A new “inside-out” hypothesis on the pathogenesis of rheumatoid arthritis suggests that joint damage may arise from within adjacent bone marrow, rather than—or in addition to—arising from outside via the synovial membrane, according to Dr. Georg Schett and Dr. Gary S. Firestein and published online in the journal Annals of the Rheumatic Diseases.
The conventional “outside-in” hypothesis holds that the primary pathogenic event in RA is the alteration of a synovial membrane. The altered membrane recruits immune cells, resulting in an onslaught of inflammation, cell accumulation from unbalanced proliferation and cell death, and perhaps a synovial immune response.
Either of two scenarios could lead to alterations in the synovial membrane. In one scenario, there's a confluence of environmental and genetic factors and the breakdown of tolerance. Alternatively, the synovial membrane could be changed by systemic processes.
The inside-out hypothesis holds that lesions within the bone marrow could begin to destroy the inner cortical bone surface, eventually opening pathways to the synovium. Mesenchymal elements could migrate through these cortical pores, stimulating joint inflammation, wrote Dr. Schett, professor of internal medicine, rheumatology, immunology, and oncology at the University of Erlangen-Nuremberg (Germany), and Dr. Firestein, professor of medicine of the University of California, San Diego.
Lesions within the bone marrow have been observed with MRI in the earliest stages of the disease. Microscopically, these lesions are sites where bone marrow fat has been replaced by inflammatory tissue dominated by lymphocytes. Other studies have demonstrated that these lesions are associated with structural damage in joints. “Different forms of arthritis may preferentially use either the outside-in or inside-out mechanism.…Preference for one of these two mechanisms may better explain some of the clinical differences of the various forms of arthritis.” (Arch. Rheum. Dis. 2010 March 18 [doi:10.1136/ard.2009.121657
Disclosures: The investigators stated that they had no conflicts of interest.