Introduction
Background
Argyria results from prolonged contact with or ingestion of silver salts. Argyria is characterized by gray to gray-black staining of the skin and mucous membranes produced by silver deposition. Silver may be deposited in the skin either from industrial exposure or as a result of medications containing silver salts.
The most common cause of argyria is mechanical impregnation of the skin by small silver particles in workers involved in silver mining, silver refining, silverware and metal alloy manufacturing, metallic films on glass and china, electroplating solutions, and photographic processing. Colloidal silver dietary supplements are marketed widely for cancer, AIDS, diabetes mellitus, and herpetic infections.1,2,3 Cases have followed the prolonged use of silver salts for the irrigation of urethral or nasal mucous membranes, in eye drops, wound dressing, and the excessive use of an oral smoking remedy containing silver acetate.4,5
Argyria has also been attributed to surgical and dental procedures (eg, silver amalgam-tattooing, silver sutures used in abdominal surgery). Blue macules have appeared at sites of acupuncture needles and silver earring sites.6,7 Great individual variability exists in the length of exposure and total dose needed to result in argyria.
Pathophysiology
Localized argyria occurs in the conjunctiva or oral mucous membrane after long-term topical treatment with silver salt solutions or short-contact acupuncture.
Universal argyria can develop after long-term systemic treatment with drugs that contain silver salts. This used to occur in patients who had taken silver protein suspension for chronic gastritis or gastric ulcer or as nose drops.8 Argyria also happens as an occupational disease in workers who prepare artificial pearls or who are employed in the cutting and polishing of silver (absorption of silver dust).
The normal human body contains approximately 1 mg of silver; the smallest amount of silver reported to produce generalized argyria in humans ranges from 4-5 g to 20-40 g. Silver at 50-500 mg/kg body weight is the lethal toxic dose in humans.
Bianchi et al report a possible genetic predisposition for argyria.9
Frequency
United States
Argyria has become a rare dermatosis, mainly because of the avoidance of silver-containing compounds as medicinals and a decrease in occupational exposure in the silver industry. Exposure to silver was common in the early part of this century. The famous Blue Man, a member of the Barnum and Bailey Circus sideshow, had a classic case of argyria.
Clinical
History
A careful history is necessary. Be sure to inquire about possible occupational and environmental exposure, the use of dietary supplements in general, and colloidal silver protein dietary supplements in particular.
- Habitual use of silver-based nose drops may produce pigmentation most apparent on the nose and the nail lunulae.10
- Scar-localized argyria may occur secondary to silver sulfadiazine cream.11
Physical
- Early on, a gray-brown staining of the gums develops, later progressing to involve the skin diffusely. The cutaneous pigmentation usually is a slate-gray, metallic, or blue-gray color and may be clinically apparent after a few months, but clinical appearance usually takes many years and depends on the degree of exposure.
- The hyperpigmentation is most apparent in the sun-exposed areas of skin, especially the forehead, nose, and hands.
- In some patients, the entire skin acquires a slate blue-gray color.
- The sclerae, nail beds, and mucous membranes may become hyperpigmented.
- Viscera tend to show a blue discoloration, including the spleen, liver, and gut, findings evident during abdominal surgery or at postmortem examination.
Causes
Although pigmentary changes occur primarily in sun-exposed sites, granules are evenly deposited throughout all skin. Differing theories exist as to why the blue-gray pigmentation is restricted to sun-exposed sites. Some believe that silver compounds complexed with proteins in the skin are reduced to elemental silver by light, similar to the process of photo imaging. Others contend that silver plus light stimulates melanogenesis, which results in the blue-gray color.
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References
Bouts BA. Images in clinical medicine. Argyria. N Engl J Med. May 20 1999;340(20):1554. [Medline].
Fung MC, Bowen DL. Silver products for medical indications: risk-benefit assessment. J Toxicol Clin Toxicol. 1996;34(1):119-26. [Medline].
Gulbranson SH, Hud JA, Hansen RC. Argyria following the use of dietary supplements containing colloidal silver protein. Cutis. Nov 2000;66(5):373-4. [Medline].
Brandt D, Park B, Hoang M, Jacobe HT. Argyria secondary to ingestion of homemade silver solution. J Am Acad Dermatol. Aug 2005;53(2 Suppl 1):S105-7. [Medline].
Gaslin MT, Rubin C, Pribitkin EA. Silver nasal sprays: misleading Internet marketing. Ear Nose Throat J. Apr 2008;87(4):217-20. [Medline].
Legat FJ, Goessler W, Schlagenhaufen C, Soyer HP. Argyria after short-contact acupuncture. Lancet. Jul 18 1998;352(9123):241. [Medline].
Rackoff EM, Benbenisty KM, Maize JC, Maize JC Jr. Localized cutaneous argyria from an acupuncture needle clinically concerning for metastatic melanoma. Cutis. Nov 2007;80(5):423-6. [Medline].
Prescott RJ, Wells S. Systemic argyria. J Clin Pathol. Jun 1994;47(6):556-7. [Medline].
Bianchi L, Orlandi A, Di Stefani A, Ricci R, Chimenti S. "Familial" generalized argyria. Arch Dermatol. Jun 2006;142(6):789-90. [Medline].
Menaguale G, Fazio R, Fazio M. Argyria: a case following the prolonged use of a rhinologic drug. Esper Dermatol (Roma). 2003;4:299-303.
Fisher NM, Marsh E, Lazova R. Scar-localized argyria secondary to silver sulfadiazine cream. J Am Acad Dermatol. Oct 2003;49(4):730-2. [Medline].
Graham SA, O'Meara JM. The feasibility of measuring silver concentrations in vivo with x-ray fluorescence. Phys Med Biol. Aug 7 2004;49(15):N259-66. [Medline].
Lee SM, Lee SH. Generalized argyria after habitual use of AgNO3. J Dermatol. Jan 1994;21(1):50-3. [Medline].
Robinson-Bostom L, Pomerantz D, Wilkel C, et al. Localized argyria with pseudo-ochronosis. J Am Acad Dermatol. Feb 2002;46(2):222-7. [Medline].
Sato S, Sueki H, Nishijima A. Two unusual cases of argyria: the application of an improved tissue processing method for X-ray microanalysis of selenium and sulphur in silver-laden granules. Br J Dermatol. Jan 1999;140(1):158-63. [Medline].
Rhee DY, Chang SE, Lee MW, Choi JH, Moon KC, Koh JK. Treatment of argyria after colloidal silver ingestion using Q-switched 1,064-nm Nd:YAG laser. Dermatol Surg. Oct 2008;34(10):1427-30. [Medline].
Further Reading
Keywords
argyria, universal argyria, localized argyria, ingestion of silver salts, contact with silver salts, staining of skin, silver staining
