Localized Cutaneous Argyria at the Site of a Prior Melanoma Excision Confirmed by Scanning Electron Microscopy With Energy Dispersive X-ray Analysis.

ABSTRACT: Localized cutaneous argyria is a rare condition caused by the accumulation of silver particles in the skin, leading to blue-gray discoloration. Argyria may mimic melanoma and lead to misdiagnosis. We present a patient with a history of melanoma that developed a blue-gray nodule at a prior melanoma graft. The diagnosis was confirmed using scanning electron microscopy and energy dispersive x-ray analysis. These techniques differentiate argyria from melanoma and can be performed on formalin-fixed, paraffin-embedded, tissue sections. Health care providers should be alert that argyria may mimic recurrent melanoma in patients unaware of silver exposure.

Distribution, metabolism, excretion, and toxicity of implanted silver: a review.

Some implantable medical devices contain silver. We aimed to assess at what amount implanted silver becomes toxic. Silver was elevated in bodily fluids and tissues surrounding silver-containing implants. Silver released from implants also distributes to blood and other tissues; there is evidence to suggest silver can pass the blood-brain-barrier. Silver can be deposited as nano-sized particles in various tissues. Such particles, in addition to silver, often contain other elements too, e.g., selenium and sulfur. Silver released from implants seems to stay in the body for long periods (years). Reported excretion pathways following implantation are urinary and fecal ones. Reported toxicological effects were virtually all local reactions surrounding the implants. Argyria is a blue-gray discoloration of the skin due to deposited silver granules. Localized argyria has been described after the implantation of acupuncture needles and silver-coated prostheses, although the presence of silver was tested only for and shown in the former. Other toxicological effects include local tissue reactivity and examples of neurotoxic and vascular effects. We did not include genotoxicity studies in the present publication as we recently evaluated silver to be genotoxic. Carcinogenicity studies were absent. We conclude that local toxicity of implanted silver can be foreseen in some situations.

Occupational Localized Cutaneous Argyria With Pseudo-Ochronosis in a Jeweler.

ABSTRACT: A case of localized argyria in a 36-year-old female jeweler is described who presented with 2 discrete and asymptomatic bluish-black pigmented macules on the pulp of her left middle finger. A skin biopsy from both lesions demonstrated deposition of brown/black pigmented granules along the basement membrane zone of eccrine glands, blood vessels, nerves, and the dermo-epidermal junction fully in keeping with silver deposition. In addition, there was yellow-brown deposition seen within the interstitial dermis mimicking an early form of ochronosis, so called "pseudo-ochronosis." This latter feature is rarely described in cases of argyria. Transmission electron microscopy and energy dispersive x-ray spectroscopy confirmed the presence of electron dense particles up to 150 nm in diameter and the presence of silver, respectively. On further questioning, the patient had a history of localized and chronic exposure to silver, which specifically involved holding and manipulating silver wires and rings over the left middle finger. This case highlights an unusual and rare presentation of localized argyria in a jeweler. In addition, our case showed preferential silver deposition on dermal elastic fibers which has not been previously described in the literature.

Localized cutaneous argyria: Review of a rare clinical mimicker of melanocytic lesions.

Localized cutaneous argyria is a rare cutaneous disorder that has been associated with occupational exposure, dental procedures, topical agents, acupuncture, earrings, and nasal piercings. In this paper, we review the current literature on localized cutaneous argyria, highlight its clinical and histologic diagnostic features, and then discuss the clinical and histological differential diagnoses for blue-gray skin and black dermal pigment, respectively. We also discuss the utility of ancillary techniques, such as deeper histologic levels, special stains, darkfield microscopy, and advanced micro-analytical techniques in helping diagnose localized cutaneous argyria. Furthermore, we emphasize that a thorough clinical history and astute clinico-pathologic correlation can be the most important diagnostic techniques in correctly diagnosing this rare disorder. Our review aims serve as a reminder to clinicians and pathologists of the importance of including localized cutaneous argyria in the clinical and histological differential diagnosis of pigmented lesions.

A clinical mimicker of melanoma with distinctive histopathology: Topical silver nitrate exposure.

Exposure to silver-containing compounds can result in reversible discoloration of the skin, presenting as an irregular brown or black macule, which can have a clinical appearance similar to melanoma. Both the clinical scenario and the histopathology are unique. Silver nitrate darkens with exposure to light, and the area can appear to change over time. On microscopic examination, there are coarse pigmented granules dispersed throughout the corneal layer, and largely absent from the remainder of the epidermis-although the precise location may depend on the duration of topical exposure. While argyria, its irreversible counterpart, has been well-characterized, only a single source has previously reported the histopathology of transient topical silver nitrate exposure. We present two cases, review the clinical and histopathologic differentials, and detail the distinctive histopathology that enables a diagnosis to be suggested in this clinical mimicker of melanoma.

Argyria, an Unexpected Case of Skin Discoloration From Colloidal Silver Salt Ingestion.

BACKGROUND: Argyria is a rare condition characterized by gray/blue dislocation of the skin caused by chronic exposure to silver salts. CASE REPORT: We review the case of an 81-year-old man who presented to the emergency department after a motor vehicle accident, was incidentally found to have skin discoloration, and was ultimately diagnosed with argyria. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although most emergency physicians will not complete a toxicology fellowship, all emergency physicians are on the front line of toxicological presentations and should be able to recognize argyria and differentiate this condition from other causes of skin discoloration.

Case Report: In Vivo Confocal Microscopic Appearance of Corneal Argyrosis.

SIGNIFICANCE: This report details the natural history of corneal argyrosis over 3 years using in vivo confocal microscopy to document regression of hyperreflective deposits, as well as effects on corneal nerves and endothelial cell morphology. PURPOSE: To report the in vivo confocal microscopic features and clinical characteristics of a case of bilateral corneal argyrosis. CASE REPORT: A 52-year-old man referred to us 3 months following cautery of the palpebral conjunctiva of both eyes with a silver nitrate stick was observed over the course of 3 years, during which slit-lamp photography and in vivo confocal microscopy were performed. At the first visit, slit-lamp examination showed a light blue-green discoloration and a thick, yellow, oval discoloration in the right and left cornea, respectively. One year later, under slit-lamp examination, the right cornea appeared nearly transparent, and the discoloration in the left cornea had remarkably regressed. In vivo confocal microscopy done at that time showed highly reflective deposits in Descemet membrane of the right cornea and throughout Bowman layer, the stroma, and Descemet membrane of the left cornea. Three years later, no accumulation of silver was observed during slit-lamp examination of either eye. In vivo confocal microscopy of the right cornea did not reveal any silver deposits, and the corneal structure appeared normal. In the left cornea, some silver deposits were still evident in Descemet membrane, and alterations of corneal nerve and endothelial cell morphology were also evident. CONCLUSIONS: This report reviews the 3-year natural history of a patient with corneal argyrosis. In vivo confocal microscopy demonstrates that over time the corneal argyrosis gradually resolves without any treatment. However, the presence of silver in the cornea may impact the corneal nerves and endothelial cells.

Mucocutaneous Hyperpigmentation in a Patient With a History of Both Minocycline and Silver Ingestion.

Minocycline is a derivative of tetracycline. It has been widely used in dermatology for the treatment of acne and rosacea. One of its adverse effects is pigmentation of various body tissues. Clinically, 3 main distinct types of hyperpigmentation by minocycline have been distinguished: type I, with blue-gray to black pigment on the face in areas of scarring or inflammation; type II, with blue-gray pigment on normal skin of the legs, forearms and on the shins; and type III, with a diffuse muddy-brown discoloration in areas of sun exposure. In the current report, we present the case of a 50-year old man with a history of severe acne treated with minocycline in the past, who currently complained about discoloration of his face. He had also taken colloidal silver supplements for "good health" about 16 years ago. Physical examination revealed gray-blue discoloration on the face, sclera, hard palate and back. Histologic examination showed intracellular pigment deposits in macrophages of the superficial dermis in a perivascular and an interstitial distribution. The pigment stained with Fontana-Masson and von Kossa, whereas it was Perls' iron negative. This case does not fit well into any of the previously described patterns of minocycline-related hyperpigmentation.

In vivo reflectance confocal microscopy characterization of silver deposits in localized cutaneous argyria.

Localized cutaneous argyria is a rare condition secondary to skin deposition of silver following exposure to substances containing this metal. The clinical appearance and dermoscopy findings require deep melanocytic lesions and particularly melanoma metastasis to be ruled out. Silver deposits are usually confirmed by scanning electron microscopy and/or energy-dispersive X-ray spectroscopy. Herein we describe the in vivo reflectance confocal microscopy (RCM) features observed in one case of localized cutaneous argyria. These features include the presence of a hyperrefractile network in the papillary dermis and a periadnexal dotted bright pattern. In vivo RCM might be a useful tool for an early diagnosis of this uncommon entity.

Diffractive microscopy in dermatopathology.

Diffraction is the process by which a beam of light is spread out as a result of passing through a narrow aperture or across an edge. Light diffraction can be produced by closing the aperture diaphragm beyond the recommended setting, by flipping the condenser cone down, or by using an opaque object such as the microscopist's hand to block the column of light and force it to bend around the edge. Any of these techniques results in greater refractility of objects in the path of the light. We studied 77 biopsy specimens from a variety of conditions selected to compare the value of diffractive microscopy, and found that it worked best in the evaluation of alopecia, tumor stroma, hemosiderin, argyria and imipramine pigmentation. In amyloidosis stained with Congo red and silica granuloma, polarized microscopy was superior to diffraction microscopy, and neither diffractive microscopy nor polarized microscopy was superior to routine light microscopy in the evaluation of melanin, chrysiasis or ochronosis.

Diagnostic methods in ocular argyrosis: case report.

PURPOSE: The aim of this report is to present a case of a patient, metal foundry worker, who had been exposed to industrial silver salts for over 20 years. It is well established that chronic exposure to silver compounds can cause accumulation of silver deposits in various tissues. This condition is referred to as argyrosis or argyria, whereas changes related to eye tissues are defined as ocular argyrosis. METHODS: A complete eye examination, corneal confocal microscopy, kinetic and static visual field test, posterior segment optical coherent tomography, pattern visual evoked potentials (PVEP), flash visual evoked potentials, multifocal electroretinogram, pattern electroretinogram (PERG), full-field electroretinography (FERG) and electrooculogram were all performed. RESULTS: Eye examination revealed decreased visual acuity, corneal deposits and drusenoid changes within the macula. Although electrophysiology tests did not show changes in the function of retinal pigment epithelium, they revealed abnormal function of photoreceptors in the central and peripheral retina. PERG abnormalities and delayed latency of P100 wave in PVEP confirmed impaired function of the inner layers of the retina in the macular region. CONCLUSIONS: Corneal confocal microscopy and electrophysiological tests may help confirm the diagnosis of ocular argyrosis.

Pauci Immune crescentic glomerulonephritis in a patient with T-cell lymphoma and argyria.

BACKGROUND: Silver is a transition metal, toxic when ingested in significant amounts, causing argyria (skin deposition) and argyrosis (eye deposition). It is excreted mainly via the gastrointestinal tract with only small amounts eliminated by the kidneys, and rarely have cases of nephrotoxicity due to silver been reported. Here we present the case of a woman who used colloidal silver as an alternative remedy for a T cell lymphoma, who subsequently developed argyria and a pauci-immune crescentic glomerulonephritis with evidence of extensive glomerular basement membrane silver deposition. CASE PRESENTATION: A 47 year old woman of Indo-Asian descent with a T-cell lymphoma who refused conventional chemotherapy for 18 months but self-medicated with a remedy containing colloidal silver, was admitted with acute dialysis-dependent kidney injury. A kidney biopsy demonstrated a pauci-immune crescentic glomerulonephritis with deposition of silver particles in the mesangium and along the glomerular basement membranes. The patient was treated with intravenous methylprednisolone and intravenous cyclophosphamide and recovered independent renal function. CONCLUSION: Chronological evolution of the the pauci-immune glomerulonephritis suggests that a cellular immune-mediated process was induced, potentially mediated by lymphomatous T cells directed at the glomerular basement membrane, following silver deposition. Immunosuppressive therapy improved the situation and allowed cessation of haemodialysis, supporting the hypothesis of an immune-mediated process.

Localized cutaneous argyria: Report of two patients and literature review.

BackgroundLocalized cutaneous argyria is a rare skin condition caused by direct contact with silver or silver particles. It presents as asymptomatic gray or blue-gray macules that appear similar to blue nevi. Histologic features include brown-colored or black-colored silver granules in the basement membrane and dermis, most commonly surrounding eccrine glands, elastic fibers, and collagen fibrils. The condition is most frequently observed in individuals who are regularly exposed to small silver particles, such as silversmiths and welders. However, localized cutaneous argyria has also been associated with acupuncture needles, silver earrings, and topical medications containing silver nitrate. Although the condition is benign, patients who are concerned about the cosmetic features of localized cutaneous argyria may benefit from laser therapy.PurposeWe describe the clinical and pathologic findings of two women who developed localized cutaneous argyria. We also review the characteristics of other patients with localized cutaneous argyria and summarize the differential diagnosis and treatment options for this condition.Materials and methodsThe features of two women with localized cutaneous argyria are presented. Using PubMed, the following terms were searched and relevant citations assessed: acquired localized argyria, acupuncture, argyria, argyrosis, colloidal silver, cutaneous argyria, and localized cutaneous argyria. In addition, the literature on localized cutaneous argyria is reviewed.ResultsTwo women presented with small, asymptomatic blue-gray macules appearing at sites directly adjacent to ear piercings. A punch biopsy was performed on one woman. Microscopic examination revealed a yellowish-brown colored granular material found adjacent to elastic fibers. Based on correlation of the clinical presentation and histopathologic findings, a diagnosis of localized cutaneous argyria was established. The second woman did not undergo a biopsy. However, the clinical presentation was highly suggestive of localized cutaneous argyria. Both women were reassured of the benign nature of the condition and agreed to return for clinical follow-up if they observed any changes in the appearance of the lesions.

1064 nm Q-switched Nd:YAG laser for the treatment of Argyria: a systematic review.

Argyria is a benign skin disease characterized by blue to slate-grey discoloration that is caused by deposition of silver granules in the skin and/or mucus membranes as a result of long-term ingestion of ionized silver solutions or exposure to airborne silver particles. The skin discoloration can be generalized or localized and is exacerbated by sunlight. The skin discoloration is usually permanent, and until recently, there has been no effective treatment for argyria. Over the past 6 years, a number of case reports and one case series have described cases of argyria that were successfully treated with a 1064 nm Q-switched (QS) neodymium-doped yttrium aluminium garnet (Nd:YAG) laser; however, a review of these studies has never been reported in the dermatologic literature. To review the use of the 1064 nm QS Nd:YAG laser for the treatment of argyria. A search of the National Library of Medicine's PubMed Database and the SCOPUS Database was performed to find articles that detailed the treatment of argyria with 1064 nm QS Nd:YAG laser. Six articles were selected for inclusion in this review. Each article was reviewed and summarized in a table. A 1064 nm QS Nd:YAG laser offers a novel and effective treatment for argyria. A systematic review of the dermatologic literature revealed a limited number of case reports and case series using this treatment. However, the results gleaned by the authors from the literature review provide important information to the clinician. For patients with argyria, a single pass of the 1064 nm QS Nd:YAG laser offers immediate, effective and sustained pigment clearing without any long-term adverse effects.

Resident Rounds: Part III - Case Report: Argyria ­ A Case of Blue-Gray Skin.

Argyria is an uncommon blue-gray pigmentation of the skin (increased in sun-exposed areas), nail unit, and mucous membranes caused by prolonged silver exposure. Commonly occurs in the setting of occupational exposure, silver-containing medications, or systemic absorption from use of silver sulfadiazine on extensive burns/wounds. Recently, there appears to be an increase in the practice of colloidal silver ingestion given the popularity and easy availability of alternative medicines and dietary supplements containing various silver-containing compounds. We report a case of argyria in a 72-year-old male following ingestion of colloidal silver as a supplement for over 10 years. He had a diffuse, blue-gray discoloration of his face and nails. A skin biopsy was performed and histology supported the clinical diagnosis of argyria. Our objective is to increase the awareness for this rare dermatologic entity by highlighting the clinical and histological features through a case report. Dermatologists should warn patients in regards to the use of colloidal silver for alternative health practices.