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Process of cartilage destruction by the pannus in rheumatoid arthritis.

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The results demonstrated by Shiozawa and colleagues correspond to the phase of transition from granulation tissue to an early pannus. This is proven by the mixed
cell picture, the loose layering of the cell elements, the
significant new formation of fibers, and the proportion of
newly formed blood vessels.
Our observations indicate that the destruction of
cartilage and bone in rheumatoid arthritis does not have an
inflammatory character, but rather is the work of repeated
assaults by invasive, compact, homogenous, immature synovial cell clusters which destroy the joint structures.
Antiphlogistic therapy may in fact influence the
inflammatory synovitic process, but not the tumor-like cell
clusters which are responsible for the destruction process.
These observations suggest that joint destruction may be
influenced not by antiphlogistics, but rather through cytostatic agents.
H. G. Fassbender, MD
Mainz, West Germany
I . Shiozawa S, Shiozawa K , Fujita T: Morphologic observations in
the early phase of the cartilage-pannus junction. Arthritis Rheum
26:472-478, 1983
2. Fassbcnder HG, Simmling-Annefeld M, Stoffet E: Transforma-
tion der Synovialzellen bei rheumatoider Arthritis (Transformation of synovial cells in rheumatoid arthritis). Vcrh Dtsch Ges
Pathol 64:193-212, 1980
3. Fassbender HG, Simmling-Annefeld M: The potential aggressiveness of synovial tissue in rheumatoid arthritis. J Pathol
1391399-406, 1983
4. Fassbcnder HG: Histomorphological basis of articular cartilage
destruction in rheumatoid arthritis. Coll Relat Kes 3: 141-155,
Process of cartilage destruction by the pannus in
rheumatoid arthritis
To the Editor:
We thank Dr. Fassbender for his interest in and
favorable comments on our paper.
According to our study ( l ) , there are 3 stages in the
process of cartilage destruction by the pannus in rheumatoid
arthritis. 1) The pannus extends over the surface of rheumatoid cartilage, morphologically as the layers of fibroblast-like
cells. At this stage, the pannus does not invade the cartilage
matrix. 2) Then the invasion of the cartilage matrix by
macrophage-like cells starts beneath this layer of fibroblastlike cells. The invading edge of the pannus is usually focal,
and often- continuous into the lacunar spaces of chondrocytes. The invading portion consists predominantly of macrophage-like cells. We believe this part of the pannus corresponds to the cell cluster of “tumor-like proliferation”
suggested in Dr. Fassbender’s letter.
3 ) In the more advanced stage, the pannus becomes
thick with cellular infiltrations. Here, the pannus could be
divided into 2 parts by the presence of the fibroblast-like cell
layers. It is important to note, when comparing the sides of
the pannus above and below the layer offibroblast-like cells,
that the pannus beneath this layer is either active or inactive
in morphology when the upper part is morphologically
However, if the upper part is inactive and fibrous,
the lower part of the pannus is always inactive in morphology. We also have observed that the proliferative activity of
the invading front of the pannus is short-lived, as was
observed by Dr. Fassbender. Therefore, for the pannus to
continually invade, the presence of active inflammation in
the upper part of the fibroblast-like cell layers is necessary.
Probably some factors, either humoral or cellular, will be
transferred through capillaries or by diffusion.
Immune complexes (2-5) or fibronectin (6,7) may be
an important inducer for the extension of pannus over the
surface of cartilage at stage 1. As discussed by Dr. Fassbender, we do not know about the factor(s) stimulating the
proliferative invasion of the pannus at stage 2. However, this
factor(s) will be of primary importance, as Dr. Fassbender
indicates, in the pathogenesis of cartilage destruction by the
Although we do not know the cause of the aggressive
invasion, we consistently observed that the invasive front of
the active pannus easily turned into inactive fibroblastic
scar. Therefore, we believe that the influence of active
inflammation in the rheumatoid synovium plays a key role in
the invasiveness of the pannus at stage 3 .
Shunichi Shiozawa, MD
Kobe Universio School of Medicine
Kobe, Japan
1. Shiozawa S, Shiozawa K , Fujita T: Morphologic observations in
the early phase of the cartilage-pannus junction. Arthritis Rheum
26:4?2478, 1983
Cooke TD, Hurd ER, Jasin HE, Bienenstock J, Ziff M: Identification of immunoglobulins and complement in rheumatoid articular collagenous tissues. Arthritis Rheum 18:541-551, 1975
Ishikawa H, Smiley JD, Ziff M: Electron microscopic demonstration of immunoglobulin deposition in rheumatoid cartilage. Arthritis Rheum 18563-576, 1975
Jasin HE, Cooke TD: The inflammatory role of immune complexes trapped in joint collagenous tissues. Clin Exp lmmunol
33:416-424, 1978
Shiozawa S, Jasin HE, Ziff M: Absence of immunoglobulins in
rheumatoid cartilage-pannus junctions. Arthritis Rheum 23:816821, 1980
Rich AM, Pearlstein E, Weissmann G , Hoffstein ST: Cartilage
proteoglycans inhibit fibronectin-mediated adhesion. Nature
293~224-226, 1981
Noms DA, Clark RAF, Swigart LM, Huff JC, Weston WL,
Howell SE: Fibronectin fragment(s)are chemotactic for human
peripheral blood monocytes. J Immunol 129:1612-1618, 1982
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pannus, process, destruction, arthritis, cartilage, rheumatoid
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