section name header

Information

Editors

DagNyman

Lyme Borreliosis (LB)

Essentials

  • Lyme borreliosis, is a bacterial disease occurring worldwide, spread by ticks and manifesting in various organs.
  • The primary manifestation of Lyme disease is a characteristic skin rash known as erythema migrans (EM). Recognizing EM and starting antimicrobial medication without delay in primary health care form the basis of treatment for preventing later symptoms. No laboratory tests are needed at this stage.
  • If there is an area of erythema more than 5 cm in diameter at the site of a tick bite and more than one week has elapsed since the bite, it should be regarded as EM. A typical rash of more than 5 cm in diameter should be treated immediately.
  • About half of patients with untreated EM will have later manifestations of the disease.
  • At later stages, diagnosis must always be based on three factors: the possibility of having been bitten by a tick carrying Borrelia bacteria, clinical findings and laboratory tests.
  • The clinical picture shows varying progression. Various symptoms may occur simultaneously. The main skin, nervous system and musculoskeletal symptoms caused by borreliosis should be kept in mind.
  • There is a separate guideline for antimicrobial treatment of later stages of the disease.
  • Persistent or chronic Borrelia infection is extremely rare in patients who have received appropriate treatment. If diagnosis and treatment are significantly delayed, symptoms associated with the convalescence or with permanent tissue damage may occur even after the infection has been cured. In such cases repeated antimicrobial treatments are not indicated.

Prevalence

Infection

  • Lyme borreliosis (LB) is caused by the spirochete Borrelia burgdorferi sensu lato and its subspecies. The most common species in Europe are B. afzelii, B. garinii and B. burgdorferi sensu stricto, as well as B. bavariensis and B. spielmanii. In the USA, nearly all cases are caused by B. burgdorferi sensu stricto. New and potentially pathogenic Borrelia species found in ticks are B. valaisana of the group B. burgdorferi s.l. and B. miyamotoi of the febris recurrentis group.
  • Small rodents, birds, raccoon dogs, hares and wild rabbits act as animal reservoir hosts for Borrelia. Deer, cows, sheep, horses, dogs or cats are not competent reservoir hosts.
  • Spirochetes are transmitted to humans through the bite of an infected tick (Ixodes ricinus). In Finland, another type of tick, the so-called taiga tick (Ixodes persulcatus) has been seen in places. The taiga tick may also be a vector of Borrelia bacteria but has more significance in spreading the Siberian form of the tick-borne encephalitis virus (TBEV). The disease caused by this virus is more severe than that caused by the European virus form (mortality 2-8% vs. 1-2%).
  • Borrelia bacteria are spread by adult ticks and by nymphs.
  • In most cases, the infection is asymptomatic. Infection occurs slowly, within 12 to 72 hours after the bite. In areas where 30% of ticks carry Borrelia, the risk of infection within 3 months after a tick bite is about 3%.
  • As being infected with Borrelia will not produce protective immunity, repeated infection may lead to repeated disease.

Symptoms

  • At an early stage, borreliosis causes local skin symptoms. Spirochetes spread into tissues and within 6 months about 25% of untreated patients with primary phase infection show symptoms of disseminated borreliosis of the nervous system, joints or skin. Ocular and cardiac borreliosis do also occur in Europe but rarely.
  • If early infection is not treated, as many as 50% of patients may develop symptoms of disseminated disease. These may occur several weeks or months after the EM skin rash. Absence of a rash does not necessarily exclude disseminated disease.

Early skin manifestations of Borrelia infection

Erythema migrans (EM) skin rash

  • Erythema migrans, "migrating redness", (pictures 1 2 3 4 5 6 7 8) is an early local manifestation of Borrelia infection, occurring in about 75% of all cases. It appears within a few days to a couple of weeks after tick bite.
  • EM spreads centrifugally, its diameter growing at a rate of about 1 cm/day. EM may have an annular, homogeneous or ”bullseye” appearance. There is often a bite mark at the centre of the skin rash or it is known that a tick has been removed from that site. By consensus, features of ”typical EM” include time of no less than 2 days from detected tick bite to beginning rash, expansion continuing for more than a week, diameter exceeding 5 cm, and an epidemiological connection to ticks 25.
  • EM often disappears within a few weeks even if untreated but it may persist for a couple of months or even longer.
  • EM is not a dermatological disease but the first stage of Borrelia infection.
  • A ”typical” rash cannot always be detected. Varying atypical forms of EM may present as/with:
    • non-expanding (mini) EM
    • no clear margin
    • infiltration
    • blistering at the centre
    • vague staining
    • visible only when warming the skin (shower)
    • no bite site.
  • In differential diagnosis, insect stings and bites Insect Stings and Bites, other skin infections Erysipelas Lymphangitis Dermatological Diagnosis at a Glance Paediatric Skin Problems Herpes Simplex Infection of the Skin, erythema anulare and allergic or toxic reactions Allergic Contact Dermatitis Hives (Urticaria) Hypersensitivity to Drugs Photodermatitis Exanthem (Eruptive Skin Rash) Latex Allergy should be considered.
  • Foreign body granuloma may develop after tick removal due to parts of the tick's mouth remaining in the skin. Treatment is surgical.
  • Diagnosis of EM may be challenging. Overdiagnosis of ‘typical' EM occurs in about 20% of cases due to underdiagnosis of skin rash due to bite reaction or other cause. About 25-30% of cases of EM are atypical, and in as many as 70% of these, the PCR finding is positive.
  • Typical EM is the only phenomenon due to borreliosis that can be identified purely clinically and treated immediately without the need for further examinations. Antibody assays are not useful for diagnosis.
  • Local symptoms, such as itching, lymphadenitis or pain, are mild, occurring in about 50% of cases. Unspecific general symptoms, such as fatigue, joint or muscle pain or a slight rise in body temperature occur in about 30% of patients. They are of no diagnostic significance for EM but if they continue for a few days, they may suggest haematogenous spread of the infection.
  • Early spread of infection is very common: Culture or PCR have shown 40 to 50% of patients to already have Borrelia in their blood at the EM stage.
  • EM may also appear to be absent (because the bite is at a site where it goes undetected, such as a skin fold), and in some cases it may actually be absent.

Multiple lesions

  • EM may cause multiple lesions 9, which is a sign of early haematogenous spread of infection from the bite site.
    • About 5 to 15% of EM patients have multiple lesions.
    • Such disease should be classified as disseminated borreliosis and treated without delay and without laboratory tests (cf. below).
    • EM causes multiple lesions in children more often than in adults. 25% of children with multiple EM have been found to have mild lymphocytic pleocytosis (presence of an abnormally large number of lymphocytes) in their CSF as a sign of subacute meningitis.

Benign cutaneous lymphocytoma

  • Lymphocytoma is a rarer (less than 10%) form of cutaneous borreliosis appearing later than EM as a soft, painless, blueish or reddish swelling (picture 10). It may appear at or near the tick bite (in which case it is classified as disseminated infection) in soft tissue, such as the earlobe, nipple or scrotum. Lymphocytoma is 3 times more common in children than in adults.
  • Borrelia antibodies are found in serum in nearly every case. In unclear cases, histological examination is necessary.
  • Lymphocytoma rarely resolves without treatment.

Chronic atrophic acrodermatitis (ACA), late cutaneous form of borreliosis

  • ACA is a late form of disseminated cutaneous borreliosis (pictures 11 12), appearing several months or years after infection, most often on the extensor surfaces of arms or legs.
  • Unspecific signs include slowly developing blueish swelling of the skin and atrophy developing with time. Fibrotic lumps can often be found. The inflamed area may be tender and painful. Local sensory nerve disorder is common. Symptoms in joints and tendons are common.
  • In ACA patients, antibody tests are always positive. To confirm the diagnosis, it is recommended to perform a histological examination and a PCR study for Borrelia from a skin biopsy specimen, both important for differential diagnosis.
  • There is a wide range of differential diagnoses: nodular gout, rheumatoid arthritis, chronic venous insufficiency, scleroderma, etc.

Other types of disseminated borreliosis

  • After primary infection, Borrelia may spread haematogenously according to the organotropism of the species, causing topical symptoms not only on the skin but usually also in nerve tissue and the musculoskeletal system.
  • The clinical pictures are not specific for borreliosis, and further examination is important for differential diagnosis.

Neuroborreliosis

  • Early neuroborreliosis is the most common clinical form of disseminated infection and appears within 6 months after the bite, often at the EM stage, already.
  • The infection damages peripheral and cranial nerves, with functional damage resulting most often from axonal mononeuritis but also from neuritis affecting the brachial or lumbosacral plexus.
  • CNS infection appears as subacute meningitis with few symptoms or as painful meningoradiculitis (Bannwarth's syndrome, if the patient has concomitant facial palsy).
  • A rare but important form of acute borreliosis is cerebral vasculitis, which is associated with circulatory disturbances and causes TIA or stroke symptoms. Pleocytosis in the CSF may lead to the diagnosis of borreliosis.
  • Encephalitis observed in MRI or symptomatic myelitis is present in less than 10% of patients with neuroborreliosis.
  • If neuroborreliosis is suspected, the examinations needed to confirm the diagnosis or for differential diagnosis must be performed before treatment but without delaying it.
  • Facial nerve palsy caused by Borrelia is a form of peripheral neuroborreliosis; about two patients in three are found to have lymphocytic meningitis. Immediate antimicrobial treatment is needed. This must be distinguished from Bell's palsy Peripheral Facial Paralysis, requiring quite different treatment (immediate administration of glucocorticoids).
  • Neuroborreliosis is considered chronic if the symptoms have continued untreated for more than 6 months. Tissue damage will then have proceeded, focal symptoms may have developed and there may be permanent functional impairment. If the ependyma, the lining of the ventricles in the brain, is inflamed, obstructive hydrocephalus may develop, causing reversible motor or memory disturbances.
  • Late neuroborreliosis (previously ‘3rd stage'): symptoms developing slowly over several months or years. This is a rare manifestation (less than 2% of cases of neuroborreliosis) with no clear clinical definition. In most patients with this type of neuroborreliosis, some other diagnosis is found in differential diagnostic investigations.
  • Antimicrobial treatment of neuroborreliosis is effective, and the prognosis is good; objective symptoms rarely occur after 6 months (in < 5% of patients).

Musculoskeletal symptoms of borreliosis

  • Migrating joint and muscle pain may already occur at the EM stage of borreliosis, without any objective evidence of inflammation. The symptoms disappear as the skin rash is treated.
  • If the primary stage is not treated, about 3-5% of children as well as adults may develop arthritis a few weeks or months (6 months, on an average) after a tick bite. This is often preceded by general symptoms and pain around the joints, as well as in muscles and tendons. Patients typically have fluctuating mono- or oligoarthritis of big joints with abundant fluid. They may simultaneously show symptoms of Baker's cyst, tendinitis, bursitis or enthesitis but with notably little pain or local inflammatory symptoms. Lyme arthritis is rarely seen in several joints at a time.
  • Symptoms continue for several weeks or months, calm down for a few weeks and recur. This pattern may continue for a couple of years, after which spontaneous recovery may occur.
  • Patients with Lyme arthritis are usually in good general health. Slightly elevated body temperatures and local lymph node reactions are relatively frequent. The joint is swollen and tender, often with abundant fluid, and the local skin temperature is elevated. Swelling impairs movement.
  • The differential diagnosis includes various types of reactive arthritis, psoriatic arthropathy, other forms of bacterial arthritis, viral arthritis, osteoarthritis, gout, pseudogout, atypical rheumatoid arthritis, sarcoidosis, trauma, etc. It is important to perform immediately any differential diagnostic examinations that are required.
  • Unspecific inflammatory markers, i.e. ESR, blood leukocytes and plasma CRP, are usually only slightly elevated.
  • If Lyme arthritis is suspected, intra-articular glucocorticoid injections should not be given.
  • Arthritis responds well to antimicrobial treatment: more than 90% of patients recover. Persistent arthritis resistant to antimicrobial drugs is rare. Rare arthritis recurring after antimicrobial treatment represents a chronic infection. It is treated with disease-modifying antirheumatic drugs, and, if necessary, synovectomy.
  • See also articles on Clinical examination of patients with joint inflammation in primary health care Clinical Examination of Patients with Joint Inflammation in Primary Health Care and Juvenile arthritis Arthritis in Children).

Diagnostic work-up

Principles

  • The absolute requirements for the diagnosis of borreliosis are epidemiological factors.
    • Exposure (knowledge that the patient has moved in terrain where tick bite is possible)
    • Regional prevalence of borreliosis
    • Clinical symptoms consistent with borreliosis
    • Serological findingsand local seroprevalence.
  • Serology is the most important diagnostic tool for identifying disseminated or late borreliosis. The principal laboratory test is the determination of specific antibodies to one or more Borrelia antigens.
    • Different laboratories still use different serological methods and antibodies. Therefore, the laboratory should always provide instructions for interpretation or, alternatively, an individual statement based on the clinician's referral.
    • The testing should be based on the assay of Borrelia burgdorferi (Bb) IgG antibodies.
      • These can be detected 2-4 weeks after symptom onset.
      • A positive finding may indicate infection but may also be a remnant of an old infection, which significantly affects the diagnostic significance of serology.
      • A negative finding must be checked in 2-4 weeks, depending on the symptoms; a positive finding at this stage suggests infection.
      • Repeatedly negative findings in a patient with symptoms excludes active borreliosis with a high level of certainty.
      • The performance of a method of analysis varies depending on the antibody levels the method is capable of detecting (check this with the laboratory).
    • IgM antibodies are not useful for diagnosis and have not been shown to reflect disease activity.
    • Assaying Borrelia antibodies in CSF is very important and should be done without too much hesitation because specific antibodies may be produced in the CNS in patients with minor clinical symptoms.
    • If doubts remain as to the specificity of detected antibodies, for instance, the result can be confirmed by immunoblot assay, which can usually be performed on the first sample stored at the laboratory.
  • Increased concentrations of the chemokine CXCL13 in CSF are a sign of active inflammation. See Central nervous system neuroborreliosis below.
  • Detection of Borrelia DNA by PCR is an accurate method for examining untreated patients. However, it should be remembered that this test measures DNA, not just live bacteria. The test done on a skin biopsy sample is valuable for the diagnosis of EM, lymphocytoma and ACA, with a sensitivity of 70 to 80% and specificity of nearly 100%.
    • PCR is a good further examination particularly for the diagnosis of Lyme arthritis. When performed on synovial fluid, the sensitivity of PCR is 65 to 90%, on synovial biopsy samples even higher, and its specificity is close to 100%.
  • Borrelia culture is not clinically feasible due to the long incubation time and low sensitivity.
  • In areas endemic for Borrelia, seropositivity is common in the population, reducing the diagnostic specificity considerably. In hyperendemic regions the prevalence of seropositivity may be 50% or even higher, particularly in older age groups, and even in less endemic areas it may be 5 to 10%.
  • The diagnostic significance of serology is, unfortunately, poor due to the prevalence of seropositivity in the population and to the varying sensitivity and specificity of antibody detection by the test. Specificity always depends on the prevalence of seropositivity.
    • Serological testing shows contact with Borrelia indirectly, not active infection; therefore, interpretation of the test result is needed.
    • In areas with borreliosis, the share of healthy seropositive people is usually 20-30%; the prevalence of active borreliosis is rarely known. Based on these givens, the diagnostic value of a positive test can be calculated by calculating the likelihood ratio.
    • A positive likelihood ratio (LR+) exceeding 10 suggests high probability of disease. The performance of serology can be calculated using the formula LR+ = sensitivity / 1 − specificity. Example: the sensitivity of the test for showing antibodies is usually 0.90 and the underlying seropositivity is 20% (specificity 0.80); thus, LR+ = 0.9/0.8 = 1.25, i.e., of no diagnostic value!
    • Furthermore, the antibody level based on a single test has no relation to the diagnosis.
  • Pharmacies sell rapid tests to detect the presence of Borrelia bacteria in a tick. These are not, however, to be recommended because the tests are poorly documented. In addition, only a fraction, i.e. about 7.5% of bites by ticks that carry Borrelia bacteria lead to an infection. Using these tests and starting antimicrobial medication in every positive case would thus lead to significant overtreatment. Therefore, ESGBOR (European Study Group for Lyme Borreliosis) explicitly advises against using these and other rapid tests.
  • Tests suggested by some, such as so-called direct microscopy, ELISPOT, CD57+ NK cells, or Borrelia antigen-induced IL-1 production by macrophages should not be used, since they have been found unfit for the purpose.
  • Diagnostic tests for various situations are listed in table T1.

Recommended diagnosis of borreliosis

ManifestationSerology (Borrelia antibodies)Expected sensitivity of antibody testsClinical and laboratory findings supporting the diagnosis
Tick biteNot recommended.No significanceNot recommended
Erythema migransNot recommended. The diagnosis is based on clinical findings.
Serology tests can be used in patients with atypical, prolonged clinical picture, as considered necessary.		Approx. 50%Skin biopsy: histology and PCR test positive for B. burgdorferi
LymphocytomaRecommended. A positive antibody test is required to confirm the diagnosis>80%Skin biopsy: histology and PCR test positive for B. burgdorferi
Erythema migrans concomitantly or in the history
NeuroborreliosisSerological tests should be done concomitantly in serum and CSF.
Intrathecal antibody production, or an elevated IT index, is required for the diagnosis.		Duration of symptoms less than 6 weeks: 77% (67-85%)
Duration of symptoms more than 6 weeks: > 99%		CSF sample:
  • lymphocytic pleocytosis (Leuk > 5 × 106 /l)
  • Increased CXCL13 concentration
  • PCR test positive for B. burgdorferi (low sensitivity)
Erythema migrans concomitantly or in the history
Chronic atrophic acrodermatitisRecommended. A positive IgG antibody test is required for the diagnosis.98% (84-100%)Skin biopsy: histology and PCR test positive for B. burgdorferi
Lyme arthritisRecommended. A positive IgG antibody test is required for the diagnosis.96% (93-100%)Synovial sample: PCR test positive for B. burgdorferi (differential diagnosis: cells, crystals, bacterial culture, bacterial nucleic acid detection)
Lyme carditisRecommended. A positive IgG antibody test is required for the diagnosis.>80%Erythema migrans concomitantly or in the history or neurological symptoms
Eye manifestationsRecommended. A positive IgG antibody test is required for the diagnosis.?PCR test positive for B. burgdorferi in the eye
Other manifestation of borreliosis concomitantly or in the history
Republication from the Finnish Medical Journal article Kortela E, Kanerva M, Kurkela S, et al. [Lyme borreliosis: recommendations for diagnosis and treatment] by permission. Suom Lääkäril 2023;78(37-38):1428-32 30.

Erythema migrans (EM)

  • No laboratory tests are used to diagnose erythema migrans. A typical rash of more than 5 cm in diameter should be treated immediately. Erythema less than 5 cm in diameter should be monitored for a week and treated if it grows or if a known bite is followed by an asymptomatic period with the erythema appearing only after the asymptomatic period. In uncertain cases the situation may be further monitored for a couple of days; the erythema grows approximately 1 cm/day. If there are general symptoms, however, treatment may be started immediately. A patient with multiple lesions (see above) should always be treated immediately.
  • Differential diagnostic investigations are important in the case of atypical EM: a skin biopsy specimen for PCR study, as necessary, histological investigations and possibly consultation of a dermatologist. Positive serology will not help in the diagnosis but negative serology after 2-4 weeks of symptoms suggests that there is no borreliosis. An expanding rash should be treated keeping in mind that the diagnosis of EM is inconclusive. If the symptoms persist or get worse after the treatment, they are probably caused by something other than borreliosis.
  • If, for some reason, it is necessary to try to make an objective diagnosis of EM, Borrelia DNA in a skin biopsy sample can be examined by PCR technique. This is not a routine examination and must not delay the beginning of treatment.
  • Lymphocytoma at the tick bite site is diagnostic for primary borreliosis and requires immediate treatment. Histological examination, PCR and antibody assay may be necessary for differential diagnosis.

Neuroborreliosis

Peripheral neuroborreliosis

  • Facial nerve palsy is the most typical manifestation of peripheral nervous system borreliosis. It may begin soon after infection, during EM, already, when serum IgG antibodies may still be negative. Positive IgM antibodies may be suggestive but are not suitable for diagnosis here, either. Facial nerve palsy does not always mean that the patient has meningitis; CSF is normal in about 30% of cases.
  • CSF assays and examinations of intrathecal antibody production are important.
  • For differential diagnosis versus other peripheral nerve damage, such as axonal neuropathy and plexitis, electrophysiological examinations, for example, are needed.
  • In Lyme neuritis, IgG antibodies are positive but the examination is not sufficiently specific for diagnosis.

Central nervous system neuroborreliosis

  • The symptom picture is very multifaceted, and same symptoms occur also in other infections of the central nervous system, which is why serological and differential diagnostic testing is necessary.
  • CSF must always be examined, in specialized care, as necessary.
  • Lymphocytic pleocytosis in CSF is a sign of inflammation supporting the diagnosis.
  • Serum and CSF concentrations of IgG Borrelia antibodies should be examined. Serum IgG antibody concentrations are always increased 4 weeks after the onset of symptoms.
  • Intrathecal production of specific antibodies should be calculated. In CNS neuroborreliosis, the intrathecal antibody index is elevated 10 to 14 days after the onset of symptoms. After neuroborreliosis, the index may remain elevated for several years, which reduces its diagnostic usefulness.
  • Increased concentrations of the chemokine CXCL13 in the CSF are a useful and important general sign of inflammatory activity, with clearly increased concentrations in CNS neuroborreliosis. This can be found earlier than pleocytosis and an elevated antibody index, and helps decisively in diagnosis. A slight increase is also seen in patients with multiple sclerosis (MS), clinically isolated syndrome (CIS) and optic neuromyelitis, as well as in viral and bacterial meningitis. CXCL13 concentrations are moderately increased in about 1 in 3 patients with TBE up to about 400 pg/ml. In addition to borreliosis, high levels are also seen in syphilis and meningeal lymphoma.
  • Imaging (cranial MRI) should be considered for differential diagnosis.

Lyme arthritis

  • Serum IgG antibody concentrations are always clearly increased. There is no point in determining antibody levels in synovial fluid because they are at the same level as in serum.
  • Synovial fluid PCR is recommended.
  • Blood and synovial fluid tests and imaging for differential diagnosis form part of the diagnostic workup.

Acrodermatitis

  • Serum IgG antibody concentrations are always increased.
  • The histological findings are typical, and PCR of a skin biopsy sample is an alternative that can be recommended for diagnosis.

Treatment

A tick bite alone without any kind of symptoms suggestive of Lyme borreliosis

  • There is no indication for an antimicrobial drug in a healthy patient!
  • Even seroconversion would not be a sign of a disease in the absence of symptoms.
  • During pregnancy, prophylactic antimicrobial treatment may be considered if exposure to ticks is probable (consult a specialist in infectious diseases).

Antimicrobial treatment of active borreliosis

  • A Finnish expert group has drawn up a consensus statement on the diagnosis and antimicrobial treatment of borreliosis. The central principles of treatment according to the statement are presented below in tables T2 and T3.
  • Oral treatment is recommended in most indications.
  • Overly long periods of treatment should be avoided.

Antimicrobial treatment in manifestations of Lyme borreliosis

DrugDuration of treatmentAspects to note
Early skin manifestations
Erythema migrans without general symptoms, and lymphocytoma500 mg oral amoxicillin 3-4 times daily
For children, 50 mg/kg/day, divided into 3 doses, max. 500 mg 3 times daily
2 weeksDosage 4 times daily is probably the most effective for extensive disease or severely obese patients.
100(-150) mg oral doxycycline 2 times daily, initial dose 2 tablets, or 200(-300) mg
For children, 4-5 mg/kg/day, divided into 2 doses, max. 200 mg/day		2 weeksThe standard dose for adults is 100 mg twice daily.
May cause sensitivity to sunlight.
Simultaneous use of dairy products may negatively affect absorption.
Avoid use during pregnancy.
For children below 8 years, only if other oral antibiotics cannot be used.
For allergic patients only:
500 mg oral azithromycin once daily
For children, 10 mg/kg once daily, max. 500 mg/day		6 daysTreatment failure has been reported.
Prolongs the QT interval.
Consider drug interactions.
Avoid use during breastfeeding.
500 mg oral cefuroxime axetil twice daily
For children, 30 mg/kg/day divided into 2 doses, max. 500 mg twice daily		2 weeksMay require special permit.
Often causes intestinal adverse effects.
Cephalexin is not effective in the treatment of Lyme borreliosis.
Early dissemination
Multiple erythema migrans and erythema migrans + general symptoms: arthralgia, myalgia, headaches, low-grade fever100(-150) mg oral doxycycline 2 times daily, initial dose 2 tbl.
For children, 4-5 mg/kg/day, divided into 2 doses, max. 200 mg/day		2(-3) weeksSee Early skin manifestations above
For adults, primarily doxycycline.
For children, primarily amoxicillin
Duration of treatment in children 2 weeks.
500 mg oral amoxicillin 3-4 times daily
For children, 50 mg/kg/day divided into 3 doses, max. 500 mg 3 times daily
For allergic patients, see Early skin manifestations above		See Early skin manifestations above
Facial palsy or other cranial nerve palsy, neuritis, radiculitis, meningitis100(-150) mg oral doxycycline 2 times daily, initial dose 2 tbl
For children, 4-5 mg/kg/day, divided into 2 doses, max. 200 mg/day
2 g intravenous ceftriaxone once daily
For children, 75-100 mg/kg once daily, max. 2 g/day		2(-3) weeksSee Early skin manifestations above
Oral doxycycline is as effective as ceftriaxone
The duration of treatment in children is 2 weeks.
Safety monitoring tests once a week: complete blood count, ALT 18
Duration of symptoms less than 6 months: encephalitis, cerebral vasculitis, myelitis2 g intravenous ceftriaxone once daily
For children, 75-100 mg/kg once daily, max. 2 g/day		2-3 weeksThe duration of treatment in children is 2 weeks.
Safety monitoring tests once a week: complete blood count, ALT 18
Carditis:
Mild first degree AV block, PR time < 300 ms		500 mg oral amoxicillin 3-4 times daily
For children, 50 mg/kg/day divided into 3 doses, max. 500 mg 3 times daily		2-3 weeksSee Early skin manifestations above
100(-150) mg oral doxycycline 2 times daily, initial dose 2 tbl
For children, 4-5 mg/kg/day, divided into 2 doses, max. 200 mg/day
For allergic patients: azithromycin or cefuroxime axetil		See Early skin manifestations above
Serious second to third degree AV block, PR time HASH(0x2ed5390) 300 ms2 g intravenous ceftriaxone once daily
For children, 75-100 mg/kg once daily, max. 2 g/day		Hospital treatment, temporary pacing may be necessary.
Safety monitoring tests once a week: complete blood count, ALT 18
When the patient's condition is stabilized, antimicrobial drug may be switched to doxycycline or amoxicillin
Eye symptoms:
conjunctivitis, episcleritis		100(-150) mg oral doxycycline 2 times daily, initial dose 2 tbl
For children, 4-5 mg/kg/day, divided into 2 doses, max. 200 mg/day		2 weeksSee Early skin manifestations above
Keratitis, scleritis, uveitis, retinitis2 g intravenous ceftriaxone once daily
For children, 75-100 mg/kg once daily, max. 2 g/day		3 weeksDoxycycline has poor intraocular penetration.
Safety monitoring tests once a week: complete blood count, ALT 18
Republication from the Finnish Medical Journal article Kortela E, Kanerva M, Kurkela S, et al. [Lyme borreliosis: recommendations for diagnosis and treatment] by permission. Suom Lääkäril 2023;78(37-38):1428-32 30.

Antimicrobial treatment of late symptoms of Lyme borreliosis

Late symptomsDrugDuration of treatmentAspects to note
Arthritis500 mg oral amoxicillin 3-4 times daily For children, 50 mg/kg/day divided into 3 doses, max. 500 mg 3 times daily
100(-150) mg oral doxycycline 2 times daily, initial dose 2 tbl. For children, 4-5 mg/kg/day divided into 2 doses, max. 200 mg/day		4 weeksSee Table T2 Early skin manifestations
In recurrent arthritis, antimicrobial treatment can be repeated once, either oral medication for 4 weeks or in disease with severe symptoms ceftriaxone for 2-4 weeks.
For allergic patients:
500 mg oral cefuroxime axetil twice daily
For children, 30 mg/kg/day divided into 2 doses, max. 500 mg 2 times daily
Duration of symptoms more than 6 months: encephalitis, myelitis2 g intravenous ceftriaxone once daily
For children, 75-100 mg/kg once daily, max. 2 g/day		3 weeksSafety monitoring tests once a week: complete blood count, ALT 18
Peripheral neuropathy100(-150) mg oral doxycycline 2 times daily, initial dose 2 tbl
For children, 4-5 mg/kg/day, divided into 2 doses, max. 200 mg/day		3 weeksSee Table T2 Early skin manifestations
2 g intravenous ceftriaxone once daily
For children, 75-100 mg/kg once daily, max. 2 g/day		Safety monitoring tests once a week: complete blood count, ALT 18
Chronic atrophic acrodermatitis100(-150) mg oral doxycycline 2 times daily, initial dose 2 tbl
For children, 4-5 mg/kg/day, divided into 2 doses, max. 200 mg/day		3-4 weeksSee Table T2 Early skin manifestations
500 mg oral amoxicillin 3-4 times daily
For children, 50 mg/kg/day divided into 3 doses, max. 500 mg 3 times daily		See Table T2 Early skin manifestations
Republication from the Finnish Medical Journal article Kortela E, Kanerva M, Kurkela S, et al. [Lyme borreliosis: recommendations for diagnosis and treatment] by permission. Suom Lääkäril 2023;78(37-38):1428-32 30.

Assessment of treatment results

  • Assessment of response to treatment requires patience from both patient and doctor. The main criterion is the final clinical status, which can often only be seen 2 to 3 months after the end of treatment.
  • IgM antibody assays are not useful here, either, and are therefore unnecessary.
  • Decrease of IgG antibody concentrations to no more than a half of baseline levels indicates successful treatment, but this may take as long as 6 months and occurs in only 50% of cases.
  • Assay of the inflammatory marker CXCL13 in CSF is useful; the levels decrease significantly as soon as 2 weeks after successful treatment even if pleocytosis persists.
  • Borrelia DNA may be found by the PCR method as late as one or two months after antimicrobial treatment but it may consist of spirochete debris and does not, in principle, show continued infection.

Persistent symptoms after treatment

  • If symptoms persist after appropriate treatment of Lyme disease, they are most often caused by something other than continued Borrelia infection. This condition is often inappropriately called 'post-treatment Lyme disease', which may be misleading because the patient is going through symptomatic recovery from the infection and may possibly also have even permanent tissue damage.
  • The feared chronic active Borrelia infection is highly unlikely in patients treated according to guidelines. The situation is challenging for a physician and requires thorough assessment by experienced experts.
  • Patients may suffer from fatigue, cognitive dysfunction and impaired exercise tolerance as long as 3 to 6 months after the treatment of neuroborreliosis. This does not indicate continued infection, and further antimicrobial treatment is not warranted.
  • Symptomatic treatment, planned rehabilitation and support are important for avoiding chronic fear of borreliosis.
  • After Lyme arthritis, persistent arthritis may continue in the absence of infection. In this case, if the situation has not improved after 2 months despite two appropriate courses of treatment, the patient has post-treatment Lyme arthritis, or PTLA, not chronic infection. The causative mechanism behind such arthritis resistant to antimicrobial drugs is not fully understood. Individual characteristics related to the regulation of inflammatory reactions, such as the HLA-DR4 genotype, are often decisive. In animal tests, molecules of Borrelia antigen, without living bacteria, have been found to have established themselves in tissues, causing inflammatory reactions. This does not, however, mean a chronic infection. The condition should best be treated in cooperation with a rheumatologist.
  • The designation "post-treatment Lyme disease syndrome" or PTLDS should be used with caution, since the symptoms may often be caused by some other underlying aetiology that has not been noticed in differential diagnosis.
  • Symptoms should never be downplayed; they may, for example, be due to permanent tissue damage or other disease. Psychophysical stress is another possible cause but this should not be used as an excuse for stopping examinations too soon.

Prevention

  • Ixodes ricinus thrives in forests (berry pickers!), smaller wooded areas rich in alder trees, grassy areas, pastures, meadows, and generally in terrain favoured by its host animals and in moist micro-climate.
  • Obviously, the best prevention is to avoid being bitten by ticks. There are no ticks in rocky and dry terrain and there is thus no danger in such areas.
  • When walking in terrain favoured by ticks, the middle of the footpath should be used and long trousers (light-coloured to help identifying the ticks), tucked into the socks, should be worn.
  • The skin should be inspected and any ticks removed every day.
  • An embedded tick should be removed mechanically by pulling it straight out with tweezers. Scraping off embedded ticks should be avoided, as parts of ticks may remain in the skin and cause a purulent infection. Such remaining parts will eventually come out spontaneously with wound discharge. The method of removing the tick is not currently considered to influence the risk of Borrelia infection.
  • An embedded tick should be detected and removed within the first day, as the risk of infection increases with time.
  • Experiments have been performed with vaccines against Borrelia burgdorferi in many places, including Finland. So far, the development of a practicable vaccine has not been successful.

Pictures

    References

    • Kortela E, Kanerva M, Kurkela S, et al. [Lyme borreliosis: recommendations for diagnosis and treatment]. Suom Lääkäril 2023;78(37-38):1428-32. Available in Finnish at http://www.laakarilehti.fi/tieteessa/katsausartikkeli/lymen-borrelioosi-suositus-diagnostiikasta-ja-hoidosta/.
    • Mistry R, Rawson TM, Troise O, et al. Haematological and hepatic adverse effects of ceftriaxone in ambulatory care: a dual-centre retrospective observational analysis of standard vs high dose. BMC Infect Dis 2022;22(1):959 [PubMed]
    • Schotthoefer AM, Green CB, Dempsey G, et al. The Spectrum of Erythema Migrans in Early Lyme Disease: Can We Improve Its Recognition? Cureus 2022;14(10):e30673 [PubMed]
    • Stanek G, Strle F. Lyme borreliosis-from tick bite to diagnosis and treatment. FEMS Microbiol Rev 2018;42(3):233-258. [PubMed]
    • Dessau RB, van Dam AP, Fingerle V, et al. To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis: a position paper of ESGBOR, the ESCMID study group for Lyme borreliosis. Clin Microbiol Infect 2018;24(2):118-124 [PubMed]
    • van Gorkom T, Sankatsing SUC, Voet W, et al. An Enzyme-Linked Immunosorbent Spot Assay Measuring Borrelia burgdorferi B31-Specific Interferon Gamma-Secreting T Cells Cannot Discriminate Active Lyme Neuroborreliosis from Past Lyme Borreliosis: a Prospective Study in the Netherlands. J Clin Microbiol 2018;56(4): [PubMed]
    • Laaksonen M, Sajanti E, Sormunen JJ, et al. Crowdsourcing-based nationwide tick collection reveals the distribution of Ixodes ricinus and I. persulcatus and associated pathogens in Finland. Emerg Microbes Infect 2017;6(5):e31 [PubMed]
    • Sormunen JJ, Klemola T, Vesterinen EJ, et al. Assessing the abundance, seasonal questing activity, and Borrelia and tick-borne encephalitis virus (TBEV) prevalence of Ixodes ricinus ticks in a Lyme borreliosis endemic area in Southwest Finland. Ticks Tick Borne Dis 2016;7(1):208-215 [PubMed]
    • Schutzer SE, Berger BW, Krueger JG, et al. Atypical erythema migrans in patients with PCR-positive Lyme disease. Emerg Infect Dis 2013;19(5):815-7 [PubMed]
    • Strle F, Lusa L, Rućiž-Sabljiž E, et al. Clinical characteristics associated with Borrelia burgdorferi sensu lato skin culture results in patients with erythema migrans. PLoS One 2013;8(12):e82132 [PubMed]
    • Bockenstedt LK, Gonzalez DG, Haberman AM, et al. Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy. J Clin Invest 2012;122(7):2652-60 [PubMed]
    • Nordberg M, Forsberg P, Nyman D, et al. Can ELISPOT Be Applied to A Clinical Setting as A Diagnostic Utility for Neuroborreliosis? Cells 2012;1(2):153-67 [PubMed]
    • Fryland L, Wilhelmsson P, Lindgren PE, et al. Low risk of developing Borrelia burgdorferi infection in the south-east of Sweden after being bitten by a Borrelia burgdorferi-infected tick. Int J Infect Dis 2011;15(3):e174-81 [PubMed]
    • Rizzoli A, Hauffe H, Carpi G, et al. Lyme borreliosis in Europe. Euro Surveill 2011;16(27): [PubMed]
    • Mygland A, Ljøstad U, Fingerle V et al. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol 2010;17(1):8-16, e1-4. [PubMed]
    • O'Connell S. Lyme borreliosis: current issues in diagnosis and management. Curr Opin Infect Dis 2010;23(3):231-5. [PubMed]
    • Marques A, Brown MR, Fleisher TA. Natural killer cell counts are not different between patients with post-Lyme disease syndrome and controls. Clin Vaccine Immunol 2009;16(8):1249-50. [PubMed]
    • Ljøstad U, Skogvoll E, Eikeland R ym. Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial. Lancet Neurol 2008;7(8):690-5. [PubMed]
    • Stanek G, Fingerle V, Hunfeld KP, Jaulhac B, Kaiser R, Krause A, Kristoferitsch W, O'Connell S, Strle F, Gray J. Ljøstad U, Henriksen TH. Management of neuroborreliosis in European adult patients. Acta Neurol Scand Suppl 2008;188():22-8. [PubMed]
    • Oksi J, Nikoskelainen J, Hiekkanen H et al. Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind, randomized, placebo-controlled, multicenter clinical study. Eur J Clin Microbiol Infect Dis 2007;26(8):571-81. [PubMed]
    • Wilske B, Fingerle V, Schulte-Spechtel U. Microbiological and serological diagnosis of Lyme borreliosis. FEMS Immunol Med Microbiol 2007;49(1):13-21. [PubMed]
    • Steere AC, Angelis SM. Therapy for Lyme arthritis: strategies for the treatment of antibiotic-refractory arthritis. Arthritis Rheum 2006;54(10):3079-86. [PubMed]