eMedicine Specialties > Dermatology > Diseases of Pigmentation

Argyria: Differential Diagnoses & Workup

Author: Kamila K Padlewska, MD, PhD, Professor, Warsaw Academy of Cosmetics and Health Care; Chief Executive, Cosmetic-Medical Cooperative, Poland
Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Contributor Information and Disclosures

Updated: Mar 13, 2009

Differential Diagnoses

Ochronosis

Other Problems to Be Considered

Medications (ie, phenothiazines, antimalarials, amiodarone, minocycline)
Hemochromatosis
Polycythemia vera
Addison disease
Diffuse melanosis in metastatic melanoma
Heavy metals (ie, mercury, bismuth, arsenic, gold, lead)
Central cyanosis (impaired pulmonary function, anatomic shunt, hemoglobin abnormalities, methemoglobinemia)
Peripheral cyanosis (reduced cardiac output)

Workup

Imaging Studies

In vivo silver concentrations can be measured using x-ray fluorescence.13

Procedures

The diagnosis of argyria is established by skin biopsy with formaldehyde-fixed paraffin-embedded sections stained with hematoxylin-eosin.

Histologic Findings

Small, round, brown-black granules appear singly or in clusters and are evident with routine staining. They spare both the epidermis and its appendages, appearing in greatest numbers in the basement membrane zone surrounding sweat glands. These silver granules also favor the connective-tissue sheaths around pilosebaceous structures and nerves. They have a predilection for elastic fibers and are best visualized as strikingly refractile with dark-field illumination. An increase in the amount of melanin in exposed skin also appears to occur.

Electron microscopy demonstrates electron-dense granules. In early cases, they are located within fibroblasts and macrophages, while later most are present extracellularly. Neutron activation analysis, atomic absorption spectrophotometry, or x-ray dispersive microanalysis can be used to confirm that the granules contain silver and often also sulfur and less commonly selenium.14,15,16 A simpler option is to decolorize the silver by placing histologic sections into 1% potassium ferricyanide in 20% sodium thiosulfate.

More on Argyria

Overview: Argyria
Differential Diagnoses & Workup: Argyria
Treatment & Medication: Argyria
Follow-up: Argyria
References
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References

  1. Bouts BA. Images in clinical medicine. Argyria. N Engl J Med. May 20 1999;340(20):1554. [Medline].

  2. Fung MC, Bowen DL. Silver products for medical indications: risk-benefit assessment. J Toxicol Clin Toxicol. 1996;34(1):119-26. [Medline].

  3. Gulbranson SH, Hud JA, Hansen RC. Argyria following the use of dietary supplements containing colloidal silver protein. Cutis. Nov 2000;66(5):373-4. [Medline].

  4. Brandt D, Park B, Hoang M, Jacobe HT. Argyria secondary to ingestion of homemade silver solution. J Am Acad Dermatol. Aug 2005;53(2 Suppl 1):S105-7. [Medline].

  5. Gaslin MT, Rubin C, Pribitkin EA. Silver nasal sprays: misleading Internet marketing. Ear Nose Throat J. Apr 2008;87(4):217-20. [Medline].

  6. Legat FJ, Goessler W, Schlagenhaufen C, Soyer HP. Argyria after short-contact acupuncture. Lancet. Jul 18 1998;352(9123):241. [Medline].

  7. Rackoff EM, Benbenisty KM, Maize JC, Maize JC Jr. Localized cutaneous argyria from an acupuncture needle clinically concerning for metastatic melanoma. Cutis. Nov 2007;80(5):423-6. [Medline].

  8. Prescott RJ, Wells S. Systemic argyria. J Clin Pathol. Jun 1994;47(6):556-7. [Medline].

  9. Bianchi L, Orlandi A, Di Stefani A, Ricci R, Chimenti S. "Familial" generalized argyria. Arch Dermatol. Jun 2006;142(6):789-90. [Medline].

  10. Menaguale G, Fazio R, Fazio M. Argyria: a case following the prolonged use of a rhinologic drug. Esper Dermatol (Roma). 2003;4:299-303.

  11. Fisher NM, Marsh E, Lazova R. Scar-localized argyria secondary to silver sulfadiazine cream. J Am Acad Dermatol. Oct 2003;49(4):730-2. [Medline].

  12. Shelley WB, Shelley ED, Burmeister V. Argyria: the intradermal "photograph," a manifestation of passive photosensitivity. J Am Acad Dermatol. Jan 1987;16(1 Pt 2):211-7. [Medline].

  13. Graham SA, O'Meara JM. The feasibility of measuring silver concentrations in vivo with x-ray fluorescence. Phys Med Biol. Aug 7 2004;49(15):N259-66. [Medline].

  14. Lee SM, Lee SH. Generalized argyria after habitual use of AgNO3. J Dermatol. Jan 1994;21(1):50-3. [Medline].

  15. Robinson-Bostom L, Pomerantz D, Wilkel C, et al. Localized argyria with pseudo-ochronosis. J Am Acad Dermatol. Feb 2002;46(2):222-7. [Medline].

  16. Sato S, Sueki H, Nishijima A. Two unusual cases of argyria: the application of an improved tissue processing method for X-ray microanalysis of selenium and sulphur in silver-laden granules. Br J Dermatol. Jan 1999;140(1):158-63. [Medline].

  17. Rhee DY, Chang SE, Lee MW, Choi JH, Moon KC, Koh JK. Treatment of argyria after colloidal silver ingestion using Q-switched 1,064-nm Nd:YAG laser. Dermatol Surg. Oct 2008;34(10):1427-30. [Medline].

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Further Reading

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Keywords

argyria, universal argyria, localized argyria, ingestion of silver salts, contact with silver salts, staining of skin, silver staining

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Contributor Information and Disclosures

Author

Kamila K Padlewska, MD, PhD, Professor, Warsaw Academy of Cosmetics and Health Care; Chief Executive, Cosmetic-Medical Cooperative, Poland
Kamila K Padlewska, MD, PhD is a member of the following medical societies: Academy of Medical Royal Colleges
Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Smeena Khan, MD, Private Practice, Adult and Pediatric Dermatology Associates
Smeena Khan, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey J Miller, MD, Associate Professor of Dermatology, Penn State University College of Medicine; Staff Dermatologist, Penn State Milton S Hershey Medical Center
Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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