Lyme disease: what symptoms? What screening tests?

In 2021, it is estimated that nearly 47,000 cases of Lyme disease were diagnosed in general practice, i.e. an incidence of 71 cases per 100,000 inhabitants in France, reports Santé Publique France (source 1). The disease is transmitted by the bite of a tick, infected with bacteria of the type Borrelia. But the diagnosis remains difficult to establish.

Symptoms of Lyme borreliosis are specific are few. One of the main ones, in its early form, is “ erythema migrans, a red spot centered on the tick bite (more than five centimeters in diameter). Present in 95% of cases, it appears three to thirty days later, then it disappears spontaneously. It easily goes unnoticed, especially when the tick clings to the back or the scalp.

Of the late forms of the diseasesometimes more than six months after the bite, can manifest with joint pain, cardiac, neurological or ophthalmological disorders.

In very rare cases, patients may present with what the Haute Autorité de Santé (HAS) calls a “ polymorphic persistent syndrome after a possible tick bite” with multiple pains, intense fatigue and cognitive impairment present for more than six months; and this, even if the screening blood test is negative.

Diagnosis of Lyme borreliosis is based on three argumentsexplains Dr. Raffetin, infectiologist and coordinator of the Reference Center for Tick Vector Diseases North (CRMVT).

“You have to ask yourself if you have been recently exposed to ticks “, reports the doctor. For example, if you have recently been to a place where ticks live: wooded and humid areas (forests, carpets of dead leaves, brush, etc.), but also meadows (tall grass), parks, etc.

It is necessary to identify suggestive clinical signs of Lyme disease. “The main manifestation is theerythema migrans “says the doctor. “When patients notice this lesion, some do not consult, whereas it should be done immediately”. Indeed, in the presence of tick-related erythema – a typical symptom – there is no need to confirm the diagnosis with a test.

In case of doubt, or for scattered forms of Lyme disease – that is to say in which there is no erythema migrans but other clinical signs rather articular or neurological”, a blood test (also called serology) is carried out in search of specific antibodies, reports Dr. Raffetin.

If there are techniques for direct biological diagnosis (direct examination under a microscope, culture of the bacteria, gene amplification of specific DNA by PCR), serology currently remains the most commonly used technique in the laboratoryreports a group of researchers in an article published in 2018 in the Weekly Epidemiological Bulletin (BEH) (source 2).

The purpose of serology is to test the blood for specific anti-Borrelia antibodies. If the serology is positive, it indicates that the patient has indeed encountered Borrelia – but it does not necessarily mean that he has Lyme,” explains Dr Raffetin.

Indeed, “a positive serology does not necessarily mean that the symptoms are related to Lyme disease; it only translates a contact with Borrelia but does not make it possible to affirm that it is about an evolutionary infectious process”, continue the authors of the article published in the BEH.

Then, “the challenge is to know whether the patient is currently ill and needs to be treated, or if he made antibodies without ever developing clinical signs. Most people will develop antibodies without ever being sick in their life,” underlines Dr. Raffetin.

The serology takes place in two stages:

• A first-line serological test, usually by a ELISA technique ;
• Followed, if the ELISA result is positive or doubtful, confirmation of the specificity of these antibodies by a second reaction called immunoblotting or Western blotas recommended.

“By optimizing sensitivity, then specificity, the combination of these two serological techniques makes it possible to get closer to the desired objective: be surefaced with a patient presenting signs compatible with the existence of a disseminated infection, that he has been in contact with pathogensand that consequently the diagnosis of Lyme borreliosis can be evoked”, report the authors of the article.

“The ELISA test is prescribed by doctor who, looking at the argument tick exposure and suggestive clinical signs. will prescribe serology. It costs approx. 10 euros “says Dr. Raffetin. It is reimbursed by Social Security.

Western blot test is not refunded to the patient that if the results of the ELISA test have been shown positive. In a written question to the Government in July 2023MP Fabien Genet draws the attention of the Minister of Health and Prevention to the reimbursement by social security of preventive tests for Lyme disease, and asks him in particular if he ” consider allowing unconditional refund of Western Blot test in order to allow better management and better diagnosis of Lyme disease”.

This question has indeed been the subject of controversy for several years. No test currently available in France gives a 100% sure result. The HCSP expressed doubts about the performance of serological tests.

Nevertheless, ” the blood test has very good performance, there are therefore very few false positives and false negatives”, emphasizes Dr. Raffetin. “We are talking about a sensitivity and specificity of 98% “, Continues the infectiologist – knowing that the minimum performance recommended by theEuropean Union Concerted Action on Lyme Borreliosis (EUCALB) are 90% specificity in ELISA and 95% for Western blot,” the researchers write in the BEH article.

Many tests to diagnose Lyme disease have been developed in recent years, but none are as effective as serology. “Some labs offer other tests that are not scientifically validated and therefore perform much worse than the blood test. I strongly advise against experimental tests which are very expensive and are not reimbursed, because we will not know what to do with the results, and this will not advance the care of the patient, ”adds Dr Raffetin.

Current tests for Lyme disease only look for antibodies against Borrelia. Gold, ticks transmit other bacteria (Anaplasma, Rickettsia…) but also parasites and viruses.

“Our research in the Sénart forest shows that half of the ticks are infected with a pathogen and, among them, half carry several,” observes Muriel Vayssier-Taussat, research director at INRA (National Institute for Agronomic Research).

However, these agents are responsible for pathologies that sometimes resemble Lyme disease. “Unfortunately, most of my colleagues do not look for these co-infections”, regrets Dr Ghozzi.

In conclusion, taking into account the three arguments is essential to make the diagnosis of Lyme disease, recalls Dr. Raffetin, and “the results of serology must always be interpreted according to the clinical and epidemiological context”, recalls the article published in the BEH. “For example, if we do a serology on someone who is tired, even if the serology is positive, that does not necessarily mean that the person has Lyme disease, because fatigue can evoke other illnesses. To confirm the diagnosis of Lyme, you need fatigue but also other clinical signs suggestive of Lyme, ”explains the infectious disease specialist.

“The whole challenge for doctors is to not to miss a Lyme when there really is one, and not to diagnose a Lyme when there is none”.