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Reiter's syndrome

The development of a spondyloarthropathy phenotype is the result of a complex interaction between environmental triggers acting on a genetically susceptible individual . The striking specificity of these diseases for individuals with B-27 remains the single most striking genetic clue to the etiology and the pathogenesis, however it is also quite clear that there are many other genes involved in determining susceptibility. For example, twin studies have shown that HLA-B 27 positive monozygotic twins have a concordance rate.

With regard to environmental triggers, there is the obvious well known triggering action of bacterial pathogens, particularly JRAM negative organisms. But there are some rather recent variance modeling studies to suggest that the majority of the susceptibility is actually genetic, implying that whatever the environmental triggers are they are probably relatively ubiquitous.

The predominant hypothesis in the last decade or so to explain the role that HLA-B 27 plays in disease pathogenesis argues that it is a result of its peptide binding specificity. So it is hypothesized that B 27 can select and present arthritogenic peptides and these peptides presumably are arthritogenic because they resemble in some way a pathogen derived peptide and thus can stimulate the proliferation of auto-reactive B 27 restricted T cells. This hypothesis has really not been proven, in fact to date there are no arthritogenic peptides that have been identified and studies looking for auto-reactive CD-8 positive B 27 restricted T cells are fairly limited.

Immuno-histochemical analyses of very early sacroiliac lesions in patients with ankylosing spondylitis reveal a preponderance of CD-4 positive T cells. Lots of CD-14 positive or activated macrophages and increased levels.

So I emphasize right now that this is theoretical, although clearly HLA-B 27 miss-folds, the consequences are unknown and their relation to pathogenesis is unknown. But the main point that I want to leave you with is that miss-folding presents an alternative to the arthritogenic peptide hypothesis and may be important in pathogenesis.

Let me first show you some of the examples that are these diseases. These poor boys got a spondyloarthropathy. All of them are 27 boys. All of them got peripheral arthritis in their initial months of disease and some of them for a few years. Then _ affecting the lower limbs. Throughout the course of their disease they present a series of symptoms that define their final diagnosis. Some of those symptoms were involving the axial joints, specifically the sacroiliac joints and the spinal joints. Some of them presented at extraarticular sites, for example the eye. But at the end they were recognized by the clinical features they had at the beginning:

This form of the disease results from the swelling of the synovial sheaths, involvement of the antithesis of the tarsal area and now we have found that there is some swelling that is becoming around the synovial area and we don’t know where it is coming from. This is the posterior view of those feet and those are very characteristic.

Reiter's syndrome is the most well-described disease in children but there are some problems. First is name and diagnosis in accordance to adult concept disease parameters. So maybe this is one of the reasons why this disorders were rarely seen in the past, or diagnosed in the past. The diagnosis of ankylosing spondylitis requires the presence of spinal symptoms, radiographic sacroiliac which occur many years before or after peripheral arthritis. Clinical features at onset, severity of disease and some genetic markers, differentiate juvenile and adult onset forms. So this is also important at onset, especially at onset, clinical symptoms are different. Children with ankylosing spondylitis present with peripheral arthritis. Adults most of the time present with actual involvement. This is also an example. This is a group of patients with ankylosing spondylitis. All of them have got the same disease but they develop actual symptoms at different times. Some of them have got juvenile ankylosing spondylitis, some of them have got adult ankylosing spondylitis. And this is happening in many racial and geographic areas in the world. So the most common form of the onset of this disease, as mentioned before, C syndrome. Actual disease becomes 5-10 years after onset.