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Silver sulfadiazine therapy in widespread bullous disorders: Potential for toxicity

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Silver sulfadiazine therapy in widespread bullous disorders: Potential for toxicity
Emily M Mintz, Dornechia E George, Sylvia Hsu
Dermatology Online Journal 14 (3): 19

Department of Dermatology, Baylor College of Medicine, Houston, TX, USA


Silver sulfadiazine (SSD) cream, most known for its use in the treatment of extensive burn wounds, is commonly used in the management of erosions in bullous disorders. The beneficial antibacterial effect of SSD use is not without risk, as silver toxicity has been well documented in burn patients. Renal insufficiency accelerates silver accumulation and thus toxicity. Data on silver toxicity in patients with primary blistering disorders is scarce; however the literature regarding silver toxicity in burn patients may be applicable to patients with bullous diseases. Hence we recommend that clinicians exercise caution when prescribing protracted wound care with SSD for blistering disorders.

Silver sulfadiazine (SSD) cream, known for its antibacterial effects when used as a dressing for extensive burn wounds, is used commonly to treat bullous disorders, such as pemphigus vulgaris, epidermolysis bullosa, and toxic epidermal necrolysis. The association of SSD cream use and silver toxicity is well-demonstrated in the literature with reference to burn patients. Prolonged and excessive use of SSD cream in the treatment of extensive and chronic blistering disorders likely confers significant risk of systemic absorption and toxicity.

Prolonged use of SSD cream may lead to argyria. Silver also deposits in the labial mucosa, gingiva, cornea, and internal organs. Hepatic, renal, and neurological toxicity may ensue [1]. Leucopenia is commonly reported during the first two to three days of therapy with SSD cream but generally resolves spontaneously with continued treatment [2]. It is thought that this transient leucopenia portends little risk for the patient [3].

Silver sulfadiazine is eliminated via renal excretion. The sulfadiazine portion is eliminated quickly, whereas the silver portion persists longer [4]. Renal insufficiency accelerates silver accumulation. Boosalis et al noted modestly elevated serum silver levels and markedly elevated urinary silver excretion in 23 patients with second- and third-degree burns treated with SSD cream. Burn size, and thus amount of cream used, positively correlated with urinary silver excretion [5]. Iwasaki et al reported elevated serum silver levels and rapid deterioration of mental status in a burn patient with end stage renal disease treated with SSD cream for 2 weeks [6]. Conversely, Chaby et al reported a case of acute renal failure and leucopenia with neutropenia induced by large-scale application of SSD cream to pyoderma gangrenosum wounds of the lower extremities. The patient was found to have elevated serum and urine silver levels. Signs and symptoms resolved after withdrawal of SSD cream and hemodialysis [7].

In burn patients, maximum silver absorption occurs during the initial inflammatory and migratory phases of wound healing [5, 8, 9]. Chronic repair, prolonged therapy, and potentially widespread distribution of bullous lesions predispose these patients to increased silver absorption. In partial thickness burns, the blood supply remains intact and is exposed, enhancing SSD absorption and distribution [8]. This feature may also be seen with bullous disorders. As the wound heals and forms granulation tissue, the rate of silver absorption from SSD cream decreases due to improved barrier function and greater degree of silver-bound tissue [8]. At this point in therapy, SSD would be an ideal choice if an endpoint in therapy is expected. However, patients with chronic blistering disorders may never reach this point.

In light of the existing literature on SSD use in burn patients, as well as the scarcity of data on SSD use in patients with primary blistering disorders, we recommend that clinicians exercise caution when prescribing protracted wound care with SSD for blistering disorders, particularly when renal failure is concurrent or imminent. Serum silver levels and urinary silver excretion may be monitored as a surrogate marker of toxicity.


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