Hajime Ishikawa

Comparison of gastroduodenal, renal and abdominal fat biopsies for diagnosing amyloidosis in rheumatoid arthritis.

Abstract: The aim of the study was to determine the frequency of amyloidosis detected by gastroduodenal biopsy in rheumatoid arthritis (RA) patients, and to investigate correlations between the results of gastroduodenal biopsy and abdominal fat and renal biopsies. A total of consecutive 1006 RA patients underwent gastroduodenal biopsy. The 71 patients who tested positive for gastrointestinal (GI) amyloidosis were asked to undergo renal and abdominal fat biopsies, and 21 did so. Renal biopsies were also performed on 12 patients with no amyloidosis but indicators of drug-induced renal damage, and abdominal fat biopsies were performed on 50 RA patients with no indication of amyloidosis. The prevalence of GI amyloidosis was 7.1%. Urinary abnormalities and GI symptoms were common in GI amyloidisis, and inflammatory markers were elevated. Sixty-one (86%) had either depressed creatinine clearance or urinary symptoms. Nineteen of the 21 patients (91%) with GI amyloidosis who underwent renal biopsies also had renal amyloid deposits. Eleven of the 21 (52%) had amyloidosis on abdominal fat biopsy. None of the 12 patients without GI amyloidosis had renal amyloidosis on renal biopsy, and none of the 50 patients without GI amyloidosis had amyloidosis on abdominal fat biopsy. Gastroduodenal biopsy reveals a high prevalence of amyloidosis in RA patients. Amyloidosis is often associated with signs of renal impairment. Results of GI biopsy are highly correlated with those of renal biopsy, but the results of fat biopsy are not. We recommend GI biopsy for RA patients for the screening of systemic amyloidosis.

Rheumatoid wrists treated with synovectomy of the extensor tendons and the wrist joint combined with a Darrach procedure

Forty-three rheumatoid wrists in 43 patients with bilateral wrist involvement were treated with synovectomy of the extensor tendons and wrist joint combined with a Darrach procedure in the period from 1966 to 1986. Clinical and radiologic assessment of the wrists was carried out after an average follow-up period of 11 years, with comparison of the treated and the opposite untreated wrists. The authors confirmed what others have concluded regarding the operation: pain was generally decreased, forearm rotation increased, and wrist extension and palmar flexion changed little. Radiologically, carpal collapse and palmar carpal subluxation progressed nearly parallel to the opposite wrists, but ulnar carpal shift was much greater in the surgically treated wrists. Therefore it is suggested that some measure to prevent ulnar carpal shift, such as Claytons tendon transfer or radiolunate arthrodesis, should be included in this operation.

Limited arthrodesis for the rheumatoid wrist

Limited arthrodesis of the proximal carpal row to the radius, synovectomy of the extensor tendons and the wrist joint, and a Darrach procedure were carried out in 25 unstable painful rheumatoid wrists that had ulnar shift and/or palmar subluxation of the carpus. The average follow-up period after the operation was 3 years. Satisfactory results were obtained with relief of pain, improved forearm rotation, and increased grip strength. The average degree of extension and flexion was reduced, respectively, 70% and 54% at follow-up compared with the preoperative range. Postoperative x-ray films showed deterioration in the lunocapitate joint in 12 wrists; however, the wrists remained stable and painless.

Procalcitonin is a specific marker for detecting bacterial infection in patients with rheumatoid arthritis.

Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by many complications, and serious infections are associated with many of the advanced therapeutics used to treat it. We assessed serum procalcitonin (PCT) levels to distinguish bacterial infection from other complications in patients with RA. Methods. One hundred eighteen patients experiencing an RA flare, noninfectious complication of RA or its treatment, nonbacterial infection, or bacterial infection were studied. Serum PCT concentrations were determined with a chemiluminescent enzyme immunoassay. Results. All patients experiencing an RA flare showed negative PCT levels (≤ 0.1 ng/ml; n = 18). The PCT level was higher in the bacterial infection group (25.8% had levels ≥ 0.5 ng/ml) than in the other 3 groups (0.0–4.3% had levels ≥ 0.5 ng/ml) and the difference was significant among groups (p = 0.003). Conversely, no statistically significant difference was observed among the groups with C-reactive protein (CRP) concentration ≥ 0.3 mg/dl (p = 0.513), white blood cell (WBC) count > 8500/mm3 (p = 0.053), or erythrocyte sedimentation rate (ESR) > 15 mm/h (p = 0.328). The OR of high PCT level (≥ 0.5 ng/ml) for detection of bacterial infection was 19.13 (95% CI 2.44–149.78, p = 0.005). Specificity and positive likelihood ratio of PCT ≥ 0.5 ng/ml were highest (98.2% and 14.33, respectively) for detection of bacterial infection, although the sensitivity was low (25.8%). Conclusion. Serum PCT level is a more specific marker for detection of bacterial infection than either CRP, ESR, or WBC count in patients with RA. High PCT levels (≥ 0.5 ng/ml) strongly suggest bacterial infection. However, PCT < 0.5 ng/ml, even if < 0.2 ng/ml, does not rule out bacterial infection and physicians should treat appropriately.

The use of grommets for flexible hinge toe implants. A case report.

The postmortem examination of bilateral first metatarsophalangeal flexible hinge toe implants in a 66-year-old woman with rheumatoid arthritis is reported. The prosthesis had been inserted with grommets in 1 joint and without grommets in the other 2.5 years before her death. The implants were removed, and the bone/implant interfaces were examined microscopically by hematoxylin eosin stains and an electron probe microanalyzer. Surfaces of the implants were examined by scanning electron microscopy. Silicone particles within the fibrous tissue at the bone/implant interface, and a tear and significant scuffing of the implant surface, were detected in the joint without grommets. Such changes were not detected in the joint with grommets. These findings suggest that grommets may improve implant durability and preventing silicone synovitis.

A comparison of the ultrasonography images of the joints of patients with rheumatoid arthritis and the corresponding synovial histological findings.

Abstract Objectives: The objective of this study is to investigate whether ultrasonography (US) images of joints that underwent surgery reflected the synovial histological findings or clinical indicators and to compare the results of the findings related to large joints (LJs) with those of small joints (SJs). Methods: The operations were performed on 215 joints in 177 patients with rheumatoid arthritis (RA). The 215 joints included 64 LJs and 151 SJs. The joints with the power Doppler (PD) signal grades 0 and 1 were assigned to group L, while those with grades 2 and 3 were assigned to group H. The Rooney score, Disease Activity Score-erythrocyte sedimentation rate (DAS28), serum matrix metallopeptidase 3 (MMP-3), and C-reactive protein (CRP) levels were determined. Results: The Rooney score, DAS28, MMP-3, and CRP levels of the LJs were significantly lower in group L than in group H. In group H, similar results were found in the LJs and SJs, with a significant increase in the disease activity, CRP and MMP-3 levels and the histological findings in comparison to group L. Conclusions: The PD signal grade was one of the indicators that reflected the degree of synovitis in the histological findings of the active joints of RA patients.

Interleukin-2 Levels are Elevated in the Bone Marrow Serum of Patients with Mutilans-Type Rheumatoid Arthritis

Abstract: In order to investigate the pathogenesis of mutilans-type rheumatoid arthritis (RA), we measured cytokine levels in the bone marrow serum of patients with RA. We studied 35 patients with non-mutilans RA, 19 with mutilans RA, and 20 patients with osteoarthritis (OA) undergoing joint surgery. At the time of surgery, iliac bone marrow and peripheral blood were sampled from all 74 patients and cytokine levels measured. The serum levels of five cytokines (IL-1β, IL-2, IL-3, IL-6 and GM-CSF) were measured by ELISA. Haematologic and inflammatory factors were also measured. Levels of IL-2, IL-6 and GM-CSF in bone marrow serum were significantly higher in all RA patients than in those with OA. Mean (þSD) IL-2 levels were significantly higher in patients with mutilans-type RA (309.8þ686.3 pg/ml) than in patients with other types of RA (66.5þ173.1 pg/ml; P<0.01). IL-2 was detected significantly more often in patients with mutilans-type RA than in patients with other types of RA (P<0.01). Inflammatory factors were higher in all RA groups than in OA patients. However, the haematologic and immunologic variables were no different between mutilans RA and other types of RA. No correlations were observed between IL-1β, IL-2, IL-3, IL-6 and GM-CSF levels and these laboratory variables. In patients with mutilans-type RA, IL-2 levels in the bone marrow serum were significantly higher than in patients with other types of RA or with OA. This elevation does not appear to be related to systemic inflammation, as there was no correlation with other inflammatory factors.

Serum Fibroblast Growth Factor 23 (FGF23) in Patients with Rheumatoid Arthritis

Objective Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by periarticular and systemic osteoporosis. Fibroblast growth factor 23 (FGF23), which is mainly produced by osteocytes, circulates to the kidneys and regulates bone metabolism. We herein assessed serum FGF23 and its relationship to inflammation and osteoporosis in patients with RA. Methods Sixty-one patients with RA were included. Serum concentrations of FGF23 were determined using a sandwich enzyme-linked immunosorbent assay. Results The mean (± standard deviation) serum FGF23 concentration was 34.9±9.2 (range, 21.0-61.0) pg/mL. The serum FGF23 level was significantly and positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, disease activity score-28 based on the ESR (DAS-28 ESR) and DAS-28 CRP (r=0.261, p=0.044, r=0.280, p=0.029, r=0.409, p=0.001 and r=0.421, p=0.001, respectively). The serum matrix metalloproteinase-3 level was also significantly and positively correlated with the serum FGF23 level (r=0.331, p=0.015). Concentrations of type I collagen cross-linked N-telopeptide in the serum was significantly correlated with the serum FGF23 level (r=0.272, p=0.034). Neither the bone mineral density in the femoral neck nor lumbar was significantly correlated with the serum FGF23 level. Serum phosphate, calcium, 25-hydroxy vitamin D, and intact parathyroid hormone were not related to the serum FGF23 level. Conclusion In patients with RA, serum FGF23 is correlated with inflammation, the disease activity of RA, and bone absorption markers. Serum FGF23 may be associated with abnormal bone absorption related to RA inflammation. Further studies are necessary to clarify the mechanism underlying this association.

The Rate of Decrease in the Disease Activity of Rheumatoid Arthritis during Treatment with Adalimumab Depends on the Dose of Methotrexate

OBJECTIVE The aim of this study was to analyze the efficacy of adalimumab (ADA) in patients with rheumatoid arthritis treated with or without methotrexate (MTX) and determine impact of the MTX dose. METHODS Pearsons product-moment correlation coefficient was used to assess the correlations between the improvement in the Disease Activity Score (DAS) 28- erythrocyte sedimentation rate (ESR) score and the MTX dose in patients receiving treatment with MTX at a dose of <8 mg/week, 8 mg/week and >8 mg/week. PATIENTS ADA therapy was initiated in 68 rheumatoid arthritis patients between July 2008 and June 2013. The mean MTX dose was 9.6 ± 2.6 mg/week, and the patients were followed for 24 weeks. RESULTS The mean DAS28-ESR scores at baseline and week 24 were 4.6 ± 1.3 and 2.7 ± 1.2 in the 60 patients treated with MTX and 4.5 ± 1.0 and 4.2 ± 1.5 in the eight patients treated without MTX, respectively. Clinical remission was achieved in 48% and 25% of the patients, respectively, by week 24. Moreover, 90.0% of the patients taking MTX continued to receive ADA until week 24, while 50.0% of the patients not taking MTX continued to receive ADA until week 24. Among the 35 patients receiving MTX at a dose of >8 mg/week, the DAS28-ESR scores decreased rapidly from 4.4 ± 1.2 at baseline to 3.2 ± 1.1 at week 4 and further decreased to 2.4 ± 1.0 at week 24. Meanwhile, clinical remission was achieved in 57% of the patients receiving MTX at a dose of >8 mg/week and 36% of those receiving MTX at a dose of ≤8 mg/week. A significant correlation was noted between the improvement in the DAS-ESR score and the MTX dose. CONCLUSION In this study population, enhanced clinical efficacy of ADA was achieved in combination with the administration of a sufficient dose of MTX, determined to be >8 mg/week.

Extensor tendon rupture and three-dimensional computed tomography imaging of the rheumatoid wrist

PurposeExtensor tendon rupture on the dorsum of the wrist is commonly seen in patients with rheumatoid arthritis (RA). The diagnosis of tendon rupture is usually straightforward, but it is sometimes difficult in the hand with complex deformity. The purposes of this study were to investigate the reliability of three-dimensional computed tomography (3DCT) imaging of extensor tendons in the rheumatoid wrist and in the normal wrist and to clarify the validity of its clinical application to the diagnosis of tendon rupture in the rheumatoid wrist.MethodsPreoperative 3DCT images of 48 wrists of 45 patients with RA and 3DCT images of 38 wrists of 38 healthy volunteers were reviewed retrospectively by six orthopaedic surgeons who were unaware of all other study data. Extensor tendon rupture was verified by operation on 20 rheumatoid wrists.ResultsRegarding interobserver and intra-observer reliabilities of 3DCT imaging of the extensor tendons, agreement with respect to tendon rupture in this study group was high, and Cohens kappa (κ) coefficient was variable, depending on the individual tendon. Positive predictive value (PPV) of tendon rupture in the extensor digiti minimi (EDM), extensor digitorum communis (EDC) V and IV and extensor pollicis longs (EPL) tendons was more than 60%, but those for the other extensor tendons were less than 50%. Negative predictive value (NPV) was more than 96% in all extensor tendons, in both rheumatoid and normal wrists.ConclusionsExtensor tendons in normal and rheumatoid wrists were well depicted by 3DCT imaging. In the rheumatoid wrists, extensors of the ring and little fingers and the thumb were depicted more accurately than those to the other fingers. 3DCT imaging was clinically applicable to wrists for which it was difficult to diagnose by physical examination a definite cause for the loss of extension of the fingers.