Combined effects of irritants and allergens. Synergistic effects of nickel and sodium lauryl sulfate in nickel- sensitized individuals

Knowledge of the combined effects of irritants and allergens is of interest with respect to accurate risk assessment. The threshold for elicitation of allergic contact dermatitis in previously sensitized individuals may theoretically be markedly influenced by the simultaneous presence of irritants and allergens. Combined exposures have, however, only been studied infrequently. In the present study, the combined effect of an irritant and an allergen was evaluated in a dose-response designed experimental study. 20 nickel-sensitized subjects were exposed to patch testing with varying concentrations of NiCl2 (nickel chloride) and sodium lauryl sulfate (SLS) alone and in combination. Evaluation of skin reactions was performed by colorimetry, measurement of transepidermal water loss and clinical evaluation, and the data were analyzed by logistic dose-response models. A synergistic effect was found of combined exposure to NiCl2 and SLS, as compared to each of the substances applied separately, as evaluated by colorimetry and clinical scoring. This means that the effect produced by the combined exposure was substantially greater than the effect produced by either of the substances alone. A synergistic effect of combined exposure on skin barrier impairment was not found, since the barrier function is significantly influenced by SLS-exposure only and not by NiCl2. Concentration limits are used by industry and government agencies to protect consumers. The present results clearly illustrate that elicitation thresholds and concentration limits may be influenced considerably by combined exposure to allergens and irritants.     

Epidemiology of occupational skin disease in Singapore 1989-1998

This is an epidemiologic study of occupational skin disease in Singapore. All patients diagnosed with occupational dermatoses in the National Skin Centre, Singapore, over the 10-year period 1989-1998 were studied retrospectively. Irritant contact dermatitis was found to be more common than allergic contact dermatitis. The major sources of occupational dermatitis in Singapore were the metal/engineering, building/construction, electrical/electronics and transport industries. The main irritants were detergents/wet work, solvent and oil/grease. The main allergens were chromate, rubber chemicals and nickel. We concluded that the main sources of occupational skin disease and main allergens in Singapore had remained the same compared to a similar study of occupational skin diseases in 1984-85. Weak irritants are still the predominant causes of occupational irritant contact dermatitis, though the main irritants have changed compared to the previous study, where cutting fluids, cement and solvent were the most common irritants.     

Irritants in combination with a synergistic or additive effect on the skin response: an overview of tandem irritation studies

Sodium lauryl sulfate (SLS) has often been chosen as a model for irritant contact dermatitis (ICD) to study the effect of irritants in combination (1-14). Recently 'tandem', or sequential, exposures with SLS have been performed to study the mechanism of skin barrier impairment in ICD (1-6, 15). The assessment of reactions have been documented with visual scoring, transepidermal water loss (TEWL), skin colour reflectance measurements, skin blood flow; among which TEWL has been noted as the most sensitive value (16). The matched control groups were treated with either a single exposure to a single irritant or in tandem with the same irritant repeatedly. Synergistic and additive effects have been reported for various tandem pairs of irritants, however, the mechanism for both remains unclear. The results of tandem irritation studies were evaluated to define and investigate the responses produced and deduce a possible mechanism of action. Clinical ramifications, albeit complex, are discussed.     

CONTINUING MEDICAL EDUCATION REVIEW Occupational skin disease in hairdressers

Hairdressers belong to an occupational group that is commonly affected by occupational skin disease, specifically contact dermatitis, which may be allergic or irritant and, less commonly, contact urticaria. Occupational contact dermatitis predominantly affects apprentices, and atopy is a recognized risk factor associated with a poor prognosis. Repetitive wet work leading to irritant contact dermatitis, followed by exposure to allergens and the development of allergic contact dermatitis, are the main factors contributing to occupational contact dermatitis. Once developed, it is often difficult to manage and is a cause of significant morbidity. Early education, training and prevention is the best approach to the management of this disorder that is endemic among hairdressers.     

Contact dermatitis of the vulva

ABSTRACT:  Vulvar diseases rarely stand alone. They are often caused or worsened by primary irritant or allergic contact dermatitis, and this should be considered when evaluating any vulvar complaint. All irritants should be avoided in all women, and those with vulvar dermatoses should be patch tested to help define or rule out allergens.     

An animal model for altering the irritability threshold of normal skin

Theory behind conditioned hyperirritability (autoeczematization) predicts the lowering of the irritation threshold in the presence of a pre-existing dermatitis. We have attempted to develop an animal model that parallels the syndrome seen in man. Groups of 10 guinea pigs were shaved and depilated; irritation thresholds to benzalkonium chloride and trichloroacetic acid were determined using 1 cm diameter open patches. Reactions were scored 24 h later on the basis of erythema and induration. Animals having as little as 1.56 cm2 of skin acutely inflamed with a known irritant had lowered irritation thresholds to the same irritant on normal skin at remote sites (p less than 0.01). Mild irritation of a much larger surface area produced the same effect (p less than 0.01). More extensive, severe dermatitis did not lower the irritation threshold further. Acute dermatitis induced by a contact allergen (DNCB) lowered the irritation threshold of normal skin to the same level as that obtained with irritants (p less than 0.01). Induction of chronic cutaneous ulcers 3-4 cm in diameter lowered the irritation threshold of normal skin to the same point defined by the acute studies (p less than 0.01). These results indicate that an acute irritant or contact dermatitis, as well as chronic skin ulceration, may alter the reactivity of unaffected normal skin to exhibit a heightened response to irritation. This model appears to differ from that seen in humans, in that a more extensive or chronic dermatitis did not further heighten the susceptibility to irritation.     

Skin protection in nursing work: promoting the use of gloves and hand alcohol

Nursing has been identified as a wet-work occupation, with a high prevalence of occupational irritant contact dermatitis. Reduction of exposure to skin irritants contributes to the prevention of occupational skin disease in nurses. The role of the use of soap and water, hand alcohol and gloves in prevention programmes is discussed. 2 additional measures for reducing exposure to skin irritants are postulated: use of hand alcohol instead of soap and water in disinfection procedures when the hands are not visibly dirty; use of gloves in wet activities such as patient washing to prevent the hands from becoming wet and visibly dirty. We investigated the effectiveness of these recommendations in a model. Mean daily wet-work exposure during nursing work was modelled: regular model. We also modelled exposure to skin irritants in combination with the implementation of these recommendations: prevention model. The hands of healthy volunteers were exposed to the regular or the prevention model over 3 weeks for 5 days a week. The change in transepidermal water loss (TEWL) on the back of the hands was measured after 3 weeks of exposure to these wet-work simulations. An increase in TEWL occurred with the regular model, while mean TEWL decreased in the prevention model. Skin irritation from occlusion by gloves appeared to be more pronounced in the regular model compared to the prevention model. The results of this study justify the conclusion that in nursing work, hand alcohol is the preferred disinfectant. Although the prevention model implies increased occlusive exposure, this has no additional irritant effect, probably because of the absence of soap exposure.     

Industrial airborne irritant or allergic contact dermatitis

Industrial airborne irritant or allergic contact dermatitis is commonly observed in many factories. Examples of airborne irritants include fibres (such as fibreglass or rockwool), various kinds of dust particles (such as cement, slag, sludge, insulating foam, wood chips), acids and alkalis, gasses and vapours. Airborne contact allergens are unequivocally numerous. The clinical symptoms of both irritant and allergic airborne contact dermatitis are reviewed.     

Abnormal epidermal barrier in the pathogenesis of contact dermatitis

A crucial role of the epidermal permeability barrier is obvious in contact dermatitis. An intact skin barrier prevents the penetration of harmful substances into the skin. Irritants and allergens that stay on the skin surface and come into contact with the stratum corneum only do not harm the skin. After disruption of the skin barrier, however, irritants may penetrate into the living epidermal layers, injure the keratinocyte membrane, and release cytokines, which leads to inflammation and to irritant contact dermatitis. The skin barrier is often disrupted by chronic exposure to water plus detergents, solvents, or other irritants. A disrupted barrier in irritant contact dermatitis also allows for the penetration of allergens. Allergens may come into contact with Langerhans and T cells, induce immunological reactions, and cause inflammation, which results in allergic contact dermatitis. Treatments in contact dermatitis should restore the skin barrier to prevent relapse of the disease. Topical corticosteroids, most often used in treating contact dermatitis, reduce immunological reactions and inflammation but do not lead to a complete barrier repair. Skin barrier repair is more complete after treatment with calcineurin inhibitors and bland lipid-based emollient; therefore, these preparations should be preferred for long-term treatment of contact dermatitis.     

Allergic contact dermatitis from di-isodecyl phthatate in a polyvinyl chloride identity band

An animal model for the evaluation of skin protective creams against chemical irritants is described. The irritants were applied daily for 2 weeks to shaved back skin of young guinea pigs: sodium tauryl sulphate (5% aq.: 30 min), sodium hydroxide (0,5% aq.; 2 min). and toluene (20′i. eth.; 2 mint. “The harrier cream was applied 2 h prior to and immediately after exposure to the irritant. Control animals were treated with the irritant only. The irritant reaction was scored on a 4–point scale for erythema and quantified with regard to transepidennal water loss (TEWL) by evaporime-try and skin blood flow volume (BFV) by laser Doppler velocimetry. A total of 90 guinea pigs, consisting of” individual panels of 5 to 10 animals, was tested. While one barrier cream (Slokoderm) significantly suppressed the irritation due 10 sodium lauryl sulphate and toluene, the other (Contra-Alkalh failed to do so and even aggravated the response, which was particularly evident with sodium hydroxide. This model may be useful in developing more effective barrier creams.     

Irritation potential of bath and shower oils before and after use: a double-blind randomized study

BACKGROUND: Difficulties in avoiding weak irritants may contribute to chronic contact dermatitis. A large variety of shower and bath oils are claimed to be suitable for use on dry skin because of their mildness and because they deposit a protective oil film on the skin. OBJECTIVES: The aim of the present study was to investigate possible differences in the irritation potential of eight shower or bath oils and to investigate whether surfactant residues may form a reservoir of irritant substance on the skin. PATIENTS AND METHODS: The study was double-blind and randomized using healthy human volunteers. The inherent capacity of the products to induce irritation was determined using conventional patch test techniques. Detection of potentially irritant residues was done by occlusion of the treated and rinsed skin area, followed by evaluation of the biological response. Instrumental measurements of transepidermal water loss and superficial skin blood flow served as indicators of the injurious effects of the products. RESULTS AND CONCLUSIONS: The results showed large differences between the products in irritant potential. Some did not irritate skin more than water, whereas others demonstrated considerably damaging effects. Moreover, the study proved the presence of barrier-impairing residues on the skin after rinsing with water. Thus, instead of protecting the skin, some formulations may induce subclinical injuries and delay skin barrier function recovery with prolonged risk for patients with eczema.     

Pathological findings in cumulative irritation induced by SLS and croton oil in hairless mice

It is known that the pathological features of acute irritant contact dermatitis are specific according to the irritant. However, in chronic irritant contact dermatitis, it is not clear whether specific patterns exist. To investigate whether the specific pathology of acute irritant contact dermatitis is sustained in chronic irritant contact dermatitis, sodium lauryl sulfate (SLS) and croton oil were applied 3x a week for 2 weeks on the dorsal skin of hairless mice using Finn Chambers. The pathologic changes induced by irritants at various concentrations were evaluated using H&E and Luna's staining, as well as immunohistochemistry for 5-bromo-2-deoxyuridine (BrdU), keratin 6 and loricrin. Our results showed that epidermal hyperplasia and inflammatory infiltration were relatively marked in the groups treated with higher concentrations of irritants. These features were more prominent in the 1% croton oil treated group than in the 0.25% SLS treated group. However, lower concentrations of irritants resulted in very similar histological changes, characterized by epidermal hyperplasia with minimal inflammatory infiltration, irrespective of the chemical. Our results suggest that the histological responses to irritants vary with concentration in cumulative irritation, as in acute irritation, but repetitive mild irritation may evoke common histological changes, characterized by epidermal hyperplasia with minimal inflammatory infiltration, irrespective of the chemical used.     

Dendritic cells: biology of the skin

Allergic contact dermatitis results from a T-cell-mediated, delayed-type hypersensitivity immune response induced by allergens. Skin dendritic cells (DCs) play a central role in the initiation of allergic skin responses. Following encounter with an allergen, DCs become activated and undergo maturation and differentiate into immunostimulatory DCs and are able to present antigens effectively to T cells. The frequency of allergic skin disorders has increased in the past decades. Therefore, the identification of potential sensitizing chemicals is important for skin safety. Traditionally, predictive testing for allergenicity has been conducted in animal models. For regulatory reasons, animal use for sensitization testing of compounds for cosmetic purposes is shortly to be prohibited in Europe. Therefore, new non-animal-based test methods need to be developed. Several DC-based assays have been described to discriminate allergens from irritants. Unfortunately, current in vitro methods are not sufficiently resilient to identify allergens and therefore need refinement. Here, we review the immunobiology of skin DCs (Langerhans' cells and dermal dendritic cells) and their role in allergic and irritant contact dermatitis and then explore the possible use of DC-based models for discriminating between allergens and irritants.     

Occupational irritant and allergic contact dermatitis among healthcare workers

Contact dermatitis is the most frequent occupational dermatosis and non-specific irritants in addition to specific Type IV sensitization are involved. We reviewed our database for data from 1994 to 1998 and selected 360 consecutive patients working in healthcare environments and experiencing contact dermatitis at their hands, wrists and forearms. We found that allergic contact dermatitis and irritant contact dermatitis were considered to be work-related in 16.5% (72/436) and 44.4% (194/436) of diagnoses, respectively. Occupational irritant contact dermatitis is due to exposure to a wide range of irritants in the workplace, such as soaps, solvents, cleansers and protective gloves, which conspire to remove the surface lipid layer and/or produce cellular damage. In this study the major relevant aetiological agents that induced occupational allergic contact dermatitis were: nickel sulphate (41 patch positivities), components of disinfectants [glutaraldehyde (5) and benzalkonium chloride (7)] and rubber chemicals [thiuram mix (15), carba mix (9) and tetramethylthiuram monosulphide (6)]. The best treatment for allergic contact dermatitis is to avoid those allergens causing the rash. Whenever this is not possible, contact with them needs to be reduced using properly selected protective gloves. Finally, subjects with atopic dermatitis should avoid 'wet work' and contact with irritants, because atopic dermatitis is significantly associated with irritant contact dermatitis.     

Skin irritants and contact sensitizers induce Langerhans cell migration and maturation at irritant concentration

Skin irritants and contact allergens reduce the number of Langerhans cells (LCs). It has been assumed that this reduction is due their migration to the draining lymph node (LN) for initiating immune sensitization in a host. Skin irritation, however, as opposed to contact allergy is not considered to be an immunological disease. Nevertheless, skin irritants are also known for their adjuvant-like effects on contact allergy, resulting in skin hypersensitivity reactions like toxic dermatitis. The human organotypic skin explant culture (hOSEC) model is used to study the characteristics of chemical-induced migration of CD1a(+) LCs out of the epidermis in relation to irritancy or toxicity. We analysed cells emigrating out of hOSEC for CD1a(+) LCs, CD83(+) mature dendritic cells (DCs) and CCR7(+) LN homing cells. After exposure to a toxic concentration of a non-immunogenic irritant, an increase of CD1a(+)CD83(+) LCs was found in the culture medium. A non-toxic concentration of an sensitizer induced an increase of CD1a(+) cells. About 50% of skin emigrating CD1a(+) LCs were CD83(-) (immature) but all were CCR7(+). Skin irritation by both non-allergenic and allergenic compounds induces LC migration and maturation. In contrast, only allergenic compounds induced LC migration with partial maturation at subtoxic concentration. This effectively demonstrates that irritation is physiologically needed stimuli for inducing LC maturation.     

Long-term repetitive sodium lauryl sulfate-induced irritation of the skin: an in vivo study

Skin may adapt to topical irritants through accommodation. This study focuses on long-term exposure to irritants and attempts to demonstrate accommodation. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis at 3 concentrations (0.025% to 0.075%). Distilled water, acetone and an empty chamber served as controls. Experimental compounds were applied to forearms of 7 healthy volunteers for 24 hr before replacing by a fresh chamber for 6 non-consecutive weeks over 103 days. Possible accommodation was quantified by visual scoring (erythema and dryness) and by bioengineering parameters: transepidermal water loss (TEWL), capacitance, chromametry and laser Doppler flowmetry (LDF). Significant erythema, dryness, elevated TEWL, skin colour reflectance and LDF values occurred during the exposure periods. Upon repeat exposure, an immediate and augmented response in erythema, TEWL, skin colour reflectance and LDF developed. However, irritant skin changes were not sustained. Irritation parameters return to baseline after cessation of exposure. There was no evidence of sustained irritation or accommodation after the last exposure. Study findings do not document sustained accommodation or adaptive hyposensitivity after long-term repetitive irritant exposure under these test conditions. Alternative models should be developed to prove or disprove the accommodation hypothesis.     

Skin irritation thresholds in hairdressers: implications for the development of hand dermatitis

BACKGROUND: Individuals vary in their ability to react to irritants. OBJECTIVES: To observe the development of clinical hand dermatitis and sensitization prospectively in trainee hairdressers and to compare this with their irritant threshold to sodium lauryl sulphate (SLS). METHODS: Subjects were patch tested to a limited series of occupational importance and their irritant threshold to SLS was determined; patch testing was repeated 6 months later and subjects were assessed for hand dermatitis. RESULTS: The development of hand dermatitis was associated with a lower irritant threshold. A similar association was not found for sensitization. CONCLUSIONS: The development of clinical dermatitis in prospectively followed subjects with greater irritant reactivity has not previously been identified. The association of greater irritant reactivity with a proinflammatory cytokine polymorphism may partly explain this. Further development of the irritant threshold test could contribute to the identification of non-atopic subjects at risk of occupational skin disease.     

Contact allergens, but not irritants, alter receptor-mediated endocytosis by human epidermal Langerhans cells

Allergic contact dermatitis is a T-cell-mediated inflammation, induced by contact with sensitizers and occurring through the release of epidermal cytokines and the activation of epidermal Langerhans cells (LCs). The aim of this study was to analyse early events of LC activation induced either by contact allergens or by irritants devoid of any contact allergenic properties. in order to obtain an in vitro method to discriminate between these two groups of molecules. Various contact sensitizers and irritants were studied for their effects on the endocytosis of major histocompatibility complex class II (MHC-II) molecules by freshly-isolated human epidermal LCs. As observed by flow cytometry, a spontaneous decrease in the surface expression of MHC-II (HLA-DR) molecules, linked to spontaneous internalization of the MHC-II molecules by LCs, was obtained by moving freshly-isolated LCs from 4 degrees C to 37 degrees C. Pre-incubation of LCs with either sensitizers or irritants increased the spontaneous internalization of HLA-DR molecules with a similar magnitude, but no clear discrimination between sensitizer and irritant effects was obtained by flow cytometry analysis. In contrast, confocal microscopy enabled discrimination between the effects of sensitizers and irritants: sensitizer-treated samples showed internalized HLA-DR molecules aggregated in large vesicles with very bright fluorescence; irritant-treated samples were not different from untreated controls and showed compact HLA-DR molecules in small vesicles with diffuse fluorescence, and mostly localized in the submembranous zone. Electron microscopy demonstrated that sensitizer-treated LCs internalized HLA-DR molecules preferentially in lysosomes collected near the nucleus, whereas the irritant-treated and non-treated LCs internalized these molecules in the prelysosomes only near the cell membrane. We conclude that contact allergens and irritants induce distinct patterns of HLA-I)R endocytosis, which may be useful for the development of in vitro screening tests.     

Experimental irritant contact dermatitis due to cumulative epicutaneous exposure to sodium lauryl sulphate and toluene: single and concurrent application

In clinical practice, cutaneous exposure to a variety of irritants such as surfactants and solvents is frequent. Although the induction of irritant dermatitis by single irritants has been extensively studied in recent years, our knowledge of the effects of simultaneous application of different irritants is limited. Using non-invasive techniques for measurements of transepidermal water loss (TEWL) and skin colour reflectance, we quantified the irritant effects of single and concurrent application of 0.5% sodium lauryl sulphate (SLS) and undiluted toluene (TOL) in vivo. The irritants were applied twice daily for 30 min to the volar forearms of 20 volunteers. Repeated application of SLS and TOL induced an irritant reaction, as indicated by an increase in TEWL and skin redness. In contrast to SLS alone, the application of TOL alone induced only a moderate increase in TEWL, confirming previous results. Concurrent application of SLS/TOL and TOL/SLS induced significantly stronger reactions than those caused by twice daily application of each irritant on its own. Our results demonstrate that a mixed application of an anionic detergent and an organic solvent has an additive effect on skin irritation. It is suggested that pretreatment with SLS causes an increased susceptibility to TOL irritation and vice versa. Thus, the necessity for special precautions against skin absorption of TOL when handling detergents such as SLS is emphasized.     

Dermatitis in bulb growers

A damaged skin forms a health hazard in flower-bulb growers as it enables higher permeation rates For pesticides than normal skin. Therefore, an investigation was performed into the skin condition of 103 bulb growers and 49 controls. Contact dermatitis of the hands was of the same order (11 and 10%) in both groups. However, minor signs of dermatitis were seen more often in bulb growers (30 versus 8%, p <0.05). Most growers had contact with narcissus sap during the investigation. This irritant sap, as well as many other skin contacts with irritants such as hyacinth dust and pesticides, seemed to be responsible for many skin complaints. Contact serialization was suspected in 19 growers and 3 controls. Patch tests showed that contact sensitization existed to pesticides in probably 10, and to flower-bulb extracts in 4 growers. Reactions to propachlor were not regarded as very reliable as the test concentration seemed to be marginally irritant. There were only a few allergic reactions to narcissus (3) and tulip (2) and none to hyacinth. This investigation showed that minor irritant contact dermatitis was frequent in bulb growers, and indicated that contact sensitization to pesticides and bulbs seemed to be a less frequent but important cause of dermatitis.