[Not Available]. / Traitement médicamenteux chez la femme transplantée avec un projet de grossesse : à propos de deux cas de transplantation pulmonaire et cardio-pulmonaire.

Advances in lung transplantation allow the women of childbearing age to consider becoming mothers. When planning to become pregnant, a therapeutic drug management of immunosuppressive drugs and associated therapies is required. It must take into account teratogenic and fetotoxic drugs, as well as pharmacokinetic changes encountered during pregnancy. Increasingly data are currently available on the management of immunosuppressive drugs and associated therapies during pregnancy. We report the case management of drug therapy before and during pregnancy in two patients after a lung or heart-lung transplantation. To prevent the emergence of complications for mother and child, a literature review has been necessary to manage drug therapies of each patient.

[Utilisation of immunosuppressants in the prevention of a graft versus host reaction: report by the SFGM-TC]. / Immunosuppresseurs dans la prévention de la réaction du greffon contre l'hôte : rapport de la SFGM-TC.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here we report our recommendations regarding the use of immunosuppressive treatment in the prevention of graft versus host disease: report by the SFGM-TC.

[Management of chronic hand eczema]. / Prise en charge de l'eczéma chronique des mains.

The management of hand eczema, more readily called chronic hand dermatitis, is complex. This heaviness is related not only to the disease itself by its different clinical forms but also the multiplicity and diversity of etiological factors, triggering / maintaining or aggravating factors. The repeated therapeutic failures are ransom of incorrect information about the disease and its environment, a lack of clarity in the prescription and duration of treatment in general too short. The reference treatment is high potency topical steroids with or without occlusion for 4-8 weeks followed by alitretinoin 30 mg / day for at least 3-6 months with a monthly lipid and liver monitoring and mandatory monthly pregnancy test in women of childbearing. Associated measures and patient education are the cornerstones of successful treatment. Other alternative treatments such as phototherapy, methotrexate, cyclosporin, mycophenolate mofetil etc. can be considered in case of resistance or for clearing followed by topical treatments.

Illness representation and treatment beliefs in liver transplantation: an exploratory qualitative study.

BACKGROUND: The objective of this study was to gain detailed insight concerning liver transplanted patients' representations about transplantation, graft rejection and immunosuppressive drugs to adapt the educational follow-up. PATIENTS AND METHODS: Semi-structured interviews were conducted with 8 patients. Each interview was recorded and fully transcribed. The verbatim was first coded according to the themes of the Common Sense Model and an inductive approach for the remaining text. RESULTS: Transplantation is perceived both as a recovery and a new chronic condition. Participants feel powerless in the face of the risk of graft rejection. This risk is perceived as out of control as it is not associated with specific symptoms and external causes. The individual knowledge gained about transplantation relies on real-life experience shared between patients. Many participants feel anxiety. It responds to stress caused by immunosuppressant medication intake, routine check-ups, potential side effects and chronicity of immunodepression. Messages stressing the importance of the tacrolimus in the medication therapy are strengthened by a pre-discharge pharmaceutical consultation. DISCUSSION AND CONCLUSIONS: This study suggests that healthcare providers should systematically seek to determine illness representations to optimize the educational follow-up. The patient education program for liver transplanted patients should include three types of intervention: individualized education, behavioral intervention and psychological support. It should provide a support for stress management and acceptance of the new chronic condition. The involvement of a clinical pharmacist is relevant.

[Anti-Neutrophil Cytoplasmic Antigens (ANCA)-associated vasculitis: Current therapeutics]. / Vascularites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA) : actualités thérapeutiques.

ANCA-associated vasculitis brings together three diseases, granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. This group of diseases has benefited over the last 3 decades from major therapeutic advances both in terms of therapeutic strategies and availability of new drugs, mainly for targeted therapies. Treatments, whether conventional or not, include an induction phase followed by a maintenance phase. Induction treatment today poses few problems. It is essentially based on the combination of corticosteroids and rituximab or cyclophosphamide. Remission is achieved in less than 6 months and maintenance treatment, preventing relapses, is then started. We showed that the best maintenance treatment was rituximab, surpassing the efficacy of methotrexate or azathioprine. During this phase, corticosteroid therapy is stopped or given at a very small dose. In Eosinophilic Granulomatosis with Polyangiitis (GEPA), the strategy is slightly different and there is a lack of prospective trials to demonstrate the benefits of rituximab or mepolizumab (anti-IL5) in inducing remission. Regarding maintenance treatment, prolonged corticosteroid therapy (orally and/or inhaled) is often necessary to control asthmatic disease. Only mepolizumab has shown its ability to prevent relapses and reduce the dose of corticosteroids controlling asthma. The current questions posed by maintenance treatment are its duration which could be variable and adapted to the risk of relapse and the risks induced by prolonged immunosuppression, particularly infectious.

Title: Vascularites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA) : actualités thérapeutiques. Abstract: Les vascularites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA) réunissent trois maladies, la granulomatose avec polyangéite, la polyangéite microscopique et la granulomatose éosinophilique avec polyangéite. Ce groupe de maladies a bénéficié au cours des trois dernières décennies d'avancées thérapeutiques majeures tant en termes de stratégies thérapeutiques que de mise à disposition de nouveaux médicaments, essentiellement pour des thérapies ciblées. Les traitements, conventionnels ou non, comprennent une phase d'induction suivie d'une phase d'entretien. Le traitement d'induction pose aujourd'hui peu de problèmes. Il est essentiellement fondé sur l'association corticoïdes et rituximab ou cyclophosphamide. La rémission est obtenue en moins de 6 mois et un traitement d'entretien, préventif des rechutes, est alors initié. Nous avons montré que le meilleur traitement d'entretien était le rituximab, surpassant l'effet du méthotrexate ou de l'azathioprine. Durant cette phase, la corticothérapie est arrêtée ou donnée à très petite dose. Dans la granulomatose éosinophilique avec polyangéite (GEPA), la stratégie est un peu différente et les essais prospectifs manquent pour démontrer l'intérêt du rituximab ou du mépolizumab (anti-IL5) en induction de la rémission. En traitement d'entretien, une corticothérapie prolongée (par voie orale et/ou inhalée) est souvent nécessaire pour contrôler la maladie asthmatique. Seul le mépolizumab a montré sa capacité à prévenir les rechutes et à réduire la dose de corticoïdes contrôlant l'asthme. Les questions actuelles que pose le traitement d'entretien sont notamment sa durée qui pourrait être variable et adaptée au risque de rechute et les risques induits par l'immunodépression prolongée, notamment infectieux.

[Pure red cell aplasia: Diagnosis, classification and treatment]. / L'érythroblastopénie : diagnostic, classification, traitement.

Pure red cell aplasia (PRCA) is a rare anemia characterised by profound reticulocytopenia caused by a marked reduction in bone marrow erythroblasts, without abnormalities in other blood lineages. Blackfan-Diamond anemia is an inherited ribosomopathy responsible for a hereditary form of PRCA. Acquired PRCA are separated in primary and secondary forms, including Parvovirus B19 infection, thymoma, lymphoproliferative disorders, autoimmune diseases (lupus) and drug-induced PRCA. The pathophysiology of PRCA is not fully understood and involves both humoral and T lymphocyte autoreactive cells. In Parvovirus B19-related PRCA, treatment is based on polyvalent immunoglobulins. Thymectomy for thymoma is mandatory but results in prolonged remission in a limited number of cases. The therapeutic strategy is based on expert opinion: corticosteroids in monotherapy provide few sustained responses. The choice of an additional immunosuppressant drug is guided by the presence of an underlying disease. In most cases, cyclosporine A is the first choice providing the best response rate but requires a concentration monitoring (150 to 250 ng/mL). The second choice is cyclophosphamide in large granular lymphocyte leukaemia. Sirolimus (mTOR inhibitor) seems to be a promising option especially in refractory cases. Transfusion independence is the main objective. If the patient receives numerous red blood cell transfusions (> 20 packs), iron overload assessment is crucial to initiate an iron chelation. A retrospective and prospective national cohort (EPIC-F) has been set up and is now available to include each case of PRCA to improve the knowledge of this disease and to optimize the therapeutic strategy.

[Neurological involvement of sarcoidosis: current diagnostic and therapeutic strategies]. / Atteinte neurologique de la Sarcoïdose : stratégies diagnostiques et thérapeutiques actuelles.

Neurosarcoidosis (NS) is a rare but severe form of sarcoidosis. NS is associated with significant morbidity and mortality. Mortality is about 10% at 10 years with more than 30% of patients who have a significant disability. The most frequent features are cranial neuropathy (the facial and optic nerve most commonly affected), cranial parenchymal lesions, meningitis, spinal corn abnormalities (20-30%) and more rarely peripheral neuropathy (approximately 10-15%). The challenge of diagnosis is to eliminate other diagnoses. Atypical presentations should make to discuss the need for cerebral biopsy in order to highlight the presence of granulomatous lesions while eliminating alternative diagnosis. Therapeutic management is based on corticosteroid therapy and immunomodulators. There are no comparative prospective study to allow us to define the first-line immunosuppressive treatment and the therapeutic strategy in refractory patients. Conventional immunosuppressants such as methotrexate, mycophenolate mofetil and cyclophosphamide are commonly used. Data on the efficacy of anti-TNFα (including infliximab) in refractory and/or severe forms are increasing during the last ten years. Additional data is necessary to assess their interest in first line in patients with severe involvement and a significant risk of relapse.

[Benefit of therapeutic drug monitoring of immunosuppressants and immunomodulators in the management of autoimmune diseases]. / Intérêt des dosages pharmacologiques d'immunosuppresseurs et immunomodulateurs dans la prise en charge des maladies autoimmunes.

The pharmacokinetics of drugs, such as immunosuppressants, justify the need of measuring their blood concentrations in order to adjust their dosage. Therapeutic Drug Monitoring (TDM) of ciclosporin, tacrolimus and mycophenolate mofetil has shown its benefit particularly in the management of renal transplantees, in order to prevent graft rejection. When prescribed in autoimmune diseases, their pharmacokinetic variability and the variability of clinical response would justify TDM in practice. TDM may be useful in systemic lupus, for hydroxychloroquine, in order to monitor patient compliance. Despite insufficient data in the literature, for mycophenolate mofetil, TDM would permit to maintain clinical remission in adults and children with lupus nephritis, as well as in mucosal pemphigoid and idiopathic nephrotic syndrome in children. Studies are still necessary to validate the thresholds and TDM conditions. For azathioprine, TPMT phenotyping is recommended before prescription. For methotrexate, tacrolimus and ciclosporin, data are still sparse on the benefit of TDM, although it may improve tolerance to tacrolimus in lupus. Finally, for infliximab, in case of loss of response in maintenance, TDM may be proposed in parallel with detection of anti-drug antibodies.

[Cardiac sarcoidosis: Diagnosis, prognosis and therapeutics]. / Sarcoïdose cardiaque : stratégies diagnostiques et thérapeutiques actuelles.

Sarcoidosis is a systemic granulomatous disease characterized by pulmonary involvement in most patients and more rarely by extrapulmonary involvement such as ocular, skin, salivary, lymph nodes and joints damages. Neurological and cardiac involvements are uncommon but are associated with increased morbidity and mortality. Cardiac sarcoidosis affects 5 to 20% of patients depending on the studies and autopsy studies even report cardiac involvement in 25% of sarcoidosis patients. This review aims to summarise main data on the diagnostic value of the different imaging techniques in cardiac sarcoidosis and to also detail the management of these patients who require a multidisciplinary approach.

Interactions of radiation therapy with common and innovative systemic treatments: Antidiabetic treatments, antihypertensives, lipid-lowering medications, immunosuppressive medications and other radiosensitizing methods.

The invention and approval of innovative anticancer therapies in the last decade have revolutionized oncology treatment. Radiotherapy is one of the three traditional pillars in oncology treatment with surgery and systemic therapies. Some standard-of-care combinations of chemoradiotherapy widened the therapeutic window of radiation, while some other chemotherapies such as gemcitabine caused unacceptable toxicities when combined with radiation in lung cancers. Fast-paced progress are specially focused on immunotherapies, targeted-therapies, anti-angiogenic treatment, DNA repair inhibitors, hormonotherapy and cell cycle inhibitors. New anticancer therapeutic arsenals provided new possibilities of combined oncological treatments. The interactions of the radiotherapy with other systemic treatments, such as non-anticancer immunomodulatory/immunosuppressive medications are sometimes overlooked even though they could offer a real therapeutic benefit. In this review, we summarize the new opportunities and the risks of historical and novel combined therapies with radiation: non-anticancer immunomodulatory/immunosuppressive drugs, systemic reoxygenation, new therapies such as nanoparticles and SMAC mimetics. Key biological mechanisms, pre-clinical and available clinical data will be provided to demonstrate the promising opportunities in the years to come.

[Pregnancies after kidney transplant: What are the consequences for the cognitive development of children?] / Grossesses après une transplantation rénale : quelles conséquences sur le développement cognitif des enfants ?

Thanks to medical progress in the field of kidney transplantation, the quality of life of women suffering from kidney failure has greatly improved in recent years. As a result, their fertility has increased significantly and pregnancies are now more frequent and safer. Kidney transplantation requires constant immunosuppressive treatment during pregnancy. These products can cross the placental barrier and their prescription is therefore subject to rigorous medical monitoring. There are many environmental factors that can affect the development of the child during pregnancy and affect its subsequent cognitive development. The possible impact of these immunosuppressive treatments on the medium- and long-term intellectual development of the children concerned is as yet little documented. Even if the available data are reassuring, the methodologies used in this work nevertheless raise questions and legitimize the development of complementary research. The aim of this review is to propose a synthesis of existing data in this field and to open up avenues for future research.

[Immunosuppressive therapy in severe or chronic pediatric uveitis: Review of the literature]. / Les immunosuppresseurs dans les uvéites pédiatriques sévères ou chroniques : revue de la littérature.

Immunosuppressants are prescribed for pediatric uveitis in cases of severe involvement affecting the prognosis for vision or life, in cases of recurrent or chronic uveitis to achieve corticosteroid sparing, or in cases of corticosteroid resistance. Immunosuppressants used in children include antimetabolites (methotrexate, mycophenolate mofetil, azathioprine), cyclosporine, tacrolimus, and biologics, including infliximab, adalimumab, anakinra, canakinumab, and tocilizumab. The mechanisms of action and indications of the various immunosuppressants are described in this review.

[Vaccine recommendations for children with idiopathic nephrotic syndrome]. / Recommandations vaccinales pour les enfants avec un syndrome néphrotique idiopathique.

The specific treatment of idiopathic nephrotic syndrome is based on corticosteroid therapy and/or steroid-sparing immunosuppressive agents in children who are steroid-dependant or frequent relapsers (60-70 %). Patients have an increased infectious risk not only related to the disease during relapses (hypogammaglobulinemia and urinary leakage of opsonins) but also to treatments (corticosteroids or immunosuppressive agents) in period of remission. Vaccination is therefore particularly recommended in these patients. Potential vaccine risks are ineffectiveness, induction of vaccine disease and relapse of idiopathic nephrotic syndrome. Only live vaccines expose to the risk of vaccine disease: they are in general contra-indicated under immunosuppressive treatment. The immunogenicity of inactivated vaccines is reduced but persists. The immunogenic stimulus of vaccination may in theory trigger a relapse of the nephrotic syndrome. Nevertheless, this risk is low in the literature, and even absent in some studies. The benefit-risk ratio is therefore in favor of vaccination with respect to the vaccination schedule for inactivated vaccines, with wide vaccination against pneumococcus and influenza annually. Depending on the context and after expert advice, immunization with live vaccines could be discussed if residual doses/levels of immunosuppressive treatments are moderate and immunity preserved.

ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission induction and maintenance.

Treatment of vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA) (AAVs) has evolved dramatically in recent years, particularly since the demonstration of rituximab efficacy as remission induction and maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. In 2013, the French Vasculitis Study Group (FVSG) published recommendations for its use by clinicians. Since then, new data have made it possible to better specify and codify prescription of rituximab to treat AAVs. Herein, the FVSG Recommendations Committee, an expert panel comprised of physicians with extensive experience in the treatment and management of vasculitides, presents its consensus guidelines based on literature analysis, the results of prospective therapeutic trials and personal experience.

Clinical and therapeutic features of pediatric Vogt-Koyanagi-Harada disease.

PURPOSE: To analyze clinical, therapeutic and prognostic features of pediatric Vogt-Koyanagi-Harada (VKH) disease. MATERIAL AND METHODS: This retrospective study included 16 eyes of 8 children diagnosed with VKH disease followed at a teaching hospital over a 10 year period. Diagnosis was based on the revised criteria of VKH disease. All data were analyzed using SPSS® software. RESULTS: There were 62.5% girls and 37.5% boys. The mean age (years) was 14.6±4.4. The mean follow-up (months) was 38.7±28.7. The mean initial visual acuity (VA) (LogMAR) was 1.4 with 68.8% of eyes presenting with severe visual loss at admission. The median time (days) required for resorption of the serous retinal detachment was 10 [8.25-25]. Extraocular signs were present in 62.5% of cases. The mean time until initiation of treatment was 25.6 days. 62.5% of patients received corticosteroids alone, and 37.5% of patients received a combination of corticosteroids and immunosuppressive therapy. Final VA was 0.4 [0.1-2.3]. In our study, the time until consultation, low initial VA and recurrences were statistically associated with severe visual loss (P≤0.05). CONCLUSION: Life expectancy in pediatric cases of VKH disease justifies the early initiation of immunosuppressive treatment or even biological therapy to achieve better steroid sparing and preserve visual function.

[Radiotherapy and immune suppression: A short review]. / Radiothérapie et immunosuppression : synthèse de la littérature.

The management of patients undergoing immunosuppressive agents is really challenging. Based on precaution principle, it seems mandatory to stop immunosuppressive (or immunomodulating) agents during radiation. Yet, it is impossible in grafted patients. It is possible in patients with autoimmune disease, but in this case, the autoimmune disease might modify patient's radio-sensitivity. We provide a short review about the safety of radiotherapy in grafted/auto-immune patients. The literature is limited with data coming from outdated case-report or case-control studies. It seems that radiotherapy is feasible in grafted patients, but special dose-constraints limitations must probably be considered for the transplant and the other organs at risk. There is very little data about the safety of radiotherapy, when associated with immunomodulating agents. The most studied drug is the methotrexate but only its prescription as a chemotherapy (high doses for a short period of time) was reported. When used as an immunomodulator, it should probably be stopped 4 months before and after radiation. Apart from rheumatoid arthritis, it seems that collagen vascular diseases and especially systemic scleroderma and systemic lupus erythematous feature increased radio-sensitivity with increased severe late toxicities. Transplanted patients and collagen vascular disease patients should be informed that there is very little data about safety of radiation in their case.

[Multifocal tuberculosis complicated by a macrophage activation syndrome: about two cases]. / Tuberculose multifocale compliquée d'un syndrome d'activation macrophagique: à propos de deux cas.

Macrophage activation syndrome (MAS) is a rare disorder due to an inappropriate stimulation of macrophages in the bone marrow and in the lymphoid organs. It is defined based on clinical and cytohistological criteria as well as on laboratory tests. Primary syndrome can occur mostly in children or it can be secondary to different types of disorders: haematological, infectious diseases as well as different types of autoimmune diseases. Prognosis is poor, with a mortality rate of almost 50% from all causes. Treatment is based on specific treatment dependent upon the causative agent of the MAS and, in some cases, on etoposide, corticosteroids and immunogobulines, which should be administered at an early stage. MAS has been rarely described in association with tuberculosis. We here report two cases: an immunocompromised patient, the first case, an immunocompetent patient with multifocal tuberculosis complicated by macrophage activation syndrome, the second case. This study aims to emphasize on difficulty in treating macrophage activation syndrome associated with tuberculosis, on the need for an evaluation of benefit/risk ratio based on corticosteroid or immunosuppressant-related risk for developing immunosuppression, with possible worsening of tuberculosis.

[Eye and Behçet's disease]. / Œil et maladie de Behçet.

Behçet's disease is a chronic multisystem disorder characterized by relapsing inflammation for which the underlying histopathology is an occlusive vasculitis. The disease has a high prevalence in the Mediterranean region, Far and Middle Eastern countries. It is clinically characterized by oral and genital ulcerations, ocular inflammatory involvement, skin lesions, vascular involvement and numerous other systemic manifestations. Uveitis is by far the most common ocular manifestation of Behçet's disease. It typically presents in the form of relapsing-remitting panuveitis with retinal vasculitis that may result in severe visual loss. Management of Behçet's uveitis relies on corticosteroid therapy, conventional immunosuppressive drugs and biological agents and requires a close collaboration between ophthalmologist and internist. A better understanding of the auto-inflammatory process and of the role of cytokines implicated in the pathogenesis of Behçet's disease will enable researchers to develop more specific and effective therapy.

[Therapeutic strategy for the treatment of non-infectious uveitis proposed by an expert panel]. / Avis d'experts pour le traitement des uvéites non infectieuses.

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).