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A unique specimen of argyria is preserved in the Morgagni Museum of Pathological Anatomy at the University of Padua (Italy). It is a stuffed head belonging to a man who decided to cure his syphilis by himself with the so-called infernal stone (silver nitrate) every day for years, thus developing argyria in the second half of the nineteenth century. Paleopathological and historical studies were performed on the specimen to confirm the diagnosis of argyria. Furthermore, a morphological investigation of the specimen was conducted with histological and ultrastructural investigations, including environmental scanning electron microscopy and electron dispersive x‐ray spectroscopy, recording high presence of silver in the dermis and epidermis and also other chemical elements correlated to the “infernal stone.” A comparison with actual cases may also lead to a common feature: a potential dependence on the perceived benefits brought by silver compound that may sustain a further prolonged intake.

PURPOSE: To highlight the novel application of anterior segment optical coherence tomography (AS-OCT) to detect corneal silver deposition in a case of ocular argyrosis. METHODS: This is a case report and review of the literature. RESULTS: A 67-year-old male with a 30-year history of chronic occupational exposure to silver-halides secondary to photographic film manufacturing presented with significant ocular argyrosis. His ophthalmic exam was notable for bilateral, widespread pinpoint grey deposits throughout his conjunctiva and cornea at the level of Descemet’s membrane. Further evaluation with AS-OCT showed deposition in two distinct, diffusely hyper-reflective bands, corresponding to Bowman’s layer and Descemet’s membrane. CONCLUSIONS: AS-OCT provides a useful imaging modality in evaluating corneal deposition diseases. In this case of ocular argyrosis, AS-OCT led to the detection of a hyper-reflective Bowman’s layer as well as Descemet’s membrane, representing silver deposition in both of these anatomic locations.

Exogenous pigmentation by silver nitrate is a rare disease whose clinical manifestations appear even years after the contact, making its diagnosis difficult on occasions. It is characterized by the presence of blue-gray macules or plaques on the skin or mucosa in the contact area, sometimes very similar to melanocytic lesions and melanoma, which constitute the main differential diagnosis. We report the case of a male patient from Medellín, Colombia, with a family history of melanoma and the presence of these lesions throughout his body.La pigmentación exógena por nitrato de plata es una enfermedad poco frecuente, cuyas manifestaciones clínicas pueden aparecer años después del contacto, lo que en ocasiones dificulta su diagnóstico. Se caracteriza por la presencia de máculas o placas azul-grisáceas en la piel o las mucosas de la zona de contacto que, en ocasiones, son muy similares a las lesiones melanocíticas y al melanoma, sus principales diagnósticos diferenciales. Se reporta el caso de un paciente de Medellín, Colombia, con antecedentes familiares de melanoma y presencia de estas lesiones en todo el cuerpo.

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.

International audience; BACKGROUND:Silver-containing dressings are considered to be safe even though there have been some reports of complications, including argyria and various organ system dysfunctions. Despite the widespread use of silver dressings, little research has been done regarding the absorption and toxicity of silver.OBJECTIVE:We aimed to study the systemic absorption of silver in patients with chronic inflammatory wounds and to determine associated factors of systemic silver absorption and evaluated its association with silver toxicity.PATIENTS AND METHOD:Prospective, longitudinal, observational, multicentre, open-label pilot study. Patients from the Dermatology Departments of Lorraine (France) with the following inclusion criteria: (i) a chronic wound of more than 6 weeks and (ii) an ulcer needing silver-containing dressing were included. Before and after 28 days of treatment, clinical characteristics of the wound were recorded; hemogram, hepatic and renal functions, albumin sera and serum silver level were measured.RESULTS:Half of the cases displayed raised levels of silver after 1 month of treatment. Predictive factors for systemic silver absorption were wound area, anaemia and malnutrition with anaemia and malnutrition confirmed on multivariate analysis. Wound vascularization may also play a role, as a higher absorption was observed in cases of wound granulation without arterial components. No toxicity was detected. This work has also emphasized the slow elimination of silver from the body.CONCLUSION:Both long-term application and iterative treatments with silver dressings should be discouraged, especially in the elderly, who often suffer from malnutrition and anaemia to avoid potential cumulative toxicity.

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.To report the in vivo confocal microscopic features and clinical characteristics of a case of bilateral corneal argyrosis.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.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.

A biopsy specimen from the nasal mucosa of a 37-year-old man disclosed a subepithelial accumulation of black granules mainly running parallel to the surface in the absence of any inflammatory infiltrate. Since the mucosal pigment was negative with Perls’ stain and resisted to melanin bleach, an exogenous pigmentation was suspected. The biopsy specimen had been taken because of a diffuse steel-blue pigmentation of the nasal mucosa, incidentally discovered during routine clinical examination. A diagnosis of occupational argyria of the nasal mucosa was finally made since the patient was a silver cleaner. Argyria is a rare cause of nasopharyngeal mucosal pigmentation; it is not a precancerous condition, but it can be mistaken for a melanosis or a melanocytic tumor both clinically and histopathologically. Clinicopathological correlation is mandatory, since the final diagnosis is based on a history of chronic silver exposure.

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.

The aims of this study were to evaluate the incidence of local argyria in patients with silver-coated megaprostheses and to identify a possible association between argyria and elevated levels of silver both locally and in the blood. Between 2004 and 2011, 32 megaprostheses with silver coatings were implanted in 20 female and 12 male patients following revision arthroplasty for infection or resection of a malignant tumour, and the levels of silver locally in drains and seromas and in the blood were determined. The mean age of the patients was 46 years (10 to 81); one patient died in the immediate post-operative period and was excluded.Seven patients (23%) developed local argyria after a median of 25.7 months (interquartile range 2 to 44.5). Patients with and without local argyria had comparable levels of silver in the blood and aspiration fluids. The length of the implant did not influence the development of local argyria. Patients with clinical evidence of local argyria had no neurological symptoms and no evidence of renal or hepatic failure. Thus, we conclude that the short-term surveillance of blood silver levels in these patients is not required.Cite this article: Bone Joint J 2013;95-B:988–92.

Biofilm-producing bacteria are the principal causes of infections associated with orthopaedic implants. We previously reported that silver-containing hydroxyapatite (Ag-HA) coatings exhibit high antibacterial activity against methicillin-resistantStaphylococcus aureus(MRSA). In the present study, we evaluated the effects of Ag-HA coating of implant surfaces on biofilm formation. Titanium disks (14-mm diameter, 1-mm thickness), one surface of which was coated with HA or 0.5%–3.0% Ag-HA with a thermal spraying technique, were used. In vitro, the disks were inoculated with an MRSA suspension containing4×105 CFU and incubated for 1-2 weeks. In vivo, MRSA-inoculated HA and 3% Ag-HA disks (8.8–10.0 × 108 CFU) were implanted subcutaneously on the back of rats for 1–7 days. All disks were subsequently stained with a biofilm dye and observed under a fluorescence microscope, and biofilm coverage rates (BCRs) were calculated. The BCRs on the Ag-HA coating were significantly lower than those on the HA coating at all time points in vitro (p<0.05). Similar results were observed in vivo (p<0.001) without argyria. Ag-HA coating reduced biofilm formation by MRSA in vitro and in vivo; therefore, Ag-HA coating might be effective for reducing implant-associated infections.

Silver is used worldwide in dressings for wound management. Silver has demonstrated great efficacy against a broad range of microorganisms, but there is very little data about the systemic absorption and toxicity of silver in vivo. In this study, the antimicrobial effect of the silver-coated dressing (SilverCoat(®)) was evaluated in vitro against the most common microorganisms found in wounds, including Pseudomonas aeruginosa, Candida albicans, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae. We also performed an excisional skin lesion assay in mice to evaluate wound healing after 14 days of treatment with a silver-coated dressing, and we measured the amount of silver in the blood, the kidneys and the liver after treatment. Our data demonstrated that the nylon threads coated with metallic silver have a satisfactory antimicrobial effect in vitro, and the prolonged use of these threads did not lead to systemic silver absorption, did not induce toxicity in the kidneys and the liver and were not detrimental to the normal wound-healing process.

Keywords Minocycline .Tetracycline .Blueskinpigmentation .BlackbonediseaseCase PresentationA 61-year-old man was brought to the emergency department(ED) for shortness of breath, fatigue, frequent falls, and bluishdiscoloration of his skin. The primary care physician trans-ferred the patient due to concern for cyanosis. On presentationto the ED, the patient was oriented but appeared fatigued. Thepatient was afebrile and had the following vital signs: bloodpressure 161/88 mmHg, pulse 71/min, respiratory rate 16/min,and oxygen saturation 100 % on room air by fingertip pulseoximetry. On physical exam, pupils were 4 mm and reactivebilaterally, extraocular movements were intact, and there wasno nystagmus. Anicteric sclerae were notable for blue pigmen-tation (Fig. 1). Heart sounds were regular, without murmurs,rubs, or gallops. Lung sounds were clear to auscultation bilat-erally. Other thanataxia, the neurological exam was unremark-able. The skin had a generalized bluish tinge, especially on thearms,withdarkerpigmentationonthecheeks(Figs. 2,3and4).There was acne on the back and facial rosacea. Bluish discol-oration was also noted under the proximal nail beds (Fig. 5).When questioned about the skin discoloration, the patient andhisfamilymembersdescribedaninsidiousonset.Photographsof the patient from years ago confirmed that this was notcongenital. Medical history included acne, orthostatichypotension, and Parkinson's disease, for which a deep brainstimulator had been surgically implanted. A comprehensivemedication list was not immediately available; however, thepatientdeniedanyrecentmedicationadditionsoradjustments.The patientwasunemployed, denied anyrecent travel, andnoother members of his household were complaining of fatigueor similar blue skin discoloration.What is the Differential Diagnosis of these SkinChanges?When developing a differential diagnosis (see Table 1) forbluish skin discoloration, one must determine if the patienthas cyanosis. A significant toxicologic cause of blue skinappearance from cyanosis is methemoglobinemia. A carefulhistory may help differentiate between acquired versus con-genital methemoglobinemia. Recent exposure to dapsone,benzocaine, lidocaine, nitrates, or aniline dye raises suspi-cion foracquired methemoglobinemia. Sulfhemoglobinemiashould be considered in patients with a positive methemo-globin reading on co-oximetry, but who do not respond tomethylene blue treatment. Oxidizing agents that may causemethemoglobinemia can also produce sulfhemoglobinemiain the presence of sulfur compounds, such as sulfonamidederivatives, hydrogen sulfide, or gastrointestinal sources [1].Causes of noncyanotic skin discoloration are extensive.Metal deposition (e.g., silver, gold, bismuth) causes blueskin pigmentation. Chronic or improper exposure to silvercan result in a silvery blue or gray skin discoloration knownas argyria. Argyria is caused by silver deposition in the skin,specifically within fibroblasts, macrophages, and in the ex-tracellular matrix. These skin changes are often most signif-icant in sun-exposed areas [2]. Similarly, chrysiasis refers to

Dental amalgam restorations release mercury and silver which is absorbed and distributed in the body. Animal studies have shown that both elements may interfere with the host by activation of the immune system in genetically susceptible strains at exposure levels relevant to those from dental amalgam restorations. The aim of this study was to test the hypothesis of no change over time in concentrations of a number of immune mediators in serum after removal of all dental amalgam restorations in patients with health complaints attributed to their amalgam restorations and compare with a healthy reference group. Twenty patients previously examined at a specialty unit for health complaints attributed to dental materials were included in a clinical trial and had all amalgam restorations replaced with other dental restorative materials. Serum samples were collected before amalgam removal and 3 and 12 months after the removal was finished. Twenty blood donors matched for age and gender were used as comparison group. A fluorescent bead-based (Luminex) immunoassay kit was used to measure cytokines, chemokines and growth factors in serum. At baseline, the patient group had slightly higher values for GM-CSF, IL-6, IL-2R, IFN-alpha, IL-7, and IL-12p40/p70 compared with the reference group. After amalgam removal a decrease towards the median value of the reference group was found for GM-CSF, IL-8, and IL-7. In conclusion, removal of all dental amalgam restorations and replacement with other dental restorative materials was associated with decreased concentrations of Th1-type proinflammatory markers in serum.

Az argyria ezustvegyuletek tartos lokalis vagy szisztemas alkalmazasa nyoman kialakulo korkep. A tunetek leggyakrabban a bőron, kormokon, conjunctivan, szajnyalkahartyan jelentkeznek, kezelesuk mind a mai napig kihivast jelent. Bar napjainkban ezusttartalmu gyogyszerek, gyogyaszati eszkozok hasznalatara mersekelt gyakorisaggal kerul sor, az argyria előfordulasaval megis szamolnunk kell. A korkep leggyakoribb okava mara a paramedicinalis gyogyaszatban szeles korben alkalmazott ezustkolloid tartos fogyasztasa valt. Kozlemenyunkben 54 eves ferfi beteg esetet ismertetjuk, aki evek ota vegetarianus eletmodot folytatott. A beteg immunrendszere erősitese celjabol fogyasztott ezustkolloidot kozel ket even at, amelynek hatasara kialakult az arc diffuz, szurke elszineződese. Az anamnezis es a klinikai kep alapjan az argyria diagnozisa merult fel. A beteg kivizsgalasa soran laboratoriumi es kepalkoto diagnosztikus vizsgalatokkal belső szervi elterest nem talaltunk. Az argyria diagnozisat a tunetes bőrből vegzett hisztologiai vizsgalat alatamasztotta. A szerzők az irodalmi adatok tukreben felhivjak a fi gyelmet a paramedicinaban az ezustkolloid napjainkban tapasztalt terhoditasara, mellekhatasaira, a szerrel kapcsolatos teves informaciokra, az ezustkolloid-fogyasztas veszelyeire. Kulcsszavak: ezustkolloid, paramedicina, szurke bőrszin, argyria Grayish discoloration of the face – argyria The 54 year-old vegetarian patient has taken oral colloidal silver for two years to stimulate his immune system. The silver intake resulted in diffuse grayish discoloration on the face. His laboratory values were in the normal range, and no internal organ disease was detected. The histology of the forehead skin confi rmed the diagnosis of argyria. Argyria is a condition associated with chronic local or systemic exposure to silver-containing products. The silver is typically deposited in skin, fi ngernails, oral mucosa and conjunctival membranes. There is no effective treatment for this condition. With the availability of pharmacologic alternatives, physician-directed use of silver-containing products had signifi cantly declined. We review the literature and call attention to the adverse effects and dangers of the widely used paramedicinal colloidal silver products.

Absrracr: The functional implications of the presence of silver in the central nervous system are unknown. Since silver is present in the environment and since systemic silver poisoning leads to intraneuronal accumulations of the metal we have evaluated the possible effects of silver on the open field behaviour of mice. Argyric mice have been compared with controls in three experiments, one including long term administration of 0.015% silver nitrate in the drinking water and two in which the reactions of male and female mice to shock doses of silver lactate have been studied. In all experiments the silver treated mice were hypoactive. We suggest that this hypoactivity is due to an influence of silver upon the functional status of the CNS.

Five patients with generalized slate-gray discoloration of the skin have been diagnosed histologically as argyria in the last 35 years in the Department of Dermatology and Venereology of Rostock and Halle. Light microscopically, there was visible black pigmentation in histiocytes, fibroblasts, and multinucleated giant cells of the dermis. In the transmission electron microscope (TEM), the authors observed electron-dense deposits inside lysosomes and residual bodies of phagocytes as well as outside the cells in the connective matrix. These deposits were identified by elemental analysis in TEM and electron energy loss spectroscopy (EELS) as well as scanning electron microscope (SEM) and energy dispersive x-ray analysis (EDX) containing silver and sulfur. Therefore, they seem to consist of silver sulfide. Argyria is of low medical relevance and is very rarely induced because of silver-containing drugs. Nevertheless, there are still a lot of silver products on the market, easily available over-the-counter. Therefore, argyria should not be forgotten or missed in the diagnostics of human dermis.

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.

Background Prosthetic joint infection is a serious complication of implant therapy. To prevent prosthetic joint infection, we previously reported the features of silver oxide–containing hydroxyapatite (Ag-HA), which was prepared by mixing silver (a metal with antimicrobial activity) with HA. In this study, we evaluated the potential issues of total hip arthroplasty (THA) with an Ag-HA–coated implant. Methods We prepared an implant for THA that was coated with Ag-HA. In this study, the implant contained silver at a maximum quantity of 2.9 mg/implant. In this prospective interventional study, we performed THA with this implant in 20 patients and investigated the effects of silver. Results Blood silver levels peaked at 2 weeks after THA and gradually decreased thereafter. The highest blood silver level recorded during the postoperative follow-up was 6.0 ng/mL, which was within the normal range. The Harris Hip Scores increased in all cases, and activities of daily living improved markedly after THA with Ag-HA–coated implants. Implant failure was absent on radiography. No adverse reaction to silver was noted, and argyria was not observed in any case. No patients have developed infection after surgery. Conclusion This is the first clinical study of Ag-HA–coated implants in THA. Our Ag-HA–coated implants markedly improved patients' activities of daily living without causing any adverse reactions attributable to silver in the human body. Ag-HA is expected to reduce postoperative infections and prevent decreased quality of life in patients undergoing prosthetic arthroplasty, thus leading to more favorable outcomes.

Background: Treatment of acute burn wounds with silver sulfadiazine (SSD) has raised concern about potential silver toxicity. Numerous adverse reactions and side effects have been reported and an increasing resistance to SSD, especially in Pseudomonas strains, have motivated researchers to search for an alternative wound dressing. Methods: Recently, a silver-coated wound dressing Acticoat (Smith & Nephew, Inc.) has become available for use in burn patients. It is a three-ply dressing, consisting of an inner rayon/ polyester absorptive core between two layers of silver-coated, high-density polyethylene mesh. In a moist environment, the nanocrystals of silver are released and improve the microbial control in the wound. Results: After 1 week of local treatment with Acticoat in a young, previously healthy 17-year-old boy with 30% mixed depth burns, hepatotoxicity and argyrialike symptoms, a grayish discoloration of the patient’s face, appeared. The silver levels in plasma (107 g/kg) and urine (28 g/kg) were clearly elevated, as well as the liver enzymes. As soon as the local application of Acticoat was aborted, the clinical symptoms and liver enzymes returned to the normal values. Conclusions: This is the first report on silver toxicity in a patient with 30% burns who received Acticoat for local treatment. Due to substantial experiences with adverse SSD reactions and side effects, it is appropriate to keep the possibility of a toxic silver effect in burn patients treated with Acticoat silver-coated wound dressing in mind. The silver levels in plasma and/or urine should be monitored.

To determine the value of confocal and specular microscopy in the examination of corneal argyrosis in art silver solderers.Six patients with corneal argyrosis underwent a complete physical and ophthalmologic examination. Specular microscopy was performed in three cases, and in vivo confocal microscopy in four cases. Ultrasound biomicroscopy and corneal topography were performed in three cases. A conjunctival specimen of one patient was examined histologically in paraffin sections.Slit-lamp examination showed gray, diffuse opacities in the deep corneal stroma. Confocal microscopy showed highly reflective deposits with a granular pattern anterior to the corneal endothelium and hypereflective keratocyte nuclei with visible cytoplasm in the anterior stroma. Specular microscopy demonstrated round white bodies anterior to the corneal endothelium. Silver deposits were not found histologically.Silver solderers with long-term exposure to silver compounds are at high risk of developing corneal argyrosis. We conclude that specular microscopy and in vivo confocal microscopy provided important information for the diagnosis of corneal argyrosis.

PURPOSE: To identify the presence of silver deposits in the cornea using a new-generation confocal microscopy technique. METHODS: Case report. RESULTS: A 70-year-old man, who had been a jeweler for many years, was referred to our center for assessment of corneal opacity and ocular pigmentation. Slit-lamp examination revealed grayish, dense confluent deposits in the central and peripheral cornea, deep stroma, and Descemet's membrane. On confocal microscopy, we observed typical images of hyperreflective keratocytes across the entire stromal surface and two hyperreflective plaques coinciding with areas of metal deposition, one at Descemet's membrane and the other at Bowman's membrane. This last deposition site has not been previously identified in vivo by confocal microscopy. CONCLUSIONS: Confocal microscopy is a useful tool for the diagnosis of corneal argyrosis because it allows the in vivo visualization of silver deposits at different corneal levels.

Argyria is grayish black discoloration of skin or mucous membrane caused by silver deposition; it may be localized or diffuse. Diffuse argyria occurs as a result of elevated silver levels in blood, whereas localized argyria occurs when there is direct deposition from an external source. Exposure to silver was common in the last century; however, in the present times, argyria is an uncommon entity because of the restrictive use of silver-containing medicines and decreased industrial exposure. Occupational exposure is common among silversmiths [1], mineworkers, photographic film laboratory workers, and individuals involved in the electroplating industry. Cases after prolonged use of silver salts for wound dressing, acupuncture needles, silver earrings [2], eyedrops containing silver, and irrigation of urethral or nasal mucous membranes with silver-containing solutions have been reported. Argyria has also been seen among patients undergoing dental procedures, such as silver amalgam tattooing. 2. Case presentation A 66-year-old man had nasal blockage and intermittent drainage from both nares for many years. The drainage was watery and persistent even after being treated with multiple medications. Nasal examination revealed bilateral bluish black pigmentation of mucosa in the superior-anterior portion of the nasal septum. There was no other area of pigmentation either on the skin or elsewhere. The patient’s history is significant for stroke, myocardial infarction, and hypertension. He worked as a supervisor in the chemical sensitizing paper unit of a photographic film–producing company before retiring in 1992 and was exposed to a large number of chemicals, including silver nitrate. In 2004, a computed tomographic scan of the patient’s paranasal sinuses showed minimal mucosal thickening in the left maxillary sinus. A small biopsy specimen of the pigmented nasal mucosa was taken under local anesthesia and sent for routine histopathologic analysis. Subsequently, analysis using scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS) was also performed.

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 is an uncommon grey-blue pigmentation of skin and mucous membranes caused by prolonged silver exposure. The impetus behind this review is our experience with cases of generalized argyria resulting from a uniquely Indian socio-cultural practice and belief that it is under reported. Our objective is to increase the awareness for this esoteric entity through a review of the pertinent literature and to highlight clinical and histological features using our four well worked-up cases as examples.

We report 2 cases of patients who presented with blue macules clinically suspicious for blue nevi. One patient had no documented history of trauma or silver exposure, and the other reported exposure to silver over 30 years ago. Microscopic examination revealed a dermal population of brown-black globules predominantly adhering to collagen fibers. In both cases, no melanocytic proliferation was identified by immunohistochemistry. Analysis of the skin biopsies with scanning electron microscopy and energy dispersive x-ray spectroscopy demonstrated the presence of silver and selenium. These findings were diagnostic of localized cutaneous argyria. Our case reports highlight the importance of including localized cutaneous argyria in the differential diagnosis of pigmented lesions.

A 58-year-old man with a medical history of schizoaffective disorder, delusional parasitosis and clostridium difficile colitis (CDC) was hospitalised for worsening diarrhoea, as a result of CDC exacerbation. His physical examination revealed normal vital signs and a bluish-grey pigmentation of the skin and nailbeds (figure 1). The patient firmly believed that he had Morgellons disease (a form of delusional parasitosis). In the past, he had seen several physicians including psychiatrists to seek treatment for his delusional parasitosis. The patient reported that he had been using oral silver colloidal …

Introduction Silver-coated grafts are designed to prevent vascular graft infections. Silver is a safe element but toxic effects have been reported. We describe two cases of possible localized argyria after silver graft implantation. Report Two patients presented with perigraft groin collections after implantation of silver grafts. During reoperation, an ashen-grey necrotic substance was seen surrounding the grafts. The grafts were explanted and lower limb perfusion restored. Cultures were negative and both patients had uneventful recoveries. Discussion Our cases are highly suggestive of a possible unique adverse effect: a combination of localized silver toxicity and neutrophilic mediated tissue destruction.

A 68-year-old Caucasian man with a remote history of daily colloidal silver ingestion presented for ophthalmic examination in which he was noted to have a distinct slate gray skin discoloration. Funduscopy revealed confluent perimacular drusenoid deposits bilaterally, most of which localized at the level of or anterior to the inner segment ellipsoid band by optical coherence tomography (OCT) imaging. Enhanced depth imaging OCT demonstrated marked choroidal thinning. Fluorescein angiogram displayed a dark or silent choroid. Confirmatory serum silver levels were found to be markedly elevated. This report describes a unique geographic maculopathy with large drusenoid deposits anterior to the ellipsoid layer and severe choroidal thinning in association with ocular argyrosis. [ Ophthalmic Surg Lasers Imaging Retina. 2013;44:E20–E22.]

Legitimate medicinal use of silver-containing products has dramatically diminished over the last several decades. Recently, however, some manufacturers have begun to enthusiastically promote oral colloidal silver proteins as mineral supplements and for prevention and treatment of many diseases. Indiscriminate use of silver products can lead to toxicity such as argyria.To assist health care professionals in a risk versus benefit assessment of over-the-counter silver-containing products, we herein examine the following issues: historical uses, chemistry, pharmacology, clinical toxicology, case reports of adverse events in the literature, and the recent promotion of over-the-counter silver products. Other sources of silver exposure (including environmental and dietary) and EPA exposure standards are discussed. A list of currently available silver products is provided for easy reference and screening.We emphasize the lack of established effectiveness and potential toxicity of these products.

The authors report a case of a 71-year-old man who developed myoclonic status epilepticus and coma after daily ingestion of colloidal silver for 4 months resulting in high levels of silver in plasma, erythrocytes, and CSF. Despite plasmapheresis, he remained in a persistent vegetative state until his death 5.5 months later. Silver products can cause irreversible neurologic toxicity associated with poor outcome.

A 70-year-old male rural worker was referred to our clinic with widespread grey pigmentation of the skin and nails. The condition had been asymptomatic for its entire duration (5 years). He reported past intranasal application of 10% Silver Vitellinate. A skin biopsy was performed and histology corroborated the clinical diagnosis of Argyria. This case represents a currently rare dermatological curiosity. Although silver colloids and salts have been withdrawn and/or banned by some drug surveillance agencies, they continue to be freely sold and unregulated as food supplements and as ingredients in alternative medicines, thereby risking the emergence of new cases of silver poisoning.

Argyria is a rare cutaneous manifestation of silver deposits in the skin, characterized by a grayish blue discoloration, particularly in sun-exposed areas. We report the case of a patient with a history of schizoaffective disorder and type 2 diabetes mellitus who presented with argyria of the face and neck. The patient had a history of ingesting colloidal silver proteins (CSPs) for approximately 10 years as a self-prescribed remedy for his medical conditions. Colloidal silver protein has gained popularity among patients who seek alternative medical therapies. Argyria is the most predominant manifestation of silver toxicity. It is unclear if our patient began taking CSP because of his schizoaffective disorder or if silver toxicity may have induced somatic delusions; however, it is important for physicians to have a thorough understanding of alternative therapies on the market. We present a detailed background on silver ingestion and its systemic effects.

We describe a 53-year-old man in good general health who presented with an 8-month history of progressive gray hyperpigmentation of the face. He denied using any prescription medications; however, he admitted to taking a herbal supplement. Clinically, the differential diagnosis included hemochromatosis, Wilson's disease and hyperpigmentation secondary to supplement use. Punch biopsies from the left forehead and preauricular region showed heavily sun-damaged skin with a minimal inflammatory infiltrate. Closer inspection, however, revealed minute scattered black/brown particles distributed in the basement membrane zone of eccrine and sebaceous glands. Similar particles were also present in hair follicles, blood vessels and arrector pili muscles. The particles did not stain with Gomori methenamine silver, Fontana-Masson or iron stains. Electron microscopy with energy-dispersive x-ray analysis showed numerous particles, less than 1 µm in greatest dimension, which showed peaks for silver and sulfur. This analytical result confirmed the impression of argyria. Further history revealed that the patient had indeed been taking a silver supplement for several months under the premise that it would boost his immune system. This case is unique in that the patient's hyperpigmentation developed in a short period of time as compared with other reports in the medical literature. Bowden LP, Royer MC, Hallman JR, Lewin-Smith M, Lupton GP. Rapid onset of argyria induced by a silver-containing dietary supplement.

Argyria is a rare skin disease caused by cutaneous deposits of silver granules as a result of exposure to silver substrates or ingestion of silver salt. This pigmentation change causes cosmetic problems, and there was previously no recognized effective treatments for argyria.To evaluate the treatment effect of a low-fluence Q-switched 1064-nm Nd:YAG laser on argyria.Case report of a 49-year-old with a history of ingestion of a colloidal silver solution daily for approximately one year as a traditional remedy.After seven sessions of treatment, the patient's skin color returned to normal.A low-fluence Q-switched 1064-nm Nd:YAG laser provided safe and effective treatment for the skin discoloration associated with argyria.

Argyria is generally classified as localized or generalized condition. Distinct pigmentation of the oral mucosa in the vicinity of amalgam fillings is often referred to as amalgam tattoos. Pigmented areas can also be associated with silver-containing corrosion products of dental alloys used for prosthetic restorations. Silver-containing electron dense particles (Ag-EDPs) are frequently found in pigmented areas. We attempted to correlate results of the elemental composition of Ag-EDPs with excerpts from health profiles of our study paticipants.Eight patients with diagnosed signs of localized argyria were investigated in this study. Biopsies from distinctly pigmented gingival areas were subjected to histological examination, electron microscopy and x-ray microanalysis.Elemental composition of Ag-EDPs determined by x-ray microanalysis showed mainly silver in combination with sulfur or selenium or a combination of both chalcogens. Elemental analyzes results of Ag-EDPs were analyzed along with excerpts from the patient's clinical records. Two patients with low or undetectable selenium in the Ag-EDPs suffered from autoimmune thyroiditis, Parkinson's disease, bronchial asthma, and allergies to molds, pollen and dust.We suggest that selenium in Ag-EDPs is a product of the detoxification process for Ag(+) ions in gingival tissue and that it may reflect the availability of endogenous selenium for physiological processes in the human body. Its presence or absence might thus be used as another marker of a patient's health status.

Tooth sensitivity is a common clinical problem. This multi-center randomized clinical trial assessed the effectiveness and safety of topical diammine silver fluoride. From two sites (Lima and Cusco, Peru), 126 adults with at least one tooth sensitive to compressed air were randomly assigned to either the experimental treatment or sterile water, and pain was assessed by means of a 100-mm visual analogue scale at 24 hours and 7 days. The diammine silver fluoride reduced pain at 7 days at both sites. At the Lima site, the average change in pain scores between baseline and day 7 for the silver fluoride group was -35.8 (SD = 27.7) mm vs. 0.4 (SD = 16.2) mm for the control group ( P < 0.001). In Cusco, the average change in pain scores for the silver fluoride group was −23.4 (SD = 21.0) mm and -5.5 (18.1) mm for the control group ( P = 0.002). No tissue ulceration, white changes, or argyria was observed. A small number of participants in the silver fluoride group experienced a mild but transient increase in erythema in the gingiva near the tooth. No changes were observed in the Gingival Index. We concluded that diammine silver fluoride is a clinically effective and safe tooth desensitizer.

Electron microscopic and X-ray microanalytic studies were performed on four cases of argyria; one generalized and three localized. Deposition of electron dense granules was predominantly found on elastic fibers and around basal laminas of secretory portions of eccrine glands, although the amount of deposition was much less in the case of generalized argyria. In all four cases, X-ray microanalysis revealed that the depositions consisted mainly of silver, selenium, and sulfur. The importance of selenium in the detoxification of heavy metals was discussed.

Silver toxicity is a rare condition. The most notable feature is a grey-blue discoloration of the skin, argyria, although harmful effects on the liver and kidney may be seen in severe cases. Neurological symptoms are an unusual consequence of silver toxicity. So far no effective treatment has been described for this metal overdose. We report the case of a 75-year-old man who had a history of self-medication with colloidal silver and presented with myoclonic seizures.

Silver (Ag) is a rare, naturally occurring element. Because of its physical properties (hardness, ductility, malleability, high thermal and electrical conductivity) and antimicrobial activity, Ag has been extensively mined and utilized since antiquity in a wide variety of applications, including metallurgy, soldering, electroplating, photography, medicine and dentistry (wound and burn care, surgical devices, dental amalgams), water sanitation, cosmetics, electronics, production of coins, medals, jewellery, silverware and mirrors . Small Ag quantities are absorbed by humans through diet, even though the element fulfils no physiological role in any human tissue. In the case of occupational or iatrogenic exposure, Ag is less toxic than other xenobiotic metals (such as lead and mercury) and the most common clinical presentations are argyria (slate gray discoloration of the skin and other soft tissues, due to generalized accumulation of the metal) and argyrosis (discoloration of the eye, skin and/or external mucous membranes, caused by local Ag absorption and deposition). Additionally, soluble Ag compounds may cause liver and kidney damage, irritation of the eyes, skin, respiratory and intestinal tract, and haematological changes . Thanks to the improvement of hygiene in the workplace, and to the restrictive use of Ag-containing medications, Ag-related disorders are uncommon in current clinical practice. We describe here the clinical and pathological findings of an exceptional (nowadays) case of occupational argyrosis diagnosed in advanced age. Case Presentation