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• Gastrointestinal manifestations of Lyme disease
• Patients with direct detection agent in chronic Lyme disease: clinical, laboratory diagnosis, antibiotic therapy and disease course
• Long-term treatment with anti-infectives in persistent Lyme disease with Borrelia DNA detection by PCR
• Experience with long-term antibiosis in late borreliosis and arguments for it - knowledge about biofilms as a possible cause of chronic infections
• Babesiosis - "Malaria of the North" - Chronic infection that is underestimated in terms of its frequency, but also of its severity

Gastrointestinal manifestations of Lyme disease and co-infections to be observed - a literature review.

Paper presented at the fall meeting of the Lyme Disease Association 2005 Dr. Wolfgang Klemann

In my presentation today is once more to the "many faces" of the disease (B);

I would like to discuss today an often neglected aspect, namely the "gastrointestinal manifestations of Lyme disease" and more recent publications on this topic, with co-infections often a manifestation of gastrointestinal important role to play with.

By Steere et al (1) in 1983 was reported gastrointestinal symptoms associated with Lyme disease (in this work, in particular regard to increasing the lebertypischen enzymes in B). Meanwhile, however, we have all learned that Lyme ticks, but a whole range of other pathogens can transmit not only.

An overview of these pathogens can be found in Zaidi and Singer (2).

Pathogen in detail:

• Borrelia burgdorferi
• Ehrlichia chaffeensis and Ehrlichia phagocytophilia
• Rickettsia rickettsii (Rocky Mountain spotted fever), European counterparts: Rickettsia conori, the cause of the Mitel sea typhus (vector: "Brown tick"), but also Rickettsia prowazekii, the cause of typhus (vector: body louse), literature on this, see also (3)
• Francisella tularensis, the cause of tularemia (rabbit fever), literature on this, see also (3)
• Colorado tick fever, high fever a disease caused by a "Colti" virus; The listed Colorado tick fever corresponds i. Eyach Europe the virus, which is also in the group of Reo-virus probably belongs. Clinical course similar to the TBE with bimodal febrile period. Literature on this, see also (3)
• Tick-borne relapsing fever caused by Borrelia (B.) of the genus B. turricatae, B. hermsii and B. parkeri, carrier: Weichzecken the genus Ornithodorus, "Worldwide occurrence. Already in 1905 could be detected in ticks by Dutton and Todd responsible pathogen as spirochetes, which determines which consisted Borrelia; Borrelia relapsing fever actually differ little from the pathogens d. Lyme disease, but make violent fevers usually in 7 - day cycle. Other names: Borrelia hispanica, Crocidura, microti, etc., depending on the geographical occurrence, literature on this, see also (3)
• Q fever, caused by Coxiella burnetti, an obligate intracellular pathogen that is among the rickettsiae, the pathogen is by ticks of the genus Dermacentor to domestic animals-sheep, goats, cattle, transmitted, transmission to humans is often secondary to aerosols and also by consumption of raw milk or fresh goat cheese, which can lead to hepatitis (4)
• Babesiosis; pathogens: Babesia microti (United States), Babesia divergens (Europe), among others, include Babesia as the causative agent of malaria, the single-celled protozoa and are found in erythrocytes, can therefore be detected in the blood smear also.

In a in (2) contained tabular representation can be seen easily that only Borrelia gastrointestinal symptoms may not cause but also all listed tick-borne pathogens, with clinical symptoms are very similar or auchüberlappend represent.

Symptoms in detail:

Weight loss, nausea, vomiting, abdominal pain, diarrhea, liver enlargement of the spleen, jaundice (bilirubin), increased lebertypischer and enzymes.

Regarding the frequency of individual symptoms in each disease may I in Table 1 (2) refer to.

Remarks:

Ehrlichiosis (E): - clinical cases were reported in Europe since then only very occasionally; Ehrlichia, the actual pathogens, are related to rickettsiae, it differs in humans and a granulöcytäre moncytäre form d. E.; as well as fever, headache, muscle pain and transaminase are very characteristic, besides leukopenia u.Thrombocytopenie.

Tularemia (T) is called on German as "rabbit fever," agent: Francisella tularensis; Main reservoir are wild rabbits and other rodents, there are several means of transmission:

• First direct contact with blood of infected animals,
• 2nd Tick bites (by ticks of the genus Dermacentor and Ixodes);
• 3rd Inhalation of infectious aerosols: dead rodents were in the hay, the loading of highly infectious inhalation aerosol, which usually progress to a pneumonic form of the Baptist leads in; SA to Lit (3).

The causative agent of Q fever Coxiella burnetti is, diagnosis is usually serological protection possible and the acute form usually runs a high fever as a disease with head and limbs and pain, sometimes referred to as atypical. Pneumonia, granulomatous hepatitis as a complication can occur even see references in (4) and (3)

All of these pathogens can therefore be transmitted by ticks and can cause symptoms gastroitestinale. Depending on the clinical picture should be drawn og infection whereas in the differential diagnosis.

But now to the actual topic:

Simultaneous gastrointestinal infections of various pathogens, including Lyme disease.

Already published in 1996, Fried, Duray and Pietrucha a scientific article on pathological changes of the gastrointestinal tract in children who suffered from a disease (5).

• In this study, symptoms were 10 children 8-19 years with Lyme disease and chronic gastrointestinal investigated.
• Showed a histological inflammation of the stomach, duodenum, but also of the colon
• Histologically to evidence of spirochetes in five of the 10 cases in later works, these are identified as Borrelia burgdorferi.

Further scientific publications of the same group of authors on the same subject was followed in 1999 and 2002nd (6) and (7)

In 2002, Fried and colleagues also published a work of, in which Bartonella henselae has been associated with gastrointestinal symptoms such as heartburn, abdominal pain, mesenteric lymphadenitis, gastritis and duodenitis as well as skin redness (8). Bartonella henselae is otherwise known as the causative agent of cat scratch disease.

The latest work on this subject were published in Nov. 2004 (9), published by Fried, Adelson and Eli Mordechai (a microbiologist and molecular geneticist). It is dasVorkommen on the frequency and four in this context investigated by agents reported saying:

• Helicobacter pylori,
• Borrelia burgdorferi
• Mycoplasma fermentans and
• Bartonella henselae

Were examined 81 patients aged 8-21 years. They had been by your treating physicians or pediatricians admitted for inpatient evaluation. The spectrum of complaints and diagnostic spectrum at admission ranged from chronic abdominal pain, blood in stool, gastroesophageal reflux with heartburn, Crohn's disease, celiac disease on to failure to thrive or weight loss. All patients were examined clinically and laboratory findings, including determination of antibodies to known pathogens. They were also either ösophagogastroduodenoskopiert or kolonoskopiert, derived from mucosal biopsies were PCR tests performed on the above agents, only the detection of Helicobacter light microscopy was carried out biopsies of the upper gastrointestinal tract. In the DNA analysis for Borrelia burgdorferi-primers were for the OSP-A gene and chromosomal LY1 specifically used. For the determination of Bartonella and Mycoplasma fermentans were studied ribosomal RNA genes. In case of suspected gallbladder or bile duct involvement were abdominal sonographic studies of the supplement also carried out. In case of suspected mesenteric lymphadenitis or Apendizitis led to investigations of the abdomen by computed tomography, and stool tests for blood ocultes, Chlostridium difficile toxin, Salmonella, Shigella, Yersinia, Campylobacter, E. Coli, worm eggs and Elisa antigen tests against lamblia. Mucosal biopsies were taken from inflamed mucosal areas, either at the esophago-gastro-duodenoscopy or colonoscopy.

Results:

• In 30 of the 81 patients (or 37%) were found PCR-positive for a single infection.
• 19 of 81 (24%) and in 6 of 81 (8%) had Biopsiepositivität PCR for two or three gastrointestinal infections.
• In the 30 patients with only a single infection was Bartonella henselae in twelve cases represent the most common, followed by
• Helikobakter-pylori followed in nine cases of
• Mycoplasma fermentans in 6 cases and only fourth
• Borrelia burgdorferi, in only three cases.
• the 19 co-infections found by the Bartonella, and Mycoplasma fermentans, in 10 cases,
• Bartonella and Borellia burgdorferi in six-and
• Borellia-burgdorferi and Mycoplasma fermentans-cases were also found in 2 and were each associated with localized inflammatory mucosal changes.
• In the gastro-intestinal biopsies with triple infections were four cases in the same Bartonella, mycoplasma fermentans and Helicobacter detected during Bartonellahenselae, mycoplasma enzymes and Borrelia burgdorferi-two cases were detected in the same time.
• In the synopsis of the 81 patients were examined 35 Bartonellahenselae an infection, 24 had a mycoplasma fermentans infection, 14 had a Helikobakter-pylori infection and a total of 13 patients had a Borrelia burgdorferi-infection either simple, or as multiple infections, such as described.
• In 33% of the patients, let no infectious cause of disease to demonstrate at the stool analysis, no further infections are detected. Abdominal ultrasonography in the supplementary notes were neither gallstones nor pancreatitis, or to diseases of the galleabführenden ways.

On the basis of this small study appears to Bartonella henselae as the most commonly pathogenic agent in the patient population studied.

In patient with chronic gastrointestinal and possibly multisystemic complaints is therefore called to the occurrence of pathogens to think.

In the evaluation of chronic gastrointestinal complaints endoscopy with biopsy sampling and DNA analysis from the above organisms (by PCR method) to confirm the diagnosis recommended on.

This is especially true if there are additional neurological symptoms or arthralgia, or not to standard diagnostic result has led to one.

In the interpretation of results should be taken into account that the PCR method is not perfectly sensitive, negative results should not therefore be used clinically and serologically or perhaps even a history-exclude suspected diagnosis.

Order, and quasi-rounded patients who do justice to the subject, the same joint pain complain, I want the "Research Report 2001" of the Department of Rheumatology, Hannover Medical School indicate (Director: Prof. Henning Zeidler) (10).

Here was a special group of patients, namely patients with so-called "early undifferentiated oligoarthritis", also by PCR method

• Chlamydia trachomatis - DNA and
• Borrelia burgdorferi - DNA tested.

to clarify: only 40-50% of patients oligoarthritis (inflammation of 1-4 joints) can develop, disease, years of a defined rheumatic disease are associated with the first. The rest are known as "undifferentiated arthritis" classified. In this population there are many characteristics that infektreaktive arthritis and spondylarthritides remember, such as a cluster of hereditary characteristics HL AB 27, a preferred attack of the lower extremity or a contribution from the axial skeleton.

In the period 1994-97 were 52 patients recruited. The inclusion criteria were in accordance in all patients, the Lyme disease serology and also certain chlamydial DNA negative in morning urine, because the disease usually already as Lyme arthritis and Chlamydia-induced arthritis would have been classified.

• Fifteen of the 52 patients had a positive PCR in the synovial fluid results in 9 patients (17%) could Chlamydia trachomatis DNA in 6 patients (12%), Borrelia burgdorferi DNA was detected.
• In a control group of 31 patients with rheumatoid arthritis found no intra-articular contrast, DNA evidence, while the PCR detection control groups with confirmed chlamydia-induced arthritis in 50%, in Lyme arthritis in 69% succeeded in.

These results show that approximately one third of patients with undifferentiated arthritis using modern molecular methods, a triggering infection with either Chlamydia trachomatis or Borrelia burgdorferi can be detected.

They prove the existence of seronegative Lyme disease cases.

Literature:

(1): Steere AC, Bartenhagen NH, Craft JE, et al. The early clinical manifestations of Lyme disease. Ann Intern Med 1983; 99: 76-82

(2) :) Zaidi SA, Singer C. Gastrointestinal and hepatic manifestations of tickborne diseases in the United States.
Clin Infect Dis. 2002 May 1;34(9):1206-12. Epub 2002 Apr 2. Review.

(3) Kimmig P., Hassler D., Braun R.: Zecken, Kleiner Stich mit bösen Folgen, Verlag Ehrenwirth Ratgeber, 2000 ISBN 3-431-04018-7

(4) Dupont HT, Raoult D Brouqui P et al: Epidemiologic features and clinical presentations of acute Q fever in hositalized patients: 323 French cases, Am J Med 1992; 93: 427-34.

(5) Fried MD. Duray P, Pietrucha D. Gastrointestinal Pathology in children with Lyme Disease. J Spirochetal and Tick-Borne Diseases, 1996; 3: 101-104.

(6) Fried MD, Abel M, Pietrucha D, Yen-Hong K, Ball A. The spectrum of gastrointestinal manifestations in children aund adolescents with Lyme disease. J Spirochetal and Tick-Borne Diseases, 1999; 6: 89-93

(7) Martin D. Fried, MD; Dorothy Pietrucha, MD; Gaye Madigan, RN; and Aswine Bal, MD. Borrelia burgdorferi Persists in the Gastrointestinal tract of Children and Adolescents with Lyme Disease. Journal of Spirochetal and Tick- Borne Diseases. Vol. 9, No. 1, 2002. pp. 11-15.

(8) Fried MD, Schairer J, Madigan G, Ball A. Bartonella henselae is associated with heartburn, abdominal pain, skin rash, mesenteric adenitis, gastritis and duodenitis. J Pediatr. Gastroenterol. Nutr. 2002; 35:3 Abstract 158

(9) Fried MD, Adelson ME, Mordechai E: Simultaneous Gastrointestinal Infections in Children and Adolescnts, Practical Gastroenterology, November 2004 87-80.

(10) „Forschungsbericht 2001“ der Abteilung Rheumatologie der medizinischen Hochschule Hannover hinweisen (Direktor: Prof. Henning Zeidler)