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Background: Preclinical and retrospective clinical data suggest that ≥3T is a biomarker for poor prognosis and resistance to paclitaxel in breast cancer (BC). Preclinical studies have demonstrated that Ixa has activity in ≥3T over-expressing xenograft models resistant to taxanes and Ixa has shown clinical activity in BC patients with high ≥3T mRNA levels [Horak et al., J Clin Oncol 27:15s, 2009 (suppl; abstr 3587]. Dako and BMS have developed an IHC assay for detection of ≥3T to explore the potential of ≥3T as a biomarker to select BC patients that may benefit from Ixa. A neoadjuvant BC study comparing ixa to weekly paclitaxel employs this assay to assess ≥3T expression levels in patients’ tumor samples. Here we describe the application and initial validation testing of the assay in BC tumor samples. Methods: An IHC assay employing a murine monoclonal anti-≥3T antibody (TUJ1) was developed to assess ≥3T expression in formalin-fixed paraffin-embedded tissue specimens. Banked specimens for initial testing included 233 cases of invasive BC. Results: Patterns of ≥3T staining were typically homogeneous cytoplasmic staining with normal tissue elements such as endothelial cells and nerve cells serving as internal positive controls. Staining intensity was scored as 0, 1+, 2+ or 3+ with 0 being no visible staining and 2+ being equal to that of the internal positive control. Tumors with ≥50% cells staining ≥2+ were defined as positive for ≥3T based on previous published studies. Of the 233 breast tumors, 81 (35%) were positive and 152 (65%) were negative for ≥3T expression. HER2 status was defined for 128 of these specimens, with 37 of them (29%) found to be HER2 positive. Comparison of the samples with defined HER2 status demonstrated similar patterns of ≥3T expression, with 15 (40.5%) of the HER2+ samples being positive for ≥3T and 31 (34.1%) of HER2- specimens expressing elevated levels of ≥3T. In pathologist training exercises the inter-reader and intra-reader agreement of ≥3T scoring exceeded 85%. Antigen stability has been confirmed and other assay validation efforts are ongoing. Conclusions: These findings are consistent with previously reported data on ≥3T expression in breast cancer, and support the use of this ≥3T IHC assay in studies with ixabepilone. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-06.

Resume Introduction Plusieurs auteurs ont evalue la relation entre l’expression de la β-tubuline de classe III et le devenir des patients porteurs d’un cancer du poumon non a petites cellules (CPNPC) traites par des agents antitubulines (AAT). Etat des connaissances Un haut niveau d’expression de β-tubuline de classe III a ete correle avec une moindre reponse ou une survie plus courte chez les patients presentant un CPNPC avance traite par taxanes et vinorelbine. Deux etudes ont montre que les patients traites par paclitaxel dont les tumeurs exprimaient un haut niveau de β-tubuline de classe III avaient une moindre reponse et une survie plus vite, tandis que cette variable n’avait pas de valeur predictive chez les patients ne recevant pas d’AAT. A l’oppose, l’analyse des tumeurs des patients operes porteurs d’un CPNPC de l’essai JBR-10 a montre que la chimiotherapie par cisplatine/vinorelbine semblait neutraliser la valeur pronostique negative de l’expression de β-tubuline de classe III et que le benefice de la chimiotherapie etait plus important pour les patients ayant un haut niveau d’expression. Perspectives Dans le CPNPC avance, un haut niveau d’expression de β-tubuline de classe III pourrait orienter le choix de la chimiotherapie vers un protocole sans taxanes. Les epothilones apparaissent potentiellement interessantes dans ce contexte. Conclusions L’expression de la β-tubuline de classe III emerge comme un marqueur de resistance aux taxanes dans le CPNPC avance, ainsi qu’un marqueur pronostic pour le devenir des patients ayant une maladie localisee.

International audience; BACKGROUND:In 2014, the European Society for Immune Deficiencies (ESID) revised the common variable immunodeficiency (CVID) diagnosis criteria by incorporating new clinical and biological markers. The new definition appeared more restrictive but had not yet been evaluated in a large cohort of patients.OBJECTIVE:The objective of this study was to evaluate the impact of this new definition in a large cohort of patients with primary hypogammaglobulinemia.METHODS:Evaluation of 3 different CVID definitions (ESID/Pan-American Group for Immunodeficiency [PAGID] 1999, ESID 2014, DEFI 2015) in 521 patients included in the French DEFI study with a diagnosis of primary hypogammaglobulinemia.RESULTS:Using the ESID/PAGID 1999 definition, 351 patients were classified as CVID. The new ESID 2014 definition excluded 62 (18%) patients. Most of them (n = 56; 90%) had a less severe disease, whereas 6 (10%) presented with a severe disease with major T-cell defect. We propose different criteria (occurrence of opportunistic infection or very low naive CD4+ T-cell count) to define this population with severe T-cell defect. Sixty-two patients fulfilled these criteria, represented 20% of the initial CVID population but accounted for 77% of the deaths, with a 5-year overall survival of 67.6% (95% confidence interval, 51.0-79.6), and were considered as late onset combined immunodeficiency (LOCID).CONCLUSIONS:The new ESID definition for CVID still fails to exclude a large number of patients with severe T-cell defect. We propose a new definition (DEFI 2015) that excluded more patients with a T-cell defect and consider these patients as LOCID. This population has a poor outcome and should be considered as a distinct group requiring specific care.

Summary Background Kawasaki-like syndrome (KLS) is rare in adults; one third of these patients are infected by Human immunodeficiency virus (HIV). Our study reports cases of KLS occurring in HIV-positive adults and reviews the literature to compare their characteristics with HIV-negative adults and children with Kawasaki disease (KD). Methods Report of cases and review of the literature. Results Amongst 20 cases reviewed, including 4 who were managed at our institution, KLS was associated with severe immunosuppression and a high HIV viral load. There was frequent co-infection by hepatitis viruses. Desquamation and liver abnormalities were more frequent in HIV-negative adults whereas headaches and gastrointestinal disorders more common in HIV-positive adults. Intravenous immunoglobulin was effective therapy. Relapse was more frequent among HIV-positive patients. No cardiovascular complications or deaths occurred. Conclusions Advanced immunosuppression due to HIV may predispose to KLS. The differential diagnosis that must be considered includes drug hypersensitivity reactions and staphylococcal infections.

Gemcitabine-induced thrombotic microangiopathy is a rare event whose management is not yet consensual. The use of eculizumab could be of interest.A 68-year-old woman was treated by gemcitabine as adjuvant chemotherapy of a pancreatic adenocarcinoma. Two months later, the patient presented with mechanical hemolytic anemia, thrombocytopenia and high blood pressure that led to the diagnosis of thrombotic microangiopathy. Gemcitabine was stopped. Plasma exchange therapy was introduced since hematological and renal parameters had worsened. As clinical efficacy was insufficient, eculizumab was introduced at a dose of 900 mg per week 4 times, then 1200 mg every 2 weeks. Symptoms along with hematological and nephrological analysis were back to physiological standards after 7 intravenous injections.Eculizumab seems to be an effective treatment against gemcitabine-induced thrombotic microangiopathy in case of severe hematological and renal injuries associated with a lack of response to plasma exchange therapy.

International audience; Adult-onset Still's disease is a rare and difficult to diagnose multisystemic disorder considered as a multigenic autoinflammatory syndrome. Its immunopathogenesis seems to be at the crossroads between inflammasomopathies and hemophagocytic lymphohistiocytosis, the most severe manifestation of the disease. According to recent insights in the pathophysiology and thanks to cohort studies and therapeutic trials, two phenotypes of adult-onset Still's disease may be distinguished: a systemic pattern, initially highly symptomatic and with a higher risk to exhibit life-threatening complications such as reactive hemophagocytic lymphohistiocytosis, where interleukin-1 blockade seems to be very effective, a chronic articular pattern, more indolent with arthritis in the foreground and less severe systemic manifestations, which would threat functional outcome and where interleukin-6 blockade seems to be more effective. This review focuses on these data.

Valpromide and sodium divalproate are indicated in the treatment of maniac episodes of bipolar disorder. These drugs are metabolized into valproic acid. The occurrence of peripheral edema has been described as a very rare adverse reaction of those drugs.We report the case of a patient treated with valpromide who presented edema of the lower limbs. The increase in furosemide dose allowed regression of edema, and valpromide discontinuation resulted in rapid normalization. Recurrence of mood disorders led to the reintroduction of valpromide, which was associated with recurrence of edema. The definitive withdrawal of valpromide resulted in resolution of edema.Edema of the lower limbs can be induced by valproate. The mechanism of this reaction is unknown. These edema appear to be reversible upon discontinuation of the drug. Clinicians should be aware of a possible relationship between valproate-derived drugs and peripheral edema.

Ectopic adrenocorticotropic (ACTH) syndrome is a rare condition, generally due to lung or carcinoid tumors. 18-fluorodeoxy-glucose positron emission tomography ((18)FDG-PET) can be useful where conventional localization techniques often fail. A 50-year-old man presented with sudden diffuse oedema, hypokaliemic alkalosis, Diabetes mellitus and high serum levels of ACTH and cortisol. Ectopic ACTH syndrome was confirmed leading to ketoconazole treatment. Chest-computed tomography only revealed an aspecific anterior mediastinal nodule that was hypermetabolic on the whole body-(18)FDG-PET. A thymic tumor was suspected and the patient had a thymectomy that revealed an atypical carcinoid tumor with pleural carcinosis. The postoperative course was favorable with clinical and biochemical remission of neoplastic Cushing's syndrome.

Biotherapies used in clinical practice for the treatment of uveitis include monoclonal antibodies and fusion proteins (anti-TNFα, anakinra, tocilizumab and rituximab), interferons (IFN) and intravenous immunoglobulins (IVIg). IFN is capable of inducing prolonged remission and continued after his discontinuation, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behçet's disease. They are generally (90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIg are used for the treatment of Birdshot's disease. Tolerance of IVIg is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1r) showed interesting results in terms of efficiency in one small open study in Behçet's disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis.

Drug-induced immune haemolytic anemia occurs in one case per million and can be fatal. Our aim was to describe the main characteristics and the type of drug involved.Cases were retrospectively identified using spontaneous notifications collected by our pharmacovigilance centre and the results of immuno-hematological investigations performed by the laboratory of French blood establishment of Lyon between 2000 and 2012. Inclusion criteria were: an immune (positive direct antiglobulin test), hemolytic, anemia (haemoglobin100 g/L), with at least a plausible causal relationship with drug exposure according to the French method of imputability or the presence of drug-dependent antibodies, and exclusion of other causes of hemolysis.Ten cases (5 men and 5 women, median age 54.4 years) were identified. Causal drugs were ambroxol, beta-interferon, cefotetan, ceftriaxone, loratadine, oxacillin, oxaliplatine, piperacillin-tazobactam, pristinamycin, and quinine. The median time to onset of anemia after starting the culprit drug was 6 days (2 hours to 16 days). The median nadir of hemoglobin was 57.9 g/L (range: 34-78). The direct antiglobulin test was positive in 8 patients: IgG only (n=4), IgG and complement (n=3), and IgA (n=1). Drug-induced immune haemolytic anemia was considered as definite in 5 cases with positive drug-induced antibodies, probable in 4 cases negative for the detection of drug-induced antibodies but with plausible or likely causal relationship with drug exposure, and probable with an autoimmune mechanism in 1 case.The diagnosis of DIIHA is often difficult because of the similarities with autoimmune haemolytic anemia and the inconstant sensitivity of immunologic tests that sometimes required repetitive assessment.

Infectious aortic aneurysms are rare conditions, being responsible of 2% of aortic aneurysms. Most published results are surgical case series concerning infected abdominal aorta. In this retrospective study, we assessed clinical features and outcome of patients presenting infectious thoracic aortic aneurysms.Diagnosis was based upon a combination of imaging evidence for thoracic aorta aneurysm and evidence for an infective aetiology including a culture of a causative pathogen, or a favourable outcome with anti-infective therapy. Retrospective case series.Six men and one woman were included, with a mean age of 66 years. All the patient presented at least one cardiovascular risk factor or atherosclerosis localisation. Fever (71%) and chest pain (42%) were the most common clinical presenting manifestations. The causative pathogens were: Staphylococcus aureus (N=1), Salmonella enteritidis (N=3) and Candida albicans (N=1). The contrast-enhanced computed-tomography disclosed an aneurysm whose diameter reached more than 50 mm (N=5), that increased rapidly in size (N=5), or presented an inflammatory aspect of the aortic wall (N=4). Management was both medical and interventional: surgery (N=3) or endoluminal repair (N=4). Outcome was favourable in six patients; one patient died from aneurysm-related complications.Clinical manifestations revealing an infectious thoracic aneurysm are variable. Diagnosis should be considered in patients presenting a rapidly-growing aneurysm, especially in the presence of elevated acute phase reactants. Endoluminal repair constitutes a treatment option. The role of FDG-PET for diagnosis and follow-up remains to be defined.

To report on the various clinical presentations, etiological diagnosis, prognosis and treatment of patients with scleritis evaluated at a tertiary care eye center.Retrospective, monocentric study on a series of 32 patients in a tertiary center.The mean age of included patients with scleritis was 46.8 years (range, 22 to 77 years). Nineteen patients were women and 13 were men. Twenty-six patients (81%) had anterior scleritis (15 nodular, 8 diffuse and 3 necrotizing), six (19%) had posterior scleritis. Unilateral inflammation was present in 24 patients (75%). Twelve out of the 32 patients (37.5%) had an underlying systemic disease: granulomatosis with polyangiitis (n=3), Behçet's disease (n=2), unspecified inflammatory arthritis (n=2), psoriatic arthritis (n=1), ankylosing spondylitis (n=1), sarcoidosis (n=1), Cogan's syndrome (n=1) and ulcerative colitis (n=1). Six patients (18.8%) were suspected of having infectious disease with herpes virus: clinical context and positive treatment response with oral valacyclovir. Systemic agents and topical agents were required in 28 patients (87.5%). The first line therapy was mainly oral non-steroidal anti-inflammatory drugs in 15 patients (47%) and oral corticosteroids in 8 (25%). Immunosuppressive drugs were required in 6 patients. The mean follow-up was 16.3 months. Six patients (19%) had a decrease in visual acuity.The number of systemic disease in our series is similar to the main series in the literature. Treatment with valaciclovir might be effective in patients with suspected herpes simplex scleritis.

Parvovirus B19 causes erythema infectiosum in children, transient aplastic anemia in patients with hemoglobinopathies, pur red cell aplasia in immunocompromised persons and hydrops fetalis in pregnancy. The spectrum of clinical and biological manifestations in immunocompetent adult continues to grow up.We report on a case series of 26 patients with primary parvovirus B19 infection in immunocompetent adults. This is a retrospective study over the period 2000 to 2010 in two departments of internal medecine. The diagnostic was clinical, serological or molecular.There was a female predominance (sex-ratio 3.33/1). Median patient age at diagnostic was 38.8 years (range: 18-68). The predominant symptoms were fever (65%), peripheral and symmetrical polyarthralgia (62%) and skin rash (58%). Two patients had neurological manifestations (sixth cranial nerve palsy, distal paresthesia) and one patient had myocarditis. Abnormal laboratory values included increased acute phase reactants (73%), thrombocytopenia (43%), lymphopenia (38%) and elevated liver enzymes (37%). Antinuclear (19%), anti-DNA (28%) and anti-phospholipids antibodies (14%), and hypocomplementemia (32%) were observed. False reaction with anti-CMV and anti-EBV IgM positivity was documented in 27% of cases. Two patients had persistent parvovirus B19 infection.The diversity of the clinical manifestations of parvovirus B19 infection may be misleading for the clinician. However, the diagnosis should be suspected in immunocompetent adults to limit the risk of transmission to the patients who could develop a severe infection such as pregnant women or immunocompromised patients.

Primary immunodeficiency with granulomatosis in the adulthood mainly concern common variable immunodeficiency (CVID). Hypogammaglobulinemia in the adulthood is usually related to a secondary immunodeficiency. When a patient presents with the association of a hypogammaglobulinemia and a granulomatosis, an opportunistic infection must first be ruled out. For unknown reasons, about 10% of the patients affected by CVID also present with granulomatosis. Lesions usually affect the pulmonary tract or the mediastinum. Half of these patients are also affected by an autoimmune cytopenia. Treatment is not codified. Severe pulmonary complications can occur in about 50% of the patients.

Although primary immunodeficiencies (PID) are typically marked by increased susceptibility to infections, autoimmune manifestations have increasingly been recognized as an important component of several forms of PID. Here, we discuss two forms of PID in which autoimmune cytopenias are particularly common and may be the first manifestation of the disease in adults: autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency (CVID). Approximately one fifth of patients with CVID develop autoimmune diseases, and immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AHA) are the most common. Since autoimmune cytopenias frequently precede the diagnosis of CVID, testing for immunoglobulin levels should be performed in patients diagnosed with AITP and AHA. Patients with CVID in association with autoimmune cytopenias have a "particular phenotype" with lower susceptibility to infection and higher susceptibility to autoimmune manifestations and, for patients with AHA, a more frequent development of splenomegaly and lymphoma. Corticosteroids and high doses of intravenous immunoglobulins (IVIg) seem to have the same efficacy as in idiopathic AITP and AHA. Splenectomy and rituximab are as effective as in idiopathic autoimmune cytopenias but are associated with an increased risk of severe infection and should, in our opinion, be considered only for those rare patients with "refractory diseases". The course and outcome of autoimmune cytopenias is not affected by supportive IVIg therapy. Autoimmune destruction of blood cells affects over 70% of ALPS patients. The median age of first presentation is 24 months of age, but with increasing awareness of this condition, adults with autoimmune cytopenias are now being diagnosed more frequently. Testing for ALPS should therefore be considered in young adults with unexplained Evan's syndrome. Patients usually respond to immunosuppressive medications, including corticosteroids. Unlike many patients with idiopathic autoimmune cytopenias, the cytopenias in patients with ALPS typically do not respond to IVIg. After corticosteroids, the immunosuppressive drug that is the most studied in ALPS patients is mycophenolate mofetyl. Rituximab and splenectomy are relatively contraindicated in ALPS because of an increase risk of severe infection and should be reserved for patients who fail all other therapies.

Uveitis is a common (20-50%) and early manifestation of sarcoidosis. Typical sarcoid uveitis presents with bilateral mutton fat keratic precipitates, iris nodules, and anterior and posterior synechia. Posterior involvement includes vitreitis, vasculitis and choroidal lesions. Long-term complications are common, and cystoid macular edema is the most important and sight-threatening consequence. Diagnostic work-up of sarcoidosis usually includes chest radiography or computed tomography scan, bronchoscopy with bronchoalveolar lavage, angiotensin converting enzyme, lysozyme, gallium scintigraphy and biopsy. The gold standard for the diagnosis of sarcoidosis should be obtained with histologic examination. However, an international workshop has recently established diagnostic criteria of "intraocular sarcoidosis" (sarcoidosis uveitis) on the basis of a combination of suggestive ophthalmological findings and laboratory tests, when biopsy is not performed or is negative. More recent techniques such as PET-scan and endoscopic ultrasound-guided fine-needle biopsy of intrathoracic nodes should be assessed in future prospective studies. Corticosteroids are the mainstay of treatment. Anterior and unilateral intermediate or posterior uveitis are usually treated with topical corticosteroids. Systemic corticosteroids are indicated in uveitis not responding to topical corticosteroids or in the presence of bilateral posterior involvement, especially with macular edema and occlusive vasculitis. In 5 to 20% of the patients who are corticosteroids resistant or require an unacceptable dose to maintain remission, additional immunosuppression is used, including methotrexate, leflunomide and mycophenolate mofetil. As in systemic sarcoidosis, infliximab has been recently suggested for refractory or sight threatening disease.

Kawasaki disease (KD) is a multisystemic vasculitis affecting mainly the skin, mucosa, and lymph nodes. Coronary artery aneurysms occur in 25% of patients but their prevalence is reduced to 4% in those patients treated with intravenous immunoglobulin (IVIg) within 10 days of illness onset. Interesting data recently published relate to physiopathology and diagnosis of the disease. Investigations identified an antigen-driven IgA oligoclonal response directed against cytoplasmic inclusions in KD tissues. An algorithm using laboratory tests and echocardiography has been recently proposed to improve early detection of incomplete KD. Although KD predominantly affects children, it may be also of interest for adult physicians. First, patients may develop long-term cardiovascular event. Coronary artery aneurysms may lead to the development of coronary stenosis or thrombosis. Despite the absence of coronary lesions during the acute phase of the disease, patients may present morphological and functional sequelae of coronary and peripheral arteries at convalescent phase. These potential arterial sequelae require long-term follow-up and treatment of associated cardiovascular risk factors. Although the level of injury seems to be correlated with the severity of initial coronary lesions, long-term course of vascular injuries is poorly known. Second, KD may occur in adults with 91 cases reported in the literature. Twenty-one cases have been reported in HIV infected patients. Intravenous immunoglobulins appear to shorten the disease course. Recent studies highlight the existence of incomplete KD and symptomatic coronary aneurysms in adults. Overall, these data suggest that adult patients with biological or echocardiographic features suggestive of incomplete KD should receive prompt IVIg to prevent coronary artery sequelae.

Several investigators have addressed the relationship between expression of class III beta-tubulin and outcome in patients with nonsmall cell lung cancer (NSCLC) treated with tubulin-binding agents (TBA).High expression of class III beta-tubulin has been found to be correlated with low response rates and reduced survival in advanced NSCLC patients treated with taxane/vinorelbine--containing regimens. Two studies have shown that patients receiving paclitaxel whose tumours expressed high levels of class III beta-tubulin had a lower response rate and shorter survival, whereas this variable was not found to be predictive in patients receiving regimens without TBA. Conversely, analysis of samples from operable NSCLC patients in the JBR-10 trial showed that cisplatin/vinorelbine chemotherapy seemed to overcome the negative prognostic effect of high class III beta-tubulin expression and that the greatest benefit from chemotherapy was observed in patients with high class III beta-tubulin expression.In advanced NSCLC, high betaIII tubulin expression may prompt selection of taxane-free regimens as the preferred initial treatment approach. The epothilones may fulfil such a role in the treatment of NSCLC.betaIII tubulin expression is emerging as a valuable biomarker for taxane resistance in advanced disease, as well as offering prognostic information for outcomes among patients with earlier stage disease.

Uveitis consists of a large group of diseases characterized by intraocular inflammation involving the uveal tract. This heterogeneity makes the diagnosis and the treatment of uveitis frequently challenging. The purpose of this study was to describe the various clinical and etiologic aspects of uveitis, through the new standardized uveitis classification and the use of modern investigations for its diagnostic work-up.The medical records of 121 new patients with uveitis referred to our tertiary ophthalmologic centre between January 2002 and December 2006 were retrospectively reviewed. Uveitis associated to human immunodeficiency virus and secondary to exogenous endophthalmitis were excluded. All patients had a complete ophthalmological examination and appropriate clinical and paraclinical examination. The diagnosis was established according to the recent international criteria.One hundred and twenty-one patients were included. The four main etiologies were: toxoplasmosis (14%), sarcoidosis (11.6%), spondylarthritis or HLA B27-associated uveitis (13.2%) and Herpes virus infections (9.1%) that represented almost half of the uveitis causes (47.9%). Various diseases constituted the remaining causes of the uveitis (20.9%). Uveitis remained unexplained in the remaining 36 patients (29.7%). Overall, associated systemic diseases were diagnosed in 35.5% of our uveitis patients (34 patients), associated infectious conditions in 26.4% (32 patients) and specific ocular diseases in 8.3% (12 patients).Despite a limited number of patients, our study showed an etiologic distribution similar to that of the main series reported in the literature. Nevertheless, we observed an elevated frequency of sarcoidosis and systemic diseases, which emphasizes a management that takes into account standardized clinical and paraclinical criteria and the usefulness of a collaboration with the internist.

Hypereosinophilic syndromes rarely manifest as polyserositis. Imatinib mesylate is the reference treatment for myeloid variants of FIP1L1-PDGFRA-positive hypereosinophilic syndromes. A response to imatinib has also been reported in FIP1L1-PDGFRA-negative hypereosinophilic syndromes.We report a 25-year-old man who presented with a FIP1L1-PDGFRA-negative hypereosinophilic syndrome, with severe pericardial effusion and bilateral pleuritis. Imatinib mesylate at the dose of 100mg daily was started because of high-dose corticosteroids dependence. A response was noted after 15 days of treatment. Corticosteroids were discontinued after 7 months and the patient remained asymptomatic after 23 months of treatment.This report evidences the association of polyserositis with hypereosinophilic syndromes and the potential efficacy of imatinib mesylate even in FIP1L1-PDGFRA-negative patients.

In 2002, the French Federation of Comprehensive Cancer Centers published clinical practice guidelines (CPGs) for the management of carcinomas of unknown primary (CUP).A controlled "before-after" study at two centers (experimental in Lyon, France and control in Edmonton, Canada) to assess the impact of CPGs on CUP management. Fifty-CUP patients treated in 2000-2001, i.e. before CPG publication, and 50 patients treated in 2003-2004, were analyzed for both centers.In both groups, compliance for diagnostic workup was the same before or after CPGs publication. Non-adenocarcinoma histology and performance status (PS)2 were independent factors for CPGs compliance. In the experimental group, 75% of patients underwent inappropriate investigations. The proportion of patients from this group with unfavourable clinicopathologic entity and PSor = 1, who received cisplatin-based chemotherapy did not significantly change (2000-2001: 27% vs. 2003-2004: 37.5%; P = 0.45). However, most patients treated in the pre period received organ-specific regimens, while most patients treated in the post period received taxane or gemcitabine-based regimens. Patients from the control group generally received taxane/carboplatin.Our study show that simply distributing CUP CPGs did not change practice and underline the necessity to disseminate and implement CPGs, both to oncologists and organ-specialist physicians.

In developed countries, uveitis is quite common and chronic course is associated with a poor visual prognosis. However, no guidelines for their management have been consensually proposed. Based on the experience of ophthalmologists and internists from tertiary care centers, this article describes the management of uveitis, including the diagnostic procedure, indications and types of anti-inflammatory treatments. We focus on the interest of an exhaustive ophthalmologic examination for the diagnosis of an underlying systemic disease such as sarcoidosis. In this way, a multidisciplinary staff could be useful for an optimal management of uveitis. We also reviewed the main current treatments for severe uveitis. Whatever the origin of ocular inflammation, corticosteroids are consensually used as first line treatment. However, the identification of an underlying systemic disease helps in the refinement of further therapeutic choices. In cases of refractory and sight threatening uveitis, the short-term use of infliximab, a chimeric anti-TNF-alpha antibody, has been shown to be effective and safe. These recommendations do not constitute treatment guidelines but aim at improving the uniformity of clinical practice for the management of uveitis, until higher levels of evidence are obtained.

Ectopic adrenocorticotropic (ACTH) syndrome is a rare condition, generally due to lung or carcinoid tumors. 18-fluorodeoxy-glucose positron emission tomography ((18)FDG-PET) can be useful where conventional localization techniques often fail. A 50-year-old man presented with sudden diffuse oedema, hypokaliemic alkalosis, Diabetes mellitus and high serum levels of ACTH and cortisol. Ectopic ACTH syndrome was confirmed leading to ketoconazole treatment. Chest-computed tomography only revealed an aspecific anterior mediastinal nodule that was hypermetabolic on the whole body-(18)FDG-PET. A thymic tumor was suspected and the patient had a thymectomy that revealed an atypical carcinoid tumor with pleural carcinosis. The postoperative course was favorable with clinical and biochemical remission of neoplastic Cushing's syndrome.

Granulomatous myositis is a rare condition that has been described in association with sarcoidosis. In the absence of sarcoidosis or other underlying disease, a diagnosis of isolated granulomatous myositis is considered.A 61-year-old African man presented with progressive limitation in running and proximal atrophy of the lower limbs for the past year. Quadricipital muscle biopsy revealed non-caseating epithelioid granulomas and multinuclear giant cells. Whole body fluorodeoxyglucose positron emission tomography ((18)FDG-PET) revealed hypermetabolic activity of salivary and lachrymal glands, and mild hypermetabolism in the mediastinal lymph nodes. Minor salivary gland biopsy was consistent with sarcoidosis.To our knowledge, this is the first reported case of sarcoid myopathy demonstrating the diagnostic usefulness of (18)FDG-PET.

This is a multicentric retrospective study of aspergillosis in patients treated by corticosteroids and/or immunosuppressive drugs for systemic diseases and a review of the literature. Nine patients, 5 men and 4 women, mean age of 62.8 years old were included among which Horton's diseases (3 cases), systemic lupus erythematosus (2), polymyositis (1), microscopic polyangiitis (1), idiopathic thrombocytopenic purpura (1), rheumatoid polyarthritis (1). Aspergillosis occurred in average 28.4 month after the diagnosis of systemic disease, and 28 months after the beginning of its treatment: corticosteroids in all cases, at a dose of 50.8 mg/day (equivalent prednisone) in average, cyclophosphamide (2 cases), methotrexate (1), intravenous immunoglobulins (1), leflunomide (1). All cases were invasive or chronic pulmonary aspergillosis located in the lungs (6 cases), or in the brain (3). Revealing symptoms were mild and non specific. Lymphopenia was severe in most cases, in average 472 lymphocytes/mm3 and 283 CD4+/mm3. The diagnosis was confirmed 20.75 days after the first symptoms in invasive aspergillosis, and 18.5 months in the chronic pulmonary cases, by cultures in 7 cases (broncho-alveolar lavage: 4; cerebral biopsy: 3), and direct microscopy examination of broncho-alveolar lavage in 2 cases. Specific serology was positive in 4 cases. Patients were treated by voriconazole (4 cases), itraconazole (2), amphotericin B (1), association of caspofungin and voriconazole (1), successive voriconazole and itraconazole (1). Six patients recovered from aspergillosis with 10.8 months of following time, 3 patients died a few days after confirmation of the diagnosis. Fifty-four cases of the literature are analysed.

After exclusion of a masquerade syndrome, uveitis may be associated with infection, systemic diseases, specific ocular diseases, or may be drug-induced. In order to improve diagnostic strategy in uveitis, we performed a comparative study to assess the importance of internist and ophtalmologist's collaboration and we proposed a well-adapted diagnostic procedure.A comparative study was performed in a tertiary centre. The population was divided in two groups. The first one was retrospective and consisted of patients treated at the Ophthalmology department of Croix Rousse Hospital from 1991 to 2002 without internist's collaboration. The second one was prospective and consisted of patients referred in the same centre in 2003 and 2004 with intervention of an internist. Patients of less than 18 years of age with pre-existent diagnosis, specific ocular diseases, toxoplasmosis infection, or with human immunodeficiency virus infection were excluded.Sixty-six patients were included. Anterior uveitis was the most frequent form (25 cases), followed by panuveitis (20 cases), posterior uveitis (14) and intermediate uveitis (7). The most frequent cause of uveitis was systemic disease (19 cases) followed by infection (7 cases) and neurological entities (4 cases). The rate of diagnosis was 30.3% without internist's intervention and 60.6% when patients were referred to an internist (P=0,01). The internist intervention was contributive in 75% of diagnoses.The internist intervention significantly enhances the rate of etiological diagnoses in uveitis. These results should further strengthen the internist/ophthalmologist collaboration for patients with uveitis.