Bullous hemorrhagic dermatosis (BHD) is a non-life-threatening side-effect from administration of low-molecular weight heparin (eg, enoxaparin, dalteparin, tinzaparin, bemiparin), heparin, and unfractionated heparin, characterized by multiple tense, blood-filled vesicles or bullae near or distant from the site of injection. It is most commonly associated with enoxaparin use, which accounts for over 60% of cases reported in the literature. BHD has also been reported with fondaparinux and warfarin use.
Those affected are typically in their 60s to 80s, which may reflect the typical age of anticoagulant use, with a male to female ratio of 1.9 to 1. The lesions typically appear 2-20 days (median 7 days) after initiation of anticoagulant treatment. There are over 90 cases reported in literature, but BHD may be underreported.
The etiology of BHD is poorly understood.
Bullous hemorrhagic dermatosis
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Synopsis
Codes
ICD10CM:
L13.9 – Bullous disorder, unspecified
SNOMEDCT:
402750008 – Bullous dermatosis precipitated by drug treatment
L13.9 – Bullous disorder, unspecified
SNOMEDCT:
402750008 – Bullous dermatosis precipitated by drug treatment
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Diagnostic Pearls
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Differential Diagnosis & Pitfalls
- Heparin-induced skin necrosis – Histology shows dermal thrombi on biopsy with or without associated thrombocytopenia on CBC.
- Warfarin necrosis – Clinically characterized by painful necrotic plaques in adipose-rich areas. Histology shows fibrin and thrombi in dermal vessels.
- Atypical bullous pemphigoid – Histology classically shows eosinophilic inflammation with or without subepidermal cleft / blister; direct immunofluorescence (DIF) shows linear IgG and C3 along basement membrane zone.
- Angiokeratomas (see angiokeratoma circumscriptum) – Clinical differential; distinguished by history of chronic nature.
- Hemorrhagic spider bites
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Therapy
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Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.
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References
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Last Reviewed:02/05/2020
Last Updated:02/05/2020
Last Updated:02/05/2020
Bullous hemorrhagic dermatosis