Rheumatoid Arthritis: Lioté H

Lioté H. · Service de Pneumologie et réanimation respiratoire, Hôpital Tenon, Paris, France. · Rev Mal Respir. · Pubmed #19107015 No free full text.

Abstract: The occurrence of tuberculosis (TB) in patients treated with immunosuppressive drugs (ISD) is an old problem that has been highlighted by cases occurring in patients using anti-TNFalpha drugs. After a brief review of anti-tuberculosis immunity to highlight the immunosuppressant targets, we show how an epidemiological approach allows the control of risk in patients with drug-induced immunosuppression. The assessment and the control of this risk are usually complicated by underlying immunosuppressant disease, co-morbidities, associated drugs and local disease prevalence. Steroid therapy in systemic diseases and ISD protocols in graft rejection prevention illustrate this problem particularly well. The management strategy adopted to combat anti-TNF related tuberculosis in rheumatoid arthritis (RA) has allowed these biases to be avoided. The incidence of TB in RA has been recorded in some national databases (USA, Spain). A four fold increase was registered after the introduction of anti-TNF agents in 2001 which could be considered as the true risk of the drug. Several national health agencies proposed guidelines to screen and prevent TB risk in these patients. Their effectiveness was confirmed by the incidence of TB returning the level prior to the introduction of these agents. Recommendations could be improved by using interferon-gamma screening tests and a better benefit/risk prophylaxis. They should be observed and if possible extended to new and other ISD.

Lioté H. · Service de Pneumologie et réanimation respiratoire, Hôpital Tenon, APHP, Paris, France. · Rev Mal Respir. · Pubmed #18971804 No free full text.

Abstract: INTRODUCTION: Lung disease is the most frequent and among the most severe extra-articular manifestation of rheumatoid arthritis (RA). Several interesting advances have been made in recent years in our understanding of this respiratory disease. STATE OF ART: 1. The induction of BALT responsible for follicular lymphoid infiltrates has been demonstrated in the wall of respiratory bronchioles. These lymphoid infiltrates are similar to synovial and skin cellular infiltrates and secrete specific markers of RA (citrullinated proteins). These data strongly suggest a common pathogenic mechanism for RA in the joints and in other sites, such as the lung. 2. Improvements in high resolution computed tomography (HR- CT) increased the sensitivity of diagnosis. CT evidence of pulmonary disease is present in 50% of RA patients, but only 10% of these patients have clinical symptoms. The different lung manifestations, frequently combined, have been clearly described: pulmonary nodules (20%); small airways disease (30%): bronchiolitis, bronchiolectasis, and bronchiectasis; diffuse interstitial pneumonia of various types (20%). 3. Predictors of progression and therapeutic response remain unknown. Therefore treatment is empirical and based on usual indications and on drugs used in idiopathic fibrosis and other connective tissue pulmonary pathologies. CONCLUSIONS: New biological drugs such as TNF blocking agents or anti CD20 antibody could be beneficial. Infections and drug-induced pneumonitis are not described in this review but must be considered systematically when an RA patient presents with lung involvement.

Lioté H. · Service de Pneumologie, Hôpital Tenon, Paris, France. · Rev Mal Respir. · Pubmed #15767955 No free full text.

Abstract: INTRODUCTION: Treatment of rheumatoid arthritis (RA) has changed with the release of more efficient disease-modifying anti-inflammatory drugs (DMARDs) and biologicals, such as methotrexate, leflunomide and TNF blockers, respectively. However they are prone to trigger potential pulmonary side effects. STATE OF KNOWLEDGES: Diffuse interstitial pneumonitis with alveolar lymphocytosis are induced by methotrexate. This drug increases also the risk of opportunistic infections (Pneumocyctis carinii) and of delayed lymphomas. Many intracellular bacterial infections, about 80 cases of diffuse pneumonitis, and rare vasculitis are attributable to leflunomide. PERSPECTIVES: The TNF blocking agents (infliximab, etanercept and adalimumab) trigger immunization and consequently, rare type I and III hypersensitivity pneumonitis, serological lupus-like reactions usually without any clinical manifestations. Indeed the risk of infection with intracellular agents remains the first concern. Several hundreds of cases of pulmonary and non pulmonary tuberculosis (TB) have been described. They present as disseminated forms, with pulmonary manifestations present in half cases; of note, other sites are atypical, namely meningitis, lymph node, and digestive involvement. Pathological diagnosis can be difficult since granulomas are sparse or absent. Therefore TB can be lethal because of delayed diagnosis and treatment. CONCLUSION: To prevent this major risk when using TNF blockers, the French agency AFFSAPS recommends to screen and treat susceptible patients such as latent tuberculosis. Specifically, antituberculous drugs have to be started three weeks before anti-TNF agents. During biological therapy, physicians must regularly look for usual and unusual symptoms of TB. When TB is diagnosed, anti -TNF agents have to be discontinued, probably definitively, and appropriate antituberculosis treatment started in order to achieve an uneventful course.

Devouassoux G, Cottin V, Lioté H, Marchand E, Frachon I, Schuller A, Béjui-Thivolet F, Cordier JF, Anonymous00082. · Hospices civils de Lyon, Centre Hospitalier Lyon Sud, Service de Pneumologie, Pierre-Bénite, Université de Lyon, France. · Eur Respir J. · Pubmed #19129282 No free full text.

Abstract: The characteristics of patients with rheumatoid arthritis (RA) who develop obliterative bronchiolitis characterised by severe airflow obstruction have been hitherto poorly investigated. A retrospective study of 25 patients with RA and functional evidence of obliterative bronchiolitis (forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) <50% and/or residual volume (RV)/total lung capacity (TLC) >140% predicted) was conducted. Patients (mean+/-SD age 64+/-11 yrs) included 17 never-smokers and eight ex-smokers (10.5+/-5.4 pack-yrs). The diagnosis of RA preceded respiratory symptoms in 88% of cases. Dyspnoea on exertion was present in all patients and bronchorrhea in 44%. High-resolution computed tomography findings included: bronchial wall thickening (96%), bronchiectasis (40%), mosaic pattern (40%), centrilobular emphysema (56%), and reticular and/or ground-glass opacities (32%). Pulmonary function tests showed: FEV(1) 41+/-12% pred, FEV(1)/FVC 49+/-14%, FVC 70+/-20% pred, RV 148+/-68% pred and RV/TLC 142+/-34% pred. Lung biopsy, available in nine patients, demonstrated constrictive, follicular and mixed bronchiolitis. Patients were followed for 48.2+/-49 months. Treatment was poorly effective. Chronic respiratory failure occurred in 40% of patients, and four patients died. Obliterative bronchiolitis associated with rheumatoid arthritis is a severe and under-recognised condition leading to respiratory failure and death in a high proportion of patients.