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Overview of clinical, diagnosis and therapy of borreliosis

Epidemiology and aetiology

The "tick season" is from April to October. People who work in such professions as forest rangers, forestry workers, gardeners or those who often spend their free time in the garden or in the outdoors. In Germany, approx.
10% of the nymphs (less than 2 mm in size) and 15% to 40% of the adult ticks contain borrelia. An infection results in 10% to 20% of all tick bites. The risk of infection is high whenever a tick can suck blood for a long period of time (> 24 hours) and the tick bite takes place in a region where there is a high incidence of borreliosis. Tick bites often go unnoticed especially through the bites of larvae or nymphs.

Borreliosis infections can develop without any symptoms (elimination of pathogens = spontaneous healing) or with symptoms (borreliosis In symptomatic infections, localised skin redness around the bite area (erythema migrans) occurs within 14 to 30 days in approx. 70% - 80% of all cases.

In 30% to 40% of all cases, the borreliosis remains latent until the infection reaches the dissemination stage. A borrelia infection does not leave the victim with any lasting immunity. Reinfections are therefore possible. A prophylactic vaccination is not yet available.

The pathogens in Europe are:

  • Borrelia burgdorferi sensu stricto: mainly in arthritis
  • Borrelia garinii: often symptoms in the area of the nervous system
  • Borrelia afzelii: especially in skin symptoms which appear later

In Europe, the borrelia is transmitted by the genus Ixodes tick (Ixodes ricinus).

Stages and clinical findings of a borrelia infection

1. Borreliosis localised early: erythema migrans

Erythema migrans begins to develop with a small red macular rash or papulation 7 to 40 days after the tick bite, which spreads along the edges within days to weeks and is often accompanied with local pruritis and a burning sensation. The edge of the 4 cm to 15 cm large erythema is usually emphasised.

The morphology of an erythema migrans can vary a lot. Homogenous, non-migrating forms can also occur. Ticks like to attach in skin folds, such as the groin, the back of the knee and the armpits; in children: the head and neck areas. The erythema migrans are often accompanied by general influenza symptoms.

Diagnosis in case of a suspected primary infection:
The anamnesis (professions at risk, stays in high-risk areas, gardening), the tick bite and the existing erythema migrans are decisive criteria. Specific pathogenic antibodies are expected to become apparent only after 3 to 8 weeks after the infection. Where there is a classical clinical picture, the serological diagnostics are foregone to proceed immediately with the antibiotic therapy.

Where the clinical findings are atypical, examining the serum for borrelia burgdorferi antibodies is recommended whereby attention should be paid to a diagnostic window of 2 to 4 weeks. The new borrelia recomBead Test thereby represents an alternative to the previous Borrelia Western Blot. More. mehr

If the tick which caused the bite is still available (even killed off), it is possible to determine early whether the tick was carrying the borrelia pathogen by using PCR. If the PCR result is negative, then the chances that the borrelia was transferred to the patient are less probable, however, not ruled out.

Differential diagnoses of the erythema migrans:

  • Erysipelas
  • Local reactions to a tick bite or another insect bite (usually appear immediately after the bite)
  • Tinea corporis: reaction to medication, contact dermatitis
  • Granuloma annulare
  • Urticaria
  • Erythema exsudativum multiforme

Recommended treatment:
Length of therapy 21 days. Treatment should last until the erythema has faded away, however, at least 21 days.

First choice:
doxycyclin (> 9 years)
Adults: 200 mg daily
Children > 9 years: 1 - 2 mg/kg in two single doses, maximum 2 x 100 mg
amoxicillin (especially with children and pregnant women)
Adults: 3 x 750 mg daily
Children: 50 mg/kg KG in three single doses, maximum 3 x 750 mg

2. choice:
cefuroxim-axetil
Adults: 2 x 500 mg daily
Children: 30 mg/kg KG in two single doses, maximum 2 x 500 mg or macrolides when beta-lactam and doxycyclin are ruled out

2. Borreliosis disseminated early

In case the borreliosis is not eliminated spontaneously or continues to persist due to an insufficient antibiotic treatment of the erythema migrans or if no treatment took place, then the pathogen will disseminate into the body from the local point of infection (the bite). No erythema migrans was observed in 10% - 30% of the patients (the information in the literature varies) where the borreliosis disseminated early.

The symptoms usual began approx. 1 to 4 months after the tick bite.

General symptoms:
Influenza-like symptoms, fatigue, myalgia, arthralgia, headache, light fever, lymphoma, neck stiffness, back pain, lack of appetite

Skin symptoms:
Multiple erythema migrans;
borreliosis lymphocytoma (lymphadenosis benigna cutis): After 1 to 2 months after the infection: localised blueish-reddish papules of a soft, elastic consistency; often accompanied by regional lymphoma (often on the ear lobes, nipples, scrotum or nose)

Central nervous system symptoms:
Meningitis, cranial nerve disorders (often facialis paresis), meningoradiculitis (Bannwarth syndrome), acute enzephalomyelitis, cerebellitis, transverse myelitis

Heart symptoms:
Perimyocarditis, prominent, usually as AV block type I. - III.; rarely chronically inflammatory (dilated) cardiomyopathy

Joint symptoms:
Acute roaming arthralgia or volatile swollen joints ("episodic arthritis"), often monoarticular or asymmetric oligoarticular arthritis

Eye symptoms:
Iritis, uveitis, chorioiditis, episcleritis/scleritis, orbitale myositis, papillitis, retrobulbar neuritis

Diagnosis when disseminated borreliosis is suspected

anamnesis (tick bite?) is decisive for the diagnosis Erythema migrans? Risk behaviour?) and the current clinical picture!!

Laboratory diagnostics

  1. Serological tests can facilitate creating the diagnosis, however, they do not guarantee anything. The IgG/IgM screening test is usually primarily performed. A positive screening test must be checked for an increased rate of false positive results in the immunoblot. Since 2011, serological proof of protein-specific antibodies can be obtained (analogue to the bands in the immunoblot by applying the Borrelia recomBead Test (Mikrogen).
    In case there is a contradiction between the clinical and serological findings (seronegative, unspecific reactions, questionable animal remains of an earlier infection), then applying cellular methods can be of aid.
  2. The lymphocyte transformation test (LTT borrelia) (2)can be helpful especially if the serology is borderline or positive and if the clinical and anamnesis are uncertain (serum scar or active infection?).

It is in principle possible to cultivate proof of the pathogen (skin biopsy, fluid, blood); however, this has not acquired any significance in everyday practice (low sensitivity, high costs). Proof of the pathogen through specific DNA analysis (PCR - borrelia) can be beneficial, especially in joint punctates and biopsies (especially from the affected skin areas) as well as in fluid. Blood and urine are less suitable since false positive as well as false negative results can occur.

 

Differential diagnoses:

  • Erythema exsudativum multiforme
  • Malignant lymphoma
  • Meningitis of another aetiology (for example: viral, other bacteria)
  • Facialis paresis of another aetiology (for example: VZV infection, idiopathic)
  • Radiculoneuritis, prolapsed disc, herpes zoster (pre-eruptive), Guillain-Barré syndrome
  • Carditis: rheumatic fever, viral myocarditiis
  • Arthritis: other causes of arthritis, especially reactive or purulent types of arthritis

Recommended treatment:
At this point, refer to the current recommendations of the expert associations.

Monitoring therapy takes place primarily in the clinic. In case a failure in therapy is suspected or if there is a reinfection, then a lymphocyte transformation test for borrelia (LTT borrelia) is recommended as well as a new examination of a fluid-serum pair in the case of neuroborreliosis.

 

Specific proof of antibodies in the blood is not suitable to evaluate therapeutic success since the relevant antibodies persist in the serum for a long time. 

3. Chronic borreliosis (late symptoms)

The symptoms begin approx 4 to 6 months up to several years after the initial infection. It is often difficult to match the polymorphic symptoms to a borrelia infection which took place a longer time ago.

 

Symptoms:
"Lyme arthritis" symptoms arise after more than 6 months on average after the initial infection (erythema migrans?, tick bite?). It displays a chronic progressive course and usually affects the large joints (often the knee joint) including swelling and pain.

The symptoms of chronic borreliosis/neuroborreliosis are:

  • Enzephalomyelitis (neurological dysfunctions, subtle decline in condition) 
  • Encephalopathy (memory and concentration disorders, cephalgia, tinnitus)
  • Sleep disorders, depression, irritability, chronic fatigue
  • Normal pressure hydrocephalus
  • Cerebral vasculitis, stroke: chronic radiculoneuritis

 

The "acrodermatitis chronica atrophicans" (ACA) is a chronic inflammatory, partially oedematous process, usually found on areas of the skin exposed to the sun (usually the hands) The chronic inflammatory stage is followed by the chronic atrophic stage (parchment-like skin including typical histological findings). Attendant symptoms are hyperaesthesia, muscle weakness, muscle cramps, solitary or multiple fibrous papules, regional or general lymphoma.A chronic eye borreliosis shows symptoms of the corneal stroma clouding, marginal keratitis, episcleritis, ocular myositis, optic nerve atrophy.

 

Diagnosis in chronic borreliosis (late symptoms)
When there is a clinical suspicion of chronic neuroborreliosis, then the diagnosis is confirmed by an analysis of the fluid-serum pair, possibly by the lymphocyte transformation test (LTT borrelia). In the case of acrodermatitis chronica atrophicans, the additional histological examination is taken into consideration. 

Differential diagnoses:

  • Lyme arthritis: Rheumatoid arthritis
  • Fibromyalgia
  • Chronic neuroborreliosis: inflammatory neurological diseases of another aetiology (for example: viral, multiple sclerosis)
  • ACA: Alterations in the skin due to venous insufficiency, sclerodermia, lichen sclerosus et atrophicus

Recommended treatment:
At this point, refer to the current recommendations of the expert associations.

Monitoring therapy takes place primarily clinically (note: improvement in the condition is usually slow); when "failure to adhere to therapy" is suspected or if there is a re-infection, then a lymphocyte transformation test (LTT borrelia) or a new examination of the fluid-serum pair is recommended.

Specific proof of antibodies in the blood is not suitable to evaluate therapeutic success since the relevant antibodies persist in the serum for a long time.

4. Post Lyme syndrome (PLS) or chronic borreliosis

This is a syndrome in which partially borreliosis persists in spite of multiple antibiotic treatments. A pathogenetically protracted (auto-)immunological activation and borreliosis-induced vasculitis are under discussion.
PLS or chronic borreliosis? Antibiotic treatment yes or no? These issues are extremely controversial in the expert community. So far, this issue could not be resolved based on the laboratory diagnostic possibilities available up to now.
The most common symptoms are: fatigue, exhaustion, cognitive deficits and sleep disorders, neuropathies, pain syndromes.
Diagnostically of use are: the anamnesis (borreliosis diagnosed?) and serological tests (proof of antibodies toward borrelia burgdorferi in the screening test, immunoblot or Borreliosis recomBead Test

HLA-DR subtyping is taken into consideration to define the differential diagnoses (suspected fibromyalgia or unspecific joint or systemic diseases). more
An additional, possible test for differentiation is the lymphocyte transformation test (LTT borrelia). This test will prove negative if there is no active borrelia infection. If the LTT borrelia tests positive, then ia persisting borrelia infection is suspected.

Up to now, there is no recognised data available which absolutely favours a long-term antibiotic therapy lasting for several months.