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Updated: Mar 31, 2026

Precision Implementation of Minimal Erythema Dose MED Testing to Assess Individual Variation in Human Inflammatory Response
Published on: October 3, 2019
Vesiculobullous and hemorrhagic erythema migrans: uncommon variants of a common disease
Suchismita Paul1, Philip I Song2, Oluwatobi A Ogbechie1
1Department of Dermatology, Harvard School of Medicine, Boston, MA, USA.
Background:
The diagnosis of Lyme disease relies on the accurate diagnosis of erythema chronicum migrans (ECM) because serologic tests, culture, and polymerase chain reactions are often inaccurate. Although ECM is classically associated with a targetoid rash, there are many variants of this lesion. These variants of ECM are often initially diagnosed as cellulitis or spider bite reactions and treated with oral antibiotics. Inappropriate treatment further delays the diagnosis of Lyme disease, leading to late complications.
Methods:
We present four cases of vesiculobullous and hemorrhagic ECM, a less common variant of ECM.
Results:
All four patients had a history of exposure to wooded areas in Massachusetts during the summer months. In these patients, ECM presented with central vesicles and bullae with hemorrhage, crusting, and in some cases necrosis. Serologic testing was positive in three of the four cases at presentation. In one case, microscopic examination of a skin biopsy showed epidermal spongiosis with parakeratosis, focal necrosis, papillary dermal edema, erythrocyte extravasation, and a superficial and deep perivascular lymphocytic infiltrate with neutrophils and eosinophils of the dermis. No fungal organisms or bacteria were identified. All four patients were treated with doxycycline with complete resolution of symptoms.
Conclusions:
It is important to recognize the vesiculobullous and hemorrhagic variants of ECM in order to minimize the provision of inappropriate antibiotic treatment for other diagnoses. Early diagnosis of ECM and the initiation of appropriate antibiotics may prevent late complications of Lyme disease.
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