Development Of Contact Allergy Research Articles

Contact allergy to medical devices

Abstract Background Medical devices are not subject to any legal obligation to declare ingredients. With an increasing number of available medical devices, increasing reports of contact allergies to these devices result in a more difficult, delayed or lack of diagnosis of the trigger. Methods Elaborate chemical methods, such as gas chromatography–mass spectroscopy, were able to detect novel contact allergens in medical devices. Results Diabetic patients requiring insulin benefit from sophisticated glucose sensor measurement systems and insulin pump systems, but are limited in their choices by the development of contact allergy. Potential contact allergens in medical adhesives, plasters, and wound dressings require extensive diagnostic testing. Contact allergic reactions to cardiac electronic implants are rare. The potential relevance of a contact allergic reaction to endoluminal stents to restenosis of the treated vascular territory is discussed. Contact dermatitis to medical gloves is usually due to the vulcanization accelerators. Mouth–nose protective or FFP2 mask-associated eczema is often irritant, very rarely allergic in origin. Conclusion With continued development of medical devices, new contact allergens are introduced. The declaration of their ingredients is necessary for rapid diagnosis and future prevention.

Modern diabetes devices for continuous blood sugar measuring: Limitations due to contact allergies.

During the past years, diabetes diseases have increased significantly worldwide. However, new technologies such as continuous glucose measurement using a subcutaneous sensor are developing just as rapidly. A continuous improvement in insulin pump therapy is also contributing to an improved quality of life. A common feature of these modern devices for diabetes therapy is that they remain fixed in place on the skin for several days. In recent years, skin reactions, in particular pronounced contact dermatitis due to the devices and their adhesives have been increasingly reported. In particular, isobornyl acrylate, which used to be included in a glucose measurement sensor set, was identified as a main allergen. Development of contact allergy can result both in a necessity to quit the measuring system and in allergic cross-reactions to other systems.

Individual susceptibility to contact sensitization: the role of TNFα 308G>A polymorphism and atopy.

The significance of individual risk factors in the development of contact allergy, such as genetic variation in cytokine genes and atopy, is still not clearly defined. The aim of this study was to investigate the association between TNFα 308G>A polymorphism or atopy and contact sensitization (CS) in a cohort from the general Croatian population. The study involved 312 first-year students from the University of Zagreb (median age: 19 years). Methods included a questionnaire and skin prick and patch testing for common inhalable and contact allergens, respectively, as well as genotyping for TNFα 308G>A polymorphism based on buccal swabs. CS (positive patch test for ≥1 contact allergen) was reported in 32%, atopy (positive prick test for ≥1 inhalable allergen) in 38%, and TNFα 308G>A polymorphism in 23% of subjects. Based on multivariate analysis, atopy was confirmed as a predictor of CS, poly-sensitization, CS to p-phenylenediamine and cobalt chloride, and self-reported skin symptoms. TNFα 308G>A polymorphism was confirmed as a predictor of CS to p-phenylenediamine (OR: 5.72; 95%CI 1.20-27.28). These findings could be relevant for evaluation of individual susceptibility to developing a contact allergy, particularly among persons occupationally exposed to skin hazards.

Skin Barrier Function and Allergens.

The skin is an important barrier protecting us from mechanical insults, microorganisms, chemicals and allergens, but, importantly, also reducing water loss. A common hallmark for many dermatoses is a compromised skin barrier function, and one could suspect an elevated risk of contact sensitization (CS) and allergy following increased penetration of potential allergens. However, the relationship between common dermatoses such as psoriasis, atopic dermatitis (AD) and irritant contact dermatitis (ICD) and the development of contact allergy (CA) is complex, and depends on immunologic responses and skin barrier status. Psoriasis has traditionally been regarded a Th1-dominated disease, but the discovery of Th17 cells and IL-17 provides new and interesting information regarding the pathogenesis of the disease. Research suggests an inverse relationship between psoriasis and CA, possibly due to increased levels of Th17 cells and its associated cytokines. As for AD, a positive association to CS has been established in epidemiological studies, but is still unresolved. Experimental studies show, however, an inverse relationship between AD and CS. The opposing and antagonistic influences of Th1 (CS) and Th2 (AD) have been proposed as an explanation. Finally, there is convincing evidence that exposure to irritants increases the risk of CS, and patients with ICD are, therefore, at great risk of developing CA. Skin irritation leads to the release of IL-1 and TNF-α, which affects the function of antigen-presenting cells and promotes their migration to local lymph nodes, thus increasing the probability of CS and ultimately the development of CA.

P145 Innate immune activation through ITAM-Syk-CARD9 signaling coupling to inflammasome is essential for the development of contact allergy to organic chemical allergens

Introduction Allergic contact dermatitis (ACD) is a major cause of occupational skin diseases and is caused by T cells sensitized previously to contact allergens. One of the clinically most important categories of contact allergens are small organic molecule that are chemically reactive (chemical sensitizers). Although the sensitization process of T cells requires activation of skin dendritic cells (DCs) by chemical sensitizers, it is unclear how the sensitizers activate the innate immune system. CARD9 is an essential adaptor protein regulating NF-κB activation and inflammatory cytokine production through tyrosine-based activation motif (ITAM)-coupled receptors and the tyrosine kinase Syk on myeloid cells, and is known as a crucial molecule in the innate activation pathway for antifungal defense. However its role in allergic diseases is unknown. Methods Contact hypersensitivity (CHS) to trinitrochlorobenzene (TNCB) was sensitized by painting TNCB on skin in mice lacking MyD88 or ITAM-associated signaling molecules, or by injection of TNBS (a water-soluble form of TNCB)-modified bone marrow-derived dendritic cells (BMDCs) from the knockout mice. Elicitation and evaluation of CHS response (ear swelling, histology and the development of TNCB-specific T cells) was performed on day 5. In addition, cytokine productions and signaling activation in response to various contact sensitizers in BMDCs from the knockout mice were examined Results Expression of CARD9 in DCs and that of MyD88 in T cells are both required for sensitization of CHS to TNCB. IL-1R-MyD88-mediated signaling in T cells was required for sensitizer-activated DCs to generate TNCB-reactive T cells producing IL-17. On the other hand, activation of the signaling pathway through the ITAM-containing adaptor DAP12 and Syk was essential for ROS generation and NLRP3-dependent Caspase-1 activation induced by TNBS stimulation in DCs. Although the CARD9/BCL10 signaling was dispensable for the inflammasome activation, it was essential for contact sensitizer-indueced pro-IL-1β synthesis in DCs through NF-κB activation. In addition, we found that all contact sensitizers tested (FITC, Oxazolone and DNFB) could induce Syk activation, and that the ROS production, Caspase-1 activation and IL-1β production induced by these sensitizers were all dependent on Syk and the pro-IL-1β synthesis through NF-κB activation was all dependent on CARD9. Conclusion The ability to induce the Syk-mediated ROS production coupling to NLRP3 inflammasome activation and the CARD9-mediated NF-κB activation leading to pro-IL-1β synthesis may be a common characteristic of chemical contact sensitizers that is required for skin DCs to sensitize T cells through the IL-1β-IL-1R pathway.

Endonasal phototherapy significantly alleviates symptoms of allergic rhinitis, but has a limited impact on the nasal mucosal immune cells

The literature documents the fact that UV irradiation of cutaneous Langerhans cells (LC) in vivo prevents the development of contact allergy and produces long-lasting immunosuppression. However, not much is known about the effect of UV irradiation on the LC of the nasal mucosa and their connection with clinical scores. Local antigen presentation may be necessary for both primary and recall T cell responses to birch pollen in patients with hay fever. Endonasal phototherapy combination of UVB (5%), UVA (25%) and visible light (70%) utilises the immunosuppressive effects of UV irradiation. The aim of this study was to correlate clinical symptom scores with possible changes in the LC of the nasal mucosa induced by UV radiation. The clinical effectiveness of this form of treatment is discussed. Nasal biopsies were obtained from ten birch pollen-sensitive patients with seasonal rhinitis before and after endonasal phototherapy. All patients showed a significant clinical benefit post-treatment as assessed by standardised instruments, including total nasal symptom score, nasal congestion score, nasal itching score, sneezing score, nasal secretion score and impairment-to-health score. However, we found no significant morphological changes, to, or quantitative differences in, the CD1a+, CD4, CD8 or CD31 cells before and 14 days after treatment. Despite the positive clinical effect, the study revealed no effect of UV irradiation on the LC and other analysed cells of the nasal mucosa immune system. Possible reasons for this are discussed.

Specific Adducts Formed through a Radical Reaction between Peptides and Contact Allergenic Hydroperoxides

The first step in the development of contact allergy (allergic contact dermatitis) includes the penetration of an allergy-causing chemical (hapten) into the skin, where it binds to macromolecules such as proteins. The protein-hapten adduct is then recognized by the immune system as foreign to the body. For hydroperoxides, no relevant hapten target proteins or protein-hapten adducts have so far been identified. In this work, bovine insulin and human angiotensin I were used as model peptides to investigate the haptenation mechanism of three hydroperoxide haptens: (5R)-5-isopropenyl-2-methyl-2-cyclohexene-1-hydroperoxide (Lim-2-OOH), cumene hydroperoxide (CumOOH), and 1-(1-hydroperoxy-1-methylethyl) cyclohexene (CycHexOOH). These hydroperoxides are expected to react via a radical mechanism, for which 5,10,15,20-tetraphenyl-21H,23H-porphine iron(III) chloride (Fe(III)TPPCl) was used as a radical initiator. The reactions were carried out in 1:1 ethanol/10 mM ammonium acetate buffer pH 7.4, for 3 h at 37 degrees C, and the reaction products were either enzymatically digested or analyzed directly by MALDI/TOF-MS, HPLC/MS/MS, and 2D gel electrophoresis. Both hydroperoxide-specific and unspecific reaction products were detected, but only in the presence of the iron catalyst. In the absence of catalyst, the hydroperoxides remained unreacted. This suggests that the hydroperoxides can enter into the skin and remain inert until activated. Through the detection of a Lim-2-OOH adduct bound at the first histidine (of two) of angiotensin I, it was confirmed that hydroperoxides have the potential to form specific antigens in contact allergy.

Differential Phosphorylation of MAPK Isoforms in Keratinocyte Cell Line by Contact Allergens and Irritant

ABSTRACTMitogen-activated protein kinase (MAPK) is an important mediator of cellular signaling pathways. In an attempt to investigate the role of these kinases in contact allergen/irritant-induced signaling cascades, we have utilized keratinocyte (A431 cell line) as antigen presenting cells (APCs). This group has previously reported the applicability of A431 as an APC. The role of these kinases in the elicitation pathways of allergic contact dermatitis was investigated using interleukin-12p40 (IL-12p40) as a marker. Inhibitors of the isoforms of MAPK reduced the allergen-induced IL-12 release in the A431 cell line. This result suggests a possible role of the isoforms of MAPK in the development of contact allergy.

Atopy and contact hypersensitivity: a reassessment of the relationship using objective measures

There is a big contradiction in the medical literature regarding the relationship between atopy and contact hypersensitivity. Some researchers believe that atopy would prevent, whereas others believe that it would promote, the development of contact allergy. Possible causes of this confusion range from different study populations to different definitions of atopy. To evaluate the relationship between atopy and contact hypersensitivity in a well-defined general population sample using objectively measurable markers. I studied 135 randomly selected students from 5 vocational schools: 73 women and 62 men aged 18 to 19 years. The following atopy markers were tested: positive skin prick test results, positive Phadiatop test results, and total IgE levels greater than 120 kU/L. Contact hypersensitivity was detected by using patch tests. Statistical analyses included the Fisher exact test, the Mann-Whitney U test, and calculation of odds ratios. At least 1 positive skin prick test result was found in 23.7% (95% confidence interval [CI], 16.5%-30.9%) of study participants, positive Phadiatop test results were found in 20.0% (95% CI, 13.3%-26.7%), and total IgE levels greater than 120 kU/L were found in 23.7% (95% CI, 16.5%-30.9%). Positive patch test reactions were found in 28.1% (95% CI, 20.6%-35.7%) of participants, most frequently to thimerosal (18.5%; 95% CI, 12.0%-25.1%) and nickel (9.6%; 95% CI, 4.6%-14.6%). For persons with atopy markers, odds ratios for contact hypersensitivity ranged from 1.0 to 3.2, the highest being for nickel hypersensitivity among those with total IgE levels greater than 120 kU/L. None of these relationships were statistically significant. Atopy and contact hypersensitivity are independent phenomena.

Allergic contact dermatitis in children and adolescents.

From a clinical point of view, the prevalence of allergic contact dermatitis (ACD) among children and adolescents seems to be low. However, many children have dermatitis, most often atopic dermatitis. In selected cases, ACD is suspected, and the child is tested. The question remains, whether the prevalence of ACD in children really is low or whether the possibility of ACD is not sufficiently considered. During the last decade, reports have appeared on series of children and adolescents with contact allergy and ACD. Few cases have been reported in infants, but the development of contact allergy and ACD increases with age. Most studies include selected groups of children and adolescents with suspected ACD. Few studies have examined unselected populations, and most consider only the prevalence of contact allergy without evaluating the clinical relevance, e.g., the prevalence of ACD. Furthermore, no follow-up studies exist. Therefore, the incidence and prevalence of contact allergy and ACD in children and adolescents is largely unknown.

Frequency of contact allergy in children with atopic dermatitis: results of a prospective study of 137 cases.

The aim of our study was the evaluation of contact sensitization in pediatric patients with atopic dermatitis (AD). It seems that the frequency of contact allergies in the course of AD, and also the frequency of contact allergies in children, is underestimated in general. Our study has been performed by investigating 137 children with AD. The childrens' history was taken according standardized consultation guidelines and followed by a physical examination. Patch testing was performed systematically, including the European standard series, together with tixocortol pivalate, budesonide and the applied emollient. If necessary, optional patch tests were performed according to the child's history. The results demonstrate contact sensitization in 43% of all children tested. The most frequent contact allergens are: metals (19.3%), fragrance (4.4%), balsam of Peru (2.6%), lanolin (4.4%), neomycin (2.6%) and emollients (2.6%). No contact sensitization to corticosteroids nor any induction of active sensitization were seen. Statistical analysis demonstrates that the risk of developing a contact allergy is significantly elevated in children after the age of 5 years. Female sex is a risk factor only for nickel. Age of onset of AD or its severity is not associated with the development of contact allergy. In conclusion, the results indicate the necessity of performing systematic patch testing in the investigation of allergies in children with AD. Preventive measures from an early age are suggested to avoid exposure to the most frequent contact allergens.

Correlation between Lymphocyte Proliferative Responses and Dendritic Cell Migration in Regional Lymph Nodes following Skin Painting with Contact-Sensitizing Agents

We have investigated whether there exists a correlation between the induction of draining lymph node cell (LNC) proliferation in contact allergy and the accumulation of dendritic cells (DC) within such lymph nodes. CBA/Ca mice, which compared with mice of BALB/c strain, mount a more vigorous lymphocyte proliferative response following sensitization, also exhibited a more marked accumulation of DC in draining lymph nodes 24 h following skin painting. Moreover, studies with the skin-sensitizing fluorochromes fluorescein isothiocyanate (FITC) and rhodamine B isothiocyanate (RITC) revealed that DC-enriched fractions of draining LNC prepared from CBA/Ca mice contained a higher percentage of antigen-bearing cells than did those from BALB/c mice. A relationship between DC migration into lymph nodes and the magnitude of the induced LNC proliferative response was also indicated by experiments performed in BALB/c mice with a variety of contact allergens. It was observed that there was a direct correlation between the vigour of the proliferative response measured 3 days following exposure and the frequency of DC in draining nodes at 24 h. Collectively these data suggest that following skin sensitization the migration of DC into the draining lymph nodes influences quantitatively the primary immune response and the development of contact allergy.

Antigen-Restricted Antigenic Competition Induced by 2,4-Dinitrochlorobenzene: Association with Depression of Lymphocyte Proliferation

2,4,6-Trinitrochlorobenzene (picryl chloride) and 2,4-dinitrochlorobenzene (DNCB) fail to cross-sensitize with respect to contact sensitivity in mice. Nevertheless, topical exposure of mice to DNCB and other skin-sensitizing dinitrobenzene derivatives was found to result in a significant impairment of draining lymph node cell proliferative responses induced following epicutaneous challenge with picryl chloride 5 days later. The inhibition of picryl chloride induced proliferation was associated with an impairment of contact sensitization to this chemical. The effect of DNCB on subsequent responses to picryl chloride was transient and no longer detectable 15 days following exposure. The inhibition of proliferation and contact sensitization caused by DNCB was largely restricted to picryl chloride. Thus, DNCB failed to influence the development of contact allergy to the unrelated chemical 4-ethoxymethylene-2-phenyloxazol-5-one (oxazolone) and exerted a far less pronounced effect on oxazolone-induced proliferative responses. These data, therefore, describe an antigen-restricted form of antigenic competition which is associated with a depression of the primary lymphocyte proliferative response.

Darier's disease, familial benign chronic pemphigus (Hailey-Hailey disease) and contact hypersensitivity

17 patients with Darier's disease were tested with the standard epicutaneous test series to study an increased risk of the development of contact allergies to tropical therapy

Penetration and enrichment of flufenamic acid in calf skin from patients with stasis dermatitis.

To investigate the hypothesis that the application of medicaments to skin from the lower leg of patients with stasis dermatitis might lead to their enhanced enrichment, compared with uninvolved skin from the same region, a penetration study was performed with flufenamic acid. In 5 patients with pronounced changes of chronic venous insufficiency and in 5 control patients without chronic venous insufficiency the flufenamic acid content in skin sections parallel to the surface was determined by HPLC. In chronic venous insufficiency-skin, the flufenamic acid concentration was higher in all skin levels compared to control skin. This enrichment of the substance could lead to a prolonged and more intense contact with antigen-presenting cells in this region, thus promoting the development of contact allergies observed so frequently in this pathologic condition.

Contact allergies in patients with familial benign chronic pemphigus (Hailey-Hailey disease)

To determine whether patients with familial benign chronic pemphigus have an increased risk for the development of contact allergies to topical therapy, we performed epicutaneous tests in 15 patients with this disease. Nine had positive patch test reactions of which seven were allergic to compounds used in local treatments. Allergic reactions in more than one patient were seen to neomycin sulfate (three patients), bacitracin (two), and hydrocortisone-17-butyrate and betamethasone-17-valerate (two). Although no comparable control group was similarly studied, the frequency of sensitization appears to be increased in patients with familial benign chronic pemphigus.

Hand dermatoses and contact allergic reactions in construction workers exposed to epoxy resins.

In 23/135 (18%) workers exposed to epoxy resins, a work-related dermatosis on the hands and/or forearms had been present during the past 3 years. In 9 persons, the occupational dermatosis was still present at the time of investigation. In all workers, patch tests were performed with epoxy resin, isophoronediamine, triethylenetetramine and xylenediamine. Positive patch tests were observed in 27 of the 135 exposed workers (20%) 13 of whom had never previously experienced skin problems. Epoxy resin accounted for the majority of the positive reactions. There was no relation between a history of atopy and the development of contact allergy. Only half of all workers had received any safety instructions. The wearing of gloves (mostly cotton), intended to protect the skin, had an adverse effect.

The Langerhans cell.

Langerhans cells (LCs) function as the most peripheral outpost of the immune system. Although first identified in the skin, these cells probably originate in the bone marrow and migrate actively between the epidermis and the lymph nodes. They appear to play a critical role in immune surveillance and the development of contact allergy. The importance of these findings in the pathogenesis of cutaneous malignancy is discussed.