This is a rare and unusual complication of silver salts deposited in the skin and internal organs. Both topical and oral ingestion have been implicated.
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EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Rare ACUPUNCTURE
Blue macules of localized argyria caused by implanted acupuncture needles. Electron microscopy and roentgenographic microanalysis of deposited metal.
Tanita Y, Kato T, Hanada K, Tagami H.
Arch Dermatol 1985 Dec;121(12):1550-2 Abstract quote
Acupuncture needles implanted in the skin for more than ten years caused peculiar bluish macules, each of which clinically resembled a blue nevus in the extremities of a 63-year-old Japanese woman.
Histologically, the involved skin showed deposition of fine brownish granules in the basement membrane of the eccrine sweat glands, on the inner surface of the blood vessel walls, and along elastic fibers of the superficial dermis in addition to sparse deposits noted throughout the dermis.
Electron microscopy revealed deposits of electron-dense particles on the basal lamina of the secretory coils of the eccrine sweat glands, below the basal lamina of the dermoepidermal junction, and on elastic fibers.
Roentgenographic microanalysis of the involved skin demonstrated that most of the granules consisted of silver and chloride; silver was a major component in the removed needles.
- J Cutan Pathol. 2006 Dec;33(12):809-11. Abstract quote
Background: Argyria is often considered an entity of the past, one which has largely disappeared with the cessation of silver usage in oral medications. However, with the practice of colloidal silver ingestion in current "alternative health" treatments, argyria should be considered in the differential diagnosis of blue-gray hyperpigmentation.
Methods: A single case report with clinicopathological correlation.
Results: Histological examination of skin biopsy specimen, which showed perieccrine brown-black granules, verified that colloidal silver rather than a prescribed medication was the source of the patient's dyspigmentation.
Argyria following the use of dietary supplements containing colloidal silver protein.
Gulbranson SH, Hud JA, Hansen RC.
Good Samaritan Regional Medical Center, Phoenix, Arizona 85006, USA.
Cutis 2000 Nov;66(5):373-4 Abstract quote
The onset of argyria following the use of dietary supplements containing colloidal silver protein is presented. The patient was using a silver-containing product for cold and allergy prophylaxis.
We review the past and present medicinal roles of silver and include a differential diagnosis for argyria. The hyperpigmentation of argyria is usually permanent, and it follows a sun-exposed distribution.
This case report highlights the potential for toxicity following the use of dietary supplements and demonstrates the importance of physician inquiry regarding alternative medicines. Finally, we examine the limited role of the Food and Drug Administration (FDA) in regulating alternative medicines marketed as dietary supplements.
Argyria caused by an earring.
Sugden P, Azad S, Erdmann M.
Department of Plastic Surgery, Shotley Bridge Hospital, Consett, County Durham, DH8 0NB, UK.
Br J Plast Surg 2001 Apr;54(3):252-3 Abstract quote
The staining of skin by silver is termed argyria and is grey-blue in colour. This may be caused by a number of mechanisms such as ingestion and direct implantation.
We report an unusual case, caused by an impacted earring, where the skin discoloration was not entirely typical of argyria. This may have been due to copper impurities present in the earring. The literature on the subject is also reviewed.
DISEASE ASSOCIATIONS CHARACTERIZATION HEMODIALYSIS
Generalized argyria in two chronic hemodialysis patients.
Sue YM, Lee JY, Wang MC, Lin TK, Sung JM, Huang JJ.
Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China.
Am J Kidney Dis 2001 May;37(5):1048-51 Abstract quote
Silver can be absorbed through ingestion, topical administration, or inhalation. Generalized argyria results from deposition of silver in the skin, nails, mucous membranes, and internal organs and is characterized by a diffuse bluish-gray discoloration in sun-exposed areas.
We report two cases of generalized argyria in patients on maintenance hemodialysis (HD) therapy for more than 15 years. They presented with diffuse hyperpigmentation of the face that was mistaken to be related to uremia and bluish-gray discoloration of all nails believed to be cyanosis. Histopathologic examination of skin biopsy specimens showed characteristic findings of argyria, which was further confirmed by radiograph microanalysis. Their serum silver levels were also elevated.
No definite silver source could be determined. However, their argyria might be related to their long-term HD therapy because (1) they had been on HD therapy for more than 15 years and the discoloration appeared several years afterward, and (2) the water used for HD was not well processed in the early 1980s in TAIWAN.
Argyria should be suspected in chronic HD patients presenting with a diffuse bluish-gray discoloration of the skin and nails and evaluated carefully by skin biopsy.
Localized argyria with pseudo-ochronosis
Leslie Robinson-Bostom, MD
David Pomerantz, MD
Caroline Wilkel, MD, etal.
Providence, Rhode Island, Kingsport, Tennessee, and Boston, Massachusetts
J Am Acad Dermatol 2002;46:222-7 Abstract quote
Background: Localized argyria is uncommon and presents clinically as asymptomatic slate gray macules or blue macules resembling blue nevi. Its histopathologic features are usually similar to those of generalized argyria in which silver granules are found most commonly around the eccrine glands, in the walls of blood vessels, and along elastic fibers. Ochre swollen homogenized collagen bundles resembling ochronosis have not been previously described.
Objective: The purpose of this study is to report a series of 5 patients with localized argyria with the histologic feature of “pseudo-ochronosis.” In one patient, biopsy was performed on 2 distinct lesions.
Methods: All patients underwent skin biopsies for light microscopy and darkfield microscopy. In two patients, the biopsy specimens were analyzed with a mass spectrophotometer; scanning electron microscopy and energy-dispersive x-ray analysis were performed. In one patient, the biopsy specimen was decolorized with 1% potassium ferricyanide in 20% sodium thiosulfate. Results: All 5 patients presented with the typical clinical and histologic features of localized argyria. Ochre swollen and homogenized collagen bundles were seen in all cases. In addition, light microscopy in 4 cases revealed an ellipsoid black globule within a zone of collagen degeneration.
Conclusion: The histologic features of localized argyria include swollen and homogenized collagen bundles resembling ochronosis, “pseudo-ochronosis,” which may be more common than previously recognized.
PATHOGENESIS CHARACTERIZATION GENERAL
Generalized argyrosis in man: neurotological, ultrastructural and X-ray microanalytical findings.
Westhofen M, Schafer H.
Arch Otorhinolaryngol 1986;243(4):260-4 Abstract quote
Generalized argyrosis can produce a number of abnormalities, including skin discoloration, liver and kidney dysfunction.
We describe a patient with generalized argyrosis following long-term self-treatment with oral silver intake, in whom skin discoloration, progressive taste and smell disorders, vertigo and hypesthesia were observed. These findings were confirmed by chemosensory tests and electrophysiological investigations. The development of hypogeusia was assessed by subjective tests, while the progression of hyposmia was followed by recording olfactory evoked cortical potentials. Light and electron microscopy of tissue samplings demonstrated electron-dense mineral deposits in basal membranes, in macrophages, in the perineurium of peripheral nerves, along elastic and collagenous fibers, and in necrotic cells of the oral submucosa. Silver and sulfur deposits in affected tissues could be defined by X-ray microanalysis. The quantitative ratio between silver and sulfur in involved tissues was similar to that of an inorganic silver-sulfide (Ag2S) standard. The minute increase in the sulfur content when compared to the inorganic standard suggested a sulfur containing organic matrix of the tissue precipitates.
Our findings indicate that the affinity of silver for membrane and neuronal structures and the deposition of silver as an insoluble compound (Ag2S) induce the progression of clinical disease.
CHARACTERIZATION RADIOLOGIC LABORATORY MARKERS X-RAY MICROANALYSIS
Argyria: microanalytic-morphologic correlation using paraffin-embedded tissue.
Landas S, Bonsib SM, Ellerbroek R, Fischer J.
Ultrastruct Pathol 1986;10(2):129-35 Abstract quote
Scanning electron microscopes, which have energy dispersive spectroscopy (x-ray microanalysis) capability, can provide accurate identification of the composition of inorganic deposits in tissue.
We report a case of florid argyria in which the same deparaffinized 4-micron sections were sequentially examined by light microscopy, scanning electron microscopy, backscattered electron imaging, and x-ray microanalysis to confirm the clinical impression of argyria.
We recommend the use of x-ray microanalysis of paraffin-embedded tissue as a simple, rapid and inexpensive means of precise identification of inorganic deposits of heavy elements in tissue sections.
CHARACTERIZATION GENERAL VARIANTS BRAIN
Brain involvement in generalized argyria.
Dietl HW, Anzil AP, Mehraein P.
Clin Neuropathol 1984 Jan-Feb;3(1):32-6 Abstract quote
Cutaneous argyria was diagnosed in a 59-year-old woman. Manic depressive psychosis developed at about the same or a short time thereafter. The patient died 6 years later from a ruptured aortic aneurysm.
At autopsy silver deposits were seen in skin, mucous membranes, heart, kidney, and liver. In the central nervous system the leptomeninges and choroid plexuses contained silver granules. In addition, silver granules were visualized in the walls of many intraparenchymal vessels, particularly of the basal ganglia, hypothalamus, substantia nigra, and cerebellum. Progressive glial changes and cellular gliosis were evident in many areas of the brain.
With the electron microscope the deposition of silver granules in basal membrane structures of the choroid plexus and intracerebral vasculature was amply confirmed. Furthermore, silver deposition was seen in brain parenchymal cells inside bodies of apparently lysosomal nature. The silver content of various brain regions was determined by absorption spectrophotometry.
CORNEAL AND VISUAL ABNORMALITIES
The ocular manifestations and functional effects of occupational argyrosis.
Moss AP, Sugar A, Hargett NA, Atkin A, Wolkstein M, Rosenman KD.
Arch Ophthalmol 1979 May;97(5):906-8 Abstract quote
Thirty employees of an industrial plant involved in the manufacture of silver nitrate and silver oxide underwent ophthalmologic evaluation in an effort to evaluate the frequency and extent of ocular argyrosis.
The most frequently noted ocular abnormality was pigmentation of the conjunctiva, present in 20 workers; corneal pigmentation occurred in 15 workers. A direct relationship existed between the levels of pigmentation and duration of employment. Ocular pigmentation was seen more frequently than cutaneous pigmentation.
Ten workers noted decreased night vision, but electrophysiologic and psychophysiologic studies of seven of these ten workers demonstrated no functional deficits.
Multifocal corneal argyrosis after an explosion injury.
Schlotzer-Schrehardt U, Holbach LM, Hofmann-Rummelt C, Naumann GO.
Department Of Ophthalmology, University Nurnberg, Erlangen, Germany.
Cornea 2001 Jul;20(5):553-7 Abstract quote
PURPOSE: To document the clinical and histopathologic corneal features of a patient who developed multifocal corneal argyrosis after a chemical explosion injury with unusual involvement of the corneal stroma and keratocytes.
METHODS: The corneal button was investigated by light and transmission electron microscopy and scanning electron microscopy combined with energy-dispersive x-ray microanalysis.
RESULTS: Clinically, the patient showed dark discoloration of the lids, periocular skin, episclera, and conjunctiva and had multiple brown dots in the superficial layers of the cornea. Microscopic examination of the cornea showed diffuse deposition of silver particles in the epithelial basement membrane, Bowman's layer, and Descemet's membrane. In the corneal stroma, silver granules accumulated intracellularly within lysosomal structures of degenerative keratocytes and extracellularly in association with collagen fibers and cellular debris. Energy-dispersive x-ray analysis showed peaks of silver and sulfur.
CONCLUSION: The toxic influence of intracellular accumulation of silver in stromal keratocytes may lead to cell damage and necrosis and result in visual impairment.
Argyria: the intradermal "photograph," a manifestation of passive photosensitivity.
Shelley WB, Shelley ED, Burmeister V.
J Am Acad Dermatol 1987 Jan;16(1 Pt 2):211-7 Abstract quote
X-ray microprobe and electron microscopic study was made of the remarkable blue-black pigmentation that sunlight elicits in patients with argyria.
The patient under study had developed argyria following injection of silver nitrate as a sclerosant into his varicose veins 41 years ago. Similarities are demonstrated between the darkening of the skin and the darkening of a photographic film following light exposure. In both instances, colorless silver salts and compounds present in an inert matrix (collagen versus gelatin) are reduced by incident light to black metallic silver.
This passive photosensitivity reaction leads to silver tattooing of the light-exposed skin and to photographic imaging in the film.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Generalized argyria. Clinicopathologic features and histochemical studies.
Arch Dermatol 1978 Mar;114(3):373-7 Abstract quote
In three cases of generalized argyria, the degree of slate-gray cutaneous discoloration varied from barely perceptible to pronounced. Deposition of silver-containing granules in and around cutaneous adnexal structures was best seen with darkfield microscopy.
Histochemical studies suggested that the granules consisted of silver sulfide. Indiscriminate use of currently available silver-containing medications can result in generalized argyria.
- Scar-localized argyria secondary to silver sulfadiazine cream.
Fisher NM, Marsh E, Lazova R.
Department of Dermatology, Yale University, New Haven, Connecticut 06520-8059, USA.
J Am Acad Dermatol. 2003 Oct;49(4):730-2. Abstract quote
Silver sulfadiazine cream is a topical antibacterial agent that combines the antibacterial effects of both silver and sulfadiazine. Its reported cutaneous side effects include hypersensitivity reactions, allergic contact dermatitis, erythema multiforme, and systemic argyria.
We report the case of a patient who had localized argyria develop in a scar after the use of silver sulfadiazine cream.
In this case, the silver sulfadiazine cream was applied to and argyria developed within a postsurgical wound and area of severe contact dermatitis.
CHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE ELECTRON MICROSCOPY
Occupational argyria; light and electron microscopic studies and X-ray microanalysis.
Bleehen SS, Gould DJ, Harrington CI, Durrant TE, Slater DN, Underwood JC.
Br J Dermatol 1981 Jan;104(1):19-26 Abstract quote
Microscopic studies have been performed on skin biopsies from five patients with occupational argyria. Small brown-black granules were present in the dermis on light microscopy and were intensely refractile with dark-field illumination.
Electron microscopy showed that the granules were electron-dense, round or oval in shape and varied in size from 30 nm to 100 nm. They were most numerous in relation to the basal lamina of the eccrine sweat glands, but were also present in relation to the basal lamina of the epidermis and dermal elastic fibres.
X-ray microanalysis confirmed that many of the granules contained silver and sulphur. However, selenium, mercury, titanium and iron were also identified and it is probable that these elements were deposited in the skin also as a result of occupational exposure.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES HEART DISEASE
Argyria and cyanotic heart disease.
Am J Hosp Pharm 1977 Mar;34(3):287-9 Abstract quote
A case report in which argyria is mistaken for cyanotic heart disease is described. A discussion of argyria, a benign cosmetic condition resulting from either ingestion or the local application of silver salts or colloidal silver, is presented.
It is suggested that by obtaining comprehensive drug histories, maintaining patient profiles, and through patient counseling, pharmacists are in a position to identify and advise on known cases of argyria.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS GENERAL
Argyria: clinical implications of exposure to silver nitrate and silver oxide.
Rosenman KD, Moss A, Kon S.
J Occup Med 1979 Jun;21(6):430-5 Abstract quote
This article reports the clinical findings in a work force of 30 individuals who were exposed to silver nitrate and silver oxide.
Six individuals had argyria and 20 had argyrosis (deposition of silver in the eye). Measurements of blood silver levels were included as part of the examination. The results of this examination generally support the benign nature of argyria, although the question of silver causing a decrement in kidney function and night vision is not settled.
Periodic slit lamp examinations as well as monitoring of silver air concentrations are necessary to assure that engineering controls are actually limiting worker exposure to silver.
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