Keywords

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FormalPara Core Messages

  • Occupational and environmental acne includes oil acne, coal-tar and pitch acne, acne cosmetica, acne aestivalis (from sun), acne mechanica, tropical acne, and chloracne.

  • Chloracne is a refractory acneiform eruption clinically characterized by comedones and straw-colored cysts. The comedones predominantly affect the malar region of the cheek and the retroauricular areas.

  • Although chloracne is rare, it is a sensitive indicator of chemical exposure to certain polyaromatic halogenated hydrocarbons and may be associated with internal poisoning that should be recognized by physicians treating occupational skin disease.

  • Patients with the cutaneous manifestations of chloracne should be carefully investigated for systemic complications (such as hepatic, ophthalmic, neurologic, lipoprotein, and endocrine abnormalities).

1 Introduction

Occupational and environmental acne is a variety of acne venenata, resulting from various chemical exposures and from a variety of environmental, physical, and mechanical factors, usually encountered in the workplace but occasionally seen in nonoccupational settings. The eruption may be mild, involving localized exposure or covered areas of the body, or severe, explosive and disseminated with the involvement of almost every follicular orifice. Additionally, chloracne almost always represents a cutaneous sign of systemic exposure to highly toxic chemicals. Occupational and environmental acne comprises oil acne, coal-tar and pitch acne, acne cosmetica, acne aestivalis (from sun), acne mechanica, tropical acne, drug-induced acne, and chloracne (Table 31.1 ). This listing serves as a useful paradigm and includes the most common causes of occupational and environmental acne.

Fig. 31.1
figure 00311figure 00311

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) – a halogenated aromatic compound – is highly toxic and causes chloracne

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Table 31.1 List of types and etiologies of occupational and environmental acne
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2 Oil Acne

Oil acne or oil folliculitis is the most common form of occupational acne and consists of numerous follicular papules and pustules occurring in areas with heavy oil exposure, such as the thighs and forearms. Oil acne is most commonly observed in workers employed in the machine tooling trades. Other workers likely to be affected may include machinists, auto, airplane and truck mechanics, roofers, oil well drillers, petroleum refiners, rubber workers, textile mill workers, and road pavers. The incidence of oil acne has declined in recent years because of decreased use of pure cutting oils and improved industrial and personal hygiene practices (Kokelj 1992).

Cutting oils, especially insoluble (straight) oils, and semisynthetic coolants have been the most commonly incriminated oil acnegens (Taylor 1987). In mechanics, prolonged exposure to grease, lubricating oils, and kerosene may induce oil acne (Upreti et al. 1989). An anecdotal report of acne observed in young fast-food workers exposed to grease and fat while frying hamburgers has been termed “McDonald’s acne” (Litt 1974), although there is no other evidence that this is a separate entity.

Prolonged oil exposure produces a reactive follicular hyperkeratosis and results in sebum retention. This manifests clinically as multiple open comedones, inflammatory folliculitis, and microcystic lesions caused by the oil itself. Lesions are distributed primarily over exposed areas, such as the dorsal hands and extensor forearms. Oil-soaked clothing may produce lesions on the thighs, lower abdomen, and buttocks (Kokelj 1992). The face may be involved from wiping the brow with an oil-contaminated sleeve. Although the lesions are commonly referred to as oil boils, they usually do not develop from bacteria present in the oils (Taylor 1986). The inflammatory lesions, larger furuncular and carbuncular lesions may form, are more prominent than in chloracne and may mimic conglobate cystic acne.

Acquired perforating (transepidermal elimination) disease has been reported in oil field workers exposed to drilling fluids. The fluids contain many additives, including calcium chloride. Histopathologic examination revealed transepidermal elimination of calcium with minimal involvement of hair follicles (Knox et al. 1986).

Oil acne is treated with the usual acne vulgaris modalities, such as topical benzoyl peroxide and retinoic acid. Systemic treatment is often needed with tetracycline, erythromycin or minocycline, or with isotretinoin in severe cases. The key factor is avoiding contact with oils and grease and the practice of good hygiene. Work clothes should be changed daily and frequent cleansing of the skin with soap and water is advised.

3 Pitch or Coal-Tar Acne

Coal-tar oils, creosote and pitch can produce a comedonal type of acne, which shows a predilection for exposed areas, particularly the malar regions (Bartolini 1989) and periorbital areas in individuals exposed to pitch tar (Adams et al. 2000). Coal-tar plant workers, roofers, road maintenance workers, and construction workers are among those at risk. Coal-tar derivatives have been reported to be not only acnegenic, but also carcinogenic and photosensitizing (Adams et al. 2000). Therefore coal-tar acne may be complicated by phototoxic reactions affecting both the skin and the eyes and resulting in hyperpigmentation known as coal-tar melanosis. Late complications include the development of pitch and tar papillomas, keratoses, and acanthomas (Taylor 1987). Pitch acne responds to treatment much better than chloracne. Prevention of pitch acne includes showers and available cleansers at work facilities, clean uniforms, protective coverings, and exhaust ventilation systems (Adams et al. 2000).

4 Acne Cosmetica

In 1972, Kligman and Mills described acne cosmetica consisting chiefly of small, scattered comedones occurring mainly in women in the age range 20–50 years. These women, who were using a variety of cosmetics for prolonged periods of time, developed comedonal lesions exclusively on the face, predominantly on the chin.

Acne cosmetica may develop in actors and models who are often required to wear heavy, greasy makeup; cosmetologists may also be affected (Kligman and Mills 1972). Acne cosmetica consists of essentially noninflammatory, small, closed comedones and a few intermittent papules, and pustules. When superimposed upon acne vulgaris, the clinical picture may be obscured (Kligman and Mills 1972).

Animal models were originally used to determine the comedogenic potential of raw materials with the assumption that finished formulations containing these ingredients would also be comedogenic. Cosmetic ingredients found experimentally to be comedogenic include : isopropyl palmitate, isopropyl myristate, butyl stearate, isopropyl isostearate, decyl oleate, isostearyl neopentanoate, isocetyl stearate, myristle myristate, cocoa butter, cetyl alcohol, paraffin, stearyl alcohol, sodium lauryl sulfate (SLS), and petrolatum (Nguyen et al. 2007). Despite the fact that finished products using comedogenic ingredients are not necessarily comedogenic (Draelos and DiNardo 2006) many of these substances are avoided or modified by cosmetic manufacturers and cosmetics are frequently advertised as noncomedogenic.

Acneiform eruptions with predominantly deep-seated nodules and a few comedones situated mainly on the cheeks can occur after facial massage beauty treatment. This eruption is unlike classic acne cosmetica in being inflammatory, indolent, and often occurring a few weeks after facial massage (Khanna and Gupta 1999).

5 Acne Aestivalis (Mallorca Acne)

Acne aestivalis is a rare, infrequently described, generally, nonoccupational eruption, which can also affect performing artists. Typically, it affects women in the age range of 25–40 years and involves the cheeks, sides of the neck, chest, shoulders, and upper arms. Typical lesions are monomorphic popular, round, hard, and small lesions reported to develop after sun exposure. Comedones and pustules are absent or scarce. Lesions involute in the fall without scar formation.

The eruption is due to sun exposure, ultraviolet radiation, mainly UVA, and florescent light exposure (Plewig and Jansen 1998; Zugerman 1990). PUVA therapy and ionizing radiation are also potentially acnegenic. Acne aestivalis responds to topical retinoic acid or benzoyl peroxide but not to antibiotics (Hjorth et al. 1972). Prophylactic treatment has been reported by gradually increasing exposure to artificial UV radiation (UVB, UVA or PUVA) prior to the first exposure to natural sunlight (Plewig and Jansen 1998).

Actinic follicuitis a rare photodermatosis presenting with recurrent pustular facial eruptions, typically appearing 4–6 h after exposure to sunlight falls into the same spectrum as acne aestivalis and actinic superficial folliculitis (Veysey and George 2005).

6 Acne Mechanica

In 1975, Mills and Kligman defined acne mechanica as a process in which mechanical factors such as pressure, occlusion, friction, rubbing, or heat provoke acne lesions by inducing the rupture of microcomedones. Repeated or prolonged physical insults to the skin may produce an acneiform eruption that can be strikingly inflammatory in nature. An example is the local pressure and rubbing against seat covers which occurs in truck drivers. Acne mechanica is specifically related to sporting activities. Occupational causes of acne mechanica include the use of face masks (as in hospital workers or clean-room workers in the semiconductor industry), belts, straps, tight-fitting work clothing, football shoulder pads, football helmets, hats, and telephones (Mills and Kligman 1975). Fiddler’s neck (Brun and Baran 1984) and violinists neck is also a variant of acne mechanica (Omohundro and Taylor 1998).

Clinically, crops of inflammatory papules and pustules appear in affected areas of skin. Deep, inflammatory nodules may result from prolonged pressure. It has been emphasized that acne mechanica is a complication of acne vulgaris and that external physical forces merely exacerbate the underlying disease focally (Mills and Kligman 1975). Improvement of mechanical acne may occur promptly after removing the source of mechanical and physical factors. Skin washing and use of topical cleansing agents may reduce the risk of acne mechanica.

7 Tropical Acne

Tropical acne may result from exposure to excessively hot or humid environments and, when such exposure is required in the performance of the patient’s job, may be considered to be a form of occupational acne. Tropical acne has been observed most commonly in soldiers stationed in tropical climates, but variants may result from chronic exposure to other hot and/or humid environments as can be found in foundries (Mathias 1994).

Onset is explosive in nature and typically occurs several months after entering the hot, humid environment. This is a severely inflammatory condition, with the development of papules, pustules, nodules, and draining sinuses as in acne conglobata. Patients often feel quite ill, and acute-phase reactants may be elevated. There is characteristic involvement of the buttocks and upper thighs, but lesions may be extensive, with the neck, arms, and trunk being affected. The face is usually spared (Sperling 1994).

Cultures have not identified a consistent pathogen, and the role of bacterial infection is felt to be unimportant. Antibiotic therapy is without significant benefit. The only effective therapeutic measure is to remove the patient from the precipitating environment (Sperling 1994).

8 Drug-Induced Acne

Eruptive acneiform lesions or acneiform folliculitis can be seen as a side effect of medications, commonly known including: anabolic steroids (e.g., danazol, testosterone), corticosteroids, corticotropin, phenytoin, lithium, isoniazid, iodides, and bromides. Less often, azathioprine, cyclosporine, tetracyclines, vitamins B1, B6, B12, and D2, phenobarbital, PUVA, propylthiouracil, disulfiram, or quinidine have been incriminated. Clinically drug-induced acne presents as an abrupt, monomorphous eruption of inflammatory papules and pustules in contrast to the heterogeneous morphology of lesions of acne vulgaris (Zaenglein and Thiboutot 2008).

The inhibitors of the epidermal growth factor receptor (EGFR) erlotinib, cetuximab, and panitumumab are well-known to induce head and neck acneiform folliculitis (Osio et al. 2009). This acneiform “EGFR-inhibitor like” cutaneous side effect has also been reported with other drugs including the tyrosine kinase inhibitor imatinib mesylate (Demirci et al. 2010; Martín et al. 2006), sirolimus, thalidomide, and lenalidomide (Michot et al. 2010).

9 Chloracne

Chloracne is an acneiform dermatosis, often refractory to treatment, which results from environmental exposure to certain halogenated aromatic hydrocarbons. It is characterized by comedones with pale yellow cysts predominantly affecting the malar region of the cheek and the retroauricular areas. In more severe cases, lesions may spread to the trunk and genitalia and inflammatory lesions are found. Skin involvement in chloracne is considered one of the most sensitive indicators of biological response to these chemicals and it occurs regardless of whether chemical exposure has occurred via skin contact – the usual route, inhalation, or ingestion (Crow and Puhvel 1991).

Chloracne was first reported by Von Bettman in 1897. In (Herxheimer 1899) used the term chloracne to describe four cases of severe acne resulting from environmental contact with electrolytically produced potassium hypochlorite. Since that time, various chloracnegenic chemicals have been identified. Chloronapthalenes and polychlorinated biphenyls (PCBs) were the causative agents in the pre-World-War-II era. Since then, trace contaminants formed during the manufacture of PCBs and other polyhalogenatcd compounds, especially herbicides and insecticides, have been the major causes of chloracne. These include polyhalogenated dibenzofurans, polychlorinated dibenzo-p-dioxins, and chlorinated phenols, azo- and azoxy benzenes.

When it occurs, chloracne tends to be sporadic. It is caused primarily by exposure to chloracnegenic agents in industrial or agricultural settings. Chloracne has also been caused by nonoccupational exposures via accidental environmental pollutions and in food contaminations. A decreasing incidence of chloracne may be attributed to the advent of plastics, the substitution of chlorinated hydrocarbons with synthetic resins and the restriction of the use of polychlorinated biphenyls to only closed-system formulations (Kokelj 1992). However, the recent attempt to poison Ukrainian president, Viktor Yushenko with dioxins in 2004 raised the public attention regarding these toxic chemicals (Sterling and Hanke 2005; Sorg et al. 2009).

Chloracnegenic compounds are structurally similar (Table 31.1 ), sharing relative molecular planarity and containing two benzene rings with halogen atoms occupying at least three of the lateral ring positions. The degree of halogenation does not necessarily determine toxicity, whereas the position of halogen atoms on the outside of the molecule seems to be crucial as reduced biological activity results from halogen substitution into positions that lead to molecular nonplanarity (Crow 1981; Kokelj 1992). The main groups of chloracnegens include dioxins, naphthalenes, biphenyls, dibenzofurans, azobenzenes, and azoxybenzenes, with the chloracnegenic potential being closely correlated with the potential to induce the enzyme aryl hydrocarbon hydroxylase (Poland et al. 1976).

9.1 Chloracne-Producing Chemicals and Sources of Exposure

Table 31.2 classifies the chemical causes of chloracne. Of related interest, Table 31.3 provides a partial list of past and present sources of the various chloracnegens. The majority of chloracne cases have resulted from occupational exposure during chemical manufacturing or rarely from end-product use.

Table 31.2 Chloracne-producing chemicals
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Table 31.3 Partial list of past and present sources of chloracnegens
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9.2 Occupational Exposure

Selected outbreaks will be discussed as classified by chemical cause.

9.2.1 Dioxins

Polychlorinated dibenzo-p-dioxins (PCDDs), commonly known as dioxins, are produced as byproduct pollutants of manufacturing processes that utilize chlorine, such as in the manufacturing of herbicides, paper, and pulp bleaching; in industrial production processes and during incineration (e.g., of waste). High levels of dioxins are also emitted from metallurgical industries including copper smelters, electric furnaces in steel mills, and wire reclamation incinerators. Trace levels are detectable in emissions from motor vehicles using leaded gasoline or diesel fuel, in forest fires, and in residential wood burning. These chemicals are extremely stable in the environment, are highly lipophilic and accumulate in animal fat and plant tissues (Mukerjee 1998; Pelclova et al. 2006). Dioxins contaminate polychlorophenols, especially the herbicides 2,4,5-T and pentachlorophenol (PCP) and herbicide intermediates (2,4,5-trichlorophenol).

Of the hundreds of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the paradigm for chemicals causing chloracne and also for the biological importance of trace industrial contaminants. TCDD is one of the most toxic small molecules known to man. It is also one of the best-studied toxic chemicals, largely after intense scrutiny over its use as the main component in the herbicide Agent Orange used during the Vietnam War to clear vegetation and expose the enemy. The elimination half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans is approximately 7–11 years (Mukerjee 1998). TCDD currently serves no commercial purpose. Pure TCDD must be manufactured in a laboratory. It is made in labs in Europe, Russia, and the United States for use as a control for measuring dioxin levels (Sterling and Hanke 2005).

In 1949, the first descriptions of human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD)-contaminated chemicals were reported after a trichlorophenol reactor explosion in Nitro, West Virginia, Unites State (Sweeney and Mocarelli 2000). More than 20 outbreaks of dioxin chloracne, as well as its other health effects, have been reviewed (Taylor et al. 1977; Tindall 1985; Mukerjee 1998). Follow-up studies have shown persistence of chloracne up to 20 years from the exposure (Baccarelli et al. 2005). These studies identified an increased risk of soft-tissue sarcoma from end-product use in Sweden, occupational exposure in the Unites States and nonoccupational environmental exposure in Seveso, Italy. Although these conclusions are controversial, the International Agency for Research on Cancer has concluded that TCDD is a human carcinogen (Mukerjee 1998).

Occupational exposures to TCDD in herbicide and chemical plants were much greater than from most other nonoccupational exposures. Exposure would sometimes begin as a caustic chemical burn when the trichlorophenol reactors would over heat. These workers showed the earliest and most severe chloracne (Taylor 1979; Tindall 1985).

Chloracne is the hallmark of dioxin exposure in man; however, its absence does not exclude dioxin exposure. There is no apparent dose-response model for chloracne in exposed human populations and lesions may develop weeks or months after exposure. In Germany, six workers who developed chloracne after an industrial accident had an estimated mean TCDD body burden of 44 μg (range 9.7–124 μg) shortly after the accident. Thus, a body burden of 9.7 μg, as measured in adipose tissue, may be the lowest observable effect level for TCDD-related chloracne in humans. Thirty-two years after exposure, these German workers still had detectable levels of TCDD in adipose tissue, and one still had chloracne (Agency for Toxic Effects of Chemical Substances 1993). In a follow-up study after the Seveso accident in 1976, which resulted in one of the largest ever-reported environmental outbreaks of chloracne, residents of communities contaminated with TCDD still had elevated levels of plasma TCDD up to 20–30 years after exposure (Baccarelli et al. 2005).

A case of palmoplantar keratoderma, scleroderma, and chloracne was reported in an agricultural worker who had been a weed sprayer for 5 years. He had used 2,4,5-trichlorophenoxyacetic acid and/or 2,4 dichlorophenoxyacetic acid, both of which may contain chlorinated dibenzodioxins as impurities. He also had been chronically exposed to multiple other, non-chloracne associated herbicides, some of which have been associated with scleroderma. Safety equipment was not utilized (Poskitt et al. 1994).

Pentachlorophenol (PCP) is frequently used as a wood preservative, herbicide, and fungicide. It has additional uses in the leather and paper industry and an estimated 17,000 workers are exposed to PCP in the United States (O’Malley et al. 1990). Pentachlorophenol (PCP) is a stable and persistent compound. In humans, it is readily absorbed by ingestion and inhalation but is less well absorbed dermally. Severe exposure by any route may result in an acute and occasionally fatal illness that bears all the hallmarks of being mediated by uncoupling of oxidative phosphorylation. Tachycardia, tachypnea, sweating, altered consciousness, hyperthermia, convulsions, and early onset of marked rigor (if death occurs) are the most notable features. Pulmonary edema, intravascular hemolysis, pancreatitis, jaundice, and acute renal failure have been reported. There is no antidote and no adequate data to support the use of repeat-dose oral cholestyramine, forced diuresis or urine alkalinization as effective methods of enhancing PCP elimination in poisoned humans. Supportive care and vigorous management of hyperthermia should produce a satisfactory outcome. Chronic occupational exposure to PCP may produce a syndrome similar to acute systemic poisoning, together with conjunctivitis and irritation of the upper respiratory and oral mucosa. Long-term exposure has also been reported to result in chronic fatigue or neuropsychiatric features in combination with skin manifestations (including chloracne), chronic respiratory symptoms, neuralgic pains in the legs, and impaired fertility and hypothyroidism secondary to endocrine disruption (Proudfoot 2003).

A retrospective review of 648 medical and personnel records from individuals manufacturing PCP between 1938 and 1978 demonstrated 47 cases of chloracne occurring in a 25-year period. These workers were exposed only to PCP for 2 years prior to their diagnosis. PCP was produced by direct chlorination of phenol, monochlorophenol, dichlorophenol and/or 2,4,6-trichlorophenol in the presence of an aluminum catalyst. During the commercial synthesis of PCP, varying amounts of polychlorinated aromatic by-products, including dioxins, are produced (O’Malley et al. 1990). Russian workers who manufactured phenoxy herbicides and related compounds in the 1960s in the city of Ufa, Bashkortostan, a republic of the former Soviet Union, were studied for exposure to polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans. The patterns of the PCDDs and dibenzofurans (as defined by the specific congeners and their relative amounts) were distinctive for the type of chemical produced, with notable contributions to the TCDD toxic equivalents from the 2,3,7,8-TCDD and 1,2,3,7,8-pentachloro-p-dioxin (PnCDD) congeners.

No correlation was found between chloracne status in 1965–1967 and TCDD or toxic equivalent blood lipid concentrations in 1992. These Russian phenoxy herbicide and related chemical producers have some of the highest occupational exposure to dioxins of any cohort studied to date and seem to be unique with respect to the presence of appreciable amounts of 1,2,3,7,8-PnCDD (Ryan and Schecter 2000).

Cole et al. (1986) reported an unusual case of occupational chloracne that developed in a carpenter who assembled piers for small boat marinas using.

PCP-treated lumber. The worker, wearing only shorts and shoes, took measurements for extended periods of time while laying atop the treated lumber. After 9 months of this activity, he noted the onset of a papular acneiform eruption. Multiple small yellow-white papules were present involving the malar regions of the face, post auricular area, trunk, buttocks, thighs, and lower legs. Samples of treated lumber were tested for octachlorodibenzodioxin (OCD) and contained 1,040 times the amount of OCD than untreated wood. The yellow residue from treated wood contained 400 ppm OCD compared with technical grade PCP which contained 1600 ppm OCD. This case is unusual because the only source of PCP exposure was pressure-treated lumber; chloracne developing from this type of exposure is unusual. In the United States, the Environmental Protection Agency oversees the use of wood preservatives. In 1986, the agency proposed a level of hexachloro-p-dioxin no greater than 15 ppm, which was to be reduced to 1 ppm within 18 months (Cole et al. 1986).

9.2.2 Polyhalogenated Naphthalenes (PCNs)

Polychlorinated naphthalenes (PCNs) have a wax like consistency and have been used since the early 1900s in the electronics industry, as a dielectric material for condensers, as wire insulation, on boat hulls, as a lubricant, and as a wood preservative. Chloronaphthalenes were sold under the trademark Halowax by Koppers Company until the 1970s, but many potential uses have now been taken over by plastic and silicone. Their manufacture has been greatly curtailed (Adams).

Industrial use of the polyhalogenated naphthalenes (PCNs), occupational chloracne outbreaks and experimental human and animal studies have been reviewed. No occupational cases of PCN chloracne have been reported since 1972. Trace contamination of polychlorinated biphenyls (PCBs) with hexachloronaphthalenes and of polybrominated biphenyls (PBBs) with polybromonaphthalenes are potential current, but unlikely, sources of exposure (Taylor 1979).

9.2.3 Polyhalogenated Biphenyls (Polychlorinated Biphenyls PCBs, Polybrominatedted Biphenyls PBBs)

Chloracne has also been ascribed to exposure to polychlorinated biphenyls (PCBs), but most cases are probably due to a contamination of the PCBs with the above mentioned dioxins and dibenzofuranes. Polychlorinated biphenyls (PCBs) have been in use since 1929, and only over the last few decades have been recognized as environmental contaminants. Their use has now been confined to closed-system applications, such as in electrical capacitors and transformers. Other previous uses, such as in paints, in sealants, and in printing, have been eliminated (Zugerman 1990). Chloracne from PCBs has been demonstrated in reports in capacitor workers (Taylor et al. 1977; Tindall 1985) and in other workers (Longnecker et al. 1997). Cutaneous hyperpigmentation, eye discharge, and palpebral edema have also been reported (Taylor et al. 1977).

The greatest mass poisoning with PCBs occurred in nonoccupation settings of “oil-poisoning” in Yusho, Japan 1968 and Yu-Cheng, Taiwan 1979 when thousands of persons were affected after eating rice-based cooking oil that had been contaminated with large amounts of PCBs as described in detail below.

In 1973, polybrominated biphenyls (PBBs) were accidentally introduced into cattle feed as a result of a shipping error in Michigan. Thousands of dairy animals died or were destroyed, and farm workers were exposed to significant levels of these chemicals. Three percent of the exposed farm workers developed chloracne, but abnormal sweating and nonscarring alopecia were the more common complaints (Zugerman 1990).

9.2.4 Polyhalogenated Dibenzofurans (PHDFs)

Polychlorinated dibenzofurans were used as recently as 1974 in flame retardants; but due to their extreme toxicity they are no longer manufactured. Since polyhalogenated dibenzofuans (PHDFs) may occur as contaminants of PCBs and polyhalogenated phenols, their cutaneous effects are discussed under those headings.

9.2.5 Azo and Azoxybenzenes

We first documented cases of chloracne from a chlorobenzene compound tetrachloroazoxybenzene (TCAOB) in 1977. Tetrachloroazobenzene (TCAB) was also produced during the synthesis of 3,4-dichloro aniline or during its further conversion to herbicides. More than 90% of 41 workers in a small chemical plant developed chloracne from direct skin contact, but inhalation and ingestion were also possible routes. Family members of four workers, none of whom had been in the plant, also developed chloracne, probably from exposure at home to contaminated tools or work clothes (Taylor et al. 1977). No systemic reactions were found in any individuals. Eight years later, three of five workers with chloracne still had some evidence of chloracne and scarring. Two children who had chloracne were clear, except for mild scarring; one had acne vulgaris when seen again (Taylor and Lloyd 1982). Similar episodes of chloracne have been reported in workers exposed to TCAOB from the production of the pesticide-herbicide Proponil in Arkansas in 1977. A 38% incidence of chloracne developed among the 102 workers in the plant, and 11% were hospitalized for acute illness related to chemical exposure.

We are aware of other reports of TCAB and TCAOB chloracne in the United States and England in the 1970s and 1980s (Taylor and Lloyd 1982).

An outbreak of chloracne in 17 workers from a British plant manufacturing dichloro-aniline-derived herbicides was reported in 1993. TCAB and TCAOB were the acnegens. Comedones evolved 6–12 weeks after exposure to these chloracnegenic contaminants. Cutaneous xerosis and folliculitis on the trunk, limbs, thighs, and buttocks, previously uncommonly described, were present in 50% of exposed workers. Affected follicles were surrounded by a collarette of scale and frequently the hair shaft was twisted or broken. The pathogenesis of these lesions is unclear but may involve a disorder of keratinization. A direct toxic effect on epidermal keratinocytes or a secondary effect due to a perifollicular inflammatory reaction has been theorized (McDonough et al. 1993). They suggested that folliculitis and xerosis should be included in the clinical spectrum of chloracne.

In 1996, nine workers from a Mexican chemical plant were evaluated for the efftects of chronic exposure to chlorobenzenes (mono-, ortho- and paradichlorobenzenes). They had a mean exposure of 24 working years and worked in all stages of chemical production. Safety equipment was not used, and direct contact with the chlorobenzenes occurred via the skin and respiratory tract. The nine workers had a polymorphic acneiform eruption consisting mainly of comedones and cysts. All had comedones on the face, predominately in the malar area; lesions on the nose, axillae, chest, shoulders, arms, buttocks, and thighs were also present. Yellow cysts (2–5 mm in diameter) were found on the malar area of the face, eyelids, penis, scrotum, chest, axilla, and ears. Abnormal hyperpigmentation of the face, oral cavity, or diffuse hyperpigmentation was also observed in all patients. Chlorobenzenes were measured in the water at a concentration of 15 ppm. All workers reported chronic conjunctivitis with thick secretions from meibomian glands similar to those seen in Yusho. Hepatic involvement including elevated serum alkaline phosphatase and lower extremity peripheral neuropathy were also evident (Vazquez et al. 1996).

9.2.6 Triazoloquinoxalines

In 2009, a new chloracnegen was reported from the United Kingdom in an outbreak of chloracne among seven male pharmaceutical discovery chemists who synthesized novel polycyclic halogenated chemical compounds which were classified as triazoloquinoxalines (Gawkrodger et al. 2009). Comedones developed on the face, malar area, postauricular, periauricular, and preauricular areas with occasional inflammatory papules, pustules, and cysts. Other findings on examination included dry skin on the back and papular folliculitis on the thighs. A clinical diagnosis of chloracne was made. One subject had slightly raised serum level of alanine aminotransferase. There were no other signs of systemic toxicity. Toxicological investigations of the synthesized compounds found that the triazoloquinoxalines which showed high activity in the chemically activated luciferase gene expression (CALUX) cell bioassay for estimation of dioxin-like activity, were several times more chloracnegenic than dioxins on a weight for weight basis. Triazoloquinoxalines were synthetic intermediates in the project, being synthesized in small scale (mg g−1) quantities. Triazoloquinoxalines were not previously known as chloracnegens however, they showed the basic structural features and physiochemical properties that are typical of chloracnegens, such as high metabolic stability, a polycyclic structure, a lipophilic nature, and the potential to be halogenated (Gawkrodger et al. 2009). The chloracne in subjects mostly resolved within 18–24 months although on examination about 3 years later, five of the seven still showed minor changes of chloracne.

9.3 Nonoccupational Exposure

Nonoccupational chloracne has resulted from industrial accidents, contaminated industrial waste, and poisoned food products. A well-publicized example was the extensive environmental contamination with by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which occurred on 10 July, 1976, at the ICMESA chemical plant near Seveso, Italy. An explosion occurred during the manufacturing of trichlorophenol that resulted in the formation and ultimate discharge into the atmosphere of an estimated 2 kg of TCDD. The contaminated area encompassed more than 200 acres of land, and 135 cases of chloracne, mostly in children, were confirmed among the 2000 area inhabitants. The toxic cloud caused the death of hundreds of fowl in the first days after the explosion; the development of chloracne occurred after different time periods. Aside from chloracne, some cases of subclinical neurological damage were reported (Pocchiari et al. 1979).

In a long-term follow-up study of health status and plasma dioxin levels in chloracne cases 20 years after exposure, residents of the Seveso communities contaminated with industrial effluent dioxin levels still had elevated levels of TCDD in plasma and adipose tissues; particularly in females, in subjects who had eaten home-grown animals, and in individuals with older age, higher body mass index, and residence near the accident site. However, the health conditions of chloracne cases were similar to those of controls from the Seveso area. There was also a strong association between plasma TCDD levels and chloracne occurrence, which appeared related to younger age and light hair color (Baccarelli et al. 2005). The Seveso cancer incidence was updated to cover the 20 years period from 1977–1996 which confirmed an excess risk of lymphatic and hematopoietic tissue neoplasms in the most exposed zones. There was also elevated risk of breast cancer in very high contaminated zone females after 15 years since the accident. No cases of soft tissue sarcomas occurred (Pesatori et al. 2009).

Ingestion alone of PCBs and their thermally degraded polychlorinated dibenzofurans (PCDFs) played a major role in two mass “oil-poisoning” episodes Yusho in Japan in 1968 and Yu-Cheng in Taiwan in 1979, the largest epidemics of chloracne to date. In both countries, several thousand persons were affected after eating rice-based cooking oil that had been accidentally contaminated with large amounts of tetrachlorobiphenyl. Most clinical manifestations were observed in patients who had directly ingested the oil. Dermatologic manifestations in typical Yusho and Yucheng cases having high PCB and PCDF concentrations in blood included acneiform eruptions, hyperpigmentation, fingernail abnormalities, and hypersecretion of conjunctival meibomian glands which recovered very slowly after several years. However, elevated serum triglycerides and serum thyroxin, immunoglobulin disorders, goiter, decreased sperm mobility, dental abnormalities joint inflammation, decreased IQ score in children, headache, and numbness were persisting 30 years later (Masuda 2001).

PCBs and PCDFs can persist in human tissues with the median half-life of 2.9 years in the first 15 years after onset and 7.7 years in the next stage of 15 years (Masuda 2001) (similar dioxins have half-lives in humans of about 7 years). The offspring of exposed females are described as cola babies because of their dark color. Generalized hyperpigmentation, meibomian gland enlargement with eye discharge, and nail deformities occurred in congenitally exposed individuals. Severe chloracne scars were observed 11 years postcongenital exposure in some affected individuals in Taiwan (Hsu et al. 1995).

We studied 128 children who were transplacentally exposed to PCBs and dibenzofurans in Taiwan, their parents and siblings who were directly exposed, and 115 control children. Direct exposure of the mothers stopped in 1979 and the children were born as late as 1985. At birth, the exposed children had increased rates of hyperpigmentation, eyelid swelling and discharge, deformed nails, acne, natal teeth, and swollen gums unlike controls. On cutaneous examination in 1985, key findings were a much higher rate of dystrophic fingernails and pigmented or dystrophic toe nails than in controls. Increased rates of hyperpigmentation and acne were also seen in the exposed groups. The cutaneous findings were part of a transplacental neuroectodermal dysplasia, with dental abnormalities, a growth deficit, developmental delay, and a behavior disorder. Transplacental dermatotoxins are rare (minoxidil, phenytoin, carbamazepine and hexachlorobenzene). This syndrome is one of very few documented to result from transplacental exposure to pollutant chemicals (Rogan et al. 1988). On reexamination 6 years later, nail changes were still present and suggested prenatal injury to the nail matrix (Hsu et al. 1995). The findings in transplacentally exposed children differ from those seen in people directly exposed, particularly the higher prevalence of acne in the latter group (Rogan et al. 1988; Gladen et al. 1990; Hsu et al. 1995).

In 1982, eight members of a Spanish family were poisoned by consumption of olive oil contaminated with PCDDs and PCDFs. The entire family had varying degrees of acneform lesions, including papules, pustules, cysts, comedones, and scars located on the face, axilla, neck, trunk, groin, and genitals. Hyperpigmentation of the face was also reported. These lesions are comparable in severity to those described in the Yusho incident. The olive oil consumed was stored in a plastic container, which had presumably stored hexachlorobenzene and pentachlorophenol prior to the oil. The causative agents were identified as PCDDs, PCDFs, and PCP, each of which was recovered from the cooking oil. There were high serum levels of PCDDs and PCDFs, which returned to normal when measured 5 years after oil consumption ceased (Rodriguez-Pichardo et al. 1991).

In 1981, an electrical transformer fire occurred in Binghamton, New York. The fire began in the basement mechanical room of an 18-story office building. Approximately 180 gallons of Askarel, a dielectric fluid composed of 65% PCBs (Aroclor 1254) and 35% polychlorinated benzenes leaked from a transformer.

The fire originated in the switch gear of the secondary electrical power distribution system. Pyrolysis of the Askarel led to the formation of a fine oily soot containing PCBs, dibenzo-p-dioxins, and dibenzofurans, which spread to all areas of the building through ventilation shafts. Three-year post-exposure serum PCB concentrations increased with the degree of potential exposure, but 98% of samples tested had values similar to those found in unexposed populations. One-third of the fire fighters and other persons who were in the building for 25 h or more reported “rash” or itching.

However, no cases of chloracne, liver disease or neurological disorders were identified in the exposed individuals (Fitzgerald et al. 1989).

10 Cutaneous Manifestations

Clinical features of chloracne include multiple closed comedones and straw-colored cysts distributed primarily over the malar crescents and retroauricular folds, typically sparing the nose. This pattern of distribution is of significant diagnostic importance. Inflammatory lesions occur but are less frequent than in other forms of acne. As severity increases, the posterior neck, trunk and extremities, buttocks, scrotum, and penis may become involved. The axillae are most likely to be involved in those who ingest chloracnegens, such as in Japan’s Yusho poisoning in 1968 or in those at Seveso, Italy in 1976, who were exposed in toxic cloud (Jirasek et al. 1973).

Associated with the classic lesions of chloracne is a relatively dry appearance of the skin. Metaplasia of sebaceous epithelium occurs, with subsequent atrophy of sebaceous and meibomian glands leading to xerosis of the facial skin, skin of the chest and back and the reduction in sebum excretion seen in chloracne (Zugerman 1990; Gawkrodger et al. 2009).

Hyperpigmentation may also occur and is usually confined to the face, although in severe cases it can be generalized. Hyperpigmentation has also affected the nails, mucous membranes, lips, and mouth in those involved in Yusho and Yuchng poisoning in Japan and Taiwan respectively. Individuals exposed to chlorobenzenes and industrial polychlorinated biphenyl (PCB) poisoning may lead to similar pigmentation.

Eye involvement is relatively common and is termed “ophthalmic acne ” (Taylor 1974; Crow and Puhvel 1991). Conjunctivitis with meibomian gland involvement may be seen in severe cases of poisoning from chloracnegens, especially in the Yusho poisoning. The Yusho victims demonstrated extreme eye findings when their meibomian glands were converted to squamous cysts filled with a cheesy keratinous substance; the unusual oral route of entry and absorption of PCBs may have been an essential part of the syndrome (Tindall 1985).

Dermatologic observations associated with chloracne, which may lead to identification of specific exposures, include hyperpigmentation of the skin (PCBs, TCDD), mucous membrane and nail hyperpigmentation (PCBs), follicular hyperkeratosis (PCBs, TCDD [Seveso]), conjunctivitis and meibomian gland changes (PCBs), facial erythema and edema (trichlorophenol, hypertrichosis (TCDD), hyperhidrosis of the palms and soles (TCDD, PCBs), folliculitis and xerosis (TCAB, TCAOB), and actinic elastosis (TCDD). Erythema and edema of the exposed face and extremities associated with trichlorophenol production was also seen in the Seveso cases. These “pre-chloracne” lesions were also accompanied by vesiculobullous and necrotic lesions on finger tips and palms, and papulonodular lesions, all of which resolved within a few weeks. Hyperkeratotic, infiltrative erythematous granuloma annulare, or erythema elevatum diutinum-like lesions were also seen in association with chloracne 2 months after the explosion. Axillary involvement and follicular hyperkeratosis are linked with inhalation or ingestion of chloracnegens (Taylor 1979; Tindall 1985).

Hypertrichosis in association with chloracne has been mainly confined to the temples and may rarely be a sign of hepatic porphyria. However, hypertrichosis has also been described in chloracne patients with normal uroporphyrin levels (Jirasek et al. 1973; Crow and Puhvel 1991).

Punctate keratoderma-like lesions on the palms and soles clinically and histologically indistinguishable from keratosis punctata palmaris et plantaris (KPPP) was reported to occur in a female patient with dioxin intoxication (Geusau et al. 2000). In addition to chloracne, she also exhibited acral granuloma annulare-like lesions, distal onycholysis, hypertrichosis, and brownish-gray hyperpigmentation of the face.

Scarring may occur in the end stage of moderate to severe chloracne. It may appear as fine pits seen in atrophodermia vermiculata, or may resemble scars caused by severe acne vulgaris (Zugerman 1990).

Chloracne may occur in relatives of workers exposed at home to contaminated work clothing and tools (Taylor et al. 1977).

10.1 Onset and Duration

The clinical course of chloracne varies. After exposure to a chloracnegenic agent, there usually is a delay of 2–4 weeks until the development of chloracne. However, the onset can be delayed up to months. Lesions tend to persist for decades even without additional contact and are refractory to treatment (Crow and Puhvel 1991; Sterling and Hanke 2005).

11 Non-cutaneous Manifestations

Chloracnegen exposures to humans have been associated with increased risk of severe skin lesions such as chloracne and hyperpigmentation, altered liver function, hypertriglyceridemia, hypercholesterolemia, general weakness, weight loss, depression of the immune system, increased risk for diabetes and cardiovascular disease, various hormonal alterations, nervous-system abnormalities, effects on reproduction, impaired developmental, neurological, and cognitive function in infants. It is a potent teratogenic and fetotoxic chemical in animals. Other systemic disorders reported with chloracne include bronchitis, renal, and pancreatic involvement (Taylor 1987). Patients with chloracne should have appropriate physical examination and laboratory evaluations to exclude systemic involvement.

Epidemiologic data suggesting that high-level dioxin exposure causes liver function abnormalities and chloracne are incontrovertible (Longnecker et al. 1997). In Seveso, a transient rise in values of hepatic enzymes that reflected hepatocellular damage, that is, gamma-glutamyl transferase and alanine amino transferase occurred. Alkaline phosphatase and serum bilirubin levels were not elevated and jaundice or other signs of hepatic injury were not appreciated. Crow and Puhvel (1991) suggested that the degree of hepatic injury was dependent on the specificity of the toxicant involved, rather than as a consistent consequence of all forms of chloracnegen exposure.

Porphyria cutanea tarda (PCT) has been reported in humans following TCDD exposure (Bleiberg et al. 1964). Both normal urine porphyrin levels have been observed from individuals with severe chloracne (Strik 1979) and higher levels of urine porphyrins in workers exposed to pentachlorophenol pesticide exposure (Hryhorczuk et al. 1998). TCDD is a porphyrinogen in animal models and inhibits uroporphyrinogen decarboxylase, the enzyme precipitating PCT in some patients (Mukerjee 1998).

Peripheral neuropathy with pain and numbness may be observed, especially in persons severely exposured to chlorinated hydrocarbons (Thomke et al. 1999). Neuropathy has been confirmed by delayed nerve conduction velocity. In the 1968 Japanese epidemic of chloracne caused by ingestion of contaminated cooking oil (Yusho), these neurologic symptoms were especially apparent.

The long-term health effects of dioxin exposure in humans have not been conclusively proven. Carcinogenesis, teratogenicity, and immunosuppressive effects of these compounds are extremely controversial areas. Although animal studies with TCDD have strongly suggested that this material is carcinogenic in animal systems, these findings cannot necessarily be extrapolated to humans. Anecdotal information has pointed to TCDD as being a human carcinogen. Populations occupationally or accidentally exposed to chemicals contaminated with dioxin may have an increased incidence of soft-tissue sarcomas and non-Hodgkin’s lymphoma (Mukerjee 1998). In a long-term cohort of 2,187 male workers exposed to dioxin Bodner found no increased cancer risk from dioxin exposure and concluded that there is a wide range of cancer rates and the lack of consistency across dioxin studies (Bodner et al. 2003). However, mortality and morbidity findings during the 20-year period following the accident showed increased risk of lymphatic and hematopoietic tissue neoplasms, digestive system cancer (rectum in males, and biliary tract among females, in particular), and respiratory system cancer (lung, among males). There was also elevated risk of breast cancer in females in very high contaminated zones (Pesatori et al. 2003, 2009). In the incidence analyses, thyroid and pleural cancer were suggestively increased (Hardell and Sandstrom 1979). Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort (Pesatori et al. 2003). Because of the long-term persistence of TCDD in the human body, atherosclerosis, hypertension, diabetes and various hormonal alterations, vascular, ocular changes, effects on reproduction, neural system damage, including neuropsychological impairment, neurological, and cognitive impairments in infants can be present several decades after exposure. Such chronic effects are nonspecific, multifactorial, and may be causally linked to TCDD (Sweeney and Mocarelli 2000; Pelclova et al. 2006). Continuous long-term surveillance and follow-up is warranted to cover the long time period, even decades, often elapsing from exposure to carcinogenic chemicals and occurrence of disease.

11.1 Mechanism

The mechanism involved in the initiation of chloracne remains unknown. The interference of halogenated biphenyls, dibenzo-p-dioxins, dibenzofurans, and azo and azoxybenzenes in vitamin A metabolism and function may offer an explanation about the acnegenic effects of these compounds on human skin (Chen et al. 1992; den Besten et al. 1993; Coenraads et al. 1994). Coenraads and coworkers (1994) found that retinol concentrations in skin biopsies from nine PCP-exposed workers with chloracne were much lower in comparison with controls. This suggests that the chemicals may affect vitamin A metabolism and hence influence pilosebaceous units and the epidermis.

A reduction in sebum excretion is a hallmark of chloracne, and fewer Propionibacterium acnes organisms are present in follicles of those with chloracne than of those with acne vulgaris (Cunliffe et al. 1975). Dioxins, for example, TCDD have been shown to impede androgen action possibly through interfering with androgen receptors (Gawkrodger et al. 2009). The biological mechanisms of chloracne induction are still debated but it was suggested that dioxins have their chloracnegenic effect by activating skin stem cells and shifting the differentiation commitment of the stem cell progeny (Panteleyev and Bickers 2006).

The molecular mechanisms of dioxin-mediated chloracne have not been clarified. The action of dioxins resembles that of hormones, since their toxicity is mostly receptor-mediated. The degree of affinity of various chloracnegens for the binding protein designated as the aryl hydrocarbon (Ah) receptor (for aromatic hydrocarbons) correlated with their biological efficacy (Poland et al. 1976). One of the most important initial steps in prerequisite of chloracne pathogenesis and toxicity of dioxins is the activation of a the aryl hydrocarbon receptor a transcription factor that binds to the Ah receptor nuclear translocator (ARNT) to regulate the transcription of numerous genes, including cytochrome P450 CYP1A1, GSTA1, and TGF-alpha. The changes of genes expression may disturb normal proliferation and differentiation of human epidermis cells, and then lead to chloracne (Furness and Whelan 2009; Tang et al. 2008).

In cultures of normal human epidermal keratinocytes dioxin accelerates cell differentiation, as measured by the formation of cornified envelopes. This acceleration is mediated by the aryl hydrocarbon receptor AHR; also, dioxin increases the expression of several genes known to be regulated by Ah receptor nuclear translocator (ARNT), which have critical roles in the cornification and epidermal barrier function of the skin. It has been demonstrated that all of these responses are opposed by ligand-activation of the EGF receptor (R), an important regulator of keratinocyte cell fate. Epidermal growth factor (EGF) represses the dioxin-mediated gene transcription induction of CYP1A1 in cultured normal human keratinocytes by inhibiting the recruitment of the transcriptional coactivator protein p300 to the CYP1A1 gene. EGF also inhibits the dioxin-dependent induction of certain parameters in keratinocytes that are reflective of dioxin-induced chloracne. This epidermal growth factor receptor signaling may modulate the incidence and severity of chloracne and be of potential therapeutic relevance to human poisonings by dioxin (Sutter et al. 2009; Hankinson 2009).

11.2 Histopathology

In 1957, Hambrick studied the pathology of chloracne. Histologic changes in the skin may begin within 5 days of severe exposure to chloracnegenic chemicals (Hambrick 1957). The primary lesion of chloracne appears to be keratotic plugging of the hair follicle with collection of keratinous material in the follicular orifice. The follicular epithelium thickens, followed by atrophy of sebaceous glands and their replacement by keratinous cysts. Inflammation is minimal or absent. Histological features of chloracne are characterized by noninflammatory keratinization of pilosebaceous units with comedones and dilated infundibulum (Coenraads et al. 1994) but the specificity of these findings is unclear. A characteristic of chloracne is the rapid transformation of sebaceous glands into comedones. This appears to be pathognomic for chloracne poisoning. Biopsies from Seveso showed eccrine duct metaplasia with possible acrosyringeal cyst formation. Foreign body granulomas around detached walls of eccrine gland excretory ducts may also be present (Omohundro and Taylor 1998).

Hyperpigmentation of the lesions in chloracne has been demonstrated to result from hyperproduction of melanin by a normal number of melanocytes along the basal layer of the epidermis and infundibular epithelium.

11.3 Diagnosis

In 1984, a diagnostic criteria for chloracne was established by the Veterans Administration Chloracne Task Force including (1) exposure to a chloracnegen; (2) aggravation or onset within weeks to 2 months of exposure; (3) predominance of open comedones and straw-colored cysts; (4) atypical distribution, that is, malar crescent and “crow’s-foot” area of the face; (5) compatible histology; and (6) inflammatory cysts and abscesses on the face, behind the ears, and on the neck, buttocks, scrotum, and thighs (Veterans Administration Chloracne Task Force 1984). The diagnosis of chloracne entails a compatible clinical picture with distribution of comedones and noninflammatory cysts beyond the typical locations of acne vulgaris. It is characterized by open and closed comedones with straw-colored cysts found predominantly in the malar region, postauricular area, axilla, and scrotum. Documentation of significant exposure to known chloracnegens and the absence of other external causes is also required.

Based on cutaneous findings alone or in novel settings, it may be very difficult to differentiate chloracne from acne vulgaris and other types of environmental acne – oil folliculitis, pitch acne, and tropical acne – is listed in Tables 31.4 and 31.5 . Senile (solar) comedones of the Favre-Racouchot syndrome and Dowling-Degos’ disease also can be considered in the clinical differential diagnosis (Kersevovich et al. 1992).

Table 31.4 Clinical features of acne vulgaris compared with chloracne (After Peter Pochi, MD with permission)
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Table 31.5 Differential diagnosis of various forms of occupational and environmental acne
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11.4 Treatment

Chloracne tends to resolve slowly upon cessation of chemical exposure. Its duration correlates with the severity of the disease which usually reflects the degree and extent of exposure. Dioxins are highly lipophilic, have a long half-life in fat tissue and low turnover rate in the body. If exposure ceases, the lesions will gradually improve over many years or decades. The severely exposed victims of Yusho in 1968 had characteristic chloracne lesions that continued to develop for as long as 14 years postexposure.

Treatment of chloracne is usually unsatisfactory as the modalities that are useful in acne vulgaris are often ineffective in chloracne. Topical application of retinoic acid (0.005–0.3% concentration) or of tretinoin (Retin-A) gel or cream is of some benefit in controlling comedones, but other topical agents are of little use (Caputo et al. 1988). A combination of tetracycline and short courses of orally administered prednisone helped with severe inflammatory cases. A trial regimen of methotrexate, 25 mg every 10 days for several months was unsuccessful (Taylor et al. 1977; Scerri et al. 1995).

There are anecdotal reports of both unsuccessful use (Sterling and Hanke 2005) and efficacious use of oral 13-cis-retinoic acid (isotretinoin) which, if instituted early, may prevent cyst formation. Isotretenoin 0.3–1 mg/kg/day may be indicated in severe cases for a course of 20 weeks. The drug should be administered only by those experienced in its use and in strict accordance with current prescribing instructions. The hepatotoxicity and lipid abnormalities sometimes associated with chloracne are theoretical reasons to avoid isotretinoin. Isotretinoin is a potent teratogen with other potentially significant side effects that require close monitoring (Gawkrodger 1991).

Local therapy with acne surgery and dermabrasion has been reported. Light cautery following topical anesthesia with EMLA cream has been used successfully in six patients with resistant chloracne lesions (Yip et al. 1993).

A promising new approach to lowering blood dioxin levels employed the use of Olestra, a nonabsorbable, non-digestible, lipophilic dietary fat substitute has been reported to accelerate the patients’ intestinal excretion of TCDD by eight to ten fold. This is sufficient to reduce the normally observed elimination half-life of TCDD from about 7 years to 1–2 years (Geusau et al. 1999).