PPD were patch tested with a series of para compounds and disperse dyes. This dyes series was also tested in patients with a suspect medical history of contact allergy to hair, fabric or leather dyes. In total 610 patients were tested. As 24 patients became positive over the weekend, late readings, day 6 or 7, are important. These reactions were most probably relevant in 17/24 patients. Positive reactions to PPD correlated well with reactions to para compounds like p-aminoazobenzene and p-toluenediamine sulphate but not with disperse dyes. Reactions to Disperse Blue (106, 124) and Orange (1 and 3) were seen most frequently. PPD is a good screening agent for hair dye, but not for disperse dye, sensitivity.

Allergens↗

Patch-test-induced subjective complaints.

BACKGROUND: Many patients report subjective complaints during epicutaneous patch testing. OBJECTIVE: To demonstrate the possible relationship between the occurrence of subjective complaints and patch testing. METHODS: All consecutive patients who were referred to our clinic for patch testing, during 1 year, were investigated to study a possible association of the patch test procedure and subjective complaints like tiredness, shakiness or feeling unwell. The patients were asked to fill in a form concerning subjective complaints on the days of the investigation. Only those without complaints on the day the patches were applied were included in the study (n=102). RESULTS: Of the 102 patients, 17 had complaints on both days 2 and 3, 14 only on day 2, 6 only on day 3 and 65 did not develop any complaints at all. The number of patients with complaints on both days 2 and 3 (n=17) was larger than was to be expected from chance (n=4.6; p<0.01). There was a significant correlation between the number of positive patch test reactions and the number of complaints on day 2 (r=0.19; p<<0.001) and on day 3 (r=0.15; p<0.001). Positive patch tests were found in 72.2% of the patients who reported the complaint of shakiness; this proportion is significantly higher than expected from chance (p<0.05). CONCLUSION: The results confirm those of our earlier study and demonstrate that patch testing can cause subjective complaints, especially when positive patch tests are present.

Adolescent↗

Investigation of an unexplained skin disorder in a prison clinic in the Netherlands in 2002.

An unexplained outbreak of skin disorder with itching papules or pustules occurred among drugs body packers in a detention clinic in the Netherlands in October-November 2002. The descriptive cohort study suggests this outbreak could be associated with an expired batch of disposable linens, with an overall attack rate of 30% in the study population (n=118). No additionnal cases have been noted since this expired batch was replaced.

Abdomen↗