Table 1.
Standardized Case Definitions of Lyme Borreliosis Available for Europe
| EUCALB (Stanek et al, 2011) | |||
|---|---|---|---|
| Term | Clinical case definition | Essential laboratory evidence | Supporting laboratory/clinical evidence |
| EM | Expanding red or bluish-red patch (≥5 cm in diameter),a with or without central clearing. Advancing edge typically distinct, often intensely colored, not markedly elevated. |
None | Detection of Borrelia burgdorferi s.l. by culture and/or PCR from skin biopsy. |
| Borrelial lymphocytoma (rare) | Painless bluish-red nodule or plaque, usually on ear lobe, ear helix, nipple, or scrotum; more frequent in children (especially on ear) than in adults. | Seroconversion or positive serologyb Histology in unclear cases | Histology. Detection of B. burgdorferi s.l. by culture and/or PCR from skin biopsy. Recent or concomitant EM. |
| Acrodermatitis chronic atrophicans | Long-standing red or bluish-red lesions, usually on the extensor surfaces of extremities. Initial doughy swelling. Lesions eventually become atrophic. Possible skin induration and fibroid nodules over bony prominences. | High level of specific serum IgG antibodies | Histology. Detection of B. burgdorferi s.l. by culture and/or PCR from skin biopsy. |
| LNB | In adults mainly meningoradiculitis, meningitis; rarely encephalitis, myelitis; very rarely cerebral vasculitis. In children, mainly meningitis and facial palsy. | Pleocytosis and demonstration of intrathecal-specific antibody synthesisc | Detection of B. burgdorferi s.l. by culture and/or PCR from CSF. Intrathecal synthesis of total IgM and/or IgG and/or IgA. Specific serum antibodies. Recent or concomitant EM. |
| LA | Recurrent attacks or persisting objective joint swelling in one or a few large joints. Alternative explanations must be excluded. | Specific serum IgG antibodies, usually in high concentrations | Synovial fluid analysis. Detection of B. burgdorferi s.l. by PCR and/or culture from synovial fluid and/or tissue. |
| LC | Acute onset of atrioventricular (I–III) conduction disturbances, rhythm disturbances, and sometimes myocarditis or pancarditis. Alternative explanations must be excluded. | Specific serum antibodies | Detection of B. burgdorferi s.l. by culture and/or PCR from endomyocardial biopsy. Recent or concomitant EM and/or neurologic disorders. |
| Ocular manifestations | Conjunctivitis, uveitis, papillitis, episcleritis, keratitis. | Specific serum antibodies | Recent or concomitant LB manifestations. Detection of B. burgdorferi s.l. by culture and/or PCR from ocular fluid. |
| European Commission Definition for LNB (European Commission, 2018) | |||
|---|---|---|---|
| Term | Clinical criteria | Laboratory criteria | |
| LNB | Early LNB: Neurologic symptoms for <6 months With manifestations confined to the PNS (cranial nerves, spinal roots, or peripheral nerves) (Bannwarth syndrome) With CNS manifestations Late LNB: neurologic symptoms for >6 months With PNS manifestations With CNS manifestations |
Pleocytosis in CSF AND evidence of intrathecal production of LB antibodies, OR B burdgorferi s.l. isolation, OR nucleic acid detection in CSF, OR detection of IgG LB antibodies in blood specimen only for children (<18 years) with facial palsy or other cranial neuritis and a recent (<2 months) history of EM | |
| The U.S. Centers for Disease Control and Prevention case definitions (Centers for Disease Control and Prevention, 1997) | |||
|---|---|---|---|
| Clinical description |
A systemic, tick-borne disease with protean manifestations, including dermatologic, rheumatologic, neurologic, and cardiac abnormalities. The best clinical marker for the disease is the initial skin lesion (i.e., EM) that occurs in 60–80% of patients. |
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| Laboratory criteria for diagnosis |
Isolation of B. burgdorferi from a clinical specimen or demonstration of diagnostic IgM or IgG antibodies to B. burgdorferi in serum or CSF. A two-test approach using a sensitive enzyme immunoassay or immunofluorescence antibody followed by Western blot is recommended. |
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| Case classification—confirmed |
(a) A case with EM or (b) a case with at least one late manifestation that is laboratory confirmed. |
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| EM |
For purposes of surveillance, EM is defined as a skin lesion that typically begins as a red macule or papule and expands over a period of days to weeks to form a large round lesion, often with partial central clearing. A single primary lesion must reach ≥5 cm in size. Secondary lesions also may occur. Annular erythematous lesions occurring within several hours of a tick bite represent hypersensitivity reactions and do not qualify as EM. For most patients, the expanding EM lesion is accompanied by other acute symptoms, particularly fatigue, fever, headache, mildly stiff neck, arthralgia, or myalgia. These symptoms are typically intermittent. The diagnosis of EM must be made by a physician. Laboratory confirmation is recommended for persons with no known exposure. |
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| Late manifestations | Late manifestations include any of the following when an alternate explanation is not found. (1) Musculoskeletal system. Recurrent, brief attacks (weeks or months) of objective joint swelling in one or a few joints, sometimes followed by chronic arthritis in one or a few joints. Manifestations not considered as criteria for diagnosis include chronic progressive arthritis not preceded by brief attacks and chronic symmetrical polyarthritis. In addition, arthralgia, myalgia, or fibromyalgia syndromes alone are not criteria for musculoskeletal involvement. (2) Nervous system. Any of the following, alone or in combination: lymphocytic meningitis; cranial neuritis, particularly facial palsy (may be bilateral); radiculoneuropathy; or, rarely, encephalomyelitis. Encephalomyelitis must be confirmed by demonstration of antibody production against B. burgdorferi in the CSF, evidenced by a higher titer of antibody in CSF than in serum. Headache, fatigue, paresthesia, or mildly stiff neck alone are not criteria for neurologic involvement. (3) Cardiovascular system. Acute onset of high-grade (2° or 3°) atrioventricular conduction defects that resolve in days to weeks and are sometimes associated with myocarditis. Palpitations, bradycardia, bundle branch block, or myocarditis alone are not criteria for cardiovascular involvement. | ||
a
If <5 cm in diameter, a history of tick bite, a delay in appearance (after the tick bite) of at least 2 days, and an expanding rash at the site of the tick bite is required.
b
As a rule, initial and follow-up samples must be tested in parallel to avoid changes by interassay variation.
c
In early cases, intrathecally produced specific antibodies may still be absent.
CNS, central nervous system; CSF; cerebrospinal fluid; EM, erythema migrans; EUCALB, European Concerted Action on Lyme Borreliosis; IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M; LA, Lyme arthritis; LB, Lyme borreliosis; LC, Lyme carditis; LNB, Lyme neuroborreliosis; PCR, polymerase chain reaction; PNS, peripheral nervous system.