Absence of histologic evidence of synovitis in patients with Gulf War veterans' illness with joint pain

Abstract

Objective. An unexplained multisymptom illness, Gulf War veterans' illness (GWVI), has been described among allied force veterans of the first Gulf War (1990War ( -1991. It has been proposed that some of its symptoms reflect an immune dysfunction, and rheumatologic symptoms including joint pain and stiffness are reported frequently. However, it is unknown whether synovial inflammation causes the articular symptoms. We examined synovial tissue from individuals with GWVI and joint pain for evidence of inflammation. Methods. We compared synovial biopsy samples from 6 individuals with GWVI and joint pain with samples from 9 clinically asymptomatic controls (hematoxylin and eosin [H&E] stains only) and biopsy samples or surgically obtained specimens from 10 patients with rheumatoid arthritis (RA) and 12 with osteoarthritis (OA). Inflammatory changes were quantified in H&E stained sections with a modified synovitis score by immunostaining for CD3, CD20, CD38, CD68, Ki-67, and von Willebrand factor, and with a composite inflammation score based on these markers. Results. Normal histology was seen in the GWVI specimens, except for mild focal lining hyperplasia and rare low-grade perivascular infiltrates in 1 specimen each. Mean ؎ SEM synovitis scores were lowest and nearly identical in control (1.38 ؎ 0.30) and GWVI specimens (1.41 ؎ 0.29), intermediate in OA specimens (2.64 ؎ 0.39), and highest in RA specimens (6.0 ؎ 0.19). Likewise, inflammatory cells, cell division, vascular density, and composite inflammation score were lowest in the GWVI specimens. Conclusion. Despite significant joint pain, the GWVI synovia did not differ from normal controls. These results agree with other studies that have failed to document inflammatory or immunologic etiologies in GWVI.

Synovial Biopsy Findings in Arthritis Associated with Hepatitis C Virus Infection

“…The mean lining thicknesses were much closer to OA than to RA ( Figure 2B). Immunostains for vWF revealed that vascular densities of both HCV specimens were nearly identical to the mean measured in RA ( Figure 2C) and 90% higher than in normal synovium 3,7 . The proliferation-associated antigen Ki-67 was only detected in the subintima, at densities intermediate between OA and RA ( Figure 2D).…”

“…Synovial tissue sections from both patients were stained with H&E or immunostained for CD15 (neutrophilic granulocytes), CD3, CD20, CD38, CD68, Ki-67, and von Willebrand factor (vWF) 3,4 . A previously validated synovitis score 5 was modified in that the score of each specimen represents the average of 5-10 microscopic fields (200× magnification).…”

“…A previously validated synovitis score 5 was modified in that the score of each specimen represents the average of 5-10 microscopic fields (200× magnification). Results were compared to results from synovial membranes from osteoarthritis (OA; n = 26) and rheumatoid arthritis (RA; n = 28) 3,4,6,7 . Vascular density was also compared to normal synovium (n = 15; 7 and unpublished data).…”

Carrageenan-induced transient inflammation in a rabbit knee model: molecular changes consistent with an early osteoarthritis phenotype

“…Interestingly, synovial inflammation has only been observed in localized compartments of many OA patients and furthermore may remain asymptomatic. In fact, it has been difficult to correlate the changes observed in the synovium to the onset and progression of OA as this tissue may remain histologically normal in very painful joints [20]. In contrast, it has also been reported that chronic knee pain may be the first symptom of the development of OA in the majority of individuals [21].…”

Synergistic Actions of Pyridostigmine Bromide and Insecticides on Muscle and Vascular Nociceptors

“…Although joint pain is a frequent complaint, there is no evidence of histological changes in joints, nor is there the presence of inflammatory markers that are associated with classic joint diseases such as osteo-or rheumatoid arthritis (Diaz-Torne et al 2007;Pessler et al, 2008). Although sensory disturbances may be present, there is no evidence of significant physical nerve impairment.…”