Dermal argyria: Cutaneous manifestation of a megaprosthesis for distal femoral osteosarcoma.

We present a patient with dermal argyria as a cutaneous manifestation of a silver-coated megaprosthesis used for a distal femoral osteosarcoma. Histological and electron microscopic analyses also showed silver deposition in the dermis.

INTRODUCTION

Reconstruction using a megaendoprosthesis is the method of choice for achieving best possible level of function in patients undergoing limb salvage surgery following sarcoma.12 This kind of endoprosthesis are used for young patient with malignant bone tumors.3

However, the large surface area of the implant is predisposed to bacterial colonization.4 In addition to bacterial colonizing, a biofilm can be formed that enables bacteria to evade the host defense system and local or systemic antibiotic treatment.5 In such cases the only viable option is removal of the prosthesis and radical debridement, which is harmful for the patient.

Among metals with antimicrobial activity, silver has garnered much interest due to its excellent antimicrobial activity coupled with low toxicity.6 Toxicological side-effects in patients receiving silver-coated tumor endoprostheses have been excluded in previous studies7 and the high antimicrobial activity of silver-coated prostheses has been demonstrated in both human and animal studies.89 We describe such a case with cutaneous manifestation (dermal argyria) of a silver-coated femoral megaprosthesis 1 year postimplantation, which was confirmed via histological and electron microscopic analyses. Silver-coated prostheses are applied mainly due to the following two indications: (1) For infection prophylaxis in tumor endoprosthetics and (2) as the last option for patients after extensive trauma-related infection.3

CASE REPORT

A 14 year old girl with distal femoral osteosarcoma was treated with limb salvage surgery [Figure 1a]. A silver coated proximal tibial, distal femoral composite prosthesis (Mutars®, Implantcast, Ltd., Buxtehude, Germany) was used [Figure 1b]. She had a negative history of other diseases.

Figure 1

(a) Preoperative X-ray showing femoral osteosarcoma. (b) Postoperative X-ray after limb salvage surgery

There were no complications postoperatively or during routine followup visits. She noticed a blue-gray discolored pattern on the skin over the incision site at the proximal tibia [Figure 2] after 1 year postsurgery. Complete blood count, C-reactive protein, the erythrocyte sedimentation rate and kidney and liver function test results were normal. A diagnosis of dermal argyria was considered. A 0.5-cm skin biopsy specimen was obtained from the discolored area under local anesthesia. Histological analysis revealed silver deposition in dermal layers [Figure 3]. The same specimen was also analyzed via electron microscopic mapping, which also showed the presence of silver [Figure 4]. No additional procedures were considered, as the patient was asymptomatic. At 3 years followup (since the patient's dermal argyria was diagnosed) she was clinically well with normal blood parameters, although the peri-incisional discoloration persisted.

Figure 2

Clinical photograph of the patient's leg shows blue-grayish discoloration

Figure 3

Histological analysis shows silver deposition in the dermis (hollow arrows)

Figure 4

Electron microscopic analysis of the biopsy specimen showing dermal deposits

DISCUSSION

Coating orthopaedic implants with silver to prevent infection is not a new idea.10 In literature most of the studies are focused on silver coating external fixator pins and prosthesis.911121314 The findings of in vivo studies on the efficacy of silver for preventing infection are inconsistent.111213 Hardes et al.9 in their study have reported that silver coating of tumor megaprostheses effectively prevented infection. Their study states that in silver coated prosthesis group the rates of infection and amputation rates are low. In some cases dermal argyria could not be diagnosed due to already discolored area in that region possibly because of varicose veins and additional analyses, such as skin biopsy (as performed in the presented case) were not performed. One study reported that silver-coated prostheses were safe, based on the lack of observable signs of local or systemic argyria and serum silver levels that were below the toxic level.7

Argyria is deposition of silver products in the connective tissue of the dermis, but not the epidermis. These inert silver deposits are intracellular (lysosomal bound) or intercellular, and are long lasting or permanent. There is no association between cellular damage and altered sensory perception in the skin, the mechanism is not fully understood, but is thought to be associated with imbalances in the concentrations of soluble and insoluble silver complexes in the dermis and the action of lysosomal reductase. Argyremia (or elevated blood silver) is not always correlated with dermal manifestations.15

It seems logical to inform patients about the possible consequences of silver-coated megaprostheses, such as dermal argyria, when they are superficially located (i.e. the proximal tibia). The patient should be informed about the complications like the typical toxic side effects of silver, such as dermal argyria (i.e. blue or bluish-grey colored skin), ocular argyrosis, gastroenteritis or fever. At 3 years postdiagnosis of dermal argyria in the presented case was not associated with additional pathology and/or cellular damage, indicating that simple followup of the patient was sufficient.