When self-medication goes wrong: the case of argyria at the Padua Morgagni Museum of Pathology.

A unique specimen of argyria is preserved in the Morgagni Museum of Pathological Anatomy at the University of Padua (Italy). It is a stuffed head belonging to a man who decided to cure his syphilis by himself with the so-called infernal stone (silver nitrate) every day for years, thus developing argyria in the second half of the nineteenth century. Paleopathological and historical studies were performed on the specimen to confirm the diagnosis of argyria. Furthermore, a morphological investigation of the specimen was conducted with histological and ultrastructural investigations, including environmental scanning electron microscopy and electron dispersive x-ray spectroscopy, recording high presence of silver in the dermis and epidermis and also other chemical elements correlated to the "infernal stone." A comparison with actual cases may also lead to a common feature: a potential dependence on the perceived benefits brought by silver compound that may sustain a further prolonged intake.

Localized cutaneous argyria: Review of a rare clinical mimicker of melanocytic lesions.

Localized cutaneous argyria is a rare cutaneous disorder that has been associated with occupational exposure, dental procedures, topical agents, acupuncture, earrings, and nasal piercings. In this paper, we review the current literature on localized cutaneous argyria, highlight its clinical and histologic diagnostic features, and then discuss the clinical and histological differential diagnoses for blue-gray skin and black dermal pigment, respectively. We also discuss the utility of ancillary techniques, such as deeper histologic levels, special stains, darkfield microscopy, and advanced micro-analytical techniques in helping diagnose localized cutaneous argyria. Furthermore, we emphasize that a thorough clinical history and astute clinico-pathologic correlation can be the most important diagnostic techniques in correctly diagnosing this rare disorder. Our review aims serve as a reminder to clinicians and pathologists of the importance of including localized cutaneous argyria in the clinical and histological differential diagnosis of pigmented lesions.

Occupational Localized Cutaneous Argyria With Pseudo-Ochronosis in a Jeweler.

ABSTRACT: A case of localized argyria in a 36-year-old female jeweler is described who presented with 2 discrete and asymptomatic bluish-black pigmented macules on the pulp of her left middle finger. A skin biopsy from both lesions demonstrated deposition of brown/black pigmented granules along the basement membrane zone of eccrine glands, blood vessels, nerves, and the dermo-epidermal junction fully in keeping with silver deposition. In addition, there was yellow-brown deposition seen within the interstitial dermis mimicking an early form of ochronosis, so called "pseudo-ochronosis." This latter feature is rarely described in cases of argyria. Transmission electron microscopy and energy dispersive x-ray spectroscopy confirmed the presence of electron dense particles up to 150 nm in diameter and the presence of silver, respectively. On further questioning, the patient had a history of localized and chronic exposure to silver, which specifically involved holding and manipulating silver wires and rings over the left middle finger. This case highlights an unusual and rare presentation of localized argyria in a jeweler. In addition, our case showed preferential silver deposition on dermal elastic fibers which has not been previously described in the literature.

A clinical mimicker of melanoma with distinctive histopathology: Topical silver nitrate exposure.

Exposure to silver-containing compounds can result in reversible discoloration of the skin, presenting as an irregular brown or black macule, which can have a clinical appearance similar to melanoma. Both the clinical scenario and the histopathology are unique. Silver nitrate darkens with exposure to light, and the area can appear to change over time. On microscopic examination, there are coarse pigmented granules dispersed throughout the corneal layer, and largely absent from the remainder of the epidermis-although the precise location may depend on the duration of topical exposure. While argyria, its irreversible counterpart, has been well-characterized, only a single source has previously reported the histopathology of transient topical silver nitrate exposure. We present two cases, review the clinical and histopathologic differentials, and detail the distinctive histopathology that enables a diagnosis to be suggested in this clinical mimicker of melanoma.

Unsafe Deposits: Overlapping Cutaneous Manifestations of Porphyria Cutanea Tarda, Ochronosis, Hemochromatosis, and Argyria.

Cutaneous deposition disorders represent an array of conditions resulting from the accumulation of endogenous and exogenous substances within the skin. Many of the deposition diseases resemble each other and can also be confused with disorders not related to deposition. Porphyria cutanea tarda (PCT) results from dysfunction particularly in the fifth enzyme of the heme synthesis pathway, leading to increased skin fragility and bullae among other abnormalities. Ochronosis develops from alkaptonuria or exogenous sources, creating deposition of ocher-colored pigment in the skin. Hemochromatosis is a systemic disorder that can be inherited or acquired, altering skin pigmentation in more than 90% of patients. PCT can be an initial manifestation of hemochromatosis. Argyria is an acquired disorder of silver deposition that can also cause pigmentation similar to ochronosis. These uncommon but not rare disorders may resemble and be confused with each other in multiple ways.

Mucocutaneous Hyperpigmentation in a Patient With a History of Both Minocycline and Silver Ingestion.

Minocycline is a derivative of tetracycline. It has been widely used in dermatology for the treatment of acne and rosacea. One of its adverse effects is pigmentation of various body tissues. Clinically, 3 main distinct types of hyperpigmentation by minocycline have been distinguished: type I, with blue-gray to black pigment on the face in areas of scarring or inflammation; type II, with blue-gray pigment on normal skin of the legs, forearms and on the shins; and type III, with a diffuse muddy-brown discoloration in areas of sun exposure. In the current report, we present the case of a 50-year old man with a history of severe acne treated with minocycline in the past, who currently complained about discoloration of his face. He had also taken colloidal silver supplements for "good health" about 16 years ago. Physical examination revealed gray-blue discoloration on the face, sclera, hard palate and back. Histologic examination showed intracellular pigment deposits in macrophages of the superficial dermis in a perivascular and an interstitial distribution. The pigment stained with Fontana-Masson and von Kossa, whereas it was Perls' iron negative. This case does not fit well into any of the previously described patterns of minocycline-related hyperpigmentation.

Localized cutaneous argyria: Report of two patients and literature review.

BackgroundLocalized cutaneous argyria is a rare skin condition caused by direct contact with silver or silver particles. It presents as asymptomatic gray or blue-gray macules that appear similar to blue nevi. Histologic features include brown-colored or black-colored silver granules in the basement membrane and dermis, most commonly surrounding eccrine glands, elastic fibers, and collagen fibrils. The condition is most frequently observed in individuals who are regularly exposed to small silver particles, such as silversmiths and welders. However, localized cutaneous argyria has also been associated with acupuncture needles, silver earrings, and topical medications containing silver nitrate. Although the condition is benign, patients who are concerned about the cosmetic features of localized cutaneous argyria may benefit from laser therapy.PurposeWe describe the clinical and pathologic findings of two women who developed localized cutaneous argyria. We also review the characteristics of other patients with localized cutaneous argyria and summarize the differential diagnosis and treatment options for this condition.Materials and methodsThe features of two women with localized cutaneous argyria are presented. Using PubMed, the following terms were searched and relevant citations assessed: acquired localized argyria, acupuncture, argyria, argyrosis, colloidal silver, cutaneous argyria, and localized cutaneous argyria. In addition, the literature on localized cutaneous argyria is reviewed.ResultsTwo women presented with small, asymptomatic blue-gray macules appearing at sites directly adjacent to ear piercings. A punch biopsy was performed on one woman. Microscopic examination revealed a yellowish-brown colored granular material found adjacent to elastic fibers. Based on correlation of the clinical presentation and histopathologic findings, a diagnosis of localized cutaneous argyria was established. The second woman did not undergo a biopsy. However, the clinical presentation was highly suggestive of localized cutaneous argyria. Both women were reassured of the benign nature of the condition and agreed to return for clinical follow-up if they observed any changes in the appearance of the lesions.

Diffractive microscopy in dermatopathology.

Diffraction is the process by which a beam of light is spread out as a result of passing through a narrow aperture or across an edge. Light diffraction can be produced by closing the aperture diaphragm beyond the recommended setting, by flipping the condenser cone down, or by using an opaque object such as the microscopist's hand to block the column of light and force it to bend around the edge. Any of these techniques results in greater refractility of objects in the path of the light. We studied 77 biopsy specimens from a variety of conditions selected to compare the value of diffractive microscopy, and found that it worked best in the evaluation of alopecia, tumor stroma, hemosiderin, argyria and imipramine pigmentation. In amyloidosis stained with Congo red and silica granuloma, polarized microscopy was superior to diffraction microscopy, and neither diffractive microscopy nor polarized microscopy was superior to routine light microscopy in the evaluation of melanin, chrysiasis or ochronosis.