Chloracne

Laboratory safety requires protecting personnel from chemical exposures. Working with stock solutions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) in routine analysis of feed and food with bioanalytical or physicochemical methods raises some concerns. Since PCDD/PCDFs are considered as possibly acutely toxic, the potential risks were evaluated to determine whether supervision of their use is necessary. Based on LD50 -data for oral or dermal intake, hazard classification of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a substance (category 1) and in commercially available TCDD standard solutions (category 4) is different...

BACKGROUND: In 2015, workers dismantling a fluorescent lamp factory in Korea were affected by mercury poisoning from exposure to mercury vapor. CASE PRESENTATION: Eighteen out of the 21 workers who participated in the demolition project presented with symptoms of poisoning and, of these, 10 had persistent symptoms even at 18 months after the initial exposure to mercury vapor. Early symptoms of 18 workers included a general skin rash, pruritus, myalgia, sleep disturbance, and cough and sputum production...

Studies of TCDD toxicity stimulated identification of the responsible aryl hydrocarbon receptor (AHR), a multifunctional, ligand-activated transcription factor of the basic helix-loop-helix/Per-Arnt-Sim family. Accumulating evidence suggests a role of this receptor in homeostasis of stem/progenitor cells, in addition to its known role in xenobiotic metabolism. (1) Regulation of myelopoiesis is complex. As one example, AHR-mediated downregulation of human CD34+ progenitor differentiation to monocytes/macrophages is discussed...

BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease...

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that have the ability to disrupt the production and actions of hormones through direct or indirect interaction with hormone receptors, thus acting as agonists or antagonists. Human health is affected after either individual occupation or dietary and environmental exposure to EDCs. On the other hand, skin is one of the largest organs of the body and its main function is protection from noxious substances. EDCs perturb the endocrine system, and they are also carcinogenic, immunotoxic, and hepatotoxic to human skin...

Despite decades of intensive research physiologic Ah receptor (AHR) functions are not yet elucidated. Challenges include marked species differences and dependence of AHR function on the cell type and cellular context. Hints to physiologic functions may be derived (i) from feedback loops between endogenous ligands and substrates of major target enzymes such as CYP1A1 and UGT1A1, and (ii) from dioxin toxicity in human individuals. For example, dioxin-mediated chloracne is probably due to dysregulated homeostasis of sebocyte stem/progenitor cells...

Target cells and molecular targets responsible for dioxin-mediated chloracne, the hallmark of dioxin toxicity, are reviewed. The dioxin TCDD accumulates in sebum, and thereby persistently activates the Ah receptor (AhR), expressed in bipotential stem/progenitor cells of the sebaceous gland. AhR operates in cooperation with other transcription factors including c-Myc, Blimp1 and ß-Catenin/TCF: c-Myc stimulates exit of stem cells from quiescence to proliferating sebocyte progenitors; Blimp1 is a major c-Myc repressor, and ß-Catenin/TCF represses sebaceous gland differentiation and stimulates differentiation to interfollicular epidermis...

BACKGROUND: Dioxins are persistent organic pollutants present in the environment. They exert their biological effects by binding to an intracellular receptor, the aryl hydrocarbon receptor (AhR). Activation of AhR leads to the induction of cytochrome p450 1A1 (CYP1A1). Expression of CYP1A1 in human skin is a key marker for AhR activation, and it may induce comedogenesis resulting in acne-like lesions known as chloracne/metabolising acquired dioxin-induced skin hamartomas (MADISH). The contribution of this pathway in patients seen in a busy acne clinic is unknown...

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Many environmental acne disorders, including chloracne and oil acne, were previously thought to occur predominantly in occupational settings following polycyclic aromatic hydrocarbon exposure. Cigarette smoke has also been shown to contain a large number of these toxic polycyclic aromatic hydrocarbon components and strictly correlates with noninflammatory acneiform lesion development in postadolescent patients. We report a case of localized open comedones associated with occluded cigarette smoke exposure near the nasal cavity due to infrequently changed gauze following rhinectomy...

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...

BACKGROUND: Exposure to PCDD/PCDF (dioxin and furan) through consumption of fish and shellfish is closely related to the occurrence of skin diseases, such as chloracne and hyperpigmentation. This study aimed to determine the exposure of PCDD/PCDF and its congeners in fish and shellfish obtained from different regions of the Straits of Malacca among the fishing community. METHODS: The risk of fish and shellfish consumption and exposure to PCDD/PCDF among fishermen living in coastal areas of the Straits were evaluated based on a cross-sectional study involving face to face interviews, blood pressure and anthropometric measurements, and administration of food frequency questionnaires (FFQ)...

The aryl hydrocarbon receptor (AHR) is a cytosolic receptor for low molecular weight molecules, of which the most widely recognized ligand is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the most widely recognized effect, chloracne. Adverse effects of manipulation were most recently and graphically demonstrated by the poisoning of Viktor Yushchenko during the Ukrainian presidential elections of 2004. However, recent research has revealed a receptor with wide-ranging, and at times, paradoxical actions. It was arguably among the first biological receptors to be utilized by dermatologists, dating from the time of topical tar preparations as a therapeutic agent...

The environmental toxin 2,3,7,8 tetrachlorodibenzo p-dioxin (TCDD) plays an important role in the development of chloracne. Chloracne is characterized by hyperkeratosis of the interfollicular squamous epithelium and metaplasia of sebaceous glands. Dysregulation of keratinocyte terminal differentiation leading to accelerated formation of the cornified envelope as a result of TCDD-mediated aryl hydrocarbon receptor (AHR) activation has been implicated as one of the molecular pathogenic mechanisms contributing to the development of chloracne...

INTRODUCTION: Sorafenib is an oral multikinase inhibitor that targets tumor cell angiogenesis and proliferation. Drug-associated cutaneous adverse events, such as alopecia and hand-foot skin reaction, occur frequently. Sorafenib-related side effects affecting hair, nails, and skin are summarized and the characteristics of sorafenib-treated patients who developed acneiform facial lesions are reviewed to present the clinical features of these individuals. CASE REPORT: A man with sorafenib-associated facial acneiform lesions mimicking those of chloracne is described...

Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (dioxin-like PCBs) are identified as a family or group of organic compounds known as 'dioxins' or dioxin-like chemicals (DLCs). The most toxic member of this group is 2,3,7,8-tetrachlorodibenzo-(p)-dioxin (TCDD). Historically, DLCs have caused a variety of negative human health effects, but a disfiguring skin condition known as chloracne is the only health effect reported consistently. As part of translational research to make computerized models accessible to health risk assessors, the Concentration- and Age-Dependent Model (CADM) for TCDD was recoded in the Berkeley Madonna simulation language...

The nuclear factor erythroid 2-related factor 2 (Nrf2) is best known for its role in resistance to oxidant stress. In this issue of EMBO Molecular Medicine, Nrf2-prolonged genetic activation is shown with devastating effects on skin homeostasis. The study provides novel molecular insights into poison-induced chloracne and metabolizing acquired dioxin-induced skin hamartomas or MADISH.

The transcription factor Nrf2 is a key regulator of the cellular stress response, and pharmacological Nrf2 activation is a promising strategy for skin protection and cancer prevention. We show here that prolonged Nrf2 activation in keratinocytes causes sebaceous gland enlargement and seborrhea in mice due to upregulation of the growth factor epigen, which we identified as a novel Nrf2 target. This was accompanied by thickening and hyperkeratosis of hair follicle infundibula. These abnormalities caused dilatation of infundibula, hair loss, and cyst development upon aging...

BACKGROUND: Agent Orange, or 2,3,7,8-tetrachlorodibenzodioxin, has been shown to cause indirect DNA damage, producing malignancies. However, its connection to nonmelanotic invasive skin cancer is unclear. This study investigated whether 2,3,7,8-tetrachlorodibenzodioxin exposure increases the incidence of this cancer. METHODS: The authors retrospectively reviewed the medical records of 100 consecutive male patients with Fitzpatrick skin types I through IV who enrolled in the Agent Orange registry at the Veterans Affairs Hospital of Washington, D...

Dioxins are a family of molecules associated to several industrial accidents such as Ludwigshafen in 1953 or Seveso in 1976, to the Agent Orange used during the war of Vietnam, and more recently to the poisoning of the former president of Ukraine, Victor Yushchenko. These persistent organic pollutants are by-products of industrial activity and bind to an intracellular receptor, AhR, with a high potency. In humans, exposure to dioxins, in particular 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a cutaneous syndrome known as chloracne, consisting in the development of many small skin lesions (hamartoma), lasting for 2-5 years...