[Low-molecular-weight heparin-induced bullous haemorrhagic dermatosis associated with cell-mediated hypersensitivity].

BACKGROUND: Heparin-induced bullous hemorrhagic dermatosis is a rare, recently described side-effect of subcutaneous heparin injection. We describe a patient simultaneously presenting distant haemorrhagic bullae and eczematous reaction at the low molecular-weight heparin (LMWH) injection sites. PATIENTS AND METHODS: Subcutaneous enoxaparin sodium was initiated in a 51-year-old patient and was replaced a few days later by tinzaparin sodium. Forty-eight hours later, annular, erythematous and vesicular plaques appeared at the injection sites (thighs). Small hemorrhagic bullae were noted on the abdominal skin at the same time. Skin biopsies revealed respectively eczematous dermatitis and an intraepidermal blister filled with red blood cells. Direct immunofluorescence was negative. Standard laboratory investigations and coagulation studies were unremarkable. Skin lesions disappeared ten days after discontinuation of LMWH. Patch tests and intradermal tests were negative. DISCUSSION: The case described herein shares the stereotypical clinical picture previously reported, namely small, multiple, haemorrhagic bullae on normal skin, appearing at remote sites five to 21 days after the start of subcutaneous heparin treatment. Despite the absence of clear management guidelines, it is obviously tempting to stop the heparin if there are too many bullae for fear of more clinically significant and dangerous mucous membrane lesions. The underlying physiopathological mechanism is poorly understood; no coagulation abnormalities were recorded. In addition, our patient presented an eczematous reaction at the injection sites, raising the possibility of a type IV hypersensitivity reaction. The association of these two cutaneous side effects of heparin is perhaps not purely coincidental.