There are four stages:
1. Early local Lyme disease with a migratory rash as the only symptomsymptom
In the event of an infection, only about 80 % of cases develop a migratory red rash (erythema migrans). So about 20% of infections occur without a rash. The absence of a migratory red rash does not rule out infection.
In any case, a migratory red rash is a warning signal to be taken seriously. The German Borreliosis Society, of which I am a member, recommends therapy with the antibiotic doxycycline 100 to 200 mg in the morning and in the evening for four weeks in such cases.
2. Early disseminated (spread throughout the body) borreliosis
In 10 to 30% of patients with early disseminated Lyme disease (the data provided in the literature varies considerably), no migratory red rash was observed.
The symptoms usually develop about one to four months after the tick bite.
Symptoms can be extremely varied:
flu-like symptoms, fatigue, myalgia, arthralgia, headache, mild fever, swelling of lymph nodes, neck stiffness, back pain, loss of appetite.
Several rashes at the same time;
Borrelia lymphocytoma (lymphadenosis benigna cutis): occurs one to two months after infection. This is a localized, bluish-reddish nodule (often on earlobes, nipples, scrotum or nose) with a soft, elastic consistency; often accompanied by localized swelling of the lymph nodes.
Brain inflammation (meningitis), cranial nerve deficits (often facial paresis = facial nerve deficits), meningoradiculoneuritis (Bannwarth syndrome), acute encephalomyelitis, cerebellitis, transverse myelitis.
Inflammation of the pericardium and myocardium, usually in the form of AV block I to III degree; very rarely chronic inflammatory (dilated) myocardial inflammation.
Acute wandering joint pain or temporary swelling of the joints ("episodic arthritis"), often only one joint is affected or asymmetrical inflammation of a few joints.
If you should suffer from a loss of vision, this could be due to Lyme disease. In this case, your ophthalmologist should check Iritis, uveitis, choroiditis, episcleritis/scleritis, orbital myositis, papillitis, retrobulbar neuritis.
3. Chronic Lyme disease
Symptoms usually begin four to six months or in some cases even several years after infection. Often it is difficult to classify the highly diverse symptoms of a borreliosis infection that occurred long ago..
The "Lyme arthritis " generally develops more than six months after the primary infection (erythema migrans? tick bite?). It occurs chronically and repeatedly and in most cases affects large joints (often knee joints) with swelling and pain.
Clinical patterns of Chronic Lyme Borreliosis/Neuroborreliosis include:
- Encephalomyelitis = inflammation of the brain and spinal cord (neurological deficits, gradual deterioration of condition)
- Encephalopathy = brain disease (memory and concentration disorders, headaches, tinnitus)
- Sleep disorders, depression, irritability, chronic fatigue
- Normal pressure hydrocephalus
- Inflammation of the brain arteries, cerebral infarction - chronic inflammation of the nerve roots
Acrodermatitis chronica atrophicans (ACA) is a chronic inflammatory process, sometimes involving water retention and swelling, often in regions of the skin exposed to the sun (usually the hands). The chronic inflammatory stage is followed by the chronic atrophic stage (parchment-like skin with typical histological signs).
Associated symptoms are hypersensitivity, muscle weakness, muscle cramps, single or multiple fibrous nodules, regional or generalized lymph node swelling.
Chronic eye borreliosis could manifest itself as corneal stroma, marginal keratitis, episcleritis, ocular myositis, and optic atrophy.
4. Post-Lyme Syndrome (PLS) or chronic Lyme disease
This syndrome persists even after a number of antibiotic treatments for borreliosis. From a biochemical point of view, a permanent immunological or perhaps even an autoimmune (!) activation and a borreliosis-induced vascular inflammation are being discussed.
PLS or chronic Lyme disease? Antibiotic treatment, yes or no? These issues are highly controversial among experts. With the existing laboratory diagnostic possibilities, it has so far not been possible to resolve this issue definitively.
The most common symptoms are fatigue, exhaustion, cognitive deficits and sleep disorders, nerve pain, and pain syndromes.
Diagnostically useful: Anamnesis (established Borreliosis?) and serological tests (detection of Borrelia burgdorferi antibodies in screening test, immunoblot or Borrelia recombead test and/or lymphocyte transformation test = LTT). In any case, CD56/CD57 cells should also be tested for typical infection patterns.
HLA-DR subtyping can also be considered for differential diagnosis (especially fibromyalgia or non-specific joint and systemic diseases).
An additional test for differentiation is the lymphocyte transformation test (LTT-Borrelia). A negative result is found if there is no active Borrelia infection. A positive LTT Borrelia test indicates a possible persistent Borrelia infection.
What can HLA determination achieve in the diagnosis and assessment of the course of Lyme disease?
In about 10% of patients with Lyme disease, joint problems persist for months or years despite adequate antibiotic therapy. With such symptom persistence, we always question the cause. Was the therapy insufficient or the diagnosis wrong? This dilemma is compounded by the fact that there is no reliable laboratory-diagnostic proof or ruling out due to the complex immune response to Borrelia. Lyme borreliosis is justifiably referred to as the "great imitator" because the symptoms are extremely non-specific, making clinical diagnosis considerably more difficult.
There is an HLA association in the antibiotic-resistant course of Lyme borreliosis
Therapy-sensitive and resistant Lyme arthritis differ in their cellular and humoral response to the Outer Surface Protein (OspA) of Borrelia. Some variants of the immune response, including autoimmune reactions associated with certain HLA types, play a significant role. It has long been known that people with HLA-DR2 or -DR4 have a genetic predisposition for developing antibiotic-resistant Lyme disease ( 22-fold increase in relative risk!).
The latest studies show associations with certain HLA-DR subtypes
In a recent study using molecular biology methods to determine HLA characteristics, Steere and colleagues found significant associations between certain HLA-DR subtypes (DR*01:01, *15:01, *04:01, and *04:02) and the cellular and humoral immune response to the OspA antigen of Borrelia. OspA antigens appear to trigger a cross-reaction with the body's own structures when presented as part of the immune response to the previously mentioned HLA molecules. This so-called molecular mimicry sustains the inflammatory process through autoimmunological processes, even when the pathogen itself is eliminated. Initially, LFA1, which is partly sequence homologous to OspA, was postulated as an autoantigen, but its role in the pathogenesis of the autoimmune reaction has again become a controversial issue. It is assumed that different mechanisms associated with these HLA molecules induce and sustain such an autoimmune response. The borreliosis-associated HLA molecules mentioned above have an unusually high affinity to OspA antigen fragments and exhibit these long after elimination of the pathogens. This is associated with high levels of proinflammatory cytokines (TNFa, INFg, etc.) in the affected tissues. In genetically predisposed patients, the strong T-cell response to Borrelia is associated with inadequately high induction of inflammatory cytokines and can thus trigger an "autoimmune" reactivity against the body's own structures. It was found that carriers of two OspA-binding HLA-DR alleles have an 11-fold increased risk of developing antibiotic-resistant Lyme disease. This "gene dose effect" highlights that the immunopathogenesis of therapy-resistant Lyme arthritis is closely related to specific HLA characteristics.
The association not only affects shared epitope-bearing HLA alleles
The detection of DR subtypes in patients with antibiotic-resistant Lyme borreliosis also revealed that the association is not, as previously assumed, limited to the so-called shared epitope-bearing HLA-DR1/4 alleles. The HLA alleles DRB1*04:02 and *15:01 do not carry shared epitopes, but they do bind OspA antigens. Patients who are positive for these alleles also have an increased risk of developing a therapy-resistant course of Lyme disease.
Certain HLA alleles may be the reason for a lack of antibody formation.
In addition to the association with antibiotic-resistant Lyme borreliosis, the question of HLA-DR association with seronegativity in proven Borrelia infection (Borrelia PCR and culture positive) is also the focus of new studies. In rare cases, patients do not develop specific antibodies against Borrelia burgdorferi following Borreliosis infection. Wang & Hilton demonstrated that almost 40% of these seronegative Lyme disease patients were positive for HLA-DR1.
HLA-DR subtyping supports diagnostics in unclear cases
Lyme disease is primarily diagnosed by anamnesis and clinical symptoms, in particular, their development over time. The primary purpose of laboratory diagnostics is to confirm the suspected diagnosis. However, the clinical symptoms, especially in later phases of the disease, are often ambiguous, making diagnosis considerably more difficult. Therefore, HLA-DR subtyping can be very helpful in defining a therapy concept if a chronic persistent course of Lyme disease is suspected.
Summary of Previous Study Findings
HLA association with antibiotic resistant Lyme disease:
DR4 (DRB1*04:01, 04:02)
HLA association in patients with reduced formation of Borrelia-specific antibodies despite confirmed Borrelia infection:
DR1 allele (DRB1*01:02, *01:01,*01:04, *01:05)
Unfortunately, Lyme disease and its many co-infections are often misjudged and underestimated in official medicine. As a very young doctor, I experienced for myself what it means to have a disease that conventional medicine does not want to acknowledge.
Conventional medicine claims that treatment of Lyme disease with the antibiotic Doxycycline 100 mg in the morning and evening for a maximum of four weeks is perfectly sufficient. According to conventional medicine, if the symptoms persist, the patient is treated with painkillers and, if necessary, antidepressants for the rest of their life.
After more than 30 years of medical experience, especially in the field of Lyme disease, I consider this view of Lyme disease treatment to be wrong.
Lyme disease is currently an unrecognized epidemic. With 100,000 new infections per year in Germany, Lyme disease is one of the most common infectious diseases.
The decisive question is: Why does the immune system tolerate borreliosis? The question as to the cause(s) must be clarified.
Possible causes to clarify are:
- Nutrient deficiencies (deficiencies in minerals, trace elements, vitamins, enzymes, proteins)
- Other existing inflammation over a longer period
- Limitations of reaction and performance of the immune system
- Immunosuppressive environmental toxins
- Limited detoxification ability
- Chronic stress
- Taking immunosuppressive medication
We are Member of the German Borreliosis Society, www.borreliose-gesellschaft.de