Suchergebnisse

Anti-irritants, whether naturally occurring or man-made, are substances that provide a soothing effect to irritated skin and reduce damage by a variety of mechanisms, including reduced absorption and/or biochemical manipulation of noxious chemicals. These products show promise in reducing irritation caused by acute and chronic exposure to known irritant chemicals; however, the data on anti-irritants are incomplete. Controlled trials of the efficacy of proposed anti-irritants substances in reducing irritant contact dermatitis in human and animal models are reviewed. Based on our literature and hand search, anti-irritants seem promising in treating and preventing a variety of irritant contact dermatitis conditions, but their true effects remain <i>sub judice. </i>Many studies do not allow deduction of clinical effects. Further experimentation must be performed to assess sensitivity and specificity of each anti-irritant to their specific irritant-inducing substance.

Abstract
Irritant contact dermatitis (ICD) is the most common form of contact dermatitis. It represents the cutaneous response to the toxic/physical effects of a wide variety of environmental agents. Nowadays, it is recognized that irritancy does not represent a single monomorphous entity but rather a complex biologic syndrome with diverse pathophysiology and clinical manifestations. The clinical presentation is highly variable depending on several factors, including properties and strength of the irritant, dose, duration and frequency of exposure, environmental factors, and skin susceptibility. The pathophysiological mechanism depends on activation of the innate immune system and involves skin barrier disruption, cellular changes, and release of proinflammatory mediators that directly recruit and activate T lymphocytes. The diagnosis of irritant contact dermatitis is often clinical, and involves a comprehensive history and examination, as well as the exclusion of allergic contact dermatitis with patch testing. Recent advances in understanding the pathogenesis as well as better awareness of the clinical significance of ICD will lead to a improved care for our patients.

The fragrance material geraniol has been cited as a frequent cause of allergic contact dermatitis. A review of the literature shows that when the underlying clinical and experimental data are analyzed, a clear cause-effect relationship has infrequently or rarely been established. On the basis of the generally weak sensitizing potential of this substance coupled with its generally low exposure conditions, the prevalence of clinical cases would not be expected to be particularly high. This is not to say that geraniol is a frequent inducer of type IV allergy in members of the public. It remains to be seen, however, how often such allergy, once established, is responsible for any of the cases of allergic contact dermatitis commonly ascribed in the literature. Indeed, in some cases, patch-test conditions may not be optimal for differentiating between clinically relevant and irrelevant allergy to geraniol. Because of the numerous publications on geraniol-positive patch-test publications, a future effort to ascertain how many of these represent clinical intolerance is indicated. This will also permit determination of the NOEL (no observed effect level) in patch and use testing.

The fragrance material citronellol has been cited as a moderately frequent cause of allergic contact dermatitis. A review of the literature shows that when the underlying clinical and experimental data are analyzed, a clear cause-effect relationship has infrequently or rarely been established. On the basis of its generally weak sensitizing potential in animals and human volunteers, coupled with its generally low exposure conditions, the prevalence of clinical cases would not be expected to be particularly high. This is not to say that citronellol is a frequent inducer of type IV allergy in members of the public. It remains to be seen, however, how often such allergy, once established, is responsible for any of the cases of allergic contact dermatitis commonly described in the literature. Indeed, in some cases, patch test conditions may not be optimal for differentiating between clinically relevant and irrelevant allergy to citronellol. Clarification of patch-test-related clinical relevance may be obtained utilizing retesting, dilution series and use tests.

The fragrance material alpha-iso-methylionone, or 'gamma-methylionone', has been cited as a moderately frequent cause of allergic contact dermatitis. A review of the literature shows that when the underlying clinical and experimental data are analyzed, a clear cause-effect relationship has infrequently or rarely been established. On the basis of the generally weak sensitizing potential of this substance, coupled with its generally low exposure conditions, the prevalence of clinical cases would not be expected to be particularly high. This is not to say that alpha-iso-methylionone is a frequent inducer of low-intensity but sub-clinical, type IV allergy in members of the public. It remains to be seen however, how often such allergy, once established, is responsible for any of the cases of allergic contact dermatitis commonly ascribed in the literature. Indeed, in some cases, patch test conditions may not be optimal for differentiating between clinically relevant and irrelevant allergy to alpha-iso-methylionone. Prospective screening patch test studies combined with appropriate follow-up to ascertain clinical relevance should clarify these issues.

The fragrance material anisyl alcohol has been cited as a moderately frequent cause of allergic contact dermatitis. A review of the literature shows that when the underlying clinical and experimental data are analyzed, a clear cause-effect relationship has infrequently or rarely been established. On the basis of the generally weak sensitizing potential of this substance coupled with its generally low exposure conditions, the prevalence of clinical cases would not be expected to be particularly high. This is not to say that anisyl alcohol is a frequent inducer of type IV allergy in members of the public. However, it remains to be seen how often such an allergy, once established, is responsible for any of the cases of allergic contact dermatitis commonly ascribed in the literature. Indeed, in some cases, patch test conditions may not be optimal for differentiating between clinically relevant and irrelevant allergy to anisyl alcohol.

In practice, the clinical diagnosis of allergic contact dermatitis is often highly problematic with the identification of the specific allergen that has actually caused a patient's particular dermatitic episode being even more difficult. A large number of reports in the literature are able to identify a number of substances to which the patient is allergic without clearly indicating a causal link to the patient's current problem. For the reader of such reports, it is often difficult to judge if this link has been established, and for this reason, a number of criteria have been proposed to determine if reported positive patch test reactions are clinically relevant. These criteria include the degree of information given on the selection and condition of the patients, patch testing conditions, the intensity and duration of reactions, reactions occurring simultaneously to other patch test materials, the likelihood of confounding factors such as cross-reactions and excited skin occurring, linkage to specific consumer products or environmental sources of the putative allergen and follow-up with appropriate use testing. Criteria are also suggested for evaluating a substance's allergenic potency from reports of predictive testing. These include the availability of details on the test methodology, maximization procedures, the selection criteria for test and control subjects and of the exact test scores. The applicability of these criteria are tested in separate publications on 6 fragrance allergens, for which information is provided on patch test concentrations.

<i>Background:</i> Routine patch testing is usually performed with 2-day occlusion. Yet, shortening the application period, without diminishing diagnostic accuracy, would benefit patients. Previous studies document that differences in application time may produce variable results. <i>Objective:</i> Our objective was to determine whether 1-day application elicits similar results to 2-day application in diagnostic patch testing. <i>Methods:</i> Simultaneous duplicate patch test series were applied to the opposite sides of the upper back on 250 consecutive patients, using the TRUE test system. One set of allergens was removed after 24 and the other after 48 h. <i>Results:</i> A total of 221 positive reactions were observed either after 24 or 48 h of occlusion in 113 (46%) patients. Of these, 190 were concordant, i.e. positive, after 24 and 48 h of occlusion, and 31 were discordant. Twenty-nine of the discordant reactions were observed only after 48 h of occlusion and 2 only after 24 h of occlusion. Of the 27 (19%) patients with discordant patch test reactions, the allergen was deemed to be of definite present or past relevance in 16 (6% of the total and 14% of all patients with positive reactions). <i>Conclusion:</i> These data confirm that the overall concordance of results after 24 and 48 h of application is high. However, clinically relevant allergens would have been missed in 16 patients if only the 24-hour occlusion test was performed. In the light of these results, we consider that the standard 48-hour application remains appropriate for diagnostic patch testing.

Stratum corneum intercellular lipids regulate skin water barrier function and water-holding capacity; their modification may impair these properties. Physical and chemical stresses diminish barrier function. Acute barrier disruption by tape stripping increases sphingomyelinase and serine palmitoyltransferase activity; ceramide contents are increased to restore barrier function. Overcrowding stress induces dry skin, and the barrier function impairment correlates with decreased skin cera- mides. The effect of UV irradiation on ceramide content and barrier function varies with doses and UV wavelength. Stress-induced ceramide generation may induce apoptosis in cultured human keratinocytes and restore barrier function. This review focuses on the role of ceramides in physical and chemical stress, suggesting that refinement and extension of this academic domain may lead to therapeutic advances.

In suspected allergic contact dermatitis, the proper choice of vehicles for patch testing may be critical. The role of vehicles in diagnostic patch testing has been summarized, suggesting that improved delivery systems might significantly increase the reproducibility and reliability of patch tests. We review the literature subsequent to 1992 for advances in our knowledge of the optimization of vehicles for patch testing. A universal vehicle more efficient than petrolatum or water remains elusive; in vitro percutaneous penetration data provide insight that questions standard dogma.

The studies on the application of topical preparations are reviewed. The data obtained demonstrate that in most cases the quantities of sunscreens, industrial protective creams and topical medications may differ greatly on different anatomic sites and may also vary due to numerous factors. The data on influencing factors in various studies were partially controversial, therefore a possible study design is suggested to resolve these controversies. It is also suggested that the standard layer thickness of sunscreens, used by standardization authorities to evaluate the sun-protective factor, should be reviewed, due to the evident failure of the majority of sunbathers to comply with the standard layer thickness used now by the ASA (2 mg/m²) or DIN (1.5 mg/m²). It is also important to have a standard of applied amounts of topical medications to be able to compare the effectiveness and bioequivalence of different topical medications precisely. The use of special delivery methods (such as flurandrenolide tape) demonstrates one approach to the standardization of topical treatment dosing.

Many patients undergoing topical retinoid therapy experience erythema, scaling, dryness, burning and pruritus. These symptoms characterize the retinoid-specific irritant contact dermatitis commonly termed 'retinoid dermatitis'. Other irritants and abrasives cause similar clinical symptoms and histological changes in the skin; however, there are differences in their timing of onset and duration. Unlike that of sodium lauryl sulfate, the transepidermal water loss increase after retinoic acid application is delayed and accompanied by an overall increase in stratum corneum hydration. Tretinoin also increases dermal collagen by stimulating synthesis and inhibiting degradation. This evidence suggests a unique pharmacological activity for retinoids, which is probably a receptor-mediated process. In mice with compromised receptor function, topical tretinoin fails to induce hyperplasia, desquamation and peeling. Many retinoid actions in the skin are probably receptor mediated, and the irritation, at least the scaling and peeling component, is partly related to these pharmacological effects. While there is convincing evidence that tretinoin may repair solar damage without irritation, there is less consistent evidence that less irritating retinoids can be comparably effective in acne treatment. Taken together, we lack a precise quantification and qualification of the difference between the clinical and irritant effects of these molecules.

Skin hydration depends on the water-holding capacities of the stratum corneum. One of the techniques used to evaluate skin water content is the water sorption-desorption test. This method involves hydrating the skin with water and then observing the subsequent dehydration activity by means of serial recording with electrical instruments. Currently, three instruments are available to perform such a test: the Skicon^® 200, the Corneometer^® CM820 and the Nova DPM^® 9003. However, each device measures the skin hydration in its own unique parameter, making interexperimental comparisons difficult. Despite this shortcoming, the water sorption-desorption test is a useful tool to measure the dynamic hydration of the skin and the stratum corneum water-holding properties. Pathological skin conditions like atopic dermatitis affect corneum integrity and reduce its ability to hold water. Irritants can also damage the cutaneous barrier and result in decreased hydration. On the contrary, delipidization of the newborn skin with organic solvents increases the water-holding capacity of the stratum corneum. Since the superficial lipid layer covering the skin surface of the newborn limits the sorption of water, its removal allows more water to be absorbed, resulting in a higher water-holding capacity than before. These results have all been determined using the water sorption-desorption test. While the studies produce significant information on skin hydration kinetics, the data are reported in different units. As such, it is difficult to make comparisons between sets of experiments where different electrical instruments are used. Finding a standard parameter unit for measuring skin hydration will benefit dermatological research greatly and allow the results obtained from one instrument to aid in the interpretation of those from another instrument. The high degrees of correlation that exist among the Skicon 200, Corneometer CM820 and Nova DPM 9003 may be the key to future developments of a standardized parameter unit.

Long-standing tradition (and standard textbooks) suggest that separating irritation and allergic contact dermatitis (and their biologies) is straightforward. This overview examines this dogma, stressing that the similarities (at least in the efferent limbs) may be as great as the mechanistic differences.