About Lyme Disease

PATHOGEN

Chronic Lyme disease may be caused by species belonging to the Borrelia genus, although not all species are necessarily pathogenic.

In Europe, the most prevalent species are:

Borrelia burgdorferi
Borrelia spielmanii
Borrelia afzelii
Borrelia garinii
Borrelia bavariensis

At least these species are included in the Western Blot tests available in Hungary.

The primary vector is the common tick (Ixodes ricinus). However, not all ticks are infected, and estimates regarding infection rates vary.

Contrary to common belief, even a bite from an infected tick does not “guarantee” Lyme disease. Consider forestry workers, who may receive numerous tick bites during their lifetime without necessarily developing the disease. The bacterium entering the human body must rapidly adapt to an environment significantly different from the tick’s gut. If adaptation fails, or if the immune system mounts an adequate response in time, the bacterium does not survive this early phase.

The most characteristic symptom is the bull’s-eye rash (erythema migrans). However, it does not develop in every case, or it may go unrecognized—for example, when appearing in body folds where it may not have a circular shape. Additionally, the rash may disappear spontaneously over time.

Cases that progress to chronicity (even years or decades later) are typically those where early recognition and treatment did not occur.

It is important to note that the medical community itself remains significantly divided regarding the precise definition of pathogen–disease relationships in this context. This division is present globally, not only locally.

Infectious disease societies and non-infectious-disease Lyme specialists hold fundamentally different views on chronic Lyme disease.

Infectious disease specialists maintain that after successful therapy—even in chronic cases—Lyme disease is considered cured. They do acknowledge, however, that some patients continue to experience unusual symptom complexes. This phenomenon is referred to as Post-Lyme Syndrome, and they believe these residual symptoms are not caused by Borrelia. Unfortunately, further guidance on alternative causes is often lacking.

In contrast, Lyme specialists attribute persistent symptoms to ongoing Borrelia infection and often consider them evidence of unsuccessful treatment. They may recommend antibiotic therapy lasting months or even years.

This divergence understandably causes confusion and uncertainty among patients, who may receive diametrically opposed diagnoses and recommendations depending on which physician they consult.

Encouragingly, in recent years the positions of the two groups have somewhat converged. Infectious disease specialists have long suggested that “something else” may be responsible for persistent symptoms, while Lyme specialists increasingly suspect coinfections—particularly Bartonella and Babesia—behind treatment failures. Clinical outcomes have reportedly improved as therapeutic focus has shifted toward managing these coinfections.

From a layperson’s perspective, the term “Lyme disease” may refer to any of these interpretations. Patients often simply know that they experienced a tick bite followed by persistent symptoms. Since tick bites are associated with Lyme disease, they understandably use this term—without knowing which bacterium is responsible. Determining that is the role of medical professionals.

For clarity, it is essential to specify which pathogen is meant within the Lyme complex. In this article, we discuss chronic Lyme disease according to its official definition: Lyme Borreliosis (LB), meaning Lyme disease caused specifically by Borrelia species. This terminology, introduced in the 1990s by the renowned Dr. Béla Pál Bózsik, has been accepted and continues to be used in Hungarian medical literature, including by infectious disease societies.

The broader, lay interpretation of “Lyme disease” beyond Lyme Borreliosis is discussed in separate articles addressing coinfections (Bartonella, Babesia).

SYMPTOMS

Since the bacterium causing Lyme Borreliosis was identified more than 40 years ago, and the disease has been extensively studied, its clinical manifestations—including chronic forms—are well documented.

Although our focus here is chronic manifestations, the acute phase’s hallmark symptom, erythema migrans (bull’s-eye rash), must be mentioned. Chronicity presupposes an initial acute infection, and the rash remains an officially accepted diagnostic criterion.

Unfortunately, the rash does not appear in every case, meaning chronic infection may develop without recognized exposure.

Ticks may also transmit other pathogens, such as viral encephalitis or TIBOLA, which are not discussed here. Researchers also suspect ticks may transmit coinfections such as Bartonella and Babesia, addressed in separate articles.

In chronic Lyme Borreliosis, researchers have documented the following characteristic conditions:

Borrelia lymphocytoma
Acrodermatitis Chronica Atrophicans (ACA)
Lyme carditis
Peripheral facial palsy
Lymphocytic meningoradiculitis
Chronic neuroborreliosis
Chronic polyneuropathy
Lyme arthritis

Because some of these conditions occur in other diseases, proper diagnosis requires specialist evaluation using additional diagnostic criteria. If Lyme Borreliosis is not confirmed, further investigation for coinfections is recommended.

TESTING AND DIAGNOSIS

It is important to distinguish between the presence of a pathogen and the presence of disease.

New, increasingly sensitive direct detection methods have entered the market and may produce confusing results, potentially leading to misdiagnosis if not properly interpreted.

Dr. Bill Rawls, in Unlocking Lyme, cites a thought-provoking example: the earliest known PCR-confirmed human infected with Borrelia was a 5,000-year-old hunter discovered in the Italian Alps. Although he had mild early knee arthritis, he lived an active life and died from an arrow wound—not Lyme disease.

This illustrates that pathogen presence alone does not prove disease; infection may be effectively controlled by the immune system.

Current direct detection methods (microscopy, PCR) are insufficient to establish a definitive diagnosis of chronic Lyme Borreliosis. The goal is instead to assess the balance between the bacterium and the immune system.

ELISpot

ELISpot measures T-cell immune response. Initially promising when introduced in the 2010s, it is highly effective for diagnosing latent or reactivated tuberculosis, where it became a diagnostic standard.

In Lyme disease, however, its utility is less clear. While it detects active T-cell production, it appears unable to distinguish between active infection and residual immune response.

A Dutch clinical study found ELISpot positive in both active and resolved cases, with no correlation to clinical status. Only its negative predictive value proved reliable: a negative result effectively excluded prior exposure to Borrelia.

Serology: ELISA and Western Blot

The accepted diagnostic approach is a two-step serological process:

ELISA screening test
Confirmatory Western Blot (or Immunoblot) if ELISA is positive

ELISA frequently yields false positives; Western Blot increases specificity by detecting multiple Borrelia species and antigen components via band patterns.

After infection, IgM antibodies appear first, typically disappearing after two months, followed by IgG antibodies in the same bands. Persistent isolated IgM positivity beyond two months excludes active Borrelia infection.

Dr. Mozayeni (ILADS President, 2019–2021) reported frequent false-positive IgM Lyme patterns in patients with chronic bartonellosis.

IgG positivity may indicate past or ongoing infection. Chronic Lyme Borreliosis is associated with progressively increasing antibody production; thus, strong IgG activity is expected. Comparing paired serum samples taken approximately three months apart can reveal rising IgG intensity, confirming active chronic infection.

Stable IgG intensity suggests past infection maintained asymptomatically by the immune system.

Neuroborreliosis

Diagnosis requires cerebrospinal fluid (CSF) analysis when indicated. In active infection, inflammatory markers appear in CSF. Western Blot antibody testing can be performed on both blood and CSF.

In neuroborreliosis, intrathecal antibody production differs from serum antibody patterns; therefore, the band patterns in CSF and blood must differ to confirm diagnosis.

Properly conducted serology demonstrates a 100% negative predictive value: absence of antibody production effectively excludes chronic Lyme Borreliosis.

Available immune response tests in accredited laboratories include:

ELISA
Immunoblot
Western Blot
U.S. laboratory Western Blot panels (available via Rare Diseases Labs – Europe), particularly useful when tick exposure occurred abroad, as these panels test up to 17 Borrelia species.