[Risk factors for venous thromboembolism in hospitalized patients in internal medicine: case-control study of 150 patients]. / Facteurs de risque de la maladie thromboembolique veineuse chez des malades hospitalisés en médecine interne: une enquête cas-témoins sur 150 patients.

BACKGROUND: Risk factors for the thrombo-embolic disease are not yet completely validated in medical setting. Indeed, there is a lack of scientific data concerning their prevalence and their thrombogenic weight. METHODS: We carried out a prospective case-control study in an internal medicine unit where general acute pathologies are recruited. We have included two patients without thrombosis for each patient admitted for a thrombo-embolic event. In all patients, at admission, clinical and biological risk factors for thromboembolism were systematically analysed in a physiopathological and chronological way. RESULTS: 450 patients were included during the 27 months period of the study. Among these patients, 150 were hospitalised for a deep venous thrombosis of the leg or/and a pulmonary embolism. Height risk factors have demonstrated their high thrombogenic potential: paralysis of the legs (OR = 13; 95% CI: 1.4 to 5.1), post-thrombotic syndromes (OR = 13; CI: 1.7 to 4.3), extrinsic compressions (OR = 8; CI: 1.3 to 5.4), pregnancy (OR = 6; CI: 1.2 to 6), malignancy occurred one year before (OR = 4; CI: 1.1 to 6.7), personal history of deep vein thrombosis (OR = 3; CI: 1.6 to 4.5), varicosity (OR = 2.5; CI: 1.2 to 6.1) and venous insufficiency (OR = 1.7; CI: 1 to 7.4). Four parameters, generally considered as risk factors, didn't prove here their pathogenic power: the age over 60, obesity (BMI > 27), bedrest and the presence of an on-going malignancy. CONCLUSIONS: Only risk factors with high thrombogenic power (as paralysis or extrinsic compression for example) could be identified by this kind of study performed in polypathological patients. In this particular population, usually recognised risk factors as age, obesity and bedrest are not determinant parameters for the thomboembolic risk evaluation.

[Hypoglycemia associated with pleural fibromas. Study of insulin-like growth factors (IGF) and pathogenic considerations]. / Hypoglycémie associée aux fibromes pleuraux. Etude des insulin-like growth factors (IGF) et considérations pathogéniques.

PURPOSE: Pathogeny of hypoglycemia associated with non-islet-cell tumors is unclear. We discuss the mechanisms of this syndrome. CURRENT KNOWLEDGE AND KEY POINTS: We report three cases of spontaneous hypoglycemia revealing pleural fibroma. Endocrine tests before surgery showed low serum growth hormone and insulin-like growth factor I (IGF-I), reduced serum IGF-II levels in two patient. Insulin-like growth factor binding protein-3 (IGFBP-3) was low and electrophoretic profile of IGF-II was the 'big IGF-II' type. We discuss the mechanisms of hypoglycemia associated with non-islet-cell tumor. Impaired formation of the ternary complexes and its consequences seem the main pathogenic factor. FUTURE PROSPECTS AND PROJECTS: Analysis of IGF and IGFBP and in situ measurements of IGF mRNA could help in understanding this syndrome and allow therapeutic considerations in the management of hypoglycemia by corticosteroids and growth hormone.

Systemic medium-sized vessel vasculitis associated with chronic myelomonocytic leukemia.

OBJECTIVE: To determine the clinical aspects of systemic vasculitis associated with chronic myelomonocytic leukemia (CMML). METHODS: In this retrospective study, 8 patients suffering from systemic vasculitis associated with CMML are described. The French and English literature on systemic vasculitis associated with myelodysplasia was reviewed. RESULTS: All 8 patients had a systemic medium-sized vessel vasculitis which fulfilled the American College of Rheumatology criteria for polyarteritis nodosa in the setting of active CMML. Antineutrophil cytoplasmic antibodies (ANCA) were negative in 7 patients. One patient had cytoplasmic ANCA by indirect immunofluorescence without antiproteinase 3 or antimyeloperoxydase antibodies on the enzyme-linked immunosorbent assay. At presentation, 6 patients had fever of unknown origin, 5 had polymyalgia rheumatica, 3 had sensory hearing loss, and 4 had eosinophilia. None had viral infection or drug-associated vasculitis. Diagnostic procedures included renal or hepatic angiography in 6 patients which showed microaneurysms in 4, skin and temporal artery biopsy in 2 which showed vasculitis, and 1 postmortem examination which showed gastroduodenal arteritis. All patients were treated with corticosteroids, and 7 received immunosuppressive drugs. Death was attributable to vasculitis in 2 cases, infection in 3, and other vasculitis-related causes in 2. In a review of the French-English literature, we found 11 similar cases of ANCA-negative systemic vasculitis, generally associated with refractory anemia, with or without blast excess. CONCLUSIONS: Systemic ANCA-negative polyarteritis nodosa-type vasculitis seems closely associated to CMML. Clinical presentation is nonspecific, and systemic vasculitis should be suspected when a patient with myelodysplasia develops atypical manifestations. Renal, gastrointestinal, or hepatic angiography are useful diagnostic procedures when more invasive biopsies should be avoided because of low platelet count. The prognosis of CMML-associated systemic vasculitis is poor.

[Risk factors and incidence of venous thromboembolic disease in internal medicine: prospective descriptive study on 947 hospitalized patients]. / Facteurs de risque et incidence de la maladie thromboembolique veineuse en médecine interne: une étude descriptive prospective sur 947 patients hospitalisés.

PURPOSE: The thromboembolic risk is difficult to evaluate in medical inpatients because of the multiplicity of risk factors. The lack of scientific data leads to a certain empiricism in selection of patients who need a preventive treatment. METHODS: All patients hospitalised in an internal medicine department were included during 34 months. The pathogenic mechanism of risk factors (venous stasis or hypercoagulability) was analysed as well as their progress (transient or permanent risk factors) and their pathogenic weight (major risk factor or not). Three levels of embolic risk (high, intermediate, low) were identified. A preventive treatment was initiated only for patients at high or intermediate risk. A clinical screening for thromboembolic events was performed daily. Therefore, we have excluded patients who needed a hypocoagulant treatment. RESULTS: Nine hundred and forty-seven patients were included. Age (over 60) was the most frequent permanent risk factor (70%). Bed rest was the most frequent transient risk factor responsible for venous stasis. Fifty percent of patients had a transient and permanent risk factor and needed a preventive treatment according to our selection criteria. The incidence of thromboembolic events was 0.4% in the high-risk treated group and 0.2% in the low-risk non-treated group. CONCLUSIONS: Venous stasis factors are the more frequent risk factor in internal medicine, perhaps because of the increasing number of geriatric patients. The incidence of thromboembolic disease is low in high-risk inpatients when a preventive treatment is performed.

Systemic antineutrophil cytoplasmic antibody vasculitis associated with lymphoid neoplasia.

Two cases of systemic antineutrophil cytoplasmic antibody (ANCA) vasculitis in the setting of chronic lymphocytic leukaemia and angioimmunoblastic lymphadenopathy type T cell lymphoma are reported. The two patients had fever of unknown origin associated with cutaneous vasculitis and "pulmonary-renal syndrome" with alveolar haemorrhage. Despite anti-infectious treatments, steroids, and chemotherapy, the vasculitis had a fatal paraneoplastic course in several weeks. When infection is excluded in patients with malignancy, atypical features should be promptly investigated for systemic vasculitis, and an ANCA test performed.

[Rationalization of risk factors for venous thromboembolism in medical inpatients. A prospective study]. / Rationalisation des facteurs de risque de la maladie thrombo-embolique veineuse en milieu médical polyvalent hospitalier: une étude prospective.

BACKGROUND: In terms of preventive management of venous thromboembolism in medical inpatients, very large differences may be observed. Rationalization of behaviour requires the evaluation of simple and logical parameters, which takes into account both patient safety and economic considerations. AIM: The aim of this study was to evaluate a preventive scheme including the rationalization of the indications and the use of low molecular weight heparin. EXPERIMENTAL DESIGN: Epidemiologic investigation. SETTING AND PATIENTS: Patients hospitalized in five medical departments in the Hospital Center of Nantes, France. INTERVENTION: The risk of venous thromboembolism was rated as high, intermediate and low. Patients with high or intermediate risk were eligible for prevention therapy (table I). MEASURES: The main criterion was the occurrence during hospital stay of deep or superficial venous thrombosis of the lower limbs, pulmonary embolism, or unexplained sudden death. The screening was based on clinical features double-checked by venous doppler ultrasonography of the lower limbs and/or ventilation-perfusion lung scanning. RESULTS: 24,497 patients were eligible (table II), 15% were considered at risk and treated with Nadroparin, 6% had the same risk profile but were not treated and 14. 7% had low risk and no prevention. No bleeding event was reported. The incidence of venous thromboembolism was 0.75%, 1.7% and 0.14% respectively (p <0.01) (table III). This efficacy does not appear to depend on body weight or the existence of multiple risk factors observed (table IV and V). CONCLUSIONS: This analysis of risk factors separates two populations with rates of incidence dramatically and significantly different. The prevention of venous thromboembolism by fixed dose of low molecular weight heparin remains justified since it reduces the risk of venous thromboembolism by a factor of 2.5.

Prevalence of rheumatic manifestations and antineutrophil cytoplasmic antibodies in haematological malignancies. A prospective study.

OBJECTIVE: To evaluate the prevalence of antineutrophil cytoplasmic antibodies (ANCA) and rheumatic manifestations associated with chronic haematological malignancies. METHODS: Two groups of patients were prospectively studied (group I: 60 patients with myelodysplastic syndromes and group II: 140 patients with lymphoid malignancies) for clinical 'immune' manifestations and ANCA. RESULTS: In the myelodysplastic group, six patients had ANCA-negative systemic medium-size vasculitis, one had systemic vasculitis with cytoplasmic ANCA, one relapsing polychondritis, one giant cell arteritis, one polymyalgia rheumatica, one polyarthritis and two fasciitis. In group II, two patients had ANCA-negative systemic vasculitis, two had leucocytoclastic vasculitis associated with tuberculosis, two had polyarthritis, one polymyalgia rheumatica and one giant cell arteritis. Six sera were ANCA-positive with perinuclear pattern in four cases, atypical pattern in one and cytoplasmic pattern in one. Two sera had anti-myeloperoxidase (MPO) specificity, and others had no known specificity; none had anti-proteinase 3 (PR3) specificity. Global prevalence of ANCA in our cohort was 3%, similar to the French general population. CONCLUSION: Polyarteritis nodosa-type systemic vasculitis and polymyalgia rheumatica were the most frequent findings (18%) in myelodysplastic syndromes and particularly in chronic myelomonocytic leukaemia. ANCA were not helpful for the diagnosis of vasculitis. Vasculitis associated with infection, in particular tuberculosis, must be ruled out.

[Neuro-meningeal location of Richter syndrome]. / Localisation neuroméningée d'un syndrome de Richter.

INTRODUCTION: The authors report a case of neurologic manifestations revealing Richter's syndrome in chronic lymphocytic leukemia. EXEGESIS: Cranial nerve palsies were the initial manifestation of the disease. Computed tomography and magnetic resonance imaging were normal. Cerebrospinal fluid analysis with alkaline phosphatase-antialkaline phosphatase revealed the existence of a large-cell lymphoma. CONCLUSIONS: Clinical aspects of this unusual localization of Richter's syndrome are reviewed.

Henoch-Schönlein purpura associated with Toxocara canis infection.

We describe a case of Henoch-Schönlein purpura in the onset of Toxocara canis infection. The diagnosis was made in a 17-year-old boy based on the association of palpable purpura, oligoarthritis, acute abdominal pain, microhematuria, and cutaneous vasculitis. Toxocariasis, suggested by hypereosinophilia and domestic contact with a puppy, was confirmed by anti-Toxocara IgG and IgE and Western blot. Complete spontaneous resolution occurred within a few days. Transient presence of antinuclear antibodies and the absence of larvae in the skin biopsy favor an immunologic parasite induced disorder. A hypersensitivity vasculitis to Toxocara canis is suggested.

[Limitations of the protein profile for diagnostic orientation in initial internal medicine consultation. Prospective study on 76 patients]. / Limites du profil protéique d'orientation diagnostique en consultation initiale de médecine interne. Etude prospective chez 76 malades.

Determination of the protein profile of orientation (PPO) is now considered by some authors as a means of improving the diagnosis in internal medicine. The feasibility of systematizing this practice was investigated in 76 outpatients (79 included, three excluded secondarily) seen for pathology of undetermined diagnosis. The 79 patients (mean age: 52 years) underwent the classical biological explorations plus PPO. The physicians were divided into two groups (seniors and assistants). Two complete clinical files were established for each patient, with one difference concerning inflammatory and immunologic data: one file included the minimum number of tests considered necessary by the physician and the other the complete PPO (nine proteins). Each file (with or without PPO) was randomly distributed to one of two physicians in the same group. Each physician filled in a diagnostic evaluation sheet indicating whether there was organic pathology or not, the main diagnosis (inflammatory, neoplastic, infectious or other), the secondary diagnosis and the hypothesis of probability. The relevance of the clinical opinion was analyzed by an internal medicine specialist from outside the department with 40 years of clinical experience. The duration of symptoms before the medical visit was from 3 weeks to 5 years (mean 6 months). A diagnosis of organic pathology was reached for three out of four patients. Sixty-seven patients were seen again after a minimum of 6 months, and nine were lost to follow-up. Diagnostic efficiency was no greater for cases with PPO, which appears to be a biological examination of second intention. We suggest that the term "protein profile of orientation" be replaced by "broad protein profile."

[Acquired Willebrand syndrome with lymphoproliferative disorders]. / Syndrome de Willebrand acquis avec désordres lymphoprolifératifs.

INTRODUCTION: Willebrand's syndrome is rarely acquired. We report four cases associated with lymphoproliferative syndromes. CASE REPORTS: We observed four patients with lymphoid hemopathies who developed acquired Willebrand's syndrome. Two patients had Waldenström's disease (kappa), one had a monoclonal gammapathy of undetermined signification (kappa immunoglobulin M) and the fourth had chronic lymphoid leukemia with mast cell infiltration of the skin. Anti-vWFRCo antibodies were evidenced in only 1 case. Chemotherapy, used in 3 cases, improved hemostasis in one patient. Intravenous immunoglobulins (1 patient) and desmopressin (2 patients) were ineffective. The pathogenic mechanisms and possible therapeutic approaches to acquired Willebrand's syndrome are discussed. DISCUSSION: Acquired Willebrand's syndrome rarely occurs in association with lymphoproliferative disorders appears to be uncommon but the frequency is probably underestimated because appropriate tests are not always performed. The diagnostic search is important however since the hemostasis disorders due to acquired Willebrand's syndrome could be corrected if appropriate etiological treatment is given.

Pancytopenia and severe cytopenia induced by low-dose methotrexate. Eight case-reports and a review of one hundred cases from the literature (with twenty-four deaths)

Severe adverse effects of low-dose methotrexate (less than 20 mg per week) are believed to be rare. We report eight cases of severe tricytopenia or pancytopenia seen in two medical departments of the same hospital in patients receiving low-dose methotrexate. Three patients had been under methotrexate for less than one month. Of the six patients with joint disease, five had rheumatoid arthritis and one psoriatic arthritis. A review of the literature found 92 previously reported cases of severe tricytopenia or pancytopenia induced by low-dose methotrexate. Of the total of 100 cases, 24 were fatal and 25 occurred within one month of treatment initiation. Potential risk factors were identifiable retrospectively in at least 50% of cases but were not all predictable or present at treatment initiation. In 30% of cases, no explanation for the hematologic complication was found, and in an additional 20% missing data precluded definite conclusions. The role of the risk factors incriminated in the literature is discussed. Although infrequent, cytopenia is a severe complication of methotrexate therapy that warrants a number of precautions, including periodic creatinine clearance and serum albumin determinations. Furthermore, the weekly dosing schedule should be printed on methotrexate boxes.