Defining Clinically Relevant Fragrance Allergens: The Challenge (Part I)

A Dermatological View From Physiology to Therapy
A Dermatological View From Physiology to Therapy

Contact allergic dermatitis remains a significant public health problem. Its diagnosis and prevention are complicated by the difficulty of identifying allergens responsible for a patient’s condition (i.e., those that have actually caused the allergic contact dermatitis). This two-part examination will provide an operational definition of causative allergens by discussing the challenges and the criteria, respectively.

Although predictive tests can identify potential allergens, it is only through a multi-step clinical correlation with current contact dermatitis that truly causative allergens can be identified. This is, however, not a simple matter—for the reasons described here.


Clinical patch testing remains a partially subjective field. When a clear reaction is observed, it is not always certain that it has been due to a truly clinically relevant, allergic response. Marks et al., suggested that more than 40% of 3,000 patients with suspected allergic contact dermatitis were, in fact, suffering from irritant or some other form of nonallergic contact dermatitis. There is an association between erythematous reactions to some allergens and irritant reactions to sodium lauryl sulfate. This association is a putative marker for hyper-reactive skin, thus allowing many reactions of this type to be classified as irritant rather than allergic in nature.

Apart from false-positive reactions from irritancy, there is a possibility that other false-positive reactions can occur from cross-reactions where patients react to substances that are not the primary sensitizers that initially induced the allergic state. Similarities in chemical structure or cutaneous metabolism would appear to be major factors in cross-reactivity. More than 70 different cross-reacting pairs or families of fragrance ingredients have been cataloged. Positive correlations of concomitant reactions in different pairs of components of the fragrance mix have also been recorded in polyreactive patients.

Excited Skin Syndrome

False-positive reactions can also arise from phenomena such as the Excited Skin Syndrome in which positive test results from numerous patches cannot be reproduced when the patient is later retested. More than 40% of such positive patch reactions are lost on repatching. Indeed, some studies have involved phased patch testing schedules to avoid false-positives due to this syndrome.

Specificity and Sensitivity

Even when there is clear evidence that the reaction is allergic in nature, ascertaining the clinical relevance of the patch test requires knowledge of technical aspects relating to specificity and sensitivity issues. In nickel allergic contact dermatitis—one of the more familiar clinical correlations—there is a high ratio of false-positive and false-negative reactions. Even when an allergic reaction has been indicated, the chances that an experienced physician will accurately identify the causative allergen from clinical information is about 50% of the time, mostly when common allergens are involved; but this is reduced to 10% for less common allergens.

Clinical Relevance

There is increasing evidence that diagnostic patch testing may also elicit true allergies but these allergies are not the cause of the patient’s current contact dermatitis. Lachapelle has defined clinical relevance as “the capability of an information retrieval system to select and retrieve data appropriate to a patient’s need.” In this context, Lachapelle distinguishes between past relevance, which is not directly related to the patient’s current problems, and current relevance, and describes a system for distinguishing between the two.

Lachapelle also defines the need to determine the “intrinsic imputability” of a suspected allergen, which he defines as the “possible, and not necessarily exclusive, cause-effect relationship between each positive test to an allergen and the occurrence of a given chemical event.”

To determine true clinical relevance, Lachapelle and Maibach give strategies that establish the existence of past exposure and ensure that the patient’s exposure has indeed been responsible for the observed dermatitis. These authors also suggest several ways in which the clinician can improve evidence-based diagnosis of relevance.

  • Performing use tests with implicated products.
  • Account for possible cross-reactions.
  • Make a more rigorous and detailed examination of the case by retrieving the pertinent historical data, tracing the responsible environmental exposure and performing the appropriate tests.

Exposure Conditions

Although some allergies revealed by patch testing may pertain to past allergic clinical events, others may pertain to allergies that have been acquired by the patient but have never been clinically manifested (i.e., have never caused contact dermatitis in the patient). There is increasing experimental evidence, mainly in animal tests but also in some older studies on humans, to show that the threshold dose of elicitation varies in accordance with the conditions of induction.

This information is an excerpt from the book A Dermatological View: From Physiology to Therapy. To learn more about this topic or to purchase the entire book, visit www.alluredbooks.com.


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