Based on Stanek et al., 2010 Clinical Microbiology and Infection

Term	Clinical case definition	Laboratory evidence: essential	Laboratory/clinical evidence: supporting
Erythema migrans	Painless and extending erythema, with or without central clearing, and with a diameter > 5 cm*. Appearing at least 3 days after the tick-bite. Advancing edge typically distinct, often intensely coloured, not markedly elevated.	None	Detection of Borrelia burgdorferi s.l. by PCR from skin biopsy
Borrelial lymphocytoma (rare)	Bluish-red nodule or plaque, often painless, usually on ear lobe, ear helix, nipple or scrotum; more frequent in children (especially on ear) than in adults.	Seroconversion or positive serology**.	– Detection of B. burgdorferi s.l. by PCR from skin biopsy – Histology – Recent or concomitant EM
Acrodermatitis chronica atrophicans	Long-standing red or bluish-red lesion, usually on the extensor surfaces of extremities. Initial doughy swelling. Lesion eventually become atrophic. Possible skin induration and fibroid nodules over bony prominences.	High level of specific serum IgG antibodies**	– Detection of B. burgdorferi s.l. by PCR from skin biopsy -Histology
Lyme neuroborreliosis	In adults mainly unilateral meningo-radiculitis associated with hyperalgesia, facial palsy, meningitis; rarely encephalitis, myelitis; very rarely cerebral vasculitis. In children mainly meningitis and facial palsy.	Pleocytosis and demonstration of intrathecal specific antibody synthesis***	– CXCL-13 in CSF – Detection of B. burgdorferi s.l. by PCR from CSF if symptoms < 15 days. – Intrathecal synthesis of IgG, IgM or IgA. -Recent or concomitant EM
Lyme arthritis	Recurrent attacks or persisting objective joint swelling in one (mono-arthritis) or a few large joints (asymmetric oligo-arthritis). The knee is the most often involved joint. Discordance between the significant joint effusion and the associated mild pain. Alternative explanations must be excluded, especially if bilateral.	Specific serum IgG antibodies, usually in high concentrations**	Synovial fluid analysis. Detection of B. burgdorferi s.l. by PCR from synovial fluid and/or tissue.
Lyme carditis (rare)	Acute onset of atrio-ventricular (I-III) conduction disturbances, rhythm disturbances, 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 erythema migrans and/or neurologic disorders.
Ocular manifestations (rare)	Uveitis most often	Specific serum antibodies**	Recent or concomitant Lyme borreliosis manifestations. Detection of B. burgdorferi s.l. by PCR from ocular fluid.

*if less than 5 cm in diameter a history of tick-bite, a delay in appearance (after the tick bite) of at least 3 days and an expanding rash at the site of the tick-bite is required
**Specific antibody levels in serum may increase in response to progression of infection, or may decrease due to abrogation of the infection process. Samples collected a minimum of 3 months apart may be required in order to detect a change in IgG levels; as a rule, initial and follow up samples have to be tested in parallel in order to avoid changes by inter-assay variation.
***In early cases intrathecally produced specific antibodies may still be absent.

References

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Eldin C, Raffetin A, Bouiller K, Hansmann Y, Roblot F, Raoult D, Parola P. Review of European and American guidelines for the diagnosis of Lyme borreliosis. Med Mal Infect. 2019;49(2):121-132. doi: 10.1016/j.medmal.2018.11.011.

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Hofmann H, Fingerle V, Hunfeld KP, Huppertz HI, Krause A, Rauer S, Ruf B; Consensus group. Cutaneous Lyme borreliosis: Guideline of the German Dermatology Society. Ger Med Sci. 2017;15:Doc14. doi: 10.3205/000255. PMID: 28943834.

Mygland A, Ljøstad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I; European Federation of Neurological Societies. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010;17(1):8-16, e1-4. doi: 10.1111/j.1468-1331.2009.02862.x.

Nemeth J, Bernasconi E, Heininger U, Abbas M, Nadal D, Strahm C, Erb S, Zimmerli S, Furrer H, Delaloye J, Kuntzer T, Altpeter E, Sturzenegger M, Weber R, For The Swiss Society For Infectious Diseases And The Swiss Society For Neurology. Update of the Swiss guidelines on post-treatment Lyme disease syndrome. Swiss Med Wkly. 2016;146:w14353. doi: 10.4414/smw.2016.14353.

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