Diagnosis

Diagnosis

Lyme Borreliosis is a clinical diagnosis. Essentially, this means that diagnosing a person with Lyme disease is based more on a physician’s judgment of the whole picture – including a patient’s test results, physical symptoms, and whether he or she has been exposed to potentially infected ticks.

So, a physician who suspects the disease in a patient must be a detective who can piece together the clues from multiple sources to come to as accurate a clinical diagnosis as possible.

The Basics About Diagnostic Guidelines

In an attempt to shape the definition of Lyme disease, as well as its diagnosis and treatment, two organizations – the International Lyme and Associated Disease Society (ILADS) and the Infectious Disease Society of America (IDSA) – have established evidence-based, peer-reviewed guidelines regarding the illness.

And, while neither set of guidelines should be considered definitive (and even though they contradict on a number of crucial points), they can help practitioners identify some agreed-upon common features and telltale symptoms of Lyme disease that could aid in both diagnosing and treating patients.

In the interest of full disclosure, as an organization, Indiana Lyme Connect endorses the guidelines established by the International Lyme And Associated Disease Society (ILADS) for the treatment of Lyme disease and its associated co-infections. These guidelines – which have been adopted and published on the federal government’s National Guideline Clearinghouse – focus on evidence-based clinical judgment when diagnosing and treating Lyme disease and its co-infections.

Guidelines by the International Lyme and Associated Disease Society (National Guideline Clearinghouse)

Instead of offering specific recommendations in its guidelines about diagnosis, the ILADS focuses primarily on a patient’s treatment – leaving the diagnosis up to the judgment of the physician.

The state of the evidence in the diagnosis and treatment of Lyme disease is limited, conflicting and evolving. Accordingly, the recommendations in these guidelines reflect an evidence-based, patient-centered approach that many clinicians will find helpful; they are not intended to be viewed as a mandate or as a legal standard of care. Guidelines are not a substitute for clinical judgment. The International Lyme and Associated Diseases Society encourages clinicians to consider the specific details of an individual patient’s situation when determining an appropriate treatment plan.”

However, elsewhere, ILADS does outline a basic framework for diagnosing both early and later stages of Lyme disease.

Early Lyme Borreliosis begins 3-30 days after a tick bite and is typically identified by an erythema migrans (EM) rash. Although, the EM rash is commonly called a “bull’s eye rash,” studies have shown that less than 20% of patients have EM’s that actually take that shape. In fact, many infected patients (20% to 30%, according to the CDC) do not have EM rashes at all.

If the EM rash is present, it may be accompanied by flu-like symptoms, including:

  • Fever
  • Fatigue
  • Headache
  • Muscle pain
  • Arthralgia (i.e. joint pain, redness, stiffness, and reduced mobility)
  • Muscle pain
  • Neck stiffness

However, if an EM rash is not present, these symptoms could be the only evidence of early Lyme disease.

Late Lyme Borreliosiscan develop anywhere from a few weeks to years later and is the result of widespread infection and the possible involvement of co-infections. Symptoms in the later stage of the disease can overlap (or “mimic”) a myriad of other conditions, including:

  • Fibromyalgia
  • Chronic fatigue syndrome
  • Multiple sclerosis
  • Early ALS
  • Rheumatoid arthritis
  • Lupus
  • Neuro/psychiatric disorders.

However, while a patient’s symptoms might appear to be one of these conditions (or another condition), his or her symptom pattern will be unusual for the illness.

While the Lyme disease Western Blot and ELISA blood tests are better than having no tests at all, unfortunately, in a number of cases, they are not able to detect the presence of a Lyme Borrelia infection.

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Guidelines by the Infectious Disease Society of America (IDSA) (nowhich are no longer listed in National Guideline Clearinghouse)

The following analysis of the IDSA guidelines regarding the diagnosis of Lyme disease is presented with commentary and evidence from the ILADS perspective that serve as counterpoints to the information from IDSA.

The IDSA diagnostic criteria of Lyme Borreliosis relies heavily on three primary principles:

  1. History of Exposure to Tick Attachment(s)
  1. The presentation of Erythema Migrans rash
  1. Positive Serological Testing via the accepted two-tiered approach: ELISA and Western Blot.

When assessing if a Lyme Borreliosis infection is present, keep in mind that, while the above elements (if they show up) are important, they do not represent the onlythings that should be considered in a diagnosis. This is especially true for the EM rash (which is not present in all cases) and testing (which is insufficiently sensitive and fallible on a number of levels).

History of Exposure to Tick Attachment(s)

Providers and/or trained medical professionals identify previous history or exposure to bites and attachment by tick(s).

However, many patients report never having been bitten by tick, possibly due to a number of issues, including:

  • The tiny size of the tick (some stages are the size of a poppy seed)
  • The fact that the tick’s bite is painless
  • The tick attaching in hard to reach or see places

Additionally, while a tick bite is currently the best-known and studied mode of transmission for Lyme disease, other modes are being explored.

The Presence of an Erythema Migrans (EM) Rash

The eryththema migrans (EM) rash is commonly viewed as a hallmark symptom in the early stages of Lyme. However, because the appearance of this rash depends on the response from the patient’s immune system, it does not always appear in connection with a Lyme infection. And, the numbers about how often it appears are wide-ranging – from as few as 25% of cases to as many as 80% of instances of early Lyme disease.

Additionally, even though the terms “EM rash” and “bull’s eye rash” are often used interchangeably when it comes to a Lyme disease diagnosis, in reality, an EM rash related to the illness could take a variety of forms. While it is true that the bull’s eye version of the rash is a sure sign of a Lyme Borreliosis infection, it is not the only form that a Lyme-related EM rash can take. Or, a patient might not have a rash at all.

Chronic and/or persistent cases may develop a more serious form of rash called Acrodermatitis chronica atrophicans (ACA) – a progressive skin condition that causes irritation and swelling.

Positive Testing Using the Accepted Two-Tiered Approach: ELISA and Western Blot

Under the IDSA guidelines, in order to be considered a “true” case of Lyme disease, a patient must test positive using the two-tiered blood testing that includes:

  • The enzyme-linked immunosorbent assay (ELISA)
  • The Western Blot (WB)

This two-tiered testing is recommended as a staple diagnostic tool for a Lyme infection by a wide range of entities, including:

  • The Association of State and Territorial Public Health Laboratory Directors
  • Centers for Disease Control
  • The Food and Drug Administration
  • The National Institutes of Health
  • The Council of State and Territorial Epidemiologists
  • The National Committee for Clinical Laboratory Standards

The first tier is the ELISA – which is a test that detects the presence of antibodies that a patient’s immune system produces to fight a particular antigen. In this case, that antigen is Borrelia burgdorferi, the bacteria that causes Lyme disease.

The problems with the ELISA as a screening tool for Lyme are that:

  • It is targeted to scan for antibodies that are specific to certain strains of Borrelia (not the bactieria, itself), even though there are hundreds of strains that are outside of the test’s scope
  • It relies on the patient’s immune system to mount a profound response by creating enough antibodies for the test to detect (if the immune system ever gets a chance to respond, at all)
  • It assumes that the patient was exposed to specific antigens on microorganisms that can take on many forms (or stages) to protect themselves from detection by the patient’s immune system.

The ELISA has also been shown in repeated studies to be insufficiently sensitive to be used as a Lyme Borreliosis “screening” test.

The second tier of testing is the Western Blot (WB) – also know as the Western immunoblot. For Lyme disease screening purposes, this is a confirmation test that is generally performed only if the ELISA results were positive.

Like the ELISA, the WB is used to detect the formation of antibodies that the patient’s immune system creates to fight specific antigens that are related to infection. The test detects two types of antibodies, IgM and IgG.

The IgM is the first antibody produced in response to infection and is most sensitive during early cases of disease, while the IgG is part of the secondary immune response and is generally persistent and produced in large quantities.

The recommendations regarding WB results that have been made by the committees listed above are as follows:

It was recommended that an IgM immunoblot be considered positive if two of the following three bands are present: 24 kDa, 39 kDa and 41 kDa. It was further recommended that an IgG immunoblot be considered positive if five of the following 10 bands are present: 18 kDa, 21 kDa, 28 kDa, 30 kDa, 39 kDa, 41 kDa, 45 kDa, 58 kDa, 66 kDa, and 93 kDa.”

One thing to keep in mind is that these significant bands of the IgM and IgG were selected for surveillance criteria – meaning that they were designed to track the spread of those particular strains of the Lyme. These bands were never meant to be used as a diagnostic tool, but were chosen because they were more common. However, there are other Western Blot bands that have also been shown to be important components in a Lyme diagnosis.

The sensitivity of this two-tiered testing approach varies considerably based on:

  • The duration of illness
  • Clinical manifestations of the disease (i.e. signs and symptoms)
  • The response by individual patient’s immune system to the illness

When used together properly, the ELISA/WB testing combination is estimated to have an overall sensitivity around 53.7% with a relative specificity >90% – which is no better than the flip of a coin.

Again, in the absence of definitive objective manifestations or laboratory markers, there is rationale and precedence for the use of empirical judgment by practitioners to effectively diagnose and treat the patient based on the presentation of symptoms, concerns of the patient and elimination of other potential culprits. Lyme disease is denoted by the International Lyme and Associated Diseases Society, the Infectious Disease Society of America and the Centers for Disease Control as a clinical diagnosis and is left to the judgement of the physician whether or not to treat based on objective and empirical evidence.