Lyme disease has become a global public health problem and a prototype of an emerging infection. Both treatment-refractory infection and symptoms that are related to
Lyme disease is a worldwide-distributed multisystem animal-borne disease, caused by
Lyme disease is the most common vector-borne disease in the USA and Europe with more than 300,000 new cases in the USA [
Chronic Lyme disease (CLD) is considered a constellation of persistent symptoms in patients with or without evidence of Bb infection [
There is growing and well-documented evidence to the concept of persistent Bb infection in both animals [
Because of the absence of solid evidence on prevalence [
A systematic review method was used to document the complexity and multidimensionality of CLD. In addressing the objective of this review, we used a parallel search strategy via Medline, The Cochrane Library of Systematic Reviews, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and PRE-CINAHL, complemented with a reference review of key articles. Articles had to be published between October 2009 and October 2014.
Articles were selected if they dealt with (1) CLD care complexity; (2) CLD case (patient) complexity; (3) the complexity of CLD quality assessment; and (4) complexity of CLD at the health system level. In addition the studies had to produce insights into the complexity of CLD with relevance to family medicine. Nonsystematic reviews, opinions, and grey literature were excluded from the search. The search strategy included a combination of Medical Subject Headings (MeSH) terms with regard to Lyme disease. We also scrutinised extra sources for further identification of studies by hand-searching the reference lists of all articles. By focusing on CLD care, case, quality assessment, and health systems complexity, we further build on four major and interrelated components of complexity in chronic care that have been described by Borgermans et al. [
Two authors carried out independent screening of titles and abstracts using the specific inclusion and exclusion criterion reported on previously. We ordered the full text of all citations that met the eligibility criteria or appeared relevant or where relevance/eligibility was not clear from the abstract. In the final screening, two authors independently scrutinised the full texts of studies and recorded the reasons when articles were excluded resolving disagreements by discussion and when necessary referred to a third author. A tool-based assessment of the methodological quality of the studies was not part of this review.
The flow diagram (Figure
Flow diagram of study selection process.
A total of 967 studies were identified. Finally 945 articles were included for assessment. 72 studies provided insights on CLD care complexity, 9 studies provided insights on CLD case complexity, 2 studies provided insights on CLD quality complexity, and 6 studies provided insights on CLD health system complexity with relevance to family medicine.
It is current practice for physicians to base themselves primarily on clinical signs and symptoms when CLD is suspected. Patients often cannot recall being bitten by a tick or if erythema migrans has occurred. Erythema migrans is pathognomonic and does not require any further laboratory investigations [
There is consistent evidence that the two-tier testing lacks sensitivity, cannot distinguish between current and past infection, cannot be used as a marker for treatment, is often dependent on subjectively scored immunoblots, and is considered expensive [
Another novel method including culturing spirochetes from the serum of patients uses a two-step preenrichment process, followed by immunostaining with or without polymerase chain reaction (PCR) analysis [
Recent evidence has shown that the presence or absence of chronic Lyme borreliosis may be objectively adjudicated by tissue examinations which demonstrate or which fail to show pathogenic microbes in patients who have received a full course of antibiotics [
Overall, studies highlight the need for standardization in diagnostic (serological) testing, as well as the need for studies that discriminate between active disease and past infection.
A factor that complicates the diagnosis of CLD is that it does not present with isolated subjective symptoms [
Overall, studies show the need for a careful differential diagnosis in patients with suspected CLD and persistent complaints.
The diagnosis of CLD is even more complex when tick-borne coinfections occur in association with Lyme disease [
Overall, studies highlight the importance of coinfections since they can complicate the diagnostic process and their pathological synergism can exacerbate CLD or induce similar disease manifestations.
Treatment options are complicated since the population of individuals reporting CLD are heterogeneous with guidelines contradicting each other. Recommendations about the type and duration of treatments in patients with CLD have no factual basis [
Recent evidence shows that novel therapeutic targets for the treatment of the disease should acknowledge a central role of the neutrophil-activating protein A (NapA) of Bb in promoting both regulatory T-cell response and immune suppression in the cerebrospinal fluid of patients with chronic Lyme borreliosis [
Overall, studies show that various therapeutic regimens are used in patients with CLD reflecting the need for individualized approaches.
The vector model of complexity (VMC) [
Complexity in CLD along the biology/genetics axis is important since gender distribution in patients with Lyme borreliosis has recently been demonstrated. Patients with cutaneous manifestations of Lyme borreliosis tend to be predominantly female, whereas those with noncutaneous manifestations are predominantly male [
Complexity in CLD is introduced along the environment axis with a growing number of studies to document the important relationship between the increase in outdoor activities in wooded areas and the incidence of Lyme disease [
Complexity in CLD is also introduced along the behavioral axis as CLD has considerable implications on daily life. Patients report a significant and severe decline in health status associated with chronic Lyme disease [
The complexity of quality assessment is reflected by the lack of tools at the present time that can assess the quality of care delivered to patients with CLD. A limited number of quality indicators at the structure, process, or outcome level of care for patients with CLD exist [
Health system complexity is of relevance to health seeking behaviour of patients with CLD. There is an abundance of studies on health seeking behaviour highlighting the importance of health system characteristics and their influence on an individual’s behaviour at a given time and place [
We have outlined the importance of case, care, quality assessment, and health system complexity in patients with CLD. The majority of studies focus on CLD care and case complexity with a minority of studies to report on CLD quality assessment and health system complexity.
While specialists are an essential element of the total health care continuum, the majority of patients with CLD will continue to access the health care system through family physicians [
Another component of the care responsibility of family physicians is ensuring that patients receive preventive interventions. Prevention of mortality and morbidity may depend on correct early diagnosis and treatment [
The controversy on CLD needs to be solved because of the heavy burden of illness associated with CLD in patients with or without evidence of Bb infection. There is a need for the development and establishment of new clinical diagnostic tools with increased accuracy, sensitivity, and specificity, as well as novel treatment approaches that may reduce the burden of illness and concomitant costs posed by CLD. Family physicians have a crucial role to play in the prevention and treatment of the disease fostering an integrative multidisciplinary approach to care.
The authors declare that there is no conflict of interests regarding the publication of this paper.