[Diagnostic value of lymphadenopathy associated with fever and inflammation of unknown origin: a study of 69 patients]. / Valeur diagnostique des adénopathies associées aux fièvres et syndromes inflammatoires d'origine inconnue : à propos d'une série de 69 patients.

PURPOSE: The diagnosis of fever or inflammation of unknown origin (FUO/IUO) is guided by the search of clinical clues. Lymphadenopathy is thought to be helpful but its actual contribution has never been tested, and little is known about the main causes of FUO/IUO with lymphadenopathy. The aim of this study was to clarify these issues from the experience of two departments of internal medicine. METHODS: We retrospectively studied a cohort of 69 consecutive inpatients with FUO or IUO and lymphadenopathy, hospitalized from January 2002 to February 2008. The patients were coded according to the final diagnosis and age. Recorded data included lymph node location, fever, CRP level, lymphocyte and platelet counts, presence of hyperbasophilic cells, hypogammaglobulinemia, monoclonal gammopathy, LDH level, and the results of histological and or cytological lymph node examination. RESULTS: Malignancy accounted for 54%, granulomatosis for 23%, mainly of infectious (60%) or malignancy-related origin (18%), the group classified as non-specific adenitis represented 17% of the cases and systemic diseases 4%. Diagnosis was obtained by histological examination of a lymph node biopsy in 80% and by cytology alone in 13% of the patients; no correlation was found between anatomic location, clinical and biological data and any pathological group. Univariate age-independent analysis showed significant correlation between intra-abdominal lymphadenopathy (P=0.05), increased serum CRP (P=0.01) and LDH levels (P=0.05) and malignancy, whereas superficial unique lymph node location (P<0.05), absence of deep site location (P<0.01), and presence of hyperbasophilic cells (P<0.01) were all related to benign non specific adenitis. CONCLUSION: FUO/IUO with lymphadenopathy must be considered as a separate entity, mostly represented by malignancies and granulomatosis, mainly of infectious or malignancy related origin. Fever, intra-abdominal lymphadenopathy, serum CRP and LDH levels and hyperbasophilic cells are relevant indicators.

[Recurrent aphthosis: safety of low dose thalidomide]. / L'aphtose récurrente: innocuité du thalidomide à faible dose.

PURPOSE: Thalidomide is an effective treatment for recurrent aphthosis but its effectiveness at low dose has been rarely assessed. METHODS: Single-centre non-randomized retrospective open study. RESULTS: Forty-seven patients were treated with thalidomide for recurrent aphthosis (41 patients) or Behçet disease (six patients). Remission was obtained with a dose of 25 mg daily. Discontinuation of treatment for side effects was not observed in this case series. CONCLUSION: Low dose thalidomide below 50 mg daily is an effective and well tolerated treatment of aphthosis.

[Autoimmune autonomic ganglionopathy: a case series of six patients and literature review]. / Ganglionopathie autonomique auto-immune : une série de six observations et revue de la littérature.

PURPOSE: Auto-immune autonomic ganglionopathy is a recently described clinical entity within the spectrum of autonomic neuropathies. Patients with auto-immune autonomic ganglionopathy typically present with rapid onset of severe autonomic failure. Acetylcholine receptor ganglionic antibodies, directed against ganglionic synapsis, disrupt synaptic transmission in autonomic ganglia and lead to autonomic failure. These antibodies are specific for auto-immune autonomic ganglionopathy and are present in 50% of patients. METHODS: Descriptive retrospective study. We report six French patients who presented with auto-immune autonomic ganglionopathy diagnosed between 1996 and 2002. RESULTS: Four patients were men and the median age at diagnosis was 45 years. All patients presented with a subacute autonomic failure with constant severe orthostatic hypotension. Serological testing of acetylcholine receptor ganglionic antibodies was performed in four out of the six patients and was found positive in three. All the patients received intravenous immunoglobulin and a clinical improvement was observed in four of them. CONCLUSION: Auto-immune autonomic ganglionopathy is an unusual and overlooked disorder. However, this autonomic neuropathy deserves to be better known as most of the patients respond to immunomodulatory therapy.

Rituximab treatment of stiff-person syndrome in a patient with thymoma, diabetes mellitus and autoimmune thyroiditis.

Stiff-person syndrome (SPS) is an autoimmune neurological disorder characterized by stiffness of the skeletal muscle with superimposed spasms and production of autoantibodies to glutamic acid decarboxylase (GAD) and amphiphysin. The disorder results from B cell-mediated clonal production of autoantibodies, requiring treatment with immunosuppressors; however, treatment results have been somewhat inconsistent. We report the results of rituximab treatment in a patient with SPS associated with a thymoma, diabetes mellitus, autoimmune thyroiditis and the presence of anti-GAD and anti-amphiphysin autoantibodies. The patient experienced a partial improvement following a thymectomy and the administration of prednisone, intravenous immunoglobulins and mycophenolate mofetil. Treatment with rituximab was followed by a complete sustained remission and the disappearance of serum anti-amphiphysin antibodies.

Peripheral Neuropathy and VIth Nerve Palsy Related to Randall Disease Successfully Treated by High-Dose Melphalan, Autologous Blood Stem Cell Transplantation, and VIth Nerve Decompression Surgery.

Randall disease is an unusual cause of extraocular motor nerve (VI) palsy. A 35-year-old woman was hospitalized for sicca syndrome. The physical examination showed general weakness, weight loss, diplopia related to a left VIth nerve palsy, hypertrophy of the submandibular salivary glands, and peripheral neuropathy. The biological screening revealed renal insufficiency, serum monoclonal kappa light chain immunoglobulin, urinary monoclonal kappa light chain immunoglobulin, albuminuria, and Bence-Jones proteinuria. Bone marrow biopsy revealed medullar plasma cell infiltration. Immunofixation associated with electron microscopy analysis of the salivary glands showed deposits of kappa light chains. Randall disease was diagnosed. The patient received high-dose melphalan followed by autostem cell transplantation which led to rapid remission. Indeed, at the 2-month followup assessment, the submandibular salivary gland hypertrophy and renal insufficiency had disappeared, and the peripheral neuropathy, proteinuria, and serum monoclonal light chain had decreased significantly. The persistent diplopia was treated with nerve decompression surgery of the left extraocular motor nerve. Cranial nerve complications of Randall disease deserve to be recognized.

[Kappa light chain deposition disease, presenting as Sjögren's syndrome, successfully treated by high-dose melphalan and autologous blood stem transplantation]. / Maladie de Randall, simulant une maladie de Gougerot-Sjögren, traitée avec succès par chimiothérapie et autogreffe de moelle osseuse.

INTRODUCTION: Light chain deposition disease is a systemic disorder characterised by tissue deposition of monoclonal immunoglobulin light chains without tinctorial properties. It has been exceptionally reported with salivary involvement mimicking Sjögren's syndrome and peripheral neuropathy. CASE REPORT: We report a case of light chain deposition disease associated with plasma cell dyscrasia presenting as sicca syndrome with salivary glands hypertrophy and polyneuropathy successfully treated by high dose melphalan and autologous blood stem transplantation. CONCLUSION: Light chain deposition disease should be recognized as an aetiology of sicca syndrome and peripheral neuropathy. Further studies should assess the prevalence of sicca syndrome in light chain deposition disease and better characterise the neurological manifestations.

[Fever of unknown origin: diagnostic strategies and tactical approaches]. / Diagnostic des fièvres prolongées inexpliquées: tactiques et stratégies.

PURPOSE: Diagnosis of fever of unknown origin (FUO) is a major challenge for internists, as emphasized by the high rate of diagnostic failure, despite the fast-moving progress in medical technology. Numerous clues are available in clinical and standard biological data; a better use of the available tests is warranted. KEY POINTS: Improvement in diagnostic accuracy might be expected by developing strategies targeted toward a more systematic search of diagnosis clues. Intuition and the hypothetic-deductive method that are the most common clinical strategies are the most perfectible. It implies to enjoy the fun of clinical examination, to have a large experience in bedside training, to be confident in his/her own semiological skills, to refer frequently to heuristics, and to use carefully Occam's razor principle. Laboratory tests might be revisited; immunological and serological tests are of little value; standard biological tests provide many insufficiently exploited clues. Imaging procedures depend on objectives: whole body CT scan should be performed early within the first days of hospitalisation, preceded by standard chest radiograph and abdomen ultrasonography; followed by either indium-111 or technetium-99m, labelled leukocytes if deep abscesses are suspected or 18-FDG PET scan in the case of suspected inflammatory disease involving tissues, lymph nodes or arteries. Early identification of the best tissue to be the site of biopsy is one of the most decisive procedures. CONCLUSION: Strategies and tactical approaches for the diagnosis of FUO might be driven by the search of significant clues. Self-clinical experience driven by a wide bedside training is of major concern. Standard laboratory tests might be better used and the choice of imaging depends on objectives. Identification of the most appropriate tissue to be sampled for histological examination is one of the most beneficial step.

[Usefulness of antineutrophil cytoplamic antibodies in giant cell arteritis]. / Valeur des anticorps anticytoplasme des polynucléaires neutrophiles dans la maladie de Horton.

PURPOSE: The relevance of antineutrophil cytoplasmic antibody (ANCA) during giant cell arteritis is not established. The purpose of our study was to estimate the ANCA frequency and their impact on disease course of giant cell arteritis. METHODS: Thirty patients were followed-up for giant cell arteritis and had a detection of ANCA. RESULTS: Nine patient had positive ANCA (30%). These patients had no significant differences regarding clinical and biological data or number of relapses in comparison with patients having negative ANCA testing. However, the relapse occurred earlier in the presence of ANCA (six months versus 31.5 months). CONCLUSION: In giant cell arteritis, detection of ANCA seems predictive of a premature relapse and should be associated with an acute monitoring of ANCA positive patients.

Incidence of amyloidosis over 3 years: the AMYPRO study.

OBJECTIVES: There is a lack of epidemiological information concerning amyloidosis, particularly in France. We started a 3-year prospective study (AMPYRO) to analyze the epidemiological features of amyloidosis in the eastern part of France. METHODS: From 2003 to 2005, all patients with a tissue sample showing amyloid deposits, were included in this study. Immunohistochemistry using anti-P component, anti-SAA, anti-light chains immunoglobulins and anti-transthyretin was applied for each tissue sample. For each patient, past and present medical histories along with biological features were recorded. RESULTS: Seventy-six patients with amyloid were identified over 3 years. The age-standardized incidence rate of amyloidosis was estimated at 14 cases per million person-years. The final entire population included in the AMYPRO study was composed of 66 patients with a mean age of 71.7+/-11.5 years old. The amyloid typing after clinical, biological and immunohistochemistry revealed senile amyloid in 40 cases (60.6%), AL amyloid in 13 (19.7%) and AA amyloid in 9 (13.6%). Neither clinical nor biological features differed significantly between the transthyretin-positive and transthyretin-negative populations. CONCLUSION: Regarding only tissue samples, senile amyloid was the most prominent amyloid type identified. Therefore, the clinician needs to be aware that in most of the amyloid cases identified on the pathologic examination there is no need for additional examination unless there are clinical or biological signs of a primary or secondary amyloidosis.

[Stiff person syndrome associated with thymoma. Efficacy of thymectomy]. / Syndrome de la personne raide associé à un thymome: efficacité de la thymectomie.

INTRODUCTION: Stiff person syndrome is a rare autoimmune neurologic disorder characterized by axial muscular rigidity and intermittent painful spasms. Three distinct forms are described: auto-immune, paraneoplastic and idiopathic. EXEGESIS: We report the case of a 51-year-old man with an history of Stiff Person Syndrome with typical clinical, electrophysiological and immunological findings. Anti-glutamic acid decarboxylase antibodies were present, as well as anti-amphiphysin antibodies, commonly reported in the paraneoplastic syndrome. CT scan revealed a thymoma. Surgical resection was followed by reduction of the neurologic symptoms, without lowering the auto antibodies titer. CONCLUSIONS: The association between Stiff Person Syndrome and thymoma is exceptional. Thymectomy is an effective treatment and may act without change of the autoantibodies titer. Patients with Stiff Person Syndrome should be systematically tested for thymoma.

[Pseudo-myasthenic myopathy in a woman with anorexia nervosa]. / Pseudomyasthénie grave chez une anorexique.

Skeletal myopathy, although foreseeable in severe malnutrition, has been rarely reported in patients with anorexia nervosa. We report a case of oculo-oropharyngeal myopathy mimicking myasthenia in a 42-year-old woman with an history of anorexia nervosa, completely reversible after refeeding with carbohydrate diet, mainly chocolate. Nutritional myopathies are not well known and therefore rarely looked for in patients with anorexia nervosa. Classical presentation is a myogenic syndrome with severe type 2 fibre atrophy and biochemical characteristics similar to Mac Ardle's disease. A clinical form mimicking myasthenia gravis has never been reported. Refeeding programme leads to total recovery within a few days.

[Pronostic value of C-reactive protein measure in elderly patient with acquired pneumonia: correlation with Fine's score]. / Valeur pronostique du dosage de la protéine C réactive (CRP) dans les pneumopathies aiguës infectieuses du sujet âgé: corrélation avec le score de Fine 97.

UNLABELLED: The Fine's score, a predictive score of infectious pneumonia gravity, does not integrate inflammatory parameters, which are routinely used in the management of infectious pneumonia. The aim of our study was to establish a correlation between the Fine's score and C reactive protein. PATIENTS AND METHODS: One hundred patients hospitalized for infectious pneumonia, 57 men and 43 female, with an average age of 85 years were retrospectively recorded. RESULTS: The median level of C reactive protein was 157 mg/L. Global mortality rate was 26% and respectively 5, 16 and 45% in the grades III, IV, V of the Fine's score. Beyond 75,5 mg/L C reactive protein concentration, the mortality rate was contained between 28 and 32%. The comparison of the ROC curves of the Fine's score and C reactive protein did not showed any difference. CONCLUSION: C-Reactive protein is less precise than the Fine's score to assess infectious pneumonia gravity but seems to be an indicator of the potential gravity of the pneumonia.

[Influenza vaccination among health-care workers. Vaccination rates in universitary hospital of Besançon, winter 2003-2004]. / La vaccination antigrippale du personnel hospitalier. Enquête de prévalence au CHU de Besançon, hiver 2003-2004.

BACKGROUND: Influenza vaccination reduces the mortality of the patients when the vaccination rates of healthcare workers is important. PURPOSE AND METHOD OF THE STUDY: To investigate the vaccination rates at the Universitary Hospital of Besançon by anonymous questionnaire. RESULTS: Three thousand hundred seventy-seven answers were analyzed (228 men and 1145 women). Two hundred seventy-seven persons declared receiving the vaccine (20.1%) corresponding to sixty-three men (27.6%) and two hundred thirteen women (18.6%) (P = 0.001). The average age of the healthcare workers vaccined was of 38.9+/-11 years. Among most than 50 years, 34% was vaccined. Among the doctors, 40.5% were vaccined against 20.6% of the nurses. In the services of geriatrics, 78.5% of the staff was vaccined. CONCLUSIONS: Our results indicate a weak rate of influenza vaccination in our establishment and a misunderstanding of the character nosocomial of the influenza among the nurse.

[Oncogenic osteomalacia: the role of the phosphatonins. Diagnostic usefulness of the Fibroblast Growth Factor 23 measurement in one patient]. / L'ostéomalacie oncogène : rôle des phosphatonines. Intérêt du dosage du fibroblast growth factor 23 démontré chez un malade.

INTRODUCTION: Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia induced by phosphaturic factors which are secreted by some tumors of mesenchymal origin. Fibroblast Growth Factor 23 (FGF-23) belongs to this family. Measurement of FGF-23 might improve the diagnosis of OO. EXEGESIS: We report the case of 71-year-old Caucasian man who had a history of severe osteomalacia with multiples fractures and extreme hypophosphatemia with hyperphosphaturia and normal serum calcium level. Serum FGF-23 was 199 RU/ml (N < 100 RU/ml). The tumor, detected by F-18 FDG PET/CT SCAN was localized in the mandible. Surgical removal of the tumor relieved all symptoms with normalization of serum phosphate levels within 3 days after surgery. CONCLUSION: We conclude that FGF-23 measurement is likely to be of considerable importance for facilitating early diagnosis of OO.

Oncogenic osteomalacia: diagnostic importance of fibroblast growth factor 23 and F-18 fluorodeoxyglucose PET/CT scan for the diagnosis and follow-up in one case.

A case of oncogenic osteomalacia is reported in a 71-year-old man who presented with bone pain, muscle weakness, and severe hypophosphatemia. The tumor which was localized in the left lower mandible was not detected by tomodensitometry, resonance magnetic imaging, and (111)IN-octreotide scintigraphy, but was easily localized by F-18 fluorodeoxyglucose PET/CT SCAN (F-18 FDG PET/CT SCAN). To our knowledge, the value of this technique for detecting tumors in oncogenic osteomalacia has never been reported. Secondly, this case provided an opportunity for confirming the usefulness of serum fibroblast growth factor 23 (FGF23) measurement for the diagnosis and follow-up. We conclude that FGF23 measurements combined with F-18 FDG PET/CT SCAN were decisive tools in a case of oncogenic osteomalacia and are likely to be of considerable importance for facilitating early diagnosis and follow-up in the future.

[Medical practice analysis in internal medicine: a national descriptive study]. / Analyse des pratiques des spécialistes de médecine interne: une enquête transversale descriptive nationale.

PURPOSE: This descriptive and epidemiological study was conducted in Mars 2002 in Internal Medicine in order to (1) participate in elaborating a White Book about the speciality, (2) analyse the post-university formation needs of the specialists in Internal Medicine. METHODS: A questionnaire was sent to all specialists in Internal Medicine listed on the ADELI file (n = 2155). For the first three patients seen in consultation and during hospital stay, questioned specialists had to mention the age, sex, origin, motive of the visit, nature of symptoms, complexity of the problem and the nature of the required abilities. They also had to precise the main diagnosis of all patients seen in the same day. RESULTS: Three hundred and sixty answers have been received. Three hundred and thirty two were exploitable. Five thousand six hundred and eleven main diagnosis were listed. Fifteen percent of the questioned specialists did practise in other specialities than Internal Medicine. Orphaned diseases were the most common pathologies carried out in consultation (17%). Patients seen during their hospital stay suffered more frequently from infectious, haematological and malignant diseases. In 55% of the cases, patients were seen in second or third line after a visit to a general practitioner or another specialist. The abilities of the Internal Medicine specialist alone were sufficient in 70% of the cases to solve the problem. Complexity of the problem was evaluated by the specialists themselves at about 45/100 on an analogical scale. CONCLUSIONS: This study inform the medical community about the type of patients treated by the specialists in Internal Medicine, precise the exact nature of their professional exercise and their real need in medical post-university formation.