The polar manifestations of mycobacterial diseases and of Crohn's disease.

Mycobacterial disease.

Disease caused by mycobacteria (and by some other bacteria) do not have a uniform appearance across a group of patients. Instead, they present a range of possible symptoms, with some symptoms present, and others absent. This range of symptoms is usually broken into two main groups, known as the aggressive and contained forms.

Leprosy, a chronic disease known to be caused by the obligate pathogen, Mycobacterium leprae, is experienced by sufferers in two main forms, the contained tuberculoid form and the aggressive lepromatous form. Tuberculosis, caused by the obligate pathogen, Mycobacterium tuberculosis, is also experienced by sufferers in contained and aggressive forms.

Other mycobacterial diseases display similar "dual presentation" characteristics. These extremes are referred to as the "polar manifestations" of the disease. Individual patients usually do not experience the extremes described above, but exhibit an immune response that is somewhere between the two extremes.

For more information on the dual presentation of mycobacterial diseases, see the page "Immune reactions to mycobacteria".

The proposed polar forms of Crohn's disease

Crohn's disease may also have a dual-presentation. Attention was drawn to the possibility that Crohn's disease may display these polar manifestations by Greenstein et al. in their papers "Molecular evidence for two forms of Crohn disease" and "On the Etiology of Crohn Disease". The two polar forms of the disease described are

• The aggressive "perforating"form. This form of the disease is experienced by people whose immune system is incapable of controlling the Mycobacterium paratuberculosis infection, and the bacterium rages uncontrolled in the body, causing extensive damage. The symptoms of this form are perforation of the intestinal wall, and fistulisation, where abnormal connections grow between the intestines and other internal organs, or between the intestines and the skin. It is not clear if M paratuberculosis is capable of interfering with the immune system in some individuals, leading to the aggressive form of the disease in those individuals.

• The contained "nonperforating" form. In this form of the disease, the sufferers immune system is strong enough to control the Mycobacterium paratuberculosis infection, but creates extensive damage in the process. The method of controlling Mycobacterium paratuberculosis is to seal them inside granulomas, a hard lump formed of T cells. If the body is exposed to continual infection with Mycobacterium paratuberculosis, then more and more granulomas will form, eventually leading to obstruction (blockage) of the intestines, requiring surgical removal of the obstructed section.

In actual CD patients, there is a whole spectrum of presentations, with individual patients displaying symptoms that lie somewhere between the two extremes. The stronger the patients CMI (T cell) reaction, the more likely it is that that individual will develop the contained form of the disease. To see how the CMI reaction might fail, leading to the aggressive disease, see the page "Anergy to Mycobacterium paratuberculosis".

To quote "On the Etiology of Crohn Disease":-

"Only the lack of identifiable acid/alcohol fast bacilli on Ziehl-Neelsen staining on histopathological specimens differentiates Crohn's disease from intestinal tuberculosis. Thus, the thesis that Crohn's disease may be due to mycobacterial infection is appealing. However, failure of well-performed clinical trials with empirical Anti-mycobacterial treatment has led many to conclude that Crohn's disease cannot be ascribed to a mycobacterial infection. Although controversial, there is clinical, epidemiological and molecular evidence indicating that there are two distinct clinical manifestations of Crohn's disease. These Crohn's disease subclassifications have been designated as "perforating" and "nonperforating" forms. Patients with perforating Crohn's disease have abscesses and/or free perforation. Perforating Crohn's disease is the more aggressive form, with a higher reoperation rate. In contrast, nonperforating Crohn's disease has a more indolent clinical course and is associated with obstruction and bleeding. This dual clinical presentation renders Crohn's disease analogous to other mycobacterial diseases such as leprosy, which has two clinical manifestations, the contained tuberculoid and the uncontrolled lepromatous forms. Another mycobacterial infection with a dual presentation in humans is tuberculosis, which has the contained (Ghon focus or pulmonary apical scarring) form rather than the aggressive (miliary) form. We hypothesized that Crohn's disease may indeed be due to a mycobacterial infection, possibly from M. paratuberculosis. We speculate that the inability to document a response to empirical antimycobacterial therapy of Crohn's disease might be ascribable to the failure to separate the Crohn's disease patients into perforating and nonperforating clinical forms before study."

Failure to divide mycobacteriosis into its polar forms.

To date, no research into Crohn's disease, relating to analysis, diagnosis, or treatment, has divided the study population into the polar forms of Crohn's disease. If such forms do exist, then research runs the risk of producing results that incorrect, since the proportion of different forms of the disease in the study population are unknown. Sufferers with different forms of the disease would be grouped together for the purposes of statistical analysis.

Source: http://archive.crohn.ie/polar.htm
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