M. Covelli

Gastrointestinal symptoms and motility disorders in patients with systemic scleroderma

BackgroundStudies on gastrointestinal symptoms, dysfunctions, and neurological disorders in systemic scleroderma are lacking so far.MethodsThirty-eight scleroderma patients (34 limited, 4 diffuse), 60 healthy controls and 68 dyspeptic controls were scored for upper and lower gastrointestinal symptoms (dyspepsia, bowel habits), gastric and gallbladder emptying to liquid meal (functional ultrasonography) and small bowel transit (H2-breath test). Autonomic nerve function was assessed by cardiovascular tests.ResultsThe score for dyspepsia (mainly gastric fullness) was greater in scleroderma patients than healthy controls, but lower than dyspeptic controls who had multiple symptoms, instead. Scleroderma patients with dyspepsia had a longer disease duration. Fasting antral area and postprandial antral dilatation were smaller in scleroderma patients than dyspeptic and healthy controls. Gastric emptying was delayed in both scleroderma patients (particularly in those with abnormal dyspeptic score) and dyspeptic controls, who also showed a larger residual area. Despite gallbladder fasting and postprandial volumes were comparable across the three groups, gallbladder refilling appeared delayed in dyspeptic controls and mainly dependent on delayed gastric emptying in scleroderma. Small intestinal transit was also delayed in 74% of scleroderma and 66% of dyspeptic controls. Bowel habits were similar among the three groups. Autonomic neuropathy was not associated with dyspepsia, gastric and gallbladder motility and small intestinal transit.ConclusionIn scleroderma patients dyspepsia (mainly gastric fullness), restricted distension of the gastric antrum and diffuse gastrointestinal dysmotility are frequent features. These defects are independent from the occurrence of autonomic neuropathy.

CHONDROCYTE PHENOTYPING IN HUMAN OSTEOARTHRITIS

Cell-ECM (extracellular matrix) interactions are believed to play a key role in maintaining the normal structure of tissues such as cartilage. Cell surface adhesion molecules have been reported to mediate chondrocyte binding to ECM proteins in human normal cartilage but the behaviour of these molecules in human osteoarthritic cartilage is unknown. We studied receptor matrix proteins on freshly isolated chondrocytes obtained from 10 patients with osteoarthritis (OA). Chondrocytes were isolated by enzymatic digestion from three zones of the articular cartilage with a different degree of macroscopic and microscopic damage and chondrocyte phenotype was defined by flow cytometry. Chondrocytes strongly expressedβ1 integrin but notβ3 integrin. LFA-1 (CD18/CD11a) and ICAM-1 (CD54) antigens were almost undetectable. Interestingly,β1 expression was significantly higher in the minimally damaged zone than in the zones with medium and maximum damage. These data show thatβ1-integrin-mediated chondrocyte-ECM interactions decrease in osteoarthritic cartilage suggesting that perturbations of chondrocyte-matrix signalling occurs during OA.

Safety of long‐term biologic therapy in rheumatologic patients with a previously resolved hepatitis B viral infection

European and Asian studies report conflicting data on the risk of hepatitis B virus (HBV) reactivation in rheumatologic patients with a previously resolved HBV (prHBV) infection undergoing long‐term biologic therapies. In this patient category, the safety of different immunosuppressive biologic therapies, including rituximab, was assessed. A total of 1218 Caucasian rheumatologic patients, admitted consecutively as outpatients between 2001 and 2012 and taking biologic therapies, underwent evaluation of anti–HCV and HBV markers as well as liver amino transferases every 3 months. Starting from January 2009, HBV DNA monitoring was performed in patients with a prHBV infection who had started immunosuppressive biologic therapy both before and after 2009. Patients were considered to have elevated aminotransferase levels if values were >1× upper normal limit at least once during follow‐up. We found 179 patients with a prHBV infection (14 treated with rituximab, 146 with anti–tumor necrosis factor‐alpha, and 19 with other biologic therapies) and 959 patients without a prHBV infection or other liver disease (controls). The mean age in the former group was significantly higher than the controls. Patients with a prHBV infection never showed detectable HBV DNA serum levels or antibody to hepatitis B surface antigen/hepatitis B surface antigen seroreversion. However, when the prevalence of elevated amino transferases in patients with prHBV infection was compared to controls, it was significantly higher in the former group only for aminotransferase levels >1× upper normal limit but not when aminotransferase levels >2× upper normal limit were considered. Conclusion: Among patients with a prHBV infection and rheumatologic indications for long‐term biologic therapies, HBV reactivation was not seen; this suggests that universal prophylaxis is not justified and is not cost‐effective in this clinical setting. (Hepatology 2015;62:40‐46)

Safety of long term biologic therapy in rheumatologic patients with a previously resolved HBV infection

European and Asian studies report conflicting data on the risk of hepatitis B virus (HBV) reactivation in rheumatologic patients with a previously resolved HBV (prHBV) infection undergoing long‐term biologic therapies. In this patient category, the safety of different immunosuppressive biologic therapies, including rituximab, was assessed. A total of 1218 Caucasian rheumatologic patients, admitted consecutively as outpatients between 2001 and 2012 and taking biologic therapies, underwent evaluation of anti–HCV and HBV markers as well as liver amino transferases every 3 months. Starting from January 2009, HBV DNA monitoring was performed in patients with a prHBV infection who had started immunosuppressive biologic therapy both before and after 2009. Patients were considered to have elevated aminotransferase levels if values were >1× upper normal limit at least once during follow‐up. We found 179 patients with a prHBV infection (14 treated with rituximab, 146 with anti–tumor necrosis factor‐alpha, and 19 with other biologic therapies) and 959 patients without a prHBV infection or other liver disease (controls). The mean age in the former group was significantly higher than the controls. Patients with a prHBV infection never showed detectable HBV DNA serum levels or antibody to hepatitis B surface antigen/hepatitis B surface antigen seroreversion. However, when the prevalence of elevated amino transferases in patients with prHBV infection was compared to controls, it was significantly higher in the former group only for aminotransferase levels >1× upper normal limit but not when aminotransferase levels >2× upper normal limit were considered. Conclusion: Among patients with a prHBV infection and rheumatologic indications for long‐term biologic therapies, HBV reactivation was not seen; this suggests that universal prophylaxis is not justified and is not cost‐effective in this clinical setting. (Hepatology 2015;62:40‐46)

Isolated sternoclavicular joint arthritis in heroin addicts and/or HIV positive patients: Three cases

SummaryThe authors describe three patients in whom septic arthritis of the sternoclavicular joint (SCJ) occurred, drug addiction and human immunodeficiency virus (HIV) infection representing the predisposing conditions. Infectious arthritis is well known in intravenous drug users, but it is rare in HIV positive patients, who are prone to bacterial infections from usual or unusual microorganisms. In one case, staphylococcus aureus methicillin sensitive was responsible for septic arthritis. In another case, SCJ infection was associated with pneumonitis.

Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc–positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study

Objective. Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc–positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis. Methods. Thirty-three HBsAg-negative/anti-HBc–positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1–8) over 34 months (range 0–80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated. Results. None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs–negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0–70) after RTX discontinuation, no HBV reactivation was observed. Conclusion. The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.

Digital laser doppler flowmetry may discriminate "limited" from "diffuse" systemic sclerosis.

OBJECTIVES To investigate skin blood flux and microvascular functional changes by laser Doppler flowmetry (LD) in patients with systemic sclerosis (SSc) at baseline and following dynamic stimulations. METHODS Skin blood flux of the dorsal hands was recorded by LD at baseline and after the cold test and the post-occlusive hyperemia test in 59 SSc patients (49 limited cutaneous, 10 diffuse cutaneous). Twenty-five patients with primary Raynauds phenomenon (PRP), and 31 healthy donors (HD) were studied as controls. RESULTS After the cold test, SSc patients had a significantly higher reduction of the blood flux (-38.4%+/-28) than PRP (-21.1%+/-37) and HD (-22.1%+/-23) subjects (p<0.05). Within the SSc group, the cold test flux was significantly reduced in limited-SSc (-399%+/-28, p<0.05), but not in diffuse-SSc (-31.2%+/-29), whereas, the time needed to recover the basal flux after the occlusive/ischemic test was significantly longer in diffuse-SSc (18.8s+/-21)than in limited-SSc (4.5s+/-4, p<0.01) or HD (2.2s+/-2, p<0.01) or PRP (0.4s+/-0.7, p<0.01). CONCLUSIONS These data clearly indicate an impairment of vascular tone regulatory mechanisms in SSc and suggest that a peculiar pathogenic mechanism may be involved in different SSc subset. Nevertheless, it has clear that PRP and SSc-associated RP have a distinct pattern at LD evaluation, and monitoring patients with PRP could be helpful to understand whether a change in the LD pattern might predict the development of SSc.

Lipid profile of rheumatoid arthritis patients treated with anti-tumor necrosis factor-alpha drugs changes according to disease activity and predicts clinical response.

Postmarketing Phase IV

Monoclonal antibody investigation in rheumatoid arthritis: presence of a T cell subpopulation bearing a double marker

SummaryUsing a double marking technique of peripheral blood lymphocyte (PBL) from 23 patients suffering from rheumatoid arthritis (RA) and 12 normal healthy subjects (NHS), the authors were able to demonstrate that there was no alteration in the OKT8 + ve population of RA patients, when compared with NHS. On the contrary, an increased percentage of the subpopulation of lymphocytes OKT4 + ve was detected. Finally, the presence of a subpopulation of T cells carrying both the receptors for monoclonal antibodies OKT4 and OKT8 has been detected.

A false occult hepatitis B virus infection developed in a patient with psoriatic arthritis under infliximab and methotrexate therapy

Despite lacking of international guidelines about the management of patients with occult hepatitis B virus infection (OBI) starting TNF-α blockers, there is some evidence from real life settings that these drugs are safe in OBI patients with rheumatic diseases. On the contrary, the management of the so-called false OBI patients appears still undefined. We describe a case of acute hepatitis B virus (HBV) infection occurred in an anti-HBs and anti- HBc positive patient affected by psoriatic arthritis, who had been treated for five years with infliximab. Baseline HBV-DNA analysis had not been performed. Although HBs Ag was still negative and the transaminases in the normal range, HBV-DNA serum analysis surprisingly showed high replication rate. Entecavir was added, and three months later HBV-DNA was no longer detectable. Even if HBs Ag is persistently negative, the assessment of HBV-DNA should be recommended at least at baseline in order to rule out hidden active necro-inflammatory liver disease.