Valentina Germano

Autoimmune hepatitis associated with infliximab in a patient with psoriatic arthritis

We read with interest the debate about liver toxicity of infliximab in psoriatic arthritis (PsA).1,2 We describe the case of a 53 year old woman with a 4 year history of refractory PsA who developed transaminasitis during infliximab treatment. Despite combination treatment (ciclosporin 300 mg/day, fluocortolone 10 mg/day, and methotrexate (MTX)15 mg/week intramuscularly), disease activity was still high, and intravenous infliximab at 3 mg/kg was administered initially at weeks 0, 2, 6, 14 and then every 6 weeks. Ciclosporin was withdrawn. Within 3 weeks she improved, fluocortolone was gradually stopped while methotrexate (MTX) 20 mg/week intramuscularly, was continued. After the sixth infusion, she developed a mild transaminasitis and MTX, initially tapered, was stopped. After the eighth infusion transaminases continued to rise and in the absence of any other plausible cause, infliximab was withdrawn. She was admitted to our department with persistently high values of aspartate aminotransferase and alanine aminotransferase and a flare of PsA. …

Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFα blockers: Safety and immunogenicity

Twenty-eight patients with low-moderate, stable rheumatoid arthritis (RA), under treatment with tumor necrosis factor (TNF) alpha blockers, were immunized at least once with non-adjuvanted trivalent influenza vaccine during three consecutive influenza seasons. Antibodies toward A influenza antigens significantly increased and reached protective levels, still detectable 6 months after vaccination, both in RA patients and healthy controls. Response to B antigen instead was only observed from the second year for healthy controls and in the third year for patients. No significant difference in disease activity and anti-nuclear antibodies was observed as a consequence of vaccine administration, whereas T regulatory cells showed a significant increase 30 days after immunization in RA patients. This study confirms safety of influenza vaccine administration in RA patients treated with TNFalpha blockers. The cohort follow-up revealed the overcoming of poor B vaccine antigen immunogenicity via repeated vaccinations. Finally, protective antibody response was still observed 6 months after vaccination.

Nailfold capillaroscopy changes in systemic lupus erythematosus : correlations with disease activity and autoantibody profile

In systemic lupus erythematosus (SLE) nailfold capillaroscopy (NC) studies have described many different nonspecific patterns. We decided to evaluate NC changes in 44 SLE patients, comparing them with the main clinical, demographic and laboratory parameters, thus to define the real role for NC and its abnormalities in the management of this disease. Fifteen patients (34%) complained of Raynaud’s phenomenon; nine of them (20%) showed relevant capillaroscopic changes (capillaroscopic score >1). In details: three patients (6.8%) had loss of capillaries, while 18 (41%) had a capillary length variability, 16 (36.5%) showing shorter and two (4.5%) longer capillaries; tortuous, meandering, bizarre, ramified and/or bushy capillaries were found in 26 (59%), seven (16%), two (4.5%), three (7%) cases, respectively. An irregular distribution of the capillary array was present in six cases (14%) while microhaemorrhages were found in four cases (9%). 4 patients (9%) showed enlarged capillaries and changes of blood flow. A capillaroscopic score >1 was more frequently associated with higher ECLAM (P < 0.005) and SLEDAI (P < 0.01) activity scores, with the presence of anti-cardiolipin (P < 0.04) and anti-Sm (P < 0.04) antibodies, and also with the presence (P < 0.04) and higher titer (P < 0.001) of anti-dsDNA antibodies. No statistically significant correlation was found among the different capillaroscopy findings, age, disease duration, or treatment, nor with any clinical manifestation of the disease, such as cutaneous, renal or neurological. Our findings confirm the importance of the microvascular involvement in SLE. The NC abnormalities seem to be related to the disease activity and to the presence of many different antibodies, highly involved in the expression of SLE. NC proved to be an easy-to-perform noninvasive technique, able to achieve useful data to better evaluate such a pleomorphic disease as SLE.

Viscosupplementation in the management of ankle osteoarthritis: a review

IntroductionOsteoarthritis (OA) is a disease of synovial joints and is the most common cause of chronic pain. Viscosupplementation (VS) with hyaluronic acid (HA) is largely used for knee osteoarthritis therapy but the evidence for its usefulness in ankle osteoarthritis is limited. The objective of this review is to assess the efficacy of viscosupplementation treatment of ankle osteoarthritis in the current literature.MethodsThe following databases were searched: Medline (period 2006–2008), Database of Abstract on Reviews and Effectiveness and Cochrane Database of Systematic Reviews. Reference lists of relevant articles were controlled for additional references. The search terms Review, Viscosupplementation (VS), Osteoarthritis (OA), Hyaluronic acid (HA), Hyaluronan, Sodium hyaluronate, Ankle OA, Ankle joint were used to identify all studies relating to the use of VS therapy for the ankle OA. Methodological quality of included studies was assessed by assigning level of evidence as previously defined by the Centre for Evidence Based Medicine (CEBM).ResultSeven articles concerning the efficacy of a total of 275 patients undergoing VS treatment for ankle OA were included. One European study, one Taiwanese study, one Italian study, one Turkish study and three American studies with level of evidence ranging from I to IV evaluated the following products: Hyalgan®, Synvisc®, Supartz®, Adant®.ConclusionViscosupplementation is used widely in knee OA and is included in the professional guidelines for treatment of the disease in this joint. The potential for treating osteoarthritis of the ankle joint by viscosupplementation has been suggested in the literature, however, no dosing studies have been published to date, and dosing in the ankle joint remains an area for discussion. Viscosupplementation could potentially provide an useful alternative in treating such patients with painful ankle OA.

Infection risk in Rheumatoid Arthritis and Spondyloarthropathy patients under treatment with DMARDs, Corticosteroids and TNF-α antagonists

BackgroundInfections which complicate rheumatic diseases such as Rheumatoid Arthritis (RA) and Spondyloarthropathy (SpA) (Psoriatic Arthritis [PA] and Ankylosing Spondylitis [AS]), may cause significant morbidity and mortality. However, among the studies on the incidence rate (IR) of infections in such patients, very few have involved controls and the results have been controversial, probably due to methodological difficulties.To estimate infection rates in RA and SpA patients under disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids (CS) and tumor necrosis factor (TNF)α antagonists, alone or combined, a single-centre retrospective observational cohort study has been performed.Patients and methodsIncidence rates/100 patient-years of any infections were evaluated in RA and SpA outpatients observed in the period November 1, 2003 through December 31, 2009 and stratified according to therapy. Infection incidence rate ratios (IRR) were calculated using Poisson regression models which adjusted for demographic/clinical characteristics of the patients.ResultsThree hundred and thirtyone infections [318 (96.1%) non-serious and 13 (3.9%) serious] have been registered among 176 of the 341 patients (52%). The IR/100 patient-years of all infections was 36.3 ranging from 12.4 (DMARDs + CS) to 62.7 (anti-TNFα + CS). The most frequent infection site was respiratory tract, and bacteria were responsible for three quarters of all infections. In the multivariate analysis, adding anti-TNFα to DMARDs doubled the IRR compared to DMARDs alone, anti-TNFα + CS significantly tripled it, whereas anti-TNFα + CS + DMARDs only increased the risk 2.5 times. The degree of disease activity was strongly and significantly associated with the infection risk (severe or moderate versus mild, IRR = 4). Female sex was significantly associated with increased infection risk, while duration of disease and anti-influenza vaccination were protective, the latter even for cutaneous/soft-tissue (mainly herpetic) infections.ConclusionThe combination anti-TNFα with CS was found to be the most pro-infective treatment, whereas DMARDs alone were relatively safe. Physicians, therefore, should be aware that there may be an increased risk of infection when using anti-TNFα and CS therapy together. Anti-influenza vaccination appears to provide broad protection, adding evidence to support its use in these patients, and deserves further study.

Erratum to: Intra-articular injection of hyaluronic acid (MW 1,500–2,000 kDa; HyalOne®) in symptomatic osteoarthritis of the hip: a prospective cohort study

INTRODUCTION Clinical trials have demonstrated the safety and efficacy of hyaluronic acid-based products for the treatment of hip osteoarthritis, but data from observational studies of normal medical practice are scarce. This study investigated the long-term efficacy and tolerability of ultrasound-guided intra-articular sodium hyaluronate (MW 1,500-2,000 kDa; Hyalone) injections in daily clinical practice. METHODS In this observational, cohort study of patients with hip osteoarthritis, Hyalone was administered under the ultrasound guidance, every 6 months, with the possibility of an additional injection at the intervening 3-month intervals on clinical request. Efficacy measurements included the Lequesne algofunctional index, self-reported pain via the visual analogue scale (VAS), the concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and safety. The patients were followed up for 18 months after the first intra-articular injection. RESULTS Data from 120 patients were collected. During the study, a statistically significant reduction in algofunctional indexes was demonstrated at 3 months after study product injection, while at 12 months 80% of the patients achieved a decrease of at least 30% in symptoms. These results were maintained over time through cyclical and personalized repetition of ultrasound guided injections, at least one injection every 6 months. CONCLUSIONS The study treatment reduced pain and improved mobility in osteoarthritis of the hip. These results in daily clinical practice demonstrate a beneficial effect and the safety of the study product and suggest adding intra-articular injections of HyalOne to the armamentarium of conservative management of symptomatic hip osteoarthritis.

Abatacept (cytotoxic T lymphocyte antigen 4-immunoglobulin) improves B cell function and regulatory T cell inhibitory capacity in rheumatoid arthritis patients non-responding to anti-tumour necrosis factor-α agents

The use of biological agents combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients has strongly improved disease outcome. In this study, the effects of abatacept on the size and function of circulating B and T cells in RA patients not responding to anti‐tumour necrosis factor (TNF)‐α have been analysed, with the aim of identifying immunological parameters helpful to choosing suitable tailored therapies. We analysed the frequency of peripheral B and T cell subsets, B cell function and T regulatory cell (Treg) inhibitory function in 20 moderate/severe RA patients, according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, primary non‐responders to one TNF‐α blocking agent, who received abatacept + MTX. Patients were studied before and 6 months after therapy. We found that abatacept therapy significantly reduced disease activity score on 44 joints (DAS)/erythrocyte sedimentation rate (ESR) values without causing severe side effects. The size of the circulating B and T cell compartments in RA patients was not significantly different from healthy donors, but B cell proliferation and plasma cell differentiation was impaired before therapy and restored by abatacept. While Treg cell frequency was normal, its inhibitory function was absent before therapy and was partially recovered 6 months after abatacept. B and Treg cell function is impaired in RA patients not responding to the first anti‐TNF‐α agent. Abatacept therapy was able to rescue immune function and led to an effective and safe clinical outcome, suggesting that RA patients, in whom anti‐TNF‐α failed, are immunologically prone to benefit from an agent targeting a different pathway.

Interstitial Lung Disease in Rheumatoid Arthritis in the Era of Biologics

Interstitial lung disease (ILD) represents a severe manifestation in connective tissue diseases (CTD), with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA), observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT) and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFα inhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT) is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered.

Imaging Progression despite Clinical Remission in Early Rheumatoid Arthritis Patients after Etanercept Interruption

The aim of this preliminary study is to evaluate clinical and imaging response in twenty patients with early Rheumatoid Arthritits (eRA) treated with Etanercept (Etn) + Methotrexate (Mtx) and to investigate whether clinical and MRI remission may be maintained after biological therapy interruption. Assessment included: radiography, Visser score and anti-CCP antibodies at baseline; disease activity score in 44 joints (DAS44), rheumatoid factor (RF), Magnetic Resonance Imaging (MRI) of hands and wrists at baseline (T0), 12 (T1), and 24 months (T2). MRI was scored for synovitis, bone oedema and erosions (OMERACT study); patients who reached clinical and imaging remission at T1 were considered eligible for interrupting Etn. At T1 8/20 (40%) patients showed a total remission [DAS44 from 5 (T0) to 1.4 (T1); p<0.02], whereas the other 12/20 (60%) showed an improvement, without complete remission [DAS44 from 4.8 (T0) to 2.8 (T1); p<0.05]. Etn was therefore interrupted in the first group of patients (group A), whereas it was continued in the other group (group B). At T2, group A maintained clinical remission and group B showed further not significant DAS44 reduction from T1. At T1, a significant reduction in synovitis, bone oedema and total score (p<0.01) was observed both in group A and in group B. At T2, group A showed an increase in all the MRI scores that was significant for the synovitis and total score, whereas group B exhibited a further not significant reduction. This preliminary study reports an excellent clinical and imaging response in eRA patients treated with Etn with total remission in 40% of them after a 1-year therapy period. However, it indicates that joint damage may progress, despite a sustained clinical remission, after Etn suspension

Safety and immunogenicity of co-administered MF59-adjuvanted 2009 pandemic and plain 2009–10 seasonal influenza vaccines in rheumatoid arthritis patients on biologicals

Rheumatoid arthritis (RA) patients under immunosuppressive therapy are particularly susceptible to infections, mainly of the respiratory tract, thus vaccination may represent a strategy to reduce their incidence in this vulnerable population. In the 2009–10 influenza season, the safety and immunogenicity of co‐administered non‐adjuvanted seasonal and MF59‐adjuvanted pandemic influenza vaccines were evaluated in this study in 30 RA patients under therapy with anti‐tumour necrosis factor (TNF)‐α agents or Abatacept and in 13 healthy controls (HC). Patients and HC underwent clinical and laboratory evaluation before (T0), 1 (T1) and 6 months (T2) after vaccinations. No severe adverse reactions, but a significant increase in total mild side effects in patients versus HC were observed. Both influenza vaccines fulfilled the three criteria of the Committee for Proprietary Medicinal Products (CPMP). Seroconversion rate for any viral strain in patients and HC was, respectively, 68 versus 45 for H1‐A/Brisbane/59/07, 72 versus 81 for H3‐A/Brisbane/10/07, 68 versus 54 for B/Brisbane/60/08 and 81 versus 54 for A/California/7/2009. A slight increase in activated interferon (IFN)‐γ‐, TNF‐α‐ or interleukin (IL)‐17A‐secreting T cells at T1 compared to T0, followed by a reduction at T2 in both patients and HC, was registered. In conclusion, simultaneous administration of adjuvanted pandemic and non‐adjuvanted seasonal influenza vaccines is safe and highly immunogenic. The largely overlapping results between patients and HC, in terms of antibody response and cytokine‐producing T cells, may represent further evidence for vaccine safety and immunogenicity in RA patients on biologicals.