[Life-threatening flare of an underlying «paraneoplastic¼ dermatomyositis in a patient with lung adenocarcinoma treated with anti-PD-1 pembrolizuma]. / Poussée sévère d'une dermatomyosite pré-existante chez une patiente avec un adénocarcinome pulmonaire traité par pembrolizumab, un anti-PD-1.

Dermatomyositis is an autoimmune disease mainly characterized by muscle and skin involvement. Its association with cancer is known but the term «paraneoplastic¼ remains debated. We report here the case of a 71-year-old woman with a new diagnosis of dermatomyositis with, at the same time, the discovery of a lung adenocarcinoma. Lung cancer was treated with pembrolizumab, an immune checkpoint inhibitor directed against the "Programmed cell Death protein 1" (PD-1) receptor. Three weeks later, the patient presented a severe flare of dermatomyositis. Administration of intravenous corticosteroids and infliximab were ineffective. Intravenous immunoglobulins were then administered, followed by subcutaneous methotrexate, with a progressive positive evolution. Flares of pre-existing autoimmune diseases are observed under immune check point inhibitors, even when the evolution of the cancer is favourable. These immune-related adverse events are often «mild to moderate¼ and severe immune related side effects are not more frequent when the patient has a pre-existing autoimmune disease. Treatment can be maintained in the majority of cases. However, as demonstrated in this clinical case, although immune checkpoint inhibitors are not contraindicated in autoimmune diseases, the presence of myositis requires special attention given the potential severity of flares.

: La dermatomyosite est une maladie auto-immune principalement caractérisée par une atteinte musculaire et cutanée. Son association avec le cancer est connue, mais le terme «paranéoplasique¼ reste débattu. Nous rapportons ici le cas d'une patiente de 71 ans avec un nouveau diagnostic de dermatomyosite et, au même moment, la découverte d'un adénocarcinome pulmonaire. La néoplasie pulmonaire a été traitée par pembrolizumab, un inhibiteur des points de contrôle immunitaire dirigé contre le récepteur «Programmed cell Death protein 1¼ (PD-1). Trois semaines plus tard, la patiente présentera une poussée sévère de dermatomyosite, ne répondant pas à la corticothérapie intraveineuse ni à l'infliximab. Des immunoglobulines intraveineuses sont alors administrées, suivies de méthotrexate sous-cutané, avec une évolution progressivement positive. On observe des poussées de maladies auto-immunes préexistantes sous inhibiteurs de points de contrôle immunitaire, même quand l'évolution néoplasique est favorable. Ces effets secondaires immuno-induits sont souvent «légers à modérés¼ et on n'observe pas plus de manifestations indésirables «sévères¼ lorsque le patient présente une maladie auto-immune pré-existante. Le traitement peut être maintenu dans la majorité des cas. Toutefois, comme démontré dans ce cas clinique, bien que les inhibiteurs de points de contrôle immunitaire ne soient pas contre-indiqués en cas de maladie auto-immune, la présence d'une myosite nécessite une attention particulière vu la gravité potentielle des poussées.

[Remarkable medical advances in rheumatology : may be ]. / Une révolution thérapeutique en rhumatologie : oui, mais .

The development of new drugs is a significant activity in a university hospital that favors access to therapeutic novelties to patients. Rheumatology, whose drug armamentarium was poor in the 1980s, has benefited from the huge progresses of immunology in the 1980-1990s, allowing a therapeutic revolution in whom the academic hospital of Liège (CHU Liège) has been strongly implicated. First protocols with anti-TNF-? monoclonal antibodies have been applied in 1997. Sixty-one protocols have been initiated in rheumatoid arthritis, 12 in ankylosing spondylitis, 10 in psoriatic arthritis, 9 in systemic erythematosus lupus, 3 in giant cell arteritis, 1 in polymyalgia rheumatica, 5 in osteoarthritis and 4 in osteoporosis. Potential and pitfalls will be discussed disease by disease and also by drug categories. The balance remains globally positive, but remission is far from be reached.

La recherche clinique médicamenteuse est une activité importante dans un hôpital universitaire. Elle valide des nouveautés thérapeutiques et fait bénéficier les patients de traitements novateurs bien avant leur mise sur le marché. La rhumatologie est une discipline dont l'arsenal thérapeutique était pauvre dans les années 1980, et les immenses progrès de l'immunologie, réalisés entre 1980 et 1995, lui ont permis de vivre une véritable révolution thérapeutique à laquelle notre service a amplement participé. C'est en 1997 que les premiers traitements par anticorps monoclonaux anti-TNF-? (les traitements dits biologiques) ont été utilisés au CHU de Liège. Soixante et une études seront initiées dans la polyarthrite rhumatoïde, 12 dans la spondylarthrite ankylosante, 10 dans la polyarthrite psoriasique, 9 dans le lupus érythémateux disséminé, 3 dans l'artérite temporale de Horton, une dans la pseudopolyarthrite rhizomélique, une dans la sclérodermie, 5 dans l'arthrose, 4 dans l'ostéoporose. Les espoirs et les déceptions observées dans les différentes indications, et avec les différentes molécules, sont analysées. Le bilan est globalement positif, mais les résultats encore insuffisants que pour arriver au concept de rémission.

Rituximab prescription patterns and efficacy in the induction treatment of ANCA-Associated Vasculitis in a Belgian multicenter cohort.

Introduction: The RAVE trial has revolutionized induction treatment of anti-neutrophil cytoplasmic antibodies (ANCA)-Associated Vasculitis (AAV)by demonstrating the non-inferiority of rituximab (RTX) compared with cyclophosphamide.Objectives: We studied AAV patients' characteristics, RTX prescription practices and efficacy in AAV induction treatment in four Belgian university hospitals. The patient population, selected according to the Belgian reimbursement criteria, was relatively homogeneous and comparable to the one of RAVE trial.Methods: 57 patients, receiving RTX as AAV induction therapyfrom May 2014 to June 2017 were enrolled in an observational retrospective multicenter trial involving four Belgian university hospitals. We focused on the type of AAV, ANCA specificity, prescriber's specialty, used reimbursement criteria, organ involvements, severity of the flares and finally RTX efficacy in AAV induction treatment by considering the RAVE primary (complete remission without prednisone) and secondary (complete remission with prednisone <10 mg) outcomes at 6, 12, 18 and 24 months.Results: 66.7% of the patients reached complete remission with prednisone <10 mg at 6 months, 55.3% at 12 months, 40% at 18 months and 25% at 24 months. The rates of complete remission without steroids were very low at 6, 12, 18 and 24 months. The rates of relapses were high between 18 and 24 months. Conclusions: Our results confirm those of RAVE regarding complete remission rates with prednisone <10 mg/day, in a 'real-life' cohort of patients selected according to data of RAVE trial. The high prevalence of relapses - especially after 18 months - underlines the need to optimize maintenance treatment after an induction treatment with RTX..

[Pattern of biological changes in interstitial lung diseases]. / Comment j'explore Les modifications biologiques dans les pathologies infiltrantes pulmonaires.

Interstitial lung diseases (ILD) are a part of a vast and heterogeneous clinicopathological entity. The work-up have to rule out a granulomatosis or a secondary cause, before making the diagnosis of an idiopathic ILD. The etiological diagnosis is based on a multidisciplinary approach integrating a network of clinical and paraclinical datas. If the diagnosis remains unclear, a lung biopsy is suggested with a transbronchial approach (mainly cryobiopsy) or with a surgical approach (video-assisted thoracoscopy). This review article mainly describes the biological analyses that contribute to explore ILDs.

Les pathologies infiltrantes diffuses pulmonaires (PID) font partie d'une entité clinico-pathologique vaste et hétérogène. L'enjeu de la mise au point est d'exclure une granulomatose ou une étiologie secondaire, qu'elle soit de cause connue ou inconnue, avant de conclure à une PID idiopathique. Le diagnostic étiologique repose sur une approche multidisciplinaire intégrant un faisceau d'arguments issus de l'évaluation clinique et paraclinique. En cas de doute diagnostique, une biopsie pulmonaire est proposée par voie endotrachéale de type cryobiopsie ou par voie chirurgicale vidéo-assistée. Cette revue de littérature met principalement en exergue les éléments à rechercher d'un point de vue biologique chez un patient atteint d'une PID.

[Acute respiratory distress revealing antisynthetase syndrome]. / Détresse respiratoire aiguë révélatrice d'un syndrome des antisynthétases.

Antisynthetase syndrome is a clinical entity characterized by specific anti-aminoacyl-tRNA-synthetase antibodies usually associated with inflammatory myopathy and interstitial lung disease. The classic presentation of the pathology is the pulmonary interstitium involvment, wich commonly determines the global prognosis. The subsequent diagnosis of antisynthetase syndrome in patients with acute respiratory distress syndrome (ARDS) is unusual, even more so when a veino-veinous (VV) extracorporeal membrane oxygenation (ECMO) is required. This article presents a clinical case of antisynthetase syndrome with severe ARDS successfully treated with immunosuppressive agents and ECMO.

Le syndrome des antisynthétases (SAS) est une pathologie multi-systémique auto-immune rare caractérisée par un trépied diagnostique associant la présence d'auto-anticorps anti-aminoacyl-ARNt synthétase, une myopathie inflammatoire et une pneumopathie interstitielle diffuse. L'atteinte pulmonaire parenchymateuse est la plus fréquemment rencontrée et détermine, de manière presque systématique, le pronostic global de la pathologie. L'identification d'un syndrome des antisynthétases dans le décours d'un syndrome de détresse respiratoire aigüe (SDRA) est rare, d'autant plus lorsque la mise en place d'un système d'oxygénation par membrane extracorporelle (ECMO) veino-veineuse (VV) est requise. Cet article présente un cas de SAS avec SDRA sévère, traité avec succès par immunosuppresseurs et ECMO.

[Brain abcesses associated with a systemic infection by Nocardia Farcinica]. / Abcès cérébraux a Nocardia Farcinica dans le cadre d'une infection systémique.

The prevalence of nocardia infections is increasing because of both improved detection laboratory techniques and a higher number of immunosuppressed patients. We report the case of a patient with brain abcesses resulting from nocardia farcinica cerebral dissemination associated with lung infection, endocarditis and ocular lesions for which we suspected a similar origin. This case gives the opportunity to discuss the main issues of these infections and the current therapeutic guidelines.

La prévalence des infections à nocardia est en augmentation depuis plusieurs années en raison, d'une part, de l'amélioration des techniques de détection de ces germes en laboratoire et, d'autre part, d'un nombre accru de patients immunodéprimés. Nous rapportons ici l'histoire d'un patient porteur d'une infection multifocale à Nocardia Farcinica associant des abcès cérébraux, une infection pulmonaire, une endocardite et une atteinte ophtalmique. Ce cas permet de discuter les principales caractéristiques de ces infections, ainsi que les recommandations thérapeutiques actuelles.

[Rituximab (MabThera): a new therapy for ANCA vasculitis]. / Le médicament du mois. Rituximab (MabThera): nouveau médicament dans les vascularites associées á ANCA.

Three recently published randomized studies have demonstrated the efficacy of rituximab in the induction and maintenance therapy of ANCA vasculitis. This is a major advance since these types of vasculitis entail a high morbity and mortality.

[The management of systemic lupus erythematosus with biological therapies]. / Traitement du lupus érythémateux dissémine par les médicaments biologiques.

The efficacy and safety of targeted biological therapies have been analyzed in patients suffering from systemic lupus erythematosus. In renal lupus, infliximab has shown prolonged improvement of the renal function after the induction period (small open studies), whereas abatacept had no significant efficacy (randomised controlled study). In renal and non renal lupus, rituximab did not confirm its efficacy in two randomised controlled studies. In non renal lupus, epratuzumab has shown efficacy in a phase IIb. Belimumab at the high posology of 10 mg/kg has also shown significant efficacy in two large randomised controlled studies.

[Rhupus: when rheumatoid arthritis meets lupus]. / Le rhupus: à la frontière entre polyarthrite rhumatoïde et lupus érythémateux disséminé.

There exists diseases in rheumatology fulfilling classification criteria for either rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). They are called "rhupus". We retrospectively analyzed the data base "GLIMS" of the CHU de Liège from the starting date of november 2005 until april 2011 to identified those patients that were positive for the anti-sDNA antibody marker of SLE and for the anti-CCP antibody, marker of RA. Fourteen patients were identified and two other patients were added, one suffering from SLE, and the other from RA, and likely to be rhupus. Of the 16 patients analyzed, 9 were real RA with anti-dsDNA antibodies induced by anti-TNF-alpha therapies. Seven were candidates to be rhupus and 6 were retained. They were all women, with a median age of 51 years and in addition were all anti-SS-A antibody positive.

[Genetic and environmental interactions on the development of rheumatoid arthritis]. / Interactions de la génétique et de l'environnement sur le développement de la polyarthrite rhumatoïde.

Rheumatoid arthritis (RA) more and more becomes a syndrome, rather than a disease, with genetic, hormonal and environmental influences, among which smoking and the microbiota generate focused interest. The shared epitope and PTPN22 loci are associated with RA, and, particularly, with the "classical" form with anti-citrullinated peptide antibodies (ACPA) and IgM-rheumatoid factor (IgM-RF) positivity. Pregnancy is associated with a--temporary--remission of RA. Epidemiological studies have shown that oral contraception, parity and hormonal replacement therapy influence the severity of RA, and, this is still discussed, its incidence. Smoking is the first environmental factor strongly associated with RA, specifically with the shared epitope and with ACPA. The study of the microbiota is a novel emerging field that will help us to better understand patterns and evolution of RA.

[Targeted therapy in inflammatory disease: cytokines]. / Thérapies ciblées en rhumatologie: les cytokines.

Summarizing 15 years of therapeutic development of a discipline into a few lines is not an easy thing to do. There are many potential targets involved in the inflammatory of auto-immune diseases. Due to the development of biotherapies the choice has become larger, and it is now possible to target practically any molecule (cytokine, chemokine or surface receptor for example). Cytokines represent the first example of therapeutic target that played a major role in the revolution of our discipline. The first part of presentation will focus on the pro-inflammatory cytokines (TNFalpha, and interleukines 1 and 6). We shall then, detail the development of a new cytokinic target: BLyS (B lymphocyte stimulator) whose role in the autoimmune diseases appeared recently.

[Pregnancy and systemic lupus erythematosus: compatible?]. / Lupus erythémateux systémique et grossesse: incompatibles?

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease that predominantly occurs in women of childbearing age. The risk of obstetric complications in lupus parturients is significant. In addition, pregnancy may be associated with flares of the disease requiring immunosuppressive therapy. For these reasons, SLE pregnancies are considered high risk and involve careful collaboration of the obstetrician and rheumatologist. Through the latter and medical advances including a better and better understanding of the binomial mother-child, most pregnancies end in a success.

[Biological therapies in rheumatology]. / Les traitements biologiques en rhumatologie.

Biological therapies consisting of monoclonal antibodies and soluble receptors have revolutionized the care of rheumatologic patients. These therapies ensued from a better understanding of the physiopathology of rheumatologic disorders. Most of the latter have been concerned: rheumatoid arthritis (for about 10 years), psoriatic arthritis and ankylosing spondilitys (for more or less five years). Rheumatology was among the first disciplines to make use of these advances; it continues to benefit from the results of intense research efforts. These developments request from clinicians an increased expertise in immunology.

[Biological therapy of inflammatory diseases]. / Le traitement biologique des maladies inflammatoires à médiation immune. Le cas de la dermatologie et de la rhumatologie.

The pathophysiology and the treatment of diseases with clinical presentation so different as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and psoriasis vulgaris have been revolutionized by the discovery of common pro-inflammatory effector mechanisms involving TNF-alpha and by the use of targeted therapies, the anti-TNF-alpha antibodies. In the past 10 years, our experience has helped several hundreds of patients who were treated with novel drugs, years before they became routinely available. In parallel tools of metrology were developped that can now be applied to the routine patient. Lastly, clinical research on these new drugs has also generated derived research works allowing the university hospital to satisfactorilly fullfil its specific missions.