Cutaneous borreliosis in children - a challenging problem.

Borreliosis, also known as Lyme disease, is a vector-borne disease caused by different species of the Borrelia burgdorferi complex. It is frequent in Europe and Northern America. The major vectors are ixodoid ticks. Paediatric borreliosis is common and peaks in children between five to nine years. In Europe, the leading symptom of early infection is erythema migrans, in contrast to Northern America where arthritis is the dominating clinical finding. In this review, we focus on Europe, where cutaneous borreliosis is mainly caused by infection with B. afzelii. The cutaneous symptoms include erythema migrans, lymphocytoma, chronic atrophic dermatitis and juxta-articular nodules. In children, lymphocytoma is very common but chronic atrophic dermatitis is rare. Clinical symptoms, diagnosis, peculiarities of childhood disease and treatment are also reviewed. It is important to note that after haematogeneic spread, signs of infection may be non-specific, and this is a challenge for diagnosis.

[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.

Cranial nerve involvement, visual complications and headache syndromes in Lyme disease.

PURPOSE OF REVIEW: To provide a summary of the visual manifestations and cranial neuropathies seen in Lyme disease. RECENT FINDINGS: Lyme facial palsy remains the most common manifestation of Lyme neuroborreliosis. Recent investigations show likely evidence of vagal involvement in Lyme disease. SUMMARY: The literature on Lyme neuroborreliosis continues to evolve. Lyme disease can affect nearly any cranial nerve in addition to causing various headache syndromes. The most common manifestation is Lyme disease facial palsy, occurring in up to 5-10% of patients with documented Lyme disease. Headache syndromes are common in the context of facial palsy but can occur in isolation, and more specific headache syndromes including trigeminal and geniculate neuralgias can occur rarely. Signs and symptoms indicative of vestibulocochlear nerve involvement are relatively common, although it could be that these represent other vestibular involvement rather than a specific cranial neuropathy. Optic neuritis is a controversial entity within Lyme disease and is likely overdiagnosed, but convincing cases do exist. Physicians who see any cranial neuropathy, including optic neuritis, in an endemic area can consider Lyme disease as a possible cause.

The Great Imitator: A Case of Lyme Carditis Mimicking ST Elevation Myocardial Infarction.

Lyme disease, caused by Borrelia burgdorferi and transmitted via Ixodes ticks, is a common vector-borne illness in the United States, with an estimated 476,000 annual cases. While primarily known for its neurological and rheumatological manifestations, Lyme disease can also involve the cardiac system, known as Lyme carditis, which occurs in about 4% to 10% of cases. This case report details a rare instance of Lyme carditis presenting as ST-segment elevation myocardial infarction (STEMI) in a 31-year-old female with no significant medical history. The patient exhibited symptoms of chest pressure and shortness of breath, with laboratory results showing significantly elevated troponin levels and other indicative markers. Notably, cardiac catheterization revealed no coronary occlusion, suggesting an alternative diagnosis to acute coronary syndrome (ACS). Further testing confirmed Lyme carditis through positive serological tests for Lyme-specific IgM antibodies. The case underscores the importance of considering Lyme myopericarditis in differential diagnoses for STEMI in Lyme-endemic areas and in patients without typical risk factors for coronary artery disease. This report aims to increase clinical awareness of this condition, highlighting the need for thorough investigation in atypical cardiac presentations.

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.

Animal models of Lyme carditis. Understanding how to study a complex disease.

Lyme carditis, a well-established manifestation of Lyme disease, has been studied in animal models to improve understanding of its pathogenesis. This review synthesizes existing literature on these models and associated disease mechanisms. Searches in MEDLINE, Embase, BIOSIS, and Web of Science yielded 53 articles (47 mice models and 6 other animal models). Key findings include: 1) Onset of carditis correlates with spirochete localization in the heart; 2) Carditis occurs within 10 days of infection, progressing to peak inflammation within 30 days; 3) Infiltrates were predominantly composed of Mac-1+ macrophages and were associated with increases in TNF-α, IL-1 and IL-12 cytokines; 4) Resolution of inflammation was primarily mediated by lymphocytes; 5) Immune system is a double-edged sword: it can play a role in the progression and severity of carditis, but can also have a protective effect. Animal models offer valuable insights into the evolution and pathophysiologic mechanisms of Lyme carditis.

Sleep fragmentation disrupts Lyme arthritis resolution in mice.

STUDY OBJECTIVES: Lyme arthritis is a common late-stage complication of infection by Borrelia burgdorferi, the agent of Lyme disease. Patients with Lyme arthritis report increased levels of sleep disturbance associated with pain. Using a mouse model of experimental Lyme arthritis, we investigated the effect of disrupted sleep on the development and resolution of joint inflammation. METHODS: Lyme arthritis-susceptible C3H/HeJ mice (n = 10/group) were infected with B. burgdorferi and were left either alone (control) or subjected to sleep fragmentation (SF). Arthritis development or resolution were monitored. The impact of SF on immune and inflammatory parameters such as arthritis severity scores, anti-borrelia antibody production, and bacterial clearance was measured. We also determined the effect of SF on arthritis resolution in C3H mice deficient in leukotriene (LT) B4 signaling (BLT1/2-/-) who display delayed Lyme arthritis resolution. RESULTS: SF had no significant impact on Lyme arthritis development or inflammatory parameters regardless of whether SF treatment began 1 week prior to or congruent with infection. However, initiation of SF at the peak of arthritis resulted in a significant delay in arthritis resolution as measured by joint edema, arthritis severity scores, and decreased bacterial clearance from the joint. This was accompanied by significant changes in joint cytokine transcription levels (e.g., increased TNFα and decreased IL-4). SF has no significant impact on Lyme arthritis resolution in the BLT1/2-/- mice. CONCLUSIONS: Poor sleep, especially near the peak of arthritis inflammation, may delay initiation of resolution programs possibly through altering cytokine production and host immune responses, leading to defects in spirochete clearance and prolonged disease.

[A rare manifestation of Lyme disease]. / Seltene Manifestation einer Borreliose.

A 33-year-old man presented to the authors' general medical practice with a striking alteration to the left nipple. After extensive diagnostic investigation to identify in particular hemato-oncological diseases, a rare manifestation of an infection with Borrelia burgdorferi due to a tick bite was diagnosed. Antibiotic treatment with doxycycline over a period of 3 weeks led to complete restitution of the alteration.

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.

Dermatoscopic Features of Early Erythema Chronicum Migrans.

Dear Editors, A 37-year-old man from a Lyme disease-endemic area presented with a one-week old rapidly expanding rash on his right calf. He lacked other comorbidities or symptoms such as fever, weakness, lack of appetite, or joint pain, but recalled removing a tick from the same region three weeks earlier. Inspection revealed a round, bluish-red erythematous patch with a central clearing (Figure 1). The patient experienced no discomfort, but the rash was warm and faded easily when palpated. Dermatoscopic inspection revealed collarette-shaped white scales encircling the punctum of the tick bite in the center (Figure 2, left inset). There were three distinct background zones towards the periphery: skin-colored, bluish-red, and bright red. The transitions between the zones were not fully discernable. Red purpuric dots and clods were randomly distributed over these backgrounds, gradually increasing towards the periphery (Figure 2). The rash was diagnosed as erythema chronicum migrans (ECM), and the patient was started on doxycycline 100 mg BID. The expansion of the rash was stopped, while the speed of central clearing was increased. Half of the rash had healed by the third day (Figure 1, left inset), and it had completely disappeared by the seventh (Figure 1, right inset). Anti-Borrelia burgdorferi antibodies were initially negative for IgM and positive for IgG, but both tested positive two weeks later. ECM is the hallmark of early-stage lyme disease, but it is not always present. In addition to the classically described bull's eye appearance, ECM may appear as homogenous erythematous patches, interrupted annular patches, or patches with hemorrhagic or purpuric components (1). It can manifest anywhere except in the palmoplantar region, but it is more common around large joints. Despite the morphological variations of ECM, the clinical presentation is often clear and distinct enough for dermatologists to correctly diagnose more than 90% of patients (1). Diagnostic procedures such as ELISA or Western blot are employed in cases when the ECM is absent or atypical. However, their reliability is low due to the lack of standardization, limited coverage of Borrelia spp., and significant false-positive and false-negative rates (1). Seropositivity owing to previous asymptomatic infection in individuals residing in endemic areas may result in incidental positive findings. Alternative methods, including isolating the pathogen or PCR testing from biopsy samples have similar drawbacks (1). Histopathological investigations are another practical method that yields supportive findings. ECM exhibits diffuse perivascular and interstitial inflammation, including lymphocytes, eosinophils, and plasma cells (2), which corresponds to background erythema in dermatoscopy. As the inflammation develops, the newly-developed regions are superficial and brilliant red, but the surface inflammation fades over time, leaving bluish erythema, which correlates to deeper inflammation (2,3) dermoscopy is gaining appreciation in assisting the diagnosis of nonneoplastic diseases, especially inflammatory dermatoses (inflammoscopy). Extravasated erythrocytes combined with perivascular inflammation (2) generate purpuric pinkish-red dots and clods. Given the greater efficacy of early treatment and the ambiguity surrounding diagnostic methods, clinical findings should be deemed adequate to commence therapy, particularly in endemic regions (1). Dermatoscopic examination of ECM offers a quick and low-cost alternative approach for supporting the diagnosis. However, as emphasized by Errichetti, dermatoscopic examination in non-neoplastic diseases should be regarded as the second step of a "2-step procedure", with differential diagnoses established first by history and clinical examination (3). A systematic investigation of early and late, typical and atypical lesions would improve the reliability and utility of this method.

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.

An Unusual Case of Lyme Carditis With Persistent Third-Degree Heart Block.

Lyme's carditis and neuroborreliosis are common manifestation of disseminated Lyme disease. However, third-degree atrioventricular blocks with Lyme's carditis requiring permanent pacemaker with neuroborreliosis and Lyme's disease-associated immunodeficiency are uncommon. Here we present a case of 64-year-old female presenting with neurological symptoms and electrocardiogram changes suggestive of complete heart block with no improvement in the degree of heart block with intravenous antibiotics, requiring permanent pacemaker implantation and course complicated by fungemia.

IMPACT OF CLINICAL CHARACTERISTICS OF LYME BORRELIOSIS ON PATIENTS' LIFE QUALITY.

OBJECTIVE: The aim: To study the impact of clinical characteristics of the disease on the life quality of patients with Lyme borreliosis. PATIENTS AND METHODS: Materials and methods: Forty-eight (33 women and 15 men) patients with Lyme borreliosis aged 23-77 years and 48 individuals who did not have any somatic diseases that would impact the quality of life (experimental group) were examined. The MOS 36-item Short Form Health Survey (SF-36) was used to study the quality of life. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). RESULTS: Results: According to the SF-36 questionnaire, patients with Lyme borreliosis had a significant decrease in scores for all indicators of physical health (р < 0.001), as well as impaired social (р < 0.001) and emotional (p = 0.027) functioning compared with healthy individuals. The deterioration of the quality of life indicators essentially depends on the clinical characteristics of the disease, namely its duration, the presence of Lyme arthritis, neuroborreliosis, cognitive disorders, multiple organ involvement, disease stage. CONCLUSION: Conclusions: Lyme borreliosis and its certain clinical characteristics have a significant impact on the life quality of patients.

Sensitivity of Two-Tiered Lyme Disease Serology in Children With an Erythema Migrans Lesion.

In our prospective cohort of 192 children with a physician-diagnosed erythema migrans (EM) lesion, two-tier Lyme disease serology had higher sensitivity in children with multiple EM lesions (76.8% multiple lesions vs. 38.1% single EM; difference 38.7%, 95% confidence interval 24.8%-50.4%). The diagnosis of cutaneous Lyme disease should be based on careful physical examination rather than laboratory testing.

Secondary Intracranial Hypertension in Pediatric Lyme Meningitis.

Lyme disease is the most common vector-borne disease in the United States and has been associated with secondary intracranial hypertension. We reviewed 11 pediatric patients with Lyme-associated secondary intracranial hypertension. All patients presented with headache, ten had papilledema, 7 with a rash, and 5 with a cranial nerve palsy. All patients were treated with acetazolamide, and 3 received combination therapy with furosemide. Three patients were considered to have fulminant intracranial hypertension because of the severity in their presenting courses. Two of the fulminant intracranial hypertension patients were treated with a temporary lumbar drain in addition to medications, whereas 1 fulminant intracranial hypertension patient was treated exclusively with medical therapy alone. The addition of a lumbar drain decreased the time to resolution of papilledema compared to medical management alone. Final visual acuity was 20/20 in each eye of all patients, suggesting that a titrated approach to therapy depending on the severity of presentation can result in good visual outcomes in these cases. Additionally, symptoms can recur after medication wean, so patients should be monitored closely with any discontinuation of intracranial pressure lowering medications.

Multippel erythema migrans, borrelialymfocytom og nevroborreliose hos eit barn.

BACKGROUND: Lyme disease after a tick bite often presents as erythema migrans, yet less frequent variants of this disease, such as Borrelia lymphocytoma, multiple erythema migrans and neuroborreliosis, are also seen occasionally. CASE PRESENTATION: We report a case of a tick-bitten child who first presented with an indistinct macular erythema around the left eye and a more distinct macular erythema on and around the left ear. The next day, she developed a facial palsy. INTERPRETATION: The case was interpreted as facial multiple erythema migrans and Borrelia lymphocytoma on the ear, followed by neuroborreliosis. The diagnosis of lymphocytoma was made from clinical findings and PCR of skin biopsy. She recovered quickly after intravenous ceftriaxone and is now healthy.