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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.

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.

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 ...

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.

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.

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.

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.

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