[Empirical treatment of granulomatous hepatitis of unknown origin: practice investigation in the French National Society of Internal Medicine]. / Traitement d'épreuve d'une hépatite granulomateuse symptomatique de cause indéterminée: enquête de pratique au sein de la Société nationale française de médecine interne.

PURPOSES: Ten to fifteen percent of granulomatous hepatitis are idiopathic. If symptoms like prolonged fever are present, empirical treatment is discussed. The goal of this study is to describe the empirical treatment proposed in this situation by French specialists of internal medicine. METHODS: We conducted a practice investigation among the French national society of internal medicine (SNFMI), using an anonymous questionnaire that related a case of idiopathic granulomatous hepatitis. This questionnaire was proposed to all French internists present at the SNFMI congress in June and December 2004. French specialists of internal medicine had to answer if they would prescribe an empirical treatment and if so, to specify this treatment. RESULTS: Thirty-six French specialists of internal medicine answered to the questionnaire. In the proposed situation, 89% of them initiate an empirical treatment. In 18/36 cases (50%), a first-line anti-tuberculosis empirical treatment is proposed (quadritherapy in 11 cases). In 7 cases (19%), an empirical treatment with prednisone, 0.4 mg/kg/d (N=1) and 1 mg/kg/d (N=6), would be prescribed. Seven internists (19%) would prescribe an empirical treatment with cyclins at the dose of 100 to 400 mg/d. Median duration of the empirical treatment would be 28 days (range: 8-252d). The evaluation parameters mentionned are: fever (69%), weight (59%), seric level of C-reactive protein (59%), and liver biology (53%). In case of failure of first-line empirical treatments, 69% of all questionned internists prescribe a second-line treatments: prednisone at the dose of 0.4 to 2 mg/kg/d (72%), anti-tuberculosis treatments (16%), cyclins 200 mg/d (12%), with a median duration of 28 days. Seven internists (19%) propose to combine two empirical treatments. DISCUSSION: Faced with a problem of idiopathic granulomatous hepatitis, French internists questionned propose four therapeutics options: no treatment, anti-tuberculosis treatment, cyclins or steroids treatment. First-line anti-tuberculosis treatment is a coherent proposition regarding to the high prevalence of tuberculosis. There are only few data available concerning empirical treatment with steroids or cyclins. Specific proposition of such empirical treatments should be defined. CONCLUSIONS: The management of idiopathic granulomatous hepatitis is difficult. Our study shows that therapeutics practices of French internists are heterogenous. The main proposition consists in a first-line anti-tuberculosis empirical treatment, that has to be evaluated after four weeks, and switched with steroids (prednisone, 1 mg/Kg/d) in case of failure. This study is not an expert proposition but contributes to suggest clinical practice guidelines for a rare, complex, heterogenous, and typically internist situation.

[Place of azathioprine in the treatment of giant cell arteritis]. / Utilisation de l'azathioprine dans le traitement de l'artérite à cellules géantes.

OBJECTIVE: The aim of this bicentric retrospective study was to describe the use of azathioprine in giant cell arteritis, and to appreciate its corticosteroid-sparing effect in glucocorticoid-dependent patients or with severe glucocorticoid related side effects. METHODS: We retrospectively reviewed the medical records of patients diagnosed with giant cell arteritis between 2000 and 2011 in two departments of internal medicine. Only the patients treated with azathioprine were included in this study. Sociodemographic, clinical, biological, radiological and therapeutic data were collected by a standardized questionnaire. A comparative analysis of daily prednisone dose at the initiation and 1 year after the prescription of azathioprine was made. RESULTS: Of the 28 patients included, 21 responded to azathioprine. At 1 year of follow-up after the initiation of azathioprine, 18 patients (64%) were still in sustained response, asymptomatic, without increase in acute phase response laboratory markers, and with a daily dose of prednisone<10 mg. Three patients (11%) experienced a relapse during azathioprine treatment. Mean daily dose of prednisone were 25.4 mg at the time of initiation of azathioprine, and 4.7 mg at 1 year of treatment, suggesting a corticosteroid-sparing effect (P<0.001). Ten patients experienced azathioprine serious side effects, leading to discontinuation of treatment in seven cases. CONCLUSION: Azathioprine may be an alternative treatment for patients with giant cell arteritis requiring prolonged high dose glucocorticoid therapy or developing severe glucocorticoid related side effects. However, given the potential adverse effects of azathioprine, a close monitoring is necessary.

[Primary localized amyloidosis of the urinary tract. A case series of five patients]. / Amylose primitive localisée à l'appareil urinaire. A propos de cinq cas.

PURPOSE: To describe the clinical and radiographic features of patients with primary localized amyloidosis of the urinary tract. METHODS: We report a case of localized amyloidosis of the ureters and bladder. The medical records of four other cases from the French Register of localized amyloidosis were reviewed. RESULTS: The mean age of three men and two women was 53 years. All patients presented with gross hematuria, four patients presented with renal colic, only one patient had irritative lower urinary tract symptoms. Ureter and bladder were involved in three patients, both ureters in two patients and the bladder only, in one patient. Clinical and radiographic presentations mimicked a neoplasia excluded by histologic analysis. Immunohistochemical study was performed in only two cases and revealed lambda light chain amyloidosis. The median follow-up was eight years. Various treatments were performed, and recurrences occurred in two cases. None of the five patients developed monoclonal gammapathy or systemic amyloidosis. CONCLUSION: Primary localized amyloidosis of the urinary tract is a rare disorder and can easily be confused with a neoplasm. The physiopathology is unknown, the prognosis is usually good. There is no specific treatment, and repeated work-up for systemic amyloidosis is unnecessary as local recurrences appear to be the main complication.

Evaluation of indium-111-labeled antifibrin monoclonal antibody for the diagnosis of venous thrombotic disease.

The potential advantage of using 111In-antifibrin (111In-AF) monoclonal antibody for the diagnosis of deep venous thrombosis (DVT) was studied in 44 patients with suspected DVT (27 underwent heparin therapy before 111In-AF injection). All patients had contrast venography (considered as the gold standard) and 111In-AF scintigraphy within 24 hr. Two to 3 mCi of 111In-AF were injected intravenously, and planar scintigraphy of the limbs was recorded within 10 min (17 times), 3 hr (44 times), and 18 hr (39 times). Indium-111-AF images were then interpreted without knowledge of the results of the other examinations. The DVT diagnostic accuracy of 111In-AF was greater when interpretation was based on images recorded at different time periods after injection. Indium-111-AF sensitivity for diagnosis of DVT was 85% (29/34) and was not apparently decreased by heparin therapy. None of the 10 patients with negative contrast venography had a positive 111In-AF scan. The results demonstrate the importance of recording serial images and the excellent accuracy of 111In-AF for diagnosing DVT.

Primary Epstein-Barr virus infection with clonal T-cell lymphoproliferation.

A case of fatal Epstein-Barr virus infection in a previously healthy girl who was first found to have severe infectious mononucleosis with spontaneous recovery is reported. Because an abnormal immune response to the virus persisted, the disease relapsed, manifesting in cutaneous and pulmonary lesions associated with hemophagocytic syndrome responsible for death. Pathologic findings were characterized by polymorphous atypical lymphoid infiltrate, prominent necrosis, and histiocytic hyperplasia. Lymphoid cells displayed CD8 phenotype and clonal T-cell receptor gene rearrangement. Viral genome was detected in lesions by Southern blot and located in nuclei of lymphoid cells by in situ hybridization. Pathologic findings suggested fatal infectious mononucleosis; however, phenotype and genotype favored a malignant diagnosis. Clonality was demonstrated to have arisen during primary infection. Virologic examination indicated that Epstein-Barr virus was a causative agent. Such a process belongs to the recently recognized spectrum of Epstein-Barr virus-related T-cell lymphoproliferative disorders that might overlap fatal infectious mononucleosis in patients who are especially vulnerable to the virus.

Comparison of technetium-99m aerosol and krypton-81m in ventilation studies for the diagnosis of pulmonary embolism.

A new method of producing aerosols (technegas) in which 99Tcm is bound to carbon atoms (99Tcm-C) was evaluated by comparing 99Tcm-C images with those obtained with 81Krm in the same patients. Twenty-five patients with suspected pulmonary embolism (PE) were studied. Immediately after the last 99Tcm-C view, the patients remained in supine position and inhaled 81Krm at tidal volume. Immediately after the 81Krm ventilation views were recorded, 4-7 mCi of MAA were injected IV. The same four views (ant, lop, rop, post) were recorded after inhalation of 99Tcm-C and 81Krm (200 kcounts) and 99Tcm MAA injection (400 kcounts). The mean penetration index of 99Tcm-C (0.91) was lower than that of 81Krm (1.04) (P less than 0.03). The apex to base lung distribution of 99Tcm-C and 81Krm appeared to be similar. The mean heterogeneity of 99Tcm distribution was 23, greater than that of 81Krm (14) (P = 10(-4)). The 99Tcm-C ventilation image quality was considered very good for 16 patients and good for 6 others. Significant foci of high bronchial uptake were infrequent. Interpretation of the examinations performed after inhalation of 99Tcm-C and 81Krm was concordant in all cases. No patient had an 81Krm/99Tcm MAA examination suggestive of PE when 99Tcm-C/99Tcm MAA indicated a low probability of PE, and vice versa. 99Tcm-C aerosols enable good quality ventilation images to be obtained in nearly all cases. Thus 99Tcm-C aerosols could be used in preference to 81Krm in ventilation studies for the diagnosis of PE.

99Tcm-labelled anti-fibrin Fab' fragment for evaluating the course of venous thrombosis in the rabbit.

Immunoscintigraphy was performed using the Fab' fragment of 99Tcm-labelled T2G1s anti-fibrin monoclonal antibody in a rabbit experimental model of venous thrombosis of known and increasing age (1, 3 and 7 days). Scans were positive in 3/7 cases for 1-day thrombosis (fibrin-poor network) and in 7/7 cases for 3-day thrombosis (fibrin-rich network). In rabbits with 7-day thrombosis, the scan was positive (2/4 cases) only when connective tissue was not present in the clot. Scintigraphic results were concordant with those of biodistribution studies showing the mean percentage of injected dose per gram 99Tcm-T2G1s present in the thrombosed vein wall (0.043, 0.082 and 0.07 for thrombi at 1, 3 and 7 days, respectively). Mean thrombosed vein wall-to-blood ratios were 1.027, 2.291 and 1.301, respectively. Immunoscintigraphy with T2G1s anti-fibrin monoclonal antibody thus enabled hematological status to be evaluated.

Plethysmographic cold test for diagnosis and evaluation of the severity of Raynaud's phenomenon. Validation of the method by factorial analysis of correspondences in 541 patients.

The purpose of this study was to analyze the reactivity to cold in a series of 541 patients with Raynaud's phenomenon and to search for possible correlations with the functional severity and the etiologic diagnosis of the acrosyndrome. Digital reactivity to cold was quantified by a plethysmographic cold test performed under standardized conditions, using mercury-strain-gauge plethysmography. The functional severity of Raynaud's phenomenon was assessed by the weekly frequency of attacks during winter. Topographic evaluation of the acrosyndrome sought to determine the possible extension of attacks to the thumb. Factorial Analysis of Correspondences indicated a high correlation between the intensity of reactivity to cold and the frequency of thumb involvement (p = 0.0001) or the weekly frequency of attacks during winter (p < 10(-4)). There was also a close dependence between reactivity to cold and the etiologic diagnosis of the acrosyndrome (p < 10(-4)). Significant correspondences were found between mild or major types of reactivity and primary Raynaud's disease, between very severe reactivity to cold and scleroderma. This study contributes to a clinical validation of the plethysmographic cold test. During Raynaud's phenomenon, it is indicative of clinical severity and can in a certain way guide the etiologic diagnosis, particularly concerning the risk of scleroderma.

Experimental venous thrombosis: what animal model?

A new experimental venous thrombosis model is described and its role relative to other models is defined. Previous models are not satisfactory for all types of investigation. Opposite, present model based on the three classic thrombogenic factors is suitable for venous scintigraphy and evaluation of different forms of therapy for venous thrombosis of the limbs. So this model permits research on diagnosis and therapy of thromboembolic disease.

Primary Raynaud's phenomenon. Age of onset and pathogenesis in a prospective study of 424 patients.

Many authors consider that late onset is a suspect criterion for differentiating primary Raynaud's phenomenon (Raynaud's disease, RD) from Raynaud's syndrome (RS). However, many cases of late-onset Raynaud's phenomenon in patients over forty years of age remain without etiologic diagnosis and therefore deserve the designation "late-onset RD." One hundred and ninety-four patients with RD (143 women, 51 men) were selected among 424 patients with Raynaud's phenomenon, according to Allen and Brown's criteria with negative serologic investigations and normal capillaroscopy. The purpose of the study was to consider the possible discriminant value of age of onset in distinguishing between RD and RS. The following epidemiologic features were studied: age of onset, sex, family history of Raynaud's phenomenon and migraine, and smoking and working habits. Microcirculation was assessed by capillaroscopy and strain-gauge plethysmography. Maximal digital flow at 45 degrees C and reactivity to cold were determined for each patient. Results were related to age of onset. The existence of true cases of late-onset RD in patients over forty years of age was confirmed (prevalence 27%), showing a correlation with a family history of Raynaud's phenomenon inferior to that found in early-onset cases (p < 0.0001). Microcirculation studies generally indicated a strong correlation between reactivity to cold, familial RD, and early onset, whereas no correlation was found with migraine or smoking. Nor was there any clinical or plethysmographic evidence for arteritis as a possible pathogenetic factor in late-onset RD. These results indicate that late-onset RD is a valid designation and that its pathogenesis seems less dependent on genetic sensitivity to cold than that of early-onset cases. In the absence of underlying arteritis, neurovascular dysfunction or a hemorheologic mechanism may be suggested as plausible causes of late-onset RD.

A quantitative test for measuring reactivity to cold by the digital plethysmograph technique: application to 66 control subjects and 65 patients with Raynaud's phenomenon.

The authors have developed a vascular reactivity test to cold using the digital plethysmograph technique with a mercury strain gauge. Three types of arterial reactivity were determined: local reactivity after immersion of the hand in 11 degrees C water, general reactivity after thorax ventilation, and cumulative reactivity associating both of these cooling modes. The method is based on measurement of the digital plethysmographic signal expressed as a ratio of a reference warm amplitude obtained after immersion of the hand in 45 degrees C water for 3 min. The method was tested and perfected in 66 control subjects before being applied to 65 patients with Raynaud's disease. Significant differences were noted between these 2 groups, especially in cumulative reactivity (p less than 10(-9)), which led to numerical expression of results in 5 types of increasingly important reactivity. It would appear that the test has diagnostic and prognostic value in the exploration of vascular acrosyndromes and their therapeutic follow-up.

[Methods for studying vasodilator agents in Raynaud's phenomenon]. / Méthode d'étude des vasodilatateurs dans le phénomène de Raynaud.

Raynaud's phenomenon is usually a benign acrosyndrome which few of the currently available therapies improve significantly. This makes the evaluation of the efficacy of vasodilators very difficult, especially as there are no standardised complementary investigations to quantify their effects. Assessment is based essentially on careful interrogation and the use of an analogical scale remains the method of reference. The multiplicity of factors inducing the acrosyndrome necessitates cross-over trials versus placebo over sufficiently long periods of observation (if possible, one month). As regards follow-up and objective evaluation, reactivity to cold is a promising method providing the tests can be standardised with respect to methodology and expression of results.

[Evaluation of digital venous reactivity to cold by plethysmographic measurement of compliance to cold and hot. Application of the method to 80 patients with Raynaud's phenomena and 36 controls]. / Evaluation de la réactivité veineuse digitale au froid par mesure pléthysmographique de la compliance à froid et à chaud. Application de la méthode à 80 phénomènes de Raynaud et 36 témoins.

A method is described for measuring digital venous compliance to cold by venous occlusion plethysmography (Perivein-Janssen apparatus). Determinations are made firstly to heat during immersion of the hand at 45 degrees C and then to cold during its immersion at 11 degrees C. In each case compliance is measured directly from a curve derived from successive venous occlusions of 1 mm Hg up to 120 mm Hg and by a standardized rate of recording. For pressures between 30 and 80 mm Hg a tracing is obtained that is assimilable to a linear slope from which compliance is calculated from the ratio delta P/delta V expressed as percentage variation of volume per cm Hg. The method was applied to 36 control subjects (19 men and 17 women) and 80 cases of Raynaud's phenomenon. Comparison of findings showed a significantly more marked fall in compliance to cold between: the female and male control subjects (p less than 10(-2)) the group of men with Raynaud's syndrome and male control subjects (p less than 10(-3)), the group with Raynaud's syndrome and Raynaud's disease (p less than 0.05). The findings suggest a possible pathogenic role of venospasm from cold in the determination of the syncopal phase of Raynaud's phenomenon and with respect to its predominance in members of the female sex.

[Importance of the Allen test in the diagnosis of distal arteriopathy in Raynaud's phenomenon. Prospective study on a continuous series of 576 patients]. / Intérêt du test d'Allen dans la recherche d'une artériopathie distale au cours du phénomène de Raynaud. Etude prospective sur une série continue de 576 patients.

From a prospective study concerning 576 patients with Raynaud's phenomenon, the authors studied the results of Allen's clinical test and their etiologic significance. These results were compared to those obtained by the instrumental technique using the Doppler probe to locate and compress radial and ulnar arteries and digital plethysmography to measure the effects of this compression. This instrumental technique makes it possible to investigate hand vascularization when Allen's clinical test is non interpretable or impossible which corresponds to 30% patients. A pathological Allen's test, whether it be clinical or instrumental, rather favors a Raynaud's syndrome (p < 10(-4)). The absence of ulnar vascularization was the abnormality most often noted and was rather found in severe Raynaud's phenomena, the sclerodermatous particularly (p < 10(-4)).

[Value of echography in the diagnosis of post traumatic pathology of the ulnar artery, in manual workers]. / Intérêt de l'échographie dans le diagnostic de la pathologie post traumatique de l'artère cubitale, chez le travailleur manuel.

Three cases of hypothenar hammer syndrome are reported in manual workers who experienced repeated traumatism of the palm of the hand either because of personal habit or the use of professional tools. Hemodynamic examination of the upper limb was performed by plethysmography (Perivein Etna) and Doppler ultrasound (8 MHz) complemented by angiography by direct puncture of the humeral artery. Ultrasonography was performed using a 7.5 MHz probe (Sononranger) for exploration of the ulnar artery at the wrist and in its course through the palm. The 3 patients presented aneurysmal dilatation of the ulnar artery in the palm, complicated by postembolic thrombosis of the collateral arteries of the fingers. The ulnar artery lesion was permeable 1 time, already thrombosed 1 time and thrombosed secondarily 1 time. Ultrasonography of the palm showed suspected aneurysm of the ulnar artery in 2 patients: one case was confirmed by angiography, whereas the other remained only suspect since the thrombosed ulnar artery was not opacified. The third patient presented an ulnar artery thrombosis without true aneurysmal dilatation. It may be concluded that ultrasonography can show suspected aneurysmal dilatation of the ulnar artery and be complementary to arteriography when the ulnar artery is thrombosed.

[Value of digital plethysmography in the positive diagnosis and prognostic evaluation of digital arteriopathies]. / Intérêt de la pléthysmographie digitale pour le diagnostic positif et l'évaluation pronostique des artériopathies digitales.

Maximal digital pulse (M.D.P.) is measured by digital plethysmographic technic with strain gauge. Our normal values are: 0.19 +/- 0.06% delta V. Diagnostic and prognostic significance of this parameter were studied on ten patients with digital necrosis. An arteriography of the hand was performed in each case. We have demonstrated that any value of P.D.M. below 0.10% delta V was always correlated with digital arteriopathy and with high risk of trophic complications. A normal value didn't exclude an arteriopathy. However, in these cases, the risk of trophic complications was get off.

[Clinical hemorheologic study of 65 inflammatory syndromes explored using standard biologic examination and total blood filtration test]. / Etude hémorhéologique clinique de 65 syndromes inflammatoires explorés par bilan biologique standard et test de filtration de sang total.

The hemorrheologic impact of an inflammatory syndrome was investigated in a prospective biological study of 65 patients by using an erythrocyte filtration test on total blood. Impact was assessed by a statistical study of correlations between relative filtration time (RFT), inflammation-reactive proteins (IRP) and the different parameters of the hemogram. A stepwise multiple regression test (SMRT) indicated the dominant role of fibrinogen in determining acceleration of the sedimentation rate (p less than 10(-3) and lengthening of RFT (p less than 10(-3). Moreover, RFT appeared to be very significantly correlated with polymorphonuclears (R = 0.55; p less than 10(-3] hematocrit as measured by the centrifugation technique (R = 0.34; p = 0.005) and corpuscular concentration in hemoglobin (CCHM) (R = 0.30; p = 0.01). A chart predictive of microcirculatory risk was deduced from the study based on fibrinogen values and hematocrit. However, the relatively low rate of reduction in the total variance observed during SMRT suggests the quite relative role of the studied parameters in erythrocyte filtration disturbances during an inflammatory syndrome.

[Pelvic phlebitis presenting as paradoxical arterial embolism]. / Phlébite pelvienne révélée par une embolie artérielle paradoxale.

The authors report the case of a 24-year-old woman with paradoxical embolism of the right arm subsequent to childbirth. Patent foramen ovale was diagnosed by right cardiac catheterization and contrast echocardiography. On the basis of clinical, immunoscintigraphic and radiologic data, the pelvic region was the only possible origin of the embolic process. The main interest of this case is that arterial ischemic signs were indicative of an embolic process of pelvic origin diagnosed by scintigraphy using radiolabeled antifibrin antibody.

[Aortic thrombosis during acute endocarditis caused by Staphylococcus aureus]. / Thrombose de l'aorte au cours d'une endocardite aiguë à staphylocoque doré.

The authors report a case of acute bacterial (Staphylococcus aureus) endocarditis in a 70-year-old woman, revealed by a febrile cerebral ischemic accident. Ultrasonography confirmed the presence of a large posterior mitral valve vegetation interfering with left ventricular filling. The sudden onset of complete paraplegia and acute ischemia of the lower limbs suggested thrombosis of the abdominal aorta, which was confirmed by aortography. These features indicated that a vegetation fragment had migrated, obstructing the aortic bifurcation and causing secondary thrombosis. This led in turn to involvement of the medullary arteries and the onset of paraplegia. Unfortunately, acute renal insufficiency and major left heart failure rapidly developed, and the patient died. Autopsy confirmed the diagnosis of aortic thrombosis with involvement of the renal arteries. Multiple visceral infarcts were noted as well as the large mitral vegetation. This case illustrates the potential severity of systemic embolism complicating endocarditis due to Staphylococcus aureus. The accident was remarkable because of the aortic acute occlusion and the association with paraplegia, an unusual neurologic complication.

[Vascular manifestation of thoracic outlet syndrome. Prospective study of 104 patients]. / Les manifestations vasculaires du syndrome de la traversée cervico thoracique. Etude prospective de 104 patients.

On the basis of a prospective study of 104 patients, the authors discuss the diagnostic value of the clinical symptoms revealing the thoracic outlet syndrome (TOS), as well as the specificity of the vascular functional exploration carried out to establish the diagnosis. Non-systematized pain and dysesthesia in the upper limb, with a postural or nocturnal onset, and Raynaud's sign are the most frequently observed signs. The "candlestick" maneuver still is the most reliable clinical triggering maneuver. The clinical features and the vascular functional explorations (capillaroscopy and digital plethysmography) allow demonstrating the existence of a true Raynaud's syndrome secondary to the TOS. The results of the arterial Doppler study distinguish the symptomatic and asymptomatic sides in the same patient, though without any correlation with the symptoms observed. The Doppler examination therefore seems to be reliable to demonstrate an anatomical duct, but remains insufficient to establish a causal relationship with the signal symptoms in most cases.