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"Knudtzen, Fredrikke Christie"
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Disseminated Marginal Zone Lymphoma in a Patient with Lyme Neuroborreliosis: A Case Report
by
Weisbjerg, Dorit Kraft
,
Knudtzen, Fredrikke Christie
,
Andersen, Nanna Skaarup
in
Antibiotics
,
Antibodies
,
Arachnids
2025
Abstract
Introduction:
Lyme borreliosis has been associated with lymphoma, particularly cutaneous lymphomas. The literature is conflicted regarding the effect of antibiotic therapy in cutaneous marginal zone lymphomas (MZLs) in individuals with Lyme borreliosis. We present a patient diagnosed with Lyme neuroborreliosis (LNB) and disseminated MZL.
Case Presentation:
A 67-year-old man was seen due to 6 weeks of neuropathic pain with nightly worsening, headache, and 5 kg weight loss. Two weeks prior to symptom debut, he had a tick bite in the left groin, no subsequent rash. A lumbar puncture revealed mononuclear pleocytosis and elevated CSF protein. The patient was admitted and started on ceftriaxone. The Borrelia burgdorferi intrathecal test showed intrathecally produced Borrelia antibodies, and treatment was changed to doxycycline with a total treatment duration of 21 days. A PET/CT revealed enlarged lymph nodes with increased FDG uptake. On pathological examination, the CSF showed 62% clonal B cells – compatible with low-grade B-cell lymphoma. Examination of bone marrow and an inguinal lymph node confirmed disseminated MZL. A control lumbar puncture 8 weeks later showed declining pleocytosis and clonal B cells. At last follow-up 20 months later, he was still asymptomatic and had not required antineoplastic treatment.
Conclusion:
To our knowledge, this is the first published case of LNB with non-cutaneous B-cell lymphoma treated and remitting on antibiotics alone. Antibiotic treatment for Borrelia-positive lymphomas has yet to be investigated with high-evidence study designs, so clinicians are encouraged to publish both positive and negative findings relevant to this. We believe this case brings new perspectives to future diagnosis and treatment of lymphomas in patients with verified Lyme borreliosis.
Journal Article
Characteristics and Clinical Outcome of Lyme Neuroborreliosis in a High Endemic Area, 1995–2014
by
Knudtzen, Fredrikke Christie
,
Skarphédinsson, Sigurdur
,
Andersen, Nanna Skaarup
in
Adolescent
,
Adult
,
Anti-Bacterial Agents - therapeutic use
2017
Despite a well-described symptomatology, treatment delay and sequelae are common in patients with Lyme neuroborreliosis (LNB). The aim of this study was to contribute to the knowledge about the symptomatology and epidemiology of LNB.
We conducted a retrospective study of all LNB cases verified by a positive Borrelia intrathecal antibody index test performed at the Department of Microbiology, Odense University Hospital, Denmark, from 1995 through 2014.
The study included 431 patients; 126 were children. The mean incidence was 4.7 per 100 000 inhabitants per year. The median delay from neurological symptom debut to first hospital contact was 20 days and significantly longer for patients with symptom debut in the winter/early spring. The most common clinical symptoms were painful radiculitis (65.9%), cranial nerve palsy (43.4%), and headache (28.3%). A total of 30.6% were seen in >1 hospital department, and 85.6% were admitted during their course of treatment. Serum Borrelia immunoglobulin M and immunoglobulin G at the time of positive Borrelia intrathecal antibody index test were negative in 67 patients (15.5%). We found a median treatment delay of 24 days, with no improvement in our 20-year study period. Residual symptoms following treatment were found in 28.1% of patients, and risk of residual symptoms was significantly associated with delay from symptom debut to initiation of treatment.
The association between treatment delay and residual symptoms and the lack of improvement in treatment delay during the study period highlight the need for standardized diagnostic routines and a better follow-up for LNB patients. Our findings disprove that all patients with LNB develop positive serum Borrelia antibodies within 6 weeks after infection.
Journal Article
The predictive value of CXCL13 in suspected Lyme neuroborreliosis: a retrospective cross-sectional study
by
Christie, Knudtzen Fredrikke
,
Nilsson, Anna Christine
,
Skarphedinsson Sigurdur
in
Antibiotics
,
Antibodies
,
Borreliosis
2020
The role of CXCL13 as a marker of Lyme neuroborreliosis (LNB) is under investigation, and CXCL13 is not part of routine diagnostics in suspicion of LNB. Our aim was to find the optimal cut-off value of CXCL13 for LNB in a Danish population and to investigate the role of CXCL13 both in early LNB and as a discriminatory marker between LNB and other neuroinflammatory disorders. We conducted a retrospective cross-sectional study including all patients with a cerebrospinal CXCL13 test performed at the Department of Clinical Immunology, Odense University Hospital, Denmark, between 1 January 2015 and 31 December 2018. We included 619 patients, of which 51 had definite LNB, 14 patients had possible LNB with neurological symptoms suggestive of LNB and pleocytosis but no intrathecal Borrelia antibodies, eight patients had prior LNB and 546 had no LNB. With an optimal CXCL13 cut-off of 49 ng/L we found a sensitivity of 100% and specificity of 94% (AUC 0.988, 95% CI 0.980–0.996) when patients treated with antibiotics prior to lumbar puncture were excluded (n = 130). All patients with possible LNB had a CXCL13 value above the cut-off value; 18/546 patients (3.3%) without LNB had a CXCL13 value ≥ 50 ng/L. While CXCL13 cannot be used as a stand-alone test, it can be used as a reliable additional marker in treatment-naive patients suspected of LNB. CXCL13 can be used to monitor treatment response in LNB patients.
Journal Article
SARS-CoV-2 viral load as a predictor for disease severity in outpatients and hospitalised patients with COVID-19: A prospective cohort study
by
Knudtzen, Fredrikke Christie
,
Lindvig, Susan Olaf
,
Rasmussen, Line Dahlerup
in
Biology and life sciences
,
Cohort analysis
,
Confidence intervals
2021
We aimed to examine if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) cycle quantification (C.sub.q) value, as a surrogate for SARS-CoV-2 viral load, could predict hospitalisation and disease severity in adult patients with coronavirus disease 2019 (COVID-19). We performed a prospective cohort study of adult patients with PCR positive SARS-CoV-2 airway samples including all out-patients registered at the Department of Infectious Diseases, Odense University Hospital (OUH) March 9-March 17 2020, and all hospitalised patients at OUH March 10-April 21 2020. To identify associations between C.sub.q -values and a) hospital admission and b) a severe outcome, logistic regression analyses were used to compute odds ratios (OR) and 95% Confidence Intervals (CI), adjusting for confounding factors (aOR). We included 87 non-hospitalised and 82 hospitalised patients. The median baseline C.sub.q -value was 25.5 (interquartile range 22.3-29.0). We found a significant association between increasing C.sub.q -value and hospital-admission in univariate analysis (OR 1.11, 95% CI 1.04-1.19). However, this was due to an association between time from symptom onset to testing and C.sub.q -values, and no association was found in the adjusted analysis (aOR 1.08, 95% CI 0.94-1.23). In hospitalised patients, a significant association between lower C.sub.q -values and higher risk of severe disease was found (aOR 0.89, 95% CI 0.81-0.98), independent of timing of testing. SARS-CoV-2 PCR C.sub.q -values in outpatients correlated with time after symptom onset, but was not a predictor of hospitalisation. However, in hospitalised patients lower C.sub.q -values were associated with higher risk of severe disease.
Journal Article
Fatigue and cognitive impairment in neuroborreliosis patients posttreatment—A neuropsychological retrospective cohort study
by
Knudtzen, Fredrikke Christie
,
Sigurdardottir, Anna Helena
,
Nymark, Anita
in
Antibiotics
,
cognition
,
Cognition & reasoning
2022
Background The aim of this study was to determine the prevalence of fatigue and cognitive impairment in patients with neuroborreliosis (NB) posttreatment and to determine whether delayed treatment initiation led to higher levels of fatigue and cognitive impairment. Methods The study population consisted of 88 patients with NB included between October 10, 2014, and August 21, 2020, at the Clinical Center for Emerging and Vector‐borne Infections at Odense University Hospital, Denmark. The Symbol Digit Modalities Test (SDMT) was used as a cognitive screening test, and the Modified Fatigue Impact Scale (MFIS) was used to assess the patients’ level of fatigue over the course of a year. Results Overall, 14.3% of patients had an SDMT score indicative of cognitive impairment, and 38.8% of patients reported experiencing fatigue 12 months posttreatment. We found no statistically significant differences in fatigue or cognitive impairment when comparing the patients who had a treatment delay of ≤14 days and those with a treatment delay of >14 days (p > .05) 12 months posttreatment. A random effects regression model showed a significant positive correlation between longer treatment delay and higher MFIS scores, indicating higher levels of fatigue. Conclusions The results of this study show that both the early and late treatment groups improved significantly over a 12‐month period in terms of both cognitive symptoms and fatigue. However, it also showed that a substantial subgroup of patients with NB still suffer from fatigue and cognitive impairment 12 months posttreatment.
Journal Article
Spatial and temporal patterns of Lyme Neuroborreliosis on Funen, Denmark from 1995–2014
by
Knudtzen, Fredrikke Christie
,
Bødker, Rene
,
Andreasen, Amalie Muus
in
692/699/375/1367
,
692/700/478/174
,
Animal populations
2020
In Europe, Lyme neuroborreliosis (LNB) is the most severe manifestation of Lyme borreliosis and has recently been added to the communicable disease surveillance list for EU/EEA by the European Commission. In Northern Europe, LNB is primarily caused by the spirochete
Borrelia garinii
and transmitted by the tick
Ixodes ricinus
. This Danish observational epidemiologic case-control study includes every identified LNB patient (n = 401) on Funen, Denmark, from 1995-2014. We display spatial and temporal LNB incidence variation, seasonal distribution of cases and local spatial case clustering. Seasonal patterns show LNB symptom-onset peaking in July and a significant seasonal difference in number of cases (p < 0.01). We found no significant change in seasonality patterns over time when dividing the study period into 5-year intervals. We identified a significant local geographical hot-spot of cases with a relative risk of 2.44 (p = 0.013). Analysis revealed a significantly shorter distance to nearest forest for cases compared with controls (p < 0.001). We present a novel map of the focal geographical distribution of LNB cases in a high endemic borreliosis area. Continued studies of case clustering in the epidemiology of LNB are of key importance in guiding intervention strategies.
Journal Article
An intervention in general practice to improve the management of Lyme borreliosis in Denmark
by
Knudtzen, Fredrikke Christie
,
Skarphédinsson, Sigurdur
,
Andersen, Nanna Skaarup
in
Antibodies
,
Borreliosis
,
Care and treatment
2022
Background
Our objectives were to improve the following outcomes in patients with Lyme borreliosis (LB) through an educational intervention in general practice: (i) increase the number of hospital referrals on suspicion of LB, (ii) increase the number of cerebrospinal fluid (CSF) tests examined for Borrelia burgdorferi antibody index, (iii) decrease the number of serum-B. burgdorferi antibody tests ordered, (iv) shorten delay from symptom onset to hospital in Lyme neuroborreliosis (LNB) patients, (v) increase LB knowledge among general practitioners.
Methods
A prospective non-blinded non-randomized intervention trial on the island of Funen, Denmark. The intervention included oral and written education about LB and was carried out in areas with an LNB incidence ≥4.7/100.000 between 22 January 2019 and 7 May 2019. Results were compared between the intervention group (49 general practices) and the remaining general practices in Funen (71 practices) 2 years before and after the intervention.
Results
In the study period, 196 patients were referred on suspicion of LB, a 28.9% increase in the intervention group post-intervention, 59.5% increase in the control group (P = 0.47). The number of CSF-Borrelia-antibody index tests increased 20.8% in the intervention group, 18.0% in the control group (P = 0.68), while ordered serum-B. burgdorferi antibody tests declined 43.1% in the intervention group, 34.5% in the control group (P = 0.30). 25.1% had the presence of serum-B. burgdorferi antibodies. We found no difference in LNB pre-hospital delay before and after intervention or between groups (P = 0.21). The intervention group performed significantly better on a follow-up questionnaire (P = 0.02).
Conclusion
We found an overall improvement in LB awareness and referrals among general practitioners but could not show any effect of the intervention on clinical outcomes of LNB.
Journal Article
Severe Bartonella henselae bone infection in a kidney transplanted young man
by
Knudtzen, Fredrikke Christie
,
Christensen, Heidi Dahl
,
Madelung, Ann Brinch
in
Abdomen
,
Antibiotics
,
Bartonella henselae
2022
We present a case of a young kidney transplanted man. He was admitted with lymphadenopathy, fluctuating fever and night sweats 2 months after a cat bite. After admission, he developed severe pain around his right hip. An 18 F-fluorodeoxyglucose (FDG)-positron emission tomography/CT revealed intense FDG-uptake in lymph nodes, spleen and bone, suggestive of lymphoma. An extracted lymph node showed confluent granulomas, microabscesses with neutrophils and scattered multinucleated giant cells histologically. The patient had history of latent tuberculosis and proteinase 3 -anti-neutrophil cytoplasmic antibodies associated (PR3-ANCA) vasculitis, making differential diagnostic considerations complicated. Bartonella henselae antibodies was detected in blood and B. henselae DNA in a lymph node. He was started on doxycycline and rifampicin. Due to severe drug interactions with both tacrolimus and increasing morphine doses, rifampicin was changed to azithromycin. He received 12 days of relevant antibiotic treatment and responded well. He was discharged after 16 days with close follow-up and was still in habitual condition 12 months later.
Journal Article
Lung ultrasound may be a valuable aid in decision making for patients admitted with COVID-19 disease
by
Dahlerup Rasmussen, Line
,
Falster, Casper
,
Davidsen, Jesper Rømhild
in
ARDS
,
Coronaviruses
,
COVID-19
2021
INTRODUCTION: COVID-19 is associated with a risk of severe pneumonia and acute respiratory distress syndrome (ARDS), requiring treatment at an intensive care unit (ICU). Since clinical deterioration may occur rapidly, a simple, fast, bedside, non-invasive method for assessment of lung changes is warranted. The primary aim of this study was to investigate whether lung ultrasound (LUS) findings within 72 hours of admission were predictive of clinical deterioration in hospitalized patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
METHODS: Patients admitted to a dedicated COVID-19 unit were subject to daily LUS examinations. Number of present consolidations and pleural effusions were registered and a Mongodi score was calculated. These findings were correlated with initial chest x-ray and clinical deterioration, defined as ICU-admission, ARDS diagnosis, death.
RESULTS: In total, 29 of 83 patients had LUS performed during admission, 18 within 72 h of admission. Of these, four patients died during admission, six were transferred to the ICU and 13 were diagnosed with ARDS.
Initial Mongodi-score did not differ significantly between patients with and without clinical deterioration (p = 0.95). Agreement between initial LUS and chest x-ray findings were fair with Cohen's Kappa at 0.21.
CONCLUSION: LUS performed within 72 h in patients admitted to a dedicated COVID-19 unit could not predict ARDS, ICU admission or death. However, consecutive investigations may be of value, as sudden substantial changes may herald disease progression, enabling earlier supplementary diagnostics and treatment initiation.
Journal Article