Association Between Tick-Borne Illness and Other Chronic Infections

Severe, lingering symptoms seen in some patients after Lyme disease treatment

By Marin Hedin, John Hopkins Magazine, Baltimore, Maryland
February 4, 2018
https://hub.jhu.edu/2018/02/02/lingering-severe-chronic-lyme-disease-symptoms/
In a study of 61 people treated for the bacteria that causes Lyme disease, Johns Hopkins researchers conclude that fatigue, pain, insomnia, and depression do indeed persist over long periods of time for some people, despite largely normal physical exams and clinical laboratory testing. “Post-treatment Lyme disease syndrome (PTLDS) is a real disorder that causes severe symptoms in the absence of clinically detectable infection,” says John N. Aucott, associate professor of medicine at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Lyme Disease Clinical Research Center.

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability.
Morris G, Berk M, Walder K, Maes M.
Molecular Neurobiology, online first, 2015 Jun 17.
http://doi.org/10.1007/s12035-015-9262-7
Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure.

Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioural, Psychiatric, Autoimmune and Fatiguing Illnesses
Garth L. Nicolson and Jorg Haier, British Journal of Medical
Practitioners, 2010;3(1):301.
Part 1
http://www.bjmp.org/content/role-chronic-bacterial-and-viral-infections-neurodegenerative-neurobehavioral-psychiatric-au
Part 2
http://www.bjmp.org/content/role-chronic-bacterial-and-viral-infections-neurodegenerative-neurobehavioural-psychiatric-a
Chronically ill patients with neurodegenerative and neurobehavioural and psychiatric diseases commonly have systemic and central nervous system bacterial and viral infections. In addition, other chronic illnesses where neurological manifestations are routinely found, such as fatiguing and autoimmune diseases, Lyme disease and Gulf War illnesses, also show systemic bacterial and viral infections that could be important in disease inception, progression or increasing the types/severities of signs and symptoms. Evidence of Mycoplasma species, Chlamydia pneumoniae, Borrelia burgdorferi, human herpesvirus-1, -6 and -7 and other bacterial and viral infections revealed high infection rates in the above illnesses that were not found in controls. Although the specific roles of chronic infections in various diseases and their pathogeneses have not been carefully determined, the data suggest that chronic bacterial and/or viral infections are common features of progressive chronic diseases.

Hello from the Other Side: How Autoantibodies Circumvent the Blood–Brain Barrier in Autoimmune Encephalitis
Maryann P. Platt, Dritan Agalliu and Tyler Cutforth
Front. Immunol., 21 April 2017
https://doi.org/10.3389/fimmu.2017.00442
Antibodies against neuronal receptors and synaptic proteins are associated with autoimmune encephalitides (AE) that produce movement and psychiatric disorders. In order to exert their pathological effects on neural circuits, autoantibodies against central nervous system (CNS) targets must gain access to the brain and spinal cord by crossing the blood–brain barrier (BBB), a tightly regulated gateway formed by endothelial cells lining CNS blood vessels. To date, the pathogenic mechanisms that underlie autoantibody-triggered encephalitic syndromes are poorly understood, and how autoantibodies breach the barrier remains obscure for almost all AE syndromes. The relative importance of cellular versus humoral immune mechanisms for disease pathogenesis also remains largely unexplored. Here, we review the proposed triggers for various autoimmune encephalopathies and their animal models, as well as basic structural features of the BBB and how they differ among various CNS regions, a feature that likely underlies some regional aspects of autoimmune encephalitis pathogenesis. We then discuss the routes that antibodies and immune cells employ to enter the CNS and their implications for AE. Finally, we explore future therapeutic strategies that may either preserve or restore barrier function and thereby limit immune cell and autoantibody infiltration into the CNS. Recent mechanistic insights into CNS autoantibody entry indicate promising future directions for therapeutic intervention beyond current, short-lived therapies that eliminate circulating autoantibodies.

The Clinical, Symptom, and Quality-of-Life Characterization of a Well-Defined Group of Patients with Posttreatment Lyme Disease Syndrome
Rebman AW, Bechtold KT, Yang T, Mihm EA, Soloski MJ, Novak CB, Aucott JN.
Frontiers in Medicine. 2017 Dec 14;4:224. eCollection 2017.
https://doi.org/10.3389/fmed.2017.00224
Although physical exam and clinical laboratory tests showed few objective abnormalities, standardized symptom questionnaires revealed that patients with PTLDS are highly and clinically significantly symptomatic, with poor health-related quality of life. PTLDS patients exhibited levels of fatigue, musculoskeletal pain, sleep disturbance, and depression which were both clinically relevant and statistically significantly higher than controls. Our study shows that PTLDS can be successfully identified using a systematic approach to diagnosis and symptom measurement. As the prevalence of PTLDS continues to rise, there will be an increased need for physician education to more effectively identify and manage PTLDS as part of integrated patient care.

Sleep Quality in Well-defined Lyme Disease
Weinstein ER, Rebman AW, Aucott JN, Johnson-Greene D, Bechtold KT.
Sleep, online first 2018 Feb 14.
https://doi.org/10.1093/sleep/zsy035
Participants with early LD experienced poor sleep quality, which is associated with typical LD symptoms of pain and fatigue. In the subset of patients who developed PTLDS, sleep quality remains affected for up to one year post-treatment and is commonly associated with pain. Sleep quality should be considered in the clinical picture for LD and PTLDS.

Not all sleep is equal when it comes to cleaning the brain.
University of Rochester Medical Center.
ScienceDaily. ScienceDaily, 27 February 2019.
www.sciencedaily.com/releases/2019/02/190227173111.htm
New research shows how the depth of sleep can impact our brain’s ability to efficiently wash away waste and toxic proteins. Because sleep often becomes increasingly lighter and more disrupted as we become older, the study reinforces and potentially explains the links between aging, sleep deprivation, and heightened risk for Alzheimer’s disease.

Isolation of live Borrelia burgdorferi sensu lato spirochetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis
N. Rudenko, M. Golovchenko ,M. Vancova, K. Clark, L. Grubhoffer, J.H. Oliver Jr.
Clinical Microbiology and Infection, online first, December 7, 2015.
http://dx.doi.org/10.1016/j.cmi.2015.11.009
It is known that Lyme borreliosis is mimicking multiple diseases that were never proven to have a spirochete etiology. Using complete modified Kelly-Pettenkofer medium we succeeded in cultivation of live B. burgdorferi sensu lato spirochetes from samples of humans who suffered from undefined disorders, had symptoms not typical for Lyme borreliosis, but undergone antibiotic treatment due to suspicion of having Lyme disease even though they were seronegative.

Retrospective Analysis of a Cohort of Internationally Case Defined Chronic Fatigue Syndrome Patients in a Lyme Endemic Area
Samuel Shor, Bulletin of the IACFS/ME. 2011;18(4):109-123.
http://www.iacfsme.org/BULLETINWINTER2011/Winter2011ShorCFSinLyme109123/tabid/458/Default.aspx
Of the total 210 included in the analysis, 209 or 99% were felt to represent a high likelihood of “seronegative Lyme disease.” Initiating various antimicrobial regimen, involved at least a 50% improvement in clinical status in 130 or 62%. Although not achieving the 50% threshold according to the criteria discussed, another 55 patients subjectively identified a beneficial clinical response to antimicrobials, representing a total of 188 or 88% of the total identified as having a high potential for seronegative Lyme disease. A potentially substantial proportion of patients with what would otherwise be consistent with internationally case defined CFS in a Lyme endemic environment actually have a perpetuation of their symptoms driven by a persistent infection by Borrelia burgdorferi. By treating this cohort with appropriately directed antimicrobials, we have the ability to improve outcomes.

Factors Affecting Duration of Chronic Fatigue Syndrome in Pediatric Patients
Dmitriy Petrov, Daniel Marchalik, Michael Sosin and Aswine Bal
Indian Journal of Pediatrics, online before print, May 27, 2011.
http://dx.doi.org/10.1007/s12098-011-0463-4
A total number of 53 predominantly white (98.1%) patients with CFS, aged 9-18 years, were included in the study. Other than fatigue, headaches and sleep disturbance were the most common symptoms of pediatric CFS. Seropositive status for Borrelia burgdorferi (B. burgdorferi) and Epstein-Barr virus (EBV) was identified in 66% of the patients with the diagnosis of CFS by CDC criteria.

Long-Term Assessment of Fatigue in Patients with Culture-Confirmed Lyme Disease
Gary P. Wormser, M.D, Erica Weitzner, B.S, Donna McKenna, N.P, Robert B. Nadelman, M.D, Carol Scavarda, R.N, John Nowakowski, M.D
The American Journal of Medicine, online before print, 15 October 2014
http://doi.org/10.1016/j.amjmed.2014.09.022
Severe fatigue was found in 9 (9%) patients with culture-confirmed early Lyme disease at 11 to 20 years after presentation.

Correlates of Perceived Health-Related Quality of Life in Post-treatment Lyme Encephalopathy.
Chandra AM, Keilp JG, Fallon BA.
Psychosomatics, online before print, 2013 Jul 8. pii: S0033-3182(13)00078-9.
http://dx.doi.org/10.1016/j.psym.2013.04.003
Marked functional impairment has been reported by patients with post-treatment Lyme disease syndrome (PTLDS). Fatigue was the most important contributor to perceived impairments in overall physical functioning, and fatigue and depression significantly predicted perceived impairments in overall mental functioning.

A Case of Early Disseminated Neurological Lyme Disease Followed by Atypical Cutaneous Manifestations
Kantamaneni V, Sunder V, Bilal M, Vargo S.
Case Reports in Infectious Diseases, online first, 2017 Apr 23.
https://doi.org/10.1155/2017/6598043
Not all patients have the classic “targetoid” EM rash on initial presentation, rash could develop after neurological manifestations, and prompt initiation of antibiotics without awaiting serology is paramount to making a quick and a full recovery. There should be a high index of suspicion for early disseminated LD, as presentations can be atypical.

Inflammation and Central Nervous System Lyme Disease
Brian A. Fallon, Elizabeth S. Levin, Pernilla J. Schweitzer and David Hardesty
http://cait.cpmc.columbia.edu:88/dept/pi/nyspi/LymeDisease/documents/Fallon_Inflammation-and-central-nervous-system-Lyme-disease_2009.pdf
Lyme disease, caused by the bacterium Borrelia burgdorferi, can cause multi-systemic signs and symptoms, including peripheral and central nervous system disease. This review examines the evidence for and mechanisms of inflammation in neurologic Lyme disease, with a specific focus on the central nervous system, drawing upon human studies and controlled research with experimentally infected rhesus monkeys. Directions for future human research are suggested that may help to clarify the role of inflammation as a mediator of the chronic persistent symptoms experienced by some patients despite antibiotic treatment for neurologic Lyme disease.

Estimation of cognitive and affective disorders occurrence in patients with Lyme borreliosis
Oczko-Grzesik B, Kepa L, Puszcz-Matlinska M, Pudlo R, Zurek A, Badura-Glabik T.
Annals of Agricultural and Environmental Medicine, 2017 Mar 1;24(1):33-38.
https://doi.org/10.5604/12321966.1229002
An increased frequency of depressive and neurotic disorders was observed in patients with LB, particularly in patients with neuroborreliosis. Neurotic disorders, mainly adaptive, were most common in males with LB, while depressive disorders were more frequent in females. An increased frequency of cognitive deficits was observed in patients with neuroborreliosis, particularly in females.

The prevalence of Lyme disease and associated coinfections in people with persistent post concussive syndrome
Sergio Azzolino and Frederick R. Carrick
Frontiers in Neurology, Conference Abstract: International Symposium on Clinical Neuroscience 2018. Published online December 14, 2018.
https://doi.org/10.3389/conf.fneur.2018.60.00047
According to the Centers for Disease Control and Prevention (CDC), Lyme disease is the most commonly reported vector-borne illness and the fifth most common disease in the National Notifiable Diseases Surveillance System, making it an important public health concern. Neurological manifestations of Lyme disease, called Neuroborreliosis, are reported in up to 15% of patients with Lyme disease. We have identified an alarming number of individuals suffering from PCS that are refractory to care and that have serologically tested positive for Lyme disease. As a consequence we started to routinely test PCS patients for Lyme disease that had no history of or testing for Lyme disease.

Long-term Assessment of Post-Treatment Symptoms in Patients With Culture-Confirmed Early Lyme Disease
Weitzner E, McKenna D, Nowakowski J, Scavarda C, Dornbush R, Bittker S, Cooper D, Nadelman RB, Visintainer P, Schwartz I, Wormser GP.
Clinical Infectious Diseases, pii: civ735. Online before print, 2015 Sep 18.
http://doi.org/10.1093/cid/civ735
PTLDS may persist for >10 years in some patients with culture-confirmed early Lyme disease. Such long-standing symptoms were not associated with functional impairment or a particular strain of B. burgdorferi.

Lyme arthritis in children presenting with joint effusions
Milewski MD, Cruz AI Jr, Miller CP, Peterson AT, Smith BG.
The Journal of Bone and Joint Surgery (American). 2011 Feb;93(3):252-60.
http://dx.doi.org/10.2106/JBJS.I.01776
For any child presenting with a joint effusion in a Lyme-endemic area of the Northeastern United States, the likely prevalence of Lyme arthritis is 31% overall and 45% in the presence of knee effusion. Children with joint effusions resulting from Lyme disease are more likely to have knee involvement, a lower peripheral white blood-cell count, and a lower joint fluid cell count, and they are less likely to have fever or complete refusal to bear weight, when compared with children with septic arthritis.

Divergent opinions of proper Lyme disease diagnosis and implications for children co-morbid with autism spectrum disorder.
Kuhn M, Bransfield R.
Medical Hypotheses. 2014 Jun 16. pii: S0306-9877(14)00233-3.
http://dx.doi.org/10.1016/j.mehy.2014.06.005
Through an online survey parents of 48 children who have a diagnosis of an ASD and have been diagnosed with Lyme disease were asked to fill out the Autism Treatment Evaluation Checklist (ATEC) before they started antibiotic therapy and after treatment. Of the 48 parents surveyed 45 of them (94%) indicated their child initially tested negative using the two-tiered CDC/IDSA approved test. Protein bands OSP-A and/or OSP-B (Western Blot band 31) and (Western Blot band 34) were found in 44 of 48 patients. These two bands are so specific to Borrelia burgdorferi that they were targeted for use in vaccine trials, yet are not included in the IDSA interpretation of the Western Blot.

Uncommon manifestations of neuroborreliosis in children
Baumann M, Birnbacher R, Koch J, Strobl R, Rostásy K.
European Journal of Paediatric Neurology, Volume 14, Issue 3, May 2010, Pages 274-277.
http://dx.doi.org/10.1016/j.ejpn.2009.08.003
We report four unusual cases of childhood neuroborreliosis and show that seizures with regional leptomeningeal enhancement, acute transverse myelitis, meningoradiculitis with pain and paraesthesia and cranial nerve palsies other than facial nerve palsy can be the leading symptoms of children with neuroborreliosis.

A Nationwide Study in Denmark of the Association Between Treated Infections and the Subsequent Risk of Treated Mental Disorders in Children and Adolescents
Ole Köhler-Forsberg, MD; Liselotte Petersen, PhD; Christiane Gasse, PhD; et al Preben B. Mortensen, DrMedSci; Soren Dalsgaard, PhD; Robert H. Yolken, MD; Ole Mors, PhD; Michael E. Benros, PhD
JAMA Psychiatry. Published online December 5, 2018.
doi:10.1001/jamapsychiatry.2018.3428
This nationwide register-based cohort study that included 1 098 930 individuals born in Denmark between 1995 and 2012 found that severe infections requiring hospitalizations increased the risk of hospital contacts due to mental disorders by 84% and the risk of psychotropic medication use by 42%. Less severe infection treated with anti-infective agents increased the risks by 40% and 22%, respectively; the risks differed among specific mental disorders.

Suicide and Lyme and associated diseases
Bransfield RC
Neuropsychiatric Disease and Treatment, online first, June 16, 2017.
https://doi.org/10.2147/NDT.S136137
LAD contributed to suicidality, and sometimes homicidality, in individuals who were not suicidal before infection. A higher level of risk to self and others is associated with multiple symptoms developing after acquiring LAD, in particular, explosive anger, intrusive images, sudden mood swings, paranoia, dissociative episodes, hallucinations, disinhibition, panic disorder, rapid cycling bipolar, depersonalization, social anxiety disorder, substance abuse, hypervigilance, generalized anxiety disorder, genital–urinary symptoms, chronic pain, anhedonia, depression, low frustration tolerance, and posttraumatic stress disorder. Negative attitudes about LAD from family, friends, doctors, and the health care system may also contribute to suicide risk. By indirect calculations, it is estimated there are possibly over 1,200 LAD suicides in the US per year.

A Nationwide Cohort Study of the Association Between Hospitalization With Infection and Risk of Death by Suicide
Helene Lund-Sørensen, BM1,2; Michael E. Benros, PhD1,2; Trine Madsen, PhD1,2; et al Holger J. Sørensen, MD1,2; William W. Eaton, PhD3; Teodor T. Postolache, MD4,5,6; Merete Nordentoft, DrMedSc1,2,7; Annette Erlangsen, PhD2,3
JAMA Psychiatry. 2016;73(9):912-919. September 2016
doi:10.1001/jamapsychiatry.2016.1594
Findings suggest that infections might be linked to the development of psychiatric disorders and suicidal behavior. Large-scale studies are needed to investigate the effect of infection on the risk of suicide.

People with rage disorder twice as likely to have latent Toxoplasma gondii Infection.
Emil F. Coccaro, Royce Lee, Maureen W. Groer, Adem Can, Mary Coussons-Read, Teodor T. Postolache.
The Journal of Clinical Psychiatry, 2016; 334
DOI: 10.4088/JCP.14m09621
Individuals with a psychiatric disorder involving recurrent bouts of extreme, impulsive anger — road rage, for example — are more than twice as likely to have been exposed to a common parasite than healthy individuals with no psychiatric diagnosis. In a study involving 358 adult subjects, researchers found that toxoplasmosis, a relatively harmless parasitic infection carried by an estimated 30 percent of all humans, is associated with intermittent explosive disorder and increased aggression.

The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study
Psychosomatic Medicine. 79(8):936–946, OCT 2017
https://insights.ovid.com/crossref?an=00006842-201710000-00014
Publication Date: 2017/10/01
Sian M.J. Hemmings; Stefanie Malan-Müller; Leigh L. van den Heuvel; Brittany A. Demmitt; Maggie A. Stanislawski; David G. Smith; Adam D. Bohr; Christopher E. Stamper; Embriette R. Hyde; James T. Morton; Clarisse A. Marotz; Philip H. Siebler; Maarten Braspenning; Wim Van Criekinge; Andrew J. Hoisington; Lisa A. Brenner; Teodor T. Postolache; Matthew B. McQueen; Kenneth S. Krauter; Rob Knight; Soraya Seedat; Christopher A. Lowry
Inadequate immunoregulation and elevated inflammation may be risk factors for posttraumatic stress disorder (PTSD), and microbial inputs are important determinants of immunoregulation; however, the association between the gut microbiota and PTSD is unknown. In this exploratory study, measures of overall microbial diversity were similar among individuals with PTSD and TE controls; however, decreased total abundance of Actinobacteria, Lentisphaerae, and Verrucomicrobia was associated with PTSD status.

Cervical Radiculopathy as the Initial Presentation for Lyme neuroborreliosis
Anas Hannoun and Jeffrey Gudin
Neurology, April 18, 2017, 88:16 Supplement P1.311; 1526-632X.
Abstracts: American Academy of Neurology, 69th Annual Meeting, Boston. http://www.neurology.org/content/88/16_Supplement/P1.311.short
21-year-old male with no past history of spinal or neurological disease, presented with acute right cervical neck pain radiating to the right trapezius and right occipital and temporal regions. Lyme studies showed the IgM antibody level for Borrelia burgdorferi elevated with normal IgG levels. Oral Doxycycline 100mg twice a day was started. The following day, the patient re-presented to the ED with acute right lower motor neuron facial droop. Other symptoms included intermittent fevers, myalgias, and neck stiffness. Lumbar puncture demonstrated cell count of 268 with lymphocytic predominance. Protein level was elevated at 114. IgM antibody level for Borrelia burgdorferi was positive. He was diagnosed with Lyme disease complicated by neurological symptoms and meningitis and started on 2gm of ceftriaxone IV daily.

The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia
Geeta Ramesh, Lenay Santana-Gould, Fiona M Inglis, John D England and Mario T Philipp
Journal of Neuroinflammation, 2013, 10:88. Published online July 18, 2013.
http://doi.org/10.1186/1742-2094-10-88
In this model, B. burgdorferi induced an inflammatory response and neuronal apoptosis of DRG. These pathophysiological processes could contribute to peripheral neuropathy in LNB.

Validation of a Clinical Prediction Rule to Distinguish Lyme Meningitis From Aseptic Meningitis
Cohn KA, Thompson AD, Shah SS, Hines EM, Lyons TW, Welsh EJ, Nigrovic LE.
Pediatrics, online before print, December 19, 2011.
http://dx.doi.org/10.1542/peds.2011-1215
We identified 423 children, of whom 117 (28% [95% confidence interval (CI): 24%–32%]) had Lyme meningitis, 306 (72% [95% CI: 68%–76%]) had aseptic meningitis, and 0 (95% CI: 0%–1%) had bacterial meningitis.

I Can’t Move My Face! A Case of Bilateral Facial Palsy
Marna Rayl Greenberg, DO, MPH; Megan C. Urquhart, DO; Jessica K. Eygnor, DO; Charles C. Worrilow, MD; Nicole Ceccacci Gesell, DO; Bernadette Glenn Porter, BS; Andrew C. Miller, DO
Journal of the American Osteopathic Association, October 1, 2013 vol. 113 no. 10, 788-790.
http://doi.org/10.7556/jaoa.2013.048
The authors present a case of bilateral facial palsy in a 52-year-old man. The patient presented to an emergency department in Pennsylvania, describing left-sided neck pain and headache from “sleeping wrong,” symptoms which eventually progressed to facial diplegia by his fourth visit in 2 weeks. His admitting diagnosis was Bell palsy; he was ultimately tested for and found to have Lyme disease.

Lymphoadenopathy during Lyme Borreliosis Is Caused by Spirochete Migration-Induced Specific B Cell Activation.
Tunev SS, Hastey CJ, Hodzic E, Feng S, Barthold SW, et al.
(2011) PLoS Pathog 7(5): e1002066.
http://dx.doi.org/10.1371/journal.ppat.1002066
Lymphadenopathy is a hallmark of acute infection with Borrelia burgdorferi, a tick-borne spirochete and causative agent of Lyme borreliosis, but the underlying causes and the functional consequences of this lymph node enlargement have not been revealed. The present study demonstrates that extracellular, live spirochetes accumulate in the cortical areas of lymph nodes following infection of mice with either host-adapted, or tick-borne B. burgdorferi and that they, but not inactivated spirochetes, drive the lymphadenopathy.

5 cases of Lyme arthritis following an operation
Lyme Science Blog, by Daniel Cameron, MD, MPH, Mt. Kisco, New York
Dr. Cameron is a nationally recognized leader for his expertise in the diagnosis and treatment of Lyme disease and other tick-borne illnesses.
July 26, 2019
http://danielcameronmd.com/5-cases-of-lyme-arthritis-following-an-operation/
A review article by Hess and colleagues published in Sports Health explores the incident rate of Lyme arthritis in postoperative patients. One out of every three patients reports having arthritis as one of their initial symptoms of Lyme disease. In turn, a majority of patients are often first evaluated by orthopedic surgeons. Lyme arthritis, however, “has rarely been reported as a postsurgical complication.”

The association of lyme disease with loss of sexual libido and the role of urinary bladder detrusor dysfunction.
Puri BK, Shah M, Julu PO, Kingston MC, Monro JA.
International Neurourology Journal. 2014 Jun;18(2):95-7.
http://dx.doi.org/10.5213/inj.2014.18.2.95
The 2 groups were matched with respect to age, sex, body mass index, and mean arterial blood pressure. None of the 34 subjects was taking medication that might affect sexual libido or had undergone a previous operative procedure involving the genitourinary tract. Of the 16 Lyme disease patients, 8 (50%) had no loss of libido, and of the 18 controls, none had loss of libido (P<0.001). In the Lyme disease patient group, there was no statistically significant relationship between loss of libido and urinary bladder detrusor dysfunction (P=0.61). This pilot study suggested an association between Lyme disease and loss of libido. Moreover, this loss of libido did not seem to be associated with urinary bladder detrusor dysfunction.

Post-Treatment Lyme Syndrome and Central Sensitization
Batheja S, Nields JA, Landa A, Fallon BA.
The Journal of Neuropsychiatry and Clinical Neurosciences, online before print, 2013 Feb 27.
http://dx.doi.org/10.1176/appi.neuropsych.12090223
Central sensitization is a process that links a variety of chronic pain disorders that are characterized by hypersensitivity to noxious stimuli and pain in response to non-noxious stimuli.

Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia
Arseny A. Sokolov, MD, Reto Lienhard, MSc, Renaud Du Pasquier, MD, Véronique Erard, MD
Annals of Emergency Medicine, published online February 25, 2015.
http://dx.doi.org/10.1016/j.annemergmed.2015.01.011
This report for the first time illustrates that acute-onset language and motor symptoms may be directly related to Lyme neuroborreliosis. Neuroborreliosis may mimic other acute neurologic events such as stroke and should be taken into diagnostic consideration even in the absence of classic symptoms and evolution.

The association between infectious burden and Parkinson’s disease: A case-control study.
Bu XL, Wang X, Xiang Y, Shen LL, Wang QH, Liu YH, Jiao SS, Wang YR, Cao HY, Yi X, Liu CH, Deng B, Yao XQ, Xu ZQ, Zhou HD, Wang YJ.
Parkinsonism Related Disorders, pii: S353-800(5)0033-3. Online first, 05 May 30.
http://dx.doi.org/10.1016/j.parkreldis.2015.05.015
Higher infectious burden was found in PD patients. Individuals with higher infectious burden had higher alpha-synuclein levels in serum. Subjects with higher infectious burden had higher IL-1beta and IL-6 levels in serum. This study supports the role of infection in the etiology of PD.

A Highly Expressed Human Protein, Apolipoprotein B-100, Serves as an Autoantigen in a Subgroup of Patients with Lyme Disease
Crowley JT, Drouin EE, Pianta A, Strle K, Wang Q, Costello CE, Steere AC.
Journal of Infectious Diseases, online first, 2015 May 26.
http://doi.org/10.1093/infdis/jiv310
A subset of LA patients have high levels of apoB-100 in their joints and autoreactive T and B cell responses to the protein, which likely contributes to pathogenic autoimmunity in patients with antibiotic-refractory LA.

Recent-onset dilated cardiomyopathy associated with Borrelia burgdorferi infection.
Kuchynka P, Palecek T, Havranek S, Vitkova I, Nemecek E, Trckova R, Berenová D, Krsek D, Podzimkova J, Fikrle M, Danek BA, Linhart A.
Herz. Online first, 2015 May 5.
http://doi.org/10.1007/s00059-015-4308-1
Several recent small studies have suggested a causal link between Lyme disease and dilated cardiomyopathy (DCM) by demonstrating the presence of the Borrelia burgdorferi (Bb) genome in the myocardium of patients with recent-onset DCM. The aim of this study was to further investigate the effect of targeted antibiotic treatment of Bb-related recent-onset DCM in a larger cohort of patients.

Brainstem abnormalities and vestibular nerve enhancement in acute Neuroborreliosis
Nadja A Farshad-Amacker, Hans Scheffel, Thomas Frauenfelder and Hatem Alkadh
BMC Research Notes 2013, 6:551.
http://doi.org/10.1186/1756-0500-6-5
Patients infected with neuroborreliosis may present with unspecific neurologic symptoms and magnetic resonance imaging as a noninvasive imaging tool showing signal abnormalities in the brain stem and nerve root enhancement may help in establishing the diagnosis.

Cerebrovascular Manifestations of Lyme Neuroborreliosis – A Systematic Review of Published Cases
Garkowski A, Zajkowska J, Zajkowska A, Kulakowska A, Zajkowska O, Kubas B, Jurgilewicz D, Hladunski M, Lebkowska U.
Frontiers in Neurology. 2017 Apr 20;8:146. eCollection 2017.
https://doi.org/10.3389/fneur.2017.00146
This study included 88 patients with a median age of 46 years. The median interval from onset of symptoms suggesting Lyme disease to first symptoms of cerebrovascular manifestations of LNB was 3.5 months. The most common cerebrovascular manifestation of LNB was ischemic stroke (76.1%), followed by TIA (11.4%). The posterior circulation was affected alone in 37.8% of patients, the anterior circulation in 24.4% of patients, and in 37.8% of cases, posterior and anterior circulations were affected simultaneously. The most common affected vessels were middle cerebral artery—in 19 cases, basilar artery—in 17 cases, and anterior cerebral artery—in 16 cases. A good response to antibiotic treatment was achieved in the vast number of patients (75.3%). The overall mortality rate was 4.7%. Cerebral vasculitis and stroke due to LNB should be considered, especially in patients who live in or have come from areas with high prevalence of tick-borne diseases, as well as in those without cardiovascular risk factors, but with
troke-like symptoms of unknown cause.

Complete AV block in Lyme carditis: an important differential diagnosis.
Semmler D, Blank R, Rupprecht HJ.
Clinical Research in Cardiology, published ahead of print on May 13, 2010.
http://www.ncbi.nlm.nih.gov/pubmed/20464556
We report on a 37-year old male, who was admitted to the emergency department because of dizziness and generalized tiredness. Physical examination and the initial laboratory values revealed no abnormalities. The patient’s electrocardiogram on admission revealed newly diagnosed bradycardia due to atrioventricular heart block. The ventricular heart rate was 35/min. The patient was admitted to the ICU. Lyme serology and Western blot were positive for Borrelia antibodies. After institution of antibiotic therapy with ceftriaxone, atrioventricular heart block resolved rapidly. We therefore have to assume that in this patient Lyme carditis was the cause of third-degree AV block.

Lyme disease presenting with facial palsy and myocarditis mimicking myocardial infarction
Gilson J, Khalighi K, Elmi F, Krishnamurthy M, Talebian A, Toor RS.
Journal of Community Hospital Internal Medicine Perspectives, 2017 Dec 14;7(6):363-365.
https://doi.org/10.1080/20009666.2017.1396170
This is a rare case of Lyme myocarditis associated with markedly elevated Troponin I, normal left ventricle function, and an absence of conduction abnormalities. To the best of our knowledge, Lyme myocarditis mimicking acute coronary syndrome with such high levels of Troponin I and neurologic compromise has not been previously described. Lyme myocarditis may be a challenging diagnosis in endemic areas especially in patients with coronary artery disease risk factors, presenting with typical chest pain, EKG changes and positive cardiac biomarkers. Therefore, it should be considered a differential diagnosis in patients presenting with clinical symptoms suggestive of acute coronary syndrome.

Neuroborreliosis-associated cerebral vasculitis: long-term outcome and health-related quality of life.
Back T, Grunig S, Winter Y, Bodechtel U, Guthke K, Khati D, von Kummer R.
Journal of Neurology, online before print, 2013 Jan 18.
http://dx.doi.org/10.1007/s00415-013-6831-4
Neuroborreliosis can cause recurrent stroke or TIA on the basis of cerebral vasculitis.

Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview
Rhee H, Cameron DJ
International Journal of General Medicine, February 2012,
Volume 2012:5, pages 163-174.
http://dx.doi.org/10.2147/IJGM.S24212
The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection.

INTRAVENOUS IMMUNOGLOBULIN FOR THE TREATMENT OF AUTOIMMUNE ENCEPHALOPATHY IN CHILDREN WITH AUTISM
Autoimmune targets in Cunningham Panel™ predict IVIG treatment response in subset of autism patients
Connery et al. Translational Psychiatry (2018)8:148.
doi 10.1038/s41398-018-0214-7
The paper addresses how brain targeted autoantibodies in an individual with CNS dysfunction point to an autoimmune encephalopathy (AIE). AIE’s have generally seen good response with IVIG therapy.  Dr. Richard Frye, senior author, concludes that high levels of either the anti-lysoganglioside GM1 antibody or CAMKII are associated with tics and OCD behavior and high anti-dopamine D2L to D1 antibody ratio is associated with irritability, a frequently targeted ASD symptom.  The Cunningham Panel™ of Tests predicted response to IVIG treatment with an accuracy of 81%, 88% and 88% on the ABC, SRS, and parental evaluations, respectively.  Study suggests that two of the autoantibodies in particular, the anti-Tubulin and anti-D2R were associated with responsiveness to IVIG treatment, suggesting that these could be biomarkers to select individuals who might benefit most from IVIG treatment. It also may be that the autoantibodies identified as predictive or responsive to IVIG may be closely associated with modulation of behavior as has been suggested in Sydenham Chorea and PANDAS.

Cerebral vasculitis and intracranial multiple aneurysms in a child with Lyme neuroborreliosis
Kortela E, Hytönen J, Numminen J, Overmyer M, Saxen H, Oksi J.
JMM Case Reports. 2017 Apr 21;4(4):e005090.
https://doi.org/10.1099/jmmcr.0.005090
We describe a paediatric patient with sensorineural auditory dysfunction, headache, fatigue and epileptic seizures as sequelae of meningoencephalitis/Lyme neuroborreliosis (LNB) caused by B. burgdo rferi. Brain magnetic resonance imaging revealed widespread enhancement of the leptomeninges, cranial nerves and artery walls compatible with vasculitis and disturbances in cerebrospinal fluid (CSF) circulation. The patient was treated with ceftriaxone for 2 weeks. Two years later, the patient had an ischemic stroke. Brain magnetic resonance angiography revealed multiple aneurysms, which were not present previously. The largest aneurysm was operated rapidly. The patient was treated with another course of intravenous ceftriaxone for 4 weeks and pulse therapy with corticosteroids. He recovered well. This unique case demonstrates complications of LNB that can result in serious morbidity or even mortality. Lumbar puncture and analysis should be considered for paediatric patients with epileptic seizures or cerebrovascular events living in a Lyme borreliosis endemic area.

Lyme disease presenting as multiple ischaemic strokes
Sui Li, Michal Vytopil, Kinan Hreib, Donald E Craven
Practical Neurology, 2015;15:284-288.
http://doi.org/10.1136/practneurol-2014-001072
Central nervous system Lyme disease occasionally presents with ischaemic strokes; this case is unusual in showing vasculopathy on brain imaging, supporting meningovasculitis as the likely mechanism.

Postural orthostatic tachycardia syndrome following Lyme disease.
Khalil Kanjwal, Beverly Karabin, Yousuf Kanjwal, Blair P. Grubb
Cardiology Journal (formerly Folia Cardiologica), Vol. 18 No. 1, 2011
http://www.ncbi.nlm.nih.gov/pubmed/21305487
All of the patients in this report had suffered from LD in the past and were successfully treated with antibiotics. All patients were apparently well, until years later when they presented with fatigue, cognitive dysfunction and orthostatic intolerance. These patients were diagnosed with POTS on the basis of clinical features and results of the tilt table (HUTT) testing. In an appropriate clinical setting, evaluation for POTS in patients suffering from post LD syndrome may lead to early recognition and treatment, with subsequent improvement in symptoms of orthostatic intolerance.

A Tale of Two Syndromes: Lyme Disease Preceding Postural Orthostatic Tachycardia Syndrome.
Noyes AM, Kluger J.
Annals of Noninvasive Electrocardiology, online before print 2014 May 15.
http://doi.org/10.1111/anec.12158
The pathogenesis of postural orthostatic tachycardia syndrome (POTS) is poorly understood. However, it has been suggested that altered immune activity or denervation of the autonomic system following illness may be an important trigger. Patients infected with Lyme disease have a small incidence of post-Lyme disease syndrome that share similar characteristics to POTS.

Clinical association: Lyme disease and Guillain-Barre syndrome
Patel, Kinner et al.
The American Journal of Emergency Medicine, online first, July 6, 2017.
http://dx.doi.org/10.1016/j.ajem.2017.07.030
In this case we report a 31-year-old male who was diagnosed with Lyme disease and GBS with relevant clinical presentation including progressive numbness and weakness in bilateral hands and feet for the past 1 week along with areflexia. Initiation of medical therapy with intravenous immunoglobulin and parenteral ceftriaxone resulted in resolution of his symptoms. The treatment of both diseases early can help prevent further central nervous complications leading to high morbidity and mortality.

Atypical Lyme Neuroborreliosis, Guillain-Barré Syndrome or Conversion Disorder:  Differential Diagnosis of Unusual Neurological Presentations
Teodoro T., Oliveira R. and Afonso P.
Case Reports in Neurology 2019;11:142–147.
https://doi.org/10.1159/000499901
Nervous system Lyme disease and Guillain-Barré syndrome are common neurological conditions that may present with unusual symptoms rendering differential diagnosis difficult. We report the case of a 62-year-old woman presenting with asymmetrical tetraparesis and hyporeflexia.
Initially the presumed diagnosis of Guillain-Barré syndrome with a possible functional component was suspected and treatment with intravenous immunoglobulin was initiated. Due to partial response to therapy and further test results including positive serologies and cerebrospinal fluid antibodies for Borrelia, the diagnosis of neuroborreliosis was considered. Further exploring revealed the possibility of exposure to ticks although there was no report of typical skin lesions.
Daily physical therapy and appropriate antibiotic treatment with parenteral ceftriaxone resulted in significant improvement of motor symptoms and functional status. The patient was discharged with marked functional improvement and indication for further physical rehabilitation.

Primary cutaneous marginal zone lymphoma associated with juxta-articular fibrotic nodules in a teenager.
Ghatalia P, Porter J, Wroblewski D, Carlson JA.
Journal of Cutaneous Pathology, 2013 May;40(5):477-84.
http://dx.doi.org/10.1111/cup.12102
Primary cutaneous marginal zone lymphoma (PCMZL) has rarely been reported in teenagers and is occasionally associated with Borrelia burgdorferi infection. Juxta-articular fibrotic nodules represent a unique, localized fibrosing response to spirochete infections, namely Borreliosis.

Lyme Disease Manifestations in the Foot and Ankle: A Retrospective Case Series
Miller JR, Dunn KW, Braccia D, Ciliberti LJ Jr, Becker DK, Hollinger JK, Brand SM.
Journal of Foot & Ankle Surgery, 2016 Nov – Dec; 55(6):1241-1244.
http://doi.org/10.1053/j.jfas.2015.06.006
We present a retrospective case series of 11 cases of painful arthritis in the foot and ankle with confirmatory Lyme disease testing.

Long-term intrathecal infusion of outer surface protein C from Borrelia burgdorferi causes axonal damage.
Tauber SC, Ribes S, Ebert S, Heinz T, Fingerle V, Bunkowski S, Kugelstadt D, Spreer A, Jahn O, Eiffert H, Nau R.
Journal of Neuropathology and Experimental Neurology. 2011 Sep;70(9):748-57.
http://dx.doi.org/10.1097/NEN.0b013e3182289acd
Lyme neuroborreliosis (LNB) is the most frequent tick-borne infectious disease of the central nervous system. In acute LNB and the rare chronic state of infection, patients can experience cognitive deficits such as attention and memory disturbances. During LNB, single compounds of Borrelia burgdorferi sensu lato are released into the subarachnoid space. Continuous exposure to intrathecal B. burgdorferi OspC led to activation of microglia and axonal damage without demonstrable cognitive impairment in experimental mice. These results suggest that long-term intrathecal exposure to OspC resulted in axonal damage that may underlie the neurologic manifestations in chronic LNB.

Early Disseminated Lyme Disease Masquerading as Mononucleosis: A Case Report
Tumminello R, Glaspey L, Bhamidipati A, Sheehan P, Patel S.
The Journal of Emergency Medicine online first, 2017 Oct 25.
https://doi.org/10.1016/j.jemermed.2017.09.005
We report a case of early-disseminated Lyme disease presenting with Borrelia meningitis and concomitant Lyme carditis, which was misdiagnosed as mononucleosis. A young, previously healthy patient had been hiking in the woods of upstate New York and 4 weeks later developed fever, night sweats, and myalgias. He was diagnosed with mononucleosis via a positive rapid heterophile agglutination antibody test to the Epstein-Barr virus at a walk-in clinic and was started on medications, but then subsequently developed left hip pain, a facial droop, and a very long first-degree atrioventricular conduction block. He went to the Emergency Department, where he had testing that confirmed disseminated Lyme disease.

Lyme Disease and MS Can Overlap
Conference Coverage – Americas Committee for Treatment and Research in Multiple Sclerosis – ACTRIMS 2016
By Gale Scott, MD Magazine, Plainsboro, New Jersey February 19, 2016
http://www.hcplive.com/conference-coverage/actrims-2016/lyme-disease-and-ms-can-overlap
Lyme Disease can cause neurological symptoms, some of which overlap with clinical and radiological findings in multiple sclerosis. Of the 90 patients, 7.8% were positive for Lyme.

On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics
BO Frykholm
Medical Hypotheses, available online 6 March 2009.
http://dx.doi.org/10.1016/j.mehy.2008.11.045
Close similarities in the courses of multiple sclerosis and schizophrenia laid the theoretical ground for attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae, which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is postulated that since rickettsial microorganisms are ubiquitous in human populations they and the human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of them may become aggressive and pathogenic. The otherwise promising results of the pilot study seem to warrant further and controlled clinical trials with treatment with antibiotics of patients with psychotic symptoms. As the second patient with psychotic symptoms to enter the study, had a long standing history of chronic fatigue, where an initial treatment with the antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided, when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic in February and March 2007, to include them in the study. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement.

Lyme neuroborreliosis and dementia
Blanc F, Philippi N, Cretin B, Kleitz C, Berly L, Jung B, Kremer S, Namer IJ, Sellal F, Jaulhac B, de Seze J.
Journal of Alzheimers Disease. 2014;41(4):1087-93.
http://doi.org/10.3233/JAD-130446
Among 1,594 patients seen for dementia, we prospectively identified and studied 20 patients (1.25%) with dementia and a positive AI. Patients underwent a battery of neuropsychological tests brain, MRI, FDG-PET, and cerebrospinal fluid (CSF) analysis. An etiological diagnosis of the dementia was made at the end of the follow-up of 5.0 ± 2.9 years. Results: We found two groups of patients with dementia, the first (n = 7, 0.44%) with certain neuroborreliosis and stability or mild improvement of dementia after treatment by antibiotics and the second (n = 13, 0.81%) with progressive worsening of dementia, despite the antibiotics.

Do Infections Cause Alzheimers Disease
By Lauren Ingeno, Drexel News Blog, Drexel University, Philadelphia, Pennsylvania, February 10, 2016

Do Infections Cause Alzheimer’s Disease?


A study from Drexel researchers offers new evidence to support a controversial hypothesis: Alzheimer’s disease results from the body’s inflammatory response to chronic infections. The scientists believe that bacteria create slimy, impenetrable biofilms in the brain, prompting the immune system to destroy surrounding tissue. This intriguing idea — though supported by a growing body of documentation — is still contested by many in the scientific community.

Alzheimer’s Disease: a novel hypothesis integrating spirochetes, biofilm, and the immune system
Herbert B. Allen, Diego Morales, Krister Jones, Suresh Joshi
Journal of Neuroinfectious Diseases 2016, 7:200.
http://www.omicsonline.com/open-access/neuroinfectious-diseases-abstract.php?abstract_id=67274
In the light of recent studies showing the presence of spirochetes in the brains of Alzheimer’s disease (AD) patients, we have studied (post mortem) the hippocampus region in the brains of similarly affected AD patients utilizing both pathology and immunohistochemistry. Our findings demonstrate that the plaques, which are characteristically found in AD brains, reveal the presence of biofilms.

Do Microbes Trigger Alzheimer’s Disease? The once fringe idea is gaining traction among the scientific community.
By Jill U. Adams, The Scientist, Midland, Ontario, Canada
September 1, 2017
http://www.the-scientist.com/?articles.view/articleNo/50208/title/Do-Microbes-Trigger-Alzheimer-s-Disease-/
In late 2011, Drexel University dermatology professor Herbert Allen was astounded to read a new research paper documenting the presence of long, corkscrew-shape bacteria called spirochetes in postmortem brains of patients with Alzheimer’s disease. Combing data from published reports, the International Alzheimer Research Center’s Judith Miklossy and colleagues had found evidence of spirochetes in 451 of 495 Alzheimer’s brains. In 25 percent of cases, researchers had identified the spirochete as Borrelia burgdorferi, a causative agent of Lyme disease. Control brains did not contain the spirochetes.

A study on the association between infectious burden and Alzheimer’s disease.
Bu XL, Yao XQ, Jiao SS, Zeng F, Liu YH, Xiang Y, Liang CR, Wang QH, Wang X, Cao HY, Yi X, Deng B, Liu CH, Xu J, Zhang LL, Gao CY, Xu ZQ, Zhang M, Wang L, Tan XL, Xu X, Zhou HD, Wang YJ
European Journal of Neurology, online before print, 2014 Jun 9.
http://doi.org/10.1111/ene.12477
IB consisting of CMV, HSV-1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.

Growing list of eye problems in Lyme disease
Blog: All Things Lyme, by Daniel Cameron, MD, MPH, a nationally recognized leader for his expertise in the diagnosis and treatment of Lyme disease and other tick-borne illnesses.
October 23, 2016
danielcameronmd.com/growing-list-eye-problems-lyme-disease/
Ophthalmic manifestations of tick-borne diseases are increasing in the United States, according to a review published recently in Current Opinion in Ophthalmology. And, “although ocular involvement can be self-limited, delays in diagnosis may result in vision impairment and even blindness,” stated Sathiamoorthi from the Mayo Clinic.

Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options
Gerhard J Molderings,corresponding author Stefan Brettner, Jürgen Homann, and Lawrence B Afrin
J Hematol Oncol. 2011; 4: 10.
doi: 10.1186/1756-8722-4-10
Mast cell activation disease comprises disorders characterized by accumulation of genetically altered mast cells and/or abnormal release of these cells’ mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing. In most cases of mast cell activation disease, diagnosis is possible by relatively non-invasive investigation. Effective therapy often consists simply of antihistamines and mast cell membrane-stabilising compounds supplemented with medications targeted at specific symptoms and complications. Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or patients in whom a definitively diagnosed major illness does not well account for the entirety of the patient’s presentation.

The eye and tick-borne disease in the United States
Sathiamoorthi S, Smith WM.
Current Opinion in Ophthalmology 2016 Nov;27(6):530-537.
http://doi.org/10.1097/ICU.0000000000000308
Purpose of review Tick-borne diseases are increasing in incidence and geographic distribution. Several diseases endemic to the United States have ophthalmic manifestations, including the most common tick-borne disease, Lyme borreliosis. As ocular complaints may lead a patient to seek medical evaluation, it is important to be aware of the systemic and ophthalmic manifestations of tick-borne diseases in order to make the correct diagnosis. Recent findings Vision-threatening ophthalmic manifestations are relatively common in Lyme disease and Rocky Mountain spotted fever. Ocular involvement is rare in babesiosis, tick-borne relapsing fever, Powassan encephalitis, ehrlichiosis, anaplasmosis, and Colorado tick fever.There are clear guidelines for diagnosis and treatment of Lyme disease; however, confusion and misinformation among the general public as well as controversy about chronic or late-stage Lyme disease can impact the evaluation of ophthalmic disease. Furthermore, there are many gaps in our knowledge regarding the pathophysiology of ocular borreliosis although it seems likely that Lyme uveitis is rare in the United States.

Seroprevalence against Rickettsia and Borrelia Species in Patients with Uveitis: A Prospective Survey
Madsen KB, Wallménius K, Fridman Å, Påhlson C, Nilsson K.
Journal of Ophthalmology. 2017;2017:9247465. Online first, 2017 Nov 26.
https://doi.org/10.1155/2017/9247465
The findings are indicative for an association between infection or exposure to Rickettsia spp. and uveitis with a seropositivity among patients with recurrent uveitis in concordance with the spread of rickettsial exposure in a tick-exposed population.

Isolated trochlear palsy secondary to Lyme neuroborreliosis
Bababeygy SR, Quiros PA.
International Ophthalmology, online before print, December 20, 2011.
http://dx.doi.org/10.1007/s10792-011-9482-4
The objective of the study is to report the first case of isolated trochlear palsy secondary to Lyme neuroborreliosis in an adult. A 22-year-old male presented with history of flu-like illness and headache, accompanied by vertical binocular diplopia, worse on downgaze and better in upgaze and right head tilt. Physical examination revealed trochlear palsy on the left side with a compensatory head tilt to the opposite side. Immunoglobulin (Ig)M and IgG antibodies against Borrelia burgdorferi were positive in serum and cerebral spinal fluid (CSF). Symptoms of double vision completely resolved after 3 weeks of antibiotic treatment with intravenous ceftriaxone.

Bacterial tick-borne diseases caused by Bartonella spp., Borrelia burgdorferi sensu lato, Coxiella burnetii, and Rickettsia spp. among patients with cataract surgery.
Chmielewski T, Brydak-Godowska J, Fiecek B, Rorot U, Sedrowicz E, Werenowska M, Kopacz D, Hevelke A, Michniewicz M, Kecik D, Tylewska-Wierzbanowska S.
Medical Science Monitor. 2014 Jun 5;20:927-31.
http://doi.org/10.12659/MSM.890149
Presence of DNA of yet uncultured and undescribed species of Bartonella in eye liquid indicates past infection with this pathogen. Specific antibodies to B. burgdorferi sensu lato and Bartonella sp. are detected more frequently in patients with cataract compared to the control group. This could indicate a possible role of these organisms in the pathological processes within the eyeball, leading to changes in the lens. Further studies are needed to identify Bartonella species, as well as to recognize the infectious mechanisms involved in cataract development.

Lyme neuroborreliosis: a treatable cause of acute ocular motor disturbances in children
M H Correll, N Datta, H S S Arvidsson, H A Melsom, A K Thielberg, M Bjerager, M C Brodsky, J P Saunte
British Journal of Ophthalmology, online first, April 13, 2015.
http://doi.org/10.1136/bjophthalmol-2015-306855
LNB can present as acute ocular motor disorders in conjunction with fatigue and other clinical manifestations. In endemic areas, children with unexplained, acquired ocular motor abnormalities should be evaluated for LNB, a treatable medical condition.

Lyme disease: sudden hearing loss as the sole presentation.
Espiney Amaro C, Montalvão P, Huins C, Saraiva J.
The Journal of Laryngology & Otology, online before print, 2015 Jan 26.
http://dx.doi.org/10.1017/S0022215114003417
In this report, a very unusual presentation of this condition is described, in which sudden onset sensorineural hearing loss was the sole presenting symptom.

Lyme Disease Associated With Sudden Sensorineural Hearing Loss: Case Report and Literature Review.
Peeters N, van der Kolk BY, Thijsen SF, Colnot DR.
Otology and Neurotology, online bofore print, 2013 Jan 7.
http://dx.doi.org/10.1097/MAO.0b013e31827c9f93
Literature suggests that sudden sensorineural hearing loss may coincide with Borrelia burgdorferi infection. A higher incidence of confirmed positive serology for Borrelia burgdorferi in patients with sudden deafness seems to be depending on the country and on the tests used to confirm Lyme disease. This should be taken into account if serologic testing for Lyme disease in patients with sudden deafness is considered.

Hyperosmia in Lyme disease
Puri BK, Monro JA, Julu PO, Kingston MC, Shah M.
Arquivos de Neuro-Psiquiatria. 2014 Aug;72(8):596-7.
http://dx.doi.org/10.1590/0004-282X20140109
Neurological involvement in Lyme disease has been reported to include meningitis, cranial neuropathy and radiculoneuritis. While it is known that in some cases of asceptic meningitis patients may develop hyperosmia, the association between hyperosmia and Lyme disease has not previously been studied.

Pediatric otolaryngological manifestations of systemic diseases
Pignataro L, Torretta S, Capaccio P, Esposito S, Marchisio P.
International Journal of Pediatric Otorhinolaryngology, Vol 73, Supplement 1, December 2009, Pages S33-S37.
http://dx.doi.org/10.1016/S0165-5876%2809%2970007-2
Systemic bacterial and fungal infections may sometimes present local manifestations within otolaryngological district whose early detection may be useful in establishing a correct diagnosis and more appropriate treatment. This paper reviews certain systemic bacterial and fungal diseases presenting ENT manifestations in the pediatric population from an otolaryngological perspective.

Exacerbation of chronic pain after dental extractions in a patient with post-treatment Lyme disease syndrome
Lim S, Kinjo S.
Saudi Journal of Anesthesia 2018;12:112-4.
https://doi.org/10.4103/sja.SJA_47_17
A subset of patients who had Lyme disease experience postinfectious signs or symptoms called post-treatment Lyme disease syndrome (PTLDS). PTLDS is a chronic condition including pain in joints and muscles, neurological symptoms including demyelinating diseases, peripheral neuropathy, headaches, sleep disturbances, fatigue, and cardiac conditions. We report a case of difficult acute pain management in a patient with PTLDS who underwent dental extractions and required admission to an intensive care unit for pain control.

Unilateral phrenic nerve lesion in Lyme neuroborreliosis.
Djukic M, Larsen J, Lingor P, Nau R.
BMC Pulmonary Medicine. 2013 Jan 18;13:4.
http://doi.org/10.1186/1471-2466-13-4
Among a variety of more common differential diagnoses, the aetiology of acute respiratory failure includes Lyme neuroborreliosis. Diaphragmatic weakness should be considered in the differential workup because of its potentially treatable nature.

Urinary bladder detrusor dysfunction symptoms in lyme disease.
Puri BK, Shah M, Julu PO, Kingston MC, Monro JA.
International Neurourology Journal, 2013 Sep;17(3):127-9.
http://doi.org/10.5213/inj.2013.17.3.127
This first systematic controlled study confirms that Lyme disease is associated with urinary bladder detrusor dysfunction. Further evaluation of detrusor function is warranted in this disease.

Dysarthria and thrombocytopenia after tick bite
Muhammad A. Mir
Blood, Oct 2013; 122: 2538.
http://doi.org/10.1182/blood-2013-06-506410
A 63-year-old woman presented with fever, confusion, dysarthria (slurred speech), new-onset thrombocytopenia and mild transaminitis 2 weeks after a tick bite to the left thigh.

Pancytopenia in Lyme disease
Raman Mehrzad, Joseph Bravoco
British Medical Journal Case Reports, online March 4, 2014
http://doi.org/10.1136/bcr-2013-201079
We present a 49-year-old man with subacute onset of fever, weakness, shortness of breath, unilateral lower extremity oedema and pancytopenia who was found to have positive serology for Lyme disease. The patient presented with an intravascular haemolytic pattern on laboratory findings where an extensive infectious disease and haematological workup ruled out ehrlichiosis, anaplasmosis, babesiosis, Rocky Mountain spotted fever, HIV, hepatitis B and other parasitic infections. This left a very atypical presentation of Lyme disease.

A Cluster of Startling Lyme Disease Cases in the Upper Midwest
Press Release: The American Council on Science and Health
By Julianna LeMieux, Washington, DC
January 26, 2018
https://www.acsh.org/news/2018/01/26/cluster-startling-lyme-disease-cases-upper-midwest-12473
Rarely, Lyme disease manifests as a neuroinvasive condition called Garin-Bujadoux-Bannwarth syndrome or, more frequently, just Bannwarth syndrome. This complicated version of Lyme Disease is characterized by a few telltale signs. They are, painful meningoradiculoneuritis (inflammation of one or more roots of the spinal nerve) that leads to motor weakness, facial nerve palsy and neuropathy usually in the hands and feet. The other is lymphocytic pleocytosis (an abnormally large number of lymphocytes) in the cerebrospinal fluid (CSF). Because it is not a reportable disease, it is not well understood how much of the disease is popping up across the country. That said, five cases in the same few weeks seemed strange enough for these authors to report it.

Case Report: Bilateral diaphragmatic dysfunction due to Borrelia Burgdorferi.
Basunaid S, van der Grinten C, Cobben N, Otte A, Sprooten R, Gernot R.
F1000Research. 2014 Oct 6;3:235. eCollection 2014.
http://doi.org/10.12688/f1000research.5375.1
Lyme disease should be considered in the differential diagnosis of diaphragmatic dysfunction. It is a tick-borne illness caused by one of the three pathogenic species of the spirochete Borrelia burgdorferi, present in Europe. A delay in recognizing the symptoms can negatively affect the success of treatment. Non-invasive mechanical ventilation (NIV) is considered a treatment option for patients with diaphragmatic paralysis.

A case of CNS Lyme disease presenting with multiple cranial neuropathies and mimicking a B cell lymphoma
Christopher Perrone, Denise Xu, Taneeta Ganguly, Donna Kurowski, Michael Mullen and Amy Pruitt
Neurology, April 18, 2017, 88:16 Supplement P1.312.
Abstracts: American Academy of Neurology, 69th Annual Meeting, Boston. http://www.neurology.org/content/88/16_Supplement/P1.312.short
This case highlights how Lyme disease should be considered in the differential diagnosis for multiple cranial neuropathies. Further, as prior case reports of CNS Lyme patients have shown polyclonal and monoclonal lymphocyte expansion, this case demonstrates the diagnostic uncertainty regarding whether flow cytometry reflects a reactive process to infection or a new lymphoma. Treatment with antibiotics and clinical improvement helped to clarify the etiology in this case.

Ticks and salt: an atypical case of neuroborreliosis
Siddiqui N, St Peter DM, Marur S.
Journal of Community Hospital Internal Medicine Perspectives, 7(6):358-362.
https://doi.org/10.1080/20009666.2017.1407209
It is well documented that central nervous system (CNS) infections may lead to syndrome of inappropriate anti-diuretic hormone secretion (SIADH), but diagnosing these can prove difficult in patients with atypical presentations. Our case demonstrates the need to screen for Lyme disease in endemic areas in patients presenting with neurologic symptoms and SIADH.

American neuroborreliosis presenting as cranial polyneuritis and radiculoneuritis 
Erwin Wang, Prasad R. Shirvalkar, Carolina B. Maciel, Alexander E. Merkler, Joseph Safdieh, and Ajay Gupta
Neurology: Neuroimmunology & Neuroinflammation, online before print, October 1, 2014.
http://doi.org/10.1212/NXI.0000000000000030
While facial nerve involvement represents about 80% of cranial neuritis in Lyme neuroborreliosis (LNB), other cranial nerves may also be individually involved.

Borrelia infection and risk of celiac disease
Alaedini A, Lebwohl B, Wormser GP, Green PH, Ludvigsson JF.
BMC Medicine, 2017 Sep 15;15(1):169.
https://doi.org/10.1186/s12916-017-0926-1
Environmental factors, including infectious agents, are speculated to play a role in the rising prevalence and the geographic distribution of celiac disease, an autoimmune disorder. In the USA and Sweden where the regional variation in the frequency of celiac disease has been studied, a similarity with the geographic distribution of Lyme disease, an emerging multisystemic infection caused by Borrelia burgdorferi spirochetes, has been found, thus raising the possibility of a link. We aimed to determine if infection with Borrelia contributes to an increased risk of celiac disease.

Septolobular Panniculitis in Disseminated Lyme Borreliosis
Dittmer M, Willis M, Selby J, Liu V.
Journal of Cutaneous Pathology, online first, 2018 Jan 2.
https://doi.org/10.1111/cup.13100
A rare cutaneous manifestation that is increasingly reported in Lyme patients is panniculitis, which develops after dissemination of the spirochete. We present such a case in a patient who was initially treated for cellulitis as well as neck and radicular leg pain, thereby expanding the cutaneous spectrum of Lyme disease.

Disseminated Lyme Disease Presenting With Nonsexual Acute Genital Ulcers
Finch JJ, Wald J, Ferenczi K, Khalid S, Murphy M.
JAMA Dermatology. Online before print, 2014 Aug 27.
http://doi.org/10.1001/jamadermatol.2014.1072
Importance Nonsexual acute genital ulceration (NAGU) is a rare vulvar skin condition typically affecting girls and young women, characterized by acute onset of singular or multiple painful vaginal ulcers. The etiology of this ulcerative dermatosis has not been identified, although it has been associated with systemic infections. To our knowledge, this is the first report of an association with Lyme disease.

Lobular panniculitis due to Borrelia burgdorferi infection mimicking subcutaneous panniculitis-like T-cell lymphoma.
Kempf W, Kazakov DV, Kutzner H.
The American Journal of Dermatopathology. 2013 Apr;35(2):e30-3.
http://doi.org/10.1097/DAD.0b013e31827132cb
The authors present an unusual case of lobular panniculitis caused by Borrelia burgdorferi senso latu infection in a 56-year-old man.

Exploring the Association Between Morgellons Disease and Lyme Disease.Identification of Borrelia Burgdorferi in Morgellons Disease Patients
Marianne J Middelveen, Cheryl Bandoski, Jennie Burke, Eva Sapi, Katherine R Filush, Yean Wang, Agustin Franco, Peter J Mayne, Raphael B Stricker
BMC Dermatology, 2015;15(1).
http://www.medscape.com/viewarticle/841141
Our study using multiple detection methods confirms that MD is a true somatic illness associated with Borrelia spirochetes that cause Lyme disease. Further studies are needed to determine the optimal treatment for this spirochete-associated dermopathy.

Disseminated Lyme borreliosis preceded by hepatitis in an African American male.
Fathi R, Huang WW, Brown K.
Dermatology Online Journal. 2012 Oct 15;18(10):4.
http://escholarship.org/uc/item/9d7813rh
Lyme disease is the most common tick-borne disease in the United States and has a multitude of systemic effects. Infrequently, however, Lyme disease is seen to cause liver dysfunction. Dermatologists should be aware that early, disseminated borreliosis can present with multiple erythema migrans plaques and hepatitis.

Babesiosis Presenting as Acute Liver Failure
Nassar Y, Richter S.
Case Reports in Gastroenterology. 2017 Dec 18;11(3):769-773. eCollection 2017 Sep-Dec.
https://doi.org/10.1159/000485373
Babesiosis is a zoonotic, tick-borne infection caused by the protozoan Babesia. It is transmitted by the Ixodes ticks which transmit the infection to humans. Babesia microti, Babesia duncani, Babesia divergens, and Babesia venatorum are species that have been identified as being infectious to humans worldwide. The most common species causing infection to humans is B. microti which is endemic to the Northeast and Midwestern United States with most infections occurring between the months of May and October. We report a case of an elderly man with acute liver failure due to an infection with B. microti.

A New Perspective on the Possible Cause of Alzheimer’s Disease: Microbes
Press Release: Journal of Alzheimer’s Disease
15 March 2016
http://www.j-alz.com/content/new-perspective-possible-cause-alzheimers-disease-microbes
A landmark Editorial issued by 33 senior scientists and clinicians from a dozen countries across the world has been published in the highly regarded peer-reviewed journal, Journal of Alzheimer’s Disease. This major call for action is based on substantial evidence indicating that some microbes – a specific virus and particular bacteria – are likely major causes of the disease. Almost all research in the field has focused on alternative hypotheses – over 400 clinical trials of such anti-Alzheimer agents have been carried out, but all have failed.

Aggressiveness, violence, homicidality, homicide, and Lyme disease
Bransfield RC.
Neuropsychiatric Disease and Treatment, 2018 Mar 9;14:693-713.
https://doi.org/10.2147/NDT.S155143
No study has previously analyzed aggressiveness, homicide, and Lyme disease (LD). LD and the immune, biochemical, neurotransmitter, and the neural circuit reactions to it can cause impairments associated with violence. Many LD patients have no aggressiveness tendencies or only mild degrees of low frustration tolerance and irritability and pose no danger; however, a lesser number experience explosive anger, a lesser number experience homicidal thoughts and impulses, and much lesser number commit homicides. Since such large numbers are affected by LD, this small percent can be highly significant. Much of the violence associated with LD can be avoided with better prevention, diagnosis, and treatment of LD.

Obsessive-compulsive symptoms in adults with Lyme disease
Johnco C, Kugler BB, Murphy TK, Storch EA.
General Hospital Psychiatry. 2018 Jan 31;51:85-89.
https://doi.org/10.1016/j.genhosppsych.2018.01.009
OCS were common, with 84% endorsing clinically significant symptoms, 26% of which endorsed symptoms onset during the six months following their Lyme disease diagnosis. This study highlights the common co-occurrence of OCS in patients with Lyme disease. It is unclear whether OCS are due to the direct physiological effects of Lyme disease or associated immunologic response, a psychological response to illness, a functional somatic syndrome, or some combination of these.

Association of Lyme Disease and Schizoaffective Disorder, Bipolar Type: Is it Inflammation Mediated?
Mattingley DW, Koola MM.
Indian Journal of Psychological Medicine. 2015 Apr-Jun;37(2):243-6.
http://doi.org/10.4103/0253-7176.155660
Lyme disease has been reported to be associated with various psychiatric presentations. Borrelia burgdorferi (Bb) can present with symptoms similar to schizophrenia and bipolar disorder. It has been suggested that inflammation incurred during the Bb infection leads to neurodegenerative changes that result in schizophrenia-like presentations.

Chronic Lyme Disease Linked to ADHD in Adults
By Megan Brooks, Medscape Medical News
http://www.medscape.com/viewarticle/763458
“The association between ADHD and CLD has not been identified previously,” principal investigator Joel L. Young, MD, medical director, Rochester Center for Behavioral Medicine, Rochester, Minnesota, told Medscape Medical News. The survey results also corroborate earlier findings of a relationship between CLD and anxiety and depression, he said.

Perineuritis in acute lyme neuroborreliosis
Marwa Elamin, Yazan Alderazi, Gerard Mullins, Michael A. Farrell, Sue O’Connell, Timothy J. Counihan
Muscle & Nerve, Volume 39, Issue 6, Pages 851 – 854. Published Online: 13 May 2009
http://dx.doi.org/10.1002/mus.21289
Perineuritis is an unusual cause of direct peripheral nerve injury. We describe the clinicopathologic features of a 56-year-old man with mononeuritis multiplex due to Lyme disease; sural nerve biopsy demonstrated florid perineuritis. Treatment with intravenous ceftriaxone resulted in marked neurologic improvement. This study supports the notion that perineuritis forms part of the pathogenesis in acute Lyme neuroborreliosis.

Inflammation in the Pathogenesis of Lyme Neuroborreliosis
Geeta Ramesh, Peter J. Didier, John D. England, Lenay Santana-Gould, Lara A Doyle-Meyers, Dale S. Martin, Mary B. Jacobs, and Mario T. Philipp
American Journal of Pathology, Online first, April 16, 2015.
http://dx.doi.org/10.1016/j.ajpath.2015.01.024
Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis.

Acute transverse myelitis in Lyme neuroborreliosis
Bigi S, Aebi C, Nauer C, Bigler S, Steinlin M.
Infection, online before print, May 27, 2010.
http://dx.doi.org/10.1007/s15010-010-0028-x
Clinical symptoms and signs of neuroborrelial ATM may be minimal, even in cases with severe involvement of the spine, as shown by imaging studies. The CSF/blood index can be negative in the early stages and does not exclude Lyme neuroborreliosis; if there is strong clinical suspicion of Lyme neuroborreliosis, appropriate treatment should be started and the CSF/blood index repeated to confirm the diagnosis.

Diastolic heart murmur, nocturnal back pain, and lumbar rigidity in a 7-year girl: an unusual manifestation of lyme disease in childhood.
Kameda G, Vieker S, Hartmann J, Niehues T, Langler A.
Case Reports in Pediatrics. 2012(2012):976961. Published online 2012 Sep 29.
http://dx.doi.org/10.1155/2012/976961
A 7-year-old girl presented with nocturnal pain in her back and legs. The physical examination revealed a loud opening sound of the mitral valve and lumbar rigidity. With the exception of significantly increased anti-nuclear antibody (ANA) levels, the immunological findings did not show any other abnormal parameters, also spinal magnetic resonance imaging (MRI) and ultrasound examination of the abdomen and pelvis yield no pathological findings.

Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain.
Ramesh G, Maclean AG, Philipp MT.
Mediators of Inflammation, vol. 2013, Article ID 480739, 20 pages, 2013.
http://dx.doi.org/10.1155/2013/480739
This review will focus on how cytokines and chemokines affect neuroinflammation and disease pathogenesis in bacterial meningitis and brain abscesses, Lyme neuroborreliosis, human immunodeficiency virus encephalitis, and neuropathic pain.

Neuroborreliosis Mimicking Leptomeningeal Carcinomatosis in a Patient With Breast Cancer: A Case Report
Stefanie Fischer, Johannes Weber, Isabelle Senn-Schonenberger, Thomas Cerny, and Thomas Hundsberger
Journal of Investigative Medicine High Impact Case Reports January 2014 2: 2324709614529417
Online before print, March 28, 2014.
http://doi.org/10.1177/2324709614529417
Leptomeningeal carcinomatosis is a serious complication of advanced cancer. Various clinical manifestations may present, such as headache, nausea, seizures, cranial neuropathies. In this article, we report the case of a 65-year-old woman with metastatic breast cancer who was admitted to hospital suffering from facial palsy, which was suspected to be caused by leptomeningeal tumor infiltration. Assessment of cerebrospinal fluid found no malignant cells but investigation for infectious diseases established the diagnosis of neuroborreliosis. Antibiotic treatment with doxycycline was performed. After completion of treatment, follow-up MRI scans found complete regression of meningeal enhancement. Hence, initial diagnosis of leptomeningeal carcinomatosis was rejected. This case report should alert oncologists to carefully rule out infectious diseases before leptomeningeal carcinomatosis is diagnosed.

Filament formation associated with spirochetal infection: a comparative approach to Morgellons disease
Middelveen MJ, Stricker RB
Clinical, Cosmetic and Investigational Dermatology 2011, 4:167-17.
http://dx.doi.org/10.2147/CCID.S26183
Morgellons disease is an emerging human dermopathy characterized by the presence of filamentous fibers of undetermined composition, both in lesions and subdermally. While the etiology of Morgellons disease is unknown, there is serological and clinical evidence linking this phenomenon to Lyme borreliosis and coinfecting tick-borne agents.

Babesiosis-associated immune thrombocytopenia
Narurkar R, Mamorska-Dyga A, Agarwal A, Nelson JC, Liu D.
Stem Cell Investigation, 2017 Jan 17;4:1. eCollection 2017.
http://doi.org/10.21037/sci.2017.01.02
Thrombocytopenia is a common feature of babesiosis. The mechanism for thrombocytopenia in babesiosis remains elusive. We report a case of babesiosis with severe new onset immune thrombocytopenia (ITP).

Neutropenia in Congenital and Adult Babesiosis
Wormser GP, Villafuerte P, Nolan SM, Wang G, Lerner RG, Saetre KL, Maria MH, Branda JA.
American Journal of Clinical Pathology. 2015 Jul;144(1):94-6.
http://doi.org/10.1309/AJCP2PHH4HBVHZFS
Four (80%; 95% confidence interval [CI], 36%-98%) of five infants with congenital babesiosis whose neutrophil count was reported were neutropenic. Among 51 adult cases with babesiosis, 11 (22%; 95% CI, 12%-35%) were neutropenic on clinical presentation, and seven others developed neutropenia over the next 1 to 21 days. Thus, a total of 18 (35%; 95% CI, 24%-49%) of the adult patients with babesiosis had neutropenia.

Neutropenia appears to be a common finding in infants with congenital babesiosis and is also observed not infrequently in adults with this infection. Severe human monocytic ehrlichiosis presenting with altered mental status and seizures
Geier C, Davis J, Siegel M.
BMJ Case Reports 2016 Oct 6;2016. pii: bcr2016215967.
http://doi.org/10.1136/bcr-2016-215967
A previously healthy 66-year-old woman living in the Mid-Atlantic USA presented to the hospital with lethargy, ataxia and slurred speech. 2 weeks prior she had removed a tick from her right groin. She reported malaise, fevers, diarrhoea, cough and a rash.

Babesiosis-Induced Acute Kidney Injury With Prominent Urinary Macrophages.
Luciano RL, Moeckel G, Palmer M, Perazella MA.
American Journey of Kidney Diseases, online before print, 2013 May 2, pii: S0272-6386(13)00674-4.
http://dx.doi.org/10.1053/j.ajkd.2013.02.376
We present a case of severe babesiosis complicated by dialysis-requiring AKI with the unique finding of large macrophages containing engulfed erythrocyte fragments in urine sediment. This urinary finding raised the possibility of another diagnosis distinct from acute tubular injury.

Is Localized Scleroderma Caused by Borrelia burgdorferi?
Zinchuk AN, Kalyuzhna LD, Pasichna IA.
Vector-Borne and Zoonotic Diseases, online first, 2016 Jul 7.
http://doi.org/10.1089/vbz.2016.2004
Despite considerable achievements in the study of localized scleroderma, the etiology of the disease has not been investigated completely. Borrelia burgdorferi—the agent of Lyme disease—is suggested to be one of the possible etiological factors of localized scleroderma. Diagnostic levels of IgM and/or IgG were detected in 18.8% of patients with localized scleroderma, which is more than in the population (p? <?0.01).

Scleroderma linearis: hemiatrophia faciei progressiva (Parry-Romberg syndrom) without any changes in CNS and linear scleroderma “en coup de sabre” with CNS tumor.
Bergler-Czop B, Lis-Swiety A, Brzezinska-Wcislo L.
BioMed Central Neurology 2009, 9:39
Published: 27 July 2009
http://www.biomedcentral.com/1471-2377/9/39
We present two cases of a disease: a case of a 49-year-old woman with a typical image of hemifacial atrophy, without any changes of the nervous system and a case of a 33-year-old patient with an “en coup de sabre” scleroderma and with CNS tumor.
CONCLUSION: We described typical cases of a rare diseases, hemifacial atrophy and “en coup de sabre” scleroderma. In the patient diagnosed with Parry-Romberg syndrome, with Borrelia burgdoferi infection and with minor neurological symptoms, despite a four-year case history, there was a lack of proper diagnosis and treatment. In the second patient only skin changes without any neurological symptoms could be observed and only a precise neurological diagnosis revealed the presence of CNS tumor.

State: Tick bite can be deadly
By Cynthia McCormick, Cape Cod Times, Hyannis, Massachusetts
December 22, 2013
http://www.capecodonline.com/apps/pbcs.dll/article?AID=/20131222/NEWS/312220338
Public health officials report that at least 10 people in Massachusetts died last year after contracting diseases carried by the freckle-sized tick. One was a young adult who, as reported last week by the Centers for Disease Control and Prevention, collapsed in November 2012 after suffering a rare cardiac event known as Lyme carditis.

New insights into Lyme disease
Peacock BN, Gherezghiher TB, Hilario JD, Kellermann GH.
Redox Biology, 5:66-70. Online first, 2015 Mar 16.
http://doi.org/10.1016/j.redox.2015.03.002
– Positivity of Borrelia burgdorferi infection was assessed by a Lyme ELISPOT assay.
– Assessed levels of mitochondrial superoxide and cytosolic calcium in patient PBMCs.
– Lyme borreliosis patients showed a marked increase in mitochondrial superoxide.
– Levels of cytosolic calcium were significantly lower in Lyme borreliosis patients.
– Suggesting that Lyme borreliosis may lead to a state of mitochondrial dysfunction

Acute Babesiosis in Pregnancy: A Novel Imitator of Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome
Gulersen M, Brost BC, Bobrovnikov V, Bornstein E.
Obstetrics & Gynecology, 2016 Jul;128(1):197-200.
http://doi.org/10.1097/AOG.0000000000001445
Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a serious complication of pregnancy associated with significant maternal and fetal morbidity and mortality.

Babesiosis-associated immune thrombocytopenia
Narurkar R, Mamorska-Dyga A, Agarwal A, Nelson JC, Liu D.
Stem Cell Investigation, 2017 Jan 17;4:1. eCollection 2017.
http://doi.org/10.21037/sci.2017.01.02
Thrombocytopenia is a common feature of babesiosis. The mechanism for thrombocytopenia in babesiosis remains elusive. We report a case of babesiosis with severe new onset immune thrombocytopenia (ITP).

Atraumatic splenic rupture from Babesia: A disease of the otherwise healthy patient
F.R. Farber, A. Muehlenbachs, T.E. Robey
Ticks and Tick-borne Diseases, Volume 6, Issue 5, July 2015, Pages 649-652.
http://dx.doi.org/10.1016/j.ttbdis.2015.05.010
We describe a case of spontaneous splenic rupture in an otherwise healthy woman that required emergent splenectomy. Recent case reports suggest that splenic rupture occurs in people without known risk factors for severe babesiosis. Physicians should be aware of this acute presentation in otherwise healthy individuals.

Neurological manifestations of human babesiosis.
Usmani-Brown S, Halperin JJ, Krause PJ.
Handbook of Clinical Neurology, 2013;114:199-203.
http://dx.doi.org/10.1016/B978-0-444-53490-3.00014-5
Babesiosis is a worldwide emerging infectious disease caused by intraerythrocytic protozoa that are transmitted by Ixodid ticks, or less commonly through blood transfusion or transplacentally. Although headache and lethargy are common symptoms, babesiosis is uncommonly associated with specific neurological dysfunction in humans. Decreased level of consciousness or coma are rare complications that are associated with severe and often fatal disease but the pathogenesis is unclear.

Autoimmune hemolytic anemia associated with babesiosis
Narurkar R, Mamorska-Dyga A, Nelson JC, Liu D.
Biomarker Research, 2017 Apr 8;5:14. eCollection 2017.
https://doi.org/10.1186/s40364-017-0095-6
Babesia infection is commonly associated with anemia, thrombocytopenia, hyponatremia and elevated liver enzymes. Autoimmune hemolytic anemia (AIHA) is known to be caused by parasitic and viral infections but has not been well characterized.

Bartonella henselae Bloodstream Infection in a Boy With Pediatric Acute-Onset Neuropsychiatric Syndrome
Edward B Breitschwerdt, Rosalie Greenberg, Ricardo G Maggi, et al.
First Published March 18, 2019
https://doi.org/10.1177/1179573519832014
With the advent of more sensitive culture and molecular diagnostic testing modalities, Bartonella spp. infections have been documented in blood and/or cerebrospinal fluid specimens from patients with diverse neurological symptoms. Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by an unusually abrupt onset of cognitive, behavioral, or neurological symptoms. Between October 2015 and January 2017, a 14-year-old boy underwent evaluation by multiple specialists for sudden-onset psychotic behavior (hallucinations, delusions, suicidal and homicidal ideation).

Rheumatological presentation of Bartonella koehlerae and Bartonella henselae bacteremias: A case report.
Mozayeni BR, et al.
Medicine (Baltimore). 2018.
https://www.ncbi.nlm.nih.gov/m/pubmed/29703000/
Systemic Bartonella spp. infections are being increasingly reported in association with complex medical presentations. Individuals with frequent arthropod exposures or animal contact appear to be at risk for acquiring long standing infections with Bartonella spp. To facilitate early and directed medical interventions, systemic bartonellosis should potentially be considered as a differential diagnosis in patients with incalcitrant rheumatological symptoms and frequent arthropod exposures or extensive animal contact.

Bartonella henselae osteoarthritis of the upper cervical spine in a 14-year-old boy.
Mirouse G, Journe A, Casabianca L, Moreau PE, Pannier S, Glorion C.
Orthopaedics & Traumatology: Surgery & Research. pii: S1877-0568(15)00092-4. Online first, 2015 Apr 13.
http://doi.org/10.1016/j.otsr.2015.02.007
We report a case of Bartonella henselae, an agent of cat scratch disease, C1-C2 osteoarthritis with osteolysis of the lateral mass of C2 in a 14-year-old boy. Oral antibiotics did not successfully treat the infection and surgery was necessary to treat the septic arthritis. The case opens discussion about bacterial osteoarthritis of the cervical spine and bone involvement in disseminated bartonellosis.

Ophthalmic manifestations of bartonella infection
Amer R, Tugal-Tutkun I.
Current Opinion in Ophthalmology. 2017 Nov;28(6):607-612.
https://doi.org/10.1097/ICU.0000000000000419
The eye is commonly affected in disseminated cat scratch disease (CSD) caused by Bartonella species. This article reviews recently published data on epidemiology of CSD, clinical features of ocular involvement, diagnosis and treatment.

Onset of cutaneous vasculitis and exacerbation of IgA nephropathy after Bartonella henselae infection
E. Cozzani, E. Cinotti, P. Ameri, A. Sofia, G. Murialdo and A. Parodi
Clinical and Experimental Dermatology, online before print October 10, 2011.
http://dx.doi.org/10.1111/j.1365-2230.2011.04177.x
Bartonella henselae is the aetiological agent of cat-scratch disease. Recently, there have been reports of other conditions associated with this bacterium, including leucocytoclastic vasculitis, thrombocytopenic purpura, maculopapular and urticarial eruptions, granuloma annulare, erythema nodosum, erythema marginatum and erythema annulare.

A pediatric case with peripheral facial nerve palsy caused by a granulomatous lesion associated with cat scratch disease
Nakamura C, Inaba Y, Tsukahara K, Mochizuki M, Sawanobori E, Nakazawa Y, Aoyama K.
Brain and Development, online first 2017 Sep 18.
http://dx.doi.org/10.1016/j.braindev.2017.09.001
Cat scratch disease is a common infectious disorder caused by Bartonella henselae that is transmitted primarily by kittens. It typically exhibits a benign and self-limiting course of subacute regional lymphadenopathy and fever lasting two to eight weeks. The most severe complication of cat scratch disease is involvement of the nervous system, such as encephalitis, meningitis, and polyneuritis. Peripheral facial nerve palsy associated with Bartonella infection is rare; few reported pediatric and adult cases exist and the precise pathogenesis is unknown.

Eschar and neck lymphadenopathy caused by Francisella tularensis after a tick bite: a case report
Sophie Edouard, Khira Gonin, Yves Turc, Emmanouil Angelakis, Cristina Socolovschi and Didier Raoult
Journal of Medical Case Reports 2011, 5:108 Published: 19 March 2011.
http://www.jmedicalcasereports.com/content/5/1/108
Francisella tularensis DNA was found in the skin biopsy and the serology showed titres consistent with tularaemia. This is, to the best of our knowledge, the first reported case of scalp eschar and neck lymphadenopathy after tick bite infection caused by F. tularensis.

Rhabdomyolysis-induced Acute Kidney Injury Secondary to Anaplasma phagocytophilum and Concomitant Statin Use
Stephen R. Talsness, BA; Sanjay K. Shukla, PhD; Joseph J. Mazza, MD; Steven H. Yale, MD
Wisconsin Medical Journal, Volume 110, Issue 2 (April 2011), pp. 82-84.
http://www.wisconsinmedicalsociety.org/wmj/110/2
We report the case of a patient with rhabdomyolysis-induced acute renal failure occurring in the setting of Anaplasma phagocytophilum infection based on the presence of morulae in neutrophils and concomitant statin use. Although the pathogenesis is unknown, we believe the combination of concurrent statin use in the setting of the infection promoted this complication.

Multiorgan Involvement Confounding the Diagnosis of Bartonella henselae Infective Endocarditis in Children With Congenital Heart Disease
Ouellette CP, Joshi S, Texter K, Jaggi P.
Pediatric Infectious Disease Journal. 2017 May;36(5):516-520.
https://doi.org/10.1097/INF.0000000000001510
These 2 cases highlight the potential multiorgan involvement that may confound the diagnosis of culture-negative infective endocarditis caused by B. henselae.

Meningitis Due to a Bartonella washoensis-like Human Pathogen
Will Probert, Janice K. Louie, James R. Tucker, Rose Longoria, Robin Hogue, Silvia Moler, Margot Graves, Heather J. Palmer, Joseph Cassady, and Curtis L. Fritz
Journal of Clinical Microbiology, published online ahead of print on 13 May 2009.
http://dx.doi.org/10.1128/JCM.00511-09
We report the second human case of infection caused by an organism identified as the proposed Bartonella species, B. washoensis. The organism was isolated from the blood of a patient presenting with meningitis and early sepsis. Oropsylla montana fleas were implicated as the vector for disease transmission in this case.

Clinical Presentation and Outcomes of Children With Human Granulocytic Anaplasmosis
Schotthoefer AM, Hall MC, Vittala S, Bajwa R, Frost HM.
Journal of the Pediatric Infectious Diseases Society, online first 2017 May 16.
https://doi.org/10.1093/jpids/pix029
Of 187 children identified with possible HGA, 17 (9%) had confirmed, 75 (40%) had probable, and 91 (49%) had suspected infections. The number of cases rose sharply in 2010 and has remained between 16 and 36 cases per year since that time. A minority of children with confirmed or probable infections had elevated liver transaminase levels (33%), leukopenia (24%), thrombocytopenia (17%), or anemia (8%); 6 (7%) of these children required hospitalization. Children with evidence of concurrent HGA and Lyme disease (27% of confirmed or probable cases) had a higher risk of hospitalization (odds ratio, 6.55 [95% confidence interval, 1.11–38.78]). None of these children had life-threatening disease or died.

Severe Human Granulocytic Anaplasmosis With Significantly Elevated Ferritin Levels in an Immunocompetent Host
Camacci ML, Panganiban RP, Pattison Z, Haghayeghi K, Daly A, Ojevwe C, Munyon RJ.
Journal of Investigative Medicine High Impact Case Reports, published online 2018 Feb 13.
https://doi.org/10.1177/2324709618758350
Human granulocytic anaplasmosis (HGA) is a tick-borne, infectious disease caused by Anaplasma phagocytophilum that generally presents with nonspecific symptoms such as fever, chills, headache, malaise, and myalgia. If not treated immediately, HGA can cause hemophagocytic lymphohistiocytosis (HLH), a well-documented but underrecognized sequela of severe HGA. Our case shows the challenges in the timely diagnosis of HGA and highlights the role of serum ferritin in aiding this diagnosis. Although our patient did not fulfill the HLH diagnostic criteria, our report demonstrates the importance of recognizing HGA as a reversible cause of HLH.

Tick Bite Alopecia (hair loss/bladness): A Report and Review
Lynch MC, Milchak MA, Parnes H, Ioffreda MD.
The American Journal of Dermatopathology. 2016 Nov;38(11):e150-e153.
http://doi.org/10.1097/DAD.0000000000000598
Tick bites can cause a number of local inflammatory reactions, which are often difficult to differentiate from those induced by other arthropod bites or stings. These include erythematous nodular or pustular lesions, erosive plaques, annular lesions of erythema chronicum migrans, and both scarring and nonscarring inflammatory alopecia.

Association between Borrelia burgdorferi antibodies and amyotrophic lateral sclerosis in a case-control study.
Visser AE, Verduyn Lunel FM, Veldink JH, van den Berg LH.
European Journal of Neurology. 2017 Jan;24(1):227-230.
http://doi.org/10.1111/ene.13197
Previous studies, mostly case reports and uncontrolled studies, provide a low level of evidence for the hypothesized link between Lyme disease and amyotrophic lateral sclerosis (ALS). No difference in seroprevalence of Borrelia was found between patients (4.1%) and controls (5.9%). Clinical characteristics and survival were similar between seropositive and seronegative patients.

The Lyme disease pathogen Borrelia burgdorferi infects murine bone and induces trabecular bone loss
Tang TT, Zhang L, Bansal A, Grynpas M, Moriarty TJ.
Infection and Immunity, online first, 2016 Dec 12.
http://doi.org/10.1128/IAI.00781-16
Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice.
Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice, and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption.

Notes from the field: update on lyme carditis, groups at high risk, and frequency of associated sudden cardiac death – United States.
Forrester JD, Meiman J, Mullins J, Nelson R, Ertel SH, Cartter M, Brown CM, Lijewski V, Schiffman E, Neitzel D, Daly ER, Mathewson AA, Howe W, Lowe LA, Kratz NR, Semple S, Backenson PB, White JL, Kurpiel PM, Rockwell R, Waller K, Johnson DH, Steward C, Batten B, Blau D, DeLeon-Carnes M, Drew C, Muehlenbachs A, Ritter J, Sanders J, Zaki SR, Molins C, Schriefer M, Perea A, Kugeler K, Nelson C, Hinckley A, Mead P.
Morbidity and Mortality Weekly Report (MMWR). 2014 Oct 31;63(43):982-3.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6343a4.htm?s_cid=mm6343a4_w
Of cases with this information available, 69% were diagnosed during the months of June–August, and 42% patients had an accompanying erythema migrans, a characteristic rash. Relative to patients aged 55–59 years, carditis was more common among men aged 20–39 years, women aged 25–29 years, and persons aged =75 years.

Cardiac Tropism of Borrelia burgdorferi
Muehlenbachs, Atis et al.
The American Journal of Pathology, online first March 8, 2016.
http://dx.doi.org/10.1016/j.ajpath.2015.12.027
Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues.

Presence of Borrelia burgdorferi sensu lato antibodies in the serum of patients with abdominal aortic aneurysms
European Journal of Clinical Microbiology & Infectious
Diseases, Vol. 31, No. 5 (2012), 781-789.
http://dx.doi.org/10.1007/s10096-011-1375-y
Our findings suggest a relationship between AAAs and B. burgdorferi sl. We hypothesize that the underlying mechanism for B. burgdorferi sl in AAA formation is similar to that by the spirochete Treponema pallidum; alternatively, AAAs could develop due to induced autoimmunity via molecular mimicry due to similarities between some of the B. burgdorferi sl proteins and aortic proteins.

Infections and cardiovascular disease: is Bartonella henselae contributing to this matter?
Salvatore P, Zullo A, Sommese L, Colicchio R, Picascia A, Schiano C, Mancini FP, Napoli C.
Journal of Medical Microbiology, pii: jmm.0.000099. Online first, 2015 Jun 11.
http://doi.org/10.1099/jmm.0.000099
In this review, we summarize the rationale to suggest that Bartonella henselae could favor atherogenesis by infecting and damaging endothelial progenitor cells, thus reducing their vascular repair potential. These mechanisms suggest a novel link between communicable and non-communicable human diseases, and put forward the possibility that Bartonella henselae could enhance the susceptibility and worsen the prognosis in cardiovascular disease.

Parry-Romberg syndrome: a case with a possible association with Lyme disease
di Meo N, Stinco G, Nan K, Pinzani C, Trevisan G.
Acta Dermatovenerologica Alpina Pannonica et Adriatica 2015 Dec;24(4):77-9.
http://dx.doi.org/10.15570/actaapa.2015.20
Parry–Romberg syndrome is an acquired slowly progressive disease characterized by an atrophy mostly involving half of the face. The pathogenesis of this disfiguring condition is still controversial. The relationship between Parry–Romberg syndrome and Lyme disease needs to be considered in depth. We cannot exclude a coincidence, however, of the bacteriological and serological evidence. Moreover, the interruption of the disease progression after the antibiotic therapy is difficult to ignore without claiming that this association is at least suggestive.

Evaluating the Child with Acute Hip Pain (“Irritable Hip”) in a Lyme Endemic Region 
Richard G. Bachur, Cynthia M. Adams, Michael C. Monuteaux
The Journal of Pediatrics, online before print, October 25, 2014.
http://dx.doi.org/10.1016/j.jpeds.2014.09.040
Lyme infection occurred in approximately 5% of children with acute, nontraumatic hip pain who were evaluated in a pediatric emergency department in a Lyme endemic region.

Identification of Mycoplasma fermentans in Synovial Fluid Samples from Arthritis Patients with Inflammatory Disease
Sheena Johnson, David Sidebottom, Felix Bruckner, and David Collins
J Clin Microbiol. 2000 Jan; 38(1): 90–93.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC86027/
Since 1970 Mycoplasma fermentans has been suspected of being associated with rheumatoid arthritis. However, this association has been difficult to prove, and this has been our goal. M. fermentans was detected in 23 of 26 (88%) rheumatoid arthritis patients, and four different strains were found. It was also found in 7 of 8 (88%) of the nonrheumatoid inflammatory arthritis patient group, which consisted of one patient with reactive arthritis, one patient with pauciarticular juvenile chronic arthritis, two patients with gout, two patients with ankylosing spondylitis, and two patients with psoriatic arthritis, only one of whom was infected with M. fermentans. It was not detected in any of the 10 osteoarthritis patients. M. fermentans was therefore found to be a variable and very common organism in arthritic patients with inflammatory joint exudates and may well prove to be important in the etiology of the diseases.

Infectious agents is a risk factor for myxomatous mitral valve degeneration: A case control study
Tiveron MG, Pomerantzeff PMA, de Lourdes Higuchi M, Reis MM, de Jesus Pereira J, Kawakami JT, Ikegami RN, de Almeida Brandao CM, Jatene FB.
BMC Infectious Diseases. 2017 Apr 21;17(1):297.
https://doi.org/10.1186/s12879-017-2387-8
The presence of infectious agents, inflammatory cells and collagenases in mitral valves appear to contribute to the pathogenesis of MVD. Mycoplasma pneumoniae was strongly related with myxomatous mitral valve degeneration. Despite of low percentage of Borrelia burgdorferi in MD group, this agent was correlated with myxomatous degeneration and this may occour due synergistic actions between these infectious agents likely contribute to collagen degradation.

Emerging Cases of Powassan Virus Encephalitis in New England: Clinical Presentation, Imaging, and Review of the Literature.
Piantadosi A, Rubin DB, McQuillen DP, Hsu L, Lederer PA, Ashbaugh CD, Duffalo C, Duncan R, Thon J, Bhattacharyya S, Basgoz N, Feske SK, Lyons JL.
Clinical Infectious Diseases, online first, 2015 Dec 13.
http://www.ncbi.nlm.nih.gov/pubmed/26668338
Background. Powassan virus is a rarely diagnosed cause of encephalitis in the United States. In the Northeast, it is transmitted by Ixodes scapularis, the same vector that transmits the causative agent of Lyme disease, and the prevalence of Powassan virus among animal hosts and vectors has been increasing. Here we present eight cases of Powassan virus encephalitis from Massachusetts and New Hampshire in 2013-2015.

Multiorgan failure related to human monocytic ehrlichiosis.
Yachoui R.
BMJ Case Reports. 2013May 22;2013. pii: bcr2013008716.
http://dx.doi.org/10.1136/bcr-2013-008716
Human monocytic ehrlichiosis (HME) is a tick-born disease that presents predominantly as a mild to moderate acute illness. Severe life-threatening disease has been reported with a case death rate of approximately 3%, often in immunosuppressed persons. A delay in therapy initiation has been proven to increase the morbidity of the disease.

First reported case of Ehrlichia ewingii involving human bone marrow
Allen MB, Pritt BS, Sloan LM, Paddock CD, Musham CK, Ramos JM, Cetin N, Rosenbaum ER.
Journal of Clinical Microbiology. 2014 Nov;52(11):4102-4.
http://doi.org/10.1128/JCM.01670-14
A 65-year-old female with a history of multiple tick bites presented with fever and pancytopenia. Intracytoplasmic rickettsial morulae were detected on peripheral smear and bone marrow biopsy specimens, and PCR amplified Ehrlichia ewingii DNA from both specimens. To our knowledge, this is the first report of E. ewingii infection of human bone marrow.

Ticks Can Spread Allergy to Red Meat
Blog: D-brief, A Blog About Energy and the Environment
Written by: Lisa Raffensperger, Discover Magazine, Kalmbach
Publishing Coompany, Waukesha, Wisconsin
http://goo.gl/eOuim
We’re in the thick of tick season, and that tends to trigger mental associations with Lyme disease. But as the arachnids emerge this year, attention is also being paid to a rare allergy that ticks may be spreading, and it’s a carnivore’s worst nightmare: itchy hives every time you eat red meat.

Beware of babesiosis: A rare and severe case causing death
Greenberg K, Tahseen M, Davidson A.
The American Journal of Emergency Medicine, online first, 2018 Aug 27.
https://doi.org/10.1016/j.ajem.2018.08.063
Babesiosis is an infectious disease caused by protozoa of the genus Babesia which is primarily transmitted by tick vectors. Most cases are asymptomatic or only mild to moderate, but some cases may be severe causing death.
A 57 year old male with no reported travel outside the country was escorted by Emergency Medical Services to our Pennsylvania hospital in July of 2018 presenting with hypoglycemia, jaundice, and hypotension. Initial assessment further revealed the patient to be severely hypothermic. Resuscitative efforts began immediately and the laboratory reported parasites observed on the patient’s peripheral blood smear. The patient was admitted to the intensive care unit with severe septic shock and disseminated intravascular coagulation. The patient was ultimately transferred to a tertiary care center for exchange transfusion therapy and veno-arterial extracorporeal membrane oxygenation support, but expired 36?h after presentation. Current CDC data reflects a steady rise of tick borne disease in the United States, but as of 2016 there have been no reported cases of babesiosis in the state of Pennsylvania, let alone fatalities. Clinicians need to be aware of the risk of fulminant illness when practicing in known endemic regions.

Neuropsychiatric Lyme Borreliosis: An Overview with a Focus on a Specialty Psychiatrist’s Clinical Practice
Bransfield RC.
Healthcare. 2018 Aug 25;6(3). pii: E104.
https://doi.org/10.3390/healthcare6030104
There is increasing evidence and recognition that Lyme borreliosis (LB) causes mental symptoms. This article draws from databases, search engines and clinical experience to review current information on LB.
LB causes immune and metabolic effects that result in a gradually developing spectrum of neuropsychiatric symptoms, usually presenting with significant comorbidity which may include developmental disorders, autism spectrum disorders, schizoaffective disorders, bipolar disorder, depression, anxiety disorders (panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, intrusive symptoms), eating disorders, decreased libido, sleep disorders, addiction, opioid addiction, cognitive impairments, dementia, seizure disorders, suicide, violence, anhedonia, depersonalization, dissociative episodes, derealization and other impairments.
Screening assessment followed by a thorough history, comprehensive psychiatric clinical exam, review of systems, mental status exam, neurological exam and physical exam relevant to the patient’s complaints and findings with clinical judgment, pattern recognition and knowledgeable interpretation of laboratory findings facilitates diagnosis.
Psychotropics and antibiotics may help improve functioning and prevent further disease progression. Awareness of the association between LB and neuropsychiatric impairments and studies of their prevalence in neuropsychiatric conditions can improve understanding of the causes of mental illness and violence and result in more effective prevention, diagnosis and treatment.

Manifestation of anaplasmosis as cerebral infarction: a case report
Kim SW, Kim CM, Kim DM, Yun NR.
BMC Infectious Diseases, 2018 Aug 17;18(1):409.
https://doi.org/10.1186/s12879-018-3321-4
Background
Human granulocytic anaplasmosis is a tick-borne zoonotic disease caused by Anaplasma phagocytophilum, an obligate intracellular granulocytotropic bacterium.
Case presentation
A 70-year-old female patient was admitted with the clinical signs of fever and an altered state of consciousness 1 week after experiencing a tick bite while planting lawn grass. Magnetic resonance imaging, performed at the time of admission, indicated cerebral infarction in the left basal ganglia, whereas increasing immunofluorescence assay antibody titers for A. phagocytophilum were also documented. A. phagocytophilum was identified using groEL and ankA targeted polymerase chain reaction and sequencing. Because of severe thrombocytopenia, only doxycycline was administered, without any antiplatelet agents. Subsequently, the symptoms improved without any focal neurologic sequela.
Conclusion
This is the first reported case of cerebral infarction occurrence in an anaplasmosis patient.

Early Disseminated Lyme Disease Masquerading as Mononucleosis: A Case Report
Tumminello R, Glaspey L, Bhamidipati A, Sheehan P, Patel S.
The Journal of Emergency Medicine. 2017 Dec;53(6):e133-e135.
https://doi.org/10.1016/j.jemermed.2017.09.005
Background
Disseminated Lyme disease can be difficult to diagnose, as it begins with nonspecific signs and symptoms, which, if not treated correctly, can lead to atrioventricular conduction blocks and meningitis. In addition, the diagnosis can be further complicated by potentially false-positive test results.
Case Report
We report a case of early-disseminated Lyme disease presenting with Borrelia meningitis and concomitant Lyme carditis, which was misdiagnosed as mononucleosis. A young, previously healthy patient had been hiking in the woods of upstate New York and 4 weeks later developed fever, night sweats, and myalgias. He was diagnosed with mononucleosis via a positive rapid heterophile agglutination antibody test to the Epstein-Barr virus at a walk-in clinic and was started on medications, but then subsequently developed left hip pain, a facial droop, and a very long first-degree atrioventricular conduction block. He went to the Emergency Department, where he had testing that confirmed disseminated Lyme disease.
Why Should an Emergency Physician Be Aware of This?
This case highlights the difficulty in early diagnosis of disseminated Lyme disease and how a potentially false-positive laboratory test can lead to the complications of Borrelia meningitis and Lyme carditis in untreated young healthy patients. Emergency physicians need to consider Lyme disease in patients with nonspecific signs and symptoms, especially if they have been outdoors for prolonged periods of time in Lyme-endemic areas.

Babesiosis as a cause of false-positive HIV serology
Smotrys M, Magge T, Alkhuja S, Gandotra SD.
BMJ Case Reports. 2018 Jun 8;2018. pii: bcr-2017-223738.
https://doi.org/10.1136/bcr-2017-223738
This is a case of a 71-year-old homosexual man who presented with a 4-day history of fever, weakness and headaches, near syncope, nausea and poor oral intake.
The patient denied recent travel or sick contacts but had significant tick bites in the last 4weeks. A peripheral blood smear showed 0.5% parasitaemia with signet ring appearance organisms consistent with Babesia microti. Serology testing for HIV 1 and 2 by ELISA and western blot were positive.
Treatment for Babesia was started and the patient improved. Repeat serology testing for HIV was negative.
To the best of our knowledge, this is the first case of false-positive HIV serology that is associated with active babesiosis. In this case, the positive HIV serology turned negative after successful treatment of babesiosis.

Clinical evaluation of Morgellons disease in a cohort of North American patients
Fesler MC, Middelveen MJ, Stricker RB.
Dermatology Reports. 2018 Apr 24;10(1):7660.
https://doi.org/10.4081/dr.2018.7660
Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi, the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association.
A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods.
Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and i (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections.
This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study.

Cat-scratch disease: ocular manifestations and treatment outcome
Habot-Wilner, Z., Trivizki, O., Goldstein, M., Kesler, A., Shulman, S., Horowitz, J., Amer, R., David, R., Ben-Arie-Weintrob, Y., Bakshi, E., Almog, Y., Sartani, G., Vishnevskia-Dai, V., Kramer, M., Bar, A., Kehat, R., Ephros, M. and Giladi, M.
Acta Ophthalmologica, online first 5 March 2018.
https://doi.org/10.1111/aos.13684
Results
Mean age was 35.1 ± 14.2 years. Median follow-up was 20 weeks (range 1–806 weeks). Of 94/107 (88%) eyes with swollen disc, 60 (64%) had neuroretinitis at presentation, 14 (15%) developed neuroretinitis during follow-up, and 20 (21%) were diagnosed with inflammatory disc oedema. Optic nerve head lesion, uveitis, optic neuropathy and retinal vessel occlusion were found in 43 (40%), 38 (36%), 34 (33%) and 8 (7%) eyes, respectively. Good VA (better than 20/40), moderate vision loss (20/40–20/200) and severe vision loss (worse than 20/200) were found in 26/79 (33%), 35/79 (44%) and 18/79 (23%) eyes at baseline and in 63/79 (80%), 11/79 (14%) and 5/79 (6%) eyes at final follow-up, respectively (p < 0.001). Significant VA improvement (defined as improvement of =3 Snellen lines at final follow-up compared to baseline) occurred in 12/24 (50%) eyes treated with antibiotics compared with 14/16 (88%) eyes treated with antibiotics and corticosteroids (p = 0.02). Multivariate logistic regression was suggestive of the same association (odds ratio 7.0; 95% CI 1.3–37.7; p = 0.024).
Conclusion
Optic nerve head lesion is a common and unique manifestation of ocular CSD. Most patients improved and had final good VA. Combined antibiotics and corticosteroid treatment was associated with a better visual outcome.

Sternoclavicular Arthritis as a Clinical Presentation for Lyme Disease
Ramgopal S, Rosenkranz M, Nowalk AJ, Zuckerbraun NS.
Pediatrics. 2018 Apr;141(Suppl 5):S466-S469.
https://doi.org/10.1542/peds.2017-0725
Lyme disease is caused by Borrelia burgdorferi and can lead to dermatologic, neurologic, cardiac, and musculoskeletal manifestations. The arthritis of Lyme disease is typically monoarticular, with the knee being most commonly involved. Lyme arthritis of small joints has not previously been well described.
We report 3 children who presented with sternoclavicular joint swelling and who were found to have Lyme disease based on enzyme-linked immunosorbent assay and Western blot. This description of sternoclavicular Lyme arthritis highlights the importance of considering Lyme disease in the differential and diagnostic workup of new onset, small joint arthritis in patients presenting from or with travel to Lyme endemic regions.

Effect of Helminth-Induced Immunity on Infections with Microbial Pathogens
Salgame, P., Yap, G. S., & Gause, W. C. (2013). Nature immunology14(11), 1118-1126.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955540/
Helminth infections are ubiquitous worldwide and can trigger potent immune responses that differ from and potentially antagonize host protective responses to microbial pathogens……M2 macrophages and helminth-modulated dendritic cells influence the protective immune response to concurrent coinfections.

Infectious Mononucleosis and Lyme Disease as Confounding Diagnoses: A Report of 2 Cases
Koester TM, Meece JK, Fritsche TR, Frost HM. Clinical Medicine & Research, online first 2018 Aug 30.
https://www.ncbi.nlm.nih.gov/pubmed/30166498
Lyme disease and infectious mononucleosis are common illnesses that share similar clinical presentations. Significant cross-reactivity is known to occur between Lyme and EBV serologic assays complicating the diagnosis. To date, no prior cases of concurrent acute Lyme and EBV infections have been reported. We describe the clinical presentation of two children with confirmed early Lyme disease and features suggestive of infectious mononucleosis, including one case of probable Lyme and EBV co-infection.

Neurocognition in Post-Treatment Lyme Disease and Major Depressive Disorder
Keilp JG, Corbera K, Gorlyn M, Oquendo MA, Mann JJ, Fallon BA.Archives of Clinical Neuropsychology, online first 2018 Nov 12.
https://doi.org/10.1093/arclin/acy083
MDD and PTLDS can be confused neuropsychologically because both exhibit similar levels of psychomotor slowing. However, problems on memory-related tasks, though mild, are more pronounced in PTLDS. PTLDS patients with poorer memory also exhibit poorer language fluency, and less deficit in processing speed and attention compared to MDD.

Acute Transverse Myelitis – A Rare Clinical Manifestation of Lyme Neuroborreliosis
Dumic I, Vitorovic D, Spritzer S, Sviggum E, Patel J, Ramanan P.
IDCases. 2018 Dec 29;15:e00479. eCollection 2019. 
https://doi.org/10.1016/j.idcr.2018.e00479
We present a case of a previously healthy 25-year-old man who presented with secondary erythema migrans, aseptic meningitis and clinical features of transverse myelitis including bilateral lower extremity motor and sensory deficits manifesting as weakness and numbness, urinary retention and constipation. Despite negative serum antibodies against Borrelia burgdoferi, cerebrospinal fluid (CSF) was positive for Borrelia burgdorferi PCR. Following treatment with methylprednisolone and ceftriaxone, he attained complete recovery apart from neurogenic bladder necessitating intermittent self-catheterization. We report rare manifestation of a common disease and emphasize the importance of considering LD in the differential diagnosis of acute transverse myelitis, particularly in residents of endemic areas.

Association of Small Fiber Neuropathy and Post Treatment Lyme Disease Syndrome
Novak P, Felsenstein D, Mao C, Octavien NR, Zubcevik N.PLoS One. 2019 Feb 12;14(2):e0212222. eCollection 2019.
https://doi.org/10.1371/journal.pone.0212222
SFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS.

Rheumatological presentation of Bartonella koehlerae and Bartonella henselae bacteremias: A case report
Mozayeni, Bob & Maggi, Ricardo & Meredith Bradley, Julie & Breitschwerdt, Edward. (2018).
Systemic Bartonella spp. infections are being increasingly reported in association with complex medical presentations. Individuals with frequent arthropod exposures or animal contact appear to be at risk for acquiring long standing infections with Bartonella spp.

Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069946/
Molderings, G. J., Brettner, S., Homann, J., & Afrin, L. B. (2011).  Journal of hematology & oncology4, 10.
Mast cell activation disease comprises disorders characterized by accumulation of genetically altered mast cells and/or abnormal release of these cells’ mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing. In most cases of mast cell activation disease, diagnosis is possible by relatively non-invasive investigation. Effective therapy often consists simply of antihistamines and mast cell membrane-stabilising compounds supplemented with medications targeted at specific symptoms and complications. Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or patients in whom a definitively diagnosed major illness does not well account for the entirety of the patient’s presentation.

Systemic Sarcoidosis Associated with Exposure to Borrelia burgdorferi in a 21-Year-Old Man
van Dee L, Stehouwer M, van Bemmel T.
European Journal of Case Reports in Internal Medicine. 2018 Oct 24;5(10):000942. eCollection 2018.
https://doi.org/10.12890/2018_000942
Here we describe a rare case of systemic sarcoidosis in a healthy young man with neuroborreliosis as a putative trigger. Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. This case suggests that an infection with B. burgdorferi, the causal agent of Lyme disease, could act as a trigger for sarcoidosis.

A Rare Case of Bartonella Encephalitis With Hemiplegia
Rosas L, Rao K, McGough C, Becker A.
Child Neurology Open, online first 2019 Jan 31. eCollection 2019.
https://doi.org/10.1177/2329048X19826480
The authors describe a 12-year-old girl with an atypical presentation of Bartonella encephalitis. She presented with fever and altered mental status and developed flaccid paralysis of her left upper extremity a day later.

Autonomic dysfunction, small fiber neuropathy and Lyme disease
Lyme Science Blog, by Daniel Cameron, MD, MPH, Mt. Kisco, New York
March 7, 2019
http://danielcameronmd.com/autonomic-dysfunction-small-fiber-neuropathy-and-lyme-disease/
Sensory symptoms and pain reported by some patients with ongoing Lyme disease symptoms may be caused by small fiber neuropathy and a low cerebral blood volume, according to the authors of a new study.

Bartonella henselae Bloodstream Infection in a Boy With Pediatric Acute-Onset Neuropsychiatric Syndrome
Edward B Breitschwerdt, Rosalie Greenberg, Ricardo G Maggi,
B Robert Mozayeni, Allen Lewis, Julie M Bradley
Journal of Central Nervous System Disease, online first March 18, 2019.
https://doi.org/10.1177/1179573519832014
This case report suggests that B henselae bloodstream infection may contribute to progressive, recalcitrant neuropsychiatric symptoms consistent with PANS in a subset of patients.

An Interesting Presentation of Lyme Pseudothrombophlebitis
Sandelich S, DePiero A.
Pediatric Emergency Care, online first 2019 Mar 21.
https://doi.org/10.1097/PEC.0000000000001826
An 8-year-old boy presented to the emergency department with swelling and pain of his left knee and calf for approximately 1 week. His examination was significant for moderate knee effusion and swelling of the posterior calf with erythema and warmth of the affected areas. The diagnosis of Lyme pseudothrombophlebitis was made through Lyme serology testing of aspirated fluid. He improved after this drainage but required a prolonged antibiotic course.

Lyme disease manifests as autoimmune disorder, Sjögren’s syndrome
Lyme Science Blog, by Daniel Cameron, MD, MPH, Mt. Kisco, New York
March 28, 2019
http://danielcameronmd.com/lyme-disease-manifests-as-autoimmune-disorder-sjogrens-syndrome/
Lyme disease symptoms can mimic many other illnesses and have been linked to several autoimmune diseases including Sjögren’s syndrome, Dermatomyositis, and Guillain-Barre syndrome. A case report by Smiyan entitled “Sjögren’s syndrome and lymphadenopathy unraveling the diagnosis of Lyme disease,” reflects the importance of a thorough clinical evaluation.

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