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Generalized Argyria from Oral Ingestion of Supplements: A Case Report and Discussion Shiva Kheradmand, BA,* Sarah Neumann, MMS, PA-C,** Christine Moussa, DO,*** Richard Bernert, MD, FASDP****

*Medical Student, OMS IV, Arizona College of Osteopathic Medicine, Glendale, AZ **Ahwatukee & Laser, Phoenix, AZ *** Resident, PGY4, Alta Dermatology/Kansas City University of Medicine and Biosciences, Mesa, AZ ****Dermatopathologist, Aurora Diagnostics Arizona Dermatopathology, Scottsdale, AZ

Disclosures: None Correspondence: Shiva Kheradmand; [email protected]

Abstract Argyria is a rare condition of slate-gray discoloration of the skin, nails, mucosa and internal organs caused by exposure to silver-containing compounds.1 Histopathologic evaluation is extremely helpful in making the diagnosis, with silver-granule deposition seen predominantly in the basement membrane zone of the eccrine glands. Herein, we describe a case of a 79-year-old female with a history of delusions of parasitosis who presented to the dermatology clinic with gray discoloration of her face, upper extremities, and torso of six months’ duration. She admitted to ingesting an over-the-counter colloidal silver supplement for over one year as treatment for self-diagnosed Morgellons . We report this case to serve as a reminder of the importance of reviewing patients’ and of inquiring specifically about non-prescription therapeutics, which may have detrimental effects. Additionally, physicians can caution patients with clinically diagnosed delusions of parasitosis to avoid advertised colloidal silver solution to prevent additional cases of argyria.

Introduction examination of a representative lesion of the left differential diagnosis for slate-gray discoloration of Argyria is a rare cutaneous condition resulting arm showed non-parasitic debris. In addition, an the skin is broad, including exposure to other heavy from persistent exposure to silver compounds, insect identification test was negative. , central cyanosis, , leading to deposition of silver granules in the skin During these initial visits, there was no mention Addison’s disease and drug-induced pigmentation of plans to use a colloidal silver supplement. from medications such as antimalarial therapy, that can be localized or generalized. It can occur 12 from a variety of causes, including occupational The patient was provided with basic wound care amiodarone, and minocycline. However, exposure, inappropriate use of silver-containing treatment and counseled to avoid further scratching, histopathologic examination can aid in diagnosis, as topical medications, such as silver sulfadiazine, and continued surveillance was recommended. skin biopsy of either normal or discolored skin will dietary supplements, and .2,3 Patients show characteristic silver granules in the basement The patient’s medications included treatments for considering alternative therapies can be educated membrane zone of the eccrine lobules. hypertension, hypothyroidism and asthma, with no on the development of argyria with ingestion recent changes. In addition, she was using topical of silver supplements. The U.S. Environmental mupirocin and anti-itch hydrogel daily. Her family Protection Agency (EPA) has established a daily history, social history, and surgical history were intake limit of 5 micrograms of silver per kilogram non-contributory. per day. For an individual who is 60 kg, ingestion of 300 μg of silver per day would lead to a high risk 4 Physical examination revealed diffuse blue-gray of argyria. Evidence suggests the concentration of patches on her face, torso, and bilateral upper silver required to cause these changes in the skin extremities with scattered white atrophic patches, and internal organs does not lead to functional 5 more prominent in photo-exposed areas (Figure 2). impairment. She was seen by specialists in hematology-oncology and cardiology to evaluate for other possible causes Diagnosis can be difficult, and evaluation must of this discoloration, with a negative workup. Her involve a thorough drug review, particularly for history and physical examination were suspicious drug-induced pigmentary changes, as can be seen for a diagnosis of argyria, and two 4-mm punch with antimalarials and minocycline. Clues to the biopsies were obtained from the left preauricular diagnosis of argyria include the involvement of and left lateral forehead. Histopathologic evaluation the photo-exposed skin and proximal nail bed, of both areas revealed deposits of dark staining, particularly the lunula of the fingernails. Serum minute granular material within the eccrine units, silver is raised, and histopathologic examination is confirming a diagnosis of argyria (Figure 3, H&E). diagnostic, showing silver granules in the dermis, 1,6 The patient was counseled to avoid further ingestion especially around eccrine ducts. We report a case of the colloidal silver solution and to use sunscreen of argyria in a 79-year-old female with a history of to prevent skin darkening. delusions of parasitosis who ingested colloidal silver solution as treatment for imagined bugs in her skin. Discussion Argyria is characterized by a blue to gray staining of Case Report the skin and mucous membranes secondary to silver A 79-year-old female presented with a six-month deposition from exposure to silver compounds. It history of extensive blue-gray discoloration of the 5 was first described by Fuchs in 1840. Recently, there face, torso, and bilateral upper extremities. The has been a resurgence in argyria cases due to online patient reported daily ingestion of an over-the- advertisements claiming colloidal silver to be an counter colloidal silver solution for 12 months effective alternative treatment for various ailments, prior to presentation, which she discontinued including respiratory infections, gastritis, AIDS, upon noticing the discoloration. Based on an 1,7–9 diabetes, and cancer. There are case reports of online advertisement, she had been using this argyria secondary to ingestion of silver solutions in therapy to eliminate what she believed to be bugs patients with psychiatric disorders, including one in her skin. Two years previously, she was seen in patient with schizoaffective disorder and another our dermatology clinic for recurrent, scattered, 10,11 with delusions of parasitosis. Our patient also erythematous excoriations ranging from 2.5 cm to suffered delusions of parasitosis, which led her to 4 cm on her cheek, forehead and left arm, as well ingest colloidal silver solution for a prolonged period as under her breasts (Figure 1). Histopathologic of time, resulting in her cutaneous presentation. The

KHERADMAND, NEUMANN, MOUSSA, BERNERT Therapy is difficult, and the primary focus ison References discontinuation of contact with or ingestion of 1. Prescott RJ, Wells S. Systemic argyria. J Clin silver compounds. The discoloration may improve Pathol. BMJ Group; 1994;47(6):556–7. slowly over time, but often persists. It is also recommended that patients avoid sun exposure to 2. Fisher NM, Marsh E, Lazova R. Scar-localized prevent further skin darkening. Treatment with argyria secondary to silver sulfadiazine cream. J Am hydroquinone or dermabrasion has been ineffective, Acad Dermatol. 2003;49(4):730–2. as these modalities target primary epidermal pigmentation.13 However, treatments that are too 14 3. Legat FJ, Goessler W, Schlagenhaufen C, Soyer aggressive can lead to unwanted dyspigmentation. HP. Argyria after short-contact acupuncture. There are case reports showing some success with Lancet. 1998;352(9123):241. the use of Q-switched ruby, Q-switched 1064- nm Nd:YAG, Q-switched alexandrite and, most 4. US EPA. Risk Information System Division I. 14–16 recently, picosecond 755-nm alexandrite lasers. Silver [Internet]. 1991 Dec 1[cited 2016 Oct 24]. Available from: https://cfpub.epa.gov/ncea/iris2/ Conclusion chemicalLanding.cfm?substance_nmbr=99. Argyria from ingestion of colloidal silver solution associated with delusions of parasitosis is a rarely 5. Aronowitx PB. Hospital Images: A Clinical reported occurrence. Histopathologic evaluation Atlas. Hoboken: Wiley-Blackwell; 2012. p9. confirms the diagnosis, showing silver granular deposits around eccrine lobules. Therapy involves 6. Shelley WB, Shelley ED, Burmeister V. Argyria: discontinuation of the offending agent. This the intradermal photograph; a manifestation of case emphasizes the importance of reviewing passive photosensitivity. J Am Acad Dermatol. patients’ medications, including home remedies, 1987;16:211–7. homeopathic treatments and over-the-counter supplements, as these seemingly innocuous 7. Bouts BA. Argyria. N Engl J Med. therapies can be the cause of unusual presentations 1999;340(20):1554. such as argyria. 8. Gulbranson SH, Hud JA, Hansen RC. Argyria following the use of dietary supplements containing colloidal silver protein. Cutis. 2000 Nov;66(5):373– 4.

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GENERALIZED ARGYRIA FROM ORAL INGESTION OF SILVER SUPPLEMENTS: A CASE REPORT AND DISCUSSION