Lymphoma complicating rheumatoid arthritis: results from a French case-control study.

OBJECTIVES: To study the characteristics of B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. METHODS: A multicentre case-control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. RESULTS: 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. CONCLUSION: Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.

[Disc herniation-induced sciatica: medical or surgical treatment?]. / Conduite à tenir devant une lomboradiculalgie.

Radiculopathy is a common condition, characterized by a spontaneous regression: in 95 percent of patients, it resolves without surgery, within 1 to 12 months. To shorten the course of this disease, enable patients to resume social and professional activities and avoid chronicity, several therapeutic solutions have been assessed. Based on scientific evidence supporting effectiveness, physicians may prescribe analgesics, NSAID and epidural infiltrations, which probably relieve the pain and improve the quality of life without really modifying the mid-term prognosis. Following a specialized physical, social and professional assessment, surgery may be offered to patients who keep experiencing radicular (and not lumbar) pain. The complication rate is approximately 1 to 3 percent. The effectiveness of surgery is well established, especially with an improved recovery time (50 percent as compared to medical treatment). However, the superiority of a particular surgical technique has not been demonstrated. To date, we are still lacking evidence to demonstrate the effectiveness of percutaneous techniques in good methodological conditions. Finally, confinement to bed, cortisone administered per os or IV, localized spinal manipulations, corsets, vertebral tractions and physiotherapy have no demonstrated impact on the course of sciatica.

Herpes zoster: Risk and prevention during immunomodulating therapy.

Herpes zoster can be serious or incapacitating, particularly in patients whose immune system is compromised by a disease or treatment. Immunomodulating drugs can increase the risk of infection. Well-established risk factors include advanced age and glucocorticoid therapy. The data are somewhat conflicting for medications such as methotrexate, tofacitinib, TNFα antagonists (infliximab, adalimumab, etanercept, certolizumab, and golimumab), abatacept, tocilizumab, and rituximab. Nevertheless, the risk of herpes zoster is increased in patients taking biological agents, because of the underlying diseases and/or effects of the drugs. A live attenuated herpes zoster vaccine has been proven effective and safe in immunocompetent individuals. At present, however, it is not recommended for patients with immunodeficiencies, including those taking biological drugs, as no studies have assessed its risk/benefit ratio in this population. This situation may change in the near future, as recent data support the effectiveness and safety of the herpes zoster vaccine in patients who take biotherapies or have other causes of immunodeficiency. Alternative approaches designed to protect these patients from herpes zoster and its complications are also under evaluation. There is a need to define the indications of the herpes zoster vaccine in terms of the target population, timing, modalities, and frequency, according to the underlying chronic systemic disease, age group, varicella-zoster virus status, and exposure to therapeutic agents.

Fabry disease: a review.

Fabry disease is an inherited deficiency of the lysosomal hydrolase alpha-galactosidase A (alpha GalA) due to mutations in the Gal gene at Xq22. The result is intralysosomal accumulation of glycosphingolipids. In males who carry the mutation (1/40,000), severe multisystem disease develops in childhood or adolescence. Attacks of acute pain lasting a few minutes to a few days occur in the hands and feet, joints, muscles, and abdomen, sometimes with a fever. Highly suggestive skin lesions called angiokeratomas develop, as well as cornea verticillata characterized by corneal deposits without visual impairment. Stroke, seizures, heart disorders (conduction disturbances, valve disease, and left heart failure) and kidney disorders (proteinuria and chronic renal failure) develop in the third or fourth decade of life. Women who are heterozygous for the Gal gene can transmit the disease to their sons but are usually free of symptoms, although many have cornea verticillata. However, they may have moderate or severe disease related to uneven chromosome X inactivation. Late-onset variants with predominant neurological, cardiac, or renal manifestations have been described. The diagnosis is difficult when the family history is negative for Fabry disease. Tests on plasma and leukocytes show very low levels of alpha GalA activity in affected men, confirming the diagnosis. The Gal gene mutation should be looked for to detect heterozygous women. Symptomatic treatments include analgesics, antihypertensives, antiplatelet agents or anticoagulants to treat ischemic events, and hemodialysis or kidney transplantation to treat chronic renal failure. The recent introduction of enzyme replacement therapy with recombinant agalsidase alpha or beta has been a major breakthrough in the treatment of Fabry disease. Enzyme replacement therapy relieves the pain and decreases the risk of complications. The safety profile is good. Given the high cost of agalsidase therapy (about 160,000 euro/year/patient) and the low incidence of Fabry disease, patients should be referred to highly specialized centers (see addresses on the France Orphanet web site).

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS): definition, semiology, prognosis, pathogenesis, treatment, and place relative to other periodic joint diseases.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant inherited condition of periodic fever and pain. Most patients are of northern European descent. The attacks manifest as fever and pain in the joints, abdomen, muscles, skin, or eyes, with variations across patients. An acute-phase response occurs during the attacks. Patients with TRAPS are at risk for AA amyloidosis, the most common targets being the kidneys and liver. Soluble TNFRSF1A is usually low between the attacks and may be normal during the attacks, when TNF levels are high. TNFRSF1A is found in abnormally high numbers on leukocyte cell membranes. TRAPS is the first condition for which naturally occurring mutations in a TNF receptor were found; the mutations affect the soluble TNFRSF1A gene in the 12p13 region. In some patients, the pathogenesis involves defective TNFRSF1A shedding from cell membranes in response to a given stimulus. Thus, TRAPS is a model for a novel pathogenic concept characterized by failure to shed a cytokine receptor. This review compares TRAPS to other inherited periodic febrile conditions, namely, familial Mediterranean fever, Muckle-Wells syndrome, cold urticaria, and hyper-IgD syndrome. The place of TRAPS relative to other intermittent systemic joint diseases is discussed. Colchicine neither relieves nor prevents the attacks, whereas oral glucocorticoid therapy is effective when used in dosages greater than 20 mg/day. The pathogenic hypothesis involving defective TNFRSF1A shedding suggests that medications targeting TNF may be effective in TRAPS.

Agreement between rheumatologist visit and lay interviewer telephone survey for screening for rheumatoid arthritis and spondyloarthropathy.

OBJECTIVE: To evaluate agreement between a rheumatologist visit and a telephone interview by a patient organization member, regarding the diagnosis of rheumatoid arthritis (RA) or spondyloarthropathy (SpA) and the classification criteria for these two conditions. METHOD: Patients underwent a standardized interview and physical examination by hospital-based rheumatologists, who diagnosed RA in 230 cases, SpA in 175, and other conditions (controls) in 195. Members of patient organizations then used a standardized questionnaire to interview the patients by telephone about their diagnosis and about 1987 ACR classification criteria for RA and the ESSG criteria for SpA. RESULTS: Agreement between the two sources of data was poor for the classification criteria but satisfactory for the diagnosis (kappa, 0.84 (0.81-0.87) for RA and 0.78 (0.75-0.81) for SpA). CONCLUSION: Standardized telephone interviews conducted by patient organization members accurately identify the diagnosis made by rheumatologists based on a physical examination and medical record review, whereas agreement is poor regarding classification criteria for RA and SpA.

Systemic diseases and biotherapies: understanding, evaluating, and preventing the risk of hepatitis B reactivation.

Hepatitis B virus (HBV) reactivation can occur in chronic carriers of the HBV surface antigen (HBsAg) and constitutes a well-known complication of immunosuppressive therapy. HBV reactivation has also been reported after contact with the HBV. The increasing use of biological agents (TNFα antagonists, rituximab, abatacept, and tocilizumab) to treat systemic diseases has resulted in numerous publications about the risk of HBV reactivation. The relevant scientific societies have issued recommendations designed to prevent HBV reactivation. The main measures consist of screening for markers indicating chronic HBV infection (HBsAg) or HBV infection in the distant past (antibodies to the HBV core antigen) before initiating biological therapies, vaccinating marker-negative patients, and considering close follow-up or antiviral treatment before immunosuppressive treatment initiation or in the event of HBV reactivation. Here, we discuss the pathophysiological mechanisms underlying HBV reactivation during biological treatments, most notably in patients with occult HBV infection or markers for remote HBV infection, whose hepatocyte nuclei may contain a resistance form of HBV DNA known as covalently closed circular DNA (cccDNA). Assessment of the risk of reactivation relies on the HBV status, drugs used, and data from the literature. Finally, we discuss the various recommendations and modalities for HBV vaccination, preemptive treatment, and patient management, according to the level of risk and to the circumstances in which reactivation occurs.

Therapeutic approach to giant cell arteritis.

Giant cell arteritis (GCA) affects middle-sized or large arteries in individuals over 50 years of age. GCA is characterized by a combination of focal inflammation responsible for arterial stenosis or occlusion and of systemic inflammation manifesting as polymyalgia rheumatica, a decline in general health, and inflammatory anemia. In addition to the typical involvement of the branches of the external carotid arteries, relatively common sites of involvement include the aorta, most notably in its thoracic segment, and the subclavian, axillary, brachial, vertebral, and femoral arteries. The treatment of GCA rests on daily glucocorticoid administration, which should be started on an emergency basis in patients with incipient visual impairments (diplopia or amaurosis fugax). The duration of glucocorticoid therapy is unpredictable and side effects are common. Initial megadose glucocorticoid therapy does not decrease subsequent glucocorticoid requirements. Glucocorticoid therapy regulates the Th17 pathway, which is involved in the prominent vascular and systemic manifestations; but not the Th1 pathway, which may underlie the chronic course of the disease (whereas aspirin, in addition to decreasing platelet aggregation, blocks the Th1 mediator interferon-gamma). Although GCA is classically described as resolving within 1 to 3 years, clinical practice often teaches otherwise. Many patients experience rebound abnormalities in laboratory tests and/or relapses, and some of them have recurrences after an apparently full recovery. Histological documentation is useful to confirm the diagnosis. The effect of methotrexate and TNFα antagonists is modest at best. A few patients have responded to tocilizumab, which suppresses IL-6, a key cytokine in GCA. Life expectancy in GCA patients is similar to that in same-age controls except for a slight excess in vascular mortality shortly after the diagnosis.

Abatacept therapy and safety management.

OBJECTIVES: To develop and/or update fact sheets about abatacept treatment, in order to assist physicians in the management of patients with inflammatory joint disease. METHODS: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable 2. identification and review of publications relevant to each topic 3. development and/or update of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The experts were rheumatologists and invited specialists in other fields (dermatologist, cardiologist, pediatric rheumatologist, endocrinologist, hematologist, immunologist, infectiologist), and they had extensive experience with the management of chronic inflammatory diseases, such as rheumatoid arthritis (RA). They were members of the CRI (Club Rhumatismes et Inflammation), a section of the French Rheumatology Society (Societe Francaise de Rhumatologie). Each fact sheet was revised by several experts and the overall process was coordinated by three experts. RESULTS: Several topics of major interest were selected: contraindications of abatacept treatment; management of adverse effects and concomitant diseases that may develop during abatacept treatment; and management of common situations such as pregnancy, surgery, patient older than 75 years of age, and patients with co-morbidities (such as dialysis, hemoglobinopathy, or splenectomy). After a review of the literature and discussion among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA, initiation and monitoring of the abatacept treatment, management of patients with specific past histories, and specific clinical situations such as pregnancy 2. diseases other than RA, such as juvenile idiopathic arthritis, spondylarthropathies, or autoimmune diseases (systemic lupus erythematosus and other systemic autoimmune diseases) 3. models of letters for informing the rheumatologist and general practitioner 4. patient information about the use of abatacept in RA 5. and data on the new abatacept formulation for subcutaneous administration (approved by the FDA in August 2011 for patients with moderate-to-severe RA). CONCLUSION: These fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on abatacept. They will be available continuously on www.cri-net.com and will be updated at appropriate intervals.

Rheumatoid anemia.

Rheumatoid anemia is a typical example of anemia of chronic disease. It differs from other forms of anemia, such as iron deficiency anemia or iatrogenic anemia. Rheumatoid anemia is normochromic, normocytic or, less often, microcytic, aregenerative, and accompanied with thrombocytosis. Serum transferrin levels are normal or low, transferrin saturation is decreased, serum ferritin levels are normal or high, the soluble transferrin receptor (sTfR) is not increased (a distinguishing feature with iron deficiency anemia), and the sTfR/log ferritin ratio is lower than 1. This review discusses the prevalence and impact of rheumatoid anemia based on a review of the literature. Iron metabolism, absorption, diffusion, storage, and use by the bone marrow are described using published data on transferrin, ferritin, and hepcidin. Hepcidin is now recognized as a key factor in rheumatoid anemia, in conjunction with the cytokine interleukin-6 (IL-6). Hepcidin is a hormone that lowers serum iron levels and regulates iron transport across membranes, preventing iron from exiting the enterocytes, macrophages, and hepatocytes. In addition, hepcidin inhibits intestinal iron absorption and iron release from macrophages and hepatocytes. The action of hepcidin is mediated by binding to the iron exporter ferroportin. Hepcidin expression in the liver is dependent on the protein hemojuvelin. Inflammation leads to increased hepcidin production via IL-6, whereas iron deficiency and factors associated with increased erythropoiesis (hypoxia, bleeding, hemolysis, dyserythropoiesis) suppress the production of hepcidin. Data from oncology studies and the effects of recombinant human IL-6 support a causal link between IL-6 production and the development of anemia in patients with chronic disease. IL-6 diminishes the proportion of nucleated erythroid cells in the bone marrow and lowers the serum iron level, and these abnormalities can be corrected by administering an IL-6 antagonist. IL-6 stimulates hepcidin gene transcription, most notably in the hepatocytes. Studies involving human hepatocyte exposure to a panel of cytokines showed that IL-6, but not TNFα or IL-1, induced the production of hepcidin mRNA. Recent data on hepcidin level variations in patients with rheumatoid arthritis are reviewed. Rheumatoid anemia is best corrected by ensuring optimal control of systemic disease activity. The role for iron supplementation (per os or intravenously) and erythropoietin in the treatment of rheumatoid anemia is discussed. Given the cascade of interactions linking IL-6, hepcidin, and anemia, IL-6 antagonists hold considerable promise for the management of rheumatoid anemia.

Early-onset progressive osteoarthritis with hereditary progressive ophtalmopathy or Stickler syndrome.

Stickler syndrome is a group of rare genetic conditions (incidence, 1/7500 births) related to mutations in the collagen genes. Both the mutations and the clinical features vary widely across affected patients. The main manifestations are craniofacial birth defects, bone and joint symptoms, ocular abnormalities, and hearing loss. Stickler syndrome may be revealed at birth (25% of cases) by a combination of cleft palate, retrognathism, and micrognathism known as Pierre Robin sequence, which may cause neonatal respiratory problems. The ocular abnormalities include severe myopia, abnormalities of the vitreous, and a high risk of retinal detachment (60% of cases), which may cause blindness (4% of cases). Severe hearing loss with onset in early childhood may impair performance at school. Osteoarthritis (75% of patients) with onset before 30 years of age is a severe manifestation that causes chronic hip and low back pain and functional impairments. Joint replacement surgery is often required. The risk associated with multiple anesthesias is highest in patients with craniofacial defects. The bone status may deserve to be evaluated, as the combination of genetic abnormalities and physical impairments may promote bone loss. Clinicians should be cognizant of Stickler syndrome so that they can detect the disease in patients and their family members, prevent functional impairments, organize a multidisciplinary management strategy, and arrange for genetic counseling.

TNF alpha antagonist therapy and safety monitoring.

OBJECTIVES: To develop and/or update fact sheets about TNFα antagonists treatments, in order to assist physicians in the management of patients with inflammatory joint disease. METHODS: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development and/or update of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of chronic inflammatory diseases, such as rheumatoid. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Société Francaise de Rhumatologie. Each fact sheet was revised by several experts and the overall process was coordinated by three experts. RESULTS: Several topics of major interest were selected: contraindications of TNFα antagonists treatments, the management of adverse effects and concomitant diseases that may develop during these therapies, and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA and SpA, initiation and monitoring of TNFα antagonists treatments, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information. CONCLUSION: These TNFα antagonists treatments fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on these therapies. They will be available continuously at www.cri-net.com and updated at appropriate intervals.

Computed microtomography of bone specimens for rapid analysis of bone changes associated with malignancy.

Breast and prostate cancers are specially metastasizing to bone. Metastases from breast cancer usually exhibit a mixed osteolytic/osteosclerotic aspect, with osteolysis predominating. Osteosclerosis is a common finding in prostatic cancer although osteolysis occurs within the sclerotic lesions. B-cell malignancies (lymphoma, myeloma) are also associated with marked osteolysis. Histopathological examination of bone biopsies was used for the diagnosis of malignancies and, prior to embedding, microcomputed tomography (microCT) was done on the bone specimens. Patients (247) who presented either a bone metastasis, an overt myeloma, a lymphoma or a monoclonal gammopathy of undetermined significance were studied. All patients had a bone biopsy studied by 2D histomorphometry for the histopathology. During the fixation time, the bone cores were analyzed by microCT. On the 3D reconstructed models provided by microCT, signs of osteolysis/osteosclerosis were searched: excess of bone resorption, focal disorganization of microarchitecture, bone metaplasia, osteosclerosis. A strong agreement was obtained between histomorphometry and microCT results using Cohen's kappa test (kappa = 0.713). MicroCT identified excess bone resorption on trabecular surfaces when eroded surfaces were >10.5% by histomorphometry. MicroCT failed to identify some patients with smoldering myeloma or some lymphomas with microresorption. MicroCT data are obtained within 4 hr and suggest the malignant invasion of bone marrow when excess of bone resorption/formation is obtained. MicroCT can be used in the immediate postbiopsy period making possible a fast identification of malignancy. However these signs are not specific and must be confirmed by histopathological analysis.

Whipple's disease diagnosed during biological treatment for joint disease.

OBJECTIVES: Increased susceptibility to infections is among the main safety concerns raised by biological agents. We describe five cases of Whipple's disease diagnosed during treatment with biological agents. METHODS: We retrospectively identified five cases of Whipple's disease diagnosed between 2003 and 2009 in patients treated with TNFalpha antagonists in five French hospitals. RESULTS: Five patients (four male; mean age: 50.4 years; range: 38-67) underwent biological therapy according to prior diagnoses of rheumatoid arthritis (n=2), ankylosing spondylitis (n=2), or spondyloarthropathy (n=1). Biological therapy failed to control the disease, which responded to appropriate antibiotics for Whipple's disease. Retrospectively, clinical symptoms before biological therapy were consistent with Whipple's disease. All five patients had favorable outcomes (mean follow-up, 29 months [13-71]). CONCLUSIONS: Biological therapy probably worsened preexisting Whipple's disease, triggering the visceral disorders. Whipple's disease must be ruled out in patients with joint disease, as patients with this spontaneously fatal condition should not receive immunosuppressive agents.

Tocilizumab: therapy and safety management.

OBJECTIVES: To develop fact sheets about tocilizumab, in order to assist physicians in the management of patients with inflammatory joint disease. METHODS: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The 20 experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of RA. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Société Francaise de Rhumatologie. Each fact sheet was revised by several. experts and the overall process was coordinated by three experts. RESULTS: Several topics of major interest were selected: contraindications of tocilizumab; the management of adverse effects and concomitant diseases that may develop during tocilizumab therapy; and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: Several topics of major interest were selected: contraindications of tocilizumab; the management of adverse effects and concomitant diseases that may develop during tocilizumab therapy; and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA, initiation and monitoring of tocilizumab therapy, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information. CONCLUSION: These tocilizumab fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on tocilizumab therapy. They will be available continuously at www.cri-net.com and updated at appropriate intervals.

Abatacept therapy and safety management.

OBJECTIVES: To elaborate a how-to-use abatacept material intended to help physicians in the management of patients with inflammatory diseases treated with this drug in routine practice. METHODS: 1) Selection of the relevant domains by a rheumatologists' panel; 2) Search for published evidence in each domain; 3) Elaboration of the clinical tool guide with a 3-level gradation of evidence (evidence-based medicine EBM, official recommendations and expert's opinion). The experts were 11 academic rheumatologists with a large experience in prescribing abatacept and in managing rheumatoid arthritis. They were all members of the CRI (Club Rhumatismes et Inflammation), a section of the French Rheumatology Society dedicated to the inflammatory rheumatic diseases. Each fact sheet was reviewed by two other experts; 4) Regular updating based on medical literature and postmarketing surveillance data. RESULTS: Four domains were considered relevant: abatacept contraindications, management of side effects or associated diseases appearing during abatacept treatment, management of "practical situations" such as surgery or pregnancy, physician and patient information. After the literature analysis and discussion during an experts' meeting, a consensus was reached on: a pre-treatment checklist aimed at searching abatacept contraindications; a what-to-do document when facing side effects or associated diseases (autoimmune pathology, bacterial or viral infections, cardiovascular diseases, intolerance to abatacept, solid or haematological malignancy) or "practical situations" (surgery, pregnancy, vaccination, travel, drug-drug interactions); an example of standard information letter to be addressed to the attending physician (rheumatologist and general practitioner); an example of standard information letter to be addressed to the patient. CONCLUSION: Based on both an EBM approach and an expert's opinion approach, this abatacept clinical tool guide should provide assistance to all physicians attending patients treated with abatacept. For a better implementation in clinical practice, this tool guide will be available online at www.cri-net.com and regularly updated.

Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary Sjögren's syndrome.

OBJECTIVE: To investigate the safety and efficacy of rituximab (RTX) for systemic symptoms in patients with primary Sjögren's syndrome (pSS), and changes in B cell biomarkers. PATIENTS AND METHODS: The records of 16 patients with pSS according to the American European consensus group criteria were reviewed retrospectively. RESULTS: Patients, all women, had a median age of 58.5 (range 41-71) years and a disease duration of 9.5 (range 0-25) years. RTX was prescribed for lymphoma (n = 5), refractory pulmonary disease with polysynovitis (n = 2), severe polysynovitis (n = 2), mixed cryoglobulinaemia (n = 5), thrombocytopenia (n = 1) and mononeuritis multiplex (n = 1). The median follow-up duration was 14.5 (range 2-48) months. Three patients experienced adverse events, including one mild serum sickness-like reaction with the presence of human antichimeric antibodies. Efficacy of treatment was observed in 4 of 5 patients with lymphomas and in 9 of 11 patients with systemic involvement. Dryness was improved in only a minority of patients. Corticosteroid dose was reduced in 11 patients. RTX induced decreased rheumatoid factor, gamma-globulin and beta2-microglobulin levels, and the level of B cell activating factor of the tumour necrosis factor family (BAFF) increased concomitantly with B cell depletion. Five patients were re-treated, with good efficacy and tolerance, except for one with probable serum sickness-like reaction. CONCLUSION: This study shows good efficacy and fair tolerance of RTX for systemic features. In addition, RTX allows for a marked reduction in corticosteroid use. Except for BAFF, the level of which increases, serum B cell biomarker levels decrease after taking RTX. Controlled trials should be performed to confirm the efficacy of RTX in pSS.