Hugues Rousset

Angioimmunoblastic T-cell lymphoma: clinical and laboratory features at diagnosis in 77 patients.

We retrospectively analyzed 77 patients with pathologically diagnosed angioimmunoblastic T-cell lymphoma from a single city. There were 43 men and 34 women; the median age was 64.5 years (range, 30-91 yr). Average time between first symptoms of the disease and diagnosis was 3.6 months. At diagnosis, peripheral nodes were present in all but 1 patient, and were generalized in 90% of cases. Constitutional symptoms were reported in 77% of cases and spleen enlargement in 51%. A cutaneous eruption-morbilliform, urticarial, or more polymorphic-was present in 45% of patients; in one-third of them, the eruption occurred after drug administration. Other clinical manifestations included pleuritis (22%); arthralgia or arthritis (17%); ear, nose, and throat involvement (14%); central or peripheral neurologic manifestations (10%); and ascites (5%). Most patients presented with advanced disease at diagnosis (bone marrow involvement in 60% of cases). The main laboratory abnormalities were elevated lactate dehydrogenase levels (71%), inflammatory syndrome (67%), hypergammaglobulinemia (50%), anemia (51%), and lymphopenia (52%). Auto- or disimmune manifestations were reported in one-third of patients: autoimmune hemolytic anemia was present at diagnosis in 19% of patients and thrombocytopenic purpura in 7%. Documented vasculitis was described in 12% of cases. Clonality was analyzed in lymph nodes in 47 patients: T-cell and B-cell clones were found in 45 (96%) and 20 (45%) patients, respectively. Chromosomal abnormalities were identified in 62% of cases: trisomies 3, 5, 18, 19, additional X chromosome, and deletion of chromosome 7 were the most common abnormalities. The current study underlines the diversity of presenting manifestations of angioimmunoblastic T-cell lymphoma. Abbreviations: AITL = angioimmunoblastic T-cell lymphoma, AILD = angioimmunoblastic lymphadenopathy with dysproteinemia, CSF = cerebrospinal fluid, EBERs = Epstein-Barr virus-encoded small RNAs, ENT = ear, nose, and throat, HIV = human immunodeficiency virus, Ig = immunoglobulin, IL = interleukin, IPI = International Prognostic Index, LDH = lactate dehydrogenase, PCR = polymerase chain reaction, TCR = T-cell receptor.

Yield of Bone Marrow Examination in Diagnosing the Source of Fever of Unknown Origin

BACKGROUND Fever of unknown origin (FUO) still remains a diagnostic challenge, while diagnosis may remain obscure for several weeks or months. The role of tissue biopsy is crucial in the diagnostic approach. We report a series of 130 consecutive patients with FUO who had undergone a bone marrow biopsy (BMB). METHODS Among 280 consecutive nonimmunocompromised patients hospitalized between 1995 and 2005 for a febrile illness of uncertain cause, lasting at least 3 weeks, with no diagnosis after an appropriate minimal diagnostic workup, 130 underwent BMB. RESULTS Overall, a specific diagnosis was achieved by BMB and histological examination in 31 cases (diagnostic yield, 23.7%). Three types of diseases were found: hematological malignant diseases in 25 cases, including 19 patients with malignant lymphoma, 4 with acute leukemia, 1 with hairy cell leukemia, and 1 with multiple myeloma; infectious diseases in 3 cases; systemic mastocytosis in 2 cases; and disseminated granulomatosis in 1 case. Thrombocytopenia (odds ratio, 4.9; 95% confidence interval, 1.04-9.30) and anemia (odds ratio, 3.24; 95% CI, 1.13-9.34) were the most reliable predictive factors regarding the usefulness of BMB. Bone marrow cultures had very limited value in our cohort. Finally, corticosteroid use did not seem to affect the yield of BMB. CONCLUSIONS Bone marrow biopsy is a useful technique for the diagnosis of prolonged fever in immunocompetent patients. Thrombocytopenia and anemia seem to be correlated with the value of this test.

Prevalence and pattern of antinuclear autoantibodies in 347 patients with non-Hodgkin's lymphoma

Summary. The presence of antinuclear autoantibodies (ANA) was investigated in a large cohort of patients with non‐Hodgkins lymphoma (NHL) in order to assess their frequency, specificity and prognostic relevance. ANA were analysed in 347 patients with different histological subgroups of NHL and in 213 controls using an indirect immunofluorescence technique on HEp2 cells. As the appearance of autoantibodies may be found after treatment of NHL, samples were collected at the time of diagnosis of NHL before any therapy. Sixty‐six (19%) NHL patients and 12 (5·6%) patients from the control group displayed ANA. The prevalence between the two groups was found to be significantly higher in NHL patients (P < 0·0001) with a marked increased prevalence in follicular and mantle cell lymphoma subgroups. Autoantibodies directed against mitotic proteins or mitotic‐associated proteins were found in 6·9% of NHL patients versus 0·5% in the control group (P < 0·001), with a significantly increased incidence in follicular and mantle cell lymphoma subgroups (P < 0·0001). Some 28% of the patients with positive ANA displayed clinical symptoms that could correspond to classical autoimmune manifestations, this frequency appearing to be higher in the marginal zone/mucosa‐associated lymphoid tissue lymphoma subgroup. These data demonstrate a significant incidence of ANA before any treatment in NHL occurrence, which seems to be higher in some histological subgroups with particular ANA, such as ANA directed against mitotic proteins or mitotic‐associated proteins.

Recurrent cerebral venous thrombosis revealing paraneoplastic angiitis in Hodgkin’s lymphoma

Recurrent cerebral venous thrombosis (CVT), as a manifestation of paraneoplastic angiitis and revealing of nodular lymphocyte predominant Hodgkin’s disease (NLPHD), is an extremely rare condition. We herein report a 55-year-old man who developed recurrent CVT despite efficacious anticoagulant therapy and subsequent stenting of the superior longitudinal sinus. Progressive neurological deterioration ensued and a body scan revealed axillary lymph nodes. Pathological analysis led to a diagnosis of NLPHD. Conventional angiography showed CVT and multiple arterial narrowings. A paraneoplastic primary cerebral angiitis with prominent venous structure involvement was suspected. Immunotherapy using rituximab and steroids provided a dramatic recovery. This case of CVT due to paraneoplastic cerebral angiitis is a rare condition and represents a new, very rare manifestation of nodular lymphocyte predominant Hodgkin’s disease.

Clinical Significance of Anti-Histidyl-tRNA Synthetase (Jo1) Autoantibodies

Abstract:  The clinical significance of a discovery of anti‐histidyl‐tRNA synthetase (Jo1) autoantibodies patients was established in the early diagnosis of antisynthetase syndrome (ASS) as the common form of this pathology is characterized by interstitial lung disease (ILD), inflammatory muscle disease, and production of anti‐Jo1 autoantibodies. However, the specificity of such autoantibodies has to be evaluated in daily clinical practice. In this study, the clinical and prognostic profiles of 45 patients displaying anti‐Jo1 autoantibodies were determined. Among 36 patients with a titer of anti‐Jo1 autoantibodies above the cutoff value suggested by the manufacturer (40 AU/mL), three different groups were identified. The first group (n= 26) suffered from a complete or incomplete ASS and showed anti‐Jo1 autoantibodies mostly above 60 AU/mL. A second group (n= 7) suffered from another autoimmune disease, that is, a systemic lupus erythematosus, cutaneous lupus and rheumatoid arthritis, and Crohns disease with anti‐Jo1 autoantibodies mostly below 60 AU/mL. The third group (n= 3) did not suffer from any autoimmune disease and presented anti‐Jo1 autoantibodies below 60 AU/mL. The nine doubtful cases (titer of anti‐Jo1 autoantibodies of 30–39 AU/mL) were from patients with no ASS nor myositis. Only 27 out of 45 patients showed antinuclear antibodies with 15 sera showing a pattern characteristic of anti‐Jo1 autoantibodies by indirect immunofluorescence on HEp2 cells. In conclusion, this study underlines the need to search for anti‐Jo1 autoantibodies even if antinuclear antibodies are negative by indirect immunofluorescence and underlines the usefulness of anti‐Jo1 antibodies of titer above 60 AU/mL in the diagnosis of complete or incomplete ASS.

Prise en charge de l’asthénie associée au cancer

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.