[Cutaneous Lyme disease: not always a rash with a central clearing]. / Cutane lymeziekte: lang niet altijd een rode ring.

During the past four decades the number of reported Lyme disease diagnoses in the Netherlands has increased to 27.000 a year, with a yearly incidence of Lyme disease between 111 (95% CI 106-115) to 131 (95% CI 126-136) per 100,000 person years. A large part of all Lyme disease diagnoses concern the skin; in the Netherlands, 77-89% erythema migrans, 2-3% borrelia lymfocytoom and 1-3% acrodermatitis chronica atrophicans. These skin manifestations have a variable clinical expression, reason why they can be difficult to diagnose. Early recognition and treatment is important to prevent the development of systemic manifestations.

A prospective study of patients with post treatment Lyme disease syndrome treated with modified VFEM energy.

BACKGROUND: We previously demonstrated a possible therapeutic benefit of VFEM (variable frequency electromagnetic energy) technology for the treatment of Post Treatment Lyme Disease Syndrome (PTLDS) or Chronic Lyme Disease (CLD). As a result, we prospectively enrolled 10 patients, all having significant debility, to determine to what extent we could improve their quality of life. Eight patients completed the 10 treatments. RESULTS: All eight patients had a significant improvement in quality of life within a 4-month time frame. CONCLUSION: VFEM is a stand-alone modality that appears to demonstrate a significant improvement in quality of life in PTLDS or CLD with little or no risk or side effects of treatment.

Shorter versus longer duration of antimicrobial therapy for early Lyme disease: A systematic review and meta-analysis.

BACKGROUND: Antibiotic therapy for patients with early Lyme disease is necessary to prevent later-stage Lyme disease complications. This systematic review and meta-analysis compares shorter versus longer antibiotic regimens in treating early Lyme disease. METHODS: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted up to November 2023. We examined treatment failure, complete response, and photosensitivity. Short vs. long therapy was defined as ≤10 days vs. >10 days. Subgroup analyses included antibiotic type and varying treatment durations. Analysis utilized RStudio 4.1.2. PROSPERO registration: CRD42023423876. RESULTS: Seven studies, encompassing 1,462 patients, were analyzed. No significant differences in treatment failure, 12-month complete response, final visit complete response were found between short and long durations of antibiotic therapy. Subgroup and sensitivity analyses corroborated these findings. CONCLUSION: Shorter and longer antibiotic regimens for early Lyme disease show similar efficacy, highlighting the potential of ≤10-day courses, as effective treatment options.

Lyme disease and Whipple's disease: a comprehensive review for the rheumatologist.

Despite their rarity, Lyme disease and Whipple's disease are of significant importance in rheumatology, as both can manifest as chronic arthritis, presenting challenges in the differential diagnosis of inflammatory arthropathies. In Lyme disease, arthritis typically emerges as a late manifestation, usually occurring six months after the onset of erythema migrans. The predominant presentation involves mono- or oligoarthritis of large joints, with a chronic or remitting-recurrent course. Even with appropriate antimicrobial treatment, arthritis may persist due to inadequate immunological control triggered by the disease. In contrast, Whipple's disease may present with a migratory and intermittent seronegative poly- or oligoarthritis of large joints, preceding classic gastrointestinal symptoms by several years. Both disorders, particularly Whipple's disease, can be misdiagnosed as more common autoimmune rheumatic conditions such as rheumatoid arthritis and spondyloarthritis. Epidemiology is crucial in suspecting and diagnosing Lyme disease, as the condition is transmitted by ticks prevalent in specific areas of the United States, Europe, and Asia. On the contrary, the causative agent of Whipple's disease is widespread in the environment, yet invasive disease is rare and likely dependent on host genetic factors. In addition to erythema migrans in Lyme disease and gastrointestinal manifestations in Whipple's disease, neurological and cardiac involvement can further complicate the course of both. This article offers a comprehensive review of the epidemiological, pathophysiological, clinical, and therapeutic aspects of both diseases.

Screening Marine Microbial Metabolites as Promising Inhibitors of Borrelia garinii: A Structural Docking Approach towards Developing Novel Lyme Disease Treatment.

Lyme disease caused by the Borrelia species is a growing health concern in many parts of the world. Current treatments for the disease may have side effects, and there is also a need for new therapies that can selectively target the bacteria. Pathogens responsible for Lyme disease include B. burgdorferi, B. afzelii, and B. garinii. In this study, we employed structural docking-based screening to identify potential lead-like inhibitors against the bacterium. We first identified the core essential genome fraction of the bacterium, using 37 strains. Later, we screened a library of lead-like marine microbial metabolites (n = 4730) against the arginine deiminase (ADI) protein of Borrelia garinii. This protein plays a crucial role in the survival of the bacteria, and inhibiting it can kill the bacterium. The prioritized lead compounds demonstrating favorable binding energies and interactions with the active site of ADI were then evaluated for their drug-like and pharmacokinetic parameters to assess their suitability for development as drugs. Results from molecular dynamics simulation (100 ns) and other scoring parameters suggest that the compound CMNPD18759 (common name: aureobasidin; IUPAC name: 2-[(4R,6R)-4,6-dihydroxydecanoyl]oxypropan-2-yl (3S,5R)-3,5-dihydroxydecanoate) holds promise as a potential drug candidate for the treatment of Lyme disease, caused by B. garinii. However, further experimental studies are needed to validate the efficacy and safety of this compound in vivo.

Isolated Intracranial Hypertension as a Presentation of Pediatric Lyme Borreliosis: A Case Report and Literature Review.

BACKGROUND: It is extremely rare for Lyme borreliosis to present solely with features of increased intracranial pressure. The treatment of pediatric Lyme neuroborreliosis with oral versus intravenous antibiotics remains controversial. METHODS: Case report and literature review. RESULTS: A 13-year-old male presented with five days of binocular diplopia, several weeks of headache, and a history of multiple tick bites six weeks prior. His examination showed a left eye abduction deficit and bilateral optic disc edema. Magnetic resonance imaging (MRI) of the brain with contrast showed tortuosity of the optic nerves, prominence of the optic nerve sheaths, and enhancement of the left fifth and bilateral sixth cranial nerves. Lumbar puncture showed an elevated opening pressure and a lymphocytic pleocytosis. Lyme IgM and IgG antibodies were positive in the serum and cerebrospinal fluid. The patient was treated with intravenous ceftriaxone for two days empirically followed by doxycycline by mouth for 19 days. Symptoms began improving after 48 hours. The strabismus resolved after two weeks, and the papilledema improved slowly with complete resolution at six months. CONCLUSIONS: Lyme neuroborreliosis can present as isolated intracranial hypertension in the pediatric population; it can be differentiated from idiopathic intracranial hypertension on MRI, and lumbar puncture and can be confirmed with serum antibody testing. Oral doxycycline can be considered for Lyme neuroborreliosis in children.

Discrepancy between IDSA and ESGBOR in Lyme disease: Individual participant meta-analysis in Türkiye.

BACKGROUND: The evidence on the prevalence of Lyme borreliosis (LB) is limited, but there is a suspicion of overdiagnosis of LB in recent years. We reviewed the LB diagnosis and treatment-related data in Türkiye, based on the Infectious Diseases Society of America (IDSA) 2020 and European Society of Clinical Microbiology and Infectious Diseases Study Group for Lyme Borreliosis (ESGBOR) 2018 guidelines. By detecting the disagreements between these two, we outlined the areas to be improved for future guidelines. METHODS: We performed a literature search according to the PRISMA guidelines in PubMed, Ovid-Medline, Web of Science, Turkish Medline, Scopus, CINAHL, ULAKBIM TR Index, Google Scholar and Cochrane Library databases. We included the published cases in a database and evaluated according to IDSA and ESGBOR guidelines. We outlined the reasons for misdiagnoses and inappropriate uses of antibiotics. RESULTS: We included 42 relevant studies with 84 LB cases reported from Türkiye between 1990 and December 2022. Among 84 cases, the most common clinical findings were nervous system findings (n = 37, 44.0%), erythema migrans (n = 29, 34.5%) and ophthalmologic findings (n = 15, 17.9%). The IDSA 2020 and ESGBOR 2018 guidelines agreed on the diagnosis of 71 (84.5%) cases; there was an agreement that 31 cases (36.9%) were misdiagnosed and 40 cases (47.6%) were correctly diagnosed, and there was disagreement for 13 cases (15.5%). Serum immunoglobulin M (IgM), IgG measurements by ELISA and western blot were widely performed, and they were effective in definitive diagnosis merely when used according to guidelines. Inappropriate use of antibiotics was detected in 42 (50.0%) of cases which were classified in the following categories: incorrect LB diagnosis, inappropriate choice of antibiotic, inappropriate route of drug administration and prolonged antibiotic treatment. CONCLUSION: Overdiagnosis and non-adherence to guidelines is a common problem. The discordance between seroprevalence and clinical studies necessitates a consensus over the best clinical approach.

Host glycosylation of immunoglobulins impairs the immune response to acute Lyme disease.

BACKGROUND: Lyme disease is caused by the bacteria Borreliella burgdorferi sensu lato (Bb) transmitted to humans from the bite of an infected Ixodes tick. Current diagnostics for Lyme disease are insensitive at the early disease stage and they cannot differentiate between active infections and people with a recent history of antibiotic-treated Lyme disease. METHODS: Machine learning technology was utilized to improve the prediction of acute Lyme disease and identify sialic acid and galactose sugar structures (N-glycans) on immunoglobulins associated specifically at time points during acute Lyme disease time. A plate-based approach was developed to analyze sialylated N-glycans associated with anti-Bb immunoglobulins. This multiplexed approach quantitates the abundance of Bb-specific IgG and the associated sialic acid, yielding an accuracy of 90% in a powered study. FINDINGS: It was demonstrated that immunoglobulin sialic acid levels increase during acute Lyme disease and following antibiotic therapy and a 3-month convalescence, the sialic acid level returned to that found in healthy control subjects (p < 0.001). Furthermore, the abundance of sialic acid on Bb-specific IgG during acute Lyme disease impaired the host's ability to combat Lyme disease via lymphocytic receptor FcγRIIIa signaling. After enzymatically removing the sialic acid present on Bb-specific antibodies, the induction of cytotoxicity from acute Lyme disease patient antigen-specific IgG was significantly improved. INTERPRETATION: Taken together, Bb-specific immunoglobulins contain increased sialylation which impairs the host immune response during acute Lyme disease. Furthermore, this Bb-specific immunoglobulin sialyation found in acute Lyme disease begins to resolve following antibiotic therapy and convalescence. FUNDING: Funding for this study was provided by the Coulter-Drexel Translational Research Partnership Program as well as from a Faculty Development Award from the Drexel University College of Medicine Institute for Molecular Medicine and Infectious Disease and the Department of Microbiology and Immunology.

Tick-borne infections in children in North America.

PURPOSE OF REVIEW: Because both incidence and awareness of tick-borne infections is increasing, review of major infections and recent advances related to their diagnosis and management is important. RECENT FINDINGS: A new algorithm, termed modified two-tier testing, for testing for antibodies to Borrelia burgdorferi , the cause of Lyme disease, has been approved and may replace traditional two-tier testing. In addition, doxycycline is now acceptable to use for treatment of and/or prophylaxis for Lyme disease for up to 21 days in children of any age. Borrelia miyamotoi , a bacterium in the relapsing fever type of Borrelia, is the first of this type of Borrelia that is transmitted by hard-bodied ticks such as Ixodes scapularis. SUMMARY: Awareness of these infections and advances in their diagnosis and treatment is important to assure the best outcomes for affected patients. Table 1 contains a summary of infections discussed.

Pediatric Lyme disease: systematic assessment of post-treatment symptoms and quality of life.

BACKGROUND: Lyme disease is common among children and adolescents. Antibiotic treatment is effective, yet some patients report persistent symptoms following treatment, with or without functional impairment. This study characterized long-term outcome of pediatric patients with Lyme disease and evaluated the case definition of post-treatment Lyme disease (PTLD) syndrome. METHODS: The sample included 102 children with confirmed Lyme disease diagnosed 6 months-10 years prior to enrollment (M = 2.0 years). Lyme diagnosis and treatment information was extracted from the electronic health record; parent report identified presence, duration, and impact of symptoms after treatment. Participants completed validated questionnaires assessing health-related quality of life, physical mobility, fatigue, pain, and cognitive impact. RESULTS: Most parents reported their child's symptoms resolved completely, although time to full resolution varied. Twenty-two parents (22%) indicated their child had at least one persistent symptom >6 months post-treatment, 13 without functional impairment (PTLD symptoms) and 9 with functional impairment (PTLD syndrome). Children with PTLD syndrome had lower parent-reported Physical Summary scores and greater likelihood of elevated fatigue. CONCLUSIONS: In the current study, most children with Lyme disease experienced full resolution of symptoms, including those who initially met PTLD syndrome criteria. Effective communication about recovery rates and common symptoms that may persist post-treatment is needed. IMPACT: The majority of pediatric patients treated for all stages of Lyme disease reported full resolution of symptoms within 6 months. 22% of pediatric patients reported one or more symptom persisting >6 months, 9% with and 13% without accompanying functional impairment. Effective communication with families about recovery rates and common symptoms that may persist post-treatment of Lyme disease is needed.

Lyme borreliosis in pediatric population: Clinical, diagnostic and therapeutic features.

INTRODUCTION: Lyme borreliosis (LB) in the paediatric population is an understudied entity with certain peculiarities. The objective of this study is to describe the characteristics of paediatric patients with LB, and their diagnostic and therapeutic processes. METHODS: Descriptive and retrospective study in patients up to 14 years old with suspected or confirmed LB between 2015 and 2021. RESULTS: A total of 21 patients were studied: 18 with confirmed LB (50% women; median age 6.4 years old) and 3 false positive of the serology. Clinical features in the 18 patients with LB were: neurological (3, neck stiffness; 6, facial nerve palsy), dermatological (6, erythema migratory), articular (1), and non-specific manifestations (5). Serological diagnosis was confirmatory in 83.3% of cases. A total of 94.4% patients received antimicrobial treatment (median duration, 21 days). All recovered with resolution of symptoms. CONCLUSIONS: LB diagnosis is difficult in the paediatric population and presents clinical and therapeutic peculiarities, with favourable prognosis.

Costs associated with informal health care pathway for patients with suspected Lyme borreliosis.

OBJECTIVES: To compare the direct and indirect medical costs for patients with suspected Lyme borreliosis according to whether or not they had used an informal care pathway. PATIENTS AND METHODS: We retraced the care pathways of participating patients by a prospective questionnaire survey and a retrospective analysis of care records. Direct and indirect costs were estimated using a micro-costing method from different perspectives. We compared the costs of patients who had consulted a "Lyme Doctor" (informal care pathway) with those who had only used the formal care pathway. Non-parametric tests were appraised the significance of the differences between the two groups of patients. RESULTS: Out of 103 eligible patients, 49 (including 12 having used an informal health care pathway) agreed to be investigated. Five expenditure items entirely borne by patients were significantly higher for patients following an informal care pathway: productivity loss (3041 ± 6580 vs 194 ± 1177 euros, p = 0.01), alternative therapies (3484 ± 7308 vs 369 ± 956 euros), biological tests sent abroad (571 ± 1415 vs 17 ± 92 euros, p < 0.01), self-medication (918 ± 1998 vs 133 ± 689, p = 0.02) and transport (3 094 ± 3456 vs 1 123 ± 1903p = 0.01). CONCLUSIONS: From the patient's standpoint, the informal care pathway involving consultation with a Lyme Doctor is far more expensive than the formal care pathway. More specifically, the patient has to bear the costs of alternative treatments and repeated, non-recommended examinations.

Hemarthrosis in a Pediatric Patient With Immune Thrombocytopenia and Lyme Arthritis.

The presentation of immune thrombocytopenia is dependent on the degree of thrombocytopenia, with no to mild bleeding symptoms, primarily mucocutaneous bleeding. Severe bleeding in other organ systems is a rare complication. Spontaneous hemarthrosis is rare in patients without hemophilia. We report a child presenting with oral and cutaneous petechial lesions and left knee hemarthrosis without trauma. Laboratory findings showed severe thrombocytopenia consistent with immune thrombocytopenia. Serologic tests were consistent with Lyme disease. Hemarthrosis was presumed secondary to Lyme disease monoarticular joint inflammation with bleeding exacerbated by severe thrombocytopenia. Hemarthrosis resolved and platelet counts normalized following immunoglobulin infusion, steroid course, and antibiotics.

Nonsexual Acute Genital Ulcerations as a Rare Presentation of Disseminated Lyme Disease in a Pediatric Patient.

Nonsexual acute genital ulcerations (NAGUs), also known as Lipschütz ulcers, are vulvar ulcers occurring predominantly in adolescent females. Although the pathogenesis is unknown, NAGUs are commonly associated with systemic infections. Here, we present a female child with NAGU along with disseminated Lyme disease. We believe this is the first reported pediatric case of this phenomenon.

Time to Diagnosis and Treatment of Lyme Disease by Patient Race.

This cross-sectional study compares stages at which Lyme disease was diagnosed by race in a specialty clinic in the US.

Determinants of persistent symptoms after treatment for Lyme borreliosis: a prospective observational cohort study.

BACKGROUND: Patients treated for Lyme borreliosis (LB) frequently report persistent symptoms. Little is known about risk factors and etiology. METHODS: In a prospective observational cohort study with a follow-up of one year, we assessed a range of microbiological, immunological, genetic, clinical, functional, epidemiological, psychosocial and cognitive-behavioral variables as determinants of persistent symptoms after treatment for LB. Between 2015 and 2018 we included 1135 physician-confirmed LB patients at initiation of antibiotic therapy, through clinical LB centers and online self-registration. Two reference cohorts of individuals without LB (n = 4000 and n = 2405) served as a control. Prediction analyses and association studies were used to identify determinants, as collected from online questionnaires (three-monthly) and laboratory tests (twice). FINDINGS: Main predictors of persistent symptoms were baseline poorer physical and social functioning, higher depression and anxiety scores, more negative illness perceptions, comorbidity, as well as fatigue, cognitive impairment, and pain in 295 patients with persistent symptoms. The primary prediction model correctly indicated persistent symptoms in 71.0% of predictions (AUC 0.79). In patients with symptoms at baseline, cognitive-behavioral responses to symptoms predicted symptom persistence. Of various microbiological, immunological and genetic factors, only lower IL-10 concentrations in ex vivo stimulation experiments were associated with persistent symptoms. Clinical LB characteristics did not contribute to the prediction of persistent symptoms. INTERPRETATION: Determinants of persistent symptoms after LB were mainly generic, including baseline functioning, symptoms and cognitive-behavioral responses. A potential role of host immune responses remains to be investigated. FUNDING: Netherlands Organisation for Health Research and Development (ZonMw); the Dutch Ministry of Health, Welfare and Sport (VWS).

Diagnosis and treatment of "chronic Lyme": primum non nocere.

BACKGROUND: Approximately 10% of patients experience prolonged symptoms after Lyme disease. PTLDS (post treatment Lyme disease syndrome) is a controversial topic. It has been described as a source of overdiagnosis and off-label treatment. This review aims to describe the diagnostic errors and adverse events associated with the diagnosis and treatment of PTLDS. METHODS: systematic review of the literature in the Medline and Cochrane Library databases, according to PRISMA criteria, including randomized clinical trials (RCT), observational studies, and case reports addressing diagnostic errors and adverse events published between January 2010 and November 2020 in English or French. Selection used a quadruple reading process on the basis of the titles and abstracts of the different articles, followed by a full reading. RESULTS: 17 studies were included: 1 RCT, 6 observational studies and 10 case reports. In the 6 observational studies, overdiagnosis rates were very high, ranging from 80 to 100%. The new diagnoses were often psychiatric, rheumatological and neurological. Disorders with somatic symptoms were often cited. Diagnostic delays were identified for cancers and frontoparietal dementia. In the RCT and observational studies, prolonged anti-infective treatments were also responsible for adverse events, with emergency room visits and/or hospitalization. The most common adverse events were diarrhea, sometimes with Clostridium difficile colitis, electrolyte abnormalities, sepsis, bacterial and fungal infections, and anaphylactic reactions. CONCLUSION: This review highlights the risks of prolonged anti-infective treatments that have not been proven to be beneficial in PTLDS. It emphasizes the ethical imperative of the "primum non nocere" principle, which underscores the importance of not causing harm to patients. Physicians should exercise caution in diagnosing PTLDS and consider the potential risks associated with off-label treatments.