Abstract: INTRODUCTION: 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. CASE REPORT: 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. CONCLUSION: This report evidences the association of polyserositis with hypereosinophilic syndromes and the potential efficacy of imatinib mesylate even in FIP1L1-PDGFRA-negative patients.
Abstract: Lung cancer is a leading cause of death among adults. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. For more than half of all patients diagnosis does not occur until the disease has metastasised. At this advanced stage, the 5-year survival rate is just 15%. Platinum-based chemotherapy forms the backbone of treatment for patients with advanced NSCLC and forms an important component of the therapeutic regimen for many patients with earlier stage disease. However, although a number of agents are available to partner the platinum-based compounds, treatment selection is largely empiric, and chemoresistance is a considerable barrier to improving outcomes. The identification of biologic and other markers to guide treatment selection, thus ensuring patients receive the most effective regimen for their individual tumour and avoid exposure to toxic agents from which they are unlikely to benefit, will be critical to improve outcomes for patients with NSCLC. The development of alternative agents for those patients who express predictors of a negative clinical response is of vital importance. A variety of biomarkers are emerging, including expression of DNA repair enzymes, ribonucleotide subunits and betaIII tubulin. Treatment algorithms based on elucidation of such markers to guide treatment selection can already be envisaged. For example, those patients with high betaIII tubulin expression should be considered for epothilone therapy as an alternative to taxane-based regimens. The epothilones may be preferred option as the evidence suggests that these agents retain activity versus taxane-resistant cancers. This paper reviews the evidence base for betaIII tubulin expression as a prognostic and predictive biomarker in NSCLC and briefly explores the implications for clinical decision making of this and other emerging biomarkers.
Abstract: Background. Parvovirus B19 infection (PVB19) has been linked with a broad spectrum of clinical syndromes. In addition to erythema infectiosum and asymptomatic infection, other less common manifestations include transient aplastic crisis in patients with hemoglobinopathies, pure red cell aplasia and pancytopenia in immunocompromised persons, nonimmune hydrops fetalis, chronic arthritis, myocarditis, and hepatitis. Purpose. Only 19% of patients had peripheral nervous system damage, mainly including brachial plexitis and carpal tunnel syndrome. Two cases of cranial nerves palsies have been described in children in the literature, including one case of peripheral facial nerve palsy and one case of velopalatine hemiparalysis. We report the first case of acute ophthalmoparesis associated with PVB19 infection. Methods. We present a 40-year-old man with PVB19 with acute sixth cranial nerve palsy, diagnosed on the basis of serology and polymerase chain reaction carried out both on serum and cerebrospinal fluid. Conclusions. Clinicians should be aware of this possible clinical presentation.
Abstract: BACKGROUND: Spinal cord involvement in sarcoidosis is rare, occurring in <1% of patients with sarcoidosis. METHODS: We report seven cases of spinal cord sarcoidosis, seen in two French hospitals over a 13-year period. Presentation of disease, methods of diagnosis and response to treatment, with quantification according to the reduction of the modified Rankin scale (MRS), were noted. RESULTS: Six patients presented insidious paresthesias or weakness and one a sudden paraplegia. Average MRS at diagnosis was to 2. Spine MRI showed one or several intramedullary lesions in all cases. Diagnosis was confirmed by extra-neural tissue biopsies in all cases, including mediastinoscopy (two patients), coelioscopy (one patient), bronchoscopy (one patient), salivary gland biopsy (one patient) and skin biopsy (two patients). The average follow-up for the group was 49.4 months. All patients responded to corticosteroid therapy with a median reduction of MRS of one point. Five patients received immunosuppressive therapy: cyclophosphamide (two patients), methotrexate (two patients), azathioprine (one patient), mycophenolate mofetyl (one patient), with an inconstant benefit. Patients who received cyclophosphamide presented severe fungaemia. CONCLUSION: Based on our study and literature analysis, we propose an algorithm for treatment of spinal cord sarcoidosis.
Abstract: 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.
Abstract: BACKGROUND: Case reports and small short case series have described patients with sarcoidosis and melanoma. OBJECTIVES: To examine the relation between sarcoidosis and melanoma. METHODS: Computerized search of all patients seen at our department of dermatology between 1998 and 2007 and review of the literature using a Medline search from 1985 to June 2008. RESULTS: We identified 7 cases in our population of 1,199 melanoma inpatients. Including these cases, 20 cases of sarcoidosis have been described in melanoma patients. Fifteen patients had their sarcoidosis diagnosed after melanoma. In 7 cases, sarcoidosis was related to immunotherapy. Sarcoidosis presented mainly as pulmonary disease without severe organ involvement, with a benign evolution. CONCLUSION: Our referral center study shows a prevalence of sarcoidosis of 0.58% among melanoma inpatients. Clinicians should be aware of the possibility that sarcoidosis may initially manifest itself in melanoma patients, especially after treatment with immunotherapy, and mimic metastatic disease.
Abstract: BACKGROUND: In 2002, the French Federation of Comprehensive Cancer Centers published clinical practice guidelines (CPGs) for the management of carcinomas of unknown primary (CUP). METHODS: 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. RESULTS: 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 PS < or = 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. CONCLUSIONS: 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.
Abstract: OBJECTIVE: To describe the prevalence, main characteristics, and treatment of severe autoimmune cytopenias [autoimmune hemolytic anemia (AIHA), autoimmune thrombocytopenic purpura (AITP)] in patients with chronic hepatitis C virus (HCV) infection. METHODS: Retrospective chart review of patients with chronic HCV infection seen at our institution. Two additional departments contributed eight more patients to assess therapy of HCV-related autoimmune cytopenias. RESULTS: Eight patients (seven AITP, one AIHA) fulfilled the inclusion criteria in our population of 4345 HCV-infected patients. The number of patients with AITP was much greater than would be expected by chance (P<0.0001). Patients with HCV-related AITP were older and demonstrated more immunological markers than a group of 40 controls. Eight additional patients (six AITP, two Evans syndrome) were included. We only assessed the response for AITP patients because of the single case of AIHA. Patients with AITP had a poor response to initial corticosteroids [one complete response (CR), three partial response (PR), and four failures]. Intravenous immunoglobulins led to transient efficacy in three of four patients. In second-line therapy, five of seven patients responded to splenectomy. Rituximab proved effective in increasing platelets in two patients. Of eight patients treated with antiviral therapy (IFN-alpha+/-ribavirin), five responded (three CR, two PR). CONCLUSION: AITP occurs more commonly in patients with chronic HCV infection than would be expected by chance. HCV-positive AITP requires a treatment strategy different from that used in HCV-negative AITP. On the basis of the results from our study and a literature analysis, we propose an algorithm for treatment of severe HCV-related autoimmune cytopenias.
Abstract: BACKGROUND: We have investigated predictors of 90-day-mortality in a large cohort of non-specific cancer of unknown primary patients. METHODS: Predictors have been identified by univariate and then logistic regression analysis in a single-center cohort comprising 429 patients (development cohort). We identified four predictors that produced a predictive score that has been applied to an independent multi-institutional cohort of 409 patients (validation cohort). The score was the sum of predictors for each patient (0 to 4). RESULTS: The 90-day-mortality-rate was 33 and 26% in both cohorts. Multivariate analysis has identified 4 predictors for 90-day-mortality: performance status>1 (OR = 3.03, p = 0.001), at least one co-morbidity requiring treatment (OR = 2.68, p = 0.004), LDH>1.5 x the upper limit of normal (OR = 2.88, p = 0.007) and low albumin or protein levels (OR = 3.05, p = 0.007). In the development cohort, 90-day-mortality-rates were 12.5%, 32% and 64% when the score was [0-1], 2 and [3]-[4], respectively. In the validation cohort, risks were 13%, 25% and 62% according to the same score values. CONCLUSIONS: We have validated a score that is easily calculated at the beside that estimates the 90-days mortality rate in non-specific CUP patients. This could be helpful to identify patients who would be better served with palliative care rather than aggressive chemotherapy.
Abstract: Hepatic angiosarcoma is a rare malignant vascular tumor, which accounts for up to 2% of all primary liver tumors. The most frequent symptoms on presentation are weight loss, weakness and abdominal pain. Diagnosis of diffuse hepatic angiosarcoma can be challenging. We report an original case of diffuse liver angiosarcoma revealed by haematological abnormalities initially diagnosed as an Evans syndrome. Anaemia and thrombocytopenia are rarely the first manifestations of this pathology. They are explained by combination of several mechanisms. Diagnosis of diffuse liver angiosarcoma can be extremely difficult and physicians should be aware of these presentation.
Abstract: PURPOSE: To assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in patients with unexplained chronic uveitis. METHODS: Retrospective review of 19 (18)F-FDG PET scans. All patients had normal chest CT. In the final analysis, the authors used criteria similar to the criteria of Abad et al. (Abad S, Meyssonier V, Allali J, et al. Association of peripheral multifocal choroiditis with sarcoidosis: a study of thirty-seven patients. Arthritis Rheum. 2004;51:974-982) for the diagnosis of sarcoidosis-associated uveitis. RESULTS: Ten (53%) whole-body scans were consistent with sarcoidosis. At the end, subsequent mediastinal biopsies proved sarcoidosis in 3 patients; 2 patients were considered as presumed sarcoidosis, and 6 indeterminate sarcoidosis. CONCLUSION: (18)F-FDG PET may show focal uptake suggestive of sarcoidosis in patients with unexplained uveitis.
Abstract: Relapsing polychondritis is an episodic and progressive systemic inflammatory disease characterized by auricular chondritis, polyarthritis, nasal and respiratory tract chondritis. About 30% of the patients have additional autoimmune and or hematological diseases, most frequently systemic vasculitis, rheumatoid arthritis, myelodysplastic syndromes or systemic lupus erythematosus. So far, only one case of coexisting relapsing polychondritis and sarcoidosis in a patient with AIDS has been reported. We describe here a case of sarcoidosis and relapsing polychondritis in an immunocompetent patient. Physicians should be aware of this possible association.
Abstract: On the basis of preclinical studies that show overexpression of class III beta-tubulin is associated with resistance to tubulin-binding agents, several investigators have addressed the relation between class III beta-tubulin and outcome in patients treated with such agents. High expression of class III beta-tubulin has been found to be correlated either with low response rates in patients treated with regimens containing taxanes or vinorelbine or with reduced survival in patients with non-small-cell lung cancer, in breast, ovarian, and gastric cancers, and in cancers of unknown primary site. Two studies have shown patients with advanced non-small-cell lung cancer receiving paclitaxel whose tumours expressed high levels of class III beta-tubulin had a lower response to paclitaxel and shorter survival, whereas this variable was not found to be predictive in patients receiving regimens without tubulin-binding agents. Conversely, analysis of samples from patients in the JBR-10 trial, which compared adjuvant chemotherapy to no further therapy in operable non-small-cell lung cancer, showed that chemotherapy seemed to overcome the negative prognostic effect of high levels of expression of class III beta-tubulin and the greatest benefit from cisplatin/vinorelbine was seen in patients with high levels of expression of class III beta-tubulin. Further analyses in operable and advanced non-small-cell lung cancer showed a relation between high expression of class III beta-tubulin and baseline factors such as age under 60 years, adenocarcinoma and large-cell carcinoma histologies, and advanced stage of disease. These results suggest that class III beta-tubulin could be both a prognostic and a predictive factor. Large randomised studies are warranted to determine the prognostic or predictive value of class III beta-tubulin in different settings and tumours.
Abstract: Our study aimed to determine the frequency of uveitis among MS patients through the Lyon MS Database and compare the clinical spectrum and time course of MS in patients with or without uveitis. Twenty-eight patients with uveitis were detected. The prevalence of uveitis in our population was 0.65% (28/4,300). Uveitis preceded onset of MS in 46% of the patients; it occurred simultaneously or after MS, in 18% and 36% of the cases, respectively. The topography and timing of uveitis were not associated with any significant difference in MS course and prognosis. There was no difference in the course and prognosis in patients with or without uveitis.
Abstract: 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.
Abstract: INTRODUCTION: Cancer-related fatigue is very common but its management remains frustrating. We thus sought to review current knowledge in this field: epidemiologic data, pathophysiological mechanisms, assessment, and treatment. METHODS: We queried the Medline database for all articles on this topic published between 1997 and 2007 and analyzed the articles published in English and French, as well as some of the essential earlier work. RESULTS: Approximately 60 to 96% of patients treated for cancer report fatigue. The prevalence of fatigue that persists after the disease is considered to be in remission is substantial. Fatigue is a multidimensional problem with biological, psychological, social, and personal aspects. Physical causes must be systematically considered (comorbidities, anemia, and endocrine disorders), but most cases remain unresolved. Many may be attributed to deconditioning. There is not now any pharmacological therapy that treats this symptom effectively. Some psychostimulants are being tested, but the initial results of the studies are contradictory. Exercise is the intervention for which there is the most evidence of effectiveness. CONCLUSION: Cancer-related fatigue is a very common symptom for which no specific cause can usually be identified. In this situation, rest may be more harmful than exercise.
Abstract: To describe the main characteristics and treatment of autoimmune hemolytic anemia (AHA) in patients with common variable immunodeficiency (CVID), we analyzed data from 18 patients, 4 from an earlier study and 14 from the French DEF-I cohort on adult patients with primary hypogammaglobulinemia. To be included, patients had to have CVID and a previous history of AHA with a hemoglobin level < or =90 g/L at onset. To determine whether AHA is associated with a particular clinical phenotype of CVID, we conducted a case-control study from the DEF-I cohort. The estimated frequency of AHA in CVID patients from the DEF-I cohort was 5.5% (14/252). Median age at AHA diagnosis was 26 years (range, 1-57 yr), and 27.5 years (range, 5-61 yr) at CVID diagnosis. CVID was diagnosed before the onset of AHA in only 2 patients (11%). CVID was diagnosed more than 6 months after AHA in 10 cases (55.5%), and the 2 conditions were diagnosed concomitantly in 6 cases. The 14 patients included in the DEF-I cohort were compared with 238 control patients with CVID but without AHA. Corticosteroids were used as initial treatment for all patients in the current study. An initial response was obtained in 15 of 18 (83%) patients. Overall, 9 of these (60%) achieved a lasting response with steroids alone (7 patients) or in combination with intravenous immunoglobulin (2 patients). Seven patients underwent splenectomy, and 5 additional splenectomies were performed for associated autoimmune thrombocytopenic purpura. After splenectomy, a lasting response was obtained in 3 of the 7 patients with AHA. However, 5 of the 12 splenectomized patients experienced life-threatening infection. Severe infection occurred in 2 of 4 patients receiving immunosuppressive drugs. At the end of follow-up, 13 of 18 (72%) patients were in treatment-free remission (13 complete responses), and 4 of 18 (22%) were in remission while on prednisone < or =20 mg/d. One patient had died, of cancer.
Abstract: AIM: To determine the prognostic value of microtubule component expression in tumors of patients with carcinomas of unknown primary site (CUP). PATIENTS AND METHODS: Class III beta-tubulin, Delta2-alpha-tubulin and tau protein were examined immunohistochemically in 51 CUP tumors from patients receiving paclitaxel and compared with their response to treatment. RESULTS: The overall response rate was 18.4% among 49 evaluable patients. Delta2-alpha-Tubulin and tau were not correlated with response or patient outcome. High class III beta-tubulin expression was correlated with both resistance to chemotherapy and shorter overall survival, while there was no relation with progression-free survival. In multivariate analysis taking into account clinical factors, class III beta-tubulin expression was independently correlated with overall survival. CONCLUSION: These findings show that in tumor cells a high level of expression of class III beta-tubulin, but not Delta2-alpha-tubulin or tau, is associated with resistance to paclitaxel and a poor prognosis in CUP patients receiving paclitaxel.
Abstract: Granulomatous myositis (GM) is a rare condition that has generally been described in association with sarcoidosis. In the absence of sarcoidosis or other underlying disease, a diagnosis of isolated GM is considered. Only one study has focused on the clinical difference between isolated GM and sarcoid myopathy (SM). We report 13 cases of symptomatic GM; 8 had sarcoidosis. All patients with sarcoidosis had predominantly proximal, symmetrical lower-limb weakness, and 3 subsequently developed upper-limb or distal involvement. Three of the five patients with isolated GM had predominantly distal muscle involvement, and two had dysphagia. Corticosteroid treatment was followed by prolonged improvement in only one patient with sarcoidosis. One patient had acute sarcoid myositis and benefited from methotrexate; other immunosuppressants and etanercept proved ineffective in chronic sarcoid myopathy. Three of the five patients with isolated GM responded to corticosteroid treatment. When last examined, three patients with sarcoidosis had severe disability, whereas patients with isolated GM showed milder weakness. Thus, SM was frequently associated with severe disability and rarely improved after corticosteroid treatment, whereas most patients with isolated GM improved.
Abstract: PURPOSE: In this study, we determine the prevalence and the prognostic value of the class III beta-tubulin microtubule protein examined immunohistochemically, in tumors of 40 patients with carcinomas of unknown primary site treated with paclitaxel-based chemotherapy. METHODS: Immunohistochemical intensity of staining and percentage of cells were quantified. Clinical characteristics, response to chemotherapy, progression-free survival, and overall survival were assessed for relationships with the expression of class III beta-tubulin. RESULTS: The response rate was 17.9% (seven partial responses among 39 valuable patients), while eleven patients had a stable disease (28.2%) and 21 patients progressed on therapy (53.8%). Patients with high class III beta-tubulin expression were more resistant to taxane-based chemotherapy, defined as progression under treatment, while patient characteristics were not found to be correlated with response to chemotherapy. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter overall survival, while there was a trend for an association with progression free survival. Multivariate analysis showed that class III beta-tubulin expression was independently correlated with progression free survival and overall survival. CONCLUSIONS: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to paclitaxel and decreased survival in patients with carcinomas of unknown primary receiving paclitaxel-based chemotherapy.
Abstract: BACKGROUND: The authors conducted a comprehensive review of the efficacy of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography (FDG-PET) in the detection of primary tumors in patients with disseminated carcinoma of unknown primary site. METHODS: Ten studies (involving a total of 221 patients) tat were published between 1998 and 2006 were reviewed. Each study evaluated the role of FDG-PET in the detection of unknown primary tumors after a conventional diagnostic workup. Although 94% of patients had a single site of metastases, the studies otherwise were very heterogeneous in the studied population, study design, and additional diagnostic workup. RESULTS: In 41% of patients, FDG-PET detected primary tumors that were not apparent after conventional workup. In this group of patients, the overall sensitivity, specificity, and accuracy rates of FDG-PET in detecting unknown primary tumors were 91.9%, 81.9%, and 80.5%, respectively. FDG-PET imaging also led to the detection of previously unrecognized metastases in 37% of patients. Lung cancers represented 59% of the detected tumors. FDG-PET had a notably high false-positive rate (58.3%) in tumors of the lower digestive tract. FDG-PET altered the clinical management in 34.7% of patients. Most of those patients (53%) received specific chemotherapy for lung and pancreatic cancers; whereas 12% received specific therapy for breast, ovarian, and prostate cancers; and 14% underwent surgery with curative intent. CONCLUSIONS: FDG-PET was an efficient method for detecting primary tumors that were undetected by other modalities and was sensitive for the detection of previously unrecognized metastases. FDG-PET significantly changed clinical management in approximately one-third of the patients studied.
Abstract: PURPOSE: High class III beta-tubulin (bTubIII) expression in advanced non-small cell lung cancer is known to correlate with reduced response rates and inferior survival with anti-microtubule agents. JBR.10 showed a 12% and 15% improvement in 5-year recurrence-free survival (RFS) and overall survival (OS), respectively, with the addition of cisplatin and vinorelbine following resection of stage IB-II non-small cell lung cancer. We sought to determine the effect of bTubIII on patient outcome and benefit from adjuvant chemotherapy in the JBR.10 trial. EXPERIMENTAL DESIGN: We did a semiquantitative immunohistochemical assay for bTubIII on primary tumor tissue available from 265 of the 482 patients in JBR.10. Tumors were classified as bTubIII "low" or "high" using a validated method. We examined the prognostic effect of bTubIII in patients treated with or without chemotherapy and the survival benefit from chemotherapy in low versus high bTubIII subgroups. RESULTS: High bTubIII expression was associated with poorer RFS and OS in patients treated with surgery alone but not in patients treated with adjuvant chemotherapy. The RFS and OS benefits of adjuvant chemotherapy were greater in high versus low tubulin expressors. However, with Cox regression, the interaction between bTubIII status and chemotherapy treatment in predicting RFS or OS did not reach statistical significance. CONCLUSIONS: Chemotherapy seemed to overcome the negative prognostic effect of high bTubIII expression. Greater benefit from adjuvant chemotherapy was seen in patients with high bTubIII expression. This is contrary to what has been seen in the setting of advanced disease; possible reasons for this difference are being explored.
Abstract: 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.
Abstract: INTRODUCTION: 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. OBSERVATION: 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. CONCLUSION: To our knowledge, this is the first reported case of sarcoid myopathy demonstrating the diagnostic usefulness of (18)FDG-PET.
Abstract: We present the case of a 79-year-old female patient with chronic obstructive pulmonary disease on home oxygen therapy who was diagnosed as having Sjögren's syndrome with arthralgias and painful sensory neuropathy. She subsequently developed bilateral numb chin syndrome. Because of refractory and disabling symptoms under high corticosteroids and severe chronic obstructive pulmonary disease, we decided to treat her with rituximab rather than immunosuppressants. This resulted in significant subjective improvement in sicca syndrome while arthalgias, distal and chin paresthesias resolved completely. To our knowledge this is the first description of such a case.
Abstract: OBJECTIVE: An unusual case of a patient with Löfgren syndrome peritoneal involvement by sarcoidosis. Patient and methods: A 36-year-old woman presented with Löfgren syndrome and an increase in liver enzyme levels. An abdominal CT scan showed multiple nodules on the peritoneum mimicking peritoneal carcinomatosis. Laparoscopy was conducted with biopsy of the peritoneal nodules. RESULTS: Biopsy specimens from the peritoneum, liver, and bronchi showed noncaseating granulomas, and the search for tuberculosis was negative. Clinical and biological features resolved within 6 months, without therapy with steroids, while a thoracic CT scan as well as an abdominal CT scan showed no change. CONCLUSION: To our knowledge, this is the first reported case of peritoneal sarcoidosis associated with Löfgren syndrome. A longer follow-up will, however, be required to assess the chronicity of the disease.
Abstract: Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disorder affecting the elastic structures in the body, manifesting with cutaneous, ophthalmologic and cardiovascular findings. The association of PXE and systemic disease is rare, as only six cases have been reported in the literature. We describe herein two cases of coexisting PXE and cutaneous lupus and discuss a possible association. Although a fortuitous association cannot be excluded, the calculated prevalence of the association in our area was much less than in our observation. Given the ocular and vascular complications of PXE, clinicians who treat patients with lupus should be aware of this possible association.
Abstract: INTRODUCTION: Like Fusobacterium necrophorum, Fusobacterium nucleatum is capable causing Lemierre's syndrome. Various locations of venous thrombosis have been described associated with Fusobacterium sp. septicemia. EXEGESIS: We describe a 43-year old alcoholic patient with F.nucleatum septicemia complicated with hepatic abscesses, middle hepatic venous thrombosis, osteomyelitis and infiltrative pneumonia. A pancreatic prosthesis was the only potentially identified infectious entrance. CONCLUSION: Our patient showed an alternative presentation of Lemierre's syndrome, a "digestive variant". To the best of our knowledge, this is the first report of Fusobacterium septicemia associated with hepatic venous thrombosis. This report is close to the cases of portal thrombosis and opens the clinical sphere of the lemierre's syndrome, whose incidence is increasing.
Abstract: Monoclonal gammopathy has been reported rarely in association with infectious diseases. Viral infection has been the most frequently reported. We report a case of Bartonella quintana endocarditis in a 45-year-old homeless male associated with a monoclonal IgG kappa gammopathy. The gammopathy disappeared after 8 months of antibiotics while the Bartonella antibody titre was decreasing. This correlation suggests a causative role for B. quintana for the monoclonal gammopathy. To the best of our knowledge, this the first report of monoclonal gammopathy in the course of B. quintana infection.
Abstract: PURPOSE: Carcinoma of unknown primary site is a common clinical syndrome, accounting for 2% of cancer patients. Diagnosis is a recurrent challenge for internists. Treatment is difficult and prognosis is still poor. This review presents one synthesis of diagnosis strategies and therapeutic trials. It envisages the interest of new molecular biology methods as well as therapeutic perspectives. CURRENT KNOWLEDGE AND KEY POINTS: Pathologic examination completed with immunohistochemical tests, and, depending on cases, with electron microscopy, cytogenetics, and molecular biology is a key-point for diagnosis. Diagnosis work-up, based on histological type and on individualization of some clinical presentation, proceeds in three steps. Positron emission tomography is recommended when a curative treatment is planed, particularly in cases of isolated metastasis. Functional status analysed using the performance status and simple biologic parameters (serum lactate dehydrogenase, serum alkaline phosphatase) permit us to assess prognosis. Chemotherapy is offered for patients with a good general health status. FUTURE PROSPECTS AND PROJECTS: Further evaluation of positron emission tomography, as well as cost-benefit analyses, is warranted. Further randomised trials are necessary to determine the optimal chemotherapy regimen in good-risk patients and the interest of chemotherapy in patients with poor-risk disease. Gene expression profiling and proteomic evaluation, as well as pharmacogenomic offer new investigation fields.
Abstract: BACKGROUND: The authors investigated how lymphopenia and low serum albumin levels correlate with the prognosis of patients with carcinoma of unknown primary (CUP). METHODS: Univariate and multivariate prognostic factor analyses were conducted in a population of 317 consecutive patients with CUP who were evaluated at the Cross Cancer Institute of Edmonton, Alberta, Canada, from 1998 to 2004. RESULTS: The results from multivariate analysis showed that patients who had a performance status >/=2 (using the World Health Organization scale), a high overall comorbidity score (on the Adult Comorbidity Evaluation 27), liver metastasis, elevated serum lactate dehydrogenase (LDH) levels, lymphopenia (defined as an absolute lymphocyte count >/=0.7 x 10(9)/L), and low serum albumin levels had a worse prognosis. Based on the observation that the presence of liver metastasis and low serum albumin levels were the most powerful adverse prognostic factors, a classification scheme was delineated that took those 2 variables into account. A group of good-risk patients (no liver metastasis and normal serum albumin levels) and a group of poor-risk patients (liver metastasis and/or low serum albumin levels) were identified with median survivals of 371 days and 103 days, respectively (P < .0001). This classification was validated further in an independent data set of 124 patients who were evaluated at 2 French cancer centers: Among those patients, the median survival was 378 days in the good-risk group and 90 days in the poor-risk group (P < .0001). The new prognostic model substantially outperformed the previous standard prognostic model, which was based on performance status and serum LDH levels. CONCLUSIONS: Lymphopenia and low serum albumin levels were identified as 2 new independent markers of prognosis in patients with CUP. Although the authors confirmed the validity of the previous prognostic model, they developed and validated a more powerful, simple model based on the 2 most powerful adverse prognostic factors: liver metastasis and low serum albumin levels. These findings were confirmed in an independent cohort of patients with CUP, and consideration of the authors' improved prognostic model for survival of patients with CUP is warranted.
Abstract: BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Abstract: 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.
Abstract: BACKGROUND: The authors investigated how comorbidities, age, and performance status were related to the choice of chemotherapy and to the prognosis of patients with carcinomas of unknown primary site (CUP). METHODS: Patients in Northern Alberta who were diagnosed with CUP during 2000 to 2003 were included (n = 389 patients). Survival was compared by age at diagnosis (ages <65 years, 65-74 years, and >75 years), comorbidity score (Adult Comorbidity Evaluation-27 [ACE-27] scores of 0-1 and >2), performance status (PS), and other explanatory variables, such as gender, histology, and site and number of metastases. RESULTS: The median age was 68 years, and the median overall survival was 12 weeks. An ACE-27 overall comorbidity score >2 was found in 34% of patients, and a PS >2 was observed in 50% of patients. Multivariate analysis showed that patients who had a PS >/=2 and a high overall ACE-27 score had a worse prognosis. The impact of comorbidities on survival was limited to patients with low PS. Patients who were not evaluated at a cancer center were older, had a worse functional status, and had more moderate or severe comorbidities. Among the 257 patients who were evaluated at a cancer center, 108 patients received chemotherapy, and 121 patients had a good PS (0-1). Age was the only independent variable that was related to the likelihood of not receiving chemotherapy among patients who had a good PS. The median overall survival of the 121 patients who had a good PS was 317 days, and overall survival was not associated significantly with chemotherapy. A logistic regression analysis that included all patients who were evaluated at a cancer center identified young age, good PS, lymph node/pleural involvement, and few comorbidities as variables that were associated independently with receiving chemotherapy. CONCLUSIONS: Patients with CUP who were not evaluated at a cancer center were older, had a worse functional status, and had more moderate or severe comorbidities; this referral bias largely explained the differences between data from registries and from tertiary centers. Moderate and severe comorbidities impacted survival in patients with who had a PS > or =2. An age-related decline was observed in the percentage of adults with good PS who received chemotherapy. The current results suggested that older patients with CUP were under treated and that factors other than PS were involved in the decision to use chemotherapy for the treatment of patients with CUP.
Abstract: The aim of this study was to evaluate the response to treatment and the long-term outcome in a cohort of patients in whom severe autoimmune hemolytic anaemia (AHA) was the leading manifestation of systemic lupus erythematosus (SLE). Twenty-six women with severe isolated AHA were included. Corticosteroids were used as the initial treatment for all patients in our study. An initial response was obtained in all but one patient (96%). The overall recurrence rate was three per 100 person-years, with an expected recurrence-free proportion of 73% with a 180 months median follow-up. Seven patients (27%) experienced a relapse of AHA. We found a higher proportion of pleuritis in relapsing patients. Only three patients experienced multiple relapses despite splenectomy and several immunosuppressants. Steroid-sparing effect of hydroxychloroquine and azathioprine could not be assessed because most of the patients received these treatments for other reasons than AHA. Intravenous immunoglobulins induced transient response in three cases. Splenectomy was efficient to definitively control AHA in one patient but two patients quickly experienced relapses while one patient did not benefit. Five patients received immunosuppressants that induced only transient responses. Rituximab was long-term efficient in one case. In conclusion, severe AHA is a serious complication of SLE that warrants appropriate management. On the basis of our experience, the ideal treatment of isolated AHA should be oral corticosteroids in first-line treatment. Our study does not support an important role for splenectomy. Patients refractory to conventional therapy should be treated either with few toxic immunosuppressive drugs, danazol or rituximab.
Abstract: OBJECTIVES: To describe 2 cases of parvovirus B19 (B19) infection mimicking systemic lupus erythematosus (SLE) and to identify all cases of SLE imitated by and/or associated with B19 in the medical literature. METHODS: A computer-assisted (PubMed) search of the medical literature from 1975 to 2003 was performed using the following key words: parvovirus, B19, SLE, lupus, antibodies, auto-immunity. RESULTS: Thirty-eight patients were identified: 35 women, 3 men; mean age = 28.8 years. Clinical manifestations were as follows: fever (24 patients); articular involvement (36 patients); cutaneous lesions (28 patients); lymphadenopathy (9 patients); hepato- and/or splenomegaly (6 patients); serositis (6 patients); renal involvement (4 patients); cerebral impairment (10 patients). Cytopenia was observed in 23 cases. Antinuclear antibodies were detected in 34 patients, anti-double-stranded DNA antibodies in 20 patients, anti-Sm antibodies in 4 patients, antinuclear ribonucleoprotein antibodies in 5 patients, anti-Ro-SSA antibodies in 4 patients, anti-La-SSB antibodies in 4 patients, and anticardiolipin and/or anti-beta2-glycoprotein I antibodies in 8 patients. Hypocomplementemia was found in 15 of 26 patients. In 19 cases, the B19 infection had a self-limiting course. In 6 cases, B19 infection occurred in a context of previously established SLE, simulating SLE exacerbation. In 6 observations, symptoms persisted several months after the viral infection. In 7 cases, the exact relationship between SLE and B19 could not be determined. CONCLUSIONS: B19 infection may present a clinical and serological tableau making it difficult to distinguish between a viral infection and the first episode of SLE. Although B19 may modulate the clinical and biological features of rheumatic disease, studies in large series do not support a causative role for B19 in the pathogenesis of SLE.
Abstract: PURPOSE: Autoimmune manifestations (AIM) are associated to common variable immunodeficiency (CVI) in about 20 to 25% of the cases. This study presents the clinical, biological characteristics and the evolution of nine patients developing CVI and AIM. A peripheral B-cell compartment analysis has been performed in seven cases. METHOD: This multicenter retrospective study analyses nine patients, six men and three women, within a population of 32 CVI. RESULTS: The mean age was 27 years at the time of diagnosis of AIM and 30 years at the time of diagnosis of CVI. The diagnosis of AIM preceded the diagnosis of CVI in five cases. Thirteen AIM of different types were observed: autoimmune hemolytic anemia (AHA, 3), immune thrombocytopenic purpura (ITP, 2), Evan's syndrome (2), primary biliary cirrhosis (1), rheumatoid arthritis (1), alopecia totalis (1), myasthenia gravis (1). The peripheral B-cell compartment was investigated in seven patients: five patients with autoimmune cytopenia presented with a diminution of memory B cells (CD27+IgD-) and immature B cells (CD21-) levels; the patient with primary biliary cirrhosis and myasthenia gravis had only a diminution of memory B cells level; the last patient with ITP presented with a normal level of memory B cells. Five among the seven patients with autoimmune cytopenia required a specific treatment using corticosteroids, high dosages of intravenous immunoglobulin, then splenectomy after failure of the medical management, with severe infectious complications in one case. CONCLUSION: The association of AIM and CVI is not fortuitous. The most common AIM is autoimmune cytopenia. The peripheral B-cell compartment analyses show that a majority of patients have a defect in memory B-cells. Treatment regimens are not standardized and splenectomy increases the risk of infectious complications.
Abstract: Survival is impaired in rheumatoid pericarditis complicated by cardiac compression by either tamponade or constriction. Conventional therapy with non-steroidal anti-inflammatory agents and glucocorticoids is frequently ineffective in reversing severe cardiac impairment and/or in preventing recurrences. Colchicine, an effective and safe treatment of idiopathic and post-viral pericarditis, has not been studied in rheumatoid pericarditis. We describe the case of a 44-year-old woman with a 1-year history of rheumatoid arthritis who developed rheumatoid pericarditis complicated with tamponade. Pericardiocentesis relieved the symptoms, but pericarditis recurred at a high dose of prednisone of 70 mg/day. Colchicine at a dose of 1 mg/day prevented recurrences and had a significant sparing effect on steroids, which were reduced to 6 mg/day. This is the second case report describing the effectiveness of colchicine therapy in rheumatoid pericarditis complicated with tamponade. These cases suggest that colchicine should be considered in the treatment of rheumatoid pericarditis.
Abstract: The treatment of advanced non-small-cell lung cancer (NSCLC is based on the combination of platin and one of the following agents: taxanes, gemcitabine, vinorelbine or irinotecan. There are no significant differences in efficacy among these combinations suggesting that the maximum efficacy has been reached. In this review, we will consider the mechanisms of chemoresistance of the five groups of cytotoxic drugs commonly used in the treatment of advanced NSCLC as well as the clinical studies which have assessed the value of chemoresistance markers. Breast Cancer Related Protein (BRCP) expression has been related to irinotecan and cisplatin (CDDP) resistance. DNA repair capacity influences response to CDDP and ERCC1 gene stands out as a predictive marker of CDDP sensitivity. Preliminary studies indicate that high tubulin III and stathmin mRNA levels correlate with response to paclitaxel and vinorelbine and that high expression of class III tubulin by tumor cells assessed immunohistochemically in patients receiving a taxane-based regimen is associated with a poor response to chemotherapy, and a shorter progression-free survival. High expression levels of ribonucleotide reductase has also been related to response to gemcitabine. Uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1) genotype has been reported to be associated with time to progression and survival in patients treated with irinotecan. These data suggest that pharmacogenomic strategies may be used for developing customized chemotherapy in prospective studies. Adjuvant chemotherapy which had recently shown its usefulness in limited lung cancer represents another area of investigation for pharmacogenomic studies.
Abstract: PURPOSE: To report on a patient affected by bilateral intermediate uveitis (IU) as the initial sign of an uveomeningitic syndrome. METHODS: Thorough history, physical examination and ancillary laboratory and radiological testing were performed in this observational case study. RESULTS: A 23-year-old Caucasian man developed bilateral IU, primarily diagnosed as "idiopathic" since a detailed etiologic work-up was not indicative of underlying disease. Seven months later, he presented with poliosis and vitiligo. Lumbar puncture revealed cerebrospinal fluid pleocytosis. Optical coherence tomography showed bilateral subclinical macular edema (ME). The visual acuity was still 20/20 in both eyes. Clinical, laboratory and radiological results did not fit into any known syndrome. CONCLUSIONS: According to all the tests performed, the disease in our patient is a uveomeningitic disease with IU and ME which could be interpreted as an atypical form of Vogt-Koyanagi-Harada disease or a new uveomeningitic syndrome because there is no evidence for any other known disease.
Abstract: We present the case of a 50-year-old female with polyarthralgias and dysphonia. Indirect laryngoscopy revealed the presence of cricoarytenoid arthritis. The patient complained of dryness of the eyes and oral mucosa and was diagnosed with Sjögren's syndrome. Treatment with prednisolone quickly brought remission of systemic and laryngeal symptoms as well as improvement in the results of video-laryngostroboscopic tests. Laryngeal involvement is uncommon in Sjögren's syndrome. One case with vocal nodules, one with lymphocytic infiltration of the larynx, and one with repeated false cord swelling have been previously reported.
Abstract: Both fundamental and clinical studies suggest that class III beta-tubulin expression is associated with resistance to taxanes and constitutes a prognostic factor in several solid tumors. In this study, we assessed the prognostic and predictive value of class III beta-tubulin in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with paclitaxel-based or other regimens that did not include tubulin-binding agents. Expression of class III beta-tubulin was examined immunohistochemically in 91 tumor samples obtained before treatment from patients with stage III and IV NSCLC, including 47 who received paclitaxel-based regimens and 44 who received regimens without tubulin-binding agents. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of class III beta-tubulin protein. The response rate was 37.5% (16 responses among 45 evaluable patients) among patients receiving paclitaxel. Patients whose tumors expressed low levels of class III beta-tubulin isotype had a better response rate, longer progression-free survival, and overall survival (P < 0.001, 0.004, and 0.002, respectively), whereas this variable was not found to be predictive in patients receiving regimens without tubulin-binding agents. A multivariate analysis taking into account sex, age, histology, stage, and class III beta-tubulin confirmed that low-level class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.003) and overall survival (P = 0.003). These findings suggest that the expression levels of class III beta-tubulin in tumor cells is predictive of response to therapy and patient outcome in patients with NSCLC receiving paclitaxel-based chemotherapy but is not a general prognostic factor in this patient population.
Abstract: PURPOSE: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. RESULTS: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta2 alpha-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). CONCLUSIONS: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.
Abstract: Resistance to gemcitabine is likely to be multifactorial and could involve a number of mechanisms involved in drug penetration, metabolism and targeting. In vitro studies of resistant human cell lines have confirmed that human equilibrative nucleoside transporter 1 (hENT1)-deficient cells display resistance to gemcitabine. Overexpression of certain nucleotidases, such as cN-II, has also been frequently shown in gemcitabine-resistant models. In this study, we applied immunohistochemical methods to assess the protein abundance of cN-II, hENT1, human concentrative nucleoside transporter 3 (hCNT3) and deoxycitidine kinase (dCK) in malignant cells in from 43 patients with treatment-naïve locally advanced or metastatic non-small cell lung cancer (NSCLC). All patients subsequently received gemcitabine-based chemotherapy. Response to chemotherapy, progression-free survival (PFS), and overall survival (OS) were correlated with abundance of these proteins. Among the 43 samples, only 7 (16%) expressed detectable hENT1, with a low percentage of positive cells, 18 expressed hCNT3 (42%), 36 (86%) expressed cN-II and 28 (66%) expressed dCK. In univariate analysis, only cN-II expression levels were correlated with overall survival. None of the parameters were correlated with freedom from progression survival nor with response. Patients with low levels of expression of cN-II (less than 40% positively stained cells) had worse overall survival than patients with higher levels of cN-II expression (6 months and 11 months, respectively). In a multivariate analysis taking into account age, sex, weight loss, stage and immunohistochemical results, cN-II was the only predictive factor associated with overall survival. This study suggests that cN-II nucleotidase expression levels identify subgroups of NSCLC patients with different outcomes under gemcitabine-based therapy. Larger prospective studies are warranted to confirm the predictive value of cN-II in these patients.
Abstract: OBJECTIVES: To describe 2 cases of adult Kawasaki Disease (KD) and to review the medical literature to better define the epidemiological, clinical, laboratory, histopathological, cardiovascular, and therapeutic aspects of adult KD compared with pediatric KD. METHODS: Report of 2 cases, and review of the literature using a Medline search from 1967 to June 2003. RESULTS: Including our 2 cases, there are 57 reports of adult KD, 74% among patients aged 18 to 30 years. Nine cases of KD associated with human immunodeficiency virus (HIV) infection were described, suggesting that an immunocompromised state may predispose to this syndrome. The incidence of specific diagnostic criteria was roughly similar in adults and in children. However, cheilitis, meningitis, and thrombocytosis were observed in a larger percentage of children, while arthralgia, adenopathy, and liver function abnormality were more common in adults. Although adult KD often was diagnosed after the acute phase, when a significant beneficial effect from gammaglobulin infusion could not be expected, this treatment did appear to shorten the course of the disease. Coronary aneurysms were less frequent in adults than in children. Prognosis was more favorable in adults, with less cardiovascular complications and no deaths. CONCLUSIONS: Adult KD is a rare condition, which may go unrecognized. Other known disease processes with similar clinical presentations such as hypersensitivity drug reaction and toxic shock syndrome must be ruled out. For adult KD, exclusion criteria such as absence of hypotension, visceral impairment, staphylococcal infection, and any drug able to induce a drug hypersensitivity reaction are suggestive of the diagnosis, in the presence of the inclusion criteria, rash, conjunctival effusion, oropharynx changes, extremity changes, or adenopathy.
Abstract: Vasculitis associated with anti-neutrophil cytoplasmic antibodies has been reported in patients treated with anti-thyroid drugs and especially propylthiouracil. We report here a case of granulomatous eosinophilic vasculitis mimicking gastric neoplasm and peripheral eosinophilia in a 27-year-old man who was treated with carbimazole for 5 months for Graves' disease. Clinical and morphologic features resolved within 2 months after stopping the drug, suggesting a causative role for the drug. To our knowledge, this is the first biopsy-proven granulomatous eosinophilic vasculitis associated with this drug.
Abstract: PURPOSE: Parvovirus B19 (B19) causes many clinical disorders, of which the most common are erythema infectiosum, aplastic crisis complicating chronic hemolytic anemia, and hydrops fetalis. In young adults, the skin eruption caused by B19 is accompanied by polyarthritis and polyarthralgia in 60% of the cases. Rheumatoid factors and other antibodies including antinuclear antibodies, anti-ADN, and antiphospholipids can be produced in the wake of B19 infection. CURRENT KNOWLEDGE AND KEY POINTS: These features may simulate systemic diseases as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) (lupus-like eruption over the cheeks, cytopenia, etc.) or vasculitis (purpura, renal involvement). In addition, there have been a few reports of SLE, vasculitis and other connective tissue diseases developing shortly after a B19 infection associated with virus clearance suggesting that B19 can act as a trigger of systemic disease. However, studies in large series indicate that in fact B19 is probably an extremely rare cause of RA, SLE or vasculitis. FUTURE PROSPECTS AND PROJECTS: In fundamental studies B19 interacts with inflammatory cells by regulation of cytokines. More recently, two studies suggest that viral infection due to B19 may affect the course of SLE, leading to specific biological subsets. These preliminary findings require confirmation to elucidate the significance of the presence of B19 in systemic disease.
Abstract: OBJECTIVES: The role of hepatitis C virus (HCV) infection in the pathogenesis of non-Hodgkin's lymphoma (NHL) is controversial. A high prevalence of HCV infection in patients with NHL has been reported in Italy and Japan. By contrast, several studies in Northern Europe and Canada have not found any increased prevalence of HCV in B-cell NHL, suggesting a possible geographic variation. We sought to determine whether such an association could be found in patients treated in the Rhone-Alpes region in south-east France. Our main interest was to identify histological subtypes preferentially linked to HCV. METHODS: We determined the prevalence of anti-HCV antibodies in 212 consecutive patients with B-cell NHL diagnosed in our institution between January 1997 and December 1998. The comparison group comprised 974 patients tested for HCV before transfusion at the same hospital during the same period. RESULTS: Anti-HCV antibodies were found in six (2.8%) NHL patients. The distribution by histopathological category was as follows: three gastric mucosa-associated lymphoid tissue (MALT) lymphomas, one marginal lymphoma and two diffuse large-cell lymphomas. Anti-HCV antibodies were found in 20 (2%) of 974 comparison patients. Overall, there was a positive but non-significant trend towards an association between NHL and HCV infection (odds ratio 1.31; 95% confidence interval 0.51-3.36). However, the prevalence of HCV antibodies was significantly higher in MALT lymphoma patients than in the comparison group (odds ratio 9.87; 95% confidence interval 2.59-37.69). CONCLUSIONS: To our knowledge, this is the first French study to show an association between HCV and MALT lymphoma. These results, although derived from a small number of patients, suggest a possible role of HCV in gastric MALT lymphomagenesis.
Abstract: PURPOSE: Review of the literature on adult Kawasaki disease. CURRENT KNOWLEDGE AND KEY POINTS: Kawasaki disease is an acute multisystemic vasculitis affecting predominantly young children. Several studies have suggested that Kawasaki disease is mediated by bacterial superantigens. The diagnosis is established on clinical criteria since no specific laboratory test yet exists for this disorder. The severity of Kawasaki disease relates to the possible occurrence of coronary aneurysms in 20% of childhood cases. Treatment with intravenous immunoglobulins before day 10 is recommended to prevent aneurysm formation. The occurrence of Kawasaki disease is unusual in adults and 52 cases only have been reported in adult patients. Seventy-one per cent of cases occur between 18 and 30 years. The incidence of specific clinical features is quite similar between adults and children. However meningitis and thrombocytosis are more common in children than in adults, while conversely both arthralgias and liver function abnormalities are more common among adults. Coronary aneurysms are less common in the adults with Kawasaki disease. Other diseases with similar clinical presentation such as drug hypersensitivity reaction and the toxic shock syndrome must be ruled out. Kawasaki disease is often diagnosed after the acute phase at the step of desquamation, when it is too late to expect any beneficial effect from immunoglobulins. FUTURE PROSPECTS AND PROJECTS: Diagnostic criteria of Kawasaki disease have not been validated in an adult population. Criteria of exclusion are necessary to eliminate toxic shock syndrome and drug hypersensitivity syndrome. An international retrospective study to collect data on epidemiologic, clinical, laboratory, and cardiovascular features of adult Kawasaki disease is necessary to validate specific diagnostic criteria and to improve the knowledge on this disease.
Abstract: INTRODUCTION: Pubic osteomyelitis has been described in three situations: children in whom Staphylococcus aureus is the preeminent pathogen; elderly patients who have undergone genitourinary procedures, and parenteral drug abusers. In contrast, pubic osteomyelitis in athletes has been described less often. We report three cases of acute staphylococcal pubic osteomyelitis in young athletic men and present a review of the literature. EXEGESIS: The clinical presentation in each case was acute groin, hip, or perineal pain; fever; inability to bear weight; and pubic symphysis tenderness. The diagnosis was established by blood culture and radiologic changes. CONCLUSIONS: Staphylococcus aureus pubic osteomyelitis should be suspected in athletes who have febrile hip or groin pain. The pathogenesis of this disease is thought to involve preexisting trauma or athletic injury and subsequent seeding of this area during transient bacteremia. Prolonged antimicrobial therapy is required for the cure, and debridement with curettage may be necessary if patients have persistent infection or sequestra.
Abstract: INTRODUCTION: Necrobiotic xanthogranulomatosis is a rare cutaneous disorder usually associated with monoclonal gammopathy. Most frequently, cutaneous lesions involve the face (periorbital region) and the trunk, and are characterized by indurated xanthomatous plaques and nodules. EXEGESIS: We describe a patient presenting with necrobiotic xanthogranulomatosis that was unusual, as it was associated with IgM kappa monoclonal gammopathy of undetermined clinical significance and because no periorbital involvement was observed. CONCLUSIONS: Necrobiotic xanthogranulomatosis should be distinguished from other cutaneous manifestations associated with plasma cell dyscrasias, such as normolipemic plane xanthoma. It can be associated with IgM gammopathy.
Abstract: We report the case of a 75-year old woman presenting sarcoid myopathy with pseudohypertrophy and skin involvement. Muscular biopsy confirmed the diagnosis of sarcoidosis. Symptomatic muscle involvement in sarcoidosis is rare. Three forms are described: myopathic, myositic and nodular. The relevance of imaging techniques is reviewed. Treatment is based on corticotherapy which is less efficient in myopathic form and in this case we had to use methotrexate with success.
