Hepatitis B Virus Markers in Hematologic Patients: Relation to Transfusion Treatment and Hospitalization

Abstract. Screening tests for hepatitis B virus (HBV) markers were performed in 266 hematologic patients in order to evaluate the role of transfusion therapy in HBV infection and to identify other possible causes of the high rate of HBV markers positivity in onco-hematologic units. As control groups we tested 99 nonhematologic polytransfused patients, 66 nonhematologic, nontransfused inpatients with various diseases and 72 subjects randomly selected from the general population. Higher HBV markers prevalence was found in hematologic patients, nonhematologic polytransfused patients and nonhematologic, non-transfused inpatients than in the general population. HBV markers prevalence correlated with the length of hospitalization in all inpatients studied. Our data suggest that hospital admission is a major factor in HBV transmission in hematologic patients and in other inpatients studied. Blood transfusions represent a risk factor only when utilized as chronic treatment.     

Osteitis condensans ilii: prevalence and characteristics of a neglected mimic of sacroiliitis

Clinical Rheumatology - Osteitis condensans ilii (OCI) is a benign condition characterised by triangular sclerosis of the iliac bone which may mimic radiographic sacroiliitis. Prevalence is...     

Intracellular nucleotides of lymphocytes and granulocytes from normal ageing subjects.

Impaired lymphocyte and granulocyte function in the aged may, in part, reflect intrinsic aged-related biochemical alterations. In this study we compared the ribonucleotide contents of lymphocytes and granulocytes from young and old subjects evaluated by means of an HPLC-anion exchange method. We found that in general both populations from old subjects present higher levels of the various nucleotides, in particular: ATP, UDP, CTP, UDP-glucose in granulocytes, AMP, CTP, UDP-N-acetylglucosamine, UDP-glucose in lymphocytes. These data suggest that these molecules accumulate in aged subjects because of altered biochemical pathways. The increased pool of UDP-sugars, in particular, could be due to a depressed activity of some glycosyltransferases which therefore fail to glycosylate some plasma membrane cell proteins, thus accounting for their functional impairment.     

High in vivo expression of interleukin-17 receptor in synovial endothelial cells and chondrocytes from arthritis patients

OBJECTIVE: To evaluate the presence of interleukin-17 (IL-17) and the expression of IL-17 receptor (IL-17R) in joint tissues from subjects with different arthritides. METHODS: Immunohistochemistry was used on frozen synovial and cartilage biopsies to identify cells expressing IL-17 and IL-17R. RESULTS: IL-17 staining was present only in synovial biopsies of rheumatoid arthritis (RA) (seven out of nine cases). IL-17R was expressed by all synovial biopsies evaluated except for three cases of post-traumatic arthritis (PTA). Vascular endothelial cells mainly expressed IL-17R. The percentage of IL-17R(+) vessels was the highest in RA synovium and the lowest in PTA. Chondrocytes from all types of arthritides were negative for IL-17 staining, but expressed IL-17R; the highest percentage of positive chondrocytes was found in seronegative spondylarthritis and the lowest in RA. CONCLUSIONS: IL-17-positive cells are found exclusively in RA. On the other hand, synovial endothelial cells and chondrocytes expressing IL-17R are found in the majority of patients with different types of arthritis. This finding suggests a role for a second ligand for IL-17R, which could be either a different cytokine or a different isoform of IL-17.     

Radiographic involvement of metacarpophalangeal and radiocarpal joints in hand osteoarthritis

To evaluate, by means of a longitudinal study, radiographic involvement of metacarpophalangeal and radio-carpal joints in hand osteoarthritis, its relationship with erosive disease and its progression, 368 patients with hand osteoarthritis were enrolled. All patients underwent hand X-rays. On the basis of the presence of central erosions in interphalangeal joints, patients were divided into three groups: 0—no central erosions, 1—one joint with central erosion, and 2—two or more joints with central erosions. A longitudinal study on 44 patients and nine normal controls, whose X-rays were available after 3.9 years, was performed. The radiological involvement of metacarpophalangeal and radio-carpal joints was evaluated using Kellgren-Lawrence and OARSI scores. Low number of joints showed Kellgren-Lawrence values ≥2 group 0, 42/1290 (3.3%); group 1, 10/410 (2.4%); and group 2, 36/1980 (1.8%). Low score values were obtained for all radiographic items. Only metacarpophalangeal joint space narrowing score showed significant increase from groups 0 to 2. Subsequent adjustment for age, gender, and BMI did not confirm the statistical significance. Marginal erosions were rarely found (6.7% of joints). Metacarpophalangeal and radio-carpal radiographic per patient scores significantly worsened at follow-up, but no significant increase in joints with Kellgren-Lawrence score ≥2 was found. In normal controls, no significant radiographic worsening was found. Only a minority of metacarpophalangeal joints shows a Kellgren-Lawrence value ≥2. Metacarpophalangeal and to lesser extent radiocarpal joints had significant worsening at follow-up. Metacarpophalangeal joint involvement in hand osteoarthritis is mild but progressive. Radiocarpal involvement is negligible.     

Tocilizumab for polymyalgia rheumatica: Report of two cases and review of the literature

Background

Glucocorticoids (GC) are the mainstay of treatment of polymyalgia rheumatica (PMR). However GC-related adverse events occur frequently, particularly in patients with relapsing disease. Several studies have demonstrated that IL-6 is a key player in the pathogenesis of PMR.

Objectives

To report 2 patients with PMR treated with the anti-IL-6 receptor monoclonal antibody tocilizumab (TCZ) and to review the published evidence on the efficacy and safety of TCZ in patients with PMR.

Methods

We treated 2 GC-naive patients with newly diagnosed pure PMR with monthly TCZ infusions (8 mg/kg body weight) for 6 months. Disease activity and drug tolerability were assessed clinically, by laboratory tests, and bilateral shoulder ultrasonography before starting the treatment and subsequently every month during TCZ therapy. We performed a systematic literature search (PubMed until July 2012) using the terms “tocilizumab,” “anti-IL-6-receptor,” “polymyalgia rheumatica,” “giant cell arteritis”, and “large-vessel vasculitis” to identify published reports of patients with PMR treated with TCZ.

Results

One of our patients responded well to TCZ, while the other patient required GC therapy after the 2nd TCZ infusion because of lack of appreciable clinical response. Both patients tolerated TCZ well. The review of the literature revealed 4 reports with a total of 9 patients who received TCZ for PMR. In 7 of these 9 patients, PMR was associated with giant cell arteritis. Including our patients, 5 patients received TCZ alone and 6 TCZ plus GC. A good response to TCZ treatment was observed in all patients reported in the literature without any major adverse events.

Conclusions

TCZ both as monotherapy and in association with GC appears to be mostly effective and safe to treat patients with PMR. However, larger controlled studies are required to confirm these favorable data.     

Chemokine production by human chondrocytes.

OBJECTIVE: To evaluate the role of chondrocytes in producing CXC chemokines [interleukin 8 (IL-8), growth related gene product (GRO-alpha)] and CC chemokines [monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1alpha), RANTES] in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and subjects after traumatic injury (PT). METHODS: Articular cartilage specimens were obtained from 38 patients with OA and 18 with RA undergoing joint replacement surgery. Healthy human cartilage was obtained from femoral condyles removed after trauma in 11 subjects with no history of joint pathology (PT cases). Chondrocytes were isolated from articular cartilage by sequential enzymatic digestion and cultured in vitro. Chemokine production was investigated in unstimulated condition and after 72 h incubation with proinflammatory [IL-1beta, tumor necrosis factor-alpha (TNF-alpha)] and antiinflammatory [transforming growth factor-beta1 (TGF-beta1), IL-10] mediators. Chemokine concentrations in cell supernatants were evaluated by ELISA. RESULTS: Chondrocytes produce all these chemokines to a different extent. IL-1beta was a more potent stimulus than TNF-alpha in inducing production of all chemokines except MCP-1. We found no statistical differences among chondrocytes isolated from OA, RA, and PT for chemokine production in either basal conditions or after cytokine stimulation. IL-1beta induced chemokine production can be modulated by TGF-beta1 in different ways according to the various chemokines, while IL-10 does not affect IL-1beta induced chemokine production. CONCLUSION: Chondrocytes produce IL-8, GRO-alpha, MCP-1, MIP-1alpha, and RANTES. Proinflammatory factors (IL-1beta, TNF-alpha) effectively upregulate chemokine production, but production is scarcely modulated by the antiinflammatory mediators TGF-beta and IL-10. Chondrocyte derived chemokines may play a role in triggering the mechanisms involved in pathogenesis and persistence of joint diseases.     

Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis.

Osteoarthritis and rheumatoid arthritis are characterized by focal loss of cartilage due to an up-regulation of catabolic pathways, induced mainly by pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha). Since reactive oxygen species are also involved in this extracellular-matrix-degrading activity, we aimed to compare the chondrocyte oxidative status responsible for cartilage damage occurring in primarily degenerative (osteoarthritis) and inflammatory (rheumatoid arthritis) joint diseases. Human articular chondrocytes were isolated from patients with osteoarthritis or rheumatoid arthritis, or from multi-organ donors, and stimulated with IL-1beta and/or TNFalpha. We evaluated the oxidative stress related to reactive nitrogen and oxygen intermediates, measuring NO(-)(2) as a stable end-product of nitric oxide generation and superoxide dismutase as an antioxidant enzyme induced by radical oxygen species. We found that cells from patients with osteoarthritis produced higher levels of NO(-)(2) than those from patients with rheumatoid arthritis. In addition, IL-1beta was more potent than TNFalpha in inducing nitric oxide in both arthritides, and TNFalpha alone was almost ineffective in cells from rheumatoid arthritis patients. We also observed that the intracellular content of copper/zinc superoxide dismutase (Cu/ZnSOD) was always lower in rheumatoid arthritis chondrocytes than in those from multi-organ donors, whereas no differences were found in intracellular manganese SOD (MnSOD) or in supernatant Cu/ZnSOD and MnSOD levels. Moreover, intracellular MnSOD was up-regulated by cytokines in osteoarthritis chondrocytes. In conclusion, our results suggest that nitric oxide may play a major role in altering chondrocyte functions in osteoarthritis, whereas the harmful effects of radical oxygen species are more evident in chondrocytes from patients with rheumatoid arthritis, due to an oxidant/antioxidant imbalance.     

Clinical and radiographic distribution of structural damage in erosive and nonerosive hand osteoarthritis

Objective

To characterize the clinical and radiographic joint phenotype in erosive hand osteoarthritis (EHOA) and non‐EHOA.

Methods

A total of 446 patients with HOA (233 with EHOA and 213 with non‐EHOA) were evaluated. Demographic (sex and age at disease onset), clinical (body mass index and distribution of nodes), and radiographic features (Kellgren/Lawrence and Kallman's scores obtained from radiographs of both hands) from all patients were recorded.

Results

Patients with EHOA had a significantly earlier disease onset. Clinical and radiographic distribution of structural damage in the distal interphalangeal (DIP), proximal interphalangeal (PIP), and first carpometacarpal joints was similar in EHOA and non‐EHOA. EHOA patients showed higher percentages of nodes and more severe radiographic scores; the more severe radiographic score of joints with nodes was due to both osteophytes and joint space narrowing (JSN). A direct correlation between osteophytes and JSN scores was observed. Central erosions (CE) were more prevalent in the DIP joints than in the PIP joints. Gull‐wing pattern of CE was prevalent in the DIP joints, whereas saw‐tooth pattern was prevalent in the PIP joints. Marginal erosions (ME) were present in 100% of EHOA patients and in 80% of non‐EHOA patients. An ordinal correlation between the presence of ME and osteophyte score was found.

Conclusion

We found quantitative, but not topographic, differences in structural damage between EHOA and non‐EHOA. Heberden's nodes, severe radiologic scores, and CE were concentrated in the second, third, and fifth DIP joints of both hands. ME were also present in the majority of non‐EHOA patients.