Dioxin poisoning encompasses toxic effects of acute and chronic exposure to one or more of chemicals belonging to the dioxin group. Although environmental low dose exposure over a long period of time is the most common scenario, an acute, high-dose exposure is the most relevant from a diagnostic point of view, since it shows clear clinical signs, such as chloracne.
Dioxin poisoning mostly refers to the effects of short-term exposure to high doses of a single chemical or a mixture of congeners belonging to polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) or dioxin-like polychlorinated biphenyls (PCBs), commonly known as dioxins [1]. While long-term, environmental exposure to low doses is more prevalent, it also remains asymptomatic for years; hence, it is not the primary point of concern from a diagnostic point of view [2] [3] [4].
In acute poisoning, symptoms appear in stages and clinical manifestations may develop over months [5]. Chloracne are the most evident sign, but they are not the first to appear. Initially, patients present with symptoms of gastrointestinal as well as hepatic and pancreatic dysfunction [3] [5] [6] [7]. These symptoms, indicating poisoning but not specific for dioxins, subside within six weeks. At the same time patients may start experiencing neuropathic pain [5]. Face is affected in up to two weeks after exposure, starting with severe edema, followed by painful, inflammatory, nodular, cystic lesions - chloracne [5] [8] [9]. Severity of chloracne is dose-dependent. Lesions may spread all over the body (except for palms, soles of the feet and area around the eyes) in the months to follow [5] [8]. In some cases dioxin poisoning was accompanied by anemia and amenorrhea [3].
Both, acute and chronic exposure, are associated with delayed effects including immune effects (suppression or autoimmunity), cancer (sarcoma, gastrointestinal, hematologic etc.), endocrine disruption, diabetes, cardiovascular and respiratory diseases [3] [6] [9] [10] [11] [12] [13]. The risk for development of these conditions depends on exposure levels [9].
In severe cases, diagnostic procedure starts with checking if the patient may have been exposed to dioxins (occupational exposure is the most common one). As initial symptoms are not specific for dioxins, in cases of unknown exposure, it is important to exclude other types of poisoning to facilitate an accurate diagnosis. Given the gradual symptom development, the patient may have to be monitored over several weeks or even months [5].
Concentration of dioxins is expressed per gram of serum lipids. It is considered that levels lower than 31 pg toxic equivalent quantity (TEQ) of total dioxins per gram of lipids do not warrant a high-priority follow-up, while levels higher than 74 pgTEQ/g require further investigation [14] [15] [16]. However, patients' susceptibility to dioxin exposure varies largely, reducing the diagnostic and prognostic significance of serum level quantification [17]. Furthermore, chemical analysis, in addition to being expensive and slow, has to be aimed at a specific compound, while the toxic effects may be produced by a range of substances, similar in chemical structure [1]. Hence, serum levels of dioxins are not routinely determined nor used for screening [1] [18]. Instead, bioassays, such as chemical-activated luciferase gene expression (CALUX) and ethoxy-resorufin-O-deethylase (EROD), using in vitro cell cultures to determine the overall toxicity of a biological sample, are gaining diagnostic and screening significance [18] [19].
Due to characteristic appearance of chloracne, biopsy is not warranted. If biopsy is performed, samples show loss of sebaceous glands which are replaced by characteristic cysts. These lesions are known as hamartomas [5].
Given the wide range of dioxin toxic effects, results of usual blood analyses (biochemical and complete blood count) may be outside the reference ranges. Since these deviations are non-specific, the diagnosis cannot be established solely on their basis.