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Lyme disease is the most common tick-borne illness in the United States, and cases of Lyme disease have nearly doubled since the early 2000s. Symptoms and presentation vary based on severity of illness, with more serious complications of disease consisting of neurologic and cardiac dysfunction. Testing is often unreliable, which can lead to delayed diagnosis and management. A 38-year-old woman presented to the Emergency Department with left-sided facial droop and was subsequently diagnosed with Lyme carditis. This case depicts a classic but unique triad of symptoms caused by Lyme disease: high-degree atrioventricular (AV) blockade, Bell's palsy, and erythema migrans. The patient was promptly treated with empiric i.v. antibiotics pending serology testing for Lyme disease, and her high-degree AV block improved. Initial polymerase chain reaction testing for this patient was negative, but diagnosis was later confirmed with a positive two-tiered test. Intravenous ceftriaxone therapy improved this patient's heart block, allowing for discharge on oral antibiotics. Why Should an Emergency Physician Be Aware of This? It is important to recognize potential cases of Lyme disease early so that appropriate treatment can be initiated. Lyme disease is difficult to diagnose given the wide variety of symptoms and clinical presentations coupled with routine testing that has relatively low sensitivity. Lyme cases have been increasing over the last several years, even in areas in which Lyme disease is not generally endemic. Testing limitations make obtaining a definitive diagnosis difficult, which the emergency physician should be aware of. [ABSTRACT FROM AUTHOR]

We have developed targeted proteomics in the context of Lyme borreliosis (LM) as a new direct diagnostic tool for detecting Borrelia proteins in the skin of patients with erythema migrans. If satisfactory, this proteomic technique could be used in addition to culture and/or PCR for disseminated infections where Borrelia detection is essential to demonstrate active infection. In these infections, the diagnosis is indirect and relies mainly on serology. We recruited 46 patients with LM and 11 controls and collected two skin biopsies from each patient. One biopsy was used for Borrelia burgdorferi sensu lato PCR and culture and the other one was for targeted mass-spectrometry-based proteomics. Six markers of infection were selected for proteomics: Outer surface protein C (OspC), flagellin, enolase, lipoprotein gi|365823350, decorin binding protein A, and glyceraldehyde-3-phosphate dehydrogenase. Culturing Borrelia from the biopsies increased the sensitivity of the methods. Among the patients included for analysis, 61% (28 patients), 61% (28), and 46% (21) were detected as positive by proteomics, PCR, and culture, respectively. PCR and proteomics were complementary. OspC and flagellin were the most frequently detected protein markers of infection by proteomics, which in some patients, detected up to nine peptides for the flagellin. It is possible to identify bacterial makers from the skin by proteomics. Our approach can be used to diagnose tick-borne diseases such as LM. clinicaltrials.gov identifier: NCT02414789. [ABSTRACT FROM AUTHOR]

Simple Summary: Although Lyme Borreliosis is endemic in countries of the Northern Hemisphere, climate change, migratory birds, and the availability of ticks have favored the survival of Borreliae Lyme Group in African countries bordering the Mediterranean Sea and the Indian Ocean. Lyme borreliosis (LB) is more common in the Northern Hemisphere. It is endemic mainly in North America, where the vectors are Ixodes scapularis and Ixodes pacificus, and in Eurasia, where the vectors are Ixodes ricinus and Ixodes persulcatus. Both tick-borne diseases and LB are influenced by climate change. Africa and South America are crossed by the equator and are situated in both the Northern and Southern Hemispheres. In Africa, the LB is present on the Mediterranean and the Indian Ocean coasts. Borrelia lusitaniae is prevalent in countries bordering the Mediterranean Sea, such as Tunisia, Morocco, Algeria, and Egypt. Ticks were detected in the Ixodes Ricinus, which are carried by migratory birds and the Ixodes inopinatus and captured by the Psammodromus algirus lizards. The Borreliae Lyme Group (LG) and, in particular, Borrelia garinii, have been reported in countries bordering the Indian Ocean, such as Kenya, Tanzania, and Mozambique, transported by migratory birds from North African countries, where the vector was identified as Hyalomma rufipes ticks. This review aims to document the presence of Borreliae LG and LB in Africa. [ABSTRACT FROM AUTHOR]

Nataliya Banadyha,1 Igor Rogalskyy,2 Roman Komorovsky3 1Department of Pediatrics, Faculty of Postgraduate Education, Ivan Horbachevsky Ternopil National Medical University, Ternopil, Ukraine; 2Main Administration, State Service of Ukraine for Food Safety and Consumers Protection, Ternopil, Ukraine; 3Department of Internal Medicine II, Ivan Horbachevsky Ternopil National Medical University, Ternopil, UkraineCorrespondence: Roman Komorovsky, Email komorovsky@tdmu.edu.uaAbstract: Herein we report a case of Lyme borreliosis in a pediatric patient, highlighting the diagnostic challenges associated with this condition. An 11-year-old girl was admitted with high fever, headaches, abdominal pain, and a progressing rash. Initial symptoms included small rashes that vanished with antihistamine treatment, but maculopapular rashes later emerged on the trunk and limbs, prompting further investigation. Differential diagnosis included toxic erythema, Stevens-Johnson syndrome, and Lyme borreliosis. Despite no reported tick bite and initial doubt due to the season, Lyme borreliosis was confirmed by serologic testing, diagnosing the patient with early disseminated Lyme disease. The diagnostic complexity was increased by the rash’s atypical presentation – large, homogeneous papular rashes. This case emphasizes the necessity for physicians to adeptly gather detailed histories and employ thorough, up-to-date diagnostic methods. Effective correlation of clinical findings with laboratory results and ongoing patient observation proved critical for an accurate diagnosis. This report underscores the importance of recognizing atypical presentations of Lyme borreliosis in children and the need for careful differential diagnosis.Plain language summary: We report the case of a 11-year-old girl diagnosed with Lyme disease, caused by tick bites that are often painless and hard to detect. This makes diagnosis challenging, especially in children. Her illness began with a small rash that disappeared with treatment. Over a few days, she developed a high fever, headaches, abdominal pain, and extensive rashes on her body.Initially, we considered other conditions like toxic erythema. However, new rashes kept appearing, prompting reconsideration. Despite no known tick bite, Lyme disease was suspected. A blood test confirmed Lyme disease, and she was treated with the antibiotic doxycycline. She improved significantly within 10 days, and no new rashes appeared after 2 weeks.This case highlights the need to consider Lyme disease even without a known tick bite. It underscores the importance of careful observation, detailed patient histories, and thorough testing to accurately diagnose and treat this disease in children.Keywords: erythema migrans, borreliosis, differential diagnosis, ticks

Summary: Background: Lyme disease (LD) is caused by Borrelia burgdorferi and is the most common tickborne disease in the northern hemisphere. Although classical characteristics of LD are well-known, the diagnosis and treatment are often delayed. Laboratory diagnosis by serological testing is recommended for most LD manifestations. The objective of this study was to describe clinical characteristics and associated serological profiles in children with LD. Methods: This retrospective cohort study included children aged 0–18 years, diagnosed with LD according to current guidelines at University Children's Hospital Zurich between January 1, 2006 and December 31, 2020. Two-tier serological testing with the recomWell enzyme-linked immunosorbent assay and recomLine Western blot (MIKROGEN Diagnostik, MIKROGEN GmbH, Neuried, Germany) was performed at the Institute of Medical Microbiology, University of Zurich. Findings: In total, 469 children diagnosed with LD were included (median age, 7.9 years); 190 patients (40.5%) with Lyme neuroborreliosis (LNB), 171 (36.5%) patients with skin manifestations (erythema migrans, n = 121; multiple erythema migrans, n = 11; borrelial lymphocytoma, n = 37; and acrodermatitis chronica atrophicans, n = 2), and 108 (23.0%) patients with Lyme arthritis. We observed seasonal variations for patients with skin manifestations and LNB, with high prevalence in May–October, but not for patients with Lyme arthritis. Significant differences between LD manifestation groups were found for age, inflammatory parameters, and specificity and concentration of B. burgdorferi-specific serum antibody responses. We observed distinct patterns of pronounced serum antibody responses against B. burgdorferi antigens in LNB (IgM against VlsE, p41, and OspC) and Lyme arthritis (IgG against p100, VlsE, p58, p41, p39, and p18). Interpretation: Our study is one of the largest and most detailed for children with LD. We present unique findings regarding the differences in clinical characteristics and immune responses between various manifestations of LD in children. Funding: No specific funding to disclose for this study.

In this multicenter study conducted in France, we challenged the hypothesis of the transmission of pathogens other than Borrelia spp. in 22 patients developing erythema migrans following a tick bite. Using a combination of high-throughput microfluidic PCRs and agnostic metagenomics on skin biopsies and blood samples, no microorganisms other than Borrelia spp. was found.

Information on asplenic Lyme borreliosis (LB) patients with erythema migrans (EM) is lacking. We compared the course and outcome of 26 EM episodes in 24 post-trauma splenectomized patients (median age 51 years) diagnosed at a single clinical center in Slovenia during 1994–2023 with those of 52 age- and sex-matched patients with EM but with no history of splenectomy. All patients were followed for one year. A comparison of pre-treatment characteristics revealed that EM in splenectomized patients was of shorter duration before diagnosis (4 vs. 8 days, p = 0.034) with a smaller EM diameter (10.5 vs. 14 cm, p = 0.046), and more frequently fulfilled criteria for disseminated LB (3/26, 11.5% vs. 0%, p = 0.034). Treatment failure occurred in 5/26 (19.2%) EM episodes in splenectomized patients versus 0/52 in non-splenectomized patients (p = 0.003). The five treatment failure cases were retreated with antibiotic regimens used to treat EM and had complete resolution of all symptoms/signs. In conclusion, our study showed that splenectomized adult patients with EM differ somewhat in presentation and more often have treatment failure compared with non-splenectomized patients with EM. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The primary objective was to analyze the results of serologic testing used in the diagnostics of Lyme disease. Our second goal was to identify bacterial and viral co-infections occurring concurrently with Lyme disease. Furthermore, it was our intention to also analyze the correlation of laboratory testing with the occurrence of erythema migrans (EM). BACKGROUND: The accuracy in diagnostic testing for Lyme disease in the early stages of infection is an important factor necessary for delivering proper treatment to patients. METHODS: A total of 173 individuals with confirmed Lyme disease or with laboratory testing underway participated in the quantitative survey. RESULTS: ELISA was the first test conducted in 51% of the respondents, 28% of whom yielded positive findings of both IgM and IgG antibody classes. The positivity of ELISA test findings was confirmed by Western blot in 100% of results. Negative results of ELISA were consistent with Western blot only in less than half of the patients. More than half of the respondents had not been tested for any bacterial or viral co-infections. The results of serological testing were not consistent with clinical findings in all cases, including those with clinically discernible skin manifestation of erythema migrans. CONCLUSION: The comparison of results obtained by ELISA and Western blot revealed significant discrepancies. Simultaneous infections by vectors with several pathogens were detected (Tab. 3, Fig. 2, Ref. 15). Text in PDF www.elis.sk [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To describe the course of symptoms reported by patients with symptoms attributed to Lyme borreliosis (LB) without being subsequently diagnosed with LB. Methods: We performed a prospective cohort study with patients presenting at the outpatient clinic of two clinical LB centres. The primary outcome was the prevalence of persistent symptoms, which were defined as clinically relevant fatigue (CIS, subscale fatigue), pain (SF-36, subscale bodily pain), and cognitive impairment (CFQ) for ≥ 6 months and onset < 6 months over the first year of follow-up. Outcomes were compared with a longitudinal cohort of confirmed LB patients and a general population cohort. Prevalences were standardised to the distribution of pre-defined confounders in the confirmed LB cohort. Results: Participants (n = 123) reported mostly fatigue, arthralgia, myalgia, and paraesthesia as symptoms. The primary outcome could be determined for 74.8% (92/123) of participants. The standardised prevalence of persistent symptoms in our participants was 58.6%, which was higher than in patients with confirmed LB at baseline (27.2%, p < 0.0001) and the population cohort (21.2%, p < 0.0001). Participants reported overall improvement of fatigue (p < 0.0001) and pain (p < 0.0001) but not for cognitive impairment (p = 0.062) during the follow-up, though symptom severity at the end of follow-up remained greater compared to confirmed LB patients (various comparisons p < 0.05). Conclusion: Patients with symptoms attributed to LB who present at clinical LB centres without physician-confirmed LB more often report persistent symptoms and report more severe symptoms compared to confirmed LB patients and a population cohort. [ABSTRACT FROM AUTHOR]

Lyme borreliosis is a public health concern in India. The prevalence of the disease is still undetermined with major entomological and epidemiological gaps. The present study was conducted to determine the seropositivity of Borrelia burgdorferi in Sikkim and Arunachal Pradesh, India. A cross-sectional serosurvey was conducted in Sikkim and Arunachal Pradesh. Data collection tools were developed and standardized for the collection of clinico-socio-demographic data. Sample size for each site was calculated using the formula for the estimation of a single proportion. Qualitative detection of IgG antibodies in serum samples was done using NovaLisa™ Lyme Borrelia IgG ELISA kit. A total of 793 participants were enrolled, 484 (61%) from Arunachal Pradesh and 309 (39%) from Sikkim. Out of 793 participants, 21 (2.7%), 22 (2.8%), 6 (0.8%), 29 (3.7%), 44 (5.5%), and 16 (2.1%) gave history of tick bite, rash, erythema migrans , migratory muscle pain, migratory joint pain, and numbness, respectively, in the past one year. The adjusted seroprevalence (for sensitivity and specificity of kit) for the study is 3.7 (2.4–5.2). No signs or symptoms were found to be associated with IgG ELISA positivity. The state-wise distribution of seropositivity for Arunachal Pradesh and Sikkim was 4.1 (95% CI: 2.5–6.3) and 2.3 (95% CI: 0.9–4.6), respectively. This study establishes the state of Sikkim as a new endemic area in India of Lyme disease besides its already reported endemicity in Arunachal Pradesh. No association was conclusively established between symptoms of Lyme and IgG seropositivity emphasizing the need for detailed history taking and clinical suspicion in endemic areas. [ABSTRACT FROM AUTHOR]

Lyme borreliosis (LB) is more common in the Northern Hemisphere. It is endemic mainly in North America, where the vectors are Ixodes scapularis and Ixodes pacificus, and in Eurasia, where the vectors are Ixodes ricinus and Ixodes persulcatus. Both tick-borne diseases and LB are influenced by climate change. Africa and South America are crossed by the equator and are situated in both the Northern and Southern Hemispheres. In Africa, the LB is present on the Mediterranean and the Indian Ocean coasts. Borrelia lusitaniae is prevalent in countries bordering the Mediterranean Sea, such as Tunisia, Morocco, Algeria, and Egypt. Ticks were detected in the Ixodes Ricinus, which are carried by migratory birds and the Ixodes inopinatus and captured by the Psammodromus algirus lizards. The Borreliae Lyme Group (LG) and, in particular, Borrelia garinii, have been reported in countries bordering the Indian Ocean, such as Kenya, Tanzania, and Mozambique, transported by migratory birds from North African countries, where the vector was identified as Hyalomma rufipes ticks. This review aims to document the presence of Borreliae LG and LB in Africa.

Cutaneous lupus erythematosus (CLE) can present with a wide variety of dermatologic manifestations and is broken down into acute, subacute, and chronic subtypes. Tumid lupus, a variant of CLE, is rarely associated with systemic lupus erythematosus. Lesions of CLE and tumid lupus can mimic multiple other dermatologic conditions. We present a case of a patient with tumid lupus who was initially treated for erythema migrans and systemic symptoms suspected to represent Lyme disease. This article is intended for nurse practitioners, nurses, and other clinicians practicing in dermatology, primary care, urgent care, and emergency medicine settings in the care of patients presenting with annular skin lesions. [ABSTRACT FROM AUTHOR]

Tracing the profile of pediatric Lyme borreliosis (LB) in Europe is difficult due to the interregional variation in its incidence and lack in notifications. Moreover, the identification of LB can be challenging. This study is an 18-year case series of 130 children and adolescents aged under 18 years referred to the Pediatric Infectious Diseases Unit at L. Sacco Hospital, Milan, with suspicion of LB, between January 2005 and July 2023. The routine serological workup consisted of a two-step process: an initial screening test followed by Western blot (WB). Forty-four (34%) patients were diagnosed with LB. The median age was six years, and 45% were females. Of the children with erythema migrans (EM), 33 (57%) were confirmed as having true EM, and, of these, 4 (12%) were atypical. Ten (23%) patients had early disseminated/late diseases, including facial nerve palsy (n = 3), early neuroborreliosis (n = 1), arthritis (n = 3), relapsing fever (n = 2), and borrelial lymphocytoma (n = 1). No asymptomatic infections were documented. Over seventy percent of confirmed LB cases (n = 31/44) recalled a history of tick bites; in this latter group, 19 (61%) were from the area of the Po River valley in Lombardy. Almost half of the children evaluated for LB complained of non-specific symptoms (fatigue, musculoskeletal pain, skin lesions/rash, and persistent headache), but these symptoms were observed in only two patients with confirmed LB. Most LB cases in our study were associated with EM; two-tier testing specificity was high, but we found frequent non-adherence to international recommendations with regard to the timing of serology, application of the two-step algorithm, and antibiotic over-prescription. Most children were initially assessed for a tick bite or a skin lesion suggestive of EM by a family pediatrician, highlighting the importance of improving awareness and knowledge around LB management at the primary healthcare level. Finally, the strengthening of LB surveillance at the national and European levels is necessary. [ABSTRACT FROM AUTHOR]

In prior studies, the skin lesion erythema migrans (EM) was present for a longer time period before diagnosis of concomitant borrelial meningoradiculoneuritis (Bannwarth's syndrome) compared to EM patients without neurologic symptoms. To determine if this observation pertains to other manifestations of Lyme neuroborreliosis (LNB), we compared EM characteristics in patients with borrelial meningoradiculoneuritis (n = 122) to those with aseptic meningitis without radicular pain (n = 72 patients), and to patients with EM but without neurologic involvement (n = 12,384). We also assessed factors that might impact duration. We found that the duration of EM at diagnosis in patients with borrelial meningoradiculoneuritis was not significantly different compared with those with LNB without radicular pain (34 vs. 26 days; p = 0.227). The duration of EM for each of these clinical presentations of LNB, however, was significantly longer than in patients with EM without LNB (10 days; p < 0.001). Contributing factors to this difference might have been that patients with LNB failed to recognize that they had EM or were unaware of the importance of not delaying antibiotic treatment for EM. In conclusion, the duration of the EM skin lesion in EM patients with LNB is longer than in patients with just EM, irrespective of the type of LNB. [ABSTRACT FROM AUTHOR]

We describe a rare case of early Lyme borreliosis in France caused by Borrelia spielmanii, which manifested as a large erythema chronicum migrans rash. The patient completely recovered after a 15-day course of amoxicillin. Absence of pathognomonic signs prevented distinguishing B. spielmanii from other etiologies as cause in this case-patient.

The early diagnosis of Lyme disease is more difficult to suspect in non-endemic areas such as Southern Italy. Erythema migrans, which constitutes its primary manifestation, is not always typical and, even when it is typical, i.e. when it has the classic annular shape with central resolution, it can be confused with non-infectious lesions due to hypersensitivity to arthropods. An atypical case with secondary lymphangitis in a 7-year-old girl of the Southern Italy was described. [ABSTRACT FROM AUTHOR]

Erythema migrans (EM) is the initial and the most frequent clinical manifestation of Lyme borreliosis (LB). Herein, we report on the capacity of culture and serology for the demonstration of Borrelia infection in a cohort of 292 patients diagnosed with typical EM at a single medical center. The median duration of EM at diagnosis was 12 days, and the largest diameter was 16 cm; 252 (86.3%) patients presented with solitary EM, whereas 40 (13.7%) had multiple EM. A total of 95/292 (32.5%) patients had positive IgM, and 169 (57.9%) had positive IgG serum antibodies; the Borrelia isolation rate was 182/292 (62.3%). The most frequent species by far was B. afzelii (142/148, 95.9%) while B. garinii (2.7%) and B. burgdorferi s.s. (1.4%) were rare. IgM seropositivity was associated with a younger age, multiple EM and the absence of underlying chronic illness; IgG seropositivity was associated with the duration of EM at diagnosis, the diameter of the EM, having had a previous episode of LB and the absence of symptoms at the site of the EM. Furthermore, the Borrelia isolation rate was statistically significantly lower in patients with positive Borrelia IgM antibodies. Although microbiologic analyses are not needed for the diagnosis of typical EM, they enable insights into the etiology and dynamics of the immune response in the course of early LB. [ABSTRACT FROM AUTHOR]

Automatic classification of Lyme disease rashes on the skin helps clinicians and dermatologists' probe and investigate Lyme skin rashes effectively. This paper proposes a new in‐depth features fusion system to classify Lyme disease rashes. The proposed method consists of two main steps. First, three different deep learning models, Densenet201, InceptionV3, and Exception, were trained independently to extract the deep features from the erythema migrans (EM) images. Second, a deep feature fusion mechanism (meta classifier) is developed to integrate the deep features before the final classification output layer. The meta classifier is a basic deep convolutional neural network trained on original images and features extracted from base level three deep learning models. In the feature fusion mechanism, the last three layers of base models are dropped out and connected to the meta classifier. The proposed deep feature fusion method significantly improved the classification process, where the classification accuracy was 98.97%, which is particularly impressive than the other state‐of‐the‐art models. [ABSTRACT FROM AUTHOR]

Information on asplenic Lyme borreliosis (LB) patients with erythema migrans (EM) is lacking. We compared the course and outcome of 26 EM episodes in 24 post-trauma splenectomized patients (median age 51 years) diagnosed at a single clinical center in Slovenia during 1994–2023 with those of 52 age- and sex-matched patients with EM but with no history of splenectomy. All patients were followed for one year. A comparison of pre-treatment characteristics revealed that EM in splenectomized patients was of shorter duration before diagnosis (4 vs. 8 days, p = 0.034) with a smaller EM diameter (10.5 vs. 14 cm, p = 0.046), and more frequently fulfilled criteria for disseminated LB (3/26, 11.5% vs. 0%, p = 0.034). Treatment failure occurred in 5/26 (19.2%) EM episodes in splenectomized patients versus 0/52 in non-splenectomized patients (p = 0.003). The five treatment failure cases were retreated with antibiotic regimens used to treat EM and had complete resolution of all symptoms/signs. In conclusion, our study showed that splenectomized adult patients with EM differ somewhat in presentation and more often have treatment failure compared with non-splenectomized patients with EM.

Lyme disease, a tick-borne multisystem disease, is caused by spirochete Borrelia burgdorferi (sensu lato). It is a common illness in temperate countries, especially the United States, but the incidence is increasing across continents due to increasing reforestation, travel and adventure tourism, increased intrusion in the vector habitat, and changing habitat of the vector. Transmission primarily occurs via bite of an infected tick (Ixodes spp.). The appearance of an erythema migrans rash following a tick bite is diagnostic of early Lyme disease even without laboratory evidence. Borrelia lymphocytoma and acrodermatitis chronica atrophicans along with multisystem involvement occur in late disseminated and chronic stages. A two-step serologic testing protocol using an enzyme-linked immunosorbent assay (ELISA) followed by confirmation of positive and equivocal results by Western immunoblot is recommended for the diagnosis. Transplacental transmission to infant occurs in the first trimester with possible congenital Lyme disease making treatment imperative during antenatal period. The treatment is most effective in the early stages of the disease, whereas rheumatological, neurological, or other late manifestations remain difficult to treat with antibiotics alone. Treatment with oral doxycycline is preferred for its additional activity against other tick-borne illnesses which may occur concurrently in 10%--15% of cases. New-generation cephalosporins and azithromycin are alternative options in patients with doxycycline contraindications. No vaccine is available and one episode of the disease will not confer life-long immunity; thus, preventive measures remain a priority. The concept of post--Lyme disease syndrome versus chronic Lyme disease remains contested for want of robust evidence favoring benefits of prolonged antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background. It is difficult to confirm the diagnosis of the mixed infection of the erythema migrans form of Lyme borreliosis and tick-borne encephalitis at the onset of the disease because of delayed seroconversion. Purpose. Assessment of hemogram predictors to develop a model for early diagnosis of the mixed infection of the erythema form of Lyme borreliosis and tick-borne encephalitis. Materials and methods. The study involved 21 patients with the mixed infection of the erythema form of Lyme borreliosis and tick-borne encephalitis (Group 1) and 25 patients with the erythema form of borreliosis monoinfection (Group 2), who were hospitalized no later than the 7th day of the disease. The hemogram parameters, the leukocyte intoxication index and the body resistance index were analyzed. ROC analysis was used. The logistic regression model was developed using STATISTICA 12.0 modules. Results. The Group 1 patients compared with Group 2 demonstrated significant increases in the levels of the leukocyte intoxication index, and neutrophils, but decreases in the levels of the body resistance index, eosinophils, basophils and platelets. The leukocyte intoxication index was a “very good” predictor of the mixed infection, and the body resistance index, the number of eosinophils, basophils, neutrophils and platelets in peripheral blood had a “good” predictive values. The model included the body resistance index, the number of eosinophils and basophils. Conclusion. The developed model had a “very good” predictive value for the mixed infection early diagnosis of the erythema migrans form of Lyme borreliosis and tick-borne encephalitis.

Lyme disease, a tick-borne multisystem disease, is caused by spirochete Borrelia burgdorferi (sensu lato). It is a common illness in temperate countries, especially the United States, but the incidence is increasing across continents due to increasing reforestation, travel and adventure tourism, increased intrusion in the vector habitat, and changing habitat of the vector. Transmission primarily occurs via bite of an infected tick (Ixodes spp.). The appearance of an erythema migrans rash following a tick bite is diagnostic of early Lyme disease even without laboratory evidence. Borrelia lymphocytoma and acrodermatitis chronica atrophicans along with multisystem involvement occur in late disseminated and chronic stages. A two-step serologic testing protocol using an enzyme-linked immunosorbent assay (ELISA) followed by confirmation of positive and equivocal results by Western immunoblot is recommended for the diagnosis. Transplacental transmission to infant occurs in the first trimester with possible congenital Lyme disease making treatment imperative during antenatal period. The treatment is most effective in the early stages of the disease, whereas rheumatological, neurological, or other late manifestations remain difficult to treat with antibiotics alone. Treatment with oral doxycycline is preferred for its additional activity against other tick-borne illnesses which may occur concurrently in 10%–15% of cases. New-generation cephalosporins and azithromycin are alternative options in patients with doxycycline contraindications. No vaccine is available and one episode of the disease will not confer life-long immunity; thus, preventive measures remain a priority. The concept of post–Lyme disease syndrome versus chronic Lyme disease remains contested for want of robust evidence favoring benefits of prolonged antibiotic therapy.

Abstract Background Lyme borreliosis (LB) is the most common tick-borne disease in Europe and North America, yet its economic burden remains largely unknown. This study aimed to estimate the economic cost associated with the different clinical manifestations of LB in Belgium. Methods An incidence approach and societal perspective were used to estimate the total cost-of-illness for LB in Belgium. Costs were calculated for patients with erythema migrans (EM) or disseminated/late LB, including patients who developed post-treatment Lyme disease syndrome (PTLDS). Direct medical, direct non-medical (transportation & paid help) and indirect non-medical costs (productivity losses) were included in the analysis. Ambulatory cost data were collected through a prospective cohort study from June 2016 to March 2020, in which patients with LB were followed up 6 to 12 months after diagnosis. Hospitalization costs were retrieved from the Minimal Clinical Data registry, a mandatory registry for all Belgian hospitals, linked to the Minimal Financial Data registry. Costs were expressed in 2019 euros. Results The total annual cost associated with clinical manifestations of LB in Belgium was estimated at €5.59 million (95% UI 3.82–7.98). Of these, €3.44 million (95% UI 2.05–5.48) or 62% was related to disseminated/late LB diagnoses and €2.15 million (95% UI 1.30–3.26) to EM. In general, direct medical costs and productivity losses accounted for 49.8% and 46.4% of the total costs, respectively, while direct non-medical costs accounted for only 3.8%. The estimated mean costs were €193 per EM patient and €5,148 per disseminated/late LB patient. While patients with PTLDS seemed to have somewhat higher costs compared to patients without PTLDS, the number of patients was too small to have representative estimates. Conclusions We estimate the total annual direct medical costs, direct non-medical and indirect non-medical costs associated with LB to exceed €5.5 million per year, almost evenly distributed between EM (40%) and disseminated/late LB (60%). EM costs 26 times less per patient but occurs also 16 times more frequently than disseminated/late LB. The cost burden remains limited by comparison to other infectious diseases due to the relative lower incidence.

Lyme borreliosis (LB) is the most common vector-borne zoonotic inflammatory disease in the Northern Hemisphere. In Italy, the first case was diagnosed in 1985 in a woman in Liguria, while the second, in 1986 in Friuli-Venezia Giulia, documenting the infection in northern Italy. Both diagnoses were confirmed by serological assessment by an indirect immunofluorescence (IFI) technique. Borrelia cultivation from both Ixodes ricinus ticks and human lesions in Trieste (Friuli-Venezia Giulia) identified Borrelia afzelii as the prevalent genospecies; nevertheless, Borrelia garinii, Borrelia burgdorferi (sensu stricto), and Borrelia valaisiana (VS116 Group) were also detected, although less frequently. LB was also documented in other Italian regions: in Tuscany (1991), Trentino-Alto Adige (1995-1996), Emilia-Romagna (1998), Abruzzo (1998), and more recently, Lombardy. Nevertheless, data on LB in other Italian regions, especially in southern Italy and islands, are poor. The aim of this study is to document the spread of LB in Italy through the collection of data from LB patients in eight Italian hospitals located in different Italian regions. Diagnostic criteria for LB diagnosis are as follows: i) the presence of erythema migrans (EM) or ii) a clinical picture suggestive of LB, confirmed by serological tests and/or PCR positivity for Borrelia detection. In addition, data also included the place of residence (town and region) and the place where patients became infected. During the observation period, 1,260 cases were gathered from the participating centers. Although different in extent from northern Italy to central/southern Italy, this study shows that LB is widespread throughout Italy. [ABSTRACT FROM AUTHOR]

Annular dermatoses are a heterogeneous and extremely diverse group of skin diseases, which share in common annular, ring-like patterns with centrifugal spreading. Numerous skin diseases can sometimes display annular lesions, but some specific skin conditions are originally annular. We take the opportunity to review here mainly the causes of primary annular erythemas and their differential diagnoses, but also the rare causes of annular purpuras. [ABSTRACT FROM AUTHOR]

In prior studies, the skin lesion erythema migrans (EM) was present for a longer time period before diagnosis of concomitant borrelial meningoradiculoneuritis (Bannwarth’s syndrome) compared to EM patients without neurologic symptoms. To determine if this observation pertains to other manifestations of Lyme neuroborreliosis (LNB), we compared EM characteristics in patients with borrelial meningoradiculoneuritis (n = 122) to those with aseptic meningitis without radicular pain (n = 72 patients), and to patients with EM but without neurologic involvement (n = 12,384). We also assessed factors that might impact duration. We found that the duration of EM at diagnosis in patients with borrelial meningoradiculoneuritis was not significantly different compared with those with LNB without radicular pain (34 vs. 26 days; p = 0.227). The duration of EM for each of these clinical presentations of LNB, however, was significantly longer than in patients with EM without LNB (10 days; p < 0.001). Contributing factors to this difference might have been that patients with LNB failed to recognize that they had EM or were unaware of the importance of not delaying antibiotic treatment for EM. In conclusion, the duration of the EM skin lesion in EM patients with LNB is longer than in patients with just EM, irrespective of the type of LNB.

Tracing the profile of pediatric Lyme borreliosis (LB) in Europe is difficult due to the interregional variation in its incidence and lack in notifications. Moreover, the identification of LB can be challenging. This study is an 18-year case series of 130 children and adolescents aged under 18 years referred to the Pediatric Infectious Diseases Unit at L. Sacco Hospital, Milan, with suspicion of LB, between January 2005 and July 2023. The routine serological workup consisted of a two-step process: an initial screening test followed by Western blot (WB). Forty-four (34%) patients were diagnosed with LB. The median age was six years, and 45% were females. Of the children with erythema migrans (EM), 33 (57%) were confirmed as having true EM, and, of these, 4 (12%) were atypical. Ten (23%) patients had early disseminated/late diseases, including facial nerve palsy (n = 3), early neuroborreliosis (n = 1), arthritis (n = 3), relapsing fever (n = 2), and borrelial lymphocytoma (n = 1). No asymptomatic infections were documented. Over seventy percent of confirmed LB cases (n = 31/44) recalled a history of tick bites; in this latter group, 19 (61%) were from the area of the Po River valley in Lombardy. Almost half of the children evaluated for LB complained of non-specific symptoms (fatigue, musculoskeletal pain, skin lesions/rash, and persistent headache), but these symptoms were observed in only two patients with confirmed LB. Most LB cases in our study were associated with EM; two-tier testing specificity was high, but we found frequent non-adherence to international recommendations with regard to the timing of serology, application of the two-step algorithm, and antibiotic over-prescription. Most children were initially assessed for a tick bite or a skin lesion suggestive of EM by a family pediatrician, highlighting the importance of improving awareness and knowledge around LB management at the primary healthcare level. Finally, the strengthening of LB surveillance at the national and European levels is necessary.

Annular erythema as a clinical manifestation of locoregional recurrence of breast cancer is extremely rare. Only three papers with the description of five cases have been published in the current literature to our knowledge. Herein, we describe two additional cases of annular erythema as a cutaneous sign of recurrent ductal breast carcinoma; both were misdiagnosed as erythema chronicum migrans.

Abstract Background Patients with Lyme borreliosis (LB) may report persisting non-specific symptoms such as fatigue, widespread musculoskeletal pain or cognitive difficulties. When present for more than 6 months and causing a reduction in daily activities, this is often referred to as post-treatment Lyme disease syndrome (PTLDS). This study aimed to compare the occurrence of symptoms between LB patients and controls, to estimate the proportion of LB patients developing PTLDS and to identify risk factors. Methods A prospective cohort study was set up including three subpopulations: patients with an erythema migrans (EM) (i) or disseminated/late LB (ii) and a non-LB control group (iii). At 6- and 12-months follow-up, the occurrence of several symptoms, including six symptoms used to define PTLDS, i.e. muscle pain, joint pain, fatigue, memory problems, difficulties concentrating and problems finding words, and impact on daily activities, was compared between LB patients and controls. Finally, the proportion of LB patients developing PTLDS as defined by the Infectious Disease Society of America was estimated, including a time frame for symptoms to be present. Results Although the risk of presenting PTLDS-related symptoms was significantly higher in EM patients (n = 120) compared to controls (n = 128) at 6 months follow-up, the risk of presenting at least one of these symptoms combined with impact on daily activities was not significantly higher in EM patients, at either 6- or 12-months follow-up. A significant association was found between disseminated/late LB (n = 15) and the occurrence of any PTLDS-symptom with an impact on daily activities at both time points. The proportion of patients with PTLDS was estimated at 5.9% (95% CI 2.7–12.9) in EM patients and 20.9% (95% CI 6.8–64.4) in patients with disseminated/late LB (RR = 3.53, 95% CI 0.98–12.68, p = 0.053). No significant risk factors were identified, which may be explained by small sample sizes. Conclusions In our study, PTLDS was present in both LB cohorts, yet with a higher percentage in disseminated/late LB patients. Additional research is needed into risk factors for and causes of this syndrome. In addition, development and validation of standardized methods to assess the PTLDS case definition, easily applicable in practice, is of great importance.

Lyme borreliosis (LB) is the most common vector-borne zoonotic inflammatory disease in the Northern Hemisphere. In Italy, the first case was diagnosed in 1985 in a woman in Liguria, while the second, in 1986 in Friuli-Venezia Giulia, documenting the infection in northern Italy. Both diagnoses were confirmed by serological assessment by an indirect immunofluorescence (IFI) technique. Borrelia cultivation from both Ixodes ricinus ticks and human lesions in Trieste (Friuli-Venezia Giulia) identified Borrelia afzelii as the prevalent genospecies; nevertheless, Borrelia garinii, Borrelia burgdorferi (sensu stricto), and Borrelia valaisiana (VS116 Group) were also detected, although less frequently. LB was also documented in other Italian regions: in Tuscany (1991), Trentino–Alto Adige (1995–1996), Emilia-Romagna (1998), Abruzzo (1998), and more recently, Lombardy. Nevertheless, data on LB in other Italian regions, especially in southern Italy and islands, are poor. The aim of this study is to document the spread of LB in Italy through the collection of data from LB patients in eight Italian hospitals located in different Italian regions. Diagnostic criteria for LB diagnosis are as follows: i) the presence of erythema migrans (EM) or ii) a clinical picture suggestive of LB, confirmed by serological tests and/or PCR positivity for Borrelia detection. In addition, data also included the place of residence (town and region) and the place where patients became infected. During the observation period, 1,260 cases were gathered from the participating centers. Although different in extent from northern Italy to central/southern Italy, this study shows that LB is widespread throughout Italy.

Background: There is a need for updated incidence rates (IRs) of Lyme borreliosis (LB) in Europe, including the Netherlands. We estimated LB IRs stratified by geographic area, year, age, sex, immunocompromised status, and socioeconomic status (SES). Methods: All subjects registered in the PHARMO General Practitioner (GP) Database without prior diagnosis of LB or disseminated LB and having ≥1 year of continuous database enrolment were included. IRs and corresponding confidence intervals (CIs) of GP-recorded LB, erythema migrans (EM), and disseminated LB were estimated during the period 2015‒2019. Results: We identified 14,794 events (suspected, probable, or confirmed) with a diagnostic code for LB that included 8219 with a recorded clinical manifestation: 7985 (97%) with EM and 234 (3%) with disseminated LB. National annual LB IRs were relatively consistent, ranging from 111 (95% CI 106‒115) in 2019 to 131 (95% CI 126‒136) in 2018 per 100,000 person-years. Incidence of LB showed a bimodal age distribution, with peak IRs observed among subjects aged 5‒14 and 60‒69 years in men and women. Higher LB incidence was found in subjects who were residents of the provinces of Drenthe and Overijssel, immunocompromised, or of lower SES. Similar patterns were observed for EM and disseminated LB. Conclusions: Our findings confirm that LB incidence remains substantial throughout the Netherlands with no indication of decline in the past 5 years. Foci in two provinces and among vulnerable populations suggest potential initial target groups for preventive strategies such as vaccination. [ABSTRACT FROM AUTHOR]

Introduction: Lyme borreliosis (LB) is a growing public health concern requiring accurate and comprehensive epidemiological knowledge to inform health care interventions. This study compared the epidemiology of LB in primary care and hospital settings, using for the first time in France three sources of data, and highlighted specific populations at higher risk of developing LB. Methods: This study analyzed data from general practitioner networks (i.e., Sentinel network, Electronic Medical Records [EMR]) and the national hospital discharge database to describe the LB epidemiology from 2010 to 2019. Results: The average annual incidence rates of LB in primary care increased from 42.3 cases/100,000 population in 2010–2012 to 83.0/100,000 in 2017–2019 for the Sentinel Network and 42.7/100,000 to 74.6/100,000 for the EMR, following a marked rise in 2016. The annual hospitalization rate remained stable from 2012 to 2019 fluctuating between 1.6 and 1.8 hospitalizations/100,000. Women were more likely to present with LB in primary care setting compared with men (male-to-female incidence rate ratio [IRR] = 0.92), whereas men were predominant among hospitalizations (IRR = 1.4), with the largest discordance among adolescents aged 10–14 years (IRR = 1.8) and adults aged 80 years and older (IRR = 2.5). In 2017–2019, the average annual incidence rate peaked among persons aged 60–69 years in primary care (>125/100,000) and aged 70–79 years among hospitalized patients (3.4/100,000). A second peak occurred in children aged 0–4 or 5–9 years depending on sources. Incidence rates in Limousin and the north-eastern regions were the highest for both primary care and hospital settings. Conclusions: Analyses showed disparities in the evolution of incidence, sex-specific incidence rates, and predominant age groups between primary care and hospital settings that merit further exploration. [ABSTRACT FROM AUTHOR]

Erythema migrans (EM) is the initial and the most frequent clinical manifestation of Lyme borreliosis (LB). Herein, we report on the capacity of culture and serology for the demonstration of Borrelia infection in a cohort of 292 patients diagnosed with typical EM at a single medical center. The median duration of EM at diagnosis was 12 days, and the largest diameter was 16 cm; 252 (86.3%) patients presented with solitary EM, whereas 40 (13.7%) had multiple EM. A total of 95/292 (32.5%) patients had positive IgM, and 169 (57.9%) had positive IgG serum antibodies; the Borrelia isolation rate was 182/292 (62.3%). The most frequent species by far was B. afzelii (142/148, 95.9%) while B. garinii (2.7%) and B. burgdorferi s.s. (1.4%) were rare. IgM seropositivity was associated with a younger age, multiple EM and the absence of underlying chronic illness; IgG seropositivity was associated with the duration of EM at diagnosis, the diameter of the EM, having had a previous episode of LB and the absence of symptoms at the site of the EM. Furthermore, the Borrelia isolation rate was statistically significantly lower in patients with positive Borrelia IgM antibodies. Although microbiologic analyses are not needed for the diagnosis of typical EM, they enable insights into the etiology and dynamics of the immune response in the course of early LB.

The occurrence of skin lesions is the earliest symptom of Lyme disease, and the diagnosis of these lesions and appropriate treatment may prevent complications of the disease, which are mainly neurological. The cutaneous presentation in borreliosis is heterogeneous. There are typical lesions that constitute the basis for the diagnosis of Lyme disease, and atypical ones, which cause significant diagnostic difficulties especially when the patient does not remember the tick bite. This study aims to describe the heterogeneous skin symptoms of Lyme borreliosis, as well as offer a practical approach for the recognition of the disease. Based on pediatric cases from clinical practice, rare cutaneous presentations of Lyme disease at various stages of illness and therapy are presented. Diagnostic recommendations for recognizing individual forms are discussed. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to assess the changing incidence of Lyme borreliosis (LB) in a children’s group in Wielkopolska, and the influences of gender and age as well as erythema migrans (EM) occurrence on the development of various forms of LB in children. Material and methods: Retrospective analysis covered the medical records of 206 children diagnosed with LB, hospitalised in the Department of Infectious Diseases and Child Neurology in Poznań and consulted at its Clinic of Infectious Diseases from 1 January 2012 to 30 October 2021. For an epidemiological analysis, the study population was limited to patients from Wielkopolska. A total of 196 qualified subjects were divided into 2 time periods, the first covering the years 2012–2016, in which LB was confirmed in 52 children, and the second covering 2017–2021, in which the disease was diagnosed in 144 children. The relationship between the course of LB and the gender and age of the patients was analysed in both groups. Statistical analysis of the data was performed, and the results were compared with published data. Results: The epidemiological analysis showed a more than a twofold increase in the number of LB cases in the analysed time periods, mainly diagnosed as EM. The high incidence of LB neurological complications in children, including those with incorrectly diagnosed EM, remains constant. There was no relationship between the clinical forms of the disease and the child’s sex, but an increase in the number of EM diagnoses in younger children was confirmed. Conclusions: The study confirmed the increase in the number of LB diagnoses, analogous to the entire population of the region. The significant increase in the number of early stages of the disease and the frequent occurrence of neurological complications in children with undiagnosed and untreated EM indicate the need for ongoing education in the diagnosis of LB. [ABSTRACT FROM AUTHOR]