Woman with bull's eye rash being examined at the hospital.
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Aug 29

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

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Bullous Erythema Migrans: An Atypical Lyme Disease Rash

Erythema migrans rash does not always appear as the classic bull’s-eye lesion associated with Lyme disease. Several reports have described urticarial, linear, granulomatous, and bullous variants, which can lead to misidentification, delayed diagnosis, and delayed treatment.

In their article, “Vesiculobullous Lyme disease: A case series,” the authors describe three cases in which 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 lesion.

Key Point: An erythema migrans rash does not always look like a bull’s-eye. Bullous and other atypical Lyme rashes can be mistaken for spider bites, herpes infections, or other skin disorders.

Three Cases of 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 noninfectious disorders with neutrophilic infiltration of the skin.

Case 1

A 54-year-old woman presented with an enlarging red lesion that grew progressively darker. The authors described “a 10-cm edematous purpuric plaque with vesiculobullous change.”

Case 2

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

Case 3

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

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

Laboratory Confirmation and Treatment

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

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

Why Bullous Erythema Migrans Is Difficult to Diagnose

It can be challenging to diagnose a blistering erythema migrans rash. Lyme disease testing may not yet be positive when the lesions first appear. In addition, the histopathologic findings may overlap with other skin conditions.

“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.

This overlap can make it difficult to distinguish bullous erythema migrans from herpes infections, Sweet syndrome, or inflammatory skin disorders on appearance or biopsy alone.

Clinical Insight

Clinical Insight: Atypical Lyme rashes are one of the main reasons early Lyme disease is missed. In my practice, a rash that is blistering, painful, or unusual in shape should not rule out Lyme disease, especially in endemic areas or when systemic symptoms are present.

Clinical Implications

“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.”

References:
  1. Doughty H, O’Hern K, Barton DT, Carter JB. Vesiculobullous Lyme disease: A case series. JAAD Case Rep. Jun 2022;24:56-58. doi:10.1016/j.jdcr.2022.04.001

Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

SymptomsTestingCoinfectionsRecoveryPediatricPrevention

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1 thought on “Erythema migrans rash doesn’t always have bull’s eye appearance”

  1. Dr. Daniel Cameron
    SaraBeth Yassin

    My rash presented itself as a huge hour glass shape all over my torso. My primary care physician diagnosed me with a fungus. I told him he was wrong and to test my for Lyme. Sure enough my bloodwork confirmed my suspicions.

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