ACMT Toxicology Visual Pearl: Turning Blue

2. Colloidal silver, 30 ppm liquid solution

Background

Chronic ingestion or topical application of colloidal silver can result in deposition of silver molecules into the dermis. The resulting blue-grey skin discoloration is known as argyria and can be focal in areas of direct silver exposure or generalized following silver molecule ingestion. Unfortunately, it is irreversible.

What are the medical uses of silver?

• Silver is a naturally occurring soft metal that has been found to have antimicrobial properties in its ionized form (Ag¹⁺) [1].
• The medical use of silver dates back thousands of years; Hippocrates discussed the use of silver in wound care in his writings [2].
• Silver was commonly used to prevent and treat wound infections throughout the late 19^th and early 20^th centuries, until its use fell out of favor with the advent of antibiotics [2].
• The medical uses of silver approved by the Food and Drug Administration are limited to mucocutaneous applications for burns, open wounds, and chronic ulcers [3,4].
• Colloidal silver preparations are an alternative medicine treatment marketed as having curative properties, despite lack of evidence to support these claims [4].
• These compounds are most frequently ingested, although exposure also occurs via cutaneous application, inhalation, and eye drops.
• Long term use of colloidal silver preparations has been associated with argyria [5].

What clinical effects are seen with chronic silver exposure? [4-11]

• Argyria is the most common sequela of chronic exposure to elemental silver.
• Localized dermal discoloration can occur following occupational exposure to silver, long-term contact with silver jewelry, or application of silver-containing topical treatments.
• Argyrosis refers to the deposition of silver in the eye, which can occur from systemic silver exposure or use of colloidal silver eyedrops.
• While systemic effects of silver toxicity are rare, there are reports of toxicity to a variety of organ systems following chronic exposure to silver products.
  • Neurologic sequelae include vertigo, hyposmia, ataxia, hypoesthesia, and seizures.
  • Bone marrow suppression and anemia have been reported.
  • Renal injury and proteinuria have been seen from damage to glomeruli from renal deposition.
  • Cardiotoxicity from silver deposition in blood vessels has been reported.
  • Inhalation of silver products can result in pneumonitis and respiratory insufficiency.
  • There is no clear lifetime silver dose known to be toxic to humans, though the World Health Organization cites 10g as the no-observed-adverse-effect level in humans.

How is argyria diagnosed? [4, 5]

• Clinicians must have a high index of suspicion for the diagnosis of argyria and other systemic manifestations of silver toxicity.
• A history of occupational exposure to silver-containing compounds or reported consumer use of colloidal silver products is most beneficial in establishing the diagnosis.
• Argyria is often a diagnosis of exclusion, and other causes of blue skin discoloration should be considered before making the diagnosis.
• The definitive diagnostic modality is a skin biopsy showing brown or black granules on histopathology.
• The gold standard technique for analysis is energy-dispersive x-ray spectroscopy of a tissue sample, which identifies the chemical elements within the granules.

What else can cause blue skin discoloration? [4, 12-16]

• Cyanosis secondary to inadequate oxygenation of the tissues.
• Methemoglobinemia is a condition caused by oxidation of iron from the ferrous [Fe2+] state to the ferric [Fe3+] state, resulting in diminished oxygenation of tissues and blue-gray skin discoloration.
• Methylene blue administration has been shown to cause transient blue discoloration to the skin, mucous membranes, bodily fluids, and other body tissues.
• Melanoma lesions may cause localized dark discoloration of the skin.
• Some specific medications, including amiodarone, minocycline, and phenothiazines, have been shown to discolor the skin.
• Ochronosis is the discoloration of skin secondary to deposition of decayed phenol compounds in collagen. This can result from genetic conditions such as alkaptonuria, or exogenous agents that enzymatically inhibit homogentisate dioxygenase (e.g. quinines, resorcinol, and hydroquinone).
• The deposition of other heavy metals in the skin, such as iron and gold, should be considered in the differential of heavy metal exposures.
• Blue fabric dyes can cause temporary discoloration of skin.

How can you treat argyria or other sequelae of silver exposure? [4, 8, 16,17]

• Unfortunately, the skin discoloration from argyria is permanent, and there are no known treatments for removing silver particles from the dermis.
• Laser therapy, often used to remove tattoos, has been attempted to remove pigment in case reports.
• Chelation is not effective for treating silver toxicity.
• Management includes discontinuing the source of silver exposure and limiting sun exposure, which can worsen skin discoloration.

Bedside Pearls

• Argyria is blue-grey discoloration of mucocutaneous membranes and results from deposition of silver in the dermis following chronic exposure.
• Diagnosis involves a detailed history of contact with silver-containing products, through occupational exposures, medicinal therapies, or consumer products.
• Be sure to exclude other causes of blue skin discoloration, including cyanosis, methemoglobinemia, melanoma, medication side effects, or exposure to other heavy metals.
• While systemic effects from silver exposure are most often limited to the skin and mucosal membranes, rarely systemic symptoms have been reported.
• There is no known effective chelator for silver toxicity and the skin manifestations are often permanent.