Generalized Argyria. Case Report. -A Case Report

Transcription

1 Case Report Generalized Argyria -A Case Report Chin-Ya Yang Yi-Ju Chen Jui-Lung Shen Generalized argyria is a rare disease caused by deposition of silver in the skin, nails, mucous membranes, and internal organs. It is characterized by a diffuse slate-blue discoloration in sun-exposed areas. Here, we report a case of 38-year-old woman with generalized argyria. Pathologically, there were numerous minute fine brownish-black pigments fairly uniform in size, which were observed in the dermal interstitium, around the hair follicles, sebaceous glands, eccrine glands and the walls of capillaries. Darkfield microscopy showed refractile white particles. In this report we also review the literature about this rare disease. (Dermatol Sinica 26: 75-79, 2008) Key words: Argyria, Silver INTRODUCTION Generalized argyria is a rare disease caused by deposition of silver granules in the skin, nails, mucous membranes, and internal organs. A distinctive slate-blue pigmentation, most apparent in sun-exposed areas, is the main clinical presentation of this otherwise asymptomatic disease. Generalized argyria is now rarely reported because of the cessation of silver usage in oral medications and decreased occupational exposure. CASE REPORT A 38-year-old otherwise healthy woman presented with a 5-year history of slate-blue pigmentation. She first noticed the bluish skin color change in her face which subsequently also involved her forearms and nails. She denied having had any exposure to heavy metals or having taken any systemic medications or alternative health treatments. But she stated she had taken the breath freshener Jintan( 仁丹 )silver pills daily for the past 2 to 3 decades. Physical examination revealed diffuse slate-blue cutaneous pigmentation, most strikingly on the sun-exposed areas of her eyebrows, nose, cheeks, neck, forearms and dorsal hands. (Fig. 1, 2) A subtle bluish discoloration was present in the lanulae of the fingernails. (Fig. 3) Her toenails, sclerae and oral mucosa appeared normal. Incisional biopsy of the left side of the nose was performed under the suspicion of argyria. Histologically, there were numerous minute fine brownish-black extracellular pigments fairly uniform in size, which were observed in the dermal interstitium (Fig. 4), around the Frome the Department of Dermatology, Taichung Veterans General Hospital Accepted for publication: December 27, 2007 Reprint requests: Yi-Ju Chen, Department of Dermatology, Taichung Veterans General Hospital, No. 160, Sec. 3, Chung-Kang Rd, Taichung, Taiwan TEL: ext FAX: yjchenmd@vghtc.gov.tw 75

2 Chin-Ya Yang, et al hair follicles (Fig. 5), sebaceous glands, eccrine glands (Fig. 6) and the walls of capillaries. Darkfield microscopy revealed brilliantly refractile white particles around eccrine glands, blood vessels and were interspersed in the dermis. Generalized argyria was diagnosed based on clinical and pathological findings. However, the patient refused to undergo further examinations. Sun protection and opaque cosmetics were suggested to prevent further pigmentary change and to mask discoloration. Fig. 1 Slate-blue discoloration over the face. Fig. 2 Slate-blue discoloration over patient s forearm (left) compared with healthy person s forearm (right) Fig. 3 Slate-blue discoloration of patient s nails (left) compared with healthy person s nails (right) DISCUSSION Argyria was recorded in ancient times. Bluish discoloration of the eyes caused by silver ingestion was first described in the 8 th century. 1 Argyria was common in the 19 th century as a result of silver usage in treating mental illness, epilepsy, nicotine addiction, gastroenteritis, syphilis, and gonorrhea. Occupational exposure to silver contributed to the development of argyria in silversmiths, miners and photographers. 2 However, since the cessation of medicinal use of silver and initiation of standards for occupational exposure, reported cases of argyria have been rare. Argyria can be classified into localized and generalized forms. Localized argyria may appear as slate-blue macules. It is occasionally caused by silver earrings, acupuncture needles and topical application of silver-containing products for wounds. 3-6 In contrast, generalized argyria is characterized by a slate-blue discoloration of the entire skin surface, which is most pronounced in the sun-exposed areas such as face, neck, V area of the chest, forearms and dorsum of the hands. The nails and mucous membranes may also be involved. Silver may also be detected in internal organs. However, there have only been a few case reports of neurologic, renal and hepatic problems associated with argyria. 7 Nowadays, generalized argyria 1, 2, 8-10 is associated with colloidal silver solution, nose drops as a vasoconstrictor, 11, 12 and silver- 76 Dermatol Sinica, Jun 2008

3 Generalized Argyria coated sugar particles. 13 The smallest amount of silver reported to cause generalized argyria ranges from 4 to 5g. 14 In Japan, cases of generalized argyria due to the breath freshener Jintan silver pills, as in our patient, have been 1, 15 reported. Skin biopsy is important to differentiate argyria from other causes of hyperpigmentation. Typical histologic findings include extracellular brownish-black fine granules deposited primarily in the dermis but especially concentrated in the basement membrane zone surrounding the eccrine glands and connective tissue sheaths around pilosebaceous structures. Although histopathology is sufficient to make the diagnosis of argyria, there are other methods to confirm it. Dark-field microscopy displays numerous brilliantly refractile granules mostly around the eccrine glands. 16 Scanning electron microscopy demonstrates silver granules as electron-dense clumps of particles, distributed along the basement membranes of dermo-epidermal junction, eccrine, sebaceous glands and elastic microfibrils. 17 Scanning electron energy dispersion x-ray microanalysis can be used to confirm the presence of silver. 16 The deposition of silver in the skin is uniform. However, the slate-blue discoloration is most prominent in sun-exposed areas. 8 This occurs because the discoloration is not caused by the deposited silver compounds themselves. Instead, the discoloration is caused by the combined effect of reduction of silver compounds and an increase in melanin production. The colorless silver is reduced by sunlight to brownish-black silver sulphides and selenide within tissues. 2 The deposited silver also stimulates tyrosinase activity of melanocytes to produce more melanin. 8, 14, 18 The differential diagnosis for generalized argyria includes endogenous causes such as central cyanosis, methemoglobinemia, Addison s disease, hemochromatosis, disseminated melanoma and uremia as well as exogenous causes such as ingestion of certain compounds Fig. 4 Numerous minute fine brownish black pigments in the dermal interstitium. (H&E, original magnification x600). Fig. 5 Numerous minute fine brownish black pigments around hair follicles. (H&E, original magnification x600). Fig. 6 Numerous minute fine brownish black pigments around eccrine glands. (H&E, original magnification x600). Dermatol Sinica, Jun

4 Chin-Ya Yang, et al (antimalarials, minocycline, amiodarone, chlorpromazine) or other metals (gold, mercury, 10, 18 and bismuth). Silver deposition and the discoloration of the skin in argyria are usually permanent and 1, 11 primarily of cosmetic significance. Depigmenting creams, 19 hydroquinone, dermabrasion 2 and chelating agents such as British anti-lewisite, D-penicillamine and 2, 3-dimercaptopropane-1-sulphonate are not effective. 1, 18, 20 Sun protection and opaque cosmetics may help to prevent further pigmentary darkening and mask discoloration. Thus, we report a rare case of generalized argyria associated with breath freshener Jintan silver pills. Argyria should be considered in the differential diagnosis of patients with hyperpigmentation. REFERENCES 1. Brandt D, Park B, Hoang M, et al.: Argyria secondary to ingestion of homemade silver solution. J Am Acad Dermatol 53: S105-S107, White JM, Powell AM, Brady K, et al.: Severe generalized argyria secondary to ingestion of colloidal silver protein. Clin Exp Dermatol 28: , Morton CA, Fallowfield M, Kemmett D: Localized argyria caused by silver earrings. Br J Dermatol 135: , Tanita Y, Kato T, Hanada K, et al.: Blue macules of localized argyria caused by implanted acupuncture needles: electron microscopy and roentgenographic microanalysis of deposited metal. Arch Dermatol 121: , Kakurai M, Demitsu T, Umemoto N, et al.: Activation of mast cells by silver particles in a patient with localized argyria due to implanatation of acupuncture needles. Br J Dermatol 148: 822, Fisher NM, Marsh E, Lazova R: Scar-localized argyria secondary to silver sulfadiazine cream. J Am Acad Dermatol 49: , Payne CM, Bladin C, Colchester AC, et al.: Argyria from excessive use of topical silver sulphadiazine. Lancet 340: 126, Chang ALS, Khosravi V, Egbert B: A case of argyria after colloidal silver ingestion. J Cutan Pathol 33: , McKenna JK, Hull CM, Zone JJ. Argyria associated with colloidal silver supplementation. Int J Dermatol 42: 549, Wadhera A, fung M. Systemic argyria associated with ingestion of colloidal silver. Dermatol Online J 11: 12, Bianchi L, Orlandi A, Di Stefani A, et al.: Familial" generalized argyria. Arch Dermatol 142: , Tomi NS, Kränke B, Aberer W: A silver man. The Lancet 363: 532, Hanada K, Hashimoto I, Kon A, et al.: Silver in sugar particles and systemic argyria. Lancet 351: 960, Massi D, Santucci M: Human generalized argyria: a submicroscopic and x-ray spectroscopic study. Ultrastruct Pathol 22: 47-53, Shimamoto Y, Shimamoto H. Systemic argyria secondary to breath freshener Jintan silver pills." Hiroshima J Med Sci 36: , Robinson-Bostom L, Pomerantz D, Wilkel C, et al.: Localized argyria with pseudo-ochronosis. J Am Acad Dermatol 46: , Shall L, Stevens A, Millard LG: An unusual case of acquired localized argyria. Br J Dermatol 123: , Gulbranson SH, Hud JA, Hansen RC: Argyria following the use of dietary supplements containing colloidal silver protein. Cutis 66: , Marshall JP, Schneider RP: Systemic argyria secondary to topical silver nitrate. Arch Dermatol 113: , Sue YM, Lee JY, Wang MC: Generalized argyria in two chronic hemodialysis patients. Am J Kidney Dis 37: , Dermatol Sinica, Jun 2008

5 Generalized Argyria 全身性銀質沈著症 - 病例報告 楊智雅陳怡如沈瑞隆 台中榮民總醫院皮膚科 全身性銀質沈著症是由於銀沈積在皮膚 指甲 黏膜和內臟器官所造成的少見疾病 臨床上可在日曬處皮膚看到灰藍色的變化 本文報告一例發生在 38 歲女性的全身性銀質沈著症, 病理可見在真皮間質 毛囊 皮脂腺 汗腺和微血管壁周圍有許多細小的棕黑色色素, 暗視野顯微鏡下見到白色小點 在本文中, 我們同時回顧和此病相關的文獻 ( 中華皮誌 : 26: 75-79, 2008) Dermatol Sinica, Jun