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55655 Clin Pathol 1994;47:556-557 Systemic argyria

R J Prescott, S Wells J Clin Pathol: first published as 10.1136/jcp.47.6.556 on 1 June 1994. Downloaded from

Abstract On examination he showed a bluish dis- A 74 year old man presented with signs colouration of the of his face, neck, and and symptoms of mild cardiac failure. upper chest which he claimed had been pre- His face and chest were severely dis- sent for seven to eight years. Clinically, he coloured, which was thought to be due to was in mild cardiac failure and his blood tests cyanosis. He deteriorated and died of revealed a hypochromic, microcytic anaemia bronchopneumonia. At post mortem (haemoglobin = 108 g/l), a raised erythrocyte examination multiple organs, including sedimentation rate 34 mm/first hour and the skin, showed pigment deposi- abnormal liver function tests (asparate trans- tion; he also had a gastric malignant aminase 159 U/l (normal is <55), lactate neuroendocrine tumour. He gave no his- dehydrogenase 762 U/I (normal is <300), tory of contact with silver compounds. alkaline phosphatase 720 U/I (normal is Systemic argyria caused by chronic 30-135). His serum iron, methaemoglobin, ingestion of silver compounds is a rare and sulphaemoglobin concentrations were condition which, apart from its cosmetic within the normal range. effects, is thought to be relatively harm- An ultrasound scan showed that his liver less; it is not thought to be carcinogenic. was enlarged with multiple space occupying This condition can pose diagnostic prob- lesions, consistent with metastatic tumour. lems for both clinicians and pathologists. Argyria was diagnosed from a skin biopsy specimen and he subsequently deteriorated (J Clin Pathol 1994;47:556-557) and developed terminal bronchopneumonia. Department of Histopathology, Bolton General Case report Post mortem findings Hospital, Farnworth, A 74 year old white man presented with a one The body showed marked blue-grey dis-

Bolton, Lancashire, http://jcp.bmj.com/ BL4 OJR year history of general ill health, e:xertional colouration of the face, neck, and anterior R J Prescott dyspnoea, and ankle oedema. He hadI gone to chest wall. Bilateral arcus senilis was noted. S Wells hospital two years earlier complaining of The oesophagus showed four small polypoid Correspondence to: breathlessness when an abnormal c-omplex- nodules measuring up to 1 cm, located above Dr R J Prescott, Department of Histopathology, ion, thought to be due to central (cyanosis, the oesophago-gastric junction. The stomach Bolton General Hospital, was noted. He gave no drug historyr and, in contained a 6 cm in diameter ulcerated Farnworth, Bolton, Lancashire, BL4 OJR particular, he denied contact with atny com- tumour on the greater curvature of the gastric pounds containing silver in his occuipation as fundus. The liver contained multiple large on September 25, 2021 by guest. Protected copyright. Accepted for publication an engineer in the textile industry. He had, in metastatic tumour nodules. 27 October 1993 the past, worked on a sheep farm in AWustralia. The lungs showed bronchopneumonic consolidation of the right lower lobe and pro-

.::.....:.:; nounced oedema. The heart was of normal size but showed scarring of the anteroseptal left ventricular wall. The right coronary artery Aw was completely occluded by atheroma. The -4 ...... other organs were grossly normal. Microscopically, the skin showed fine gran-

:.j. .,:.. *: :.:.... ular deposits of black pigment within the *:.~~~~~~~~~~~~~~~~~~~~~~~...... :.Z::. basement membranes of the and ': § epidermis sweat ducts. The pigment was bleached by a solution of 1% potassium ferricyanide in 20% sodium thiosulphate, thus proving it con- a. AN,

z . .-: I.. *..: -* b The oesophageal polypi were tubulovillous ..... adenomas. The gastric tumour showed fea- tures of a malignant neuroendocrine tumour in which no argyrophilia was demonstrable. The liver contained metastatic neuroen- Fine granular deposits ofsilver pigment in a renal glomerulus. docrine tumour deposits. Systemic argyria 557

The lungs showed bronchopneumonia, The cutaneous pigment may be silver sul- mild emphysema, focal mild interstitial fibro- phide, chloride, or metallic silver which sis, and a foreign body giant cell reaction to results from photoactivated reduction of sil- aspirated food particles. The heart showed ver salts within tissues.7 A direct stimulatory myocardial fibrosis. The cause of death was effect of silver on increases the J Clin Pathol: first published as 10.1136/jcp.47.6.556 on 1 June 1994. Downloaded from bronchopneumonia. degree of skin pigmentation in areas exposed to sun which is permanent and irreversible.8 Systemic argyria has not been associated Discussion with any neoplasia and, in our case, the neu- Argyria was recorded in ancient times due to roendocrine tumour must have been a coinci- the usage of silver compounds in treating var- dental finding. In our patient no source of the ious disorders. Sola in 1647 silver ingestion could be found and the skin advocated silver nitrate for treating epilepsy, discolouration was mistakenly thought to be tabes, and chorea.2 The prevalence of argyria solely due to cardiac cyanosis, an error which increased until the late 19th century when has been documented before.5 910 silver was described.3 Acute silver Other conditions which can lead to similar may cause haemorrhage and ero- skin pigmentation are methaemoglobinuria, sive intestinal lesions,4 but in small doses metastatic melanoma with melanogenuria, silver compounds are thought to be harmless and haemochromatosis.11 despite widespread systemic deposition, Pathologists and clinicians alike should be though the cosmetic disability can be psycho- aware of this rare condition which can pose logically traumatic. diagnostic difficulties. The main route of absorption is through the gastrointestinal tract, but the respiratory mucosa or broken skin are other alternative 1 Pearse AGE. Inorganic constituents. In: Histochemistry, routes. Substances which include silver com- theoretical and applied. 3rd edn. Edinburgh: Churchill pounds include antimicrobial, astringent, and Livingstone, 1961:703-4. 2 Sola A. Opera Medicochymica quae Extant Omnia. caustic agents which produce systemic depo- Frustulatim Hactenus Diversique Linguis Excusa, nunc in sition, but, localised argyria can be seen in Unum Colecta Latinque Idiomate Edita. Frankfurt, Germany, J Beyeri, 1647. the eye or oral mucosa following topical 3 Potter SOL. Silver and other . In: Handbook of application5 or as an occupational in materia medica, pharmacy and therapeutics. 4th edn. Philadelphia: Blakiston, 1892:115-6. silver workers. Dental amalgam displaced 4 Hill WR, Pillsbury DM. Argyria: the pharmacology of silver. into oral tissues during drilling may produce Baltimore: Williams & Wilkins, 1939. 5 Marshall JP, Schneider RP. Systemic argyria secondary to localised argyria. There is a report of anti- topical silver nitrate. Arch Dermatol 1977;113:1077-9. smoking lozenges causing argyria.6 6 MacIntyre D, McLay ALC, East BW, et al. Silver - ing associated with an antismoling lozenge. In: Br Med J Although any organs may be the site of 1978;ii: 1749-50. silver deposition, the skin and connective tis- 7 Goodman LS, Gilman A. Heavy metals. In: Pharmacological basis of therapeutics. 5th edn. New York:

sues are said to have the highest concentra- MacMillan, 1975:930-1. http://jcp.bmj.com/ tions. The silver granules preferentially 8 Buckley WR. Localised argyria. Arch Dermatol 1963;88: 531-9. localise in the basal lamina of the secretory 9 Rich LL, Epinette WW, Nasser WK. Argyria presenting portion of eccrine glands, elastic fibres of the as cyanotic heart disease. Am Y Cardiol 1972;30:290-2. 10 Levine SA, Smith JA. Argyria confused with heart disease. papillary dermis, dermal collagen and, to a N EngJMed 1942;226:682-4. lesser extent, in connective tissues surround- 11 Wintrobe MM, Thorn GW, Adams RD, et al. Pigmentation of the skin and disorders of ing pilosebaceous units, arteriolar walls, per- metabolism. In: Harrison's principles of intemal medicine. Book 1978:250-5. ineural tissues and arrector pili muscles. New York: McGraw-Hill Co, on September 25, 2021 by guest. Protected copyright.