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Parenteral gold has historically been used to treat several conditions, including rheumatoid arthritis. Gold administration leads to a variety of cutaneous reactions, including chrysiasis, which is a permanent blue-grey hyperpigmentation of the skin due to dermal gold deposition. In this report, we describe the case of a patient who received parenteral gold injections 22 years before the onset of her chrysiasis for the treatment of rheumatoid arthritis. Biopsy of the macules showed dermal gold deposits aggregating around a melanocytic nevus, as well as around preexisting osteoma cutis. To the authors' knowledge, this is the first report in the literature describing a case of chrysiasis with gold deposits concentrated around a melanocytic nevus and an area of osteoma cutis.

Diseases of the skin, hair, nails and mucosa can appear as flesh-colored lesions or may present as any of the colors of the visual spectrum. Diseases associated with blue (or shades of blue) discoloration represent a unique group of conditions that occur de novo or as a reaction to either a topical or a systemic agent to which the individual has been exposed. Blue diseases can affect the skin, the nails or the mucosal membranes of the mouth (buccal mucosa, gingiva, lips, palate or tongue) or eyes (sclera). In addition to appearing blue, they can also appear as blue-black, blue-brown, blue-gray, blue-green, blue-purple, blue-red, and blue-silver. The conditions range from those secondary to exogenous agents (systemic or tattoo or topical) to syndromes to systemic diseases to tumors (adnexal, melanocytic, vascular, or miscellaneous). A comprehensive attempt to include all conditions that have been described as blue (or a shade of blue) has been performed by evaluating the following terms using the medical search engine PubMed: blue and either gingiva, lips, lunula, mucosa, nails, oral, palate, sclera, skin, or tongue. Subsequently, the conditions were organized by color (blue and shades of blue) and within each color by location (skin, nails, oral mucosa and sclera). The results are presented in organized tables; in addition, there is discussion of some of the conditions that are unique to one or more specific locations. In conclusion, 'preserve and cherish the pale blue dot' and remember that a big red rock eater with chrysiasis is the answer to the riddle, "What is big and blue and eats rocks?"

Injectable gold is known to deposit in the dermis for life, and such patients are at risk of developing chrysiasis post-laser exposure. It is unknown if patients with history of edible gold consumption would develop a similar reaction after quality-switched laser exposure. Our aim is to assess if patients with history of edible gold consumption develop chrysiasis after quality-switched laser exposure. This is a proof of concept pilot study conducted between September 2017 and September 2018 at two dermatology clinics in Riyadh, Saudi Arabia. Adult patients who have history of edible gold consumption were recruited to receive a spot test with different quality-switched lasers in a hidden, non-sun-exposed skin site. The test area was photographed before, immediately after, and 10 min after laser exposure. The test area was examined by two independent investigators for the development of chrysiasis. A total of 10 patients (five male and five female) were enrolled. The mean age was 31.7 years. Forty percent of subjects consumed edible gold more than once, and the duration of last intake ranged from 3 weeks to 3 months. Chocolate was the main source of edible gold. All participants had no chrysiasis reaction post-quality-switched laser exposure. Contrary to our hypothesis, all participants with history of short-term edible gold consumption did not develop chrysiasis after quality-switched laser exposure. Further controlled studies including more patients with longer duration and higher frequency of edible gold consumption are needed.

Cutaneous chrysiasis is gold deposition in the dermis, described after parenteral administration of gold salts or after topical exposure to gold-containing materials. Gold microparticles (GMPs) have versatile therapeutic effects and are increasingly used in medicine. This case report describes the development of a blue-gray macule following the facial application of GMPs and laser treatment of acne vulgaris. Dermoscopy showed a nonspecific homogenous blue-gray pattern, gradually fading over an 8-month-period. Reflectance confocal microscopy (RCM) detected hyperreflective, subcellular particles in the papillary dermis, localized around hair follicles, eccrine glands, and inside macrophages. Histopathological evaluation, darkfield illumination with hyperspectral imaging, and neutron activation analysis confirmed the presence of GMPs in the dermis. RCM allowed non-invasive fast visualization of aggregates of hyperreflective particles in the dermis and can potentially be used for monitoring localized cutaneous chrysiasis and other metal deposition conditions over time. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

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.

Localized chrysiasis is rare and can occur in two settings: after localized or traumatic implantation of elemental gold or gold salts or after localized laser or light therapy in someone who has been previously exposed to systemic gold therapy. We report a unique case of localized chrysiasis with associated aluminum salt deposition and sclerosing lipogranulomas because of previous injections of aurothioglucose (Solganal®). The unique histopathologic findings seen in this case have not been previously reported.

Case report A 60-year-old woman with rheumatoid arthritis of 20 years onset, on treatment with monthly intramuscular gold salts (GS) for the last 7 years. She complained of suffering from halo vision, and the examination showed a visual acuity of 0.6 in both eyes (BE). The slit lamp showed some deposits in the stroma with scattered golden granulated, without any further inflammatory reaction. Discussion GS deposits are dose-dependent and reversible, although very slowly. In this article, we introduce, for the first time, evidence of deposits of GS in all layers of the cornea, predominantly in the corneal stroma and in the endothelium.

Eleven cases of chrysiasis have been studied ultrastructurally and by electron probe microanalysis. Tissue samples were examined both with and without osmium and urany1 acetate staining. There was a significant morphological difference in the appearances of the gold deposits within aurosomes between the two groups. The untreated group showed finely granular deposits, often arranged in a linear fashion. Aurosomes from samples treated with osmium and urany1 acetate showed more electron-dense deposits and star-like formations. We propose that treatment of the tissue with osmium and urany1 acetate causes a change in the electron microscopic appearance of aurosomes, including the formation of the characteristic star-like aurosomes.

Silver and gold are transitional metals and exhibit different chemical properties. They have distinctive uses in industry, commercial applications and in medical science. The World Health Organization and various national regulatory authorities recognize that occupational exposure to silver and many other metals in the workplace pose significant health risks. In the case of silver, argyria and argyrosis with profound discolorations of the skin and eyes present a major risk associated with chronic exposure to silver. Selected clinical cases are documented to illustrate complications that arise in the use of silver. Gold dust is expected as a contaminant in the atmosphere close to mining areas, but in view of their high density, particles, can be expected to settle rapidly and present minimal risk of inhalation by workers, but appreciably greater risks have been associated with silica, mercury and cyanide in gold workers. Neutron activation analysis has been described for determination of gold in blood following clinical or occupational exposure to the metal. The present chapter discusses properties, production, uses, exposure assessment, toxic effects, and several clinical cases of these transitional metals. Keywords: argyrosis; metallic silver; hypogeusia; chrysiasis

Purpose: To describe a case of 68-year-old male industrial chemist who received a chemical injury after a gold/amine compound exploded causing bilateral eye injuries. No apparent long-term problems were anticipated. After cataract extraction 40 years later, he developed a localized ulcerative keratitis adjacent to embedded gold in the cornea. Methods: To describe the clinical features, management, and outcomes. Results: Successful treatment with topical hydrocortisone was achieved. Subsequently, 3 further episodes of ulcerative keratitis were treated with topical steroid therapy without need for systemic immunosuppression. A systemic vasculitic/autoimmune screen was normal. Discussion: Ocular chrysiasis is well recognized after systemic gold administration and is normally considered inert, but in this case exogenous gold deposition might have been a contributing factor to very localized and repeated episodes of stromal erosion in this man, many years after the original injury. To the best of our ...

A 65-year-old Caucasian woman had a 6 year history of worsening greyish blue discolouration of sun exposed areas—face, neck, arms, feet and the sclera (figs 1 and 2). She had suffered from rheumatoid arthritis for the past 20 years, with crippling disease at the onset, and was barely able to walk due to pain. After failure to respond to several disease modifying antirheumatic drugs (DMARDs), …

A case of localized argyria with chrysiasis caused by implanted acupuncture needles in a 41-year-old Japanese woman was studied by electron microscopy and x-ray microanalysis. Large amounts of silver granules with selenium and sulfur were detected around eccrine secretory cells in much greater amounts than around ductal cells. Many granules were also observed along the outer edge of the basement membrane but never within cells or intercellular spaces. The granules were also present around blood vessels, lymphatics and nerve fibers, and in elastic fibers. Small numbers of gold fragments were also seen, mostly within macrophages. These results suggest that silver deposits extracellularly as selenide and sulfide, whereas free gold is found intracellularly.

Q-switched lasers (alexandrite, Nd:YAG and ruby lasers) can successfully remove tattoos with few adverse effects. Removing professional tattoos usually entails 20–25 treatment sessions at intervals of 4–6 weeks. Residual pigment may remain, especially when multi-coloured tattoos are involved. Amateur tattoos and traumatic tattoos are usually easier to treat (5–10 sessions). Drug-induced hyperpigmentation is fairly common and tends to respond well to treatment with Q-switched laser (the exception here is chrysiasis). Frequent adverse effects are changes in pigmentation (particularly hypopigmentation), shifts in tattoo colour and changes in skin texture; the latter two are usually temporary. Scarring is possible but rare when treatment is performed correctly.

Purpose.To describe the in vivo confocal microscopy corneal findings in a patient treated with gold sodium thiomalate.Methods.A woman with rheumatoid arthritis who had been treated with gold sodium thiomalate for 32 years came to our center for an ophthalmologic examination about 5 years ago. Besides visual acuity, the examination included slit-lamp biomicroscopy, intraocular pressure, and funduscopy Confocal microscopy was performed using Confoscan 4 (Nidek Technologies, Padova, Italy) with a 40× lens.Results.Every layer of the cornea is affected by gold deposits with high reflectivity, especially in the anterior stroma, where they have a larger dimension.Conclusions.Corneal chrysiasis can be evaluated by confocal microscopy, giving information on corneal metabolism and physiology.

Chrysiasis is the phenomenon of bluish to slategray skin pigmentation induced by prolonged treatment with gold salts. The most common etiology is the administration of gold salts to patients with rheumatoid arthritis. Although parental gold salt administration is now uncommon because of the availability of biologic agents and disease-modifying antirheumatic drugs, chrysiasis may still be seen because this condition can develop decades after discontinuing gold salts. Discoloration can persist for a lifetime.

Purpose To describe the presence of gold salt deposits in the corneal tissue of a patient treated with gold sodium thiomalate through confocal microscopy and to relate our findings to temporary corneal dynamics. Methods A patient who had been treated with gold sodium thiomalate for 6 years was referred from the Rheumatology Unit of our center for an ophthalmologic examination. At the time of examination she had been treatment-free for 9 years. Besides visual acuity, the examination included slit-lamp biomicroscopy, intraocular pressure, and fundoscopy. Confocal microscopy performed using a Confoscan P4 instrument with a 40× lens to obtain 15 images per second on an S-VHS video system (Panasonic) for subsequent analysis. Results The basic layered structure of the cornea was unaffected, but the presence of highly reflective particles was noted. These particles were interpreted as gold deposits in the corneal stroma, especially in the anterior and middle stroma. Conclusion Confocal microscopy is a useful method of evaluating the deposition of gold salts in tissues, particularly the cornea. Its future use will help gain a deeper understanding of corneal metabolism.

Chrysiasis, the systemic deposition of gold pigment in patients on long term chrysotherapy, is identified histologically as small black granules within macrophages. Histological sections from 12 confirmed cases of chrysiasis were examined under crossed polarized light. This revealed a striking orange-red birefringence of the pigment not detected in other histologically similar deposits. This technique provides a valuable adjunct to the histological identification of gold without the need to resort to ultrastructural and analytical procedures.

We describe a case of chrysiasis in a 54-year-old woman. The diagnosis was confirmed by light microscopy, transmission electron microscopy, and radiographic microanalysis. The condition developed after a relatively low dose of gold. We propose that chrysiasis developed because of the patient's exposure to the intense UV light in Australia.

Deposition of gold in ocular structures, although known, is rare. A case of ocular chrysiasis in a patient of rheumatoid arthritis on gold treatment is presented

Chrysiasis is a distinctive and permanent pigmentation of light-exposed skin resulting from the administration of parenteral gold salts. We report a study of 40 Caucasian patients with rheumatoid arthritis, treated with intramuscular sodium aurothiomalate, of whom 31 had chrysiasis. Visible changes develop above a threshold, equivalent to 20 mg/kg gold content, and their severity depends upon cumulative dose. Focal aggregates of particulate gold are deposited in the reticular and papillary dermis in amounts that correlate with the degree of pigmentation. Characteristically, initially the periorbital region is affected by a mauve discoloration, which intensifies and deepens into a blue/slate-grey colour, while extending to involve the face, neck and upper limbs. Although chrysiasis develops insidiously and patients may be unaware of the changes, positive identification is important in order to avoid misdiagnosis and medical mismanagement, and afford appropriate reassurance. Prevention is difficult, but measures to reduce sunlight exposure may be helpful.

Skin biopsy specimens from five patients (three females and two males) treated parenterally with gold were investigated using transmission electron microscopy. X-ray microanalysis and electron diffraction were used to determine the dermal heavy metal content. Additional sections were stained for light microscopic examination. The amount of elemental gold administered to the patients over a period of years to alleviate rheumatoid arthritis lay between a minimum of 4.0 g and a maximum of 10.0 g. In one and the same patient dermal histiocytic gold aggregations in sun-exposed areas of skin displayed a different pattern and divergent physiochemical states from the gold deposits in non-UV-exposed skin, where aurosome-like amorphous formations are found in the cells of the upper dermis. Additional spherical particles are associated predominantly with phagolysosomes in melanophages beneath solar-irradiated epidermis. Convergent beam electron diffraction proves the crystalline nature of the spherical auriferous deposits. The occurrence of skin rash was not related to different physicochemical states of the precious metal.

A 70-year-old woman presented for elective treatment of lentigines on her face. This was her first treatment with any laser. She was treated with a Q-switched alexandrite laser (755 nm, 50 nanoseconds, 3.5 J/cm, 15 pulses of 4-mm spot diameter; Candela, Wayland, Mass), causing what appeared to be usual purpura immediately following laser exposure of 8 tan macules. Several weeks later, blue-black discoloration was present, and was attributed to postinflammatory hyperpigmentation, but failed to lighten over the next 4 months. Her medical history was significant for rheumatoid arthritis, treated with methotrexate and prednisone. Further questioning revealed that she had received a 3-year course of oral gold therapy 20 years prior. The total dosage taken could not be determined. Four months following Q-switched alexandrite laser therapy, her examination revealed 8 blue macules without texture changes located at the laser treatment sites on her cheeks and forehead ranging from 2 to 6 mm (Figure 1). The lesions did not enhance on Wood’s light examination, suggesting dermal pigmentation. In some areas, portions of the original lentigo were still visible in the center of the blue macule. There was no discoloration of the sclera, nails, or hair. A subtle blue-gray hue in the patient’s general skin color was noted at the time of reexamination. Apunchbiopsyspecimenofarepresentativeareademonstrated numerous black particles within macrophages in the dermis. A diagnosis of Q-switched laser-induced chrysiasis was made. Initially, an attempt was made to clear the hyperpigmentation using the same Q-switched laser, a technique that can often lighten or clear laser-induced cosmetic tattoo darkening. A test spot was created on the inner aspect of the right arm with the original Qswitched alexandrite laser, and the hyperpigmented macule was pulsed again with the same laser. While the center of the lesion did show some clearing, a new rim of blue hyperpigmentation was induced around the treated spot. Further treatment with a Q-switched alexandrite laser was therefore not pursued, because blue pigmentation would always be induced at the border of the treated area. Surgical excision was considered but not pursued, given the number and location of the lesions.

Background: Chrysiasis is a rare blue-gray skin discoloration that occurs in sun-exposed sites of some patients who receive gold salts. A unique case of localized chrysiasis developed immediately after Q-switched ruby laser (694 nm) irradiation for postinflammatory hyperpigmentation secondary to granuloma faciale in a patient who was receiving long-term gold sodium thiomalate therapy for psoriatic arthritis. Skin biopsy specimens showed striking changes in the ultrastructural characteristics of cutaneous gold deposits following laser treatment. Observations: A blue-gray skin discoloration developed immediately after laser exposure and persisted unchanged after 1 year. Transmission electron microscopy of skin biopsy specimens showed electron-dense gold deposits. Before laser irradiation, these deposits were 106±35 (mean±SD) nm in diameter and faceted, consistent with a crystalline structure. Posttreatment deposits were round, smaller, measured 16±4 nm, and resembled colloidal gold. Identical findings were observed in an area of sun-protected skin treated with the Qswitched ruby laser; irradiation with a pulsed dye laser at 585 nm had no effect. Conclusions: Localized chrysiasis was induced in a patient receiving parenteral gold therapy who underwent treatment with a Q-switched ruby laser. This form of chrysiasis resulted from a structural alteration in dermal gold deposits. A similar physicochemical modification in gold deposits induced by UV light may explain the localization of chrysiasis to sun-exposed skin in affected patients. (Arch Dermatol. 1995;131:1411-1414)

A 63-year-old woman had bilateral, multi-level corneal deposits distributed as fine, discrete crystals and in dense, deep geographic patches. She had a long history of sero-positive rheumatoid arthritis. Autopsy revealed an unsuspected lymphoproliferative disorder and immune-complex disease. Histologic examination of the eyes revealed eosinophilic, PAS-positive, noncollagenous deposits in the cornea at all levels and also in the ciliary processes, pars plana, and choroid. Stains for gold, amyloid, and acid mucopolysaccharides were negative. Immunoperoxidase stains were positive for IgG most strongly, and also for IgA, kappa and lambda light chains. Transmission electron microscopy showed needle-like electron-dense extracellular particles which we presume are immunoglobulins.

Corneal chrysiasis is a common consequence of parenteral chrysotherapy in patients affected by rheumatoid arthritis. Concerning the factors and conditions that could be determinant for the gold accumulation in the cornea, there are contradictory opinions. Total or weekly gold dose and its accumulation quota, and the frequency of drug administration, seemed to be parameters to which corneal chrysiasis could be related. Since all these parameters are completely different during oral gold therapy, previous investigations on corneal chrysiasis are inapplicable to patients undergoing oral treatment. This study, performed on rheumatoid arthritis patients treated with auranofin, orally administered for 8-34 months, did not reveal any appreciable corneal deposits of gold.

Two patients receiving gold therapy for rheumatoid arthritis developed skin pigmentation, chrysiasis, which in one appeared 4 months after cessation of the therapy. The diagnosis was confirmed by transmission electron microscopy and mass spectrometry laser microprobe analysis of paraffin sections and its extent demonstrated by epipolarized light. The condition is poorly reported and clinically may be confused with silver and mercury impregnation. Tissue diagnosis requires ancillary methods and of these, transmission electron microscopy and laser microprobe mass spectrometry are excellent examples. The transmission electron microscopy findings differ from previous reports and raise doubts on the hypothesis on the role of the skin in gold excretion. Because of the renewed interest in crysotherapy and the latent period that can separate this from chrysiasis, an increase in chrysiasis and the need for its diagnosis can be anticipated.

Summary A case of chrysiasis was studied by light and electron microscopy, X-ray microanalysis, and neutron activation analysis. The microscopic examination showed gold deposits in the perivascular areas in macrophages, and by electron microscopy studies gold was found exclusively in the phagolysosomes (aurosomes) indifferent ultrastructural patterns. The X-ray microanalysis confirmed that the phagolysosome contained gold. The concentration in light-exposed skin was 750–770 p.p.m. measured by the neutron activation analysis.

Gold entered the eye and was accumulated in the aqueous humor, iris-ciliary body, and cornea (measured by flameless atomic absorption spectroscopy) of rabbits given gold sodium thiomalate by subcutaneous infusion for 4 weeks. It was not detected following such exposure in the vitreous humor, lens or retina. The concentration of gold in the cornea was quite high, about 25% of that in the liver. The concentration in the aqueous humor was only about 2.5% of that in the plasma, which is similar to the fraction of gold (5%) that is not bound to plasma proteins.

Chrysiasis is a rare, permanent, pigmentation of the skin caused by the parenteral administration of gold preparations followed by subsequent exposure to ultraviolet light. We report a case of chrysiasis following gold therapy for rheumatoid arthritis, wherein ultrastructural analysis combined with x-ray energy spectroscopy afforded precise identification and localization of the gold pigment in skin biopsy specimens.

The deposition of gold in the cornea—ocular chrysiasis—is a normal event during chrysotherapy. It may reflect tissue deposition of gold and be of value in predicting clinical improvement or toxic reactions. We studied 21 patients with rheumatoid arthritis on chrysotherapy but could find no relationship between the appearance of ocular chrysiasis, clinical improvement, and toxicity.

The eyes of 11 patients with rheumatoid arthritis (RA) who received extended chrysotherapy (mean cumulative dose greater than 7 grams during a mean 6-year period) were examined biomicroscopically. Minute reddish-purple particles were seen in the cornea (corneal chrysiasis) in 5 and in the lens (lens chrysiasis) in 4 patients. Particulate deposits were absent in 11 other RA patients who had not received gold treatment. Seven crystalline lenses from 5 gold-treated patients were removed surgically because of incidental cataract formation and analyzed for gold content using neutron activation analysis. Although the mean lens gold concentration was higher in these patients than in non-gold-treated controls without RA (0.0073 microgram/grams versus 0.001 microgram/grams), the absolute gold level was markedly lower than that found in 25 diverse tissue analyzed previously. This finding is compatible with the absence of clinical gold-related lens disease or visual impairment.

2. Finkelstein, A. E., Roisman, F. R., Batista, V., de Nudelman, F. G., de Titto, E. H., Mizraji, M., and Walz, D. T.: Oral chrysotherapy in rheumatoid arthritis: Minimum effective dose. J. Rheumatol. 7:160, 1980. 3. Roberts, W. H., and Wolter, J. R.: Ocular chrysiasis. Arch. Ophthalmol. 56:48, 1956. 4. Gottlieb, N. L., and Major, J. C.: Ocular chrysiasis correlated with gold concentrations in the crystalline lens during chrysotherapy. Arthritis Rheum. 21:704, 1978. 5. Mc Cormick, S. A., DiBartolomeo, A. G., Raju, V. K., and Schwab, J. R.: Ocular chrysiasis. Oph­ thalmology 92:1432, 1985.

The particles of a tattoo are found in the dermis, both within phagocytes and extracellularly. Little is known concerning the transport of foreign particles from the dermis, although there are several reports describing such material in the epidermis. Kochs (1) has described gold particles within epithelial cells in chrysiasis. In a case of paraffinoma of the breast, Masson (2) noted the presence of paraffin in basal melanocytes. He also reported the presence of lipids and hemosiderin of endogenous dermal origin in melanocytes.

The subject of chrysiasis, or gold pigmentation of the skin, following exposure to ultraviolet radiation has recently been reviewed. 1 In all cases reported the condition followed intravenous injections of gold salts, principally sanocrysin (gold sodium thiosulfate), in large doses, totaling 150 mg. of gold sodium thiosulfate per kilogram of body weight or more. Whether this pigmentation might result from the intradermal or intramuscular administration of gold sodium thiosulfate has never been observed or experimentally tested. Schamberg, 2 however, described pale blue staining of the skin of 1 patient and 1 rabbit following the subcutaneous infiltration of a colloidal gold solution. Chrysiasis has not been produced in experimental animals, although intradermal and subcutaneous deposition of gold granules following the intravenous injection of massive doses of gold salts into mice, guinea pigs, rabbits and dogs 3 has been shown histologically and chemically. Kochs 4 experimentally produced local chrysiasis by the ultraviolet

Six patients who had received gold injections for the treatment of rheumatoid arthritis had histologically visible deposits of gold in the skin. In two of the patients, no gold had been administered for 20 years or more. The identity of the deposits was confirmed by emission spectroscopy using a laser microprobe, as well as by their resistance to microincineration and their removal by Lugol solution.