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1.1 Introduction: Claude Bernard and the Birth of Experimental Medicine

Claude Bernard (1813–1878) is universally acknowledged as the founder of experimental medicine (Fig. 1.1). His Magnum opus, written in 1865, “Introduction à l’étude de la médecine expérimentale,” was reedited in 1963 [1]. The approach includes six consecutive steps (Table 1.1): observation, hypothesis, experience, results, interpretation, and conclusion, most often abbreviated (OHERIC). Claude Bernard considered that this concise, but abridged, version was incomplete, and he added two footnotes [1]:

Fig. 1.1
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Claude Bernard

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Table 1.1 The steps related to experimental medicine, after Claude Bernard, and their application to patch testing
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  • We cannot give off hypotheses without having raised the problem to be solved, because a hypothesis is an answer possible for a question aroused by an observation.

  • The experiment is testing the verifiable consequence of the hypothesis.

1.2 Adaptation of Claude Bernard’s Methodology to Patch Testing

In my view, when Josef Jadassohn (1863–1936) (Fig. 1.2) performed the first patch test in 1895 at Breslau (now Wroclaw) University, referred to us as “Funktionelle Hautprüfung” [2], it was the very first application in dermatology of the principles of experimental medicine established by Claude Bernard [1]. The “step-by-step” strategy involved in reaching the proper conclusions is still valid today (see Table 1.1). Therefore, initially the patch test was conversely considered an “experimental” and/or a “diagnostic” tool. It has to be kept in mind that, at that time, before the advent of the concept of allergy initiated in 1906 by von Pirquet (1874–1924) (Fig. 1.3), the reproducibility of a reaction in a patient by patch testing had no real etiopathogenic meaning. In other words, there was no distinction between irritancy and allergenicity.

Fig. 1.2
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Josef Jadassohn

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Fig. 1.3
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Clemens von Pirquet

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1.3 Advances from 1895 to the Creation of the International Contact Dermatitis Research Group (ICDRG)

This period has been extensively reviewed in a recent monograph [3].

A most important contribution came from Clemens von Pirquet (1874–1929), an Austrian scientist and pediatrician who noticed in 1906 that patients who had previously received injections of horse serum or smallpox vaccine had quicker, more severe reactions to a second injection. He coined the word allergy to describe this hypersensitivity reaction. Soon after, the observation with smallpox led von Pirquet to realize that tuberculin might lead to a similar type of reaction.

Some papers have been devoted to the scientist and his discoveries [4, 5].

Charles Mantoux (1877–1947) expanded upon von Pirquet’s ideas, and the Mantoux test, in which tuberculin is injected into the skin, became a diagnostic test for tuberculosis in 1907. In the field of contact dermato-allergology, the technique of patch testing, initiated by J. Jadassohn, was extensively developed in Zurich by Bruno Bloch (1878–1933); therefore, it is sometimes called the Jadassohn-Bloch technique.

Bloch (Fig. 1.4) was an exceptional teacher and researcher. Indeed, the patch test was one of his lines of clinical research, among many others in different areas of dermatology. He suspected very early the difference between irritant and allergic contact dermatitis. He used the term “idiosyncrasy” [6, 7], which is no longer quoted nowadays; in his view, it was synonymous with allergy. Many dermatologists, coming from different countries, stayed for a rather long period of time in his department; among them was Marion Sulzberger (1895–1983) [8], who disseminated and popularized the patch test throughout the United States, and also Poul Bonnevie (1907–1990), who later became Professor of Occupational Medicine in Copenhagen (Fig. 1.5). He introduced the first standard series of patch tests, vocationally oriented towards occupational dermatology [9]. Marcussen in 1962 provided a very comprehensive statistical study about the relative frequency of positive and negative patch test results of Bonnevie’s standard series [10], unchanged over the years (period of inertia potentially linked with the events of World War II). But the series had become obsolete and did not correspond anymore to the current environmental conditions.

Fig. 1.4
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Bruno Bloch

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Fig. 1.5
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Poul Bonnevie

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Apart from Bloch’s flourishing school, many publications referring to contact dermatitis and patch testing were recorded in the literature from various countries, most of them of high scientific value [3, 11].

But it is clear that each “patch tester” throughout Europe and the United States had his or her own methodology; all parameters of use (allergens, concentrations, vehicles, reading time etc.) were not codified.

Moreover, it is noteworthy to recall that some individuals proficient in the field were reluctant to use systematically a “standard” or “baseline” series. In particular, Werner Jadassohn (son of Josef) in Geneva [12] and Jean Foussereau in Strasbourg [13] were strenuous opponents of the standard series; ultimately, however, they lost the battle.

It is important, in retrospect, to compare the advantages and disadvantages of a standard series (Table 1.2).

Table 1.2 Advantages and disadvantages of the systematic use of a standard series
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1.4 A Revolutionary Adventure: The Founding of the International Contact Dermatitis Research Group (ICDRG)

The aim was to create a group of dermatologists from different countries, experienced in the field of contact dermato-allergology, who could share the results of their own clinical observations. The ICDRG was informally founded in 1967. Eleven members were elected and met twice a year during three full days, and the presence of everyone was compulsory. The agenda was clearly delineated before each meeting. The members of the “former” ICDRG (as we call it today) were Hans-Jürgen Bandmann (Munich-Schwabing, Germany), Charles D. Calnan (London, Great Britain), Etain Cronin (London, Great Britain), Sigfrid Fregert (Lund, Sweden), Niels Hjörth (Copenhagen, Denmark), Bertil Magnusson (Malmö, Sweden), Howard I. Maibach (San Francisco, United States), Klaus Malten (Nijmegen, the Netherlands), Carlo Meneghini (Bari, Italy), Veikko Pirilä (Helsinki, Finland), and Darrell Wilkinson (High Wycombe, Great Britain).

Niels Hjörth was the leader of the group. He acted as chairman and secretary, but this function was not official, only pragmatic. After each meeting, he wrote the minutes very carefully, without any item escaping his attention.

I was elected full member later on, after Magnusson’s sudden death.

The aims of the group were clearly defined [14].

1.5 Major Contributions of the Former ICDRG

1.5.1 Terminology

A precise definition of the terms used in contact dermato-allergology was needed and was achieved by the group [15].

1.5.2 Recommendations About the Patch Testing Methodology: The Early “Tips” in Contact Dermato-Allergology

After long discussions at the biannual meetings, several rules were decided and promulgated. The main recommendations are presented in Table 1.3. For more detailed information, see reference [16].

Table 1.3 Recommendations of the (former) ICDRG related to the patch testing methodology [16]
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1.5.3 Some Items That Were Not Studied Thoroughly by the (Former) ICDRG

Some areas of investigation were incompletely covered at that time. They are listed in Table 1.4.

Table 1.4 Items that were incompletely covered by the (former) ICDRG
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1.5.4 The Retirement of Members of the “Former” ICDRG and the Revival of the Group

When most of the members retired, some of them advised the dissolution of the group, since they considered that such an adventure was unique and could not be repeated as such. Nevertheless, Howard Maibach decided to take up the challenge, and the revival was a success. At that time, Matti Hannuksela joined the group and developed the repeated open application test (ROAT) [19]. Some of the activities are summarized in Table 1.5.

Table 1.5 Some recommendations of the “new” ICDRG
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The list of the current members is presented in ICDRG members.

1.5.5 The European Environmental and Contact Dermatitis Research Group and the European Society of Contact Dermatitis

In the meantime, contact dermato-allergology, the patch testing procedure, and its additional tools of investigation flourished throughout Europe.

The foundation of the European Environmental and Contact Dermatitis Research Group (EECDRG) and soon after of the European Society of Contact Dermatitis (ESCD) played an important role in these continuous improvements. Moreover, the ESCD decided to create various working subgroups, trying to increase our knowledge about pending problems and to help the clinician in his or her practice. For example, one of the important topics was to evaluate the reliability of patch testing in drug eruptions, among many others. The continual updates in the field were presented in specific sessions during the Congresses organized by the ESCD and published in Contact Dermatitis. By the way, some members of the “new” ICDRG were and/or are members either of the EECDRG or of the ESCD. It is noteworthy that many of the “tips” presented in this monograph have been developed either by the EECDRG or the ESCD (Table 1.6).

Table 1.6 The main “tips” from the EECDRG and the ESCD
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The aim of the ICDRG is to disseminate these advances all around the world.

1.5.6 Another Adventure: The TRUE Test

Torkel Fischer and Howard Maibach [41, 42] developed the TRUE Test, a well-known technology of patch testing, as a joint venture with Pharmacia (Uppsala, Sweden) at first and with SmartPractice (Phoenix, Arizona) later on.

A detailed overview of the TRUE Test is presented in our previous book [43].