Sociodemographic and clinical profile of patients with occupational contact dermatitis seen at a work-related dermatology service, 2000 - 2014

Abstract: BACKGROUND: Occupational dermatoses are common, especially contact dermatitis. Epidemiological studies on these dermatoses are scarce in Brazil and they are necessary as part of the public policy to protect workers' health. OBJECTIVES: To identify sociodemographic and clinical profile of patients with occupational contact dermatitis seen between 2000 and 2014 at an occupational dermatology service. METHODS: It is a cross-sectional and retrospective study, based on information obtained from the service's database. RESULTS: Of 560 patients with conclusive patch test, 289 (46.9%) presented occupational dermatoses and 213 occupational contact dermatitis with predominance of the allergic type in relation to the irritative type (149:64 respectively). The odds of occupational dermatoses were higher among men and lower among patients aged 50 years or older and with higher level of education. Regarding the possibility of presenting occupational allergic contact dermatitis, only the gender variable was statistically significant. The professions most seen were cleaners, construction workers, painters, mechanics/metallurgists and cooks. The commonest allergens were nickel sulfate, potassium dichromate, cobalt chloride, carba-mix and formaldehyde. STUDY LIMITATIONS: The main limitations of this study are the fact that it was carried out in a tertiary service of occupational dermatoses and the lack of access to some allergens outside the patch test baseline series. CONCLUSIONS: It was possible to identify the sociodemographic and clinical profile of patients with suspected occupational contact dermatitis seen at the Service, beyond the professional groups and allergens related to a high risk of occupational contact dermatitis in this population.

Cobalt allergy: suitable test concentration, and concomitant reactivity to nickel and chromium.

BACKGROUND: Cobalt allergy is frequent, but knowledge about exposure is limited. The patch test concentration and relevance of positive reactions are sometimes questioned. OBJECTIVES: To assess the suitability of cobalt 1% versus 0.5% for patch testing, and to analyse the co-occurrence of allergy to cobalt, chromium, and nickel. MATERIALS AND METHODS: Consecutive dermatitis patients (n = 656) were patch tested with cobalt chloride 0.5% and 1%, potassium dichromate 0.5%, and nickel sulfate 5%, all in petrolatum. Reactions were assessed on day (D)3, and on D6 or D7, and the reactivity and development of reactions were analysed. RESULTS: Allergy to any metal was shown in 31% of patients, allergy to cobalt in 14%, allergy to chromium in 7%, and allergy to nickel in 20%. A significant proportion (37%) of cobalt allergy cases were missed by cobalt 0.5% versus 1%, whereas the reactivity profiles were similar. Cobalt allergy was solitary, without concomitant allergy to chromium or nickel, in 50% of patients. CONCLUSIONS: Cobalt chloride 1% pet. is more suitable for patch testing than 0.5%. Solitary cobalt allergy is as frequent as concomitant allergy to cobalt and nickel or chromium. Sources of skin exposure to metals need to be identified for prevention of contact allergy. This is, owing to large knowledge gaps, particularly demanding for cobalt.

Luminex LiquiChip System for the Evaluation of Cytokine Levels in Patients with Contact Dermatitis to Potassium Dichromate.

BACKGROUND: Allergic contact dermatitis (ACD) is associated with increased production of cytokines. The patch test is the "gold-standard" diagnostic method, but it poses a risk of false results. OBJECTIVE: To evaluate a novel laboratory technique, the Luminex LiquiChip, which simultaneously measures blood levels of multiple cytokines, as a diagnostic tool in patients with chrome-induced ACD. METHODS: The study group included 20 patients with ACD and relevant patch test results for potassium dichromate and 19 patients with ACD for nickel or fragrance as control. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence and absence of potassium dichromate. The Luminex LiquiChip was used to measure levels of the following cytokines: granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon-γ, and tumor necrosis factor (TNF)-α. RESULTS: Potassium dichromate-stimulated PBMCs secreted significantly higher amounts of all cytokines except TNF-α than nonstimulated PBMCs. PBMCs from patients with ACD to chromium secreted significantly higher amounts of all cytokines tested, except IL-4, compared to PBMCs from patients with ACD to nickel or fragrance. CONCLUSIONS: Potassium dichromate stimulates the production of both Th1- and Th2-type cytokines in patients with chrome allergy. The Luminex LiquiChip is a promising in vitro method and may serve as a diagnostic tool for ACD.

Heavy metal (monoclonal) bands: a link between cutaneous T-cell lymphoma and contact allergy to potassium dichromate, nickel and cobalt?

It has been proposed that chronic antigenic stimulation plays a role in the pathogenesis of cutaneous T-cell lymphoma (CTCL). By definition, antigenic stimulation triggers allergic contact dermatitis (ACD). It is therefore plausible that chronic ACD could serve as a precursor to CTCL. We report two cases of contact allergy to potassium dichromate, nickel and cobalt, where CTCL was diagnosed in one patient, and a diagnosis of CTCL is imminent in the other. We also review the literature on the diagnostic criteria for CTCL in the setting of ACD and explore potential mechanisms for the progression from ACD tos CTCL.

The triggering role of allergic contact dermatitis in discoid lupus erythematosus.

BACKGROUND: The onset and exacerbations of discoid lupus erythematosus (DLE) can be precipitated by several factors like needling, scratches, trauma, X-rays, heat, cold, pressure, tattooing, scars, allergic and irritant dermatitis and inflammatory dermatoses. OBJECTIVE: To investigate the role of allergic contact dermatitis (ACD) in devolopment and triggering of the lesions of DLE. MATERIALS AND METHODS: This study was performed on 30 patients with DLE. European baseline series and cosmetic patch test series were used. At least 1+ reaction was accepted as meaningful. RESULTS: Twenty-three (76.7%) of 30 DLE patients and 16 (40%) of 40 control group patients were allergic to at least one allergen on standard patch test series. The difference between the groups were found statistically significant. Seventeen (56.7%) of 30 DLE patients and 6 (15%) of 40 control group patients were allergic to at least one allergen on cosmetic patch test series. The difference between the groups were statistically significant. The most sensitized allergens in both the groups were nickel sulphate, paraphenylen diamine, potassium dichromate from standard patch test series; quaternium 15, cocamidopropyl betain from cosmetic patch test series, in order. CONCLUSION: This study is distinctive since it is the first study to determine the eliciting role of ACD on DLE by imposing standard and cosmetic patch test series on DLE and control group patients. Worldwide, there is no study based on this subject. In the DLE group, the results of sensitization on standard and cosmetic patch test series were higher and statistically significant. Larger studies are required to reveal the exact role.

Contact allergy to metals in adolescents: nickel release from metal accessories 7 years after the implementation of the EU Nickel Directive in Poland.

BACKGROUND: Contact allergy among adolescents is an important issue. OBJECTIVES: To assess the prevalence of contact allergy to metals in adolescents aged 15 years and nickel release from metal accessories that are in direct contact with the skin. METHODS: Three hundred and nine females and 219 males, all 15 years old, from randomly selected secondary schools were examined and patch tested with nickel sulfate, cobalt chloride, palladium chloride, and potassium dichromate. Three hundred and ninety-nine metal accessories were tested with the dimethylglyoxime (DMG) test. RESULTS: 'Metal dermatitis' was reported by 19.4% of females and 0.5% of males. Positive patch test reactions were found in 8.5% of the adolescents (12.9% in females; 2.3% in males), namely to: nickel (12.3% of females; 1.4% of males); palladium (5.2% of females; 0.5% of males); cobalt (3.2% of females; 1.4% of males); and chromium (1.3% of females; 0.9% of males). Allergic contact dermatitis caused by metals was diagnosed in 9.7% of females and in 0.5% of males. Of the metal items, 26.1% gave positive DMG test results: 10.0% of earrings, 11.4% of snaps, and 56.2% of belt buckles. CONCLUSIONS: Despite the implementation of the Nickel Directive in Poland, nickel still remains an important causal factor for allergic contact dermatitis. Numerous metal accessories do not comply with the Directive.

Strip patch test vs. conventional patch test: investigation of dose-dependent test sensitivities in nickel- and chromium-sensitive subjects.

BACKGROUND: Tape stripping the skin prior to patch testing (strip patch test, SPT) may enhance percutaneous penetration of test substances and increase skin reactivity to test substances. OBJECTIVE: To evaluate the test sensitivity of SPT in compliance with our recently presented practical method vs. conventional patch test (PT) in nickel- and dichromate-sensitive subjects. METHODS: Thirty subjects participated in the prospective, randomized, controlled, investigator-blind study. Serial dilution tests of nickel sulphate (10,000-50 ppm aq.) and potassium dichromate (1000-5 ppm aq.) were used. Tests were applied in duplicate to both sides of the upper back of the subject, where one, randomly chosen side was tape stripped. RESULTS: According to the estimated test sensitivities, SPT is more sensitive than PT in nickel- and dichromate-sensitive subjects, regardless of the interindividual different numbers of tape strips. The superiority of the SPT grows with diminishing concentrations of the allergens. CONCLUSION: Test sensitivity of SPT vs. PT is increased. If no positive results are obtained by PT, the SPT could help to detect hidden allergens in case of weak sensitization or low concentration and poor percutaneous penetration of the test substances.

[Disseminated granulomatous type IV reaction after a tattoo]. / Disseminierte granulomatöse Typ-IV-Reaktion nach Tätowierung.

Localized type-IV allergies to tattoo dyes are quite common. p-Phenylenediamine, which is used as a black pigment in temporary henna tattoos, is a particularly potent allergen. Generalized type IV reactions are very rare, however. Disseminated granulomatous reactions on tattoo dyes have so far not been reported in the literature. We describe the case of a 54-year-old female patient who had such a reaction pattern after a tattoo owing to a previously unknown sensitization to potassium dichromate.

Renal proximal tubule segment-specific nephrotoxicity: an overview on biomarkers and histopathology.

The correspondence between histopathological findings and segment-specific biomarkers was investigated in rats treated with segment-specific nephrotoxicants. Male Wistar rats were treated with a single injection of K2Cr2O7 (25 mg/kg s.c. in saline), cis-Pt (10 mg/kg i.p. in buffered MSO) or HCBD (100 mg/kg i.p. in corn oil). Twenty-four and 48 hours after treatment, the rats were sacrificed and the kidneys were drawn for histopathological and biochemical evaluation, i.e., GS activity in renal cortex and PAH uptake in renal cortical slices. Histopathological findings show that cis-Pt and HCBD cause diffuse necrosis of S3 segment of proximal tubules in the outer stripe of outer medulla, respectively. On the contrary, K2Cr2O7 damages exclusively S1-S2 segments, inducing vacuolization at 24 hr and diffuse necrosis at 48 hr after treatment. GS activity in renal tissue is significantly decreased after HCBD and cis-Pt, but not K2Cr2O7 treatment. In contrast, PAH uptake is significantly reduced by K2Cr2O7, but not by cis-Pt or HCBD treatment (even if HCBD causes a slight decrease 48 hr after treatment). The evidence of this study confirms the high specificity of GS activity as marker of S3 segment injury, that PAH uptake is prevalently active in the S1-S2 segments, and that there is complete correspondence among segment-specific nephrotoxicants, biomarkers of segment-specific damage, and histopathological findings.

Occupational asthma due to chromium and nickel salts.

BACKGROUND: Exposure to chromium and nickel salts is a poorly characterized cause of occupational asthma. METHODS: We describe four patients with work-related asthma due to metallic salts. Skin-prick tests to potassium dichromate and nickel sulfate were performed. The patients underwent methacholine inhalation tests and specific inhalation challenges (SIC) with both chromium and nickel salts. RESULTS: Two patients showed positive skin-prick tests to potassium dichromate and nickel sulfate. All patients had bronchial hyperresponsiveness to methacholine, which increased 24 h after SIC with metallic salts. SIC with potassium dichromate elicited late asthmatic reactions (LAR) in two workers, one subject had an early asthmatic reaction (EAR), and another subject showed a dual asthmatic reaction (DAR). SIC with nickel sulfate induced a DAR in one subject and a late asthmatic reaction in another. CONCLUSIONS: Chromium and nickel salts can give rise to occupational asthma in exposed workers. The underlying mechanism may be IgE-mediated in some cases.

[Effects of ionizing radiation and xenobiotics on the spermatogenic epithelium of laboratory animals]. / Vliianie ioniziruiushchego izlucheniia i ksenobiotikov na spermatogennyi épitelii laboratornykh zhivotnykh.

Intact BALB/c and CBA mice differ in the overall cellularity of the spermatogenous epithelium, in the number of normal and pathological multinuclear cells. Exposure to small-dose radiation (0.25 and 1 Gy) causes profound changes in the spermatogenous epithelium in BALB/c mice. Then the increase in the abnormal forms of multinuclear and uninuclear cells leads to the disintegration and elimination of such cells, which affects the overall cellularity of the spermatogenous epithelium. A reduction in the proportion of multicellular cells, a compensatory-and-protective response that promotes the maintenance of the size of sex cells at the level optimal for fertilization. Upon small-dose exposure of rats to sixvalent chromium, there is a decrease in the whole population of germinitive cells and an increase in the multinuclear spermatocytes and spermatids. The rise in multinuclear cells is indicative of retarded cell maturation and differentiation at some stages of spermatogenesis, which reduces the number of spermatogenous cells.

Does potassium dichromate induce apoptosis in lymphocytes?

The aim of this work was to investigate the possibility of apoptosis in the human peripheral blood lymphocytes after treatment with potassium dichromate (K2Cr2O7), a potential occupational carcinogenic and mutagenic agent. Lymphocytes were stimulated by phytohemagglutinin, cultured for 72 h and incubated with either 0.2 mM or 0.4 mM K2Cr2O7 for the last 24 h or 48 h of culture. The condensation and margination of chromatin with emerging 'half-moon' structure, characteristic of apoptosis were observed. Phosphatidylserine displaced from the inner to outer side of the cellular membrane in 54% of cells after a 48-h incubation with 0.4 mM K2Cr2O7 (annexin-V+/PI-); 39% of these cells were of late apoptotic--secondary necrotic form (annexin-V+/PI+). Following the agarose gel electrophoresis of DNA, a 'ladder pattern' typical of apoptosis, was found. The results of the present study demonstrate that K2Cr2O7 can induce in the human peripheral blood lymphocytes changes similar to apoptotic ones.

Positive nickel patch tests do not intensify positive reactions to adjacent patch tests with dichromate. Results from a double-blind multicentre study of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG).

The possible interference of neighbouring allergic patch-test reactions is still an open question. In this study, we investigated whether there is a distance-related mutual modification of neighbouring allergic patch-test reactions to nickel sulfate and potassium dichromate. We used a double-blind multicentre study design with randomized attachment of special TRUE Tests with 1, 3 and 7 cm distance between nickel sulfate and potassium dichromate patches. 589 patients with a history of nickel allergy (523 female, 66 male) were tested, with a mean age of 35 years. A log-linear modelling approach was used for statistical assessment of the relation between the distance separating neighbouring patch tests with nickel and dichromate and the reactions to the allergens. Non-reproducibility coefficients were compared by the generalized version of Fisher's exact test for arbitrary 2-dimensional contingency tables. For the left side of the back, virtually no differences (p=0.70) were found in the reaction patterns obtained for the 3 distances separating nickel and dichromate patch tests. On the right side of the back, the number of reactions to dichromate patches with only 1 cm distance from moderate/strong nickel reactions was lower than the number of positive dichromate tests at larger distances from nickel tests (on the border of statistical significance: p= 0.05). Corresponding side-related results were obtained for subgroups of patients with and without a history of atopic dermatitis. The non-reproducibility of reactions to dichromate was not significantly related to the distance between neighbouring tests. Our data argue against a "spillover" effect of strong/moderate nickel reactions, but indicate that such reactions may, under certain conditions, attenuate adjacent reactions to an unrelated allergen. In the case of future verification, this will have implications for the interpretation of patch tests.

An environmental hazard assessment of low-level dermal exposure to hexavalent chromium in solution among chromium-sensitized volunteers.

To evaluate the potential for elicitation of allergic contact dermatitis from contact with standing water in the environment, 26 persons known to be allergic to hexavalent chromium [Cr(VI)] were exposed to 25 to 29 mg/L Cr(VI) by immersion of one arm for 30 minutes per day on 3 consecutive days in a potassium dichromate bath. Sixteen of the 26 volunteers demonstrated either no or an equivocal response to the Cr(VI) challenge. Ten of the volunteers developed a few papules or vesicles (1 to approximately 15), mild redness, and pruritus on the Cr(VI)-challenged arm. Histopathological examination of the papules revealed spongiosis and perieccrine and perivascular inflammation. The responses were diagnosed as acute perieccrine reactions. It was concluded that exposure to similar concentrations of Cr(VI) in the environment does not pose an allergic contact dermatitis hazard, even to Cr-sensitized persons.

Dermal and respiratory sensitization to chromate in a cement floorer.

BACKGROUND: To report a well-documented case of both allergic contact dermatitis and occupational asthma due to chromate exposure in a 48-year-old floorer. METHODS AND RESULTS: A 48-year-old floorer, occupationally exposed to cement and with a documented chromate contact dermatitis, reported dyspnea and wheezing after work. These conditions were demonstrated by self-measured sequential peak expiratory flows. A first bronchial provocation (BPT) with potassium dichromate (K2Cr2O7) (0.3% nebulized for a total of 60 minutes) led to pronounced and sustained decreases in forced expiratory volume in 1 second (FEV1) and forced vital capacity, accompanied by pruritus, a decrease in arterial PO2, a slight rise in temperature, and peripheral blood leukocytosis. (This concentration of K2Cr2O7 is not recommended for BPT). Bronchoalveolar lavage performed 2 days later showed 18% eosinophils. Tow years later, a BPT with a lower dose of K2Cr2O7 (0.01% for the total of 31 min) led to an "earl late" reaction (FEV1 dropped by 195 compared with the initial FEV1 value), accompanied by pruritus. A BPT with dry cement, containing 12 ppm hexavalent chromium, was borderline (FEV1 dropped by 13%), and a similar result (FEV1 dropped by 14%) was obtained after smoking five cigarettes, laced with 10 mg of cement per cigarette. CONCLUSIONS: This report illustrates that a subject, with allergic contact dermatitis to chromates, may develop a respiratory allergic reaction to an airborne source of this metal. The main novelty of our report is that the smoking of cigarettes contaminated with cement may have been significant factor in the causation or elicitation of these reactions.

[Skin reactivity in subjects sensitive to different concentrations of nickel, chromium and cobalt]. / Reaktywnosc skóry osób uczulonych na rózne stezenia niklu, chromu i kobaltu.

Patch tests with serial dilutions of nickel sulphate, potassium dichromate and cobalt chloride in petrolatum were performed on 124 nickel-sensitive, 64 chromium-sensitive, and 72 cobalt-sensitive subjects. The lowest eliciting patch test concentrations were as follows: nickel sulphate--0.005, potassium dichromate--0.0025, and cobalt chloride--0.005.

Novel predictive assay for contact allergens using human skin explant cultures.

Contact allergens sensitize the immune system by the binding to and subsequent activation of Langerhans cells (LCs), the antigen-presenting cells of the skin. At present, new chemicals are usually tested for their contact allergenicity in animal models. To develop an animal-replacing predictive in vivo assay for the identification of potential contact allergens, we compared the effects of epicutaneous application of six known contact allergens, five known irritants and two dermatologically inactive chemicals on LCs in skin biopsy cultures from seven healthy donors. Immunohistochemical analysis of cryostat sections of all the biopsies treated with contact allergens showed 1) a large reduction in the number of LCs in epidermis, as evaluated by a decrease in human leukocyte antigens (HLA)-DR-expressing cells, and CD1a-expressing cells and 2) accumulation of the remaining LCs at the epidermal-dermal junction. In contrast, the irritants, inactive chemicals, and solvents did not induce these changes. Morphometrical analysis indicated that the contact allergen-induced reduction in the number of HLA-DR+ and CD1a+ LCs per millimeter of epidermis was significant and was dependent on the concentration of the contact allergens. Flow cytometric analysis of isolated epidermal cells confirmed the immunohistochemical findings. In combination, these results suggest that the culture of ex vivo human skin explants provides a promising model to predict potential allergenicity of newly produced chemical compounds and can therefore replace current animal models.