Lyme Disease Rash vs Cellulitis: When Lyme Mimics Skin Infection

Lyme disease can mimic cellulitis, a common bacterial skin infection—leading to delayed diagnosis if tick exposure is not considered.

In this case, a 40-year-old woman developed redness, swelling, pain, and a spreading rash at the site of a surgical excision.

The patient was initially treated with cephalexin and later switched to trimethoprim/sulfamethoxazole (TMP/SMX).

“Over the next 24 hours, there was a rapid expansion of abdominal redness and patchy areas of redness on her left groin and her right forearm,” the authors wrote.

The patient also complained of muscle and joint stiffness but attributed these symptoms to recent outdoor camping and exercise.

The woman was admitted for presumed postoperative cellulitis. However, because of her recent camping trip and possible tick exposure, physicians prescribed doxycycline for suspected Lyme disease.

Within hours of starting doxycycline, the patient’s abdominal rash significantly receded, the forearm and leg rashes resolved, and the joint pain and stiffness improved markedly.

The Lyme disease diagnosis was confirmed with an IgM Western blot test.

“Initial suppression of the worsening rash could have been due to a low level of TMP/SMX activity on Borrelia burgdorferi stationary phase cells,” the authors explained.

[bctt tweet=”Rashes caused by Lyme disease may be incorrectly identified and attributed to other conditions such as cellulitis.” username=”DrDanielCameron”]

The patient’s IgG Western blot test was negative.

Lyme Disease Rash vs Cellulitis

Although Lyme disease can present with erythema migrans (EM), early rashes may resemble cellulitis and be misidentified.

The authors suggested that Lyme disease should be considered in patients with cellulitis in areas where Lyme disease is endemic.

Lyme disease rashes have also been misidentified in other studies. In a case series involving 88 patients with erythema migrans, 13 had rashes that were initially misdiagnosed or treated incorrectly.

“Rashes were often misidentified by clinicians and patients as a spider bite, cellulitis, or shingles,” wrote Aucott and colleagues.

This pattern reflects a broader issue of Lyme disease misdiagnosis, where early symptoms are mistaken for more common conditions.

Until more accurate tests are available for early Lyme disease, patients without a classic EM rash must be evaluated carefully.

When cellulitis is uncertain, empiric antibiotics may need to cover both Lyme disease and common bacterial skin infections.

Clinical Insight

Editor’s note: In my practice, I sometimes prescribe cefuroxime or amoxicillin/clavulanic acid when Lyme disease is a consideration. Neither cephalexin nor TMP/SMX are effective against Lyme disease.

If Lyme disease is suspected, I typically treat longer than 7–10 days.

You can view the rash in the open-access journal article.

Clinical Takeaway

Lyme disease rashes can closely resemble cellulitis. When a skin infection does not respond as expected—or when symptoms include joint pain, fatigue, or recent outdoor exposure—Lyme disease should be considered.

Early recognition matters. Misidentification of Lyme rashes can delay appropriate treatment and prolong illness.

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