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. 2000 Aug;59(8):598–606. doi: 10.1136/ard.59.8.598

Increased cellularity and expression of adhesion molecules in muscle biopsy specimens from patients with rheumatoid arthritis with clinical suspicion of vasculitis, but negative routine histology

P Verschueren 1, A Voskuyl 1, T Smeets 1, K Zwinderman 1, F Breedveld 1, P Tak 1
PMCID: PMC1753205  PMID: 10913056

Abstract

OBJECTIVE—Histological analysis of random quadriceps muscle biopsy specimens can be used to detect vasculitis in patients with rheumatoid arthritis (RA). This study aimed at determining the immunohistological features in patients with clinical suspicion of rheumatoid vasculitis, but without a transmural infiltrate or fibrinoid necrosis of the vessel wall on routine histology.
METHODS—Three groups of patients with RA were studied: (a) without clinical signs of vasculitis (n=6); (b) with recent onset of extra-articular features and a clinical suspicion of vasculitis but normal routine histology (n=11); and (c) with recent onset of extra-articular features and vasculitis, histologically proved either in muscle or other biopsy specimens (n=14). A control group of patients with osteoarthritis was also included (n=5). Frozen sections from quadriceps muscle biopsy specimens were analysed with monoclonal antibodies to detect CD3, CD4, CD8, CD68, ICAM-1, VCAM-1, and HLA-DR. The slides were evaluated using a semiquantitative scoring system (0-4).
RESULTS—The mean scores gradually increased from group 1 to 3, leading to significant differences between groups 1 and 2, but not between groups 2 and 3 for most markers (p< 0.05). Thus the pathological changes were similar for the two groups with clinical signs of vasculitis, even when the conventional histological evaluation was negative. Higher immunohistological scores were associated with perivascular infiltrates on routine histology.
CONCLUSION—The pathophysiological events leading to vasculitis are reflected by the changes in the quadriceps muscle biopsy specimens. The data indicate that the sensitivity of examination of muscle biopsy specimens for the diagnosis of rheumatoid vasculitis can be increased by the use of new criteria.



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Infiltration by (A) CD3+ T cells, (B) CD4+ cells, (C) CD8+ cells, and (D) CD68+ macrophages, and expression of adhesion molecules (E) ICAM-1 and (F) VCAM-1, and activation marker (G) HLA-DR in muscle biopsy specimens from patients with rheumatoid arthritis without clinical suspicion of vasculitis (group 1= RA−), patients with rheumatoid arthritis with clinical evidence of vasculitis but without histological proof (group 2 = RA+), and patients with histologically proved rheumatoid vasculitis (group 3 = RV). The mean semiquantitative scores gradually increased from group 1 to group 3. Scores for the osteoarthritis (OA) control group were similar to the RA− group. (Original magnification × 400.) Figure 1A   CD3+ T cells. Figure 1B   CD4+ cells. Figure 1C   CD8+ cells. Figure 1D   CD68+ macrophages. Figure 1E   Adhesion molecule ICAM-1. Figure 1F   Adhesion molecule VCAM-1. Figure 1G   Activation marker HLA-DR.

Figure 2  .

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Infiltration by CD3+ T cells, CD4+ cells, CD8+ cells, and CD68+ macrophages, and expression of adhesion molecules ICAM-1 and VCAM-1 and the activation marker HLA-DR in muscle biopsy specimens in which perivascular infiltrates (PVI) were recorded on routine histology, compared with those in which such infiltrates were absent. Significantly higher mean semiquantitative scores for all the markers were documented when a perivascular infiltrate of more than three cell layers was present on routine histology (p<0.05).

Selected References

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