Skin diseases associated with Agent Orange and other organochlorine exposures

Abstract

Organochlorine exposure is an important cause of cutaneous and systemic toxicity. Exposure has been associated with industrial accidents, intentional poisoning, and the use of defoliants, such as Agent Orange in the Vietnam War. Although long-term health effects are systematically reviewed by the Institute of Medicine, skin diseases are not comprehensively assessed. This represents an important practice gap as patients can present with cutaneous findings. This article provides a systematic review of the cutaneous manifestations of known mass organochlorine exposures in military and industrial settings with the goal of providing clinically useful recommendations for dermatologists seeing patients inquiring about organochlorine effects. Patients with a new diagnosis of chloracne, porphyria cutanea tarda, cutaneous lymphomas (non-Hodgkin lymphoma), and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas should be screened for a history of Vietnam service or industrial exposure. Inconclusive evidence exists for an increased risk of other skin diseases in Vietnam veterans exposed to Agent Orange including benign fatty tumors, melanomas, nonmelanoma skin cancers, milia, eczema, dyschromias, disturbance of skin sensation, and rashes not otherwise specified. Affected veterans should be informed of the uncertain data in those cases. Referral to Department of Veterans Affairs for disability assessment is indicated for conditions with established associations.

Occluded Cigarette Smoke Exposure Causing Localized Chloracne-Like Comedones

“…Shelley and Kligman [16] were able to experimentally induce localized acne in healthy subjects with daily topical application of penta- and hexachloronaphthalene, further demonstrating the inherently acnegenic potential of these chlorinated organic naphthalene compounds. The dioxin family of halogenated aromatic compounds contains the most potent of the environmental chloracnegens and includes the chemical isomer 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) associated with Agent Orange in the Vietnam War and several industrial disasters [5,8,17]. PAH components have been linked to environmental and occupational acne disorders which can be subclassified into chloracne, pitch acne and oil acne, among others [4,6].…”

“…The AhR ligand complex then migrates to the nucleus where it binds to designated DNA sequences known as xenobiotic-responsive elements in genetic promoter regions and serves to modulate cellular transcription targets [2,24]. This same AhR receptor also facilitates the dermatological impairments associated with TCDD toxicity in patients with Agent Orange and dioxin exposure and may represent a common mechanistic link among the common forms of occupational and environmental acne [17]. Constitutive activation of these AhRs via chronic PAH exposure is thought to promote immune dysfunction, modifications in vitamin A metabolism and changes in proliferation and differentiation signaling of the epidermis [3,6].…”

Porphyria cutanea tarda: an intriguing genetic disease and marker

“…A contaminant in Agent Orange, 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin, came into contact with millions of soldiers and civilians during past warfare, notably the Vietnam War. It has been linked to development of PCT and is recognized as causing military‐related disabilities health conditions …”

The role of nutrition in influencing mechanisms involved in environmentally mediated diseases

“…Past contaminations resulted from the use of defoliants, such as Agent Orange in the Vietnam War, which contributed to great hardship, such as birth defects (1), cancers (2) and skin diseases (3). Other examples include past forest fires in Southeast Asia, as well as continued slash-and-burn techniques adopted by farmers in Indonesia, which have been extensively used for many years as the cheapest and easiest means to clear the lands for traditional agriculture.…”