Occupational Granulomas
Skin
ANDREA STEFANO BIGARDI, MD, PAOLO DANIELE PIGATTO, MD, PAOLO MORONI, MD
T
he term grunuloma is used to describe a histopathologic entity corresponding to a palpable and visible elementary nodular lesion. The nodule may vary from just a few millimeters to some centimeters in size’; it is round and is sometimes surrounded by an erythema, which is also present in biotic forms,2 although is more frequently absent in the case of old lesions. It is generally asymptomatic and has a hard consistency. Granuloma may involve the epidermis alone, the dermis alone, both the epidermis and dermis, or only the subcutis.3,4
Definition Granuloma is characterized by a chronic proliferative inflammatory skin reaction5 surrounded and delimited by healthy tissue. The penetration into the skin of a number of substances may give rise to a foreign-body granulomatous reaction; these substances include wood, silk, nylon, paraffin, silicon, talcum powder, starch, oils, animal and vegetable spines or bristles, and human hair.5 Histology distinguishes two types of granuloma: the more frequent foreign-body granuloma and allergic granuloma. Contact allergic granulomatous reactions have been described in subjects sensitized to zirconium, beryllium, and some tattoo colorants.6 A foreign-body granuloma may “transform itself” (histologically speaking) into an allergic skin granuloma when the etiologic agent remains in the lesion for some time and, in the final analysis, behaves as an allergen, This possibility evidently leads to a difference in patient prognosis: renewed contact with the substance present in the granulomatous lesion triggers a new clinical manifestation.3 From the Department of Dewnatofogy II and Department of Occupational Medicine, University of Milan, Milan, Italy. Address correspondence to Andrea Stefano Bigardi, Department of Dermatology II, University of Milan, Via Pace, 9, 20122 Milan, Italy.
0 1992 by Elsevier Science Publishing
Co., Inc.
l
0738-081x/92/$5.00
In both forms, microscopic examination reveals macrophages and giant cells with, at the center of the lesion, lymphocytes, monocytes, and occasionally epithelioid cells. The detection of epithelioid and giant cells and the presence or absence of a central necrotic zone with a caseous appearance are very important in making a differential histopathologic diagnosis of allergic granuloma. The presence of phagocytic macrophages is considered to be a central event in the formation of foreign-body granulomas’; this macrophagic tendency is limited or totally absent in allergic granuloma. It has been proposed that, in addition to foreign-body and allergic granulomas, it is also possible to classify and differentiate granulomas from infectious agents (as in inguinal granulomas and acute leishmaniasis) and tissue injury granulomas (such as annular granuloma and lipoidie necrobiosis).s Although, from a histopathologic point of view, it is correct to distinguish these four entities, we have adopted the classic distinction between foreign-body and allergic granulomas; from the clinical point of view, given that our main interest is in occupational diseases, etiologic classification has been considered preferable. The main target organs of external aggressive granulomatous disease are the respiratory apparatus and the skin; and in both cases, numerous forms have been reported to occur in working environments. On the basis of these premises, the most frequent causes of occupational granulomas are now analyzed, with particular reference to those affecting the skin. Occupational granuloma, dermatologic or otherwise, is a well-known and well-defined nosographic entity.6
Significant
Types
In recent years, occupational respiratory granulomatous disease has been studied and monitored because it is the cause of numerous and severe cases of occupational dis-
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ability. An emblematic case is that of mineworkers whose pulmonary picture after inhalation of mineral dusts (pneumoconiosis) is epidemiologically well known; although caused mainly by silica, pneumoconiosis may also be caused by asbestos, cadmium, beryllium, and other metals.9 The constant exposure of mineworkers to mineral dusts leads to the onset of foreign-body granulomatous lesions which create bronchial obstruction by mechanical compression and induce emphysema and dyspnea. In the case of beryllium and its salts (particularly oxide salts), occupational medicine recognizes a specific pathologic picture which bears witness to its pulmonary aggression: berylliosis. lo At an industrial level, beryllium (mainly in the form of beryllium fluoride) is used in the production of fluorescent lamps; light copper, nickel, and iron alloys; and, in small quantities, the production of steel. After penetrating the skin, beryllium causes allergic rather than foreign-body granulomas.“J* Beryllium allergic granuloma may therefore occur not only in mineworkers, but also in people working in the production of metals, fluorescent lamps, and x-ray screens.13 Cases of simultaneous lung and skin beryllium granuloma have also been described.r4J5 Highly purified zirconium is used as a deoxidant and catalyzer in the construction and lining of atomic reactors, although it is more frequently used in steel production. Zirconium contact occupational skin granulomas in workers who frequently handle steel or alloys with a high steel content have been reported16 as having a particular clinical presentation: multiple, rather than individual, lesions with a lupoid appearance. In the past, nonoccupational zirconium granulomas have been described in users of deodorants containing this metal.” The clinical manifestations were slightly pruritic yellowish axillary nodules and, as witness to their immunologic pathogenesis, patch test reactivity was type IV.12 Cadmium is a bivalent metal that is used as an anticorrosive and, in association with nickel, copper, and silver, in the production of conducting alloys. One of its salts (cadmium sulfide) is used as a colorant for paints and rubber; cadmium acetate is used in the production of craftware. In literature are reports of cadmium granulomas with a sarcoid-like appearance. l8 The frequent difficulty in making a histopathologic diagnosis is confirmed by a reported case in which it was not even possible to make a histologic distinction between sarcoidosis and foreignbody granuloma. This was a man who, 10 years after having been injured by a bomb explosion, presented with a papular nodular lesion at the same site. Bioptic examination was incapable of providing a precise diagnosis;
Figure
1.
A clinical
picture of milker’s hand.
only x-ray spectographic analysis revealed the presence of silica particles and demonstrated foreign-body etiogenesis.19 Finally, to conclude this section on granulomas caused by metals and their salts, it must be mentioned that even nickel can (albeit rarely) cause a nonoccupational contact granulomatous reaction.12,20
Infectious Granuloma So-called “milker’s hand’ has been the subject of a large number of published articles.21,23 This occupational dermatosis, which sometimes has an atypical appearance and localization,24 is due to infection following pox virus inoculation; but it may also be caused by foreign-body granulomas produced by a chronic granulomatous inflammatory response to penetration of the skin by cow Figure 2. A histological examination to demonstrate presence of a piece of the hair in the lesion.
the
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Figure 3. A magnification
of
Figure 2.
hairs during milking and their persistence in situ. The same type of disease has also been observed in people who clean dogs.i3 Painless flat or raised nodules appear on the hands and/or arms, and there is a moderate general symptomatology with locoregional lymphadenomegaly. The skin presents deep irregularly shaped rhagadiform fissures of variable length, particularly in the interdigital creases; as a result of the penetration of fragments of mammary hair during milking, the direction of the fissures is always at an angle to the cutaneous plane. The presence of hair fragments leads to the onset of a granulomatous process which subsequently becomes colliquative and suppurative with fistulation. About 15 days need to pass from the moment of inoculation to the development of granuloma. This form of dermatosis generally resolves itself over 30 to 40 days without an aftermath. From a clinical and etiopathogenetic point of view, this form is very similar to that described in barbers,4*26 which occurs when the cutis is penetrated by fragments of hair (particularly at the level of the interdigital creases) and which similarly gives rise to the appearance of granulomas and fistulas. Interdigital pilonidal sinus, or “barber’s hair sinus,” is not the only form of occupational dermatitis associated with this type of activity; allergic contact dermatitis from the constituents of hair dyes is also well known.*’ Interdigital pilonidal sinus is a foreign-body granuloma with a highly variable course. Given its asymptomatic nature, it may be observed just by chance; on the other hand, it may become suppurative even at an early stage and, thus, lead to fistulation. It presents as a cutaneous inflammatory nodule, generally localized to the second or third interdigital space on the hand, with a black spot in the center (the points of penetration of the hair); in the suppurative phase, the orifice is always cov-
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ered by a serohematic crust. Among the hypotheses concerning the pathogenesis of this condition, the most accredited is that which considers the interdigital space as a locus minoris resistentiae resulting from occupational contact with detergents, constant steeping in water, and repeated traumas from cutting instruments.28,29 It is certain that the central event is the penetration of the epidermis and dermis by a hair, followed by a foreign-body granulomatous reaction. Only a few cases have been reported in the literature, possibly because both patients and doctors consider it a disease of little count. Interdigital pilonidal sinus seems to affect only men’s hairdressers, perhaps because of the particular characteristics of men’s hair or the type of haircutting involved.27 A case of subungueal trichogranuloma has recently been described in a hairdresser for both men and women. The case appears interesting because subungual involvement is not frequently described in the literature and because the patient was suffering from psoriatic onycholysis, which can be considered a promoting disease.30 Another, albeit rare cause of occupational skin granuloma is the starch found in surgical gloves; once it penetrates the skin, the starch can give rise to a foreign-body granuloma.3 The intradermal penetration of the oils used in high-pressure air-compressed lubrication can cause oleomas (or oleogranulomas), which appear as yellowish, rarely phlegmatic nodules. A continuous cutis solution in an environment containing high concentrations of carbon particles can lead to the formation of brown indelible tattoos in exposed workers (eg, miners); histologic examination reveals the foreign-body granulomatous nature of such lesions.13 Among the biotic agents reported internationally since the 195Os, important granulomas include those caused by atypical mycobacteria, in particular Mycobacterium marinum,31-33 the manifestations of which are localized to the hands of people who, for work or pleasure, come into contact with the aquaria in which this microorganism seems to find its ideal habitat. The increasingly frequent reports of occupational contact granulomas from biotic agents (particularly aquatic microorganisms) are dealt with in another article in this issue (see article by Veraldi, Rizzitelli, and SchianchiVeraldi).
Other
Types
A number of other agents reported in the literature can be mentioned that, although they do not involve occupa-
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tional environments, can cause skin granulomas; some of these cases are very rare and anecdota13* Contact with corticosteroid dust caused annular granuloma in one woman, with lesions localized to the knees and elbows.35 The practice of tattooing can lead to the onset of granuloma because of the phagocytosis of macrophages contained in pigmenting substances. The iatrogenous origin of some granulomas can be suspected as a result of vaccine, collagen, and insulin inoculations. In the case of vaccines, this is due to the substance on which they are absorbed (aluminium hydroxide) giving rise to foreign-body granuloma3; it is also possible that allergic granuloma may appear in subjects already sensitized to the same substance.** As is the case with silica, talc (or magnesium silicate) can induce the formation of foreign-body granulomas when it is spread on open wounds.5
Conclusions
8. Epstein WL. 1977;16:574-9. 9. Harrison Vallardi,
Cutaneous
granulomas.
RT. Principi di medicina 1977;3:316-7.
Int
intema
J Dermatol
e terapia.
Milan:
10. Sneddon IB. Berylliosis: A case report. Br Med J 1955;1:1448. 11. Curtis CH. Cutaneous hypersensitivity to beryllium. Arch Dermatol 1951;64:470-82. 12. Sertoli A. Dermatologia allergologica professionale ed ambientale. Milan: 11 Pensiero Scientifico, 1991;1:169, 170. 13. Lachapelle JM. Dermatologia son, 1986:14,15.
professionale.
Milan:
Mas-
14 Chiappino G, Cirla A, Vigliani EC. Delayed-type hypersensitivity reactions to beryllium compounds. An experimental study. Arch Path01 1969:87:131-140. 15. Folesky H. Comments matosen 15:93 - 103.
on beryllium
granuloma.
Berufsder-
16. Palmer L, Walton W. Lupus miliaris disseminata faciei: Zirconium hypersensitivity as possible cause. Cutis 1967; 71744-8.
When it is not possible to remove the causal agent noninvasively, the treatment of foreign-body granuloma involves surgical excision’ in cases obviously requiring it. As has already been said, milker’s nodules usually resolve spontaneously and do not call for any treatment. On the other hand, interdigital pilonidal sinus usually requires surgical correction. Allergic granulomas need to be carefully observed over time. In addition to resolving the granuloma itself, every effort must be made to avoid contact with the sensitizing agent.
20. Stransky L. Contact granuloma tis 1987;15:106-118.
References
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Clinics in Dermatology 1992;10:279-223 29. Downing JG. Barber’s pilonidal sinus. JAMA 1952;148: 501. 30. Hogan DJ. Subungual trichogranuloma in a hairdresser. Cutis 1988;42:105-6. 31. Norden A, Line11 F. A new type of pathogenic mycobacterium. Nature 1951;168:826. 32. Alessi E, Finzi AF, Prandi G. Infezioni cutanee da Mycobacterium marinum. Considerazioni su due casi clinici. G Ital Min Dermatol 1976;111:85-90.
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33. Angelini G, Filotico R, De Vito D, et al. Infezioni cutanee professionali da Mycobacterium marinum. Boll Dermatol AIlergol Prof 1990;5:165-75. 34. Gutierrez Ortega MC, Martin Moreno L, Arias Palomo D, et al. Facial granuloma caused by cactus bristles. Cutanea Ibero-Latino-Americana 1990;18:197-200. 35. Morelli M, FumagalIi M, Ahomare GF, et al. Contact granuloma annulare. Contact Dermatitis 1988;18: 317-8.