living conditions in Vietnam, veterans developed a variety of skin conditions ranging from bacterial and fungal infections to a condition known as ''tropical acne" (Odom, 1993). However, the only dermatologic disorder consistently reported to be associated with Agent Orange and other herbicides, including the contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD, TCDD, or dioxin), is chloracne. Therefore, this discussion focuses on chloracne and its link to TCDD.

Among the numerous industrial chemicals known to cause chloracne, the most potent appears to be TCDD. However, as noted later in this discussion, individual host factors appear to play an important role in determining disease expression. Even at relatively high doses, not all exposed individuals develop chloracne, whereas others with similar or lower exposure manifest the condition.

Chloracne has a variable natural history. Longitudinal studies of exposed cohorts suggest that the lesions typically regress and heal over time. However, historical reports indicate that a chronic form of the disease can persist up to 30 years after an exposure (Suskind and Hertzberg, 1984). Like many dermatologic conditions, chloracne can reasonably be suspected on the basis of a careful medical history or appropriate questionnaire information. A key element in diagnosis is the characteristic anatomic distribution. Because acne is such a common dermatologic condition, a number of precautionary steps should be taken in any analysis attempting to link acne or chloracne with an environmental or occupational exposure; it is critical that adequate attention be paid to the clinical characteristics, time of onset, and distribution of lesions and that there be careful comparison with an appropriate control group. Definitive diagnosis may require histologic confirmation from a biopsy specimen.

Chloracne can be viewed as both a toxic outcome of exposure to TCDD and a potential clinical marker of TCDD exposure. It is the latter that has generated the most controversy. In this section, the primary focus is on the linkage of chloracne to TCDD exposure. Dose-response relationships between TCDD exposure and chloracne are addressed briefly. The inadequacies of chloracne as a human biomarker of dioxin exposure are discussed in more detail in Chapter 5. A major unresolved issue is whether TCDD exposure below the level required to cause chloracne may have other adverse health consequences such as cancer.

Summary of VAO and Update 1996

Chloracne has been linked to TCDD exposure in numerous epidemiologic studies of occupationally and environmentally exposed populations. The data on Vietnam veterans potentially exposed to Agent Orange and other herbicides are less convincing.

From the studies reviewed in VAO and Update 1996, it is apparent that higher levels of exposure to TCDD, as reflected by increased serum levels, are



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