Symptoms of a multisystemic disease

The following recommendations are meant for patients whose symptoms could not be explained by previous diagnostics. Other diagnoses should be ruled out first, before coming to the diagnosis of Lyme disease. If those diagnostics can find the origin of the complaints, then no further research is necessary. It is not always Lyme-Disease. It could also be another infection. A patient can also have two or more infections at the same time. Also other infections and tick-borne diseases can cause complaints.

We recommend considering a possible chronic infection in the case of an unclear diagnosis and/or if the symptoms are the following:

– Unexplained physical exhaustion (chronic fatigue syndrome – CFS), (6)

– Ambulant pain in muscles and articulations (2), (5)

– Erratic pain

– Neuropathic symptoms of undefined genesis

– Unclear (poly-) neuropathies

– Atypical MS, MS-like symptoms, Parkinson-like Syndrom

– suspect of Fibromyalgia

– Some auto-immune diseases (e.g. seronegative RA)

– Psychiatric troubles of undefined genesis (mayby also in cases of chronic and/or therapy-resistant depressions)


By now, there are several studies that establish a connection between chronic infections and chronic recurring ailments (see: chapter Antibiotic Treatment, literature (1), (2) and (10)). Even the general opinion does not exclude a sub-clinical (latent) infection any longer.

We only consider an infection to exist after the exclusion of any other origin of the symptoms.  It is important to always ask why the patient has those symptoms instead of just diagnosing them; we should not just name and treat them, but try to find the origin of the ailments. We spend our time enumerating symptoms and end up treating them in an isolated way. Further, we should be able to ask another question as well: what therapeutic solutions can be offered, especially for patients who have tried all the other therapeutic methods, whom cannot be helped by psychologists, who are considered “healed” and who cannot be diagnosed with psychosomatic disturbances? We have given only a small overview of the diagnoses that we regularly find in medical reports.

It is known that a chronic form illness (or “late form”) can have different symptoms than the acute form. These differences are present in the clinic as much as in the laboratory tests.


Turhan Canli: “Reconceptualizing major depressive disorder as an infectious disease”, Biology of Moods & Anxiety Disorders, 2014, 4:10;


Another study on this topic has been realized by Jeffrey H. Zimering et al. : “Acute and chronic pain associated with Lyme borrelisos: Clinical characteristics and pathophysiologic mechanisms” PAIN 144 (2014) 1435-1438,                      Comment: We realize that we do not know all the existing mechanisms. A possible lasting infection cannot be excluded. Nor can we say that a swelling of the joints must occur, especially in the chronic form (or “late form”).


A new Study about this theme:  Sam T Donta: “Lyme Disease, Chronic Fatigue and Fibromyalgia “, Chronic Dis Int. 2014;1(1):2


An interesting case report: Mirouse G. et al: “Bartonella henselae osteoarthritis of the upper cervical spine in a 14-year-old boy”, Orthop Traumatol Surg Res (2015),


A new case report: Amir Garakani and Andrew G. Mitton: “New-Onset Panic, Depression with Suicidal Thoughts, and Somatic Symptoms in a Patient with a History of Lyme Disease”, Case Reports in Psychiatry, Volume 2015, Article ID 457947, 4 pages;



Further organmanifestations:


I:    Borreliosis (or Lyme disease) can also manifest in the eye, for instance. So do certain co-infections (see also last chapter “comments and co-infections”).

A new case report for that: Correll MH, Datta N, Arvidsson HSS, et al. :  “Lyme neuroborreliosis: a treatable cause of acute ocular motor disturbances in children”,  Br 1 Ophthalmol Published Online First: [published on June 16., 2015] doi:10.1136/ bjophthalmol-2015-306855

  • Berglöff, J. et. al. „Ophthalmic Manifestations in Lyme Borreliosis“, Journal of Neuro-Ophthalmology 14 (1): 15-20, 1994.


  • Leys AM, Schönherr U., Lang GE et. al. „Bulletin de la Societe Belge D`ophtalmologie (1995, 259:205-2014)” , Department of Opthalmology, Universitaire Ziekenhuizen Leuven, Belgium.


  • Gerald W. Zeidman “The Ocular Manifestations of Lyme Disease”, International Ophthalmology Clinics, Winter 1993, Volume 33 , issue 1, ppg 9-22.


  • Lawton Smith, J. et. al. “Retinal Vasculitis in Lyme Borreliosis”, Journal of Clinical Neuro-ophthalmology 11(1): 7-15, 1991.


  • Norfarizal Ashikin Abdullah “Unilateral visual loss secondary to cat scratch disease in a healthy young man”, Asian Pacific Journal of Tropical Disease, 2015; 5(I): 77-79


  • Omar Lezrek „ Neuroretinitis in Ocular Bartonellosis“, J.Pediatr. 2014.


  • Blanc F, Ballonzoli L, Marcel C et al.: Lyme optic neuritis; 2010, J Neurol Sci 295(1-2), 117-9.


  • Fiehn Christoph et al.: “Differetialdiagnose der Uveitis”, Dtsch Ärztebl 2003; 100(39): A-2514/ B-2098/ c-1975


  • S.Kramer et al.: “Epstein-Barr Virus assoziierte Retinitis”, 96. Jahrestagung der DOG 1998, P 100,



II.    Heartmanifestation is also possible:

–    Joseph D. Forrester „Notes from the Field: Update on Lyme Carditis, Groups at High Risk, and Frequency of Associated Sudden Cardiac Death—United States “, CDC 24/7 (MMWR), October 31, 2014/ 63(43);982-983

–   Jayaprakash Shentar “Diagnosis not to be missed: Lyme carditis, rare but reversible cause of complete atrioventricular block”, Indian Heart Journal (November 2014), 1-4

–  Mannava K. “Putting Heart Block Back in the “Lyme Light”, J Cardiol Cases (2014),

–  Semmler D. et. al. “Complete AV block in Lyme carditis: an important differential diagnosis”, Clin Res Cardiol. 99(8), 519-26. doi:10.1007/s00392-010-0152-8. (2010)

–  Dolbec KW “Lyme carditis with transient complete heart block”, West J Emerg Med. 11(2), 211-2 (2010)

–  Hidri N. “Lyme endocarditis”, Clin Microbiol Infect 2012; 18: E531- E532


Very interesting new case report:

– Yoon E, Vail E, Kleinman G, Lento PA, Li S, Wang G, Limberger R, Fallon JT, Lyme disease: A case report of a 17-year old male with fatal Lyme carditis, Cardiovascular Pathology (2015), doi: 10.1016/j.carpath.2015.03.003

Comment:  It is very good that someone has even considered about looking for Lyme disease (in the tissue of the heart) and has also thought of Borrelia. Here the direct proof is possible as it is in the tissue where the bacteria is seated. Thus we all are able to learn. How many autopsies (postmortem examinations), also on adult patients, take place with this posing of question?  What about the so far generally statement, that Borrelia does not lead to deaths? How many times was this investigated so far?



III.   Maybe Lyme disease is also the cause of symptoms in some patients in the field of ENT:

Young Kaelan et al.: Burning Mouth Syndrome: A rare manifestation of Lyme Disease; Georgetown University Hospital, MedStar Health, 2016

C Espiney Amaro “Lyme disease: sudden hearing loss as the sole presentation”, The Journal of Laryngology & Otology, 1 of 4, 2015, doi:10.1017/S0022215114003417



IV:   Can also other Skin problems are associated with Borrelia-infections?

Ekta K Bhardwaj and Ralph Michel Trüeb: ” Acute diffuse and total Alopecia of the female scalp associated with Borrelia-infection”, Int J Trichology, 2015, Jan-Mar; 7(1): 26-28; doi: 10.4103/0974-7753.153454


As mentioned in the previous chapter, different Borrelia strains can manifest in different organ systems and thus, generate different symptoms (1). One tick can also transmit several different borrelia strains and other infectious pathogens.




We would like to discuss issues that can elicit background questions about symptoms:

– When discussing the origin of ambulant and erratic pain in articulations, do we think of chlamyd. trachoma., chlamyd. pneum.(2), yersinia, borrelia, mycoplasma spp (5) etc.?

– When treating chronic and/or relapsing rhinitis, sinusitis, bronchitis, dry cough during weeks after exclusion of a malignancy, do we think of chlamyd. pneum, mycoplasma pneum., legionella or aspergillus. Is there a chronic chlamydia-infection in people that have a weakened immune system? And can it really be treated sufficiently with three days of Azithromycin? Could not a seronegative RA or a seronegative borreliosis actually be a chlamydosis or a yersiniosis, or even a borreliosis from a yet unknown strain (see chapter: “General Information”)? Unfortunately, chronic forms of infections are hardly accepted to this date. Yet, they could exist (see study of Prof. Zeidler, in chapter Antibiotic Treatment, literature (1) and (10)).

– Is it true that it is only people with diabetes mellitus, alcohol-based illnesses, tumors, chemotherapies, organ transplants, genetic immune defects and the elderly that suffer from a weakened immune system and that all the others are considered immune-competent? Could it not be possible that someone with partial weakened immune system due to chronic infections and the mentioned environmental influences (of course not to be compared to HIV) could fall ill and display symptoms?

– There are many diabetic patients. This is a large group of patients. Do we think about the immunodeficiency in this patients and the possibility that they can have a chronic infection if they show unclear symptoms?

– What is the current research situation regarding the origins of some auto-immune diseases, allergies and endocrine disorders?

– When the corresponding symptoms are described, do we think of ehrlichia, bartonellosia, rickettsia, neo-ehrlichia…etc.?

– When dealing with Chronic Fatigue Sydrom (CFS), a chronic viral infection is discussed. Could it not be that chronic bacterial infections are added to it (6)?

Do we check for borrelia, chlamydia or other infectious pathogens in cases of (or suspect of) TIA or apoplectic strokes (esp. in younger patients) since they can also cause vasculitis (3) ?

– Just a few words about fibromyalgia:  Based on our researches there is no controversy about the fact that Borrelia can cause neuropathic complaints. There is a study which has shown that the pains in fibromyalgia are neuropathic pains (4). Therefore, isn’t it possible that patients with fibromyalgia could suffer from a Borrelia infection?



(1) Clark KL et al.: Geographical and genospecies distribution of Borrelia burgdorferi sensu lato DNA detected in humans in the USA; J Med Microbiol. 2014 May; 63(Pt 5): 674-84. Doi: 10.1099/jmm.0.073122-0.Epub 2014 Feb.

(2) Carter JD, Gerard HC “Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritis”, Arthritis Rheum 2009; 60: 1311-6

(3) Arseny A. Sokolov et al. “Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia”; Ann Emerg Med. 2015: 1-5;

(4) Nurcan Üceyler, Zeller Daniel et al.: “Small fibre pathology in patients with fibromyalgia syndrome”, Brain 2013: 136; 1857-1867 ; doi:10.1093/brain/awt053

(5) Matsuda K. “A novel therapeutic strategy for mycoplasma infectious diseases”, Personalized Medicine Universe (2015),

(6) Gerwin Morris et al.: “The putative role of Viruses, Bacteria, and chronic Fungal Biotoxin exposure in the Genesis of intractable Fatigue accompanied by cognitive and physical Disability”, Mol Neurobiol, doi 10.1007/s12035-01509262-7; 17.6.2015



Literature and terminology diagnostic -symptome (see on the bottom of the page : Berghoff.W (2013), a blue link, please click).

There is also existing literature (see below) on the following topics: MS and neuroborreliosis, Alzheimer and spirochetes, and psychiatric problems and lyme (from Fallon and Bransfield) on



The next studies are only for your information. We found these studies on “”:


1. Fallon Peer-Reviewed Articles Include (the list is longer): cognitiv and psychiatric problems?

Fallon BA, Vaccaro B, Romano M, Clemente D. Neuropsychiatric and Neuropathologic Aspects of Lyme Disease. Psychiatric Annals, 36:120-128, 2006.

Keilp BA, Corbera K., Slavov I., Taylor M.J., Sackeim H.A., Fallon B.A. WAIS-III and WMS-III Performance in chronic Lyme disease. J International Neuropsychological Society. 2006;12(1):119-129.

Fallon BA. Mystery Diagnosis: treatment of Neuropsychiatric Lyme Disease. In DSM-IV-TR Case Book: Experts Tell how they treated their own patients, Volume 2. Ed. Spitzer RL, First MB, Williams JBW, Gibbon M. American Psychiatric Publishing, Inc. 2006, pp 39-52.

Fallon BA. Neuropsychiatric Aspects of Non-HIV Infectious Diseases. In Comprehensive Textbook of Psychiatry, Eighth Edition. Ed. Kaplan and Sadock. Williams and Wilkins, 2005

Fallon BA, Keilp J, Prohovnik I, Van Heertum R, Mann JJ. Regional cerebral blood flow and cognitive deficits in chronic Lyme Disease. J Neuropsychiatry and Clinical Neurosciences, 2003; 15: 326-332.

Tager FA, Fallon BA. Psychiatric and Cognitive Features of Lyme Disease. Psychiatric Annals 31: 173-181, 2001.

Tager FA, Fallon BA, Rissenberg M, Jones CR, Liebowitz MR. A controlled study of cognitive deficits among children with chronic Lyme disease. J Neuropsychiatry 2001; 13: 500-507.

Plutchok JJ, Tikofsky RS, Liegner K, Kochevar JM, Fallon BA, Van Heertum RL. Tc-99m HMPAO Brain SPECT Imaging in Chronic Lyme Disease J of Spirochetal and Tick-borne Diseases 6: 117-122, 1999.

Fallon BA, Kochevar J, Nields J. The underdiagnosis of neuropsychiatric Lyme disease in children and adults. In Diagnostic Dilemmas. Edited by David Tomb. Psychiatric Clinics of North America. 1998.

Fallon BA, Schwartzberg M, Zimmerman B, Weber CA, Liebowitz MR. Late stage neuropsychiatric Lyme disease: Diagnosis & treatment. Psychosomatics, 36: 295-300, 1995

Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. American Journal of Psychiatry, 141: 1571-1583, 1994

Fallon BA, Bird H, Hoven C, Cameron D, Liebowitz MR, Shaffer D. Psychiatric aspects of Lyme disease in children and adolescents: A community epidemiologic study in Westchester, New York. Journal of Tick Borne and Spirochetal Diseases, 1: 98-100, 1994

Fallon BA, Nields JA, Parsons B, Liebowitz MR, Klein DF. Psychiatric manifestations of Lyme borreliosis. Journal of Clinical Psychiatry 54: 263-268, 1993

Fallon BA, Nields JA, Burrascano JJ, Liegner K, DelBene D, Liebowitz MR. The neuropsychiatric manifestations of Lyme Borreliosis. Psychiatric Quarterly 1992; 63: 95-117


2. Lyme Disease and Psychiatric Symptoms:

By Robert C Bransfield, MD, DLFAPA

There are several thousand peer-reviewed references demonstrating the association between infections and mental symptoms and at least 65 different microbes have been recognized as causing mental symptoms.[1] Three hundred peer-reviewed articles describe the causal association between Lyme/tick-borne diseases and mental symptoms, pathophysiology, morbidity and mortality some of which are included in the attached addendum. Lyme disease: a neuropsychiatric illness is a major and classic article summarizing this association.[2] A Controlled Study of Cognitive Deficits in Children With Chronic Lyme Disease  is a particularly useful resource for describing some of the cognitive symptoms associated with Lyme/tick-borne diseases. Attempted suicide and completed suicide associated with neuropsychiatric manifestations of Lyme disease and other tick-borne disease has been observed and reported by the author and many other clinicians.[3]  An article in the American Journal of Psychiatry,  Higher Prevalence of Antibodies to Borrelia Burgdorferi in Psychiatric Patients Than in Healthy Subjects  compared 499 psychiatric inpatients to matched pair healthy controls and found significantly more psychiatric patients were seropositive for Borrelia burgdorferi (33% vs. 19%), thereby demonstrating an association between Borrelia burgdorferi infections and psychiatric morbidity. In contrast, there are only a few poor quality articles that attempt to negate the causal association between tick-borne diseases and psychiatric illness.[4][5][6][7]

Within these articles there is significant evidence that more extensive antibiotic treatment is needed to control the psychiatric symptoms associated with Lyme disease and other tick-borne diseases.

[1] Bransfield RC. Preventable cases of autism: relationship between chronic infectious diseases and neurological outcome. Pediatric Health. (2009) April 3(2).

[2] Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994 Nov;151(11):1571-83.

[3] Fallon BA, Schwartzberg M, Bransfield R, Zimmerman B, Scotti A, Weber CA, Liebowitz MR. Late-stage neuropsychiatric Lyme borreliosis. Differential diagnosis and treatment. Psychosomatics.1995 May-Jun;36(3):295-300.

[4] Nadelman RB, Herman E, Wormser GP. Screening for Lyme disease in hospitalized psychiatric patients: prospective serosurvey in an endemic area. Mt Sinai J Med. 1997 Nov;64(6):409-12.

[5] Hassett AL, Radvanski DC, Buyske S, Savage SV, Sigal LH. Psychiatric comorbidity and other psychological factors in patients with “chronic Lyme disease”. Am J Med. 2009 Sep;122(9):843-50.

[6] Hassett AL, Radvanski DC, Buyske S, Savage SV, Gara M, Escobar JI, Sigal LH. Role of psychiatric comorbidity in chronic Lyme disease. Arthritis Rheum. 2008 Dec 15;59(12):1742-9.

[7] Grabe HJ, Spitzer C, Lüdemann J, Guertler L, Kramer A, John U, Freyberger HJ, Völzke H. No association of seropositivity for anti-Borrelia IgG antibody with mental and physical complaints. Nord J Psychiatry. 2008;62(5):386-91.

further studies (the list is very long):

  • Miklossy J: Alzheimer’s disease – a neurospirochetosis. Analysis of the evidence following Koch’s and Hill’s criteria; J Neuroinflammation, 2011 Aug 4; 8(1):90.


  • MacDonald AB: Alzheimer’s neuroborreliosis with trans-synaptic spread of infection and neurofibrillary tangles derived from intraneuronal spirochetes; Med Hypotheses, 2007; 68(4):822-5.


  • Alaedini A, Latov N: Antibodies against OspA epitopes of borrelia burgdorferi cross-react with neural tissue; J Neuroimmunol. 2005 Feb; 159(1-2):192-5.


  • Volkman D: Anti-neural antibody reactivity in patients with a history of Lyme borreliosis and persistent symptoms; Brain, Behavior, and Immunity 24 (2010).


  • Robert C. Bransfield, MD, Mason Kuhn, MS: Autism and Lyme Disease; JAMA. 2013;310(8):856 doi:10.1001/jama.2013.194747.




3. MS and Neuroborreliosis (the list is also longer):

Spirin NN, Baranova NS, Faedeeva OA et al.: Differential aspects of multiple sclerosis and chronic borrelial encephalomyelitis; 2011, Zh Nevrol Psikhiatr Im S S Korsakova 111(7), 8-12.

Mattsson N, Bremell D, Anckarsäter R et al.: Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism; 2010, BMC Neurol 51.

Blanc F, Ballonzoli L, Marcel C et al.: Lyme optic neuritis; 2010, J Neurol Sci 295(1-2), 117-9.

Fadil H, Kelley RE, Gonzalez-Toledo et al.: Differential diagnosis of multiple sclerosis are associated with primary effusion lymphoma; 2007, Int Rev Neurobiol 393-422.

Schmutzhard E: Multiple sclerosis and Lyme borreliosis; 2002, Wien, Klin Wochenschr 114(13-14), 539-43.



4. New article (also a list exists): Judith Miklossy: “Historic evidence to support a causal relationship between spirochetal infections and Alzheimer’s disease”, Frontiers in Aging Neuroscience, Volume 7, Article 46, April 2015; doi: 10.3389/fnagi 2015 00046

Priya Maheshwari and Guy Eslick: “Bacterial Infection and Alzheimer’s Disease: A Meta-Analysis”, Journal of Alzheimer’s Disease 43 (2015) 957-966, doi 10.3233/JAD-140621

Herbert B. Allen, Diego Morales, Krister Jones and Suresh Joshi: Alzheimer‘s Disease: A Novel Hypothesis Integrating Spirochetes, Biofilm, and the Immun System ; J Neuroinfect Dis 2016, 7:1,