Erythema migrans rash doesn’t always have bull’s eye appearance

An erythema migrans (EM) rash, sometimes referred to as a bull's eye rash, has been considered the signature rash for Lyme disease, leading to a definitive diagnosis. Yet only 1 in 4 erythema migrans rashes present with a bull’s eye appearance.

Several reports have found urticarial, linear, granulomatous, and bullous erythema migrans presentations associated with Lyme disease, as well. And as this case series highlights, “several erythema migrans variants have been reported, which may result in misidentification as well as delayed diagnosis and treatment.”¹

In their article, “Vesiculobullous Lyme disease: A case series,” the authors describe three cases where an erythema migrans rash presented as a blistering rash, also referred to as bullous erythema migrans. (Typically, an erythema migrans rash is more likely to present as a flat rash.)

Three cases with blistering erythema migrans rash

“All 3 cases exhibited rapidly developing bullous lesions in the presence of systemic symptoms, ranging from fatigue and malaise to fever,” the authors wrote.

Initially, the lesions were attributed to Sweet syndrome, herpes simplex virus infection, varicella-zoster virus infection, a spider bite, or atypical Lyme disease. (Sweet syndrome is a group of non-infectious disorders with neutrophilic infiltration of the skin.)

Case 1: 54-year-old woman presented with an enlarging red lesion that grew progressively darker. The authors described “a 10-cm (4 inches) edematous purpuric plaque with vesiculobullous.”

Case 2: 49-year-old woman presented with an enlarging, darkening lesion on the posterior aspect of her ankle. The authors described a “a 9-cm vesiculobullous plaque with erythema.”

Case 3: 65-year-old woman presented with a red, swollen, painful plaque on the left side of her flank.

To view case reports, along with photos of each rash, click here.

In all three cases, laboratory tests were subsequently positive for Lyme disease and were successfully treated.

“Clinicians in Lyme endemic areas should be aware that Lyme disease might exhibit a broad range of clinical and histologic findings, including bullous presentations.”

It can be challenging to diagnose a blistering erythema migrans rash. Tests for Lyme disease may not be positive at the time the lesions appear. And the histopathologic finding for blistering erythema migrans rash is similar to other diseases.

“Histopathologic features of Lyme disease often include a superficial and deep perivascular and interstitial infiltrate consisting of lymphocytes and plasma cells, and may include eosinophils and neutrophils,” wrote the authors.

“Clinicians in Lyme endemic areas should be aware that Lyme disease might exhibit a broad range of clinical and histologic findings, including bullous presentations,” the authors urge.

Therefore, “a low threshold for considering Lyme disease in the differential diagnosis of bullous lesions is warranted in endemic areas with empiric treatment and follow-up serologies for disease confirmation.”