Question 1 of 10

    Argyria (Silver Staining)

    Argyria 2b[1]

    Argyria is a rare skin condition that develops following contact with silver salts.

    Argyria is induced by the following process: Poison.

    Presentation

    Because argyria is a rare skin disorder a detailed history about silver exposure is required. It is important to delve into any past occupational history of metal exposure or use of dietary supplements containing silver. Some individuals may be using silver containing nose drops that are known to produce pigmentation on the nail lunula and nose. In burn patients, prolonged use of silver sulfadiazine may also induce scar-localized argyria.

    On physical the findings depend on how long the silver containing products have been used. In acute cases, there may be no obvious findings. After prolonged use, one may visualize a greyish brown stain on the gums as the first sign of argyria. Over time, some patients may show diffuse grayish patches on the skin. The cutaneous pigmentation may appear bluish gray, metallic or dirty silver. The skin pigmentation is often more obvious in the sun-exposed areas like the neck, face, nose, hands and fingers. In the very rare patient, the patient’s entire skin may appear a dull blue or gray color.

    Besides the skin, one may notice discoloration of the nail beds, sclera and mucus membranes. When the abdomen is explored at surgery or during post mortem examination, it may also reveal bluish discoloration of the liver, spleen, small bowel and mesentery. In extremely rare cases, some individuals may have black tears (melanodacryorrhea).

    Even though some patients may develop skin discoloration after a few months, the majority of individual develop argyria after a few years.

    Jaw & Teeth
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  • Entire body system
    Chronic Infection
    • This reduction may play a role in the worldwide epidemic of chronic infections.)[elixa.com]
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  • neurologic
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  • Skin
    Hyperpigmentation
    • What is apparent is that the degree of hyperpigmentation in patients is directly correlated with the amount of sliver present.[dermnetnz.org]
    • The hyperpigmentation of argyria is usually permanent, and it follows a sun-exposed distribution.[thedoctorsdoctor.com]
    Photosensitivity
    • PHOTOGRAPH Argyria: the intradermal "photograph," a manifestation of passive photosensitivity.[thedoctorsdoctor.com]
    Skin Patch
    • Sex distribution Age distribution Pathophysiology Following skin contact, some individuals will only develop localized skin patches of argyria.[symptoma.com]
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  • respiratoric
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  • cardiovascular
    Heart Disease
    • DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES HEART DISEASE Argyria and cyanotic heart disease.[thedoctorsdoctor.com]
    • For example: Diabetes, pancreatitis and heart disease are very real side effects of excessive usage of sugar.[thesilveredge.com]
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  • urogenital
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  • psychiatrical
    Suggestibility
    • ‘If we've evolved alongside them, then that suggests they may not be so dangerous.’[rsc.org]
    • Keep in mind that we also suggest taking a break occasionally from drinking ionic colloidal silver or from any nutritional supplement.[sharinghealth.com]
    • You are free: to share – to copy, distribute and transmit the work to remix – to adapt the work Under the following conditions: attribution – You must attribute the work in the manner specified by the author or licensor (but not in any way that suggests[commons.wikimedia.org]
    • This suggests that people with argyria ingested too much of the solution over too short a time.[health.howstuffworks.com]
    • Reports of cases of argyria suggest that gram amounts of a silver compound taken in medication in small doses over several months may cause argyria in some humans.[weird-encyclopedia.com]
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  • Eyes
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  • Workup

    Imaging 

    Plain X-rays may sometimes reveal heavy deposits of silver but the concentration can be measured by using x-ray fluorescence. However, this technique is not useful for assessing silver deposition in bone or internal organs.

    Laboratory studies

    Silver levels can be measured in blood but the testing is not readily available in all medical laboratories. If organ dysfunction is suspected, a total blood count, renal and liver function, blood glucose, and creatine kinase levels should be ordered.

    Procedures

    The definitive procedure to confirm argyria is a skin biopsy. Histology will reveal black brown granules either singly or in aggregates located in the basement membrane zone surrounding sweat glands. The silver granules also deposit around nerves and pilosebaceous glands. Silver granules have a strong affinity for elastic fibers where they often appear as refractile particles under dark field illumination.

    Electron microscopy may be performed to look for specific location of silver granules. In early cases of argyria, the granules may appear in macrophages and fibroblasts. In chronic cases, the granules may be extracellular.

    Other studies

    If the patient has neurological deficits, one may require a comprehensive neurological exam, nerve conducting tests and EMG studies. A CT scan may be ordered if a patient has seizure to rule out any mass. The role of lumbar puncture in a patient with argyria is non-productive.

    Laboratory

    Microbiology
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  • Treatment

    In general, the treatment of argyria is strictly for cosmetic reasons. The skin disorder rarely causes any symptoms but most people do not like the dark grayish cosmetic appearance and would like something done. Over the years many depigmentation solutions or bleaching agents have been developed, but none of them have proven to be effective. Isolated case reports reveal that 5% hydroquinone may decrease the number of silver granules in the upper layers of skin, around sweat glands and also lower the number of melanocytes. Hydroquinone reverses the depigmentation by inhibiting the oxidation of tyrosine to 3, 4-dihydroxyphenylalanine and inhibits melanocyte metabolic process. The agent does not actually cause reversal of most skin lesions but prevents the lesions from getting darker. Unfortunately, it does not work in everyone. Treatments like dermabrasion and use of chemical peels do not work and are more likely to induce complications.

    Various types of chelating agents have been used in the past to remove silver, but none has proven to be effective. For most people, the best treatment of the skin discoloration is wearing garments to hide the pigmentation and use of sunscreen. Because argyria can worsen with sun exposure, it is highly recommended that sunscreens be applied liberally anytime the individual ventures out of the home. Use of opaque cosmetics has been suggested as means to prevent further darkening of skin and also an aid for masking the skin pigmentation.

    Surgical care

    Some cosmetic surgeons have used the Nd:YAG laser to treat the discoloration. However, there are only isolated reports of benefit. Laser is prohibitively expensive, requires many sessions and can also cause complications that may worsen the skin discoloration. Because the silver particles are in the dermis, the intensity of laser required is high and this can be painful. Thus, some type of analgesia is also required during treatment. Laser is a last resort treatment and should only be undertaken for isolated patches. Laser is not recommended for treatment of large body areas, as the laser can be very painful.

    Medications

    Both sulfur and selenium compounds have been used to chelate to free silver and modify its toxicity. Once silver binds to selenium, the salt is insoluble and unable to penetrate tissues. Thus, this reduces the effect of free silver from interfering with enzymatic activity in various tissues. Binding of silver to sulfur also results in similar insoluble complexes, but repeated doses are required.

    Prognosis

    The prognosis for patients with argyria depends on the extent of the silver deposition [5] [10]. In individuals with just skin and mucus membrane involvement, the prognosis is good. These individuals only have a cosmetic problem, which unfortunately is permanent. For individuals who have silver depositions in organs like the kidney, brain, liver or pancreas, the prognosis is variable. Organ dysfunction can occur and progress. Because of lack of good treatment, the only way to prevent progression of disease is prevention of additional silver exposure.

    Complications

    Gastroesophageal Reflux Disease
    • In the remote past, colloidal silver suspensions were often used to treat a variety of gastrointestinal tract disorders like stomach upset, gastroesophageal reflux disease ( GERD ), peptic ulcer disease and gastritis .[symptoma.com]
    Lead Poisoning
    • Unfortunately, skin cancer and permanent staining of the skin were the result along with lead poisoning.[healpastlives.com]
    Methemoglobinemia
    • In their case, blue skin was caused by a rare genetic disease called methemoglobinemia.[livescience.com]
    • In the mildest form, methemoglobinemia causes no harm, and most of the Fugates lived well into their 80s.[abcnews.go.com]
    • Carotenodermia Chrysiasis Methemoglobinemia, another condition known for causing blue skin coloration Amalgam tattoo CDC Public Health Statement for Silver. 1990 alert from U.S.[en.wikipedia.org]
    • Some of their children suffered from a condition called methemoglobinemia, which “reduces individual’s ability to carry oxygen in blood.”[starcasm.net]
    Stroke
    • Real-life ‘Blue Man’ dies after heart attack, stroke .[decodedscience.org]
    • Misdiagnosis and Argyria Undiagnosed stroke leads to misdiagnosed aphasia : BBC News UK reported on a man who had been institutionalized and treated for mental illness because he suffered from sudden inability to speak.[rightdiagnosis.com]
    • Paul Karason died Monday after suffering a heart attack and severe stroke, his estranged wife Jo Anna Karason told Today.com Tuesday .[newsmax.com]
    • According to his estranged wife, Jo Anna Karason, "Papa Smurf" also suffered from severe stroke.[latinpost.com]
    • His death came as a result of a stroke he suffered while hospitalized for pneumonia and heat stroke.[guardianlv.com]
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  • Etiology

    Globally, the most common cause of argyria is exposure of workers to silver in the heavy metal industry (eg. silver refining, mining or metal alloy manufacture), where the individual is constantly exposed to silver particles. Other occupations where one may become exposed to silver include contact with electroplating solutions, adding metallic film on china and glassware and during photographic processing. There are also a few dietary supplements sold for the treatment of AIDS, cancer, diabetes and herpes infections that also contain silver salts. There are also several reports of argyria following use of silver salts for irrigation of nasal mucus membrane and urethra, in wound dressings, eye drops and prolonged use of an anti-smoking aid that contains silver acetate.

    The common causes of argyria include the following:

    • Mechanical impregnation of the skin by small silver particles in workers who work in the silver mining or refining industry.
    • Working with silverware and metal alloy manufacturing.
    • Etching metallic films on glass and chinaware.
    • Come in contact with electroplating and photographic processing solutions.
    • Use colloidal silver dietary supplements are marketed for treatment of cancer, diabetes, cystic fibrosis [4], weight loss, AIDS and herpetic infections.
    • Cases have occurred following the prolonged use of silver salts for the irrigation of urethral or nasal mucous membranes. 
    • Use of certain wound dressings (eg. Aquacel, Acticoat, silvercel) and eye drops (colloidal silver) may also cause argyria.
    • Excessive use of silver acetate as an aid to quit smoking has also been associated with argyria of the oral mucosa. 
    • Argyria has also been observed after dental and surgical procedures (eg, use of silver sutures in abdominal surgery and use of silver amalgam in tattooing) [5].
    • Bluish skin lesions have appeared at sites of acupuncture needles and silver earring sites.

    There is a great individual variability as to who and when argyria develops. Some people develop severe argyria after short-term exposure to silver salts and some people work for many years and only develop minor skin discoloration. However, in general, argyria is more likely to develop when one is exposed to high concentrations of silver for prolonged time period [6] [7].

    Epidemiology

    The incidence of argyria is not known because many individuals never come to medical attention. Overall, this skin disorder is rare chiefly because silver agents are no longer used as pharmaceutical and in the heavy metals industry; safe guards have been put in place to avoid skin contact and inhalation. Over the years, dysfunction of several organs has been reported after silver exposure [8] [9] [10].

    Sex distribution
    Age distribution

    Pathophysiology

    Following skin contact, some individuals will only develop localized skin patches of argyria. Such localized dermatosis may be seen after short term use of nasal or eye drops containing colloidal silver. Others may develop argyria following acupuncture near the ear. Systemic manifestations of argyria are usually seen after oral consumption of silver salts. In the remote past, colloidal silver suspensions were often used to treat a variety of gastrointestinal tract disorders like stomach upset, gastroesophageal reflux disease (GERD), peptic ulcer disease and gastritis. In addition, colloidal silver was also used to treat rhinitis, sinusitis and nasal congestion. In such cases, small amounts of silver were continuously absorbed into the systemic circulation resulting in deposition in internal organs. Argyria may also occur in people who work in the silver mining industry and in individuals who work in jewellery industry where they are frequently polishing silver. There are also reports that argyria may occur in professionals who polish artificial pearls.

    In these cases, inhalation of silver dust particles is the route of transmission. There are isolated reports that argyria may have a genetic predisposition. Even though silver salts precipitate all over the body, the pigmentary changes are usually observed on the sun-exposed areas. The exact reason for this is not known but experts believe that the silver salts once bound to protein in the skin, are chemically oxidized by light waves that result in the discoloration. Others suggest that silver plus UV light stimulates production of melanin, which then is responsible for the skin darkening. The healthy adult does not have huge amount of silver ions in the body. It is estimated that in most humans the silver concentration in the body varies from 800-1,000 micrograms. The exact amount of silver known to cause argyria is not known, but the literature indicates that exposure to more than 4 grams may initiate the process. Silver is not an innocuous metal and at doses ranging from 50-500 mg/kg, this metal can induce multiple organ failure and death.

    Prevention

    The ideal treatment of argyria is prevention. This means preventing skin exposure and oral consumption of silver salts. The consumer should be educated about preventive measures such as wearing proper garments and masks when working with silver.

    It should be understood that current belief is that mild to moderate exposure to silver may not seriously affect human health. However, if the silver deposits in critical organs like the liver, pancreas, kidney or brain, adverse effects are likely. It is believed that toxicity of silver is often prevented because of binding to endogenous substance like sulfur and selenium.

    Summary

    Argyria is an uncommon skin condition that develops following acute or chronic contact with silver salts. In even more rare circumstances, it may develop after oral consumption of silver containing salts.

    Argyria presents with either localized or systemic grayish-blue discoloration of skin and mucus membranes. Some people may develop argyria after use of medications that contain silver but others may develop internal organ discoloration after chronic exposure to silver salts while working in the mining industry [1] [2]. If silver salts are ingested orally, then the deposits may also occur in other organs of the body. In the past silver salts were used in certain sutures and dental procedures and were reported to cause argyria. Some people have also developed bluish-silver discoloration following acupuncture around ear lobes containing silver earrings [3].

    It is difficult to predict who will develop argyria because there is a great variability in exposure and formation of the skin discoloration. Some people who have had prolonged exposure and have had no problems but others have had acute short-term exposure and developed significant skin discoloration.

    Patient Information

    Argyria is an uncommon skin condition that develops due to exposure to chemical compounds of the element silver, or to silver dust. Argyria presents with either localized or systemic grayish-blue discoloration of skin and mucus membranes.

    Silver exposure is usually occupational but may also occur through the ingestion of colloidal silver, acupuncture, earrings and medications. Some people develop severe argyria after short-term exposure to silver salts and some people develop minor skin discoloration after many years.

    In general, the treatment of argyria is strictly for cosmetic reasons. The skin disorder rarely causes any symptoms.

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    References

    1. Kubba A, Kubba R, Batrani M, Pal T. Argyria an unrecognized cause of cutaneous pigmentation in Indian patients: a case series and review of the literature. Indian J Dermatol Venereol Leprol. 2013;79(6):805-801
    2. Drake PL, Hazelwood KJ. Exposure-related health effects of silver and silver compounds: a review. Ann Occup Hyg. 2005;49(7):575-585.
    3. Takeishi E, Hirose R, Hamasaki Y, Katayama I. Localized argyria 20-years after embedding of acupuncture needles. Eur J Dermatol. 2002;12(6):609-611. Review.
    4. Baker CD, Federico MJ, Accurso FJ. Case report: skin discoloration following administration of colloidal silver in cystic fibrosis. Curr Opin Pediatr. 2007;19(6):733-735.
    5. Schmalz G, Garhammer P. Biological interactions of dental cast alloys with oral tissues. Dent Mater. 2002;18(5):396-406.
    6. McClain CM, Kantrow SM, Abraham JL, Price J, Parker ER, Robbins JB. Localized cutaneous argyria: two case reports and clinicopathologic review. Am J Dermatopathol. 2013;35(7):e115-118
    7. Miyayama T, Arai Y, Hirano S. Environmental exposure to silver and its health effects. Nihon Eiseigaku Zasshi. 2012;67(3):383-389.
    8. Wadhera A, Fung M. Systemic argyria associated with ingestion of colloidal silver. Dermatol Online J. 2005;11(1):12.
    9. Hadrup N, Lam HR. Oral toxicity of silver ions, silver nanoparticles and colloidal silver--a review. Regul Toxicol Pharmacol. 2014;68(1):1-7.
    10. Lansdown AB. Critical observations on the neurotoxicity of silver. Crit Rev Toxicol. 2007;37(3):237-50.

    • " Familial" Generalized Argyria - L Bianchi, A Orlandi, A Di Stefani, R Ricci - Archives of , 2006 - Am Med Assoc
    • A case of argyria after colloidal silver ingestion - ALS Chang, V Khosravi, B Egbert - Journal of cutaneous , 2006 - Wiley Online Library
    • Argyria in a child following intranasal use of argyrol - MA Zacks - The Laryngoscope, 1933 - Wiley Online Library
    • A case of argyria following colloidal silver ingestion - HB Kwon, JH Lee, SH Lee, AY Lee - Annals of , 2009 - synapse.koreamed.org


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    1. Argyria 2b, CC BY 2.0

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