Lyme Disease Review

Lyme disease, or Lyme Borreliosis, is a tick-borne illness that has been around for a very long time. The medical community has become aware of it as a separate disease only in the 1970s, with the bacteria causing it being discovered and isolated in the 1980s. Lyme disease is the most common disease spread by ticks in the Northern Hemisphere. It is estimated to affect 300,000 people a year in the United States and 65,000 people a year in Europe (Solomon et al, 2014; Berger 2014).

Research is being conducted currently to explore multiple facets of this disease and to better understand it. It is still very difficult to establish a consensus in the medical community as to what exactly this disease is, how many different forms it can take and what the exact symptoms are. Acute Lyme disease, immediately following a tick bite, has been well documented, and treatment for it is relatively straight forward. However, when the term “chronic Lyme” is used, there is much more disparity between the medical authorities worldwide. In the following text, we will try to address some of the problems and confusion around it, as well as give our official stance. 

Firstly, a tick bite can expose a person to a variety of bacteria and other microorganisms that may make them sick (Edlow, 1999). This can occur after a single bite or through multiple tick bites. Many infectious agents are harboured in the gut of the tick and can enter the body. Not all of them will make a person sick, nor will every tick-bite result in Lyme or an infection. The statistics and risks for infection are much higher in limited areas known as endemic for Lyme (NHS Choices). Lyme disease is traditionally attributed to a single bacterium, Borrelia burgdorferi (Sigal et al, 1997). The role of co-infections and other bacteria and viruses will be discussed further in the text. 

Acute Lyme disease is established based on the presence of a tick bite and a plethora of clinically significant symptoms. Erythema migrans is the primary symptom used to diagnose acute Lyme infection (Solomon et al, 2014). Erythema migrans usually displays itself as redness or a rash present at the site of the tick bite. It is neither itchy nor painful. Standard medical guidelines state that the rash appears most often in a specific bulls-eye pattern, with the surrounding circle being red and the inside of the circle being normal (however clinical experience has shown this not to be the case, as the rash can present itself in multiple forms) (Weber et al, 1984). This represents the phase in which the bacteria are penetrating the local tissue and entering further into the body. If such redness is noticed at the site of a tick bite, the standard procedure is administering immediate antibiotic prophylaxis in order to kill off the bacteria before they can adapt to the body and infect further tissues (Nadelman et al, 2001). If that procedure is followed, it usually prevents the appearance of any symptoms and the disease is stopped at its root. However, there are several problems with this. One of them is the incidence of the tell-tale rash. Some authorities claim it to be present in 100% of the cases, while others claim a lower incidence (Feder et al, 1993; Reik et al, 1986). So there is no consensus on the necessity of the rash for a clinical diagnosis. Another problem is that the rash can be present at a site that is not easily accessible or noticeable. It can be present on the back, the scalp beneath the hair, on the soles of the feet, in the crotch or the armpits. It is suspected that many people simply do not notice the rash in time or do not give it much thought. This allows the disease to spread and enter later phases which are much more serious.  In some cases, the antibiotic treatment can seem successful at the beginning; however, the bacteria can simply transition into another form and remain dormant for a period of time, giving the patient and the physician a false sense of security (Pachner et al, 1989). 

Once the bacteria have established themselves in the body, either by not being treated with antibiotics immediately, or by becoming dormant, the disease enters the next stage. Infected individuals experience flu-like symptoms such as headache, muscle soreness, fever, and malaise (Auwaerter et al, 2004). Lyme disease can progress to later stages even in patients who do not develop a rash, meaning that the flu like symptoms will be the first visible signs of the disease. This is most often misdiagnosed as flu and not treated with antibiotics, leading to a further progression of the disease. Within days to weeks after the onset of local infection, the Borrelia bacteria may begin to spread through the bloodstream. Rashes may develop at sites across the body and not near the tick bite (Dandache et al, 2008). Another skin condition that may present itself is Borrelial lymphocytoma, a purplish lump that develops on the ear lobe, nipple, or scrotum that can start to be painful (Stanek et al,2008). Other discrete symptoms include migrating pain in muscles, joints and tendons, and dizziness. This is called an early disseminated phase, when the bacteria are entering the connective and muscle tissue as well as the internal organs. 

If left untreated or mistreated with the wrong antibiotics or weak doses, in most cases it progresses further into a late disseminated phase. This is once again a point on which there is little consensus. Some experts claim that the symptoms will only get worse and increase in intensity. The symptoms can develop into severe and chronic symptoms that affect many parts of the body, including the brain, nerves, eyes, joints, and heart. Many disabling symptoms can occur, including, in extreme cases, permanent impairment of motor or sensory function of the lower extremities. The associated nerve pain radiating from the spine is called Bannwarth syndrome, and can be debilitating and severe (Pfister et al, 1987).  A certain percentage of patients will start to exhibit neurological symptoms. A polyneuropathy that involves shooting pain, numbness, and tingling in the extremities or back may develop. A neurological syndrome called Lyme encephalopathy is associated with subtle cognitive difficulties, insomnia, a general sense of feeling unwell, changes in personality can also occur (Benke et al, 1995). Other problems, however, such as depression, multiple sclerosis and fibromyalgia, are no more common in people with Lyme disease than in the general population [the links are currently being studied, there are theories postulating that many of the incidences of multiple sclerosis and fibromyalgia are triggered by the Lyme infection (Martin et al, 2001)]. Cognitive impairment, brain fog, migraines, balance issues, weakness and in some rare cases psychosis can also develop in the late phases (Bratton et al, 2008; Hess et al, 1999; Biesiada et al, 2012; Fallon et al, 1994). Arthritic pains can grip all of the limbs and joints, causing deterioration and rupturing cysts, rendering the joints virtually useless. 

Acrodermatitis chronica atrophicans is a chronic skin disorder observed usually in elderly patients (Bhate et al, 2011). It begins as a reddish-blue patch of discoloured skin, often on the backs of the hands or feet. The lesion slowly atrophies over several weeks or months, with the skin becoming first thin and wrinkled and then, if untreated, completely dry and hairless, starting to die. 

However, some experts, including our team, believe that the bacteria can utilise its immune-evading capabilities and lay dormant for a given period of time. Only one of more severe symptoms may be present, or all of the symptoms in a much lower intensity. The clinical presentation given in the text above includes most of the observed symptoms. Not all of them need to be present, neither will they progress at the same time or appear simultaneously. The infection can also reach a temporary equilibrium with the immune system, halting the symptoms and showing a temporary improvement. The immune reaction gets exhausted however and the symptoms can relapse periodically. Some cases may remain displaying lower severity symptoms for years before exhibiting any of the more severe ones. This is one of the reasons it is so easy to mistake Lyme for a number of other diseases and syndromes which results in the physician prescribing inadequate or inappropriate treatments (Burakgazi et al, 2014; Bahrain et al, 2007). It is our opinion that many cases of Lyme are underdiagnosed or misdiagnosed by the national health authorities. 

Another contentious issue with Lyme disease is laboratory testing. Since clinical presentation can vary significantly, lab tests are also used to confirm suspicions. This is by no means a definitive solution, as laboratory tests also vary in specificity and accuracy. Several new methods are being developed with higher accuracy to help diagnose Lyme. A positive lab test is by no means the primary tool for diagnosis. The symptoms and clinical presentation also need to be evaluated in detail. Several forms of laboratory testing for Lyme disease are available, some of which have not been adequately validated. The most widely used tests are serology tests, which measure levels of specific antibodies in a patient's blood. These tests may be negative in early infection, as the body may not have produced a significant quantity of antibodies, but they are considered a reliable aid in the diagnosis especially for the later stages of Lyme disease. There is also concern about the bacteria’s ability to alter forms into cystic, at which point it presents different antigens and may easily go unnoticed (Berndston et al, 2013; Miklossy et al, 2008). 

Another issue is that the immune system, in cases of complex infections (such as Lyme disease), simply cannot mount a response to all the pathogens involved in the condition. It selects the “most dangerous” ones, usually by the sheer invasiveness and speed of replication, and attacks the most dangerous ones first. Incidentally, Borrelia lacks factors common to many bacterial pathogens, such as lipopolysaccharide, toxins, and specialized secretion systems (Tilly et al, 2008), meaning that if certain co-infections are present (most often viral infections) the immune system will simply not mount a response until it has dealt with the more pressing infection. 

The serological laboratory tests most widely available and employed are the Western blot and ELISA.  A two-tiered protocol is recommended by the Centers for Disease Control and Prevention: the sensitive ELISA test is performed first, and if it is positive or equivocal, then the more specific Western blot is run (Centers for Disease Control and Prevention). The reliability of testing in diagnosis remains controversial. Studies show that IgM blot in early disease had a sensitivity of 32% and a specificity of 100%; the IgG blot after the first weeks of infection had a sensitivity of 83% and a specificity of 95% (Dressler et al, 1993). The initial ELISA test has a sensitivity of less than 50%, but raises over time in untreated patients (Aguero-Rosenfeld et al, 2005).

Polymerase chain reaction (PCR) tests for Lyme disease have also been developed to detect the DNA of the Lyme disease spirochete. PCR tests are however, far from perfect as they can often show false negative results with blood and cerebrospinal fluid specimens, as well as false negatives due to the sheer availability of the bacterial material in the sample. Blood and CSF do not necessarily have to be the largest pools of bacteria in the body. Hence, PCR is not widely performed for diagnosis of Lyme disease, but it may have a role in diagnosis of Lyme arthritis, because it is a highly sensitive way of detecting OspA DNA in synovial fluid, for cases in which none of the other clinically significant symptoms are present.

We personally recommend the newer method of ELISPOT serological tests, as it shows the highest specificity and accuracy of available tests. Armin labs in Europe perform these types of tests, along with consultations and recommendations for patients (ArminLabs).

Once an accurate diagnosis has been established, treatment is commenced.  Treatment for Lyme disease especially the chronic form is the most fiercely debated point. Several studies have been carried out showing differing results. To date, there are only three clinically-controlled large scale studies that have evaluated treatment of Lyme disease. Of the three National Institutes of Health (NIH)-funded studies, one’s findings opposed, one’s findings were inconclusive and the other findings were supportive of, longer-term antibiotic treatment. All studies had limitations. The conclusions of all of these demonstrate that much more research is needed to provide a good insight.

The next best evidence of effective treatment is observed in case studies, treatment experience and patient reports. Several international Lyme experts, in particular Dr Jemsek and Dr Horowitz from the US, have decades of experience and have treated thousands of patients. For confirmed cases of Lyme or co-infections we favour an approach based around the use of pulsed antibiotic therapy, alongside additional therapies to support the immune system. However, antibiotic usage must be responsible, precise and as short as possible.

Another issue regarding treatment is that most available therapies fail to encompass and treat the whole spectrum that is Lyme. Typically, physicians focus on the Borrelia bacterium which is the primary cause of the disease, but not the only one. A whole plethora of co-infections occurs upon a tick bite, and it opens the gates for many more diseases, which causes a very complex chain reaction in the immune system. We will discuss some of those aspects now.

Several co-infectious agents have been identified in patients suffering from Lyme disease. Chlamydia Pneumoniae, Babesia sp, Coxsackie virus and Herpes virusamong them (Bergkhoff et al, 2012). An interesting thing to note is that Coxsackie virus infections usually last no longer than 2-3 weeks, but with patients diagnosed as Lyme patients it can be detected in the blood for a very long time, sometimes spanning several years.

Our rationale behind the persistence of the co-infections is that they work in tandem, suppressing and wearing down the immune response until it is no longer able to defend itself. These co-infections can also strengthen the symptoms and intensity of the Borrelia infection as well as reduce the immune response in clearing the rest of the bacteria after the antibiotic treatment has been issued, which can contribute to the recurrence of the Lyme symptoms. That is why a rational approach would be to focus on the primary as well as adjunct and supplemental treatment, using all available methods, including supplements and nutraceuticals to provide a holistic science based approach to treat the complex condition, along with any accompanying or underlying illnesses.

Post-Lyme Disease

In about 5% of patients treated for Lyme disease and associated co-infections and co- morbidities will continue exhibiting symptoms although there is no evidence of a bacterial infection present, or the causative agents of the disease (Blaut-Jurkowska et al, 2016). This can be due to several factors, including autoimmune disorders triggered by the infections, oxidative damage from prolonged inflammatory processes, damage from antibiotic over usage and dysbiosis.

Most commonly, a patient ill for a prolonged period by such a complex disease that affects multiple organ systems will have a wide range of symptoms and disorders as a consequence from the original disease (Aucott et al, 2013). Such patients are often misdiagnosed and dismissed as psychiatric cases or being deconditioned. In clinical practice, however, detailed testing of metabolic functions shows many small imbalances and disorders that, when put together, can cause severe symptoms.

Treatment of Post-Lyme disease can be as complex as the treatment of Lyme disease itself, and should be considered as an extension of the primary treatment. Long term use of antibiotics in patients who are diagnosed as Post-Lyme have been shown to be either ineffective (Kaplan et al, 2003) or detrimental to the patient’s health (Krupp et al, 2003).

So far, no single treatment exists for this condition. The primary treatment consists of carefully addressing key points in the metabolism, mitochondrial function, immune system, gut microbiota, neurotransmitter balance, micronutrient balance and inflammation damage in order to reduce the damage done and restore those systems in health

A Rational Approach to Lyme

Proper diagnosis and assessment of Lyme disease, Post-Lyme or any complex infection requires a multiple stage approach consisting of detailed anamnesis, symptoms assessment and grading, differential diagnosing as well as laboratory testing (for infections as well as for biochemical markers of other processes in the body).

Once the degree and severity of the disease are established, and co-morbidities identified, they must all be addressed, from multiple angles, to set up the most effective treatment program possible. Treatment options vary from patient to patient, however, in cases where testing and the clinical image give a high degree of certainty of an active bacterial infection, oral antibiotic treatment would be recommended.

Building upon the information given above about the microbiology of the multiple bacterial species involved in this disease the logical conclusion is that a combination treatment based on the bacteria present in a patient’s body should be selected and administered in a pulsed manner, in order to minimise the damage of the antibiotic to the body as well as the chances of the bacteria developing resistance in any way.

Intravenous antibiotic treatment should be reserved for more severe cases, where high intensity neurological involvement is present, or carditis and pericarditis are suspected. The combined pulsed antibiotic approach has several advantages when compared with singular high dose or long duration approaches.

Once the Borrelia bacterium feels stress from the antibiotic, much of the bacteria will transition into a round body form, which is more resilient to certain antibiotics (which are most commonly used to kill the spirochaetal form). That is why a second phase of antibiotics is administered necessary to kill off the round body form. The combinations of antibiotics and duration of the treatment phase should be regularly assessed based on testing and clinical image. Although antibiotics are considered the primary treatment, they should in no way be the only course of treatment.

It is also crucial to eliminate both the co-infections and minimise the negative impact of the antibiotic treatment on the body gut microbiota, as well as address all the associated co-morbidities and symptoms. In many cases of complex tick-borne diseases additionally to the bacteria other protozoan parasites may also be present, such as Babesia sp, Toxoplasmosis, Schistosoma and malaria agents. Where evidence of these parasites are detected, antiparasitic measures are to be taken accordingly.  One reasonable strategy would be to improve the immune response and re-condition the immune system cells, since a prolonged and chronic immune response drains the cells of the immune system of their nutrients and starves them. Those co-factors and energy substrates need to be replenished to induce an immune response capable of suppressing the bacteria alongside the antibiotics.

The importance of the treatment protocol being tailored around the patient’s specific condition, presence of infecting agents, pre-existing conditions and symptoms must be stressed, and the durations, intensity and frequency of treatments will be unique to each patient. The multi systemic approach allows tackling as many symptoms as possible and addresses all the underlying or secondary illnesses (most patients do not suffer “only” from Lyme disease, but also have accompanying illnesses). This kind of approach allows for a much greater success rate and speed of recovery.

All cases of Lyme disease are different and unique. The relation between the co- infections and the patient’s immune system and specific health problems is crucial in determining the right course of therapy. With this kind of protocol, patients will be afforded a unique personalised approach that is not a “one size fits all” policy, which has shown not to be effective in treating a large part of Lyme disease, Post-Lyme or complex infection patients.

Written by Augmented Health, copyright 2016.

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