Increased angiogenesis and cellular proliferation as hallmarks of the synovium in chronic septic arthritis.
OBJECTIVE
To characterize histologic alterations and inflammatory infiltrates in the synovium of patients with chronic septic arthritis (SeA).


METHODS
Synovial membranes from patients with SeA (9 specimens; disease duration >4 weeks) were compared with specimens from patients with septic joint prosthesis loosening (septic total arthroplasty [SeTA]; 9 specimens), rheumatoid arthritis (RA; 25 specimens), osteoarthritis (25 specimens), and normal histology (10 specimens). Sections were stained with hematoxylin and eosin, tissue gram stain, and immunostains for von Willebrand factor (vWF; blood vessels), Ki-67 (dividing cells), CD15 (neutrophils), CD3 (T cells), CD20 (B cells), CD38 (plasma cells), and CD68 (macrophages).


RESULTS
Gram stains were positive in all SeA and SeTA specimens. Mixed polymorphonuclear and mononuclear infiltrates predominated in SeA and SeTA. SeA could be differentiated from RA by higher densities of CD15+ cells (SeA:RA ratio 6.5:1; P < 0.001) or Ki-67+ cells (ratio 2.1:1; P = 0.012). The inflammatory infiltrate of SeTA was similar to SeA but contained fewer CD3+ cells (SeTA versus SeA 0.26:1; P = 0.009) and a tendency toward fewer CD20+ cells. Mean vascular density was strikingly increased in SeA (SeA:normal ratio 3.0:1; P < 0.001) and, to a lesser extent, in the vascularized areas of the SeTA specimens (SeTA:normal ratio 1.9:1). Ki-67/CD31 double immunostains demonstrated proliferating endothelial cells in small subintimal blood vessels, suggesting angiogenesis. Receiver operating characteristic curve analysis identified higher densities of CD15+ and Ki-67+ cells and vWF-positive vessels as histologic markers that differentiated SeA from RA.


CONCLUSIONS
This first analysis of the synovium in patients with chronic pyogenic arthritis identified dramatic neovascularization and cell proliferation, accompanied by persistent bacterial colonization and heterogeneous inflammatory infiltrates rich in CD15+ neutrophils, as histopathologic hallmarks.
Pessler
F
F
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. frank.pessler@uniklinikum-dresden.de
Dai
L
L
Diaz-Torne
C
C
Ogdie
A
A
Gomez-Vaquero
C
C
Paessler
M E
ME
Einhorn
E
E
Chen
L X
LX
Schumacher
H R
HR
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D018951:Antigens, CD20 / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001170:Arthritis, Infectious / Q000276:immunology* / Q000473:pathology*; D001402:B-Lymphocytes / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism; D002455:Cell Division; D002648:Child; D002908:Chronic Disease; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000473:pathology*; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010950:Plasma Cells / Q000473:pathology; D013583:Synovial Membrane / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D000097382:CD68 Molecule
D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D018951:Antigens, CD20; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D019394:Ki-67 Antigen; D016256:Lewis X Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule