Historical perspective on the use of visual grading scales in evaluating skin irritation and sensitization.

Visual assessment of skin reactions has long been used to evaluate the safety of chemicals and preparations that contact the skin, and to meet regulatory requirements. This article reviews the history of visual grading scales, and the results of investigations into the reliability of the method. Some examples are provided to illustrate the diverse array of protocols that use visual scoring to evaluate skin irritation. Furthermore, as bioengineering methods are developed that can quantitate certain aspects of skin irritant and sensitization reactions, it is important to consider whether such measures should supplement or replace visual assessment. Examples of investigations comparing the outcomes of studies that use visual scoring and those that use bioengineering methods are discussed. These examples provide little evidence that bioengineering measures provide an improvement in overall quality in comparison with current testing methods that rely on visual assessment. In addition, such measuring techniques can add considerably to the complexity of testing protocols. When benefits and cost are weighed in the balance, the visual assessment scales popularized by Draize and others remain an effective, practical method of evaluation.

Detection of contact allergy: using more extensive test series increases the diagnostic efficacy of patch tests.

BACKGROUND: Contact allergy is the most frequent type of allergy, affecting 26-40% of all adults and 21-36% children. The gold standard in the diagnosis of contact allergy is patch test. OBJECTIVE: To study the influence of the range and composition of patch test series on the efficacy of the diagnostic procedure. MATERIAL AND METHODS: Retrospective analysis of the frequency of positive reactions among patients diagnosed with patch tests at our Department during 2 periods: From December 2003 to March 2005, patients were tested with a series of 9 substances plus white petrolatum as the negative control. From April 2005 to July 2008, the series was expanded to 21 substances, while petrolatum was removed. RESULTS: In the analyzed period, 1379 patients were tested with 9 substances plus petrolatum (group referred to as "G9") and 682 patients with 21 substances ("G21"). In G9, at least one positive reaction was observed in 343 (24.9%, 95% CI: 22.6-27.2%) patients, as compared to 376 (55.1%; 95% CI: 51.4-58.7%) in G21 (p < 0.0001). The increase in the number of tested substances from 9 to 21 led to significant increase in the mean number of positive reactions per one patient (0.34 in G9 versus 0.90 in G21; p < 0.0001). We have not observed any positive reaction to white petrolatum. CONCLUSIONS: Patch testing with more extensive test series increases the chance for the detection of patient's sensitizations. As we have not observed any positive reaction to white petrolatum, using the vehicle as negative control does not seem to offer any advantage.

In pursuit of defining clinical relevance of positive patch tests results.

According to the current classification of clinical relevance of the positive patch test reactions, the positive results of patients who are allergic to various allergens that are not responsible for the present dermatitis do not fit into the category of "relevant to present dermatitis" but should be defined as "relevant to a preceding bout of dermatitis." This seems to us inappropriate and misleading because reexposure to the sensitizing agent would quickly revert their reaction to "relevant to present dermatitis." We suggest an alternative possibility to the current division of the various types of clinical relevance, namely, "relevance to a present allergy other than the presenting dermatitis."

Predicting visual assessment of allergic patch test reactions by non-invasive measurements.

The quantification of allergic patch test reactions to several compounds was evaluated on patients using laser Doppler velocimetry (LDV), transepidermal water loss and colorimetry. The correlation between visual scores and instrumental measurements was investigated by the implementation of a modern statistical method: a classification tree. The LDV showed the highest correlation with the severity of the reaction. The best prediction model was obtained when the data of the three instruments were considered together. Using the classification tree methodology, a model of classification, independent of human observation, was developed. The technique can not only predict an allergic reaction for a new patient, but can also give a measure of how reliable its predictions are. This new method, when entirely standardised and approved, could help in the harmonisation of patch test reactions in different laboratories, thus allowing a more homogenous interpretation of these reactions.

Pattern analysis of photopatch test reactions.

In a multicenter study, photopatch test results from more than 1500 patients were evaluated between 1985 and 1990 and from 614 patients between 1990 and 1992. Photopatch testing was conducted according to a standardized procedure. Nearly half of the photoreactions were unclassifiable according to the classic definitions of photoallergic or phototoxic reactions. To facilitate the interpretation of these remaining photopatch test reactions, we developed a computerized substance specific reaction pattern analysis. By sequential readings from immediately after irradiation up to 72 h later and by morphological qualification of the reactions, the time course and morphological changes of each individual reaction were monitored. The summation of each individual photoreaction resulted in an overall reaction pattern of a specific substance. Four main categories could be distinguished. The first category was characterized by a peak immediately after irradiation followed by a descrescendo reaction. The second category comprized reactions combining an immediate with a delayed reaction. The third category exhibited a plateau-like delayed reaction. The fourth category showed delayed reactions in a crescendo pattern. Whereas category 1 represents classic phototoxic and category 4 classic photoallergic reaction patterns, the underlying mechanisms of categories 2 and 3 remain to be investigated. Typical substances of category 1 were many of the tested systemic drugs, such as furosemide, most of which are well-known phototoxic agents. Disinfectants, nonsteroidal anti-inflammatory agents and phenothiazines showed the reaction patterns of categories 2 and 3. A delayed type reaction (category 4) could be demonstrated for well-known photoallergens such as fenticlor, musk ambrette, and ultraviolet adsorbents in sunscreens.(ABSTRACT TRUNCATED AT 250 WORDS)