Occupational FRANC0
Acne
KOKELJ
A
cne and acneiform eruptions can be distinguished. The former may be further classifiable into juvenile form, acne venenata, and ,acne caused physical agents. The anatomic substratum of all these forms is the pilosebaceous unit, the role of which in acne pathogenesis has been well described. Although acne vulgaris represents a pathology typical of the sebaceous follicles usually present only on the face and upper trunk, occupational acne may affect all the follicles of the body.’ Occupational acne is a form of acne venenata (venenum = “poison”); it is caused by professional contact with chemical substances as well as by the action of environmental physical agents. It may affect both people with preexistent acne and seborrhea, who worsen after contact, and people without a positive history of these diseases. Especially in the past occupational acne was considered one of the most frequent environmental skin diseases, probably second only to contact dermatitis. Specific risk factors are not necessary, although an aspecific predisposition to seborrhea and preexistent hepatic alteration may influence oil acne and chloracne. From an etiologic point of view, occupational acne may be classified into two forms: chloracne and acne caused by petroleum and its derivatives and coal tar products.
Oil and Coal Tar Acne Oil acne is the most common form of occupational acne although today it is not as frequent as in the past; it is caused mainly by greases and insoluble oils that contain high percentages of mineral oil. It is well known that these substances are comedogenic and, once in contact From
the Department
of Dermatology,
of Trieste,
University
Trieste,
Italy. Address
correspondence to Franc0 Kokelj, 34149 Trieste, Italy.
of Dermatology,
Department
University of Trieste,
0 1992 by Elsevier Science Publishing
Co., Inc.
l
0738-081x/92/$5.00
with human skin, can cause different kinds of skin diseases. The contact may be direct or indirect, through clothes, as often happens in mechanical industry workers. Machine tool operators in metal industry are those most commonly affected. Adams2 lists other workers particularly exposed to oil contact: auto, truck, and aircraft mechanics; roofers; oil well drillers; coke oven workers; petroleum refiners; rubber workers; textile mill workers; and road pavers. In different studies, the incidence of oil folliculitis ranges from 7 to 83% of the exposed people. 3-6 The lower incidence of mineral oil folliculitis reported in recent years is surely related to both the decreased use of pure cutting fluids and the improved hygienic conditions in mechanical industries. Contact with mineral oil may worsen the clinical features of juvenile acne and seborrheic dermatitis in young people. Consequently the lesions may appear in the same site as acne vulgaris, but are more common in nonaffected areas where contact with oil takes place, such as dorsa of the hands and fingers (Fig l), arms and forearms, thighs, and abdomen. The more common clinical picture of oil acne is characterized by the presence of scattered comedonic, usually black, and/or microcystic lesions caused by oil itself; after a prolonged contact with these substances, follicles are closed with consequent irritation, reactive hyperkeratosis, and sebum retention. The microsomal oxygenase enzyme system of the sebaceous gland cells seems to play an important role in the intense cytotoxic reactions to these chemicals.’ These lesions are frequently associated with follicular hyperkeratosis and hair atrophy; inflammation is rare, whereas itching is common, especially in the first phases of infection. Melanosis and dyskeratosis may occur on the face and dorsa of the hands. Polycyclic hydrocarbons can cause dermatitis also when breathed or ingested, as in gas station workers and oil refinery workers; in these cases a polymorphic erup-
213
214
Figure
Clinics in Dermatology 1992;10:213-217
KOKELJ
1.
Oil acne
tion characterized by spinulosis and hyperkeratotic folliculitis may appear, especially in people with preexistent dermatitis. Also, kerosene can cause oil acne; Upreti et al presented a study of 24 subjects chronically exposed to kerosene in a car workshop that revealed a high incidence of oil acne and other dermatologic problems.8 It is well known that certain coal tars have acneigenic, phototoxic, and carcinogenic properties. Coal tar acne shows a marked preference to the exposed areas of the body,9 in particular the malar ones, suggesting airborne distribution of the compounds such as fumes of manipulated materials.
Chloracne Chloracne is a distinctive and often severe form of occupational acne caused by exposure to various chlorinated compounds, which may be toxic not only to the skin but also to the liver and neurologic system. In 1899 Herxheimer first used the term chlorucne to describe four cases of severe acne resulting from environmental contact with potassium hypochlorite electrolytically produced.* Since then the history of chloracne has corresponded to the history of industrial development, with an increasing incidence during war periods. Between World Wars I and II a decrease in the incidence of chloracne was observed, although numerous reports stressed also the possibility of liver involvement. In recent decades a decreasing incidence of chloracne followed the advent of plastics, the gradual substitution of chlorinated hydrocarbons with synthetic resins, and restriction of the use of polychlorinated biphenyls to only closed-system formulations.’ The improvement in hygiene has made chloracne quite rare in Western industries: the most important recent reports of chloracne have not concerned workers but rather people involved in accidents, such as the poisoning by a cooking
oil in Japan in 19681°-13 and the explosion at ICMESA in Seveso, Italy, in 1969.14-16 Chloracne may be caused not only by substances capable of inducing secondary formation of aromatic chloroderivative hydrocarbons (chlorophenols) but also by the use of solvents like trichlorethylene and perchlorethylene. On the contrary, a pathogenetic role of inorganic chlorine may be excluded; in fact, chlorine added to swimming pool water does not cause or worsen acne.” Chlorinated naphthalenes and polyhalogenated biphenylenes are the most common groups of substances able to induce chloracne; they have been widely used for their chemical stability and resistance to acids and alkalis and for their high dielectric properties. It is known that among chlorinated naphthalenes only the pentachloro and hexachloro derivatives can cause chloracne, whereas the mono-, di-, tri-, tetra-, penta-, and octachloronaphthalenes are not acneigenic. 18,19Among the polyhalogenated biphenylenes the brominated compounds are more acneigenic than the chlorinated compounds.20 Chloronaphthalenes have been widely used, especially in the past, as electrical insulators and for fire-resistant materials, whereas polychlorodiphenols have been used in hydraulic fluids, plastics, adhesives, fire retardants, and sealants. Polychlorinated dibenzofurans, possible contaminants of various chlorinated phenols,*’ and azobenzene derivatives have also been reported as possible agents of chloracne. In Table 1 are listed the halogenated aromatic compounds that can cause chloracne. Chloracne may be caused both by contact of the skin with the previously mentioned substances and by ingestion and/or inhalation of fumes produced during preparation and use of chloro derivatives. Endogenous contact can cause systemic intoxication and contribute to the skin
Table 1. Halogenated Can Cause Chloracne
Aromatic
Compounds
That
Polyhalogenated naphthalenes (pentachloro and hexachloro derivatives)‘*-20 Polyhalogenated biphenyls10~11~21 Polybromobiphenyls (PBBs) Polychlorobiphenyls (PCBs) Polyhalogenated dibenzofuranP Polybromodibenzofurans Polychlorodibenzofurans Contaminants of polychlorophenol compounds 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)t4*r6 Hexachlorodibenzo-p-dioxirP Contaminants of 3,4dichloroaniline and related herbicideP 3,4,3’,4’-Tetrachloroazoxybenzene (TCAOB) 3,4,3’,4’-Tetrachloroazobenzene (TCAB) Others 1,2,3,4-Tetrachloroazobenzene2 2,6-Dichlorobenzonitrile40
Clinics in Dermatology 1992;10:213-217
damage, through the slow elimination of chloro derivatives through the pilosebaceous unit. There are many reports about environmental chloracne and related systemic impairment22-25; the massive intoxication described in 1968 in Japan and the disaster at ICMESA (Seveso, Italy) are important and paradigmatic examples of this pathology. The first event took place in 1968 in a rice cooking oil factory in Japan; the oils were contaminated by polychlorinated biphenyls (Kanechlor400) used in the heating coils. The ingestion of contaminated oil caused cliff erent degrees of intoxication in 105 7 people. Different follow-up studies showed that after 3 years, half of the patients were still symptomatic and the acneiform eruptions were the most common problem13; after 10 years skin lesions were no longer observed.26 In 1969 the accidental explosion of a reactor involved in trichlorophenol synthesis, at the ICMESA chemical plant in Seveso, Italy, released a toxic cloud in the atmosphere that contaminated the whole countryside of Seveso, causing the most important reported dioxin intoxication. Dioxin is the term used to describe 2,3,7&tetrachlorodibenzo-p-dioxin (TCDD), an aromatic chlorinated hydrocarbon found mostly as an impurity during the alkaline hydrolysis of tetrachlorobenzene in sodic 2,4,5trichlorophenol used as an herbicide. The toxic cloud containing dioxin caused the death of hundreds of fowl in the first days after the explosion; many people developed chloracne after different lengths of time. Apart from chloracne and some cases of subclinical neurologic damages, no other severe problems, birth abnormalities, or mental retardation was reported in the involved population in the numerous long-term follow-up studies.27,28 The malar region and the areas around the eyes and behind the ears are the most common sites of chloracne. The cheek, neck, and trunk may be involved too; the nose is usually spared except in severe forms. Lesions can extend centrifugally with an increase in the severity of chloracne. Arms, thighs, hands, and feet are consequently affected only in the most serious cases; on the contrary, genitals are often involved and in this site lesions are usually papulonodular. Clinical aspects of chloracne may be both mono- and polymorphic and are characterized by a variety of skin lesions; multiple closed cornedones and microcysts are the first signs of chloracne. Later, inflammatory lesions, increasing in cyst dimensions, follicular pustules, and abscess that may evolve leaving scars have been observed. Hypertrichosis, melanosis on the face, and increased skin fragility are also common. Itching may be intense in about half the patients, whereas in some cases it may even be absent. A generalized skin involvement, with the obvious exclusion of palmar and plantar areas, may be observed
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in the most severe cases. Gianotti29 described two different pictures of chloracne in children exposed to the toxic cloud at Seveso: one is characterized by erythema, xerosis, homlike cysts, and atrophy and was usually observed about 3 weeks after the explosion; in the other, diffuse follicular hyperkeratosis was observed after at least 6 weeks and was probably influenced also by endogenous mechanisms (excretion of TCDD through the pilosebaceous follicle and the eccrine sweat glands). One of the main problems with chloracne is that this pathology is often accompanied by systemic involvement; liver and neurologic dysfunction are quite common. Acute yellow atrophy of the liver and porphyria cutanea tarda, the latter especially in laboratory animals, are the most common hepatic disorders reported in the literature.2 We do not know the true incidence of these conditions, because this problem is often underestimated in the exposed workers. The neurologic impairment resulting from chloracne may be characterized by headache, irritability, lacrimation, increased palmar sweating, weakness, peripheral neuritis, and psychiatric symptoms.13,30 In some cases it represents the most important problem, as stressed in the previously mentioned epidemic episode of chloracne observed in 1968 in Japan.13 As far as carcinogenic predisposition is concerned, Cook,31 in a cohort study of workers who had probably been exposed to TCDD, reported two cases who presented with chloracne and malignant fibrous histiocytoma; one of them died of fibrosarcoma and the other of liposarcoma. As both these patients were cigarette smokers, this author hypothesizes also in the absence of an evident cause - effect link, a relationship between smoking and increased risk of soft tissue sarcomas after exposure to TCDD.
Less Common Forms of Occupational Acne Less common forms of occupational acne are characterized by both a worsening of preexistent acne and a new eruption from professional exposure to different substances and/or physical sources. Cosmetic acne and acne resulting from ultraviolet light exposure may be considered as an occupational form for some workers, for example, actors, actresses, and cosmetologists.32 Mills and Kligman reported as occupational disease a mechanical acne in truck drivers who presented with typical lesions on their back as a result of local pressure and rubbing against seat covers.33 Some cases of steroid acne are described in employers in drug companies; a study on the hygienic conditions in a pharmaceutical company where corticosteroids were produced revealed the existence of professional risks because of the presence of chemically active dusts.34 The
216 KOKELJ
Clinics in Dermatology
1992;10:213-227 skin lesions, like acne rosaceiform, erythema, and so on, usually precede systemic effects. Improvements in industrial hygienic conditions and a health education program have led to a significant decrease in systemic effects and skin disorders. Litt reports some cases of acne caused by exposure to grease encountered in and fat frying hamburgers that he calls McDonald’s acne.35 In recent years an increasing number of reports have stressed the possible role of video display terminals in inducing skin lesions and, in particular, skin rashes. Liden and Wahlberga6 studied 74 office employees who complained of skin diseases, to correlate these pathologies with work at video display terminals. Furthermore, an increased frequency of acne, seborrheic dermatitis, and rosacea was observed in the exposed group and the possibility of a relationship was accepted, although there was no evidence on the mechanisms that may produce skin damage. 37 In fact, no dangerous radiation has ever been revealed at the distance usually kept by an operator from a video display (at least 60 to 70 cm); consequently the skin eruption reported could be related to other factors, perhaps the stress of people with an aspecific predisposition to skin eruptions. Apart from the originality and curiosity of the reports, the diagnosis of these diseases as occupational may represent an important medical and legal problem to evaluate the effective relationship with the patient’s occupation.
Histology The histology of oil acne is characterized by follicular hyperkeratosis, keratinous cysts, and an aspecific dermal infiltrate with various degrees of sebaceous cell atrophy. These lesions are also observed in chloracne where follicles are usually more widely dilated, sebaceous gland atrophy is more important, and an increase in pigmentation is often present among the involved follicles.38
Diagnosis Occupational acne must be distinguished from acne vulgaris, other forms of folliculitis, and sycosis. Diagnosis of occupational acne requires a thorough knowledge of the substances with which workers may come into contact and of the possible relationship between a specific task and exposure to oils, greases, and chlorohydrocarbons. Folliculitis caused by petroleum and coal tar derivatives may be distinguished from chloracne by the different sites of the lesions; the less frequent presence of cysts, nodules, and pustular evolution; and the rapid improvement once the dangerous exposure has stopped.
Therapy The first step in occupational acne therapy is identification of the causative agent and interruption of the exposure to it. Although oil and coal tar acne usually improves spontaneously when the exposure ceases, chloracne represents a major problem both because of its resistance to common therapies and because of the frequent systemic involvement.39 The various therapeutic modalitites proposed for acne vulgaris are also suggested for treatment of occupational acne. To solve the problem at the industrial level, it is necessary to reduce contamination with the acneigenic substances.
References 1. Plewig G, Kligman AM. Acne, morphogenesis and treatment. Berlin: Springer-Verlag, 1975:162-3. 2. Adams RM. Occupational acne, including chloracne. In: Adams, RM, editor; Occupational skin disease. New York: Grune & Stratton, 1983:70-81. 3. Amado MR. Les dermatoses professionelles dans l’industrie automobile. Bull Sot Fr Dermatol Syphil 1955;62:157. 4. Borelli S, Benetto M, Manok M. Vorkommen und Haufigkeit von Hautkrankheiten in der automobilindustrie. Atti Symp Dermatol Univ Carolina Pragae 1962;1:131. 5. Yamada M, Yanai T. Supplement d’information sur les maladies professionelles de la peau. II. Sur la dermite de l’huile aux genoux. Rec. in Zblatt; 1960;106:307. 6. Meneghini CL, Angelini G. Dermatosi professionali. In: Sartorelli E, editor. Trattato di medicina de1 lavoro. Padua: Piccin editore, 1981:987-1031. 7. Taylor JS. The pilosebaceous unit. In: Maibach HI, Gellin GA, editors. Occupational and industrial dermatology. Chicago: Year Book Medical, 1982:125-36. 8. Upreti RK, Das M, Shanker R. Dermal exposure to kerosene. Lucknow: Immunological Section, Industrial Toxicology Research Center, 1989;31(1):16-20. 9. Bertolini R. Acne. A summary of the occupational health concern. Hamilton, Ontario: Canadian Centre for Occupational Health and Safety, 1989:Report No. F89-lE, pp l-7. 10. Katsuki S. Reports of the study group for “Yusho” (chlorobiphenyls poisoning). Fukuoka Acta Med 1969;60:403. 11. Tsukamoto H. The chemical studies on detection of toxic compounds in the rice bran oils used by patients of Yusho. Fukuoka Acta Med 1969;60:403. 12. Goto M, Higuchi K. The symptomatology of Yusho (chlorodiphenyl poisoning in dermatology). Fukuoka Acta Med 1969;60:409. 13. Kuratsune M, Yoshimura T, Matsuzaka J, et al. Yusho, a poisoning caused by rice oil contaminated with polychlorinated diphenyls. Hiroshima Health Rep 1972;86:1083-91.
Clinics in Dermatology 1992:10:223-217
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14. Di Domenico A, Silano V, Vivian0 G, et al. Accidental release of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) at Seveso, Italy: TCDD distribution in the oil surface layer. Ecotoxic01 Environ Safety 1980;4:228-320. C, Bonaccorsi A. TCDD contamina15. Fanelli R, Chiabrando tion in the Seveso incident. Presented at the symposium on metabolism and pharmacokinetics of environmental chemicals in man, Sarasota, Florida, June 7-12, 1981. 16. Filippini G, Bordo B, Crenna I’, et al. Relationship between clinical and electrophysiological findings and indicators of heavy exposure to 2,3,7,8-tetrachlorodibenzo-dioxin. Stand J Work Environ Health 1981;7:257-62. 17. Rosenstock L, Cullen MR. Skin disease. In: Clinical occupational medicine. Philadelphia: WB Saunders, 1986:147-73. production 18. Shelley WB, Kligmman AM. The experimental of acne by penta- and hexachloronaphthalenes. Arch Dermatol Syphilol 1957:75:689-95. study of the 19. Hambrick GW, Blank H. A microanatomical response of the pilosebaceous apparatus of the rabbit’s ear canal. J Invest Dermatol 1956:26:185-200. 20. Crow KD. Chloracne. 1970;56:79-99.
Trans St John’s Hosp Dermatol
21. Taylor JS. Environmental chloracne: Ann NY Acad Sci 1979;320:295-307.
Sot
Update and overview.
22. Dugois P, Marechal JM, Colomb L. 2,4,5-Trichlorophenol chloracne. Sot Med Hyg Trav 1957;19:626-8. 23. Carter LJ. Michigan’s PBB incident: to disaster. Science 1976;192:240-3.
Chemical
mixup
leads
24. Taylor JS, Wuthrich RC, Lloyd KM, et al. Chloracne from manufacture of a new herbicide. Arch Dermatol 1977;113:616-9. 25. Suskind RR. Chloracne. The hallmark of dioxin intoxication. Stand J Work Environ Health 1985;11:165-71.
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26. Urabe H, Koda H, Asahi M. Present state of Yusho patients. Ann NY Acad Sci 1979;320:273-6. 27. Assennato G, Cervino D, Longo G. Follow-up dei soggetti cloracneici nell’area di Seveso. Giom Ital Med Lav 1987;9:15-9. 28. Pocchiari F, Silano V, Zampieri A. Human health effects from accidental release of tetrachlorodibenzo-p-dioxin (TCDD) at Seveso, Italy. Ann NY Acad Sci 1979;320: 311-20. 29. Gianotti F. Chloracne au tetrachloro-2,3,7,8-dibenzo-pdioxine chez les enfants. Ann Dermatol Venereol 1977; 104:825-9. 30. Nomura S. Further study of chloracne. Cutis 1974;13: 585-91. 31. Cook RR. Dioxin, chloracne, and soft tissue sarcoma. Lancet 1981;1:618-9. 32. Kligman AM, Mills OH Jr. Acne cosmetica. Arch Dermatol 1972;106:843-850. 33. Mills OH, Kligman AM. Acne mechanics. Arch Dermatol 1975;111:481-3. 34. Moroni P, Pierini F, Cazzaniga R. Occupational exposure to corticosteroids. Med Lav 1988;79:142-9. 35. Litt JZ. McDonald’s acne. Arch Dermatol 1974;110:956. 36. Liden C, Wahlberg JE. Work with video display terminals among office employees. V. Dermatologic factors. Stand J Work Environ Health 1985;11(6):489-93. 37. Wahlberg JE, Linden C. Is the skin affected by work at visual display terminals? Dermatol Clin 1988;6:81-5. 38. Hofmann MF, Meneghini CL. A proposito delle follicolosi da idrocarburi aromatici clorosostituiti (acne clorica). Giom Ital Dermatol 1962;103:427-40. 39. Taylor JS. Chloracne-A continuing problem. Cutis 1974;13:585-91. 40. Deeken JH. Chloracne induced by 2,6dichlorobenzonitrile. Arch Dermatol 1974;109:245.
Acne
KOKELJ
A
cne and acneiform eruptions can be distinguished. The former may be further classifiable into juvenile form, acne venenata, and ,acne caused physical agents. The anatomic substratum of all these forms is the pilosebaceous unit, the role of which in acne pathogenesis has been well described. Although acne vulgaris represents a pathology typical of the sebaceous follicles usually present only on the face and upper trunk, occupational acne may affect all the follicles of the body.’ Occupational acne is a form of acne venenata (venenum = “poison”); it is caused by professional contact with chemical substances as well as by the action of environmental physical agents. It may affect both people with preexistent acne and seborrhea, who worsen after contact, and people without a positive history of these diseases. Especially in the past occupational acne was considered one of the most frequent environmental skin diseases, probably second only to contact dermatitis. Specific risk factors are not necessary, although an aspecific predisposition to seborrhea and preexistent hepatic alteration may influence oil acne and chloracne. From an etiologic point of view, occupational acne may be classified into two forms: chloracne and acne caused by petroleum and its derivatives and coal tar products.
Oil and Coal Tar Acne Oil acne is the most common form of occupational acne although today it is not as frequent as in the past; it is caused mainly by greases and insoluble oils that contain high percentages of mineral oil. It is well known that these substances are comedogenic and, once in contact From
the Department
of Dermatology,
of Trieste,
University
Trieste,
Italy. Address
correspondence to Franc0 Kokelj, 34149 Trieste, Italy.
of Dermatology,
Department
University of Trieste,
0 1992 by Elsevier Science Publishing
Co., Inc.
l
0738-081x/92/$5.00
with human skin, can cause different kinds of skin diseases. The contact may be direct or indirect, through clothes, as often happens in mechanical industry workers. Machine tool operators in metal industry are those most commonly affected. Adams2 lists other workers particularly exposed to oil contact: auto, truck, and aircraft mechanics; roofers; oil well drillers; coke oven workers; petroleum refiners; rubber workers; textile mill workers; and road pavers. In different studies, the incidence of oil folliculitis ranges from 7 to 83% of the exposed people. 3-6 The lower incidence of mineral oil folliculitis reported in recent years is surely related to both the decreased use of pure cutting fluids and the improved hygienic conditions in mechanical industries. Contact with mineral oil may worsen the clinical features of juvenile acne and seborrheic dermatitis in young people. Consequently the lesions may appear in the same site as acne vulgaris, but are more common in nonaffected areas where contact with oil takes place, such as dorsa of the hands and fingers (Fig l), arms and forearms, thighs, and abdomen. The more common clinical picture of oil acne is characterized by the presence of scattered comedonic, usually black, and/or microcystic lesions caused by oil itself; after a prolonged contact with these substances, follicles are closed with consequent irritation, reactive hyperkeratosis, and sebum retention. The microsomal oxygenase enzyme system of the sebaceous gland cells seems to play an important role in the intense cytotoxic reactions to these chemicals.’ These lesions are frequently associated with follicular hyperkeratosis and hair atrophy; inflammation is rare, whereas itching is common, especially in the first phases of infection. Melanosis and dyskeratosis may occur on the face and dorsa of the hands. Polycyclic hydrocarbons can cause dermatitis also when breathed or ingested, as in gas station workers and oil refinery workers; in these cases a polymorphic erup-
213
214
Figure
Clinics in Dermatology 1992;10:213-217
KOKELJ
1.
Oil acne
tion characterized by spinulosis and hyperkeratotic folliculitis may appear, especially in people with preexistent dermatitis. Also, kerosene can cause oil acne; Upreti et al presented a study of 24 subjects chronically exposed to kerosene in a car workshop that revealed a high incidence of oil acne and other dermatologic problems.8 It is well known that certain coal tars have acneigenic, phototoxic, and carcinogenic properties. Coal tar acne shows a marked preference to the exposed areas of the body,9 in particular the malar ones, suggesting airborne distribution of the compounds such as fumes of manipulated materials.
Chloracne Chloracne is a distinctive and often severe form of occupational acne caused by exposure to various chlorinated compounds, which may be toxic not only to the skin but also to the liver and neurologic system. In 1899 Herxheimer first used the term chlorucne to describe four cases of severe acne resulting from environmental contact with potassium hypochlorite electrolytically produced.* Since then the history of chloracne has corresponded to the history of industrial development, with an increasing incidence during war periods. Between World Wars I and II a decrease in the incidence of chloracne was observed, although numerous reports stressed also the possibility of liver involvement. In recent decades a decreasing incidence of chloracne followed the advent of plastics, the gradual substitution of chlorinated hydrocarbons with synthetic resins, and restriction of the use of polychlorinated biphenyls to only closed-system formulations.’ The improvement in hygiene has made chloracne quite rare in Western industries: the most important recent reports of chloracne have not concerned workers but rather people involved in accidents, such as the poisoning by a cooking
oil in Japan in 19681°-13 and the explosion at ICMESA in Seveso, Italy, in 1969.14-16 Chloracne may be caused not only by substances capable of inducing secondary formation of aromatic chloroderivative hydrocarbons (chlorophenols) but also by the use of solvents like trichlorethylene and perchlorethylene. On the contrary, a pathogenetic role of inorganic chlorine may be excluded; in fact, chlorine added to swimming pool water does not cause or worsen acne.” Chlorinated naphthalenes and polyhalogenated biphenylenes are the most common groups of substances able to induce chloracne; they have been widely used for their chemical stability and resistance to acids and alkalis and for their high dielectric properties. It is known that among chlorinated naphthalenes only the pentachloro and hexachloro derivatives can cause chloracne, whereas the mono-, di-, tri-, tetra-, penta-, and octachloronaphthalenes are not acneigenic. 18,19Among the polyhalogenated biphenylenes the brominated compounds are more acneigenic than the chlorinated compounds.20 Chloronaphthalenes have been widely used, especially in the past, as electrical insulators and for fire-resistant materials, whereas polychlorodiphenols have been used in hydraulic fluids, plastics, adhesives, fire retardants, and sealants. Polychlorinated dibenzofurans, possible contaminants of various chlorinated phenols,*’ and azobenzene derivatives have also been reported as possible agents of chloracne. In Table 1 are listed the halogenated aromatic compounds that can cause chloracne. Chloracne may be caused both by contact of the skin with the previously mentioned substances and by ingestion and/or inhalation of fumes produced during preparation and use of chloro derivatives. Endogenous contact can cause systemic intoxication and contribute to the skin
Table 1. Halogenated Can Cause Chloracne
Aromatic
Compounds
That
Polyhalogenated naphthalenes (pentachloro and hexachloro derivatives)‘*-20 Polyhalogenated biphenyls10~11~21 Polybromobiphenyls (PBBs) Polychlorobiphenyls (PCBs) Polyhalogenated dibenzofuranP Polybromodibenzofurans Polychlorodibenzofurans Contaminants of polychlorophenol compounds 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)t4*r6 Hexachlorodibenzo-p-dioxirP Contaminants of 3,4dichloroaniline and related herbicideP 3,4,3’,4’-Tetrachloroazoxybenzene (TCAOB) 3,4,3’,4’-Tetrachloroazobenzene (TCAB) Others 1,2,3,4-Tetrachloroazobenzene2 2,6-Dichlorobenzonitrile40
Clinics in Dermatology 1992;10:213-217
damage, through the slow elimination of chloro derivatives through the pilosebaceous unit. There are many reports about environmental chloracne and related systemic impairment22-25; the massive intoxication described in 1968 in Japan and the disaster at ICMESA (Seveso, Italy) are important and paradigmatic examples of this pathology. The first event took place in 1968 in a rice cooking oil factory in Japan; the oils were contaminated by polychlorinated biphenyls (Kanechlor400) used in the heating coils. The ingestion of contaminated oil caused cliff erent degrees of intoxication in 105 7 people. Different follow-up studies showed that after 3 years, half of the patients were still symptomatic and the acneiform eruptions were the most common problem13; after 10 years skin lesions were no longer observed.26 In 1969 the accidental explosion of a reactor involved in trichlorophenol synthesis, at the ICMESA chemical plant in Seveso, Italy, released a toxic cloud in the atmosphere that contaminated the whole countryside of Seveso, causing the most important reported dioxin intoxication. Dioxin is the term used to describe 2,3,7&tetrachlorodibenzo-p-dioxin (TCDD), an aromatic chlorinated hydrocarbon found mostly as an impurity during the alkaline hydrolysis of tetrachlorobenzene in sodic 2,4,5trichlorophenol used as an herbicide. The toxic cloud containing dioxin caused the death of hundreds of fowl in the first days after the explosion; many people developed chloracne after different lengths of time. Apart from chloracne and some cases of subclinical neurologic damages, no other severe problems, birth abnormalities, or mental retardation was reported in the involved population in the numerous long-term follow-up studies.27,28 The malar region and the areas around the eyes and behind the ears are the most common sites of chloracne. The cheek, neck, and trunk may be involved too; the nose is usually spared except in severe forms. Lesions can extend centrifugally with an increase in the severity of chloracne. Arms, thighs, hands, and feet are consequently affected only in the most serious cases; on the contrary, genitals are often involved and in this site lesions are usually papulonodular. Clinical aspects of chloracne may be both mono- and polymorphic and are characterized by a variety of skin lesions; multiple closed cornedones and microcysts are the first signs of chloracne. Later, inflammatory lesions, increasing in cyst dimensions, follicular pustules, and abscess that may evolve leaving scars have been observed. Hypertrichosis, melanosis on the face, and increased skin fragility are also common. Itching may be intense in about half the patients, whereas in some cases it may even be absent. A generalized skin involvement, with the obvious exclusion of palmar and plantar areas, may be observed
OCCUPATIONAL
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in the most severe cases. Gianotti29 described two different pictures of chloracne in children exposed to the toxic cloud at Seveso: one is characterized by erythema, xerosis, homlike cysts, and atrophy and was usually observed about 3 weeks after the explosion; in the other, diffuse follicular hyperkeratosis was observed after at least 6 weeks and was probably influenced also by endogenous mechanisms (excretion of TCDD through the pilosebaceous follicle and the eccrine sweat glands). One of the main problems with chloracne is that this pathology is often accompanied by systemic involvement; liver and neurologic dysfunction are quite common. Acute yellow atrophy of the liver and porphyria cutanea tarda, the latter especially in laboratory animals, are the most common hepatic disorders reported in the literature.2 We do not know the true incidence of these conditions, because this problem is often underestimated in the exposed workers. The neurologic impairment resulting from chloracne may be characterized by headache, irritability, lacrimation, increased palmar sweating, weakness, peripheral neuritis, and psychiatric symptoms.13,30 In some cases it represents the most important problem, as stressed in the previously mentioned epidemic episode of chloracne observed in 1968 in Japan.13 As far as carcinogenic predisposition is concerned, Cook,31 in a cohort study of workers who had probably been exposed to TCDD, reported two cases who presented with chloracne and malignant fibrous histiocytoma; one of them died of fibrosarcoma and the other of liposarcoma. As both these patients were cigarette smokers, this author hypothesizes also in the absence of an evident cause - effect link, a relationship between smoking and increased risk of soft tissue sarcomas after exposure to TCDD.
Less Common Forms of Occupational Acne Less common forms of occupational acne are characterized by both a worsening of preexistent acne and a new eruption from professional exposure to different substances and/or physical sources. Cosmetic acne and acne resulting from ultraviolet light exposure may be considered as an occupational form for some workers, for example, actors, actresses, and cosmetologists.32 Mills and Kligman reported as occupational disease a mechanical acne in truck drivers who presented with typical lesions on their back as a result of local pressure and rubbing against seat covers.33 Some cases of steroid acne are described in employers in drug companies; a study on the hygienic conditions in a pharmaceutical company where corticosteroids were produced revealed the existence of professional risks because of the presence of chemically active dusts.34 The
216 KOKELJ
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1992;10:213-227 skin lesions, like acne rosaceiform, erythema, and so on, usually precede systemic effects. Improvements in industrial hygienic conditions and a health education program have led to a significant decrease in systemic effects and skin disorders. Litt reports some cases of acne caused by exposure to grease encountered in and fat frying hamburgers that he calls McDonald’s acne.35 In recent years an increasing number of reports have stressed the possible role of video display terminals in inducing skin lesions and, in particular, skin rashes. Liden and Wahlberga6 studied 74 office employees who complained of skin diseases, to correlate these pathologies with work at video display terminals. Furthermore, an increased frequency of acne, seborrheic dermatitis, and rosacea was observed in the exposed group and the possibility of a relationship was accepted, although there was no evidence on the mechanisms that may produce skin damage. 37 In fact, no dangerous radiation has ever been revealed at the distance usually kept by an operator from a video display (at least 60 to 70 cm); consequently the skin eruption reported could be related to other factors, perhaps the stress of people with an aspecific predisposition to skin eruptions. Apart from the originality and curiosity of the reports, the diagnosis of these diseases as occupational may represent an important medical and legal problem to evaluate the effective relationship with the patient’s occupation.
Histology The histology of oil acne is characterized by follicular hyperkeratosis, keratinous cysts, and an aspecific dermal infiltrate with various degrees of sebaceous cell atrophy. These lesions are also observed in chloracne where follicles are usually more widely dilated, sebaceous gland atrophy is more important, and an increase in pigmentation is often present among the involved follicles.38
Diagnosis Occupational acne must be distinguished from acne vulgaris, other forms of folliculitis, and sycosis. Diagnosis of occupational acne requires a thorough knowledge of the substances with which workers may come into contact and of the possible relationship between a specific task and exposure to oils, greases, and chlorohydrocarbons. Folliculitis caused by petroleum and coal tar derivatives may be distinguished from chloracne by the different sites of the lesions; the less frequent presence of cysts, nodules, and pustular evolution; and the rapid improvement once the dangerous exposure has stopped.
Therapy The first step in occupational acne therapy is identification of the causative agent and interruption of the exposure to it. Although oil and coal tar acne usually improves spontaneously when the exposure ceases, chloracne represents a major problem both because of its resistance to common therapies and because of the frequent systemic involvement.39 The various therapeutic modalitites proposed for acne vulgaris are also suggested for treatment of occupational acne. To solve the problem at the industrial level, it is necessary to reduce contamination with the acneigenic substances.
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26. Urabe H, Koda H, Asahi M. Present state of Yusho patients. Ann NY Acad Sci 1979;320:273-6. 27. Assennato G, Cervino D, Longo G. Follow-up dei soggetti cloracneici nell’area di Seveso. Giom Ital Med Lav 1987;9:15-9. 28. Pocchiari F, Silano V, Zampieri A. Human health effects from accidental release of tetrachlorodibenzo-p-dioxin (TCDD) at Seveso, Italy. Ann NY Acad Sci 1979;320: 311-20. 29. Gianotti F. Chloracne au tetrachloro-2,3,7,8-dibenzo-pdioxine chez les enfants. Ann Dermatol Venereol 1977; 104:825-9. 30. Nomura S. Further study of chloracne. Cutis 1974;13: 585-91. 31. Cook RR. Dioxin, chloracne, and soft tissue sarcoma. Lancet 1981;1:618-9. 32. Kligman AM, Mills OH Jr. Acne cosmetica. Arch Dermatol 1972;106:843-850. 33. Mills OH, Kligman AM. Acne mechanics. Arch Dermatol 1975;111:481-3. 34. Moroni P, Pierini F, Cazzaniga R. Occupational exposure to corticosteroids. Med Lav 1988;79:142-9. 35. Litt JZ. McDonald’s acne. Arch Dermatol 1974;110:956. 36. Liden C, Wahlberg JE. Work with video display terminals among office employees. V. Dermatologic factors. Stand J Work Environ Health 1985;11(6):489-93. 37. Wahlberg JE, Linden C. Is the skin affected by work at visual display terminals? Dermatol Clin 1988;6:81-5. 38. Hofmann MF, Meneghini CL. A proposito delle follicolosi da idrocarburi aromatici clorosostituiti (acne clorica). Giom Ital Dermatol 1962;103:427-40. 39. Taylor JS. Chloracne-A continuing problem. Cutis 1974;13:585-91. 40. Deeken JH. Chloracne induced by 2,6dichlorobenzonitrile. Arch Dermatol 1974;109:245.
