Argyria an unrecognized cause of cutaneous pigmentation in Indian patients: A case series and review of the literature

Abstract

Argyria is an uncommon grey-blue pigmentation of skin and mucous membranes caused by prolonged silver exposure. The impetus behind this review is our experience with cases of generalized argyria resulting from a uniquely Indian socio-cultural practice and belief that it is under reported. Our objective is to increase the awareness for this esoteric entity through a review of the pertinent literature and to highlight clinical and histological features using our four well worked-up cases as examples.

Clinical and Forensic Aspects of the Different Subtypes of Argyria

“…Azure lunula is a bluish discoloration of the fingernails, more precisely of the lunula ( Figure 2 ), but with the possible extent to the proximal half of the fingernail that was frequently accompanying GA [ 6 , 36 , 47 , 50 , 61 , 62 ]. Another possible early sign of GA is acquired pigmentation of the oral mucosa; unlike amalgam tattoos, a diffuse gray/blue tinge will be seen [ 1 , 6 , 7 , 49 , 58 , 63 , 64 , 65 , 66 ].…”

“…After silver gains access to the dermis or other tissues, either carried by the bloodstream (leading to GA) or localized (leading to LA), it deposits in a predictable pattern, as shown by histopathological and ultrastructural studies [ 51 , 70 , 76 , 81 , 85 , 137 ]. Typically, the silver particles settle in the connective tissue underlying epithelial surfaces, arranged in rows of granules, with a propensity for the basement membranes of blood vessels, eccrine sweat glands, and other dermal adnexa, but also depositing along dermal elastic fibers and the dermo-epidermal junction, while staying clear of the epidermis [ 4 , 7 , 55 , 64 , 73 , 79 , 81 , 85 , 133 , 134 , 138 , 139 , 140 , 141 ]. Of note, the outermost skin layer also influences the macroscopical appearance of the discoloration; since it reflects light in the violet/blue spectrum more than in longer wavelengths, argyria colors are usually perceived as blue/gray at clinical evaluation.…”

“…To better characterize the suspected pigmentation and exclude the differential diagnosis, histopathological analysis of the affected tissue is particularly important [ 7 ]. After conventional tissue section processing and staining with hematoxylin and eosin, the dark deposits may be seen both in bright and dark field microscopy, with the latter being more sensitive as they appear refractile, arranged as described above in the pathophysiology section [ 7 , 55 , 84 , 87 , 133 , 139 , 213 ].…”

“…To better characterize the suspected pigmentation and exclude the differential diagnosis, histopathological analysis of the affected tissue is particularly important [ 7 ]. After conventional tissue section processing and staining with hematoxylin and eosin, the dark deposits may be seen both in bright and dark field microscopy, with the latter being more sensitive as they appear refractile, arranged as described above in the pathophysiology section [ 7 , 55 , 84 , 87 , 133 , 139 , 213 ]. Ultrastructural analysis of skin biopsies, but also of the kidney and choroid plexus, allows visualization of electron-dense particles, typically round or ovoid in shape but sometimes more irregular, and with a greater axis ranging from 10 to 1000 nanometers [ 31 , 80 , 127 , 132 , 133 , 140 ].…”

“…It occurs following excessive accidental voluntary cumulative silver exposure by the most varied causes. It is mainly a cosmetic condition whose clinical presentation will vary according to the subtype as describe below [ 2 , 3 , 7 , 8 , 9 ].…”