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Mycoplasma infectious diseases
Mycoplasma lipid-antigens
   
 


Mycoplasmas, the smallest free-living organisms known, are prokaryotes that are bounded only by a plasma membrane. Their lack of a cell wall is associated with cellular pleomorphism and resistance to cell wall-active antimicrobial agents such as penicillins and cephalosporins. The organisms’ small genomes limit biosynthesis and explain the difficulties encountered with in vitro cultivation. Mycoplasmas typically colonize mucosal surfaces of the respiratory and urogenital tracts of many animal species. Sixteen species of mycoplasmas have been recovered from humans. M. pneumoniae causes upper and lower respiratory infections. M. genitalium and Ureaplasma urealyticum are established causes of urethritis and have been implicated in other genital conditions (Haggerty et al., 2008).

Mycoplasmas are well known as the pathogens of mycoplasma pneumonia, and have also come to be recognized as causative bacterias in asthma, rheumatic diseases and neurological disorders (Waites et al., 2004; Atkinson et al., 2009; Gil et al., 2009; Kawahito et al., 2008). Also it is suspected that mycoplasmas are related to atherosclerosis and tumours (including leukaemia) (Alviar et al., 2011; Nussinovitch et al., 2010). The concept of mycoplasma-caused infectious diseases has changed to include not only pneumonia but also other serious illness, now termed mycoplasma-related disorders.

Since drug-resistant mycoplasmas have already appeared, early diagnosis and therapy of infectious diseases caused by mycoplasmas have become more important. However, there are no reliable diagnostic methods for early diagnosis of mycoplasma infections currently in clinical use. A major reason for this lack of a diagnostic method is that antigens used for conventional diagnostic methods are derived from partially purified extracts from mass cultured mycoplasmas or from recombinant proteins.


Mycoplasma pneumoniae is spread through respiratory droplet transmission. Once attached to the mucosa of a host organism, M. pneumoniae extracts nutrients, grows and reproduces by binary fission. Attachment sites include the upper and lower respiratory tract, causing pharyngitis, bronchitis and pneumonia. The infection caused by this bacterium is called atypical pneumonia because of its protracted course and lack of sputum production and wealth of extra-pulmonary symptoms. Chronic mycoplasma infections have been implicated in the pathogenesis of rheumatoid arthritis and other rheumatological diseases.
Mycoplasma atypical pneumonia can be complicated by Stevens-Johnson syndrome, hemolytic anemia, encephalitis or Guillain-Barré syndrome.
Symptoms
The symptoms are generally mild and appear over a period of 1 to 3 weeks. They may become more severe in some people.
Common symptoms include the following:
・Cough, usually dry and not bloody
・Sore throat
・Fever
・Excessive sweating
・Chills
・Headache
・Chest pain
Less common symptoms include:
・Muscle aches and joint stiffness
・Rapid breathing
・Skin lesions or rash
・Ear pain
・Eye pain or soreness
・Neck lump
Diagnosis
Persons with suspected pneumonia should have a complete medical evaluation, including a thorough physical exam and a chest x-ray -- especially because the physical exam may not always be able to tell pneumonia apart from acute bronchitis or other respiratory infections.
Depending on the severity of illness, other tests may be done, including
・Complete blood count (CBC)
・Blood tests for antibodies to mycoplasma
・CT scan of the chest
・Sputum culture to check for mycoplasma bacteria
・A urine test or a throat swab may also be done
Treatment
Antibiotics that work against Mycoplasma include macrolides, quinolones, and tetracyclines.
Control fever with aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or acetaminophen.
Prognosis
Most people recover completely even without antibiotics, although antibiotics may speed recovery. In untreated adults, cough and weakness can persist for up to a month
Possible Complications
Ear infections, Hemolytic anemia, Severe pneumonia, Skin rashes
Prevention
There is no known way to prevent atypical pneumonia. However, avoiding people who have the infection can help reduce your risk.
Infants, and persons in poor health, especially those with weakened immune systems due to HIV, organ transplants, or other conditions should avoid contact with people who have mycoplasma pneumonia.


Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath.
Asthma is caused by environmental and genetic factors. These factors influence how severe asthma is and how well it responds to medication.
Asthma may also be classified as atopic (extrinsic) or non-atopic (intrinsic).
Although asthma is a chronic obstructive condition, it is not considered as a part of chronic obstructive pulmonary disease as this term refers specifically to combinations of disease that are irreversible such as bronchiectasis, chronic bronchitis, and emphysema. Unlike these diseases, the airway obstruction in asthma is usually reversible.
The strongest risk factor for developing asthma is a history of atopic disease. The term "atopy" was coined to describe this triad of atopic eczema, allergic rhinitis and asthma.
Asthma attack
An acute asthma exacerbation is commonly referred to as an asthma attack. The classic symptoms are shortness of breath, wheezing, and chest tightness.
Exacerbation
Some individuals will have stable asthma for weeks or months and then suddenly develop an episode of acute asthma. Different asthmatic individuals react differently to various factors. However, most individuals can develop severe exacerbation of asthma from several triggering agents.
Home factors that can lead to exacerbation include dust, house mites, animal dander (especially cat and dog hair), cockroach allergens and molds at any given home. Perfumes are a common cause of acute attacks in females and children.
Both virus and bacterial infections of the upper respiratory tract infection can worsen asthma.
Respiratory infections such as Mycoplasma pneumniae, Chlamydia pneumoniae and Bordetella pertussis are correlated with asthma exacerbations.
・C.D. Shee, Wheeze and Mycoplasma pneumoniae, J R Soc Med 95 (2002) 132-133.
・A. Simon, O. Schildgen, Antimicrobial therapy in childhood asthma and wheezing, Treat Respir Med 5 (2006) 255-269.
・M. Kraft, Q. Hamid, Mycoplasma in severe asthma, J Allergy Clin Immunol 117 (2006) 1197-1198.
・M. Kraft, G.H. Cassell, J.E. Henson, H. Watson, J. Williamson, B.P. Marmion, C.A. Gaydos, R.J. Martin, Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma, Am J Respir Crit Care Med 158 (1998) 998-1001.
・P.N. Black, Antibiotics for the treatment of asthma, Curr Opin Pharmacol (2007).
・X. Xu, D. Zhang, H. Zhang, P.J. Wolters, N.P. Killeen, B.M. Sullivan, R.M. Locksley, C.A. Lowell, G.H. Caughey, Neutrophil histamine contributes to inflammation in mycoplasma pneumonia, J Exp Med 203 (2006) 2907-2917.
・S.L. Johnston, R.J. Martin, Chlamydophila pneumoniae and Mycoplasma pneumoniae: a role in asthma pathogenesis?, Am J Respir Crit Care Med 172 (2005) 1078-1089.
・F. Meloni, E. Paschetto, P. Mangiarotti, M. Crepaldi, M. Morosini, A. Bulgheroni, A. Fietta, Acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of COPD or asthma: therapeutic considerations, J Chemother 16 (2004) 70-76.
・S. Biscardi, M. Lorrot, E. Marc, F. Moulin, B. Boutonnat-Faucher, C. Heilbronner, J.L. Iniguez, M. Chaussain, E. Nicand, J. Raymond, D. Gendrel, Mycoplasma pneumoniae and asthma in children, Clin Infect Dis 38 (2004) 1341-1346.
・M.M. Montalbano, R.F. Lemanske, Jr., Infections and asthma in children, Curr Opin Pediatr 14 (2002) 334-337.
・E. Micillo, A. Bianco, D. D'Auria, G. Mazzarella, G.F. Abbate, Respiratory infections and asthma, Allergy 55 Suppl 61 (2000) 42-45.
・M. Cazzola, M.G. Matera, F. Blasi, Macrolide and occult infection in asthma, Curr Opin Pulm Med 10 (2004) 7-14.
・M. Kraft, G.H. Cassell, J. Pak, R.J. Martin, Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin, Chest 121 (2002) 1782-1788.
・T. Yano, Y. Ichikawa, S. Komatu, S. Arai, K. Oizumi, Association of Mycoplasma pneumoniae antigen with initial onset of bronchial asthma, Am J Respir Crit Care Med 149 (1994) 1348-1353.
・J.C. Gil, R.L. Cedillo, B.G. Mayagoitia, M.D. Paz, Isolation of Mycoplasma pneumoniae from asthmatic patients, Ann Allergy 70 (1993) 23-25.
・H.I. Cohen, The role of infection in childhood asthma, Pediatr Ann 6 (1977) 771-777.
・E. Huhti, T. Mokka, J. Nikoskelainen, P. Halonen, Association of viral and mycoplasma infections with exacerbations of asthma, Ann Allergy 33 (1974) 145-149.
・S. Berkovich, S.J. Millian, R.D. Snyder, The association of viral and mycoplasma infections with recurrence of wheezing in the asthmatic child, Ann Allergy 28 (1970) 43-49.
・J.C. Gil, R.L. Cedillo, B.G. Mayagoitia, M.D. Paz, Isolation of Mycoplasma pneumoniae from asthmatic patients, Ann Allergy 70 (1993) 23-25. 
・S. Kondo, M. Ito, M. Saito, M. Sugimori, H. Watanabe, Progressive bronchial obstruction during the acute stage of respiratory tract infection in asthmatic children, Chest 106 (1994) 100-104.
・S.L. Johnston, F. Blasi, P.N. Black, R.J. Martin, D.J. Farrell, R.B. Nieman, The effect of telithromycin in acute exacerbations of asthma, N Engl J Med 354 (2006) 1589-1600.
・F. Freymuth, A. Vabret, J. Brouard, F. Toutain, R. Verdon, J. Petitjean, S. Gouarin, J.F. Duhamel, B. Guillois, Detection of viral, Chlamydia pneumoniae and Mycoplasma pneumoniae infections in exacerbations of asthma in children, J Clin Virol 13 (1999) 131-139.
・D. Lieberman, D. Lieberman, S. Printz, M. Ben-Yaakov, Z. Lazarovich, B. Ohana, M.G. Friedman, B. Dvoskin, M. Leinonen, I. Boldur, Atypical pathogen infection in adults with acute exacerbation of bronchial asthma, Am J Respir Crit Care Med 167 (2003) 406-410.
・Y.T. Chang, Y.H. Yang, B.L. Chiang, The significance of a rapid cold hemagglutination test for detecting mycoplasma infections in children with asthma exacerbation, J Microbiol Immunol Infect 39 (2006) 28-32.
・F. Freymuth, A. Vabret, J. Brouard, F. Toutain, R. Verdon, J. Petitjean, S. Gouarin, J.F. Duhamel, B. Guillois, Detection of viral, Chlamydia pneumoniae and Mycoplasma pneumoniae infections in exacerbations of asthma in children, J Clin Virol 13 (1999) 131-139.


Arthritis
Reactive arthritis is classified as an autoimmune condition that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can trigger the disease. Usually, by the time the patient presents with symptoms, oftentimes the "trigger" infection has been cured or is in remission in chronic cases, thus making determination of the initial cause difficult.
The arthritis often is coupled with other characteristic symptoms; this is called Reiter's Syndrome or Reiter's arthritis. The manifestations of Reiter's Syndrome include the following triad of symptoms: an inflammatory arthritis of large joints, inflammation of the eyes in the form of conjunctivitis or uveitis, and urethritis in men or cervicitis in women.
Reactive arthritis is an RF-seronegative, HLA-B27-linked arthritis often precipitated by genitourinary or gastrointestinal infections.
Repeated attacks over many years are common, and patients sometimes end up with chronic and disabling arthritis, heart disease, amyloid deposits, ankylosing spondylitis, immunoglobulin A nephropathy, cardiac conduction abnormalities, or aortitis with aortic regurgitation. However, most people with reactive arthritis can expect to live normal life spans and maintain a near-normal lifestyle with modest adaptations to protect the involved organs.
Eye involvement occurs in about 50% of men with urogenital Reiter's Syndrome and about 75% of men with enteric reactive arthritis. Conjunctivitis and uveitis can include redness of the eyes, eye pain and irritation, or blurred vision. Eye involvement typically occurs early in the course of reactive arthritis, and symptoms may come and go.
In the oral cavity, the patients may suffer from recurrent aphthous stomatitis, geographic tongue and migratory stomatitis in higher prevalence than the general population.
In addition, some individuals with reactive arthritis develop mouth ulcers that come and go. In some cases, these ulcers are painless and go unnoticed. Some patients suffer serious gastrointestinal problems similar to those of the Crohn's disease.
Mycoplasma pneumoniae is a human pathogen that is known to cause respiratory infections, and some patients with serologically verified M. pneumoniae infections developed arthritis.
In humans, Mycoplasma fermentans has been isolated from the joints of rheumatoid arthritis (RA) patients and other seronegative patients with inflammatory arthritides and a cellular infiltrate.
Mycoplasma fermentans had previously been isolated from patients with inflammatory cellular infiltrates, such as rheumatoid arthritis, therefore, t is possible that these organisms may contribute to chronic inflammation within the joints.
Presence of Mycoplasma fermentans in the bloodstream of Mexican patients with rheumatoid arthritis and IgM and IgG antibodies against whole microorganism
・S. Johnson, D. Pitcher, Distribution of ecto 5'-nucleotidase on Mycoplasma species associated with arthritis, FEMS Microbiol Lett 192 (2000) 59-65.
・J. Haier, M. Nasralla, A.R. Franco, G.L. Nicolson, Detection of mycoplasmal infections in blood of patients with rheumatoid arthritis, Rheumatology (Oxford) 38 (1999) 504-509.
・C. Schlesinger, S. Veeraraghavan, M.N. Koss, Constructive (obliterative) bronchiolitis, Curr Opin Pulm Med 4 (1998) 288-293.
・H. Brunner, Models of mycoplasma respiratory and genital tract infections, Wien Klin Wochenschr 109 (1997) 569-573.
・K. Oen, M. Fast, B. Postl, Epidemiology of juvenile rheumatoid arthritis in Manitoba, Canada, 1975-92: cycles in incidence, J Rheumatol 22 (1995) 745-750.
・Y. Misaki, W.J. Van Venrooij, G.J. Pruijn, Prevalence and characteristics of anti-56K/annexin XI autoantibodies in systemic autoimmune diseases, J Rheumatol 22 (1995) 97-102.
・L.G. Gorina, S.A. Goncharova, A.V. Igumnov, [Laboratory diagnosis of human Mycoplasma infection], Vestn Akad Med Nauk SSSR (1991) 44-47.
・O. Faye-Petersen, S.R. Frankel, P.E. Schulman, H. Raucher, H. Spiera, M.R. Dische, Giant cell vasculitis with extravascular granulomas in an adolescent, Pediatr Pathol 11 (1991) 281-295.
・M.F. Barile, H. Yoshida, H. Roth, Rheumatoid arthritis: new findings on the failure to isolate or detect mycoplasmas by multiple cultivation or serologic procedures and a review of the literature, Rev Infect Dis 13 (1991) 571-582.
・N. Cimolai, P. Malleson, E. Thomas, P.J. Middleton, Mycoplasma pneumoniae associated arthropathy: confirmation of the association by determination of the antipolypeptide IgM response, J Rheumatol 16 (1989) 1150-1152.
・H. Tuokko, The detection of measles specific immunoglobulin M antibodies using biotinylated antigens, Apmis 96 (1988) 491-496.
・K. Lind, M. Hoier-Madsen, A. Wiik, Autoantibodies to the mitotic spindle apparatus in Mycoplasma pneumoniae disease, Infect Immun 56 (1988) 714-715.
・H.W. Clark, M.R. Coker-Vann, J.S. Bailey, T.M. Brown, Detection of mycoplasmal antigens in immune complexes from rheumatoid arthritis synovial fluids, Ann Allergy 60 (1988) 394-398.
・M.L. Christensen, L.M. Pachman, R. Schneiderman, D.C. Patel, J.M. Friedman, Prevalence of Coxsackie B virus antibodies in patients with juvenile dermatomyositis, Arthritis Rheum 29 (1986) 1365-1370.
・M. Schlesier, C. Ramb-Lindhauer, M. Gartner, H.H. Peter, Analysis of T-cell cultures and clones from a patient with classic rheumatoid arthritis--evidence for the existence of autoreactive T-cell clones in blood and synovial fluid, Rheumatol Int 4 Suppl (1984) 1-9.
・E. Jansson, A. Backman, K. Hakkarainen, A. Miettinen, B. Seniusova, Mycoplasmas and arthritis, Z Rheumatol 42 (1983) 315-319.
・A.J. van Griethuysen, C.L. van der Zee, F. Hoevenaars, [Acute polyarthritis in Mycoplasma pneumoniae infection], Ned Tijdschr Geneeskd 126 (1982) 61-63.
・D. Taylor-Robinson, Mycoplasmal arthritis in man, Isr J Med Sci 17 (1981) 616-621.
・P.C. Roberts, S.J. Hobbs, Evaluation of a new test system for rubella haemagglutination inhibiting antibodies, J Clin Pathol 30 (1977) 1011-1014. 
・L.A. Hernandez, G.E. Urquhart, W.C. Dick, Mycoplasma pneumoniae infection and arthritis in man, Br Med J 2 (1977) 14-16.
・G. Taylor, D. Taylor-Robinson, The part played by cell-mediated immunity in mycoplasma respiratory infections, Dev Biol Stand 28 (1975) 195-210.
・B.C. Cole, M.B. Taylor, J.R. Ward, Studies on the infectious etiology of human rheumatoid arthritis. II. Search for humoral and cell-bound antibodies against mycoplasmal antigens, Arthritis Rheum 18 (1975) 435-441.
・M.P. Weinstein, C.B. Hall, Mycoplasma pneumoniae infection associated with migratory polyarthritis, Am J Dis Child 127 (1974) 125-126.
・M.C. Jones, Aethritis and arthralgia in infection with Mycoplasma pneumoniae, Thorax 25 (1970) 748-750.
・H.P. Lambert, Syndrome with joint manifestations in association with Mycoplasma pneumoniae infection, Br Med J 3 (1968) 156-157.
・A.J. Silman, J.E. Pearson, Epidemiology and genetics of rheumatoid arthritis, Arthritis Res 4 Suppl 3 (2002) S265-272.


Anemia (autoimmune hemolytic anemia)
Anemia is a decrease in number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood.
Most commonly, people with anemia report nonspecific symptoms of a feeling of weakness, or fatigue, general malaise and sometimes poor concentration. They may also report dyspnea (shortness of breath) on exertion.
In very severe anemia, the patient may have symptoms related to this, such as palpitations, angina (if pre-existing heart disease is present), intermittent claudication of the legs, and symptoms of heart failure.
Causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemias), blood loss and fluid overload (hypervolemia).
Hemolytic anemia, which also usually occurs in association with  pneumonia, is a rare but severe manifestation of M. pneumoniae infection.
・Schulman P, Piemonte TC, Singh B. (1980) Acute renal failure, hemolytic anemia, and Mycoplasma pneumoniae. JAMA. 244:1823-1824.
・Wilson ML, Menjivar E, Kalapatapu V, Hand AP, Garber J, Ruiz MA. (2007) Mycoplasma pneumoniae associated with hemolytic anemia, cold agglutinins, and recurrent arterial thrombosis. South Med J. 100:215-217.
・Stéphan JL, Galambrun C, Pozzetto B, Grattard F, Bordigoni P. (1999) Aplastic anemia after Mycoplasma pneumoniae infection: a report of two cases. J Pediatr Hematol Oncol. 21:299-302.
・F. Daxbock, K. Zedtwitz-Liebenstein, H. Burgmann, W. Graninger, Severe hemolytic anemia and excessive leukocytosis masking mycoplasma pneumonia, Ann Hematol 80 (2001) 180-182.
Cold agglutinin disease
Cold agglutinin disease is an autoimmune disease characterized by the presence of high concentrations of circulating antibodies, usually IgM, directed against red blood cells.
It is a form of autoimmune hemolytic anemia, specifically one in which antibodies only bind red blood cells at low body temperatures, typically 28-31°C.
In adults, this is typically due to a lymphoproliferative disease such as lymphoma and chronic lymphoid leukemia, or infection.
In children, cold agglutinin disease is often secondary to an infection, such as Mycoplasma pneumonia, mononucleosis, and HIV.
・S. Ciaffoni, R. Luzzati, C. Roata, A. Turrini, O. Antonello, G. Aprili, Presence and significance of cold agglutinins in patients with HIV infection, Haematologica 77 (1992) 233-236.
thrombocytopenia
Thrombotic thrombocytopenic purpura (TTP) is a fatal disease characterized by widespread platelet aggregation, hemolytic anemia and fever with renal and neurological involvement.
Different factors have been associated with the development of TTP, e.g. infections, pregnancy, chemotherapy, drug therapy and bone marrow transplantation.
・Cherry JD. (1993) Anemia and mucocutaneous lesions due to Mycoplasma pneumoniae infections. Clin Infect Dis. Suppl 1:S47-51.
・Bar Meir E, Amital H, Levy Y, Kneller A, Bar-Dayan Y, Shoenfeld Y. (2000) Mycoplasma-pneumoniae-induced thrombotic thrombocytopenic purpura. Acta Haematol. 103:112-115.
・C.J. Chen, C.J. Juan, M.L. Hsu, Y.S. Lai, S.P. Lin, S.N. Cheng, Mycoplasma pneumoniae infection presenting as neutropenia, thrombocytopenia, and acute hepatitis in a child, J Microbiol Immunol Infect 37 (2004) 128-130.
・E.M. Shankar, N. Kumarasamy, P. Balakrishnan, S. Saravanan, S. Solomon, A. Vengatesan, K.G. Murugavel, U.A. Rao, Detection of pulmonary Mycoplasma pneumoniae infections in HIV-infected subjects using culture and serology, Int J Infect Dis 11 (2007) 232-238.
・E.M. Shankar, N. Kumarasamy, P. Balakrishnan, A. Vengatesan, H. Kownhar, S. Solomon, U.A. Rao, Seroprevalence of Mycoplasma pneumoniae in HIV-infected patients using a microparticle agglutination test, J Med Microbiol 55 (2006) 759-763.


acute encephalitis
M. pneumoniae was strongly implicated as the probable etiologic agent in 1-10% children with acute encephalitis.
M. pneumoniae has been implicated as a cause of immunemediated neurologic syndromes, including ADEM, transversemyelitis, and Guillain-Barre´ syndrome
Acute disseminated encephalomyelitis (ADEM)
Acute disseminated encephalomyelitis (ADEM) due to Mycoplasma pneumoniae infection in an adolescent.
Acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis developed after Mycoplasma pneumoniae infection complicating subclinical measles infection.
Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid.
・M. Koskiniemi, CNS manifestations associated with Mycoplasma pneumoniae infections: summary of cases at the University of Helsinki and review, Clin Infect Dis 17 Suppl 1 (1993) S52-57.
・S. Kusunoki, A. Chiba, S. Hitoshi, H. Takizawa, I. Kanazawa, Anti-Gal-C antibody in autoimmune neuropathies subsequent to mycoplasma infection, Muscle Nerve 18 (1995) 409-413.
・A. Bitnun, E.L. Ford-Jones, M. Petric, D. MacGregor, H. Heurter, S. Nelson, G. Johnson, S. Richardson, Acute childhood encephalitis and Mycoplasma pneumoniae, Clin Infect Dis 32 (2001) 1674-1684.
・M. Narita, H. Tanaka, T. Togashi, S. Abe, Cytokines involved in CNS manifestations caused by Mycoplasma pneumoniae, Pediatr Neurol 33 (2005) 105-109.
・S. Tsiodras, I. Kelesidis, T. Kelesidis, E. Stamboulis, H. Giamarellou, Central nervous system manifestations of Mycoplasma pneumoniae infections, J Infect 51 (2005) 343-354.
・F. Daxboeck, Mycoplasma pneumoniae central nervous system infections, Curr Opin Neurol 19 (2006) 374-378.
・S. Tsiodras, T. Kelesidis, I. Kelesidis, K. Voumbourakis, H. Giamarellou, Mycoplasma pneumoniae-associated myelitis: a comprehensive review, Eur J Neurol 13 (2006) 112-124.
・A. Harloff, S. Voigt, A. Hetzel, F.X. Glocker, T. Els, Severe axonal polyradiculoneuritis and brainstem encephalitis due to Mycoplasma pneumoniae infection, Eur J Neurol 9 (2002) 542-543.
・F. Daxboeck, A. Blacky, R. Seidl, R. Krause, O. Assadian, Diagnosis, treatment, and prognosis of Mycoplasma pneumoniae childhood encephalitis: systematic review of 58 cases, J Child Neurol 19 (2004) 865-871.
・K. Susuki, M. Odaka, M. Mori, K. Hirata, N. Yuki, Acute motor axonal neuropathy after Mycoplasma infection: Evidence of molecular mimicry, Neurology 62 (2004) 949-956.
・R. Guleria, N. Nisar, T.C. Chawla, N.R. Biswas, Mycoplasma pneumoniae and central nervous system complications: a review, J Lab Clin Med 146 (2005) 55-63.
・P.A. Mardh, B. Ursing, K. Lind, Persistent cerebellar symptoms after infection with Mycoplasma pneumoniae, Scand J Infect Dis 7 (1975) 157-160.
・M.A. Hely, P.M. Williamson, T.R. Terenty, Neurological complications of Mycoplasma pneumoniae infection, Clin Exp Neurol 20 (1984) 153-160.
・B. Goldschmidt, J. Menonna, J. Fortunato, P. Dowling, S. Cook, Mycoplasma antibody in Guillain-Barre syndrome and other neurological disorders, Ann Neurol 7 (1980) 108-112.
・W.J. Shian, C.S. Chi, Acute transverse myelitis in children: clinical analysis of seven cases, Zhonghua Yi Xue Za Zhi (Taipei) 54 (1994) 57-61.
・J.F. Albucher, D. Lauque, I. Geyer, J.D. Turc, F. Chollet, P. Carles, B. Guiraud-Chaumeil, [Transverse myelitis caused by Mycoplasma pneumoniae infection], Rev Neurol (Paris) 151 (1995) 350-353.
・M. Abele-Horn, W. Franck, U. Busch, H. Nitschko, R. Roos, J. Heesemann, Transverse myelitis associated with Mycoplasma pneumoniae infection, Clin Infect Dis 26 (1998) 909-912.
・Q. Hao, T. Saida, S. Kuroki, M. Nishimura, M. Nukina, H. Obayashi, K. Saida, Antibodies to gangliosides and galactocerebroside in patients with Guillain-Barre syndrome with preceding Campylobacter jejuni and other identified infections, J Neuroimmunol 81 (1998) 116-126.
・B.C. Jacobs, P.H. Rothbarth, F.G. van der Meche, P. Herbrink, P.I. Schmitz, M.A. de Klerk, P.A. van Doorn, The spectrum of antecedent infections in Guillain-Barre syndrome: a case-control study, Neurology 51 (1998) 1110-1115.
・R.A. Hughes, R.D. Hadden, N.A. Gregson, K.J. Smith, Pathogenesis of Guillain-Barre syndrome, J Neuroimmunol 100 (1999) 74-97.
・S. Sotgiu, M. Pugliatti, G. Rosati, G.A. Deiana, G.P. Sechi, Neurological disorders associated with Mycoplasma pneumoniae infection, Eur J Neurol 10 (2003) 165-168.
・C.W. Ang, A.P. Tio-Gillen, J. Groen, P. Herbrink, B.C. Jacobs, R. Van Koningsveld, A.D. Osterhaus, F.G. Van der Meche, P.A. van Doorn, Cross-reactive anti-galactocerebroside antibodies and Mycoplasma pneumoniae infections in Guillain-Barre syndrome, J Neuroimmunol 130 (2002) 179-183.
・S. Kuwabara, Guillain-Barre syndrome: epidemiology, pathophysiology and management, Drugs 64 (2004) 597-610.
・G.L. Nicolson, M.Y. Nasralla, J. Haier, J. Pomfret, High frequency of systemic mycoplasmal infections in Gulf War veterans and civilians with Amyotrophic Lateral Sclerosis (ALS), J Clin Neurosci 9 (2002) 525-529.
・S. Sotgiu, M. Pugliatti, G. Rosati, G.A. Deiana, G.P. Sechi, Neurological disorders associated with Mycoplasma pneumoniae infection, Eur J Neurol 10 (2003) 165-168. 
central and peripheral demyelination
M.J. Tan, A.K. Chattophadyay, P.D. Griffiths, P.S. Baxter, Acute central and peripheral demyelination associated with Mycoplasma pneumoniae, Pediatr Neurol 29 (2003) 239-241.
Miller Fisher syndrome
M. Bernal Sanchez-Arjona, E. Franco Macias, F. Villalobos-Chaves, [Miller Fisher syndrome in the course of an acute pneumonia by Mycoplasma pneumoniae], Rev Neurol 36 (2003) 235-237
Bell's palsy
C. Volter, J. Helms, B. Weissbrich, P. Rieckmann, M. Abele-Horn, Frequent detection of Mycoplasma pneumoniae in Bell's palsy, Eur Arch Otorhinolaryngol 261 (2004) 400-404
Acute sensorineural hearing loss
T. Okada, I. Kato, I. Miho, S. Minami, H. Kinoshita, I. Akao, M. Kenmochi, S. Miyabe, I. Takeyama, Acute sensorineural hearing loss caused by Mycoplasma pneumoniae, Acta Otolaryngol Suppl 522 (1996) 22-25.


Myalgic Encephalomyelitis, which includes CFS, is classified as a neurological disease in the World Health Organization’s International Classification of Diseases (ICD).
Symptoms of CFS include post-exertional malaise; unrefreshing sleep; widespread muscle and joint pain; sore throat; headaches of a type not previously experienced; cognitive difficulties; chronic, often severe, mental and physical exhaustion; and other characteristic symptoms in a previously healthy and active person. Persons with CFS may report additional symptoms including muscle weakness, increased sensitivity to light, sounds and smells, orthostatic intolerance, digestive disturbances, depression, and cardiac and respiratory problems.
Fatigue is a common symptom in many illnesses, but CFS is comparatively rare. Estimates of CFS prevalence vary widely, from 7 to 3,000 cases of CFS for every 100,000 adults, but national health organizations have estimated more than 1 million Americans and approximately a quarter of a million people in the UK have CFS. CFS occurs more often in women than men, and is less prevalent among children and adolescents. The quality of life is "particularly and uniquely disrupted" in CFS.
The Canadian Consensus Document on ME/CFS
Myalgic Encephalomyelitis” and “Chronic Fatigue Syndrome” are used interchangeably and this illness is referred to as “ME/CFS”. The Expert Consensus Panel, selected by Health Canada, established clinical criteria, and developed an integrative diagnostic and treatment approach to ME/CFS.
Many infectious agents may trigger ME/CFS.
Antibiotic treatment for mycoplasma and chlamydia: Suggested antibiotic treatments for confirmed mycoplasma or chlamydia infections
Signs and symptoms
The majority of CFS cases start suddenly, usually accompanied by a "flu-like illness"  while a significant proportion of cases begin within several months of severe adverse stress.
Most patients enjoyed a healthy, active lifestyle prior to the onset of ME/CFS.
In a review study of prognosisof studies indicated that 0% to 12% of adults return to their pre-illness level of functioning. Relapses can occur several years after remission. The prognosis for children and youth is much better.


Amyotrophic lateral sclerosis (ALS) – also referred to as motor neurone disease in some British Commonwealth countries and as Lou Gehrig's disease in North America – is a debilitating disease with varied etiology characterized by rapidly progressive weakness, muscle atrophy and fasciculations, muscle spasticity, difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and decline in breathing ability. ALS is the most common of the five motor neuron diseases.
Signs and symptoms
The disorder causes muscle weakness and atrophy throughout the body caused by degeneration of the upper and lower motor neurons. Unable to function, the muscles weaken and atrophy. Affected individuals may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel sphincters and the muscles responsible for eye movement are usually, but not always, spared.
Cognitive function is generally spared for most patients, although some (about 5%) also have frontotemporal dementia. A higher proportion of patients (30-50%) also have more subtle cognitive changes which may go unnoticed, but are revealed by detailed neuropsychological testing. Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS will maintain sight, hearing, touch, smell, and taste
Initial symptoms
The earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. About 25% of cases are "bulbar onset" ALS. These patients first notice difficulty speaking clearly or swallowing. Over time, patients experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria).
High prevalence of Mycoplasma infections among chronic fatigue syndrome patients. Examination of four Mycoplasma species in blood of chronic fatigue syndrome patients.
Nicolson GL, Nasralla MY, Haier J, Pomfret J. High frequency of systemic mycoplasmal infections in Gulf War veterans and civilians with Amyotrophic Lateral Sclerosis (ALS). J Clin Neurosci. 9:525-529. (2002)


Stevens-Johnson syndrome
Exanthem is common in Mycoplasma pneumoniae infections. Occasionally this exanthem is severe (Stevens-Johnson syndrome), and usually it occurs in association with pneumonia.
・B. Catteau, E. Delaporte, E. Hachulla, F. Piette, H. Bergoend, [Mycoplasma infection with Stevens-Johnson syndrome and antiphospholipid antibodies: apropos of 2 cases], Rev Med Interne 16 (1995) 10-14.
・L. Wang, K.C. Hong, F.C. Lin, K.D. Yang, Mycoplasma pneumoniae-associated Stevens-Johnson syndrome exhibits lymphopenia and redistribution of CD4+ T cells, J Formos Med Assoc 102 (2003) 55-58.
・N.S. Lam, Y.H. Yang, L.C. Wang, Y.T. Lin, B.L. Chiang, Clinical characteristics of childhood erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in Taiwanese children, J Microbiol Immunol Infect 37 (2004) 366-370.
・・Schalock PC, Dinulos JG. (2005) Mycoplasma pneumoniae-induced Stevens-Johnson syndrome without skin lesions: fact or fiction? J Am Acad Dermatol. 52:312-315.
Allergy
J.S. Seggev, G.V. Sedmak, V.P. Kurup, Isotype-specific antibody responses to acute Mycoplasma pneumoniae infection, Ann Allergy Asthma Immunol 77 (1996) 67-73.
H.S. Nelson, Allergen and irritant control: importance and implementation, Clin Cornerstone 1 (1998) 57-68.
H.W. Chu, J.M. Honour, C.A. Rawlinson, R.J. Harbeck, R.J. Martin, Effects of respiratory Mycoplasma pneumoniae infection on allergen-induced bronchial hyperresponsiveness and lung inflammation in mice, Infect Immun 71 (2003) 1520-1526.
bullous erythema multiforme
P.C. Schalock, J.B. Brennick, J.G. Dinulos, Mycoplasma pneumoniae infection associated with bullous erythema multiforme, J Am Acad Dermatol 52 (2005) 705-706.
Gianotti-Crosti syndrome
S. Manoharan, J. Muir, R. Williamson, Gianotti-Crosti syndrome in an adult following recent Mycoplasma pneumoniae infection, Australas J Dermatol 46 (2005) 106-109.
Adamantiades-Behcet's disease
Zouboulis CC, May T, Pathogenesis of Adamantiades-Behcet's disease, Med Microbiol Immunol (Berl) 192 (2003) 149-155.
Zouboulis CC, Turnbull JR, Mühlradt PF. (2003) Association of Mycoplasma fermentans with Adamantiades-Behçet's disease. Adv Exp Med Biol. 528:191-194.
Zouboulis CC, Turnbull JR, Mühlradt PF. (2003) High seroprevalence of anti-Mycoplasma fermentans antibodies in patients with malignant aphthosis. J Invest Dermatol. 121:211-212.


Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis. Vasculitis is primarily due to leukocyte migration and resultant damage.
According to the size of the vessel affected, vasculitis can be classified into:
Large vessel: Behçet's syndrome, Polymyalgia rheumatica, Takayasu's arteritis, Temporal arteritis
Medium vessel: Buerger's disease, Cutaneous vasculitis, Kawasaki disease, Polyarteritis nodosa
Small vessel: Churg–Strauss syndrome, Cutaneous vasculitis, Henoch–Schönlein purpura, Microscopic polyangiitis, Wegener's granulomatosis
Symptoms
Petechia and purpura on the low limb due to medication induced vasculitis.
General symptoms: Fever, weight loss
Skin: Palpable purpura, livedo reticularis
Muscles and joints: Myalgia or myositis, arthralgia or arthritis
Nervous system: Mononeuritis multiplex, headache, stroke, tinnitus, reduced visual acuity, acute visual loss
Heart and arteries: Myocardial infarction, hypertension, gangrene
Respiratory tract: Nose bleeds, bloody cough, lung infiltrates
GI tract: Abdominal pain, bloody stool, perforations
Kidneys: Glomerulonephritis


P. Elling, A.T. Olsson, H. Elling, Synchronous variations of the incidence of temporal arteritis and polymyalgia rheumatica in different regions of Denmark; association with epidemics of Mycoplasma pneumoniae infection, J Rheumatol 23 (1996) 112-119.


HSP is a systemic vasculitis (inflammation of blood vessels) and is characterized by deposition of immune complexes containing the antibody IgA.
Signs and symptoms
Purpura, arthritis and abdominal pain are known as the "classic triad" of Henoch–Schönlein purpura.
Forty percent have evidence of kidney involvement, mainly in the form of hematuria (blood in the urine), but only a quarter will have this in sufficient quantities to be noticeable without laboratory tests. More than half also have proteinuria (protein in the urine), which in one eighth is severe enough to cause nephrotic syndrome.
Problems in other organs, such as the central nervous system (brain and spinal cord) and lungs may occur, but is much less common than in the skin, bowel and kidneys.
Henoch-Schönlein purpura is a small-vessel vasculitis in which complexes of immunoglobulin A (IgA) and complement component 3 (C3) are deposited on arterioles, capillaries, and venules. As with IgA nephropathy, serum levels of IgA are high in HSP
HSP occurs more often in children than in adults, and usually follows an upper respiratory tract infection.
HSP can develop after infections with streptococci (β-haemolytic, Lancefield group A), hepatitis B, herpes simplex virus, parvovirus B19, Coxsackievirus, adenovirus, Helicobacter pylori, measles, mumps, rubella, Mycoplasma and numerous others.


Kawasaki disease (KD), also known as Kawasaki syndrome, lymph node syndrome and mucocutaneous lymph node syndrome, is an autoimmune disease in which the medium-sized blood vessels throughout the body become inflamed.
It is largely seen in children under five years of age.
The conjunctivae and oral mucosa, along with the skin, become erythematous. Edema is often seen in the hands and feet and one or both of the cervical lymph nodes are often enlarged. Also, a remittent fever is characteristic of the acute phase of the disease.
It affects many organ systems, mainly those including the blood vessels, skin, mucous membranes, and lymph nodes; however its rare but most serious effect is on the heart where it can cause fatal coronary artery aneurysms in untreated children.
Of the patients with untreated Kawasaki disease, 10-15% develope coronary artery lesions and a greater proportion develop coronary arterial dilation. Kawasaki disease is a major cause of acquired heart disease in children.
Systemic vasculitis is an inflammatory condition affecting both veins and arteries throughout the body, and is usually caused by a proliferation of cells associated with an immune response to a pathogen, or autoimmunity.
Other diseases featuring vasculitis include Polyarteritis nodosa, Wegener's granulomatosis, Henoch-Schönlein purpura, and Churg-Strauss syndrome.
Like other autoimmune diseases, the cause of Kawasaki disease is presumably the interaction of genetic and environmental factors, possibly including an infection.
Many studies support the existence of an infectious trigger for Kawasaki disease including the epidemiology of the disease by seasonal fluctuations and the reported temporal relationship to various infectious agents.
Mycoplasma infection and Kawasaki disease.
C. Leen, S. Ling, Mycoplasma infection and Kawasaki disease, Arch Dis Child 75 (1996) 266-267.
J.N. Wang, S.M. Wang, C.C. Liu, J.M. Wu, Mycoplasma pneumoniae infection associated with Kawasaki disease, Acta Paediatr 90 (2001) 594-595.
E. Merlin, H. Al Fatuhi, P. Crost, [Kawasaki syndrome and Mycoplasma pneumoniae infection], Arch Pediatr 11 (2004) 972-973.


Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks flexible (synovial) joints.
Rheumatoid arthritis can also produce diffuse inflammation in the lungs, membrane around the heart (pericardium), the membranes of the lung (pleura), and white of the eye (sclera), and also nodular lesions, most common in subcutaneous tissue.
Although the cause of rheumatoid arthritis is unknown, autoimmunity plays a pivotal role in both its chronicity and progression, and RA is considered a systemic autoimmune diseas
About 1% of the world's population is afflicted by rheumatoid arthritis, women three times more often than men. Onset is most frequent between the ages of 40 and 50, but people of any age can be affected.
In addition, individuals with the HLA-DR1 or HLA-DR4 serotypes have an increased risk for developing the disorder.
It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility if not adequately treated.
Signs and symptoms
While rheumatoid arthritis primarily affects joints, problems involving other organs of the body are known to occur. Extra-articular ("outside the joints") manifestations other than anemia (which is very common) are clinically evident in about 15–25% of individuals with rheumatoid arthritis.
Joints
The arthritis of joints known as synovitis is inflammation of the synovial membrane that lines joints and tendon sheaths. Joints become swollen, tender and warm, and stiffness limits their movement. With time RA nearly always affects multiple joints (it is a polyarthritis), most commonly small joints of the hands, feet and cervical spine, but larger joints like the shoulder and knee can also be involved.
Lungs
Fibrosis of the lungs is a recognized response to rheumatoid disease. Pleural effusions are also associated with rheumatoid arthritis. It is estimated that about one quarter of Americans with RA develop Rheumatoid Lung Disease
Heart and blood vessels
People with rheumatoid arthritis are more prone to atherosclerosis, and risk of myocardial infarction (heart attack) and stroke is markedly increased. Other possible complications that may arise include: pericarditis, endocarditis, left ventricular failure, valvulitis and fibrosis.
Eye
The eye is directly affected in the form of episcleritis which when severe can very rarely progress to perforating scleromalacia. Rather more common is the indirect effect of keratoconjunctivitis sicca, which is a dryness of eyes and mouth caused by lymphocyte infiltration of lacrimal and salivary glands. When severe, dryness of the cornea can lead to keratitis and loss of vision. Preventive treatment of severe dryness with measures such as nasolacrimal duct occlusion is important.
Hematological
Anemia is by far the most common abnormality of the blood cells. Rheumatoid arthritis may cause a warm autoimmune hemolytic anemia. The red cells are of normal size and colour (normocytic and normochromic). A low white blood cell count (neutropenia) usually only occurs in patients with Felty's syndrome with an enlarged liver and spleen. The mechanism of neutropenia is complex. An increased platelet count (thrombocytosis) occurs when inflammation is uncontrolled, as does the anemia.
Constitutional symptoms
Constitutional symptoms including fatigue, low grade fever, malaise, morning stiffness, loss of appetite and loss of weight are common systemic manifestations seen in patients with active rheumatoid arthritis.
Differential diagnoses
Osteoarthritis, Systemic lupus erythematosus (SLE), psoriatic arthritis resembles, Lyme disease, Reactive arthritis (previously Reiter's disease, usually associated with urethritis, conjunctivitis, iritis, painless buccal ulcers), Ankylosing spondylitis (RA-like symmetrical small-joint polyarthritis), Hepatitis C (RA-like symmetrical small-joint polyarthritis), etc.
Possible infectious triggers
It has long been suspected that certain infections could be triggers for this disease. The "mistaken identity" theory suggests that an infection triggers an immune response, leaving behind antibodies that should be specific to that organism. The antibodies are not sufficiently specific, though, and set off an immune attack against part of the host. Because the normal host molecule "looks like" a molecule on the offending organism that triggered the initial immune reaction—this phenomenon is called molecular mimicry. Some infectious organisms suspected of triggering rheumatoid arthritis include Mycoplasma, parvovirus B19 and rubella, etc.
Epidemiological studies have confirmed a potential association between RA and two herpesvirus infections: Epstein-Barr virus (EBV) and Human Herpes Virus 6 (HHV-6).


A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs.
Many connective tissue diseases feature abnormal immune system activity with inflammation in tissues as a result of an immune system that is directed against one's own body tissues (autoimmunity).
Autoimmune connective tissue disorders
Systemic lupus erythematosus (SLE), Rheumatoid arthritis, Scleroderma, Sjögren's syndrome, Mixed connective tissue disease


An allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. A substance that causes a reaction is called an allergen.
Cause
Risk factors for allergy can be placed in two general categories, namely host and environmental factors. Host factors include heredity, gender, race, and age, with heredity being by far the most significant. However, there have been recent increases in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes.
Hypersensitivity
Hypersensitivity (also called hypersensitivity reaction) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity.
The four-group classification was expounded by P. H. G. Gell and Robin Coombs in 1963.
Type I Allergy (immediate)
Atopy, Anaphylaxis, Asthma
IgE and IgG4
Type II Cytotoxic, antibody-dependent
Autoimmune hemolytic anemia, Thrombocytopenia, Erythroblastosis fetalis, Goodpasture's syndrome, Graves' disease, Myasthenia Gravis
IgM or IgG (Complement)
Type III Immune complex disease
Serum sickness, Arthus reaction, Rheumatoid arthritis, Systemic lupus erythematosus (SLE),Extrinsic allergic alveolitis (Hypersensitivity pneumonitis)
IgG (Complement)
Type IV Delayed-type hypersensitivity (DTH), cell-mediated immune memory response, antibody-independent
Contact dermatitis, Mantoux test, Chronic transplant rejection, Multiple sclerosis
T-cells
Type V Autoimmune disease, receptor mediated
Graves' disease, Myasthenia Gravis
IgM or IgG (Complement)