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Graphical abstract, Highlights • Silver nanoparticles and silver ions in colloidal silver are toxic. • Internet marketing of colloidal silver included false claims. • Internal use of colloidal silver was promoted by companies and users. • Distrust in authorities expressed in websites and Facebook nulled interventions., Aims The aim was to investigate the marketing practices, beliefs and health claims regarding the use of colloidal silver in Finland. Silver nanoparticles (AgNPs) are potentially toxic due to their small size and Ag+-release capabilities, and the use of colloidal silver products containing AgNPs can cause a wide variety of adverse effects such as argyria. Methods Contents of three company websites selling colloidal silver were reviewed, and the claims used in the marketing of colloidal silver were compared to the scientific information about silver. In Facebook posts and discussion about colloidal silver were analyzed. Results In Finland, the marketing of colloidal silver products on websites selling the products did not follow the regulations of authorities; several scientifically unfounded claims about the efficacy and medical use of colloidal silver were found. After the Finnish Broadcasting Company (Yle) documentary and an intervention by authorities, contents of the websites were changed, but still questionable information and misleading claims could be found. In the analyzed Facebook groups attitudes towards medical use of colloidal silver were uncritically positive, internal use was highly promoted and the restrictions of use were considered unjustified. Conclusions The use of quackery products such as colloidal silver can be dangerous, and their use and marketing should be controlled and restricted.

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.

Localized argyria is a benign rare condition resulting from impregnation of silver particles in the skin by various exposure sources such as silver jewelry,1 occupational exposures,2 topical medications,3 and medical procedures (ie, acupuncture).4 We report a case of acupuncture-induced argyria on the face, both dorsa of the hands, wrists, legs, and dorsa of the feet, successfully treated with 1 to 2 sessions of Q-switched 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser. Tissue section demonstrated refractile granules around the eccrine glands under dark-field microscopy.

Background Argyria results from silver accumulation in the skin. It is a stressful condition for patients due to skin discoloration. In the past, no effective treatments were available. However, it has been recently reported laser treatments showed promising results. Aim To review and summarize all reported laser treatment options for argyria patients. Methods We reviewed all laser treatment options for argyria in the database of the US National Library of Medicine PubMed. The search of the words "argyria and laser" was performed on the March 4, 2020. Results We found 11 studies that reported laser treatment for argyria. All of the studies were case reports demonstrating treatment responses of laser devices such as 1064 nm Nd:Yag laser and 755 nm alexandrite laser. Despite various treatment parameters, 1064 nm Nd:Yag and alexandrite lasers showed good responses in argyria. However, severe pain during the laser procedure was the main concern. We summarized laser treatment options for argyria including their parameters, treatment response, and anesthesia for laser treatment in argyria. We also report a case of argyria, which successfully responded to low fluence 1064 nm Nd:Yag laser. Conclusion Laser therapies resulted in almost complete clearing of pigment in argyria. Earlier reports showed that 1064 nm Nd:Yag laser successfully treated argyria but recent studies suggested 755 nm alexandrite was also a good treatment option for argyria. Additionally, our case achieved excellent results even in one session of low fluence Q-switched Nd:Yag laser, though we need to ensure pain control during the laser treatment.

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.

A 27-year-old female, a radiotherapy technician, was referred to our consultation with a localized gray pigmentation of the perinasal area. The condition had been asymptomatic for its entire duration of 2 years. A dermatological examination found a localized bluish-gray pigmentation in the perinasal area. Dermoscopy revealed an annular bluish-gray patch. Her occupation involved the manufacture and micromanipulation of machines, which required handling pure iron, nickel, copper, and silver with bare hands. She also reported a tic of flaring the nose. A skin biopsy was performed and histology revealed deposits of fine granules in the basal cell layer of eccrine sweat glands and along the elastic fibers of the superficial dermis, conforming with the diagnosis of argyria. The patient was given laser Q-switching treatment and showed a measurable improvement. This case studies a currently rare dermatological curiosity. Argyria is a disease caused by chronic absorption of silver-rich materials. This is the first description of argyria following the manipulation of radiopaque caches with a tic of flaring the nose.

Anushka Sharma Institute of Clinical Sciences, Imperial College School of Medicine, London, UKCorrespondence: Anushka SharmaFaculty of Medicine, Imperial College London, Exhibition Road, South Kensington, London, SW7 2BX, UKTel +447427404135Email anushka.sharma16@imperial.ac.ukAbstract: Pencil-tip injuries, although usually insignificant, have the potential to provoke granulomatous reactions. Other undesirable consequences of such injuries include pigmentation and abscess formation. Despite the rarity of such outcomes, it is important that clinicians are aware of the varying presentations of pencil-tip injury, as this can cause diagnostic uncertainty. Here, we present a case of graphite foreign body granuloma, originally thought to be a blue naevus-like localised argyria. The diagnostic work-up was complicated by the absence of a history of injury with a pencil-tip.Keywords: pencil-tip, granuloma, misdiagnosis, granulomatous reaction

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.

Argyria encompasses the different cosmetic alterations that can develop if enough silver particles deposit in a specific tissue, typically in the skin, ranging from localized dark-blue macules to a generalized slate-gray/bluish tinge following systemic absorption. This work aims to fully review the state of the art regarding pathophysiology, diagnosis, treatment, and relevant clinical and forensic features of argyria. Argyria has been diagnosed in a wide range of ages, both sexes and varied ethnicities, with no known individual predisposing factors. Ultraviolet radiation with subsequence increases of melanin production aggravates the discoloration due to a reduction in the silver deposits. Physical examination and silver exposure in the anamnesis can be highly suggestive of the diagnosis, but a histopathological analysis with Energy-Dispersive X-ray Spectroscopy is required to unequivocally determine the discoloration etiology. Safe and effective treatment has only been accomplished with laser techniques, though only a few cases have been reported and with limited follow-up time. In conclusion, argyria typically has an occupational or iatrogenic etiology. It should be suspected when a patient presents with typical skin or eye lesions. A seemingly viable treatment modality, with laser technology, is finally within the horizon.

Prosthetic joint infection (PJI) is a common complication following orthopedic megaprosthetic implantations (EPR), estimated up to 50%. Silver coatings were introduced in order to reduce the incidence of PJI, by using the antibacterial activity of silver. Three different silver coatings are available: MUTARS® (Implantcast), Agluna® (Accentus Medical), PorAg® (Waldemar Link). The aim of this review is to provide an overview on efficacy and safety of silver-coated EPR both in primary and revision surgery, comparing infection rate according to the type of implant. Through an electronic systematic search, we reviewed the articles concerning silver-coated EPRs. Infection rate, silver-related complications, local and blood concentrations of the silver were evaluated. Meta-analyses were performed to compare results from each study included. Nineteen studies were included. The overall infection rate in patients with silver-coated implants was 17.6% (133/755). Overall infection rate in primary silver-coated EPR was been 9.2% (44/445), compared to 11.2% (57/507) of non-silver-coated implants. The overall infection rate after revisions was 13.7% (25/183) in patients with silver-coated EPR and 29.2% (47/161) when uncoated EPR were used, revealing a strength statistically significative utility of silver coatings in preventing infections in this group (p: 0.019). Generally, the use of MUTARS® EPR had produced an almost constant decrease in the incidence of primary PJI but there are few data on the effectiveness in revisions. The results from the use of Agluna® in both primary and revisions implants are inconstant. Conversely, PorAg® had proven to be effective both in PJI prevention but, especially, when used in PJI revision settings. Local argyria was reported in 8 out of 357 patients (2.2%), while no systemic complications were described. Local and blood concentrations of silver were always reported very far to the threshold of toxicity, with the lowest concentration found using PorAg®. Silver-coated EPRs are safe and effective in reduction in PJI and re-infection rate, in particular when used in higher risk patients and after two-stage revisions to fight PJI.

Due to its antibacterial actions, silver sulfadiazine is widely used as a topical agent in the treatment of wounds, including burns. Widespread or prolonged topical application of silver sulfadiazine dressings can lead to argyria including systemic symptoms due to the resorption of silver. Here, we report a patient experiencing localized argyria due to sunlight exposure after topical use of silver sulfadiazine cream on his face.

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.

Ochronosis is the blue-gray discoloration of collagen-containing tissues due to homogentisic acid (HGA) deposition, secondary to endogenous alkaptonuria or exogenous enzyme inhibition. In renal disease, accumulation of HGA in serum can cause methemoglobinemia. A 60-year-old woman with renal disease and anemia presented with 3 days of weakness and months of gray skin discoloration. Her hemoglobin was 8.1g/dl with 24.5% methemoglobin. Despite treatment with methylene blue, exchange transfusion, and continuous renal replacement therapy, the patient died. Autopsy revealed gray discoloration and ochronotic pigment in the ribs and cartilage. Based on these findings, the patient was diagnosed with ochronosis, suggestive of alkaptonuria, complicated by methemoglobinemia. The differential diagnosis for blue-gray skin discoloration includes argyria, methemoglobinemia, and ochronosis. This patient's clinical and autopsy findings suggested alkaptonuria complicated by methemoglobinemia due to progressive renal dysfunction. Development of methemoglobinemia in the setting of chronic skin discoloration and renal failure should prompt consideration of alkaptonuria.

Localized cutaneous argyria is a rare condition in which the skin changes into blue-grey spots due to the absorption of silver. The lesions need to be differentiated from other pigmentary disorders and require radiographic and histological examination for more accurate diagnosis. Scanning electron microscopy and energy dispersive x-ray spectroscopy can be a confirmatory tool in the evaluation of silver elements in biopsy tissue. This report shows the localized cutaneous argyria in earlobe of a 21-year-old woman who wears silver earrings for 10 years. (Ann Dermatol 31(6) 666∼668, 2019)

Colloidal silver used as a suspension for (alternative) therapeutic purposes or silver exposure due to environmental or working conditions can lead to irreversible deposits of silver granules in the skin (bluish-gray hue of the skin), mucosa, cornea, retina and internal organs. Silver-induced discoloration of the conjunctiva should therefore be taken into account when a bluish-gray discoloration raises the suspicion of conjunctival melanoma.

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.

This study presents the case of a man who developed a temporary and asymptomatic blue tongue. The dyschromia occurred following topical contact with gelato that contained Food, Drug, and Cosmetic (FD&C) blue dye no. 1. The etiology of a blue tongue is either congenital (in individuals with blue rubber bleb nevus syndrome) or acquired. Acquired blue dyschromia of the tongue results from either endogenous conditions or exogenous agents. The endogenous conditions include not only benign (angioleiomyoma, hemangioma, melanocytic macule, and varicosities) and malignant (ovarian carcinoma) tumors but also reactive lesions (intravascular papillary endothelial hyperplasia and mucocele) and systemic disorders (argyria, cyanosis, methemoglobinemia, primary adrenal insufficiency, and thrombocytosis). Exposure to the exogenous agents can either be systemic (ingestion of medications such as haloperidol, metoclopramide, minocycline, prochlorperazine, and risperidone), traumatic (tattoo resulting from the implantation of dental amalgam), or topical (contact with FD&C blue dye no. 1). Clinical clues to the topical exogenous etiology in the reported individual included not only the fact that the dyschromia spared both the lateral aspects and the tip of the tongue but also the observation that the blue color focally appeared on his upper lip.

Argyria is a rare but cosmetically distressing and difficult-to-treat condition for which quality-switched (Q-switched) lasers have been most commonly employed. However, at least one previous report suggests that the picosecond alexandrite laser may also serve as a successful treatment modality. Herein, we present a side-by-side comparison of a picosecond 755-nm alexandrite laser and a Q-switched 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser in the treatment of argyria. Our results reveal an equivalent success of the picosecond alexandrite when compared to the more commonly employed Q-switched Nd:YAG, suggesting that the picosecond 755-nm alexandrite laser is equally effective in the treatment of argyria.

Implant-associated infections remain a major issue in orthopaedics and antimicrobial functionalization of the implant surface by antibiotics or other anti-infective agents have gained interest. The goal of this article is to identify antimicrobial coatings, for which clinical data are available and to review their clinical need, safety profile, and their efficacy to reduce infection rates. PubMed database of the National Library of Medicine was searched for clinical studies on antimicrobial coated implants for internal fracture fixation devices and endoprostheses for bone surgery, for which study design, level of evidence, biocompatibility, development of resistance, and effectiveness to reduce infection rates were analyzed. Four different coating technologies were identified: gentamicin poly(d, l-lactide) coating for tibia nails, one high (MUTARS®) and one low amount silver (Agluna) technology for tumor endoprostheses, and one povidone-iodine coating for titanium implants. There was a total of 9 published studies with 435 patients, of which 7 studies were case series (level IV evidence) and 2 studies were case control studies (level III evidence). All technologies were reported with good systemic and local biocompatibility, except the development of local argyria with blue to bluish grey skin discoloration after the use of silver MUTARS® megaendoprostheses. For the local use of gentamicin, there is contradictory data on the risk of emergence of gentamicin-resistance strains, a risk that does not seem to exist for silver and iodine based technologies. Regarding reduction of infection rates, one case control study showed a significant reduction of infection rates by Agluna silver coated tumor endoprostheses. Based on socio-economic data, there is a strong need for improvement of infection prevention and treatment strategies, including implant coatings, in fracture care, primary and revision arthroplasty, and bone tumor surgery. The reviewed gentamicin, silver Agluna, and povidone-iodine technologies have shown a good risk benefit ratio for patients. Further data from randomized control trials are desirable, although this will remain challenging in the context of infection prevention due to the required large sample size of such studies.

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.

An 84-year-old woman was referred to our clinic with grey discolouration of her face. She had a history of hypertension that was managed with amlodipine and olmesartan. She reported that she had ingested an ionic silver solution (1 mg/mL), which she purchased from a naturopathic practitioner, every

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.

Skin hyperpigmentation results from increased number of epidermal melanocytes, increased synthesis of melanin, or both. Occasionally, deposition of melanin or other exogenous pigments in the deeper dermis causes changes of skin color. Facial pigment disorders include various dermatologic entities; they may also reflect organ dysfunction or metabolic conditions (e.g., pellagra, porphyria), result from deposition of metals (argyria, mercury intoxication), or be a side effect of chemicals and drugs. Postinflammatory hyperpigmentations of different origin may occur and overlap.

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.

Background Argyria is a rare irreversible cutaneous pigmentation disorder caused by prolonged exposure to silver. Herein, we report a case of generalized argyria that developed after chronic ingestion of soluble silver-nano particles and presented with muscle weakness. Case presentation A 74-year-old woman visited our emergency room, complaining of fever and mental deterioration. She was diagnosed with acute pyelonephritis and recovered after antibiotic therapy. At presentation, diffuse slate gray-bluish pigmented patches were noticed on her face and nails. Two months prior to visiting our hospital, she was diagnosed with inflammatory myopathy and given steroid therapy at another hospital. We performed a nerve conduction study that revealed polyneuropathy. In skin biopsies from pigmented areas of the forehead and nose, the histopathologic results showed brown-black granules in basement membranes of sweat gland epithelia, which are diagnostic findings of argyria. We reviewed pathology slides obtained from the left thigh muscles and found markedly degenerated myofibers with disorganization of myofibrils without inflammatory reactions, consistent with unspecified myopathy, rather than inflammatory myopathy. The patient was diagnosed with generalized argyria with polyneuropathy and myopathy and transferred to a rehabilitation institution after being tapered off of steroids. Conclusions Clinicians should be aware of clinical manifestations of argyria and consider it in differential diagnosis when they examine patients who present with skin pigmentation and muscle weakness.

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.

Medical and non-medical uses of silver are increasing. While the health benefits of silver therapy are widely claimed, few studies address the possible side effects of resistance, allergy, or skin discoloration. In this manuscript, a review of silver absorption, mechanism of action, allergy, microbial resistance and skin changes is presented. The ideal silver-delivery system is unknown. Most studies of side effects are animal or laboratory studies, which may not correlate with human experience. There is little correlation between serum silver levels, end-organ deposition and cytotoxic effects. The multiple mechanisms of antimicrobial action make true resistance unlikely. In microbes, genotypic resistance does not necessarily confer phenotypic resistance. Most cases of argyria occur from occupational exposure or from ingestion of colloidal silver rather than from topical application. Although toxicity, resistance and chronic skin changes are a theoretic concern, the lack of reported side effects despite widespread silver use is reassuring.

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.

Background and Objective: Generalized argyria is a blue-gray hyperpigmentation of the skin resulting from ingestion or application of silver compounds, such as silver colloid. Case reports have noted improvement after Q-Switched Neodymium–Yttrium Aluminum Garnet laser (1,064 nm QS Nd:YAG) laser treatment to small surface areas. No reports have objectively monitored laser treatment of generalized argyria over large areas of skin, nor have long-term outcomes been evaluated. Study Design/Materials and Methods: An incremental treatment plan was developed for a subject suffering from argyria. A quantitative near infrared spectroscopic measurement technique was employed to non-invasively analyze tissue-pigment characteristics pre- and post-laser treatment. Post-treatment measurements were collected at weeks 1, 2, 3, and 4, and again at 1 year. Results: Immediate apparent removal of pigment was observed with 1 Q-switched 1,064 nm Nd:YAG laser treatment (3–6 mm spot; 0.8–2 J/cm 2 ) per area. Entire face, neck, upper chest, and arms were treated over multiple sessions. Treatments were very painful and general anesthesia was utilized in order to treat large areas. Near-infrared spectroscopy was used to characterize and quantify the concentration of silver particles in the dermis based on the absorption features of the silver particles as well as the optical scattering effects they impart. We were able to estimate that there was, on average, 0.042 mg/ml concentration of silver prior to treatment and that these levels went below the minimum detectable limit of the instrument post-treatment. There was no recurrence of discoloration over the 1-year study period. Conclusion: QS 1,064 nm laser treatment of argyria is a viable method to restore normal skin pigmentation with no evidence of recurrence over study period. Quantitative spectroscopic measurements: (1) confirmed dyspigmentation was due to silver, (2) validated our clinical assessment of no recurrence up to 1-year post-treatment, and (3) indicated no collateral tissue damage with treatments. Lasers Surg. Med. 2013 Wiley Periodicals, Inc.