We determined the number and functional status of CD4⁺CD25high regulatory T cells (Treg) in blood samples from patients with metastatic carcinoma, and evaluated their sensitivity to a single ...intravenous infusion of cyclophosphamide. Treg numbers were significantly higher in 49 patients with metastatic cancer (9·2% of CD4⁺ T cells) compared to 24 healthy donors (7·1%). These cells expressed the transcription factor forkhead box P3 (FoxP3), glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR) and intracellular CD152, and demonstrated a suppressive activity in vitro against CD4⁺CD25⁻ autologous proliferation. At a single intravenous infusion, cyclophosphamide failed, in association with a non-specific immunotherapy by intratumoral bacille Calmette-Guérin (BCG), to modulate significantly Treg numbers or function. Metastatic cancer is associated with an expansion of peripheral blood CD4⁺CD25highFoxP3⁺GITR⁺CD152⁺Treg cells whose immunosuppressive properties do not differ from those of healthy subjects. Moreover, cyclophosphamide administration may not represent an optimal therapy to eliminate Treg, which further underlines the need to identify specific agents that would selectively deplete these cells.
Objectives
Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and ...assessed the impact of thromboembolic history.
Methods
HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms. Factors significantly associated with an impaired HRQoL were identified.
Results
A total of 115 patients with aPL and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 ± 14.1 years old, 86 women). In 53 patients APS was diagnosed. Compared to general population norms, patients with APS had an impaired HRQoL. SLE-associated APS patients had the worst HRQoL scores (physical component summary (PCS)=40.8 ± 10.6; mental component summary (MCS)=40.6 ± 16.5) in comparison with SLE or aPL patients without thromboembolic history. In APS patients, history of arterial thrombosis significantly impaired HRQoL (PCS score: 42.2 ± 9.4 vs 49.2 ± 8.5; MCS score: 33.9 ± 13.7 vs 44.6 ± 10.3).
Conclusion
Compared to the general population, APS patients experienced a lower HRQoL. In these patients, a history of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of HRQoL should be included in APS patient management to assess the burden of the disease from a patient’s perspective and to provide patients with the support they need.
Gaucher disease (GD) is a rare genetic lysosomal storage disorder caused by a beta-glucocerebrosidase deficiency and responsible for a lysosomal storage disorder. GD is characterized by ...haematological, visceral and bone involvements. The aim of this study was to describe the diagnostic journey of type 1 GD patients as well as the role of the internist.
A retrospective multicentric study involving type 1 GD patients has been conducted in 16 centers, between 2009 and 2011.
Fifty-five type 1 GD patients were included, under the care of an internist or an haematologist. They were originally hospitalized in 8 different specialized units. Diagnosis was established by bone-marrow aspiration in 22 patients (40%), by enzymatic assay of glucocerebrosidase activity in 15 patients (27%), and by bone-marrow biopsy in 9 patients (16%). The use of enzymatic assay became more frequent after 1990. The delay between first hospitalization due to GD symptoms and definitive diagnosis was less than one year for 38 patients. Patients with suspected GD were mainly referred to an internist physician.
GD seems to be better recognized and quickly diagnosed since 1990 in spite of the multiplicity of journeys. The role of the internist seems important.
The discovery of a hyperferritinemia is most of the time fortuitous. The diagnostic approach aims at looking for the responsible etiology and at verifying if an iron hepatic overload is present or ...not. Three diagnostic steps are proposed. The clinical elements and a few straightforward biological tests are sufficient at first to identify one of the four main causes: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome. None of these causes is associated with a significant iron hepatic overload. If the transferring saturation coefficient is raised (>50%) a hereditary hemochromatosis should be discussed. Secondly, less common disorders will be discussed. Among these, only the chronic hematological disorders either acquired or congenital are at risk of iron hepatic overload. Thirdly, if a doubt persists in the etiologic research, and the serum ferritin level is very high or continues to rise, it is essential to verify that there is no iron hepatic overload. For that purpose, the MRI with study of the iron overload is the main test, which will guide the therapeutic attitude. Identification of more than a single etiology occurs in more than 40% of the cases.
Abstract Introduction Heart manifestations of Churg–Strauss syndrome (CSS) are varied. In the early stages of the disease, it is difficult to distinguish between lesions that are specific to CSS and ...those of other etiologies. The aim of our work was to compare the characteristics of patients with heart manifestations linked or not to Churg–Strauss syndrome. Material and methods We recorded all clinical symptoms of patients with CSS hospitalized between 1998 and 2008 in Burgundy, France, and determined the possible relationships between heart symptoms and CSS. Results From a cohort of 31 patients, we found 20 with heart lesions. When heart lesions were present, we noted fewer initial symptoms of digestive disorders ( p < 0.05), lower levels of lung infiltrates and fewer anti-MPO pANCA ( p < 0.05). Heart lesions were linked to CSS in 75% of cases. Their patients were thus younger than those in the other cardiac patients ( p < 0.05), were more likely to have clinical manifestations of heart involvement at diagnosis, were less likely to have lung infiltrates on the X-ray at diagnosis and during flare-ups and less likely to have lung abnormalities on X-rays during flare-ups ( p < 0.05) and higher level of leucocytes and eosinophils at diagnosis. Conclusion Heart lesions directly attributable to CSS are frequent, severe and probably underestimated. A specific physiopathology that is not mediated by ANCA seems to be involved in the genesis of CSS-related heart lesions.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of systemic vasculitis in which cardiac involvement is frequent and severe, and accounts for half of EGPA‐related deaths. ...ANCA‐positive EGPA differs from ANCA‐negative EGPA in that the former is significantly associated with renal involvement, peripheral neuropathy and biopsy proven vasculitis, whereas the latter is associated with cardiac involvement. Herein, we report a case of EGPA with myocarditis in a woman, who was successfully treated with steroids and cyclophosphamide. This report highlights the importance of diagnosing cardiac involvement in EGPA early, especially in ANCA‐negative patients.
Immune thrombocytopenia is an autoimmune disease characterized by a peripheral destruction of platelets. B lymphocytes play a key role but pathogenesis is more complex, involving humoral and cellular ...immunity associated with an inappropriate platelet production. In this article, we review the different pathogenic pathways, leading to new therapeutic strategies.
Scalp vein thrombosis is an unusual complication during giant cell arteritis. Revealed by headache, it can be misdiagnosed as a disease relapse. An ultrasound scan should rapidly be performed to make ...the diagnosis, avoiding inappropriate treatment escalation.
Systemic lupus erythematosus (SLE) has been described as a cause of thrombotic microangiopathy, especially thrombotic thrombocytopenic purpura (TTP). Haemolytic‐uraemic syndrome (HUS) is less ...frequent in SLE. We report a case of such an association during an episode of severe lupus nephritis in a young woman, who was successfully treated with steroids, cyclophosphamide and especially plasma exchange with plasma replacement. This report highlights the importance of recognising atypical HUS in SLE patients by looking for schistocytes in case of haemolytic anemia with a negative antiglobulin test, in order to begin plasma exchange.
Le purpura thrombopénique immunologique est une maladie auto-immune, caractérisée par une destruction périphérique des plaquettes, qui a longtemps été considérée comme une pathologie dépendante ...uniquement du lymphocyte B. Sa physiopathologie est en réalité beaucoup plus complexe, faisant intervenir la réponse immunitaire humorale et cellulaire, ainsi qu’un défaut de production médullaire. Nous détaillons les divers mécanismes impliqués dans l’activation de la réponse auto-immune au cours du purpura thrombopénique auto-immun, ainsi que les nouvelles pistes physiopathologiques permettant de nouvelles stratégies thérapeutiques.
Immune thrombocytopenia is an autoimmune disease characterized by a peripheral destruction of platelets. B lymphocytes play a key role but pathogenesis is more complex, involving humoral and cellular immunity associated with an inappropriate platelet production. In this article, we review the different pathogenic pathways, leading to new therapeutic strategies.
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