Atypical Lyme Disease Rash: Cellulitis-Like Lesions and Oral Findings

An atypical Lyme disease rash may resemble cellulitis rather than a classic bull’s-eye lesion.
Unusual oral findings can further complicate the diagnosis.
Early recognition and appropriate antibiotic treatment can lead to complete recovery.

An atypical Lyme disease rash can make early Lyme disease difficult to recognize. Instead of the classic bull’s-eye (erythema migrans) rash, some patients develop cellulitis-like skin lesions and unusual oral findings that can delay diagnosis. These uncommon presentations may initially suggest other infections, increasing the risk of delayed treatment.

A BMJ Case Reports article by Sharma describes a patient with early disseminated Lyme disease whose rash lacked the typical target appearance and whose unusual oral findings initially suggested an entirely different illness.

The case highlights why Lyme disease remains a clinical diagnosis and why physicians should consider the disease even when the rash is atypical or initial laboratory testing is negative.

Patient presented with an atypical Lyme disease rash

Three weeks after returning from a camping trip in northern Minnesota, a 45-year-old man developed headaches, fever, malaise, fatigue, generalized weakness, and diffuse joint, muscle, and back pain. Ibuprofen temporarily relieved his symptoms, but they soon returned with chills, profuse sweating, blurry vision, abdominal pain, leg cramps, chest pressure, and worsening headache.

On examination, physicians found a large erythematous, warm rash over the left lower abdomen without central clearing. Several smaller erythematous lesions were also present on the abdomen and back. Unlike classic erythema migrans, these lesions closely resembled cellulitis.

In addition to the skin findings, scattered white patches were noted on the tongue, consistent with an oral pseudomembrane. These unusual oral findings initially raised concern for conditions such as infectious mononucleosis, HIV infection, or oral candidiasis rather than Lyme disease.

As Sharma noted, “Our case did not exhibit typical target lesions.” Instead, the patient presented with “large erythematous, warm rash without central clearing…with similar but smaller rashes on abdomen and back and scattered white patches on surface and side of tongue.”

This case serves as an important reminder that Lyme disease does not always produce the classic bull’s-eye rash. In some patients, erythema migrans may resemble cellulitis or other inflammatory skin disorders, making careful attention to exposure history and associated symptoms essential for timely diagnosis.

Related pediatric case: 6-year-old girl with a rare cutaneous presentation of Lyme disease

Why the diagnosis was challenging

The patient’s presentation created several diagnostic challenges. The cellulitis-like rash suggested a bacterial skin infection, while the oral pseudomembrane prompted consideration of HIV infection, infectious mononucleosis, or oral candidiasis.

Physicians started intravenous vancomycin because of concern for methicillin-resistant Staphylococcus aureus (MRSA). Fluconazole was also prescribed for possible oral thrush.

Testing added further confusion. Epstein-Barr virus antibodies were positive, suggesting prior infection, while the initial Lyme screening ELISA was negative.

Early Lyme disease may not always be detected by serologic testing because antibodies may not yet have reached detectable levels. When a patient’s clinical presentation and exposure history strongly suggest Lyme disease, treatment should not be delayed solely because an initial screening test is negative. Learn more about why early Lyme disease tests can be negative.

Because clinicians maintained a high level of suspicion, the patient was empirically started on doxycycline while additional testing was pending.

Early disseminated Lyme disease was confirmed

The patient’s symptoms improved quickly after doxycycline was started. Over the following several days, his headache diminished, the cellulitis-like rash began to fade, and his overall condition improved substantially.

Subsequent laboratory testing helped clarify the diagnosis. Although the initial Lyme screening ELISA was negative, confirmatory Western blot testing later supported the diagnosis of early disseminated Lyme disease. After discussion with infectious disease specialists, vancomycin was discontinued, and the patient completed a three-week course of doxycycline. At his four-week follow-up visit, his rash had completely resolved, and he had no recurrence of symptoms.

Can Lyme disease look like cellulitis?

Yes. Although the classic erythema migrans rash is often described as having a bull’s-eye appearance, many Lyme disease rashes do not follow this pattern. Some patients develop uniformly red, warm lesions that resemble cellulitis, making a bacterial skin infection a more likely initial diagnosis.

This case illustrates how an atypical Lyme disease rash may delay diagnosis, particularly when accompanied by fever, systemic symptoms, or unusual oral findings. Physicians practicing in Lyme-endemic regions should consider Lyme disease in patients with cellulitis-like skin lesions following potential tick exposure, even when no classic target lesion is present.

Can Lyme disease affect the tongue?

Lyme disease does not typically cause tongue abnormalities. However, the patient in this case developed scattered white patches on the tongue consistent with an oral pseudomembrane. These findings initially raised concern for oral candidiasis, HIV infection, or infectious mononucleosis rather than Lyme disease.

Although an oral pseudomembrane is uncommon, this report demonstrates that early disseminated Lyme disease may occasionally be accompanied by unusual oral findings that complicate the diagnostic evaluation. Clinicians should evaluate the entire clinical picture rather than relying on any single symptom or laboratory test.

Frequently Asked Questions

Can Lyme disease cause a rash without a bull’s-eye?

Yes. Many patients do not develop a classic bull’s-eye rash. An atypical Lyme disease rash may appear uniformly red, resemble cellulitis, or have other unusual features.

Can Lyme disease look like cellulitis?

Yes. Lyme disease may occasionally produce warm, erythematous skin lesions that resemble cellulitis, particularly during early disseminated infection.

Can Lyme disease affect the tongue?

Tongue and other oral findings are uncommon. In this case, the patient developed scattered white patches and an oral pseudomembrane during early disseminated Lyme disease.

Can Lyme disease tests be negative early?

Yes. Early serologic testing may be negative because antibodies have not yet reached detectable levels. When clinical suspicion is high, physicians may consider the patient’s exposure history, symptoms, examination findings, and follow-up testing when deciding whether to begin treatment.

Clinical Takeaway

This case demonstrates that an atypical Lyme disease rash may resemble cellulitis rather than the classic bull’s-eye lesion. Unusual oral findings and an initially negative Lyme screening test further complicated the diagnosis.

Lyme disease should remain in the differential diagnosis when patients develop unusual skin lesions and systemic symptoms after possible tick exposure, even when the rash is atypical and early laboratory testing is negative.

Related Articles

How Often Is Lyme Disease Misdiagnosed?
Lyme Disease Symptoms Guide
Can Lyme Disease Cause a Positive Mononucleosis Test?
Atypical Lyme Disease Symptoms: Numbness and Abdominal Wall Weakness
Bannwarth Syndrome and Unexplained Weight Loss

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

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention