[Renal granulomatous nephritis: Histopathological point of view]. / Néphrite interstitielle granulomateuse : le point de vue du pathologiste.

Granulomatous interstitial nephritis (NIG) is a rare form of interstitial nephritis that can be related to acute or chronic clinical presentation. NIG is characterized by granulomas located to the renal interstitium and composed of either epithelioid histiocytes with giant cells and/or of foreign body reaction. The symptoms are unspecific and associate varying degrees of renal failure with abnormal urinanalysis. Extra-renal signs may point to systemic disease. Pathological examination from kidney percutaneous biopsy or surgical resection is required to assert NIG diagnosis and to guide the etiological research. The main causes of NIG are sarcoidosis, drug reactions, mycobacterial infections and crystalline nephropathies. Sarcoidosis is characterized by non-necrotic and well-formed giant cell epithelioid interstitial granulomas. Drug reactions have less well-defined granulomas with inconstant eosinophils. The presence of caseous necrosis within giant cell and epithelioid granulomas leads to infectious NIG diagnosis (tuberculosis and fungal infection). Identification of crystals within foreign body reaction can be improved by polarized light study. Xanthogranulomatous pyelonephritis and malakoplakia are rarer causes of NIG characterized by patches of histiocytes associated with inconstant giant cells. Differential diagnoses of NIG are represented by granulomatous reactions centered on glomeruli and vessels (vasculitis and emboli of cholesterol crystals). Less than 10% of NIG are idiopathic. The prognosis and the treatment vary according to the cause. The factors of poor renal prognosis are chronic irreversible tubulo-interstitial injury (tubular atrophy and interstitial fibrosis).

[What's new in internal medicine?]. / Quoi de neuf en médecine interne?

Taking advantage of the French annual dermatologic conference "Journées Dermatologiques de Paris" that took place in December 2015, this article highlights the latest clinical advances, which occurred in autoimmune, inflammatory and systemic diseases during the past year. Evaluations of new classifications, new prognostic factors, and significant results of clinical trials in such diseases are underlined. A special attention is given to the classifications of systemic lupus erythematosus and systemic sclerosis as well as the use of rituximab in idiopathic thrombocytopenic purpura or in the maintenance treatment of patients with anti-neutrophil cytoplasmic antibodies-associated vasculitis.

[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.

French recommendations for the management of non-infectious chronic uveitis.

This French National Diagnostic and Care Protocol (NDPC) includes both pediatric and adult patients with non-infectious chronic uveitis (NICU) or non-infectious recurrent uveitis (NIRU). NICU is defined as uveitis that persists for at least 3 months or with frequent relapses occurring less than 3 months after cessation of treatment. NIRU is repeated episodes of uveitis separated by periods of inactivity of at least 3 months in the absence of treatment. Some of these NICU and NIRU are isolated. Others are associated with diseases that may affect various organs, such as uveitis associated with certain types of juvenile idiopathic arthritis, adult spondyloarthropathies or systemic diseases in children and adults such as Behçet's disease, granulomatoses or multiple sclerosis. The differential diagnoses of pseudo-uveitis, sometimes related to neoplasia, and uveitis of infectious origin are discussed, as well as the different forms of uveitis according to their main anatomical location (anterior, intermediate, posterior or panuveitis). We also describe the symptoms, known physiopathological mechanisms, useful complementary ophthalmological and extra-ophthalmological examinations, therapeutic management, monitoring and useful information on the risks associated with the disease or treatment. Finally, this protocol presents more general information on the care pathway, the professionals involved, patient associations, adaptations in the school or professional environment and other measures that may be implemented to manage the repercussions of these chronic diseases. Because local or systemic corticosteroids are usually necessary, these treatments and the risks associated with their prolonged use are the subject of particular attention and specific recommendations. The same information is provided for systemic immunomodulatory treatments, immunosuppressive drugs, sometimes including anti-TNFα antibodies or other biotherapies. Certain particularly important recommendations for patient management are highlighted in summary tables.

[Peripheral neuropathies during systemic diseases: Part II (vasculitis)]. / Neuropathies périphériques au cours des maladies de système : partie II (vascularites).

Primary systemic vasculitides, mainly of the small and medium-sized vessels, are frequently associated with peripheral neuropathies. When the disease is already known, the appearance of a neuropathy should suggest a specific injury, especially when associated with other systemic manifestations. Conversely, when neuropathy is inaugural, close collaboration between neurologists and internists is necessary to reach a diagnosis. A standardized electro-clinical investigation specifying the topography, the evolution and the mechanism of the nerve damage enables the positive diagnosis of the neuropathy. Several elements orient the etiological diagnosis and allow to eliminate the main differential diagnosis: non systemic vasculitic neuropathy. The existence of associated systemic manifestations (glomerular or vascular nephropathy, interstitial lung disease, intra-alveolar hemorrhage, ENT involvement…), biological markers (ANCA, cryoglobulinemia, rheumatoid factor), and invasive examinations allowing histological analysis (neuromuscular biopsy) are all useful tools for.

[Gynecologic vasculitis revealing a giant cell arteritis: A case report and literature review]. / Vascularite des artères utérines révélant une artérite à cellules géantes : cas clinique et revue de la littérature.

INTRODUCTION: Genital vasculitis are uncommon. They may be localized or be a manifestation of a systemic vasculitis. We report a patient with a giant cell arteritis (GCA) involving uterine arteries and a literature review on genital vasculitis. CASE REPORT: A 65-year-old woman was referred to a gynecologist for a cervical intraepithelial neoplasia (CIN) associated with an ovarian mass. An unexpected diagnosis of GCA involving small to medium sized uterine arteries was made through the anatomopathological analysis while the patient was asymptomatic. Two weeks later, she presented typical cranial symptoms of giant cell arteritis (GCA). PET-scanner confirmed the diagnosis of GCA with an involvement of the ascending aorta, and the axillary and the subclavian arteries. CONCLUSION: Gynecologic vasculitis are rare and usually an asymptomatic manifestations of GCA.

[Parvovirus B19 infections in adults]. / Infection de l'adulte à Parvovirus.

Acute Parvovirus B19 (PVB19) infection is responsible for erythema infectiosum in children and non-specific polyarthralgias in immunocompetent adults associated with skin lesions and rarer manifestations (hepatic, neurological, cardiac or nephrological). In immunocompromised patients, cytopenias are more frequent and in some cases, viremia persists and is responsible for PVB19 chronic infection. PVB19 is responsible for pure red cell aplasia during chronic hemolytic diseases. Acute PVB19 infection is a differential diagnosis of some autoimmune diseases and has been suspected to be a trigger for some autoimmune diseases because of its ability to promote the emergence of autoimmune markers. Mechanisms of molecular mimicry, induction of apoptosis and activation of enzymes have been demonstrated, explaining in part the production of autoantibodies during infection. However, the demonstration of a causal relationship in the triggering of autoimmune disease remains to be done. This review provides a synthesis of the PVB19 infection clinical data in adults with a particular focus on these links with autoimmunity.

[Pathogenesis of ANCA-associated vasculitides in 2021: An update]. / Pathogénie des vascularites associées aux ANCA en 2021 : mise au point.

Anticytoplasmic neutrophil antibodies (ANCA)-associated vasculitis (AAV) are rare systemic immune-mediated diseases characterized by small vessel necrotizing vasculitis and/or respiratory tract inflammation. Over the last 2 decades, anti-MPO vasculitis mouse model has enlightened the role of ANCA, neutrophils, complement activation, T helper cells (Th1, Th17) and microbial agents. In humans, CD4T cells have been extensively studied, while the dramatic efficacy of rituximab demonstrated the key role of B cells. Many areas of uncertainty remain, such as the driving force of GPA extra-vascular granulomatous inflammation and the relapse risk of anti-PR3 AAV pathogenesis. Animal models eventually led to identify complement activation as a promising therapeutic target. New investigation tools, which permit in depth immune profiling of human blood and tissues, may open a new era for the studying of AAV pathogenesis.

[ANCA vasculitis preceded by isolated joint manifestations. Report of two cases and literature review]. / Vascularites à ANCA précédées d'une atteinte articulaire isolée. À propos de deux cas et revue de la littérature.

INTRODUCTION: Joint manifestations of ANCA (antineutrophil cytoplasmic antibody) associated vasculitis (AAV) are extremely common in the progression of systemic damages. However, the joint involvement is rarely isolated. The diagnosis and the treatment are difficult in this particular situation and few data are available on the topic. CASE REPORT: We have observed two cases of joint manifestation revealing AAV we are going to describe here. The evolution toward a more severe disease raises the question of the treatment managing. The place of the ANCA research in relation to other immune tests is also discussed. CONCLUSION: Isolated joint manifestations of ANCA vasculitis are rare but can lead to a delay in diagnosis. ANCA vasculitis should be considered in seronegative symmetrical polyarthritis by looking for ANCA in a second line biological test. Methotrexate is the first treatment option to be considered. In case of insufficient response or failure, rituximab seems an interesting option in this context.

[ANCA and anti-MBG double-positive vasculitis: An update on the clinical and therapeutic specificities and comparison with the two eponymous vasculitis]. / Vascularites double-positives ANCA et anti-MBG : mise au point sur les spécificités cliniques et thérapeutiques et comparaison aux deux vascularites éponymes.

Double-positive vasculitis with anti-polynuclear cytoplasm (ANCA) and anti-glomerular basement membrane (GBM) antibodies is a rare entity of systemic vasculitis defined by the presence of ANCA and anti-GBM antibodies. The gradual accumulation of clinical and therapeutic data shows the usefulness of identifying and differentiating this entity from the two vasculitis respectively associated with the isolated presence of each of these two antibodies. Indeed, the double-positive ANCA and anti-GBM vasculitis appears to associate the characteristics of the demography and the extra-renal and pulmonary involvement of the ANCA-associated vasculitis on the one hand, and of the histological type and severe renal prognosis of the anti-MBG vasculitis on the other hand, with the renal involvement which is the only involvement consistently observed in double-positive vasculitis. The aim of this focus is to describe the epidemiological, clinico-biological, histological and prognostic characteristics of this entity, in light of recent literature and ongoing therapeutic changes in the two eponymous vasculitis.

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.

[Drug-induced vasculitis]. / Vascularites médicamenteuses : à propos d'une série de 13 cas.

INTRODUCTION: Drug-induced vasculitis is reported in almost 10-20 % of vasculitis. Several drugs may be incriminated in their occurrence. Our study aimed to study the epidemiological, clinical, histopathological and evolutionary characteristics of drug-indced vasculitis from a series of cases and to specify the different drugs involved. METHODS: We conducted a retrospective study during the period from January 2006 to December 2015 from the cases notified to the regional pharmacovigilance center of Sousse, Tunisia. The diagnosis was established according to the criteria proposed by the group of the American college of rheumatology (ACR). RESULTS: Our study included thirteen cases of drug-induced vasculitis over a ten-year period, with an mean incidence of 1.3 new cases per year. Mean age of patients was 40.84 years. The mean delay from the treatment onset was 14.46 days with extremes ranging from 5 days to six weeks. Most patients had pure skin involvement. Association with other extracutaneous complaints was present in five cases. Cutaneous biopsy was performed in all patients showing a pathological pattern of leukocytoclastic vasculitis, associated with fibrinoid necrosis, extravasation of red blood cells and allergic capillaritis. The outcome was favorable for all patients. The offending drugs in our series were amoxicillin, pristinamycin, rifampicin, fluconazole, metformin, glimepiride, phenobarbital, gabapentin, fenofibrate, ibuprofen, allopurinol, rituximab and tinzaparin. CONCLUSION: Anamnestic, clinical, biological and histopathological findings allow the early recognition of drug-induced vasculitis. Adequate treatment prevents systemic spreading and a worse prognosis.

Treatment of ANCA-associated vasculitides: Certainties and controversies. / Traitement des vascularites à ANCA : certitudes et controverses.

Antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides are necrotizing vasculitis affecting small blood vessels and include granulomatosis with polyangiitis (formerly Wegener's), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome). Diagnosis of ANCA-associated vasculitis is based on the clinical presentation, ANCA positivity directed against proteinase 3 or myeloperoxidase, and when possible on histological evidence of vasculitis. Evolution of ANCA-associated vasculitides without treatment leads constantly to death. Under treatment, overall survival has considerably improved during the last decades, and the long-term prognosis is mainly conditioned by disease sequelae, relapses and treatment-related toxicity, especially infections and cardiovascular events. Treatment is based on an induction phase followed by maintenance. During the induction phase, glucocorticoids must be associated in most cases with cyclophosphamide or rituximab. Maintenance phase, aiming at preventing relapses particularly frequent with ANCA directed against proteinase 3, is based on rituximab, but optimal dose and duration has still to be determined.

[Anorectal manifestations in systemic diseases]. / Manifestations ano-rectales des maladies systémiques.

Numerous systemic diseases (vasculitis, connective tissue disease or sarcoidosis) can display an involvement of the perianal skin, the rectum and/or the anus. Such knowledge is important in order to treat these complications specifically when possible. Lesions of the anorectum arising from systemic diseases can sometimes cause perforations in the peritoneal cavity (if concerning the higher portion of the rectum) and/or fistulization to the anal margin. Differential diagnosis, mostly infectious or inflammatory (Crohn's disease) must be ruled out in every case. Other systemic diseases can display specific manifestations as this is the case in scleroderma which can lead to anal incontinence. Despite the relative rarity of these manifestations, their ignorance would forbid global management of these complex diseases. It should thus be detected in each consultation and a regular follow-up must be provided with a proctologist and/or a gastroenterologist when needed.

[Kidney disease care for the elderly]. / Spécificités des néphropathies du sujet âgé.

In our aging population, kidney disease management needs to take into account the frailty of the elderly. Standardized geriatric assessments can be proposed to help clinicians apprehend this dimension in their daily practice. These tools allow to better identify frail patients and offer them more personalized and harmless treatments. This article aims to focus on the kidney diseases commonly observed in elderly patients and analyze their specific nephrogeriatric care modalities. It should be noticed that all known kidney diseases can be also observed in the elderly, most often with a quite similar clinical presentation. This review is thus focused on the diseases most frequently and most specifically observed in elderly patients (except for monoclonal gammopathy associated nephropathies, out of the scope of this work), as well as the peculiarities of old age nephrological care.

[Retinal vasculitis and systemic diseases]. / Vascularites rétiniennes et maladies systémiques.

Retinal vasculitis (RV) is an inflammation of retinal blood vessels that can be associated with uveitis or be isolated, and can induce vascular occlusion and retinal ischemia. Visual acuity can be severely affected in case of macular involvement or neovessel formation. The diagnosis relies on fundoscopy and fluorescein angiography. Systemic diseases may be associated with RV, the most frequently encountered are Behçet's disease, sarcoidosis or multiple sclerosis, all predominantly associated with venous involvement, whereas systemic lupus erythematosus and necrotizing vasculitis are less frequently observed and predominantly associated with arterial or mixed vasculitis. Treatments are usually aggressive in order to preserve a good visual acuity and to reduce retinal inflammation and chronic ischemia. Steroids, immunosuppressive drugs, retinal laser photocoagulation, intravitreal anti-VEGF injections are usual treatments and more recently, anti-TNFalpha monoclonal therapeutic antibodies have been shown to be very successful.

[Myelitis as a differential diagnosis of spinal cord tumors]. / Diagnostic différentiel des tumeurs intramédullaires : les myélites.

BACKGROUND AND PURPOSE: Myelitis is common, related to multiple aetiologies and constitute in some cases a differential diagnosis for spinal cord tumors. Our objective was to review the clinical and paraclinical aspects of the main aetiologies of myelitis. METHODS: These aetiologies will be reviewed based on data not only from the scientific literature but also from our personal experience reported in different cohorts of patients. RESULTS: Multiple sclerosis is the main cause of partial myelitis in young adults. Neuromyelitis optica is now a well-known specific entity frequently revealed by a transverse myelitis. The diagnosis is based on specific criteria, including the presence of anti-NMO antibodies. In our cohorts, approximately 12 % of the patients admitted for an acute or subacute myelitis were related to infections, mainly of a viral origin. Patients with myelitis must be screened for systemic diseases. As for neuromyelitis optica, patients with myelitis related to a systemic disease should be treated in emergency. Acute myelitis is sometimes the first symptom of a systemic lupus or of a sarcoidosis. Sjögren syndrome can mimic myelitis related to primary progressive multiple sclerosis. Spinal cord imaging contributes greatly to defining the myelitis. CONCLUSION: In most cases, a routine clinical and paraclinical examination and the follow-up of the patients can contribute to establishing the aetiology of a myelitis.

[Usefulness of imaging in large vessel vasculitis]. / Place de l'imagerie dans l'évaluation des vascularites de gros vaisseaux.

The imaging is essential for the diagnosis of large vessels arteritis, in order to assess the persistent inflammation of arterial lesions, to evaluate the treatment response and search the vascular complications. In patients with giant cell arteritis (GCA), the aortitis could be suspected in 2 situations: in the presence of general constitutional symptoms or systematic screening of aortitis in patient with confirmed GCA. The frequency of aortitis varies according to the imaging method and could be detected in 40 % of patients with computed tomography and MRI, and approximately in 60 % with FDG-PET/CT. The clinical and prognostic value of systematic detection of aortitis during the GCA remains to be determined. In Takayasu arteritis, imaging is performed to diagnose the large vessels vasculitis, to determine the arterial lesions extension to assess the persistent inflammation of arterial lesions. The persistent vascular inflammation should be suspected in the presence of arterial thickness, of arterial enhancement, a parietal edema and increased arterial FDG uptake (>liver). However, the value of these parameters and the threshold remain to be determined. Thus, the value of FDG-PET/CT and MRI and of parameters used to characterize the persistent arterial inflammation should be further studied.

[Alveolar hemorrhage]. / Hémorragie intra-alvéolaire.

Alveolar hemorrhage occurs relatively rarely and is a therapeutic emergency because it can quickly lead to acute respiratory failure, which can be fatal. Hemoptysis associated with anemia and pulmonary infiltrates suggest the diagnosis of alveolar hemorrhage, but may be absent in one third of cases including patients in respiratory distress. The diagnosis of alveolar hemorrhage is based on the findings of a bronchoalveolar lavage. The causes are numerous. It is important to identify alveolar hemorrhage due to sepsis, then separate an autoimmune cause (vasculitis associated with antineutrophil cytoplasmic antibody, connective tissue disease and Goodpasture's syndrome) with the search for autoantibodies and biopsies from readily accessible organs, from a non-immune cause, performing echocardiography. Lung biopsy should be necessary only in exceptional cases. If the hemorrhage has an immune cause, treatment with steroids and cyclophosphamide may be started. The indications for treatment with rituximab are beginning to be established (forms that are not severe and refractory forms). The benefit of plasma exchange is unquestionable in Goodpasture's syndrome. In patients with an immune disease that can lead to an alveolar hemorrhage, removing any source of infection is the first priority.

[Infectious events during the course of systemic necrotizing vasculitis: a retrospective study of 82 cases]. / Événements infectieux au cours des vascularites nécrosantes systémiques: étude rétrospective de 82 cas.

PURPOSE: The aim of this study was to assess the infections occurring in a series of 82 patients followed for a systemic necrotizing vasculitis and to determine potential risk factors. METHODS: We studied retrospectively the medical files of 23 Churg and Strauss syndrome, 18 periarteritis nodosa, 14 microscopic polyangiitis, and 27 granulomatosis with polyangiitis, over a 15-year period. Infection delay corresponded to the period from treatment to first infection or between two infections. RESULTS: A total of 61 patients developed 147 infections. Causal agent was identified in 70 cases, 42 were bacterial, 20 viral and 8 fungal. Bronchopneumonia was the most frequent infection (43 %). Sixty-two percent of infections occurred within 2 years after vasculitis diagnosis. Seven infections were major, requiring intensive care, with one infection-death related. Pneumocystis prophylaxis concerned 75 % of patients on cyclophosphamide. Significant factors reducing infection delay were initial hypergammaglobulinemia, hypoalbuminemia, lymphopenia, as well as cyclophosphamide and methotrexate treatment. Large quantities of corticosteroids, cyclophosphamide or azathioprine increased infection delay. This result underlines the early occurrence of infectious complications during vasculitis course. CONCLUSION: Infectious events occurring in systemic necrotizing vasculitis are frequent and occurs early in disease course, and could be prevented with simple prophylactic measures. Vasculitis relapse and infection share similarities and this require permanent clinical vigilance.