Search

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 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.

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.

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.

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.

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.

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.

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.

Chronic hepatitis C virus (HCV) infection may be associated with numerous immune disorders, with vasculitis including polyarteritis nodosa, or with both. Cryoglobulinemia, which is often present, can also be expressed by vasculitis. We describe 2 cases of Churg-Strauss syndrome (CSS) in patients with HCV infection. We found no previous case of CSS accompanying HCV infection in the literature. The current patients were women aged 40 and 66 years. In both cases, a clinical and laboratory pattern suggesting CSS was found before the HCV infection was discovered. One patient had cryoglobulinemia. One patient was successfully treated with interferon (IFN). The other was treated for 18 months with IFN and corticosteroids. Second-line therapy consisting of IFN with ribavirin was successful. The emergence of HCV infection may have led to an induced form of CSS. The relationship among HCV, cryoglobulinemia, and CSS is not clear, but may be similar to that existing between polyarteritis nodosa and hepatitis B virus. These observations suggest that IFN-alpha therapy may be effective against CSS in HCV infected patients with or without cryoglobulinemia.

This review is aimed at defining the frequency, the clinical, biological and radiological presentation and the therapeutic possibilities for AL amyloid arthropathies. The frequency of AL amyloid arthropathy is estimated to be between 2 and 5%. There is usually a bilaterally progressive symmetrical arthritis of multiple joints (predominantly in the upper limb joints) with a chronic evolution. Neurologic or cutaneous symptoms are common. The analysis of synovial fluid sediments is a key test for the diagnosis of amyloid arthropathy. Patients with amyloid arthropathy must be screened for monoclonal gammapathies. The synovectomy is the best symptomatic treatment. A better knowledge of the pathogenesis of amyloid deposits should permit to improve therapeutical strategies.

Parotidean and ovarian lymphoma often indicate the existence of non-Hodgkin's lymphoma, involving 1-5% and 0.2% of the cases, respectively. EXEGENESIS: The authors report the case of a 70-year-old woman who presented B cell lymphoma of the parotid gland revealed by a rapid increase in the parotid size. CT scan showed the existence of a tumor located in the left ovary, later confirmed by biopsy. The proposed diagnosis was diffuse B cell type lymphoma with double glandular localization. Adenopathy and bone marrow involvement were both lacking.Lymphoma with glandular localizations always require diagnosis confirmation via histological examination and immunophenotyping, and must be considered as the local sign of a general disease.

Acquired von Willebrand disease associated with systemic lupus erythematosus (SLE) has been detected in three middle-aged women. In each case the first clinical manifestation was a bleeding syndrome. Plasma levels of von Willebrand factor (VWF) and ristocetin-induced platelet agglutination were as found in type 1 von Willebrand disease for the first patient, type 3 for the second patient, and type 2 for the third patient. Intraplatelet levels of VWF were normal for all three patients. In all cases a mixture of patient's plasma with normal plasma resulted in inhibition of ristocetin-induced binding of VWF to normal platelets. Intravenous immunoglobulin given to patients 2 and 3 corrected the plasma VWF level of the second patient but not that of the third. Therapy with corticosteroids was partially beneficial for patient 3 and patient 2. For patient 2, the severity of the cutaneous lesions also led to the use of cyclophosphamide, and this therapy resulted in total correction of VWF levels. Our observations confirm previous reports of acquired von Willebrand syndrome associated with SLE and show heterogeneity both in the phenotypic form and in the response to treatment.

Protein-losing enteropathy (PLE) is characterized by loss of essentially protein substances into the gastrointestinal tract. Few reports of PLE supervening in patients who have systemic lupus erythematosus (SLE) have appeared in the literature. We report three new cases. All three were women who had a severe form of SLE involving several organs. PLE was diagnosed on the basis of an increased clearance of alpha 1 antitrypsin. The severeness of the clinical picture in all three patients justified the use of immunosuppressive agents (corticosteroids and pulse cyclophosphamide therapy) which were effective. These cases are compared to the 24 previously reported. The frequency of PLE during an SLE flare-up is probably underestimated. It should be looked for in SLE patients who have edema by means of the simple alpha 1 antitrypsin test. PLE is often found in severe clinical forms of SLE and should be managed using corticosteroids either alone or in association with immunosuppressive drugs.

BACKGROUND Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs). METHODS The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs. RESULTS Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count