Bullous haemorrhagic dermatitis induced by heparins and other anticoagulants: 94 cases from French pharmacovigilance centres and a literature review.

Autor: Uceda-Martin M; Centre régional de pharmacovigilance de Strasbourg, HUS, 1, place de l'Hôpital, 67000 Strasbourg, France., Lambert A; Centre régional de pharmacovigilance de Strasbourg, HUS, 1, place de l'Hôpital, 67000 Strasbourg, France., Miremont G; Pôle de santé publique, pharmacologie médicale, centre de pharmacovigilance de Bordeaux, CHU de Bordeaux, Bordeaux, France., Gaiffe A; Centre régional de pharmacovigilance de Besançon, 3, boulevard Alexandre-Fleming, 25000 Besançon, France., Agier MS; Centre régional de pharmacovigilance de Tours, 2, boulevard Tonnellé, 37000 Tours, France., Studer M; Service de dermatologie, centre hospitalier de Colmar, 39, avenue de la Liberté, 68000 Colmar, France., Mahé A; Service de dermatologie, centre hospitalier de Colmar, 39, avenue de la Liberté, 68000 Colmar, France., Tebacher M; Centre régional de pharmacovigilance de Strasbourg, HUS, 1, place de l'Hôpital, 67000 Strasbourg, France., Cribier B; Clinique dermatologique, hôpitaux universitaires et université de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg, France. Electronic address: bernard.cribier@chru-strasbourg.fr.
Jazyk: angličtina
Zdroj: Annales de dermatologie et de venereologie [Ann Dermatol Venereol] 2022 Mar; Vol. 149 (1), pp. 45-50. Date of Electronic Publication: 2021 Jun 24.
DOI: 10.1016/j.annder.2021.05.003
Abstrakt: Background: Bullous haemorrhagic dermatitis (BHD) is an uncommon and highly particular side effect of various forms of heparins.
Methods: To better characterise the disease, we collected all cases from French Pharmacovigilance centres recorded over a 20-year period (37 cases) and performed a Medline literature search up to June 2020 (57 cases).
Results: In all, 94 patients were identified (male/female ratio: 2.2) of mean age 73.5±12.1 years (31-94). Patients were treated with enoxaparin (n=66), unfractionated heparin (n=11), fondaparinux (n=10), tinzaparin (n=4), bemiparin (n=1), reviparin (n=1), dalteparin (n=1), and 4 with other anticoagulants: warfarin (n=3) and rivaroxaban (n=1). All cases presented with 1 to more than 100 haemorrhagic vesicles and bullae, distant from the injection sites, located mainly on the lower (75%) or upper limbs (69%). The lesions were asymptomatic, except in 5 patients who had pruritic or painful lesions. The interval between treatment initiation and BHD ranged from 6 hours to 30 days (mean: 8.4±7 days). Biopsy (n=53) showed intraepidermal or subcorneal cavity with red cells (n=39) or junctional blisters (n=10), with eosinophilic infiltrate only rarely. Direct immuno-fluorescence was negative in 19/20 cases and indirect immunofluorescence was negative in 8/8. The outcome was favourable in all cases, including in 12 patients for whom heparin was maintained. A 93-year-old patient died of compressive haematomas unrelated to BHD. We found 5 cases similar to BHD due to other anticoagulants.
Discussion: This is the largest comprehensive series of this adverse effect due to heparins or, more rarely, to other anticoagulants. Dermatologists must be aware of BHD, since this benign side effect does not necessarily require interruption of treatment. It is rare, considering the large-scale prescription of heparins, and occurs mainly in male patients aged over 70. Although the presentation is highly typical, the physiopathology is difficult to understand, as coagulation parameters are usually normal. Aging, skin fragility or mechanical factors might play a role.
(Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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