Argyria (ISV from Greek: αργύρος argyros silver + -ia) is a disease caused by the ingestion of elemental silver, silver dust or silver compounds. The most dramatic effect of argyria is that the skin is colored blue or bluish-grey. Argyria may be found as generalized argyria or local argyria. Argyrosis is the corresponding condition related to the eye. The condition is believed to be permanent. Most recent cases are due to the over consumption of home made colloidal silver as an alternative medicine.

Since at least the early part of the 20th century, doctors have known that silver or silver compounds can cause some areas of the skin and other body tissues to turn gray or blue-gray. Argyria occurs in people who eat or breathe in silver over a long period (several months to many years). A single exposure to a silver compound may also cause silver to be deposited in the skin and in other parts of the body; however, this is not known to be harmful. It is likely that many exposures to silver are necessary to develop argyria. Once argyria develops, it is believed to be permanent. However, the condition is thought to be only a "cosmetic problem". Most doctors and scientists believe that the discoloration of the skin seen in argyria is the most serious health effect of silver (in small doses).

Reports of cases of argyria suggest that gram amounts (from 2 to 4 grams) of silver or a silver compound taken in medication in small doses over several months may cause argyria in some humans. People who work in factories that manufacture silver can also breathe in silver or its compounds. In the past, some of these workers have become argyric. However, the level of silver in the air and the length of exposure that caused argyria in these workers is not known. It is also not known what level of silver causes breathing problems, lung and throat irritation, or stomach pain in people. Studies in rats show that drinking water containing very large amounts of silver (9.8 grams of silver per U.S. gallon water or 2.6 grams per liter) is likely to be life-threatening.

There is very little information about health effects following skin contact with silver compounds. Argyria that covers the entire body is not seen following skin contact with silver compounds, although the skin may change color where it touches the silver. However, many people who have used skin creams containing silver compounds such as silver nitrate and silver sulfadiazine have not reported health problems from the silver in the medicine. In one animal study, a strong solution of silver nitrate (81 milligrams silver nitrate per liter of water) applied to the skin of guinea pigs for 28 days did not cause the animals to die; however, it did cause the guinea pigs to stop gaining weight normally. It is not known if this would happen to people if they were exposed the same way.

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Argyria of nasal mucosa secondary to occupational silver exposure
From Australian Journal of Oto-Laryngology, 5/1/03 by Wei, Benjamin P C

Objectives: The aim of this paper is to present a rare cause of nasal mucosa pigmentation from silver exposure and the management of the condition.

Materials and Methods: A case of argyria of the nasal mucosa secondary to silver exposure in the photographic processing industry is presented.

Results: The clinical, histological findings of the nasal mucosa are consistent with the patient's occupational exposure to the silver compound.

Conclusion: Argyria is a rare cause of nasopharyngeal mucosa pigmentation. The condition is suspected from patients with a history of chronic silver exposure. Biopsy of the mucosa is required for the diagnosis. Argyria does not increase the risk of nasopharyngeal carcinoma. Although silver itself is relative non-toxic to human body, appropriate occupational safety measures arc required to prevent the exposure of other toxic chemical compounds that are bound to the silver.

Key words: Aygyria, silver exposure, black pigmentation of nasal mucosa, industrial safety measures.

Introduction

Argyria is a rare condition that is caused by the permanent deposition of silver in the skin and the mucosa membrane. This results in a life long slate-grey pigmentation of the tissues. The deposition of silver in the eyes is known as argyrosis.1,2 This report includes a case of argyria of the nasal mucosa as a result of the silver exposure from the photographic film industry with the details of the management.

Case Report

The patient had worked in the photography industry for many years preparing photosensitive media. He had a past history of chronic sinusitis and had three previous sinus surgeries. The presenting complaint was of recurrent right frontal headaches. Examination of the nasal cavities resembled a bluish-black discoloration of the nasal septal mucosa, the head of the middle and the inferior turbinates. (Figure 1)

The biopsy of sinonasal mucosa showed an extensive deposits of minute brown-black granules in the collagen of the stroma with features of argyria. (Figure 2) The pigment resisted melanin bleach. Initially, Rhodanine stain for silver did not show the typical brown colour expected for silver. However, the stain was performed on paraffin sections as the specimen was fixed in formalin. When Rhodanine stain was performed on frozen sections at a later date, typical brown colouration of silver was seen in the specimen.

Discussion

Argyria of the nasal mucosa appeared as a bluish-black discoloration. The differential diagnosis of a localised pigmentation that may resemble a localised argyria include melanoma,3,4 bismuth deposition and other heavy metal staining for example mercury and gold.5 Both Addison's disease and haemochromatosis can also cause a localised black pigmentation of nasal mucosa.5

In the reported case, the patient had been working in the industry of manufacturing of photographic film for many years. In the preparation of photosensitive materials, silver nitrate is poured into a solution with sodium halides in gelatine to precipitate silver halides.6 The exposure to silver from his work is consistent with the silver deposit that was found extensively in his nasal mucosa.

In general, the diagnosis of argyria is made by occupational history and by noting the discoloration that may occur on the skin, and mucus membrane or conjunctivae. Characteristically, the workmen's face, hands, and arms develop a dark slate-grey colour, which is uniform in distribution and varies in depth depending on the degree of the exposure. The discoloration can also occur in nasal, bronchial mucosa, fingernails and toenails. Covered parts of the body are affected to a lesser degree by the discoloration.7 Procedures to confirm the silver exposure include skin, mucosa biopsy, slit lamp examination of eye and blood level measurement. Slit lamp examination appears to be the best method to measure body burden to silver.8 Blood silver levels appear to reflect recent exposure only.8 No specific treatment, such as the use of chelating agents, is available or indicated.7 There is no complete effective and safe treatment for the removal of silver from the skin or the nasal and oral-pharyngeal mucosa.6,9 The only treatment of the cosmetic disability of argyria that has shown any success was the local application of a 5% hydroquinone cream on skin over a period of one year to patients with the occupational argyria. This reduced the number of silver granules particularly in the upper dermis and around the eccrine sweat glands.

From the extensive human, animal, clinical, epidemiological studies and occupational exposure studies, excessive silver absorption does not appear to produce any conclusive and recognizable disturbance of health.2,7,8,10 It has been postulated that the toxic effects of silver is neutralised by binding with selenide as well as sulfide and then bind to a protein to form the electron dense granules.6,10,11 Interesting, Stammberger12 described the possible association between argyria and nasopharyngeal carcinoma. However this view has not been supported by the available literatures and experimental studies. There were also isolated reports of associating silver exposure and neuropathy13,14 or renal damage15. However, the exact pathogenesis of these diseases induced by the silver was unclear and other cofounders like chemical compounds that were bound with the metallic silver may have caused the problems rather than the silver itself. The possibility of renal damage was raised by Owens and colleagues study16 but when examining this paper carefully, it was probably the sulfadiazine component of the sulfadiazine silver that caused the nephrotic syndrome and not the silver itself.

Occupational Silver Exposure

The issue of the control of the silver exposure at work includes ensuring that workplace occupational exposure standard (OES) are met, wearing of protective clothing and rigorous hygiene following the shift or before eating. Although there is no proven medical risks from silver exposure, the following medical work-up is suggested for cases of occupational argyria. The surveillance should include: screening for respiratory tract irritation or discoloration;6,10 eye and skin discoloration, and burns;6,10 decreased night vision,6,10 renal function tests,10 alkaline phosphatase levels,10 and history of abdominal pain.10,17 The OES for silver compounds is 0.01mg/m^sup 3^(8 hour time-weight average reference period) with an OES for metallic silver of 0.1mg/ m^sup 3^ 18,19,20 Recent or continuing exposure can be detected by measuring blood silver levels.

Haker and Hunter21 reviewed a number of cases of occupational argyria at the beginning of the last century and also found that the handling of silver nitrate in photography caused both the localised and generalised argyria. Other authors have also found an extensive silver deposition in the nasal mucosa of workers from the silver process industry including: silver refiners,18,19 silver nitrate, silver oxide or salts (nitrate, fulminate, or cyanide) manufacturers7,17,18 silver solderers,22 silver plating, in the manufacture of silverware, tableware, coins, jewellery, in production of electrical apparatus, mirrors,6,9 indelible inks, hair dyeing, porcelain colouring, ivory etching and silver alloys.7,20

The rationale of the management strategy is to screen organ systems that may be affected by chemical compounds frequently used in association with the silver. It is important for the clinicians to be aware of that apart from occupational induced argyria of nasal mucosa, the use of silver compound in the field of rhinology can also contribute to localised and generalised argyria. The use of silver nitrate in the therapy of epistaxis had been reported by Mayall and Wild to cause permanent pigmentation resembling melanoma.23 Tanner and Gross24 reported a case of argyria of the nasal and oral mucosa from the use of 10% silver nitrate solution as nose drops to treat postnasal drip. Landas and colleagues25 also reported a similar case.

Conclusions

A case of argyria of the nasal mucosa is presented. The chronic exposure to silver compounds both in medical and industrial settings can lead to permanent bluish-black discoloration of oral and nasopharyngeal mucosa. A similar localised mucosa pigmentation can also be seen in melanoma, Addison's disease, haemachromatosis, bismuth deposition and other heavy metal staining for example mercury and gold. Biopsy of the lesion is required for the diagnosis. A detail history of the industrial exposure and the preventive measures are needed in the risk patients. There are no safe ways of removing the pigmentation and there is no association with an increase in risk of neoplasm of oral-nasopharyngeal mucosa membrane.

Reference

1. MOSS A.P., SUGAR A., NEWELL A., ET AL. The Ocular Manifestations and Functional Effects of Occupational Argyrosis. Arch. Ophthalmol 1979; 97:906-908.

2. SPENCER W.H., GARRON L.K., CONTRERAS F., ET Al. Endogenous and exogenous ocular and systemic silver deposition. Trans. Ophthal. Soc. U.K. 1980; 100(1): 171-178.

3. McMAHON J.T., BERGFELD W.F. Metallic cutaneous contaminant mimicking malignant melanoma. Cleve. Clin. Q. 1983; 50:177-181.

4. SARSFUELD P., WHITE J.E., THEAKER J.M. Silverworker's finger: an unusual occupational hazard mimicking a melanocytic lesion. Histopathology 1992; 20: 73-75.

5. HILL W.R., MONTGOMERY H. Argyria: with special reference to the cutaneous histopathology. Archives of Dermatology 1942; 44:588-599.

6. HUMPHREYS S.D.M., ROUTLEDGE P.A. The toxicology of silver nitrate. Adverse Drug React. Toxicol. Rev. 1998; 17(2/3): 115-143.

7. BROOKS S.M. Lung disorders resulting from the inhalation of metals. Clinics in Chest Medicine 1981; 2(2): 235-254.

8. PIFER J.W., FRIEDLANDER B.R., KINTZ R.T., STOCKDALE D.K. Absence of toxic effects in silver reclamation workers. Scand J Work Environ Health 1989; 15:210-221.

9. BLEEHEN S.S., GOULD D.J., HARRINGTON C.I., ET AL. Occupational argyria; light and electron microscopic studies and X-ray microanalysis. Brit. J. Dermatol 1981; 104:19-26.

10. ROSENMAN K.D., MOSS A., KON S. Argyria: clinical implications of exposure to silver nitrate and silver oxide. J Occup Med 1979; 21(6) 430-5.

11. MATSUMURA T., KUMAKIRI M., OHKAWARA A., ET AL. Detection of Selenium in Generalized and Localized Argyria: Report of four cases with x-ray microanalysis. J of Dermatol 1992; 19:87-93.

12. STAMMBERGER H. Argyrosis of the Nasal Mucosa. Laryng. Rhinol. Otol. 1982; 61: 234-237.

13. ROWLAND PAYNE C.M.E., BLADIN C., CLOCHESTER A.C.F., ET AL. Argyria from excessive use of topical silver sulphadiazine. Lancet 1992; I: 126.

14. VIK H., ANDERSEN K.J., JULSHAMN K., ET AL. Neuropathy caused by silver aborption from arthroplasty cement. Lancet 1985; 1: 872.

15. KOJIMA Y., UCHIDA K., TAKIUCHI H. ET AL. Argyrosis of the urinary tract after silver nitrate instillation: report of a case. Jinyokika kiyo 1993; 39:41-4.

16. OWENS C.J., YARBROUGH D.R., BRACKETT N.C., ET AL. Nephrotic syndrome following topically applied sulfadiazine silver therapy. Arch Intern Med 1974; 134:332-335.

17. MOSS A.P., SUGAR A., HARGETT N.A., ET AL. The ocular manifestations and functional effects of occupational argyrosis. Arch Opthamol 1979; 97:906-908.

18. WILLIAMS, N. Longitudinal medical surveillance showing lack of progression of argyrosis in a silver refiner. Occup Med (Oxford) 1999; 49(6): 397-9.

19. WILLIAMS N., GARDNER I. Absence of symptoms in silver refiners with raised blood silver levels. Occup Med 1995; 45:205-208.

20. ARMlTAGE S.A., WHITE M.A., WILSON H.K. The determination of silver in whole blood and its application to biological monitoring of occupationally exposed groups. Ann Occup Hyg 1996; 40(3): 331-338.

21. HAKER J.M., HUNTER D. Occupational Argyria. Br J Dermatol 1935; XL VII: 441-55.

22. SCROOGES M.W., LEWIS J.S., PROIA A.D. Corneal argyrosis associated with silver soldering. Cornea 1992; 11:264-269.

23. MAYALL F., WILD D. A silver tatto of the nasal mucosa after silver nitrate cautery. J Laryngol Otol 1996; 110:609-610.

24. TANNER L.S., GROSS D.J. Generalised argyria. Cutis 1990; 45:237-239.

25. LANDAS S., BONSIB S.M., and ELLERBROEK R. Argyria: microanalytic-morphologic correlation using paraffin-embedded tissue. Ultrastruct Pathol 1986; 10:129-135.

BENJAMIN P.C. WEI, STEPHEN O'LEARY and PENNY McKELVIE

Royal Victorian Eye and Ear Hospital

Victoria

Australia

Benjamin P.C. Wei M.B.B.S.

Stephen O'Leary B.Med.Sc., Ph.D., F.R.A.C.S.

Penny McKelvie M.B.B.S., F.R.C.P.A.

Department of Otolaryngology and Pathology,

The Royal Victorian Eye and Ear Hospital

Correspondence to:

Dr Benjamin Wei

1 Queensberry Street, Carlton 3053, Victoria

e-mail: bjnwie@hotmail.com

Tel: (03) 9496 5000 Fax: (03) 9662 2878

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