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HHV-8 is an oncogenic Gammaherpesvirinae discovered in 1994 during the HIV pandemic. It is the causative agent of Kaposi's sarcoma, and is also associated with the occurrence of several aggressive B lymphoproliferative disorders. Most of them occur in an immunosuppression setting, usually due to HIV infection. Multicentric HHV8-associated Castleman's disease and KSHV Inflammatory Cytokine Syndrome (KICS) are primarily reactive entities with prominent systemic features. They illustrate the cytokinic storm induced by HHV-8 in its cell host. On the other hand, HHV-8 can drive proliferation and lymphomagenesis of its plasmablastic cell host, and is associated with a risk to develop aggressive lymphomas with plasmacytic differenciation. Primary effusion lymphoma usually localizes in body cavities and may affect other extra-nodal sites ; its prognostic is poor. Diffuse large B-cell lymphoma HHV-8, NOS affect more commonly nodes and blood and evolve from infected cell of HHV-8 associated Castleman disease. On the contrary, germinotropic lymphoproliferative disorders presents mainly as localized adenopathy with indolent course, and show polyclonality. Histology plays a key role in distinguishing these different entities and need expert reviewing, especially since they may be associated with each other. Besides lymphoproliferative disorders, HHV8 is associated with various hematological manifestations. The aim of this review is to provide an update on the presentation, diagnosis, and management of immunologic and hematologic complications associated with HHV-8.

Common variable immunodeficiency disorders (CVID) are the most common symptomatic primary antibody deficiency in adults with an estimated prevalence of 1/25,000. The most frequent clinical manifestations are upper respiratory tract infections (including pneumonia, bronchitis, and sinusitis) predominantly with Streptococcus pneumoniae or H. influenzae. However, CVID are complicated in 20 to 30 % of cases of non-infectious manifestations which have been well characterized in recent years. Several complications can be observed including autoimmune, lymphoproliferative, granulomatous or cancerous manifestations involving one or more organs. These complications, mostly antibody-mediated cytopenias, are correlated with a decrease in the number of circulating switched memory B cells. Replacement therapy with polyvalent gammaglobulins has greatly improved the prognosis of these patients but it remains poor in the presence of digestive complications (especially in the case of chronic enteropathy and/or porto-sinusoidal vascular disease), pulmonary complications (bronchiectasis and/or granulomatous lymphocytic interstitial lung disease) and when progression to lymphoma. Much progress is still to be made, in particular on the therapeutic management of non-infectious complications which should benefit in the future from targeted treatments based on knowledge of genetics and immunology.

Common variable immunodeficiency disorders (CVID) are a heterogeneous group of conditions with hypogammaglobulinemia as the common denominator. These are the most common symptomatic primary immunodeficiency disorder in adults. Two different clinical forms are described: one group only develops infections, while a second includes (sometimes without infections, at least at the onset of disease course) a variety of non-infectious autoimmune, inflammatory, granulomatous and/or lymphoproliferative manifestations, sometimes revealing the disease and often observed in Internal Medicine. The international diagnostic criteria for CVID were updated in 2016 and are the subject of several comments in this general review. The recent use of new sequencing techniques makes it possible to better genetically define CVID. The identification of such a genetic disease makes it possible to treat pathophysiologically, in particular autoimmune and lymphoproliferative complications, with targeted treatments, sometimes used in other diseases. Determining a genetic disease in these patients also makes it possible to provide appropriate genetic counseling, and therefore to monitor mutated individuals, symptomatic or not.

Multirefractory immune thrombocytopenia (ITP) is defined by the absence of response to TPO receptor agonists, rituximab and splenectomy (or contraindicated or refused) and the need of treatment. The approach to multirefractory ITP must be systematic and firstly involves reconsidering the diagnosis. Inherited thrombocytopenia, lymphoid hemopathies and myelodysplastic syndrome are the main causes to be mentioned. Multirefractory ITP is often associated with secondary ITP with signs of clinical or biological autoimmunity, monoclonal gammopathy of undetermined significance and a poor response to corticosteroids. Therapeutic management is complex and is based on the combination of treatments. New treatments are being developed.

International audience; No abstract available

Azathioprine is widely used in internal medicine and frequently implicated in occurrence of adverse events. Among these adverse events the bone marrow suppression, a dose-related one, is the most serious because of is potential morbidity and mortality. Severe myelosuppression, associated with abnormal AZA metabolism, is linked to the thiopurine methyltransferase (TPMT) genetic polymorphism that results in a high variability of its activity with 89% of patients with a normal activity, 11% with an intermediate activity, and 0.3% with very low activity leading to a very high risk of bonne marrow suppression. TPMT status can be assessed prior to AZA treatment by measuring enzyme activity or genotyping techniques to identify patients for which the standard dose is not advisable. Furthermore, azathioprine metabolites monitoring is helpful for the follow up of patients, especially in therapeutic failure, to distinguish non-compliant patients from under-dosed, "shunters" or resistant patients.

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of angiogenesis associated with disabling epistaxis. Propranolol, a beta-blocker, exerts anti-angiogenic properties. In the retrospective study, nine of ten HHT patients receiving propranolol significantly improved their Epistaxis Severity Score. In the prospective study, after three months of propranolol treatment, the median duration of epistaxis per month significantly decreased as did the number of epistaxis episodes per month in 11 HHT patients. Tolerance of propranolol was quite satisfactory with only one hypotension among the overall 21 HHT patients. This article is protected by copyright. All rights reserved.

Introduction Le lupus engelure (LE), forme classique mais rare de lupus erythemateux chronique, n’a pas fait l’objet d’etudes specifiques recentes. Nous rapportons les caracteristiques cliniques, immunologiques et evolutives de 30 cas de LE. Materiel et methodes Il s’agissait d’une etude descriptive retrospective monocentrique incluant tous les patients adultes presentant un LE vus entre 2010 et 2019. Resultats Trente patients ont ete inclus, 29 femmes et 1 homme, d’âge median 52 ans (22–87). Les lesions cutanees siegeaient sur les mains (n = 26) et les pieds (n = 23), dans 20 cas de facon simultanee, associees a une atteinte du nez et des oreilles dans 2 cas. Une patiente presentait une localisation nasale isolee. Un autre type de lupus cutane etait associe au LE dans 15 cas (50 %), lupus discoide le plus souvent (n = 10), lupus erythemateux cutane subaigu (n = 4) et lupus aigu (n = 1). Il existait des anticorps (AC) antinoyaux dans 24 cas/30, de 1/160e a 1/1600e. Des AC anti-SSA chez 15 patients (SSA 52Kd et SSA 60Kd : 10 ; SSA 60Kd : 5), des AC anti-SSB dans 5 cas, des AC anti-ADN chez 3 patients et des AC anti-Sm/RNP 3 fois egalement. La recherche d’AC anticardiolipines et de cryoglobuline etait negative chez les patients testes (15 et 10 respectivement). Une diminution de C3 et/ou de C4 etait notee chez 6 patients. La duree mediane de suivi etait de 5 ans (1–15). Six patientes ont presente un lupus erythemateux systemique (LES) : 2 fois en meme temps que le LE, dans 3 cas apres le diagnostic de LE (apres 5, 8 et 9 ans) et dans un cas, deux ans avant l’apparition du LE. Associee a la protection contre le froid, c’est l’association hydroxychloroquine-inhibiteurs calciques, prescrite chez 6 patientes, qui a ete le traitement le plus efficace. Discussion Le LE se caracterise par des lesions papuleuses rouge violace, parfois hyperkeratosiques, souvent ulcerees, siegeant principalement sur les mains et les pieds, ressemblant a des engelures, tant sur le plan clinique qu’histologique, mais persistant en dehors de la saison froide. Comme dans les quelques series publiees incluant de 5 a 17 cas, nous avons note une forte predominance feminine et la presence frequente d’autres formes cutanees de lupus, en particulier un lupus discoide. Le LE est associe a un LES dans 20 % de nos cas, de 20 a 66 % dans les etudes de la litterature. La recherche des AC anti-SSA est positive chez 15 de nos patientes (50 %). A l’exception d’une etude dans laquelle ils sont presents chez 8 patients sur 9, ils sont, soit, non cherches, soit, presents dans moins de 1 cas sur 5 dans les autres etudes. Conclusion Ce travail confirme la plupart des donnees classiques sur le LE et souligne la frequence des AC anti-SSA dans cette forme de lupus cutane qui peut etre inclus dans le spectre des manifestations dermatologiques liees a ces AC.

Introduction Les atteintes faciales de la sclerodermie systemique (ScS) peuvent etre responsables d’une gene fonctionnelle importante, mais egalement esthetique qui n’est que peu ou pas prise en compte dans les echelles de qualite de vie (QV) comme le sHAQ (Scleroderma Health Assessment Questionnaire). Le questionnaire specifique « Burden of Face Affected » (BoFA) a ete elabore pour apprecier de facon rapide et reproductible le handicap lie aux manifestations cutanees faciales de la ScS. Les objectifs de cette etude etaient d’evaluer les correlations entre les signes cliniques objectifs et l’alteration de la QV liee a l’atteinte du visage, d’une part, et entre les questionnaires sHAQ et BoFA, d’autre part. Materiel et methodes Il s’agit d’une etude prospective monocentrique incluant des patients adultes vus entre fevrier et juillet 2019 pour une ScS avec des manifestations dermatologiques faciales de la maladie. Resultats Cent-sept patients ont ete inclus, majoritairement des femmes (n = 80), de 59 ans en moyenne. Quatre-vingt quatre patients (78,5 %) avaient des rides peribuccales, 78 (72,9 %) des telangiectasies, 76 (71 %) un amincissement des levres, 61 (57 %) une sclerose cutanee, 36 (33,7 %) des troubles pigmentaires et 26 (24,3 %) une disparition des plis frontaux. Le score de Rodnan modifie moyen du visage etait de 0,8/3. Le score BoFA moyen etait a 20 (±19,6) (0 : aucun impact ; 100 : impact majeur), significativement plus eleve chez les femmes (p = 0,024). En analyse multivariee, l’augmentation du score BoFA etait significativement associee au sexe feminin (p = 0,003), a la presence de telangiectasies (p = 0,028) et d’une sclerose cutanee (p = 0,001). Les femmes avaient une alteration de l’estime de soi et une gene liee au regard des autres plus importantes que les hommes (p Discussion L’atteinte faciale de la ScS, presente dans plus de 90 % des cas, est responsable d’un handicap esthetique important comme l’ont deja montre quelques etudes. Cependant les echelles de QV n’etaient pas specifiques des modifications du visage. Le questionnaire BoFA a permis de montrer que ce sont les femmes ayant des telangiectasies et/ou une sclerose faciale qui sont les plus genees. L’absence de correlation entre les scores sHAQ et BoFA suggere que le sHAQ n’est pas un bon outil pour evaluer specifiquement la QV liee au visage. En conclusion, l’evaluation de la QV liee a l’atteinte du visage de la ScS par un questionnaire specifique permet de proposer aux patients une prise en charge therapeutique personnalisee et d’en apprecier l’efficacite.

Azathioprine is widely used in internal medicine and frequently implicated in occurrence of adverse events. Among these adverse events the bone marrow suppression, a dose-related one, is the most serious because of is potential morbidity and mortality. Severe myelosuppression, associated with abnormal AZA metabolism, is linked to the thiopurine methyltransferase (TPMT) genetic polymorphism that results in a high variability of its activity with 89% of patients with a normal activity, 11% with an intermediate activity, and 0.3% with very low activity leading to a very high risk of bonne marrow suppression. TPMT status can be assessed prior to AZA treatment by measuring enzyme activity or genotyping techniques to identify patients for which the standard dose is not advisable. Furthermore, azathioprine metabolites monitoring is helpful for the follow up of patients, especially in therapeutic failure, to distinguish non-compliant patients from under-dosed, "shunters" or resistant patients.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a development disorder of the vasculature characterized by telangiectases and arteriovenous malformations in specific locations. Among monogenic disorders, it is one of the most common, though affected individuals are widely underdiagnosed. The most common features of this disorder, nosebleeds, and telangiectases on the lips, hands, and oral mucosa are often quite subtle. Mutations in at least five genes may result in hereditary hemorrhagic telangiectasia, but mutations in two genes (ENG and ACVRL1/ALK1) account for approximately 85% of cases. Optimal management requires understanding the specific clinical patterns of these vascular malformations, especially their locations and timing during life. Therapeutic modulation of angiogenesis may be an effective therapy.

Introduction The Bentall procedure is a cardiac surgery involving graft replacement of the aortic valve, aortic root and ascending aorta. Graft infection after Bentall's procedure (BGI) is infrequent but severe, and often difficult to diagnose and treat. Patients and Methods A retrospective cohort study was performed using the Bordeaux endocarditis database of adult patients admitted to the Bordeaux University Medical Hospital for BGI between 2008 and 2014. Published case reports were identified in the literature. Results We identified 10 BGI patients in the database and 13 in the literature. The majority of infections were late-onset (20/23) and occurred as a result of gram positive cocci bacterial infection (16/22). Detailed diagnoses of the described BGI were determined using echocardiography, computed tomography (CT) and positron emission tomography/CT (PET/CT). Labeled-leukocyte scintigraphy was not reported in any case. Prolonged antibiotic therapy and surgery were found to be the treatment of choice for BGI; however it was not always possible to perform a surgical intervention. Clinical relapses occurred even with a negative PET/CT, while PET/CT consistently positive for BGI occurred in the absence of clinical relapse. This suggests that the use of PET/CT for follow-up is questionable. Conclusion Diagnosis of BGI is difficult, due to the combination of clinical, biological, and radiological observations obtained through transesophageal echocardiography and CT. PET/CT is an alternative method to diagnosis BGI, but its impact on clinical management remains unclear. Current data suggests that if surgical replacement of the prosthesis is not possible, patients should be treated with prolonged antibiotic therapy.

Both intravenous and subcutaneous immunoglobulins are therapeutic modalities approved in various conditions, including primary and secondary immune deficiencies and autoimmune disorders. To date, immunoglobulins have more often been considered as a safe medication, with minor adverse effects such as hypertension, fever and chills, nausea, myalgia or headache. However, with the wider use of immunoglobulins in the treatment of autoimmune diseases, severe side effects have also been reported to occur in immunoglobulin-treated patients, especially anaphylaxis, aseptic meningitis, acute renal impairment, thrombotic events as well as haematological manifestations. This paper reviews all the potential adverse events related to immunoglobulin therapy and establishes a comprehensive guideline for the management of these events.

The human neurotropic JC virus (JCV) is responsible for progressive multifocal leukoencephalopathy (PML), an infectious demyelinating brain disease with major morbidity and mortality, usually refractory to treatment. We describe a PML in a 67-year-old woman with a destructive polyarthritis associated with anti-JO1 antibodies treated with corticosteroids. Although glucocorticoid therapy was maintained, administration of cidofovir improved the neurological condition. Our observation demonstrates the expanding clinical importance of JCV in systemic rheumatic diseases, particularly when immunosuppressive agents are used, and neurological symptoms or white matter changes on central nervous system imaging should arouse the suspicion of PML.

To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE).Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified.Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia.These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of hematopoietic stem cells. Somatic mutation in the phosphatidylinositol glycan class A (PIG-A), X-linked gene, is responsible for a deficiency in glycosphosphatidylinositol-anchored proteins (GPI-AP). The lack of one of the GPI-AP complement regulatory proteins (CD55, CD59) leads to hemolysis. The disease is diagnosed with hemolytic anemia, marrow failure and thrombosis. Thromboembolic complication occurs in 30% of patient after 10 years of follow-up and is the first event in one out of 10 patients. The two most common sites are hepatic and cerebral veins. These locations are correlated with high risk of death. Currently, these data are balanced with the use of a monoclonal antibody (Eculizumab), which has significantly improved the prognosis with a survival similar to general population after 36 months of follow-up. Anticoagulant treatment is recommended after a thromboembolic event but has no place in primary prophylaxis.

Hydroxyurea (HU) or hydroxycarbamide is an antimetabolite chemotherapy frequently used in the treatment of chronic myeloproliferative disorders. This treatment is usually well tolerated but a few cases of fever induced by the molecule have been reported in the literature. The aim of the study was to describe the clinical and biological characteristics of HU induced fever.We performed a cross sectional study of patients treated with HU and followed-up in an internal medicine department between 2006 and 2012. We added our cases of HU induced fever with those reported in the literature (Pubmed and Cochrane databases) since 1981.We identified 38 cases of HU induced fever, including our 4 cases. The mean age was 65±10.9 years and the sex-ratio 1/2. The fever appeared after a median duration of treatment of 21 days and was usually high (40°C) but clinically well tolerated. A biological inflammatory syndrome (CRP: 131±92 mg/L) was constant and one third of the patients also presented with hepatitis or lung disease. A probabilistic antibiotic treatment was introduced for 34% of the patients. For the half of the patients, HU-reintroduction test was performed, and was positive for all the patients but one. As soon as HU was withdrawn, the fever disappeared in a median of 24 hours.HU induced fever is unusual. Clinical presentation is very stereotyped. When this adverse effect is suspected, an infectious disease must first be ruled out. If infection is excluded, HU has to be stopped.

Resume Introduction Les proliferations cutanees primitives CD4+ CD56+ constituent une entite rare de description recente, remarquables par leur tropisme cutane primaire et un phenotype CD4+ CD56+ alors que les autres marqueurs B et T sont negatifs. Le nouveau cas rapporte illustre les particularites cliniques et evolutives de cette affection. Observation Un homme de 83 ans avait des lesions papulo-nodulaires infiltrees, ecchymotiques du tronc. La biopsie cutanee d’une lesion montrait une proliferation dermohypodermique de cellules CD3- CD4+ CD56+ CD43+. Il n’y avait pas d’atteinte medullaire, viscerale ou sanguine. Une polychimiotherapie de type CEOP permettait une remission complete apres six cures. Cependant apres quatre mois, les lesions cutanees reapparaissaient, associees a une atteinte sanguine. Apres une reponse initiale a une chimiotherapie de type DHAP, le malade decedait 3 mois plus tard. Discussion L’« agranular CD4+ CD56+ hematodermic neoplasm » est une entite distincte des lymphomes cutanes primitifs. Il s’agit d’une proliferation de cellules derivees de monocytes plasmocytoides predendritiques surexprimant les chaines legeres du CD123. L’histoire naturelle est marquee par un tropisme cutane initial avec des lesions ecchymotiques. Les polychimiotherapies sont inefficaces avec un echappement constant. Un espoir pourrait consister en l’utilisation d’un anticorps antiCD123 specifique des monocytes plasmocytoides.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a development disorder of the vasculature characterized by telangiectases and arteriovenous malformations in specific locations. Among monogenic disorders, it is one of the most common, though affected individuals are widely underdiagnosed. The most common features of this disorder, nosebleeds, and telangiectases on the lips, hands, and oral mucosa are often quite subtle. Mutations in at least five genes may result in hereditary hemorrhagic telangiectasia, but mutations in two genes (ENG and ACVRL1/ALK1) account for approximately 85% of cases. Optimal management requires understanding the specific clinical patterns of these vascular malformations, especially their locations and timing during life. Therapeutic modulation of angiogenesis may be an effective therapy.

Large granular lymphocyte leukemia (LGL) is a hematologic disorder characterized by a monoclonal expansion of large lymphocytes containing azurophilic granules with a T CD3(+)CD57(+) or Natural Killer (NK) CD3(-)CD56(+) phenotype. The World Health Organization (WHO) classification identifies three entities: the T LGL, the chronic lymphoproliferative disorder of NK-cells, and the aggressive NK-cell leukemia. T LGL and chronic lymphoproliferative disorder of NK-cells are indolent diseases frequently associated with cytopenias and a wide spectrum of auto-immune manifestations. Neutropenia can lead to recurrent bacterial infections, which represent an indication of initiating a treatment in most of the cases. Immunosuppressive therapies are usually used in this context. In contrast, aggressive NK-cell leukemia follows a fulminant course with a poor prognosis because patients are refractory to most of the treatments. There is now a considerable interest in the pathophysiology of the disease with the perspective of new therapeutic options.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiorgan involvement characterized by an immune response against nuclear components. SLE patients experience a waxing and waning disease course and exhibit a wide array of clinical manifestations, reflecting the systemic nature of the disease. Environmental triggers such as viruses are likely to act in the context of susceptibility genes, including genes involved in antigen/immune complex clearance, lymphoid signalling, or apoptosis, among several others, explaining why the pathogenesis of this disease remains largely uncovered. The abnormal activation of the innate immunity is central to SLE physiopathology. Dendritic cells activation and unabated secretion of IFN-alpha are the key features of the disease through their involvement in the capture and the presentation of nuclear material to the autoreactive adaptive arm (T and B lymphocytes) leading to the subsequent production of anti-nuclear autoantibodies. In this line, numerous studies have demonstrated the prominent role of immune complexes deposition throughout the body which directly can induce inflammation and tissue damage. However, animal models and recent human studies support the concept that other effector pathways including cytotoxic T-lymphocytes could be involved in SLE pathogenesis through their ability to migrate and/or target specifically different tissues. The aim of this review is not to provide a comprehensive review of the SLE pathophysiology but rather to give an overview of the immunological abnormalities associated to SLE. The treatments that are currently used or that are in development to fight against abnormal immune response in SLE will be detailed. The genetics of SLE is not the scope of this review.

Giant cell arteritis, a large-sized vessel vasculitis, may be associated with musculoskeletal proximal (polymyalgia rheumatica) or distal manifestations. A 68-year-old woman, who had inflammatory pelvic girdle pain, was diagnosed with giant cell arteritis and was successfully treated with corticosteroids. The magnetic resonance imaging and ultrasonography revealed a bilateral bursitis and pelvic girdle enthesopathy. Bursitis is the main anatomic lesion occurring in polymyalgia rheumatica and can be underlined by ultrasonography.

Autoimmune manifestations are common in splenic marginal zone lymphoma (SMZL) and are sometimes the presenting feature of the disease. Autoimmune cytopenia (anemia, thrombocytopenia) are the most frequently reported autoimmune conditions. However, other immunological manifestations may be associated with SMZL.We report a retrospective case series of six patients with SMZL associated with autoimmunity.Auto-immune manifestations were the presenting feature of lymphoma in four cases. Auto-immune manifestations included auto-immune cytopenia in three cases (two hemolytic anemia and one pancytopenia), thyroiditis in two cases, systemic lupus and Still's disease in one case each. Antinuclear antibodies were detected with a titre of 1/250 in three cases, and with a titre of 1/32,000 in the patient with systemic lupus. Testing for DNA antibodies was negative in all cases. Two patients had a circulating lupus anticoagulant, with portal venous thrombosis following splenectomy in one case. One patient had hypogammaglobulinemia. A monoclonal gammopathy was detected in three patients. All patients had spleen enlargement. Immunophenotyping of blood peripheral lymphocyte was typical in five out of the six cases. Bone marrow was infiltrated in five out of the six cases. Diagnosis was obtained by the combination of immunophenotyping and bone marrow histopathology in five cases, and by splenic histopathology in the remaining case. Hepatitis C virus serology was negative in all patient.Autoimmune disease as systemic lupus or Still's disease may be associated with SMZL before its tumoral manifestations are evident. In this mode of presentation, spleen enlargement, hypogammaglobulinemia, monoclonal gammopathy, and multiple autoimmune diseases, should alert the physician.

Human pasteurellosis is, in general, a locoregional infection due to contact with an animal. Systemic infections are rare and endocarditis is exceptionally described. The authors report two new cases of endocarditis due to Pasteurella spp, they then review 29 other published cases. Pasteurella spp. endocarditis presents as an acute form in 64% of cases and affects the aortic as often as the mitral valves. Contact with an animal is documented in 65% of cases. Pasteurella multocida is the most frequent species in this infection. The total death rate is 40% and can reach 57% of cases in case of immunodepression. The bad prognosis of this infection, justifies an early diagnosis and a rapid and adapted but not yet consensual medicosurgical treatment.

"Agranular CD4+ CD56+ hematodermic neoplasm" are rare hematologic neoplasms which were recently shown to correspond to the plasmocytoid dendritic cells.A 83-year-old presented isolated skin lesions purple, infiltrating the dermis. The biopsy has shown a dense dermal infiltration with malignant cells CD4+ CD56+ CD43+. There were no bone marrow involvement and no circulating blood cells. A chemotherapy permitted a clinical remission after six courses. Unfortunately, skin and blood relapses appear four months later. After a short success of chemotherapy by DHAP, the patient died three month later."Agranular CD4+ CD56+ hematodermic neoplasm" is a distinct entity from the cutaneous primary lymphomas. Recently plasmocytoid monocyte cells have been identified as the precursor of the malignant population with the high expression of CD123, IL3 receptor. It is a distinct clinicopathologic entity by its clinical presentation with skin tropism, bone marrow involvement with or without leukemic phase and poor prognosis independent of the kind of treatment and its particular phenotype CD4+ CD56+ CD43+. It would be interesting to use antibodies linked to CD123 in therapeutic because any treatment have efficacity in this disease.

Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto's disease is a rare anatomoclinical entity whose etiology remains unknown. It is mainly reported in young adult female, presenting with cervical lymphadenopathies, fever and asthenia. The diagnosis is based on the histological examination of a lymph node biopsy. The disease course is usually uneventful, but sometimes Kikuchi-Fujimoto's disease can reveal or evolve into a cutaneous or a systemic lupus.We report three new cases of Kikuchi's disease: the first one mimicked a systemic lupus, the second one was associated with a lupus-like rash, and a the last one was a severe case with hemophagocytic syndrome and a primo-infection with Epstein-Barr virus revealing a systemic lupus erythematosus.Clinical and biological follow-up of patients presenting with Kikuchi's disease is necessary to look for an association with a lupus. We discuss the pathogenic links between Kikuchi's disease and lupus.

Common variable immunodeficiency (CVID) is an immune defect characterized by primary hypogammaglobulinemia. Most of the time, clinical manifestations that reveal CVID are recurrent bacterial infections, but auto-immune or granulomatous events may occur.This retrospective study was conducted on 17 patients fulfilling the classical CVID definition. Lymphocyte activation level was evaluated in 12 patients through HLA-DR expression on lymphocytes subsets.This study includes 17 patients, 7 men and 10 women. The mean age at the first clinical manifestation is 23 years and the mean age at diagnosis is 39 years. Recurrent upper and lower bacterial respiratory tract infections are common to all patients. Abdominal infection due to Mycobacterium avium-intracellulare complex is found in one patient. Digestive events are dominated by chronic diarrhea caused by giardiasis, nodular lymphoid hyperplasia or villous atrophy. Seven patients developed auto-immune conditions (insulin dependent diabetes, idiopathic thrombocytopenic purpura (ITP), rheumatoid arthritis) and 7 patients have a splenomegaly. Non caseating granulomas in the spleen or in lymph node biopsies are found in 3 patients. Ten patients have a T lymphopenia, 2 have a B lymphopenia, 5 have a CD4/CD8 ratio1, and 6 have T CD4(+) lymphocytes400/mm(3). The study of HLA-DR expression on lymphocytes subsets shows that 7/12 patients have activated T CD4(+) and/or CD8(+) cells and these patients have auto-immune or tumoral manifestations. The other 5 patients do not have activated T lymphocytes but present with infectious events only.Our study allows the separation of patients with CVID according to their T lymphocytes activation level. A patient's classification is necessary to define homogeneous groups of patients to perform genetic and functional studies which will probably reveal heterogeneous molecular abnormalities.

Cold agglutinin disease is a chronic auto-immune hemolytic anemia related to a lymphoproliferative disorder with a degenerative potential and no codified treatment. This rare affection is related to the production of anti-erythrocytes immunoglobulins M. They are responsible of hemolytic crises sometimes severe and vascular acrosyndrom when submitted to cold temperature. Before rituximab, a monoclonal antibody targeted against the B lymphocyte CD20 antigen, no treatment was really efficient.We present 5 patients who have been treated with 4 weekly rituximab perfusions, and then we proceed to a review of the literature concerning the other 23 similar cases.With a good tolerance, the treatment allowed a remission in all the cases (4 partial, 1 complete). Among the 23 observations published, the rate of answer was 21/23 (of which 14 gave completes).Rituximab is an alternative treatment of cold agglutinin disease.

We report a retrospective study of 115 hospitalized non-immunocompromised adults with proved or presumed diagnosis of cytomegalovirus infection. Clinical symptoms were fever (95%), constitutive symptoms (80%), joint and muscle pain (41%), shivering (32%), abdominal pain (26%), non-productive cough (20%), cutaneous eruption (20%), and diarrhea (10%). Examination found hepatomegaly (25%), splenomegaly (23%), cutaneous rash (20%), adenopathy (19%), pharyngitis (9%), jaundice (3%) or signs of meningeal irritation (1%). Seventeen patients had a gastrointestinal form (hepatitis, jaundice, colitis, antral gastritis or cholecystitis), eight had a pattern of hemopathy, two interstitial pneumonitis, two pericarditis, two immune thrombocytopenic purpura, two a polymyalgia rheumatica-like pattern, one thrombotic thrombocytopenic purpura, one cutaneous vasculitis and one meningoencephalitis. Sixty-four percent of the patients had atypical lymphocytosis. Hepatocellular injury occurred in 90% of the patients. Nineteen of the patients had biological immune abnormalities. Cytomegalovirus infection should be mainly suspected in any patient with persistent fever, isolated or associated with signs of poor specificity, or in some patients with visceral manifestations of initially unknown origin.

Primary non-Hodgkin's lymphoma of the nasal cavity is particular. Pathological characteristics mainly associate a prevalent NK lymphocyte phenotype, a frequent exposure to the Epstein-Barr virus and a poor sensitivity to radiotherapy compared to other lymph node localizations.The authors report the case of a 38-year-old man. The patient had previously presented a chronic maxillary sinusitis. After a diagnosis of Wegener's disease, the poor course under therapy resulted in a nasal lymphoma. Natural killer cell nasal lymphoma was confirmed with a leading biopsy at the same time as a serious clinical outcome. The patient died of septic shock with multivisceral failure.The two differential diagnoses of ulcerative lymphoma of the midface are ulcerative infectious diseases and Wegener's disease. We must not miss this severe disease, with its poor prognosis and variable, though sometimes rapid speed of evolution.

This retrospective study was designed to determine the different parameters involved in the occurrence of uveitis during treatment with codofovir.This study included 10 patients out of 13 treated with cidofovir for cytomegalovirus (CMV) disease. Ocular examination, CD4+ lymphocyte count, and creatinine clearance were performed for each case of uveitis.During the 17-month study, 20 uveitis cases were analyzed. The first attack occurred after a median interval of 7.6 doses. At the time of ocular inflammation, 65% of the cases had a CD4+ lymphocyte count=100x10(6)/L, the patients thus had an improved immune function. Half of the patients had a normal creatinine clearance. The patients with a CD4+ lymphocyte count100x10(6)/L who presented one or more incidents of uveitis had an abnormal clearance, thus probably inducing intraocular storage of the drug.The occurrence of anterior uveitis during treatment with cidofovir is induced by the association of several parameters: a previous history of CMV retinitis, improvement of the immune function state, and intraocular storage of the drug.

Comprehension of cell cycle regulation mechanisms has progressed very quickly these past few years and regulators of the cell cycle have gained widespread importance in cancer. This review first summarizes major advances in the understanding of the control of cell cycle mechanisms. Examples of how this control is altered in tumoral cells are then described.The typical mammalian cell cycle consists of four distinct phases occurring in a well-defined order, each of which should be completed successfully before the next begins. Progression of eukaryotic cells through major cell cycle transitions is mediated by sequential assembly and activation of a family of serine-threonine protein kinases, the cyclin dependent kinases (CDK). The timing of their activation is determined by their post-translational modifications (phosphorylations/dephosphorylations), and by the association of a protein called cyclin, which is the regulatory subunit of the kinase complex. The cyclin family is divided into two main classes. The 'G1 cyclins' include cyclins C, D1-3, and E, and their accumulation is rate-limiting for progression from the G1 to S phase. The 'mitotic or G2 cyclins', which include cyclin A and cyclin B, are involved in the control of G2/M transition and mitosis. The cyclins bind to and activate the CDK, which leads to phosphorylation (and then inhibition) of the tumor suppressor protein, pRb. pRb controls commitment to progress from the G1 to S phase, at least in part by repressing the activity of the E2F transcription factors known to promote cell proliferation. Both the D-type cyclins and their partner kinases CDK4/6 have proto-oncogenic properties, and their activity is carefully regulated at multiple levels including negative control by two families of CDK inhibitors. While members of the INK4 family (p16INK4A, p15INK4B, p18INK4C, p19INK4D) interact specifically with CDK4 and CDK6, the CIP/KIP inhibitors p21CIP1/WAF1, p27KIP1 and p57KIP2 inhibit a broader spectrum of CDK. The interplay between p16INK4A, cyclin D/CDK, and pRb/E2F together constitute a functional unit collectively known as the 'pRb pathway'. Each of the major components of this mechanism may become deregulated in cancer, and accumulating evidence points to the 'pRb pathway' as a candidate obligatory target in multistep oncogenesis of possibly all human tumor types.Major advances in the understanding of cell cycle regulation mechanisms provided a better knowledge of the molecular interactions involved in human cancer. This progress has led to the promotion of new therapeutic agents presently in clinical trials or under development. Moreover, the components of the cell cycle are probably involved in other non-cancerous diseases and their role must be defined.

The association between dermatomyositis and cancer is clearly established, but its frequency remains difficult to define.We report the case of an association between a dermatomyositis and a cancer of the piriform antrum. Four months after surgical treatment and radiotherapy, the increased macro-CK level gave us reason to suspect a cancer relapse with pulmonary, hepatic, splenic and renal metastases without progressive clinical signs.Mitochondrial macro-CK detection must evoke the presence of neoplasia with or without metastasis, which would be a poor prognosis, as has been shown in our patient.

Eosinophilic fasciitis (EF) is a scleroderma-like disease of unknown etiology characterized by skin induration, elevated immune globulins, and peripheral eosinophilia. The hallmarks of the chronic cutaneous involvement in this syndrome are inflammation and fibrosis of the fascia. To determine how the inflammatory process in EF may be regulated, we investigated the spontaneous and mitogen induced [lipopolysaccharide (LPS), phytohemagglutinin (PHA) or both LPS+PHA] syntheses of interleukins (IL)-2, 5 and 10, interferon-gamma (IFN-gamma), and leukemia inhibitory factor (LIF) cytokines by peripheral blood mononuclear cells (PBMC) from 4 patients with active EF and compared them to those of 10 healthy individuals.We used a short term whole blood assay and culture supernatants were collected after 24 h to measure the IL-2 and IFN-gamma contents and after 48 h to evaluate IL-5, IL-10, and LIF. Supernatant cytokine concentrations were determined by ELISA.All 4 patients had similar patterns of cytokine secretion. Cytokine production did not differ between patients and controls under basal conditions or when LPS was added to the cultures. In contrast, under PHA or LPS+PHA stimulation, significantly higher amounts of all 5 cytokines were detected in samples from patients compared to those from controls.Overall, our data suggest that EF is characterized by an increased capacity of PBMC to produce IL-5 and IL-10, possibly leading to eosinophilia and immune globulin overexpression. In this context, the simultaneous elevations of type 1 cytokines (IL-2 and IFN-gamma) and LIF production by the same cells may be an attempt by the immune system to limit the exacerbation of a type 2 dominant response.

Pancreatic cancer is responsible for 6,000 deaths per year in France. During the course of the disease, venous thrombosis is common. Conversely, arterial thrombosis is rarely described.We report the case of a 59-year-old patient with pancreatic adenocarcinoma. Treatment by gemcitabine allowed rapid and persistent improvement of the body weight and a prolonged survival (18 months). Sudden complication, i.e. splenic arterial thrombosis, reversed the favorable outcome.Splenic venous thrombosis is a frequent complication occurring in the course of pancreatic cancer. It is easily diagnosed using abdominal computerized tomography. Arterial thrombosis is rarely observed. It might be due to either sporadic, unexpected, occurrence of cases related to the evolution of underlying pathological mechanisms, or to omitted treatment of vascular complications, as until the introduction of new anticancer drugs this disease was considered to be of very poor prognosis.

Cytomegalovirus (CMV) infection in non-immunocompromised adults can sometimes induce hematological and immunological disorders that may mislead diagnosis.Case reports of hospitalized non-immunocompromised adults with positive serology for CMV including the presence of immunoglobulin M or seroconversion were assessed in a retrospective study (1981-1998). We focused on clinical and biological abnormalities showing the role of CMV in disruption of functioning of hematological and immunological systems.Among 115 patients, lymphoma-like syndrome with large adenopathies and/or splenomegaly was diagnosed in eight patients, uncovering underlying CMV infection. Lymphoma was accompanied by hematoma in two patients. Three patients presented leg purpura (with thrombotic thrombocytopenic purpura in one case), one patient had cutaneous vasculitis and on other a Still's disease. Blood abnormalities were mononucleosis (64%), anemia (20%), and thrombopenia (25%) often of peripheral or hemolytic origin or due to hypersplenia. Electrophoresis of serum proteins showed an increase in immune globulins in 56% of the cases and monoclonal abnormality in nine cases. Immunological assessment was conducted in 18 patients. At least one abnormality was depicted in ten patients, consisting of either antinuclear, anti-platelet or anti smooth muscle antibodies, cryoglobulinemia, rheumatoid factor, or reduced complement fixation.Testing for CMV infection can be of value in case of blood or immunological disorders associated with clinical or biological signs. Although hematological disorders occur early, they are rarely severe. Immunological disorders are rarely symptomatic, but often raise issues regarding the potential genesis of immune diseases in at-risk patients.