Delayed-type hypersensitivity to subcutaneous enoxaparin

Enoxaparin and other low-molecular-weight heparins are widely used to prevent and treat thromboembolic disorders. Cutaneous reactions secondary to enoxaparin injections include delayed hypersensitivity skin reactions described as erythematous, infiltrated plaques at injection sites. We studied three cases of erythematous infiltrated plaques after enoxaparin injection in order to establish the allergenic importance of this low-molecular-weight heparin.

Patch tests were performed with sodium heparin, calcium heparin, calcium enoxaparin, and calcium nadroparin. A subcutaneous test with calcium heparin and an intravenous challenge test with sodium heparin were done. A punch biopsy was obtained from an erythematous plaque in one patient.

Patch tests were negative to calcium heparin in all patients, positive to enoxaparin and nadroparin in two patients, and positive to sodium heparin in one patient. In two patients, the subcutaneous challenge test was positive, the intravenous challenge test was negative, and the histopathologic appearance of the biopsy resembled a delayed-type hypersensitivity reaction.

These cases provide evidence of type IV hypersensitivity and the possibility of crossed-allergenicity among unfractionated heparin and low-molecular-weight heparins. We show that the subcutaneous challenge test is the most reliable diagnostic measure.