Table 1.

Recommended approach for the diagnosis of selected Lyme disease manifestations.

Clinical manifestations	References	Primary diagnostic testing	Supporting testing and findings
Erythema migrans	ECDC (15)	Testing is conducted on the basis of history and visual inspection of the skin lesion. Serological testing is recommended if the lesion is atypical, acute-phase, or convalescent phase.	Culture or PCR is not needed for routine clinical practice.
	ESGBOR (11)	Does not require serological confirmation.
	IDSA, AAN, ACR (16)	Clinical diagnosis rather than laboratory testing is recommended.	In atypical erythema migrans, antibody testing is performed on an acute and convalescent phase serum sample rather than currently available direct detection methods such as PCR or culture performed on blood or skin samples.
	GDS (17)	If a typical erythema migrans is present, no further laboratory diagnostic confirmation (serological, cultural, molecular, biological) needs to be performed.	Direct detection of Borrelia in patient samples using light microscopy is currently not recommended.
	NMS (18)	Serum antibody testing can be analyzed.	PCR or culture of skin biopsy can be analyzed.
Lyme neuroborreliosis	ECDC (15)	Pleocytosis and demonstration of synthesis of intrathecal antibodies to Lyme Borrelia. Serological testing is usually positive at the time of presentation; if negative, convalescent-phase sera should be tested.	Detection of B. burgdorferi s.I. by culture or PCR in CSF, intrathecal synthesis of total immunoglobulin.
	ESGBOR (11)	Specific CSF/serum antibody index.
	IDSA, AAN, ACR (16)	Antibody testing by obtaining simultaneous samples of CSF and serum to determine a CSF: serum antibody index, carried out by a laboratory using validated methodology.	Recommend against routine PCR or culture of CSF or serum.
	NMS (18)	Antibody testing by obtaining simultaneous samples of CSF and serum to determine a CSF: serum antibody index.	PCR or culture of CSF can be analyzed.
Lyme arthritis	ECDC (15)	Serological testing. As a rule, high concentrations of specific serum IgG antibodies are present.	Detection of B. burgdorferi s.I. by culture or PCR in synovial fluid.
	ESGBOR (11)	Detection of antibodies to B. burgdorferi via serum IgG.
	IDSA, AAN, ACR (16)	Serum antibody testing over PCR or culture of blood or synovial fluid/tissue.	In seropositive patients, PCR for synovial fluid or tissue rather than Borrelia culture of those samples.
	NMS (18)	Serum antibody testing can be analyzed.	PCR or culture of synovial fluid or tissue can be analyzed.
Acrodermatitis chronica atrophicans (ACA)	ECDC (15)	Serological testing. As a rule, high concentrations of specific serum IgG antibodies are present.	Histology, culture, or PCR are not needed for routine clinical practice.
	ESGBOR (11)	Detection of antibodies to B. burgdorferi via serum IgG.
	GDS (17)	When ACA is clinically suspected, the diagnosis shall be confirmed through a serological test. High IgG antibody values in the screening test, combined with a broadband pattern in the IgG immunoblot test, indicate a suspected clinical diagnosis.	When the clinical picture is ambiguous, further diagnostic clarification through biopsy and subsequent histological testing should be done. When the findings are unclear, direct detection by culture and molecular biology is recommended. Direct detection of Borrelia in patient samples using light microscopy is currently not recommended.
	NMS (18)	Serum antibody testing can be analyzed.	PCR or culture of skin biopsy can be analyzed.

IDSA: Infectious Diseases Society of America, AAN: American Academy of Neurology, ACR: American College of Rheumatology, ECDC: European Centre for Disease Prevention and Control, GDS: German Dermatology Society, ESGBOR: European Society of Clinical Microbiology and Infectious Diseases Study Group for Lyme Borreliosis, NMS: National Microbiology Standards: Infectious Diseases Laboratory Diagnosis Guide (Republic of Turkey Ministry of Health, Public Health Institution), PCR: Polymerase chain reaction, CSF: Cerebrospinal fluid.