aPhilip R. Cohen, MD; bE. Victor Ross, MD
aDepartment of Dermatology, University of California San Diego, San Diego, California; bDivision of Dermatology, Scripps Clinic, San Diego, California
Disclosure: Dr. Cohen reports no relevant conflicts of interest. Dr. Ross reports the following: honoraria, consultant, research support, loan of equipment—Alma Lasers, Cutera, Lumenis, miraDry, Palomar Medical Techniques, Inc., Syneron.
Background: Chyriasis is an uncommon side effect that occurs in patients who are receiving prolonged treatment with either intravenous or intramuscular gold as a distinctive blue-gray pigmentation of light-exposed skin. Laser-induced chrysiasis is a rarely described phenomenon in individuals who have received systemic gold and are subsequently treated with a Q-switched laser. Purpose: To describe the characteristics of patients with laser-induced chrysiasis. Methods: The authors describe a 60-year-old woman who developed chrysiasis at Q-switched alexandrite laser treatment sites. They also reviewed the medical literature using PubMed, searching the terms chrysiasis, gold, and laser-induced. Patient reports and previous reviews of these subjects were critically assessed and the salient features are presented. Results: Including the authors’ patient, laser-induced chrysiasis has been described in five Caucasian arthritis patients (4 women and 1 man); most of the patients had received more than 8g of systemic gold therapy during a period of 3 to 13 years. Gold therapy was still occurring or had been discontinued as long as 26 years prior to laser treatment. All of the patients immediately developed blue macules at the Q-switched laser treatment site. Resolution of the dyschromia occurred in a 70-year-old woman after two treatment sessions with a long-pulsed ruby laser and the authors’ patient after a sequential series of laser sessions using a long-pulsed alexandrite laser, followed by a nonablative fractional laser and an ablative carbon dioxide laser. Conclusion: Laser-induced chrysiasis has been observed following treatment with Q-switched lasers in patients who are receiving or have previously been treated with systemic gold. It can occur decades after treatment with gold has been discontinued. Therefore, inquiry regarding a prior history of treatment with gold—particularly in older patients with arthritis—should be considered prior to treatment with a Q-switched laser. Also, treatment with a long-pulsed laser should be entertained in patients with either idiopathic or laser-induced chrysiasis. (J Clin Aesthet Dermatol. 2015;8(9):48–53.)
Chrysiasis is a distinctive blue-gray pigmentation of light exposed skin occurring in individuals who are receiving parenteral gold therapy. The 755nm Q-switched alexandrite laser is effective for the treatment of facial lentigines since the melanin granules absorb a high proportion of the laser energy and other chromophores offer little competitive absorption. The authors describe a woman who developed chrysiasis at Q-switched alexandrite laser treatment sites and whose dyschromia was successfully treated with a sequential series of laser sessions using a long-pulsed alexandrite laser, followed by a nonablative fractional laser and an ablative carbon dioxide laser.
A 60-year-old-Caucasian woman with Fitzpatrick type 3 skin presented for treatment of facial solar lentigines. Her past medical history was significant for rheumatoid arthritis. However, she was not taking any photosensitizing medications.
Cutaneous examination revealed several brown macules on her malar cheeks (Figure 1). Treatment was initiated with a 532nm long-pulsed potassium-titanyl-phosphate (KTP) laser at 8J/cm2 for 20ms and 10mm spot with cooling. The response to this laser was as expected with darkening of pigmented lesions and mild perilesional erythema.
Near the end of the treatment session, some low contrast lighter lentigines were treated with a 755nm Q-switched alexandrite laser at 10 to 12J/cm2 at 50 nanoseconds with a 2mm spot. During each pulse, a “shadow like” effect at the spot that was about 10mm in diameter appeared. After 10 lesions were treated, examination of the patient’s cheeks revealed 8 to 12mm blue patches surrounding the smaller lentigines (Figure 2).
Additional history revealed that the patient had received several years of intramuscular gold (sodium aurothio-glucose) to treat her rheumatoid arthritis. However, it had been more than 26 years since her last gold treatment. Correlation of the patient’s clinical history and her subsequent facial dyschromia after treatment established the diagnosis of the bluing effect secondary to Q-switched laser-induced chrysiasis in patients previously or currently treated with gold.
The patient was distressed by her appearance. Only the blue patches remained after the resolution of her coffee ground-like lesions. Based on review of the literature,, a 755nm long-pulsed alexandrite laser with a dynamic cooling device was used to treat the blue spots; it was applied at 40J/cm2 using a 12mm spot and 3ms pulse duration. The cryogen spray cooling setting for the treatment spots was 50ms of cryogen with a 30ms delay. A total of three treatment sessions were performed at one month intervals; there was approximately a 50-percent reduction in pigment.
Subsequently, nonablative fractional laser resurfacing was applied (Fraxel Restore, Solta Medical, Hayward, California) 35mJ, treatment level 7, with a density of 250 microthermal treatment zones (MTZ)/cm2. This series of treatments reduced the pigment by another 30 percent. Finally, an ablative fractional carbon dioxide laser session was applied at 30mJ, 30-percent density (Fraxel Repair, Solta Medical).
Follow-up after the completion of these treatment sessions (which occurred 2 years after her initial treatment session) revealed that the blue macules were completely resolved (Figure 3). The patient was pleased. Not only had the blue macules resolved, but also her overall color, tone, and skin texture had improved.
Medicinal gold. The medicinal use of gold was introduced by the Chinese in 2500 BCE. In the late 19th century and the early 20th century, patients with tuberculosis were treated with gold. Subsequently, gold has been used as a therapeutic alternative in the management of several autoimmune blistering disorders, discoid and systemic lupus erythematosus, and arthritis (such as juvenile, psoriatic, and rheumatoid). The most common side effects of parenteral chrysotherapy are mucosal (glossitis and stomatitis) and cutaneous (dermatitis, lichen planus-like eruption, and pityriasis rosea-like dermatosis).[5–8]
Chrysiasis, history. Chrysiasis—also known as auriasis, chrysoderma, and hautaurosis—is an uncommon adverse cutaneous sequellae that occurs in patients who are receiving prolonged treatment with either intravenous or intramuscular gold. The condition was originally described in 1928 in a young woman who was being treated with intravenous gold therapy for tuberculosis. Subsequently, additional patients with chrysiasis were identified—predominantly Caucasian women—who were receiving intravenous chrysotherapy for psoriasis vulgaris, systemic lupus erythematosus, or tuberculosis. Parental gold salts for the treatment of rheumatoid arthritis were introduced in 19275 and utilized widely for disease management by 1934; however, it was not until 1992 that chrysiasis began to be identified in rheumatoid arthritis patients receiving intramuscular gold salts.[12–14]
Chrysiasis, clinical presentation. Chrysiasis presents as photodistributed blue to blue-gray pigmentation. It is most prominent on the face, often initially appearing symmetrically in the periorbital areas. With increased exposure to gold salts, sun, or both, the pigmentation extends across the forehead into the hairline. Eventually the discoloration can affect the entire face and other light-exposed areas, such as the posterior neck, anterior chest, and dorsal hands. In addition to cutaneous involvement, chrysiasis has also been observed to affect the mucous membranes of the eye and mouth.1,12,15,16 The cumulative dose of gold directly correlates with the degree and intensity of chrysoderma. Skin pigmentation usually begins to occur after the patient has received a total dose of 20mg/kg of elemental gold, which is equivalent to 50mg/kg of either sodium aurothiomalate or sodium aurothioglucose. Hence, for a 150lb (70kg) patient, this would be 3500mg of gold salt.,, However, following intense ultraviolet light exposure, chrysiasis occurred in a woman who had only received 1050mg of gold.
Chrysiasis, light and electron microscopy. Light microscopy of lesional areas in patients with chrysiasis shows aggregates of gold in the papillary and reticular dermis. The gold granules are usually located around blood vessels within macrophages or endothelial cells; however, they can also be extracellular., The gold particles show an orange-red birefringence when routinely processed hematoxylin and eosin stained paraffin tissue sections are evaluated using a polarizing microscope. Interestingly, evaluation of clinically normal appearing skin without evidence of chrysiasis from patients who have received 1 to 2g of gold over 2 to 5 years also shows gold granules on light microscopy. Electron microscopy of both sun-exposed and nonexposed skin from patients with chrysiasis shows aurosomes; these are electron-dense particles within macrophages. However, the pattern of aurosomes differs in sun-exposed and non-sunexposed skin. Similarly, the morphology of the electron-dense deposits of gold differs in Q-switched ruby laser-treated skin versus nontreated skin; the size of the particles is dramatically reduced.
Laser-induced chrysiasis, history. Laser-induced chrysiasis is rare; indeed, it is not mentioned in comprehensive reviews on complications of aesthetic laser dermatologic surgery., It was initially described by Trotter et al in a 59-year-old man with psoriasis and associated arthritis that had been treated for at least the last 13 years with intramuscular gold sodium thiomalate. A 694nm Q-switched ruby laser was used to treat postinflammatory hyperpigmentation on his forehead; blue-gray hyperpigmentation immediately appeared in the treated area.
Laser-induced chrysiasis, epidemiology. In addition to the authors’ patient, subsequent observations of laser-induced chrysiasis have been noted by Yun et al, by Almoallim et al, and most recently by Geist and Phillips (Table 1). Hence, this phenomenon has been reported in five individuals: four women (ranging in age from 40–70 years, median=55 years) and one man. The patients were all Caucasian. There are no reports of spontaneous resolution of the blue macules.
Laser-induced chrysiasis, gold exposure. The patients with laser-induced chrysiasis received gold treatment either for the management of their rheumatoid arthritis,,,current report or psoriatic arthritis. The cumulative dose of gold in two of these individuals ranged from 8 to 11.5 (median = 10g); however, the total amount of gold administered for one of the other women was estimated to range between 4.3 to 13.0g. In four of the patients, intramuscular gold had been administered over a period of time ranging from more than 3 to 13 years (median = 10 years). The remaining woman “…had received a three-year course of oral gold therapy 20 years prior” to laser intervention.
Laser-induced chrysiasis may occur not only during gold therapy, but also many years after gold therapy was discontinued. One patient was still receiving gold when he had his laser treatment. However, four patients had discontinued their gold therapy for at least 1 to 26 years (median = 11 years) prior to being treated with the laser.
Laser-induced chrysiasis, associated laser and site. All of the patients had been treated with a Q-switched laser—Q-switched neodymium-doped: yttrium aluminum garnet (Nd:YAG) (1 woman), Q-switched alexandrite (2 women), or Q-switched ruby laser (2 patients). Laser-induced chrysiasis occurred on the sun-exposed face of all patients; the dorsal hands and thighs were also affected treatment sites in one of the women. All of the patients immediately developed a blue to blue-gray skin discoloration of the laser treatment site.
Laser-induced chrysiasis, pathogenesis: an alteration of dermal gold. Trotter et al attempted to further characterize the pathogenesis of laser-induced chrysiasis. Six months after laser-induced chrysiasis, the investigators evaluated an area of sun-protected skin on their patient’s left inner arm. Treating with the 694nm Q-switched ruby laser again induced immediate blue discoloration. However, testing with the 585nm pulsed dye laser (at a fluence of 5.7J/cm2 for 2 pulses of 5mm spot diameter and pulse width = 450 microseconds) neither caused any skin discoloration nor change in the ultrastructural characteristics of the gold in the dermis when evaluated with electron microscopy. Based on their observations, Trotter et al hypothesized that the Q-switched lasers altered the physiochemical properties of dermal gold resulting in objective changes on electron microscopy, which may represent a change from crystalline to elemental gold.
Laser-induced chrysiasis, treatment. Subsequently, in the 70-year-old woman with Q-switched alexandrite laser-induced chrysiasis, the investigators evaluated a photoprotected site and a test spot was used to allow the same laser to create a hyperpigmented macule. Based on published observations in which either lightening or clearing of Q-switched laser-induced cosmetic tattoo darkening occurred when the same Q-switched laser was used to treat the hyperpigmented site,, the new blue spot was immediately pulsed again with the Q-switched alexandrite laser. Indeed, the center of the lesion showed some clearing; however, around the treated spot, a new rim of blue hyperpigmentation at the periphery was induced.
The researchers then tested untreated areas of the patient’s inner arm with different lasers—a Q-switched ruby laser (which resulted in blue macules), a coaxial flash lamp-pumped dye laser (which resulted in blue macules), and a normal mode ruby laser (which resulted in mild erythema and no darkening). Based on their observations, they treated the laser-induced chrysiasis test sites with a long-pulsed ruby laser; complete or substantial clearing was achieved. Prompted by these results, Yun et al treated the women’s face for two sessions using the long-pulsed ruby laser; two months after the second treatment, the blue macules had almost completely resolved.
Laser-induced chrysiasis-addition insights into pathogenesis: an irradiance-dependent phenomenon. Yun et al, based on their studies, concluded that laser-induced chrysiasis in gold-treated patients is primarily an irradiance- (power delivered per unit area = Watts/cm2) dependent rather than a fluence- (energy delivered per unit area = J/cm2) dependent phenomenon. Therefore, high-irradiance devices, such as Q-switched lasers, are prone to causing this dyschromia. They further speculated that either a chemical alteration of the gold or a mechanical alteration of the aurosome particles—occurring at high irradiance from the laser—results in chrysoderma in these individuals who have previously been treated with gold. Finally, Yun et al recommended that a millisecond-domain laser emitting about 550 and 850nm (such as the long-pulsed versions of the alexandrite, dye, and ruby lasers) should be used to treat laser-induced chrysiasis.
Treatment of idiopathic chrysiasis. After considering the seminal contributions of Trotter et al and Yun et al, Wu et al8 successfully treated a 66-year-old Caucasian woman with generalized idiopathic chrysiasis. The patient had received 33.8g of intramuscular sodium aurothioglucose over 12 years to treat her rheumatoid arthritis. Thirteen years after her last gold treatment (and 23 years after the onset of her chrysiasis), they used a 595nm pulsed dye laser (attempting to treat her facial telangiectasias) with a 7mm spot size, 3ms pulse duration, and radiant exposure initially starting at 8.5J/cm2 and subsequently moving up to 10J/cm2. A total of nine full-face treatments, at 4- to 8-week intervals, were performed; clinical improvement of her chrysoderma was observed 13 months after the first treatment. The investigators were also surprised to observe lightening of test spots on her left shoulder 16 months after treatment with the GentleLase 755nm laser (Syneron Candela, Wayland, Massachusetts) (10mm spot size, 3ms pulse duration, radiant exposure ranging from 25–50J/cm2 and cryogen spray cooling settings at 50ms of cryogen with a 30ms delay) at sites that had shown no improvement six months after treatment.
Treatment of our patient’s laser-induced chrysiasis. Our patient’s Q-switch alexandrite laser-induced chrysiasis was partially treated by using a 755nm long-pulsed alexandrite laser to achieve a 50-percent reduction of the blue macules. Subsequently, her management was optimized with nonablative fractional laser resurfacing (which resulted in another 30% clearing of the hyperpigmentation) followed by ablative carbon dioxide treatment (which provided complete resolution of the residual blue dyschromia). The authors suspect that this combination of laser technologies might also be efficacious for the treatment of individuals with generalized idiopathic chrysiasis.
Laser-induced chrysiasis has been observed following treatment with Q-switched lasers in patients who are receiving or have previously been treated with systemic gold. It is important to emphasize that this phenomenon can occur even decades after treatment with gold has been discontinued. The dyschromia secondary to chrysiasis persists. The facial discoloration in the authors’ patient with laser-induced chrysiasis was successfully diminished by sequentially using three different lasers—a long-pulsed alexandrite laser, a nonablative Fraxel restore laser, and an ablative carbon dioxide laser. In summary, although gold is less commonly used today as a therapeutic agent in medicine, inquiry regarding a prior history of treatment with gold—particularly in older patients with rheumatoid arthritis—should be considered prior to treatment with a Q-switched laser. Also, treatment with a long-pulsed laser should be entertained in patients with either idiopathic or laser-induced chrysiasis.
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