Abstract
Background: With the emergence of highly resistant betalactam gram-positive organisms, vancomycin hydrochloride usage has increased considerably. Consequently, adverse drug reactions, including unfavorable cutaneous events, have also increased. Important adverse skin reactions are linear IgA bullous dermatosis (LABD) and Stevens-Johnson syndrome (SJS). These blistering disorders can have clinical manifestations that are difficult to distinguish; however, it is important to make the distinction because treatment and prognosis are different.
Objective: The purpose of this study is to review the literature on LABD and SJS and compare important differentiating characteristics to assist physicians in making the correct diagnosis.
Methods: The authors used MEDLINE to search for all published studies on vancomycin adverse events, and combined LABD, SJS, exanthema, and skin rashes each separately with vancomycin adverse events. Furthermore, the authors searched PubMed for all meta-analyses and randomized controlled clinical trials relating to treatment of patients with SJS.
Results: Clinically, LABD and SJS both present similarly with bullae. Diagnosis is made by use of perilesional skin biopsy and direct immunofluorescence. Direct immunofluorescence shows linear IgA deposition along the basement membrane zone in LABD, whereas this is absent in SJS. The treatment for both vancomycin-induced SJS and vancomycin-induced LABD is prompt discontinuation of the drug. However, if SJS is diagnosed early, systemic corticosteroids appear to decrease morbidity.
Conclusions: In cases of SJS or LABD that are difficult to distinguish clinically, the authors recommend performing a skin biopsy and direct immunofluorescence early to confirm the diagnosis so that effective treatment can be instituted.
In the past few years, beta-lactam-resistant gram-positive organisms, including methicillin-resistant
Staphylococcus aureus, have become prevalent nosocomial pathogens in the United States. Vancomycin hydrochloride has been the most effective and reliable drug in treating methicillin-resistant
Staphylococcus aureus. Consequently, vancomycin usage has increased considerably.
1,2
Widespread use of vancomycin has also led to increased reports of adverse events. Among these, unfavorable skin reactions are the most prevalent reason for discontinuation of the medication.
2 Vancomycin-induced Stevens-Johnson syndrome (SJS) and linear IgA bullous dermatosis (LABD) are adverse cutaneous reactions that can be difficult to distinguish clinically. It is important to make a correct diagnosis, though, because the prognosis and therapy are dissimilar.
3,4 The objective of this study is to review SJS and LABD and discuss important differentiating characteristics so appropriate treatment is rendered, unnecessary use of corticosteroids is prevented, and appropriate prognosis is discussed with the patient.
We researched MEDLINE 1966–2002 for all published studies on vancomycin–adverse events. We searched LABD, SJS, exanthema, and skin rashes each separately with vancomycin, specifically surveying the literature for articles pertinent to the clinical presentation, diagnosis, treatment, and prognosis of vancomycin-induced LABD and SJS. In addition, we searched on PubMed and OVID for all randomized controlled clinical trials for the treatment of SJS and LABD. We included all publications in English and non-English publications with English abstracts.
In cases that are difficult to distinguish based on clinical manifestations, a perilesional skin biopsy and direct immunofluorescence are indicated to make an early and correct diagnosis. Histologically, SJS shows lymphocytic accumulations at the dermoepidermal junction, along with subepidermal cleft formation and keratinocyte necrosis. These features are absent in LABD. The defining test is direct immunofluorescence that demonstrates linear IgA deposition along the basement membrane zone in LABD, and this is absent in SJS. By performing an early biopsy, the correct diagnosis can be made.
If SJS is diagnosed early, it seems that a brief course of systemic corticosteroids improves the outcome of the patients by reducing mortality, fever, and the period of an acute eruption. If the diagnosis is delayed and steroids are initiated late in the course of SJS, the prognosis may be worsened. Thus, a rapid diagnosis and therapeutic intervention are necessary in SJS.
15,17 In contrast, for vancomycin-induced LABD, discontinuation of vancomycin is the only treatment necessary. The needless addition of corticosteroids increases the risk of adverse events such as psychosis, femoral head necrosis, hyperglycemia, and hypertension.
In either case, treatment of both diseases requires supportive therapy that includes pain control, fluid replacement, avoidance of any adhesive material, fluid and electrolyte management, nutritional support, and protection against infection and sepsis.
8 Empiric, prophylactic antibiotics are not generally recommended.
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Prognosis is guarded in SJS and depends on the severity of the disorder and how prompt appropriate treatment is given. Conversely, the prognosis for LABD is excellent as long as the vancomycin is discontinued and not reintroduced. With the varied prognosis, early definitive diagnosis is essential.
In summary, early biopsy with immunofluorescence is necessary to ensure appropriate therapy is initiated and that appropriate prognosis is discussed with the patient when LABD and SJS are both potential diagnoses.
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