Enoxaparin sodium-induced bullous pemphigoid-like eruption: a report of two cases

Journal of Drugs in Dermatology, Sept-Oct, 2004

The authors present a 62-year-old woman and a 31-year-old man whom developed paralysis of their lower extremities secondary to epidermal hematomas overlying their spinal cords. The women developed a bulla on her buttock six days after her injury. Her medications were oral bisacodyl, acetaminophen, psyllium, and enoxaparin subcutaneous injections. Physical examination revealed multiple broad-based tense bullae on erythematous bases and healing erosions on the left buttock. She continued to develop new bullae on the lower extremities over the next few days. A biopsy of an intact bulla showed a subepidermal blister with eosinophils along the base, compatible with bullous pemphigoid. Direct and indirect immunofluorescence studies were both negative. The diagnostic differential included bullous drug eruption. All medications except her anticoagulation (enoxaparin) were discontinued and prednisone was immediately started. The patient had no lesion for the length of prednisone therapy (one month). Several days after prednisone was discontinued, she developed new bullae. Enoxaparin was the medication that she was still on since the appearance of the bullae. Enoxaparin was replaced with oral warfarin, and the eruption resolved in two weeks.

The male patient developed blanching erythematous macules and patches on his torso and extremities. His medications included ciprofloxacin, oral bisacody (1), acetaminophen, psyllium, and enoxaparin subcutaneous injections. The initial diagnostic differential includes a bullous drug eruption, likely due to ciprofloxacin. The medication was discontinued and three days after ciprofloxacin was discontinued, he developed new tense bullae on both lower extremities. A skin biopsy of a bulla showed subepidermal blister with eosinophils, compatible with bullous pemphigoid. Direct and indirect immunofluorescence studies were both negative. The patient's only remaining medication that was new was enoxaparin and at that moment the doctors decided to discontinue the medication. His lesions cleared within one week.

JDD ARTICLE EVALUATION

A case presentation of a bullous pemphigoid (BP)/drug eruption, which would have been avoided if the doctors had been aware of the risk of hematomas while on enoxaparin, especially with procedures that involve the spinal cord (1). Although the title states it is a BP-like eruption the differential includes drug induced BP and bullous drug eruption. It is not rare to find direct and indirect immunofluorescence studies that are negative in drug induced BP, contrary to what the authors may think (2).

Low molecular weight heparins, which include enoxaparin are widely used for anticoagulation instead of warfarin and heparin. The use of these low weight heparins has increased because they have no monitoring (PT/PTT) and are easily self injectable by subcutaneous pre-filled syringes. Previous skin reactions to enoxaparin include injection site dermal necrosis (3), but this article adds a bullous eruption to the list of adverse reactions that we will be aware of in the future.

References

1. www.lovenox.com/professional/SearchAction.do

2. Lever's Histopathology of the Skin. 8th edition; Elder, et. al. Philadelphia, PA: Lippincott Willimas and Wilkins 1997.

3. Tonn ME, Schaiff RA, Kollef MH. Enoxaparin-associated dermal necrosis; a consequence of cross-reactivity with heparin-mediated antibodies. Ann Pharmacother 1997; 31(3):323-6.

Dyson SW, Lin C. Jaworsky C. J Am Acad Dermatol 2004; 51(1):141-2.

WASHINGTON WHISPERS APPEARS IN EACH ISSUE AND PROVIDES A SUMMARY AND CRITICAL EVALUATION OF THE LATEST DRUG TRIALS, STUDIES, AND REACTIONS AVAILABLE TO THE MEDICAL COMMUNITY, AS COLLATED FROM A WEALTH OF INDUSTRY SOURCES.