A comprehensive clinical and laboratory evaluation of 224 patients with persistent symptoms attributed to presumed tick-bite exposure

Abstract

Background Persistent symptoms attributed to presumed tick-bite exposure constitute an unresolved medical controversy. We evaluated whether Swedish adults who met the criteria for post-treatment Lyme disease syndrome (PTLDS) exhibited characteristics distinguishable from adults who did not, but who displayed similar symptoms and disease course after suspected previous tick-bite infection (TBI). Methods and findings During 2015–2018, 255 patients–referred to the Centre for Vector-borne Infections, Uppsala University Hospital, Sweden with symptoms lasting longer than six months–were recruited. Of this group, 224 completed the study. Each patient was examined by an infectious disease specialist and, besides a full medical history, underwent a panel of blood and cerebrospinal fluid laboratory tests including hematological, biochemical, microbiological and immunological analyses, and the RAND-36 scale to measure quality of life. For analysis purposes, patients were divided into five subgroups, of which one represented PTLDS. According to serological results indicating TBI and documented/ reported objective signs of Lyme disease, 85 (38%) patients fulfilled the criteria for PTLDS and were compared with the other 139 (62%) serologically classified patients. In the PTLDS group, erythema chronicum migrans (ECM) was documented/reported in 86% of patients, previous neuroborreliosis in 15%, and acrodermatitis chronica atroficans (ACA) in 3.5%. However, there were no significant differences regarding symptoms, laboratory results or disease course between patients with PTLDS and those without laboratory evidence of Borrelia exposition. Most reported symptoms were fatigue-related (70%), musculoskeletal (79%), neurological (82%) and neurocognitive (57%). Tick bites were recalled by 74%. The RAND-36 score was significantly below that of the general Swedish population. Signs of immunological/inflammatory reactivity with myositis antibodies were detected in 20% of patients, fibrinogen levels were moderately increased in 21% and elevated rheumatoid factor in 6%. Conclusions The PTLDS group did not differ exclusively in any respect from the other subgroups, which either lacked previously documented/reported evidence of borreliosis or even lacked detectable serological signs of exposure to Lyme disease. The results suggest that symptoms often categorized as Chronic-Lyme-Disease (CLD) in the general debate, cannot be uniquely linked to Lyme disease. However, approximately 20% of the total group of patients showed signs of autoimmunity. Further studies are needed to elucidate the underlying causes and mechanisms of PTLDS and there is reason to consider a multifactorial approach.

Seroprevalence of Antibodies against Tick-Borne Pathogens in Czech Patients with Suspected Post-Treatment Lyme Disease Syndrome

“…Although the study population was not selected for a history of tick bites, the frequency of Anaplasma IgG positivity in this work is virtually identical to the results of our study in patients with suspected PTLDS (12.6%). A very similar result (11%) was also found in the general adult population in southern Norway [46] and in patients with persistent symptoms attributed to suspected tick bite exposure in Sweden, where Anaplasma antibodies were detected in 12% of patients [47]. In a serological study in neighboring Poland, antibodies against Anaplasma were found in 11.8% of forest workers and in 9.4% of healthy control blood donors [48].…”

Laboratory Methods for Detection of Infectious Agents and Serological Response in Humans With Tick-Borne Infections: A Systematic Review of Evaluations Based on Clinical Patient Samples

“…We conclude that to date, science has no alternative diagnostic tests to offer patients with persisting symptoms post-treatment besides the well-established ones recommended for investigation of LB. In a recently published report, however, it has been shown that symptoms that are often categorized as chronic LB in the general debate could not be uniquely linked to LB ( 86 ). Instead, ~20% of the total group of patients showed signs of autoimmunity.…”

Bartonella spp. seroprevalence in tick-exposed Swedish patients with persistent symptoms

“…We purposely selected participants from an exploratory study of human tick-borne infections conducted at the Center for Vector-borne Infections (CVI), Uppsala University Hospital, Uppsala, Sweden between October 2015 and December 2018 [24]. A total of 224 patients were enrolled in the principal study during this period.…”

“…The other criteria were age ≥ 18 years; suspected tick-borne infection based on previous tick exposure; symptoms; laboratory findings; previous treatment for tick-borne infection; and/or suspicion of co-infection with other tick-borne infections. A summary of data on these patients has previously been published [24].…”

“…Serological testing (IFA) and PCR assays for Rickettsia spp. and tick-borne encephalitis virus (Immunozym FSME IgM and IgG, respectively; Progen Biotechnik GmbH, Heidelberg, Germany) and the PCR assay for Candidatus Neoehrlichia mikurensis in blood were performed at Sahlgrenska University Hospital, Gothenburg, Sweden as previously described [24].…”