Diseases Similar to Lyme Disease: Tick-Borne Diseases Doctors May Miss

Emerging tick-borne infections may mimic Lyme disease.
Testing is often limited or unavailable.
Delayed diagnosis can complicate treatment decisions.

Ticks carrying Borrelia burgdorferi may transmit far more than Lyme disease alone. In addition to common co-infections such as Babesia and Bartonella, clinicians increasingly encounter emerging and rare tick-borne diseases that complicate diagnosis and treatment.

Diseases similar to Lyme disease include Borrelia miyamotoi, Rocky Mountain spotted fever (RMSF), Bourbon virus, Heartland virus, Borrelia mayonii, and Southern tick-associated rash illness (STARI).

Many of these illnesses are underrecognized because symptoms overlap with Lyme disease, testing is limited, and clinician awareness remains variable.

For a broader overview of overlapping infections, visit our Lyme Coinfections Guide.

Borrelia miyamotoi

Borrelia miyamotoi is a relapsing fever spirochete transmitted by the same Ixodes scapularis ticks that carry Lyme disease.

Unlike Lyme disease, patients often present without the classic erythema migrans rash. Symptoms may include:

• Fever
• Headache
• Fatigue
• Muscle aches
• Relapsing flu-like illness

Standard Lyme disease testing does not reliably detect Borrelia miyamotoi, which can lead to negative Lyme testing despite ongoing symptoms after tick exposure.

Diagnosis typically requires PCR or specialized serologic testing because standard Lyme disease testing does not reliably identify Borrelia miyamotoi.

Doxycycline remains first-line treatment.

Rocky Mountain Spotted Fever (RMSF)

Rocky Mountain spotted fever is a potentially severe bacterial infection caused by Rickettsia rickettsii.

Despite its name, RMSF occurs throughout the United States and is especially common in southeastern regions.

Symptoms may include:

• High fever
• Severe headache
• Muscle aches
• Rash
• Confusion
• Gastrointestinal symptoms

The rash may appear late or may never develop, contributing to delayed diagnosis.

Because Rocky Mountain spotted fever can progress rapidly and become life-threatening, doxycycline should be started immediately when clinical suspicion is high rather than waiting for confirmatory laboratory testing.

Learn more in Atypical Presentation of RMSF.

Bourbon Virus

Bourbon virus is a rare emerging tick-borne virus first identified in Kansas in 2014.

Reported symptoms include:

• Fever
• Fatigue
• Rash
• Nausea
• Body aches
• Headache

Testing is limited to specialized laboratories, and there is currently no specific antiviral treatment.

Diagnosis generally requires testing through specialized public health laboratories because commercial testing remains limited.

Severe illness and fatal cases have been reported.

Heartland Virus

Heartland virus is another emerging tick-borne viral illness associated primarily with lone star ticks.

Symptoms may include:

• Fever
• Fatigue
• Loss of appetite
• Muscle aches
• Nausea
• Low white blood cell counts

Like Bourbon virus, treatment is supportive because no specific antiviral therapy currently exists.

Heartland virus should be considered in patients with compatible illness who fail to improve with empiric doxycycline, since antibiotics are not effective against viral infections.

The true number of infections may be underestimated because testing remains limited.

Borrelia mayonii

Borrelia mayonii is a recently identified cause of Lyme borreliosis found primarily in the upper Midwestern United States, including Minnesota and Wisconsin.

Unlike Borrelia burgdorferi, B. mayonii may produce higher levels of spirochetes in the bloodstream, known as spirochetemia. Patients may present with:

• Diffuse rash
• High fever
• Nausea and vomiting
• Marked fatigue
• Higher bacterial levels in the bloodstream

Because of this higher spirochetemia, B. mayonii has occasionally been visualized on Giemsa-stained peripheral blood smears—an unusual finding in Lyme borreliosis.

Most currently available Lyme disease tests detect B. mayonii, although diagnosis may still depend on the timing of testing and the laboratory assay used.

Treatment generally follows standard Lyme disease recommendations using doxycycline, amoxicillin, or cefuroxime.

STARI (Southern Tick-Associated Rash Illness)

STARI presents with a rash that closely resembles the erythema migrans rash seen in Lyme disease.

However, STARI occurs primarily in regions where Lyme disease is less common and is associated with lone star tick exposure.

The exact cause of STARI remains uncertain.

Because the cause remains uncertain, there is no laboratory test that confirms STARI.

Symptoms may include:

• Expanding rash
• Fatigue
• Headache
• Muscle aches

Unlike Lyme disease, STARI has not been shown to cause chronic neurologic, cardiac, or arthritic complications.

Why These Infections Are Often Missed

Rare and emerging tick-borne infections are frequently overlooked because:

• Symptoms overlap with Lyme disease
• Testing may be unavailable or limited
• Clinician awareness varies
• Geographic assumptions may bias diagnosis
• Patients may test negative for Lyme disease despite tick exposure
• Early symptoms often resemble a nonspecific viral illness

Patients with fever, rash, fatigue, neurologic symptoms, or flu-like illness after tick exposure may require broader evaluation beyond standard Lyme testing alone.

Learn more about Lyme Disease Misdiagnosis.

Why Geographic Expansion Matters

Tick populations and tick-borne pathogens continue to expand geographically because of changing climate, wildlife movement, and land use. Clinicians increasingly encounter infections that were once considered regionally limited.

As the geographic range of Ixodes and lone star ticks expands, physicians may need to consider a broader range of bacterial, protozoal, and viral infections after tick exposure.

Learn more about Prevention of Lyme Disease.

Frequently Asked Questions

What tick-borne diseases are similar to Lyme disease?

Tick-borne diseases similar to Lyme disease include Borrelia miyamotoi, Rocky Mountain spotted fever, STARI, Borrelia mayonii, Bourbon virus, Heartland virus, ehrlichiosis, anaplasmosis, Babesia, and Bartonella infections.

What are rare tick-borne infections?

Rare tick-borne infections include illnesses such as Borrelia miyamotoi, Bourbon virus, Heartland virus, RMSF, and STARI.

Can you have multiple tick-borne infections at once?

Yes. A single tick bite may transmit more than one pathogen simultaneously.

Do standard Lyme tests detect these infections?

No. Many emerging tick-borne infections require specialized testing not included in standard Lyme disease panels.

Do all tick-borne infections respond to doxycycline?

No. Some bacterial infections respond to doxycycline, but viral infections such as Bourbon virus and Heartland virus do not have specific treatments.

Why are these infections often missed?

Symptoms overlap with Lyme disease, testing is limited, early symptoms may resemble a viral illness, and some clinicians may be unfamiliar with emerging pathogens.

Clinical Takeaway

Diseases similar to Lyme disease include both established and emerging tick-borne infections that may produce overlapping symptoms while requiring different diagnostic tests and treatments.

Considering co-infections and alternative tick-borne diseases early may improve diagnostic accuracy and help clinicians choose appropriate testing and therapy before complications develop.

Related Articles

These related articles explore tick-borne co-infections, delayed diagnosis, STARI, Lyme symptoms, and prevention.

What Is Borrelia miyamotoi?
Lyme Coinfections Guide
Southern Tick-Associated Rash Illness (STARI) and Lyme Disease
Delayed Lyme Disease Diagnosis
Lyme Disease Symptoms Guide

References

1. Krause PJ, et al. Borrelia miyamotoi sensu lato seroreactivity and seroprevalence in the northeastern United States. Emerg Infect Dis. 2014;20(7):1183-1190.
2. Biggs HM, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis. MMWR Recomm Rep. 2016;65(2):1-44.
3. Pritt BS, Mead PS, Hoang Johnson DK, et al. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infect Dis. 2016;16(5):556-564.
4. Pritt BS, Fernholz EC, Replogle AJ, Kingry LC, Sciotto MP, Petersen JM. Borrelia mayonii — a cause of Lyme borreliosis that can be visualized by microscopy of thin blood films. Clin Microbiol Infect. 2022;28(6):823-824.
5. Kosoy OI, Lambert AJ, Hawkinson DJ, et al. Novel thogotovirus associated with febrile illness and death, United States, 2014. Emerg Infect Dis. 2015;21(5):760-764.
6. McMullan LK, Folk SM, Kelly AJ, et al. A new phlebovirus associated with severe febrile illness in Missouri. N Engl J Med. 2012;367(9):834-841.
7. Sanchez-Vicente S, Tokarz R. Tick-borne co-infections: challenges in molecular and serologic diagnoses. Pathogens. 2023;12(11):1371.
8. Dembek ZF, Mothershead JL, Cirimotich CM, Wu A. Heartland virus disease—an underreported emerging infection. Microorganisms. 2024;12(2):286.
9. Popov G, Bashchobanov D, Andonova R. Tick-borne co-infection in Lyme disease: clinical impact, diagnostic challenges, and therapeutic perspectives. Microorganisms. 2026;14(2):325.

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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