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The importance of the coinfections for the pathological process - i.e. their pathogenicity compared to Lyme disease - has not been clarified. Thus, in cases of double or multiple infections, a decision cannot be made as to which infection dominates in the pathological process.

In the symptomatology there are substantial overlaps between Lyme disease and the coinfections so that an unequivocal assignment of the disease manifestations to the existing infections is impossible. Many symptoms can thus be due to both a Lyme disease and the so-called coinfections.

The problematic nature of Lyme disease and coinfections always concerns the chronic course. The coinfections are thus only of importance for chronic Lyme disease (late stage, stage III). On the other hand, the synergic-pathological mechanism requires that the coinfections also are present in a chronic persistent form.

Anamnistically, one has to consider whether coinfections occurred in their acute form in the early phase because this contributes to the recognition of coinfections in the chronic phase.

In terms of laboratory diagnostic tests, only methods for indirect pathogen detection (serology, LTT) are also available for the coinfections in most cases, as is the case for Lyme disease. The prior infection can be confirmed with serological investigations. However, a positive serological finding is not proof that the infection caused the current illness. Basically, it is neither possible to prove the presence of an infectious disease nor to exclude it by means of a serological finding. Only if pathological laboratory findings occur or a deterioration of the finding can be detected in correlation with the disease are conclusions as to the disease development and situation justified to a certain degree in cases of previous seronegitivity or negative LTT in temporal parallelism to disease development.

The significant coinfections of Lyme disease are caused by Bartonella species (primarily by B. henselae), Chlamydia trachomatis, Chlamydophila pneumoniae, Yersinia enterocolitica, and Mycoplasma pneumoniae. Accordingly, these infectious diseases are highlighted in Tables 1 and 2 by the typeface.

The frequency of seropositivity and positive LTT (lymphocyte transformation test) was studied on my own clientele (n = 108). The results are presented in Table 3.
The investigations were conducted at the Institute for Medical Diagnostics (IMD) in Berlin. For more detailed information, please refer to the corresponding reference [339]. An LTT is not available for Bartonella. An LTT was not performed for Mycoplasma pneumoniae. The high incidence of the Chlamydia trachomatis LTT is conspicuous and unresolved.

According to investigations on my own clientele, CD57 NK cells are frequently diminished in chronic Lyme disease, but seldom in cases involving coinfections. However, the basic principle is that CD57 NK cells can be diminished in all chronic infectious diseases, but the phenomenon is observed relatively frequently in chronic LD.

The more important coinfections are summarized in an overview (Table 4). These more important coinfections are presented in accordance with the tabular sequence; they are then followed by the less important ones (chapter “Secondary coinfections of Lyme disease”) and finally to round out the presentation, a chapter on the socalled reactive arthritis follows.

In contrast to the USA, HGA (human granulocytic anaplasmosis, syn. human granulocytic ehrlichiosis (HGE)) and babesiosis are of little importance as coinfections in Europe.

Many interrelationships in the bartonellosis’ mode of transmission have not yet been clarified. The important infection data described in the scientific literature are summarized in Table 5.

Primary manifestations: infected skin lesion, swollen lymph nodes, multiorgan disorder (e.g. liver, spleen, nervous system, eye) [66-67], cf. Tab. 6.

Until 1993 only B. bacilliformis was known. The different Bartonella subspecies were first described [69] and their pathological significance, recognized in 1993 Bartonellosis can be expected to have substantial significance as a Lyme disease
coinfection. With regard to the health policy aspect, Lyme disease is more important because of its frequency. However, in this context it should be noted that bartonellosis has not been nearly as intensively investigated as Lyme disease.

Additionally, it is obvious from my own observations that the serology for Bartonella is frequently positive in patients with chronic Lyme disease.

With the increasing development of laboratory tests which is to be expected, the currently underestimated prevalence of bartonellosis will be more correctly registered in the future, and the importance of this disease will also be determined on the basis of its frequency.

Bartonellosis (caused by B. henselae und B. bacilliformis) can be associated with an extraordinary variety of symptoms. For further information on this see Table 8.

The bacterial-inflammatory skin infection (scratch or bite location) is in no way obligatory, i.e. bartonellosis can also occur without the typical cat scratch disease, which is characterized by the infected skin lesion and lymph node swelling.

Bartonellosis’ disease morphology can be better recognized when the most important of its many symptoms (Table 8), i.e. its main manifestations, are considered (cf. Table 6).

There are numerous overlaps with Lyme disease in the disease manifestation of bartonellosis. This fact is also mentioned in the relevant current literature [86].

The laboratory diagnostics for bartonellosis is given in Table 7.

In cases of infection with Bartonella, the blood smear initially shows pathogens on the outer membrane; in the further course the pathogens are increasingly localized intracellularly. In the process, the light colored center of the erythrocytes is lost (Fig.
1).

There is no information on the value of serology in the literature. In particular, the question as to whether seronegativity rules out the disease has not been clarified. On the other hand, as is the case for many other infectious diseases, a positive serological finding merely proves that an infection took place, but does not indicate that the disease currently exists.

Detecting Bartonella in culture is extremely problematical, and the sensitivity is very low so that this method of investigation is not part of routine diagnostics.

Detection of pathogens using PCR in biopsies appears to be very promising [87, 232], but the investigation with PCR must follow the biopsy nearly immediately [88].

The chronic course of bartonellosis has been described in numerous studies, in part, on large groups [90 - 94]. The long duration of the disease, which frequently covers many years, and the high similarity of the disease manifestations makes it extremely difficult to distinguish from chronic Lyme disease. Thus, bartonellosis is of great importance in the infectiologic differential diagnosis of Lyme disease.

In this context, attention should be paid to the fact that B. henselae has been found in ticks and that the transmission of B. henselae by ticks has been documented by means of pathogen detection in the liquor [95]. Additionally, the prevalence of B.
henselae in ticks is apparently high; scientific studies determined a prevalence of 40% [96].

According to my own surveys, 78% of the patients with chronic Lyme disease proved to be seropositive for Bartonella henselae.

A particular characteristic of Bartonella is the induction of vascularized tumors or granulomas, which occur in the region of the skin (bacillary angiomatosa), in the liver (peliosis hepatis) or in the spleen (peliosis splenitis) [97 - 99]. In this context, these
vascular tumors or granulomas exhibit a pathological sprouting of capillaries as well as enlarged and hyperproliferative vascular endothelial cells [100]. Bartonellosis is obviously accompanied by a stimulation of blood vessel formation. This corresponds
to the observation that bartonellosis, in addition to angiomatosis, also results in different other skin manifestations in which an increased vessel formation is observed [101]. In addition, the determination of VEGF (vascular endothelial growth factor) in blood could be of diagnostic importance [101].

Transmission modes /Vectors:
Bite or scratch wounds (dog, cat)
(saliva, claws)
Flea bites
Flea feces (oral)
Lice
Flies
Gadflies
Dust mites
Blood transfusions
Mother-child transmission

Infected scratch or bite wounds
Lymphadenopathy
(frequently cardinal symptom)

General symptoms
Fever
Fatigue
Drowsiness
Sleep disorders
Obesity
Swelling in different parts of the body
Sleep disorders
Weariness
Headaches
Air hunger
Fainting fits

Encephalopathy
Cognitive disorders
Concentration disorders
Blockage of thought processes
Limited memory
Instances of dyslexia and dysgraphia

Mental disorder:
Depression
Irritability
Agitation / Aggression
Disturbed impulse control
Panic attacks

Nervous system
Encephalitis
Myelitis
Neuralgias
Muscular asthenia
Paresthesias
Neuroradiculitis
Seizures
Cerebral infarction
Guillain-Baré syndrome

Musculoskeletal system
Arthritis
Arthralgias
Myalgias
Tendinitis
Osteomyelitis
Myospasm

Abdomen
Hepatopathy
(Peliosis hepatis)
(Hepatomegaly)
Splenopathy
(Peliosis splenitis)
Splenomegaly
Abdominalgia
ESR und CRP elevated
Hypercalcemia
Hepatic and splenic abscesses

Heart / Thorax
Endocarditis
Pneumonia
Pleural effusion
Myocarditis

Eye
Oculoglandular disorder
Conjunctivitis
Neuroretinitis
Papillitis
Optic neuritis
Retinochoroiditis
Uveitis: anterior, intermedia and posterior
[233]
Acute maculopathy
Choroiditis

The elementary bodies can exist extracellularly and are the infectious form. Reproduction of the elementary bodies is only possible in the host cells. After penetration, the elementary bodies are phagocytized by the host cell; intracellularly the elementary body changes into the reticulate body and as such can again divide. The elementary bodies are thus infectious, and the reticulate bodies are reproductive. Some reticulate bodies change back to elementary bodies, which are released subsequent to lysis of the host cell. The thus-produced elementary bodies then infest further host cells. Consequently, the precondition for an effective antibiosis is that the antibiotic is both intracellularly and extracellularly effective. This is the case for tetracyclines and macrolides.

The infection data for Chlamydophila pneumoniae are summarized in Table 10.

The primary disease manifestation of Chlamydophila pneumoniae is pneumonia. The incidence is 1% and predominantly affects people older than 65 years of age [132, 133]. The pneumonia is frequently accompanied by infections of the upper respiratory tract (pharyngitis, laryngitis, sinusitis). Slight disease expression initially, extrapulmonary manifestations (see Tab. 11) and a normal leukocyte count indicate an atypical pneumonia and thus also pneumonia caused by Chlamydophila pneumoniae.

In addition to pneumonia, Chlamydophila pneumoniae causes extrapulmonary manifestations [134] (cf. Table 11), which are significant with regard to the differential diagnosis of Lyme disease (LD) or Lyme neuroborreliosis (LNB).

The chronic course of Chlamydophila pneumoniae infections is documented by studies [234 - 240]. A relationship to CP was also described for Alzheimer’s disease [241]. This is a finding that is also of importance with regard to chronic LNB, for which the same associations have been demonstrated [295 - 298].

The extrapulmonary manifestations frequently extend across a long period of time, i.e. across months and years. This also applies to the so-called reactive arthritis, whose differentiation from the arthritides in Lyme disease is sometimes difficult. Attention should also be paid to the Guillain-Barré syndrome which can last for months and presents in the same manner as in the Lyme disease. The association with a myocarditis is also similar, whereas meningoencephalitis occurs in the acute phase, i.e. practically simultaneously with pneumonia.

The laboratory diagnostics for Chlamydophila pneumoniae includes serology, the lymphocyte transformation test (LTT), and the detection of the pathogenic organism using PCR (Tab. 12):

The serology results have severe inherent limitations. There is a considerable discrepancy between the serological findings, on the one hand, and pathogen detection using PCR, on the other hand [135, 136].

A single test for IgG has only a very low sensitivity [137], whereas the sensitivity is quite good in cases of a definite increase in IgG between the acute phase and the further course of the disease.

The diagnostic value of LTT for Chlamydophila pneumoniae has not yet been validated in the literature.

The chronic disease course obviously represents a chronic persistent infection. Chlamydophila pneumoniae could be detected both in the synovial fluid and in the liquor using PCR [234, 235, 236, 239, 240].

The antibiotic treatment of Chlamydophila pneumoniae is given in Table 13. The drug of choice is doxycycline; macrolides also exhibit good efficacy, particularly azithormycin; quinolones have a low efficacy [138]. However, gemifloxacin has proven to be very effective [242].

Chlamydia trachomatis

The microbiological anomaly of Chlamydia was presented in the chapter “Chlamyophila pneumoniae”. With regard to the antibiotic treatment, the fact that Chlamydia are present in their infectious form both intracellularly and extracellularly is decisive.

Chlamydia trachomatis is sexually transmitted and causes a urogenital infection. The differential diagnostic reference to Lyme disease results primarily from the arthritides, which are caused by a chronic persistent infection in both diseases. In Chlamydia trachomatis, the arthritis is assigned to the so-called reactive arthritis even though the detection of the pathogen occurred in the synovial fluid in studies [243, 244].

The arthritis occurs in 1% of the urethritis induced by Chlamydia trachomatis. Reiter’s triad (arthritis, uveitis, urethritis) occurs in 0.3% of those affected.

The disease can be easily detected by means of laboratory diagnostics (cf. Tab. 14) in cases of existing urogenital infection. In this context, NAATs (nucleic acid amplification techniques) in urethral smear or in urine are available; this examination is also reliable for asymptomatic patients [140-142]. PCR also has a high sensitivity and specificity [143].

The diagnostic value of serology and LTT has not been validated. Moreover, whether a chronic infection with Chlamydia trachomatis (as is the case with LD) can be accompanied by seronegativity has not been clarified. Seropositivity can indeed provide evidence of a previous infection, but principally does not allow any statement with regard to a disorder as a consequence of a persistent infection with Chlamydia trachomatis. Theoretically, a persistent or reproducible pathological lymphocyte transformation test indicates a prolonged infection, but scientific data for the diagnostic value are not yet available.

The significant data on the mode of transmission, symptomatology and treatment are summarized in Table 15.

Yersinia enterocolitica infection (yersiniosis)

In the differential diagnosis of Lyme disease and with regard to coinfection, the importance of yersiniosis is primarily based on the disease manifestation of a socalled reactive arthritis. As in Chlamydia infections and probably also in the bartonellosis, the arthritis is very probably the consequence of a chronic persistent infection [163, 164]. Since the so-called reactive arthritis in yersiniosis occasionally also occurs in the scope of Reiter's triad, i.e. in connection with urethritis and uveitis, the autoimmune processes are to be discussed with the pathophysiology. The thyroiditis which frequently occurs in yersiniosis and which is very probably expression of an autoimmune phenomenon as in LD is indicative of such an association.

The anamnestic research subsequent to the early phase of yersiniosis makes an important contribution to the recognition of chronic yersiniosis. The early phase of yersiniosis is essentially characterized by two disease manifestations:

• Gradually beginning gastroenteritis
• Pharyngitis

The infection data and symptomatology of yersiniosis are compiled in Table 16.

Yersinia enterocolitica was already recognized as pathogen as early as the beginning of the 20th century. However, the true significance of the pathogen, in particular, under epidemiological aspects was first described in 1995 [146].

Acute illness due to Y. enterocolitica is subject to registration (according to German law).

The pathogen penetrates into the intestinal wall and the mesenteric lymph nodes. Surface proteins and plasmid-bound virulence factors suppress the immune system of the host organism [147-150].

The disease results primarily in gastroenteritis, pseudoappendicitis, und mesenteric lymphadenitis.

In contrast to other bacterial gastroenteritides, the Yersinia enterocolitic gastroenteritis develops gradually and often becomes stressful or perceivable only after a week has passed [15 - 153]. Frequently, the infection is associated with a pharyngitis because the pathogens remain in the lymphatic tissue of the tonsils and the pharyngeal wall, where they can also be detected by means of a smear test. The concurrent occurrence of gastroenteritis with pharyngitis is typical for a yersiniosis [154].

The mean disease duration is approximately two to three weeks, but distinctly longer diseases courses have been described. The acute illness can be associated with numerous gastrointestinal complications, primarily as a consequence of a severe bacterial inflammation of the intestinal wall [155-157]. In addition, the disease can also affect many non-gastrointestinal organs [155, 156, 158 - 161].

The patients frequently remain excretory for months, even when the gastroenteritis has long since abated [152].

The yersiniosis can result in so-called reactive arthritis and is thus an important infectious disease in the differential diagnosis of Lyme disease. Since the disease can also sporadically occur [152] and frequently remains unrecognized, the anamnestic research for typical yersiniosis disease manifestations and data, particularly symptoms of the early phase is of considerable importance, particularly in the early phase.

Differentiation between LD and yersiniosis is made even more difficult by the fact that both infections can cause a multisystem disease. For information on the individual disease manifestations see Table 16.

The study by Saebo und Lassen [246], which determined many disease manifestations in a retrospective study of 458 patients, is of particular importance for the depiction of chronic yersiniosis:

The laboratory diagnostics of Yersinia enterocolitica infection is presented in Table 17.

As is the case in Lyme disease, there is often seropositivity in non-diseased people Information on a possible seronegativity in chronic yersiniosis is not available.

In the disease course the serological findings can correlate with the disease expression [165].

Yersiniosis frequently abates within a few weeks so that an antibiotic treatment is not generally recommended. This also applies with regard to the excretors. Only in cases of severe disease courses, in particular with sepsis, are antibiotics used.

Y. enterocolitica produces beta-lactamases with the consequence that penicillin, ampicillin and the cephalosporins of the first generation are ineffective [201, 205]. There is also frequently a resistance to macrolides.

It is also disputed whether early antibiotic treatment (i.e. for gastroenteritis) prevents reactive arthritis [203].

The differential diagnosis of chronic yersiniosis or chronic Lyme disease, respectively, is thus as a consequence of the many instances of overlap in the symptomology extremely difficult. In cases in which both diseases are present in their chronic form, a differentiation is often not possible at all.

Mycoplasma pneumoniae infection

The differential diagnostic differentiation between LD und Mycoplasma pneumoniae infection or the recognition of the coinfection by Mycoplasma pneumoniae is problematical because both diseases exhibit many identical disease manifestations; this applies to the extrapulmonary manifestation in Mycoplasma pneumoniae infections: disorders of the CNS, of the musculoskeletal system, of the heart, of the kidney and of the eye.

The infection data and the symptomatology are given in Table 19. In the foreground is the atypical pneumonia, frequently linked to symptoms in the region of the upper respiratory tract. There is no data on the frequency of extrapulmonary manifestations in the literature.

Mycoplasma pneumoniae is considered to be the most important pathogen of atypical pneumonia. However, pneumonia only occurs in approximately 3% - 10% of the cases in Mycoplasma pneumoniae infections [204]. In most cases, the infection results in a banal bronchitis [204], pharyngitis, rhinitis, ear aches, and sinusitis [205].

All the extrapulmonary disease manifestations listed in Table 17 are seldom [206 - 214]. In arthritis, Mycoplasma pneumoniae was detected in the synovial fluid by means of PCR [211]; this is an indication of a direct relationship to the infection.

Pathogen detection in articular effusion and the many extrapulmonary disease manifestations document the chronic disease course in cases of Mycoplasma pneumoniae. However, precise data on the chronic disease course are not available in the literature In particular, whether a chronic infection, especially with extrapulmonary disease manifestation, can persist with seronegativity is unclear. Seropositivity documents the infection, but it principally cannot serve as a diagnosis basis for a chronic persistent Mycoplasma pneumoniae infection.

The literature on the relationship between Mycoplasma pneumoniae and neurological disease manifestations is comparatively extensive. The publications primarily refer to neurological complications in pneumonia, i.e. the early phase of the Mycoplasma pneumoniae infection.

The neurological manifestations involve both the early phase, i.e. the point in time of existing pneumonia due to Mycoplasma pneumoniae, and later disease stages. Changes in the region of the brain stem [259, 267], myelitis [260, 263, 265, 269, 271, 274, 277, 279, 281, 284, 286], Guillain-Barré syndrome [261, 262, 268, 272, 282, 283], encephalitis [270, 273, 275, 276, 278, 280, 281, 285, 286], meningitis [270], polyradiculopathy [263], peripheral facial paresis [264, 266], optical neuritis and hemorrhagic leukoencephalitis [268], peripheral polyneuropathy [270], disorders of the brain nerves [282], radiculitis [282] have been described.

The frequency of neurological symptoms in connection with Mycoplasma pneumoniae varies between 1‰ [287], 1% [288], and 5% [289]. The pathogen has been repeatedly detected by means of culture methods or PCR [270, 274, 283].

Pathogen detection in serum and liquor is considered to be proof that the neurological manifestations are mediated infectiously and not immunologically [283]. However, the connection between Mp and neurological manifestations is not undisputed [290, 287].

Other extrapulmonary manifestations mentioned in the literature involve hepatitis, hemolytic anemia, Schönlein-Henoch purpura, disorders of the muscular-skeletal system, of the skin and other organs [265], macula edema [270], bilateral uveitis [291], nephritis [292], arthritis, hepatitis, pericarditis [292].

The laboratory diagnostics for Mycoplasma pneumoniae is presented in Table 20. The serology only becomes positive after several weeks, as is the case for most infectious diseases. It is therefore significant for the chronic disease course. Seropositivity substantiates the infection, but not the disease. Whether a chronic infection can also exist in cases of seronegativity has not yet been scientifically clarified.

The LTT for Mycoplasma pneumoniae has not been validated by studies.

The infection data and symptomatology are compiled in Table 22.

The pathological importance of human monocytic ehrlichiosis (HME) and human granulocytic anaplasmosis (HGA) was discovered in 1986 and 1994, respectively [35, 36]. The two infectious diseases resemble each other clinically and with regard to laboratory findings.

The pathogens develop in monocytes (HME) or in granulocytic leukocytes (HGA). Thus, their localization is exclusively intracellular.

The pathogens are transmitted by ticks, in the United States primarily via Ixodes scapularis, in Europe, via I. ricinus.

Important reservoirs: deer (HME); wood mice (HGA) In addition, other modes of transmission are being discussed: mother-child transmission, blood transfusions, direct contact with infected animals, transmission form person to person [37, 38, 41, 42, 43, 44].

Scientific reports on illnesses due to HGA in Europe are rarities [4]. However, studies in Northern Italy showed that 24% of the ticks (I. ricinus) were infected by E. chaffeensis or A. phagocytophilum. Similar figures have been substantiated in the Netherlands and in Poland, whereas in Germany they are at approximately 2% [5 - 10]. The figures for the East Coast of the United States were higher; approximately of the order of 30% - 40% [11, 12].

In patients with Lyme disease the seroprevalence for A. phagocytophilum in Europe is approximately 10% [13 - 15]. Similar figures were also obtained in the USA [16].

Since seroprevalence merely expresses something about the frequency of the infection, but nothing about the disease (HGA), no reliable statements about the frequency of the disease (prevalence of HGA) can be made. According to the laws of probability, a concurrent HGA infection in patients with Lyme disease might amount to a few percent at most.

There is no literature on chronic HGA courses. However, subacute and chronic courses are discussed [17, 19].

The determination of HGA (also as coinfection) merely on the basis of serological findings is dubious since seropositivity does not verify the presence of the disease (HGA), but only the prior infection. Also in the case of HGA, the diagnosis is based primarily on the totality of anamnesis, physical examination findings, medicinaltechnical findings, and differential diagnosis.

Doxycycline is recommended as therapy, also for children. Precise literature with regard to an adequate treatment is not available.

In summary, it can be stated that HGA as individual disease and as so-called coinfection in cases of Lyme disease is not of major importance in Europe; however, the literature in this problem complex is currently completely inadequate.

Pregnancy is a risk for the development of chronic Q fever. Untreated chronic Q fever results in a substantial morbidity and in mortality up to 60% [350]. Chronic Q fever requires a long-term antibiotic treatment, initially with doxycycline + hydroxychloroquine [350]. The antibiotic treatment must be performed for a period of at least 18 months [350].

The diagnosis is supported by serological tests. If the IFA IgG is 1:800 or higher, chronic Q fever cannot be ruled out. However, the laboratory diagnostics are not yet adequately standardized. The detection of the pathogen using PCR in tissue (e.g. heart valves) has a sensitivity of 100%, in blood of 47%; the sensitivity in buffy coat is somewhat higher. The examination of heart valves using echocardiography and, if necessary, FTG-PET, CT, MRT is also of diagnostic importance.

In 25% of the chronic Q fever cases heart valve changes can be detected echocardiographically.

Wegdam-Blans et al [350] have developed diagnostic guidelines for chronic Q fever (Tab. 25):

Frequent follow-up examinations are required during the disease course.

On suspicion of chronic Q fever:

• Echocardiography
• PET CT scan

Antibiotic treatment of chronic Q fever:

• Doxycycline
• Hydroxychloroquine
• Macrolides
  (azithromycin, clarithromycin, telithromycin)
• Fluoroquinolone
• Trimethoprim and sulfamethoxazole
  [345, 347-348]

In cases of chronic Q fever, treatment with doxycycline + hydroxychloroquine as a long-term treatment, i.e. for 18 months, is recommended [350].

Human parvovirus B19 infection

Pathogen:

• human parvovirus B19

Transmission:

• respiratory tract (droplet infection)
• Transmission during pregnancy
• Blood transfusion

Reservoir:

• human beings

Campylobacter jejuni (Cj) is a small gram-negative bacterium whose pathological significance was recognized in the 1980s. Worldwide, Cj is among the most frequent pathogens causing acute diarrhea Sources of infection are game animals and domestic animals, animal products and especially poultry [299]. The pathogen can persist in a coccoid form, but also in its normal form, for months in cases of unfavorable living conditions. It penetrates into the epithelial cells of the intestine and causes their destruction, possibly by means of toxins [303, 304].

The main manifestation of the Campylobacter jejuni infection is gastroenteritis. In the early phase (gastroenteritis), complications can occur in the abdominal region.

Cj has differential diagnostic significance due to complications in the late stage: reactive arthritis, Guillain-Barré syndrome.

Reactive arthritis in Cj infections is seldom; its frequency amounts to a maximum of 2.6% [305 - 308]. In connection with a Cj infection, the Guillain-Barré syndrome has a comparatively unfavorable prognosis [309]. Its incidence amounts to approximately 1‰ [310].

Reactive arthritis occurs approximately one to two weeks after gastroenteritis [304]; Guillain-Barré syndrome, in a period approximately two months after onset of infection [311].

The infection data and symptomatology are compiled in Table 26.

Antibiotic treatment reduces the duration of gastroenteritis. Macrolides [312] and quinolones are primarily recommended, but resistances to them can also occur [313]. Resistance to trimethoprim und beta-lactamases exists [314].

The term “reactive arthritis” is not a defined disease (nosological entity), but rather a concept for the classification of disease relationships and of the pathophysiology.

The term “reactive arthritis” is problematical because in many infections the pathogens were detected in the synovia and joint fluid in cases of such so-called reactive arthritis. This is true for Chlamydophila pneumoniae [234-236], Chlamydia trachomatis [243, 244] and for Yersinia enterocolitica [163, 164]. - Moreover, the pathogen was also found in the synovia in cases of arthritides in connection with Mycoplasma pneumoniae [211].

Reactive arthritis occurs days to weeks after the onset of infection. It predominantly affects the joints of the lower extremities. In cases involving a disease duration of less than 6 months, the term “acute reactive arthritis” was selected, for disease duration of more than 6 months, the term “chronic reactive arthritis" is used.

In 50% of the cases, joints of the upper extremities are also affected, including the small joints, and the arthritis can be accompanied by cases of tendonitis (enthesitis) [217 - 219, 220].

One of the most important differential diagnoses of reactive arthritis is Lyme arthritis (chronic Lyme disease, Lyme disease in the late stage, stage III).

Reactive arthritis can be associated with other disease manifestations; they are presented in Table 28.