D. P. Bruynzeel

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

Abstract:  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)].

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.

Venous insufficiency in male workers with a standing profession. Part 1: epidemiology.

BACKGROUND Chronic venous insufficiency (CVI) in the occupational population is often poorly recognized. The dimensions of this problem have never been thoroughly investigated in the Netherlands. OBJECTIVE To study the epidemiology and risk factors of CVI in males with a standing position at work. To develop a simple diagnostic instrument for screening an (occupational) population for CVI. METHODS 387 male workers with a standing profession were examined by means of a questionnaire, physical examination, Doppler ultrasound investigation, light reflection rheography and optical leg volume measurements. RESULTS CVI was present in 29% of the subjects and correlated with age, weight and duration of standing work. Complaints of the legs were reported by 81% of the individuals with CVI but also by 63% of the persons without CVI. The questionnaire had a predictive value of 80% in detecting CVI. CONCLUSION CVI was a major problem because of the quantity (29%) and the accompanying complaints. Neither the questionnaire nor other investigative measures proved to be as efficient in diagnosing CVI as physical examination in combination with Doppler ultrasound investigation.

Ascertainment of hand dermatitis using a symptom-based questionnaire; applicability in an industrial population

In this study, the applicability of a symptom‐based questionnaire on hand dermatitis was assessed in a population of rubber workers. The questionnaire was previously validated in a study among nurses. 224 subjects employed in 9 different companies completed a questionnaire on skin complaints. Subsequently, 202 workers attended the physical examination of the skin by a dermatologist. The ascertainment of skin complaints according to the questionnaire was compared to the medical evaluation. The 2 different diagnostic tools used for assessing dermatitis resulted in dissimilar estimates of the prevalence of active hand dermatitis, ranging from 6.9% to 38.1% of all workers. Using the medical evaluation as ‘gold standard’ we observed a moderate sensitivity and specificity (respectively 71.4%; 95% CI: 47.7–95.1 and 76.1%; 95% CI: 70.0 – 82.2), a low positive predictive value (18.2%; 95% CI: 8.0 –28.4) and a high negative predictive value (97.3%; 95% CI: 94.7 –99.9) for the classification based on the self‐administered questionnaire. When evaluated against ‘first symptoms of dermatitis’ the sensitivity decreased, while the specificity remained almost the same. The deviant findings between the present and the original validation study of the same questionnaire among nurses hamper its applicability in populations with different occupations. Therefore, if questionnaires are to be used, validity studies have to be carried out to evaluate differences in perception of skin diseases between different (occupational) populations.

Improved detection of allergen-specific T-cell responses in allergic contact dermatitis through the addition of ‘cytokine cocktails’

Abstract:  The gold standard for the diagnosis of allergic hypersensitivity is skin patch testing with the suspected allergens. This diagnostic tool, however, has distinct disadvantages, and therefore the development of alternative or complementary in vitro tests is of great importance. In this study, we evaluate the applicability of an in vitro test method, as developed earlier for nickel allergy, to detect allergen‐specific T cells in the blood of patients allergic to frequent sensitizers (chromate, cobalt, paraphenylenediamine, fragrances and chloromethyl‐isothiazolinone). Peripheral blood mononuclear cells (PBMCs) of allergic patients and healthy controls were cultured in the absence or presence of allergen. Additionally, type 1 (IL‐7 and IL‐12) or type 2 (IL‐7 and IL‐4) stimulating cytokines were added; after 6‐day proliferation, IFN‐γ and IL‐5 secretions were determined. Without the addition of cytokines, consistent allergen‐induced proliferation was observed in PBMCs of nickel‐allergic patients only. By contrast, the addition of type 1 or type 2 stimulating cytokines resulted in a significantly enhanced allergen‐specific proliferation for all allergens tested (sensitivity increased from 26 to 43% or 38%, respectively, P < 0.05). In these cultures, allergen‐induced IFN‐γ and IL‐5 secretion was also significantly increased, compared to healthy controls (P < 0.05, for IFN‐γ sensitivity 79%, specificity 93%; for IL‐5 sensitivity 74%, specificity 81%). In conclusion, these results demonstrate an increased proliferative capacity and cytokine production by allergen‐specific T cells from allergic patients, but not of healthy individuals upon stimulation with allergens in combination with type 1 or 2 skewing cytokines. The present data warrant further exploration of the application of this test to a broader set of allergens.

The Risk of Sensibilization and Contact Urticaria upon Topical Application of Fumaric Acid Derivatives

Systemic and sometimes topical therapy with fumaric acid (FA) and its derivatives is used in the treatment of psoriasis. Scattered data show that the topical application of these derivatives elicits side effects. Application of FA and some derivatives on the skin was accompanied by perilesional skin irritation, macular papular rashes and urticarial reactions. In order to determine the irritating and sensitizing properties of FA derivatives we used a cytotoxicity, flank irritation, ear swelling and guinea pig maximization test. The results of the cytotoxicity test demonstrated that dimethylfumarate (DMF) was the most toxic derivative. DMF induced also contact-urticarial reactions in contrast to mono-ethylfumarate (MEF). Challenge experiments with FA, MEF and DMF in MEF- and DMF-sensitized guinea pigs demonstrated that both MEF and DMF are moderate contact sensitizers. In DMF-sensitized animals cross-reactions with MEF were found. As DMF and MEF have cytotoxic, contact-urticarial and/or sensitizing properties, topical application should be avoided.

Development of hand eczema in junior hairdressers: an 8-year follow-up study

The development of hand eczema was evaluated in an 8‐year follow‐up study carried out in 51 junior hairdressers. Predisposing factors were investigated, Data were collected by use of u sell‐administered questionnaire: 74% response. None of the junior hairdressers presented wild hand eczema at the start of the survey. After 8 years, however, 51% had developed hand eczema. No significant difference in prevalence of hand eczema was found between practicing and non‐practicing hairdressers (58% versus 33%). Development of hand eczema was not related 10 atopic constitution or nickel sensitivity. Dry skin type was associated with increased risk of developing hand eczema.

Relevance of positive patch-test reactions to fragrance mix.

Background: Fragrances are an important cause of allergic contact dermatitis. We presume that the traditional fragrance mix (FM) detects 70 to 80% of fragrance‐allergic patients. FM has an irritant potential. Weak positive reactions may have a greater chance of being irrelevant than strong reactions. Objective: To improve the appraisal of FM patch‐test reactions, we studied the relevance of reactions of different strength. We also studied the predictive value of the following on the relevance of the initial FM patch‐test results: patch‐test results of a repeated FM test; results of patch tests with balsam of Peru, colophony, and ingredients of the mix; and (history of) atopic dermatitis. Methods: One hundred thirty‐eight patients who had doubtful positive (?+) or positive (+ to +++) reactions were included in the study. We determined relevance by history taking, location and course of the dermatitis, and additional patch testing. Patients were retested with FM and with each ingredient separately. Results: The relevance of reactions to FM increases with the strength of the reactions. Predictors of relevance are the results of retesting with FM, the results of tests with the ingredients, and a history and/or present symptoms of atopic dermatitis. Conclusion: Retesting with FM and its ingredients may add to the benefit of patch testing.

Dermal exposure, handwashing, and hand dermatitis in the rubber manufacturing industry.

Skin diseases, such as hand dermatitis, are thought to be a common problem in the rubber manufacturing industry, as workers are exposed to a wide range of chemicals with known irritant and sensitizing potential. We conducted a cross-sectional survey of a representative sample of rubber manufacturing workers (N = 202), selected from nine different rubber companies. Prevalence of hand dermatitis (“major” and “minor” dermatitis) and skin injuries was assessed on the basis of a diagnosis by a dermatologist. We investigated the possible relations between actual skin exposure, handwashing practices, and hand dermatitis. Prevalence of major hand dermatitis (7%) was comparable with that in the general population; however, minor signs of dermatitis were more common among the surveyed population (28%), as were traumata of the skin (17%). Dermal exposure to cyclohexane-soluble agents at work was related to the occurrence of major hand dermatitis, but not to the occurrence of minor hand dermatitis. Moderate and frequent handwashing especially with industrial surfactants containing scrubbing particles were found to be strongly associated with the occurrence of minor dermatitis [odds ratio = 4.27 (95% confidence interval = 0.90–20.27) and odds ratio = 6.38 (95% confidence interval = 1.33–30.17, respectively)].

Sensitization to clavulanic acid in Augmentin

6 months before presentation, a 1⁄2year-old girl was prescribed an AugmentinA (amoxicillin and clavulanic acid combination) suspension for pneumonia complicating cystic fibrosis. After a few days of taking the medicine, she developed a scarcely perceptible widespread rash, which subsided spontaneously after discontinuing the drug. During a subsequent episode, she received amoxicillin alone, without any adverse effects. A few months later, she needed antibiotics and was again prescribed Augmentin suspension. This resulted within a few days after the 1st dose in large urticarial wheals, scattered all over her body, which disappeared approximately 1week after discontinuing the treatment. There was no personal or family history of atopy. Results