[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.

Long-term outcome in idiopathic granulomatous mastitis: a western multicentre study.

AIM: To investigate the presentation, disease course and long-term outcome of a western cohort of idiopathic granulomatous mastitis (IGM) and to analyse the impact of different therapeutic strategies. METHODS: Multicentre retrospective study of 23 women followed over an extended period. Patients were recruited in nine French internal medicine departments. RESULTS: The median follow-up was 6 years. IGM presented commonly as a single inflammatory unilateral extra-areolar lump of varying size. Clinical course was heterogeneous and frequently remitting/relapsing. Most patients had at least one recurrence (18/23, 78%). The mean number of recurrences was 1.3 ± 1.5. Seven women had a bilateral evolution. Twelve women received steroids (corticosteroids). Only two of these did not respond to corticosteroids, whereas six relapsed when dose was tapered off. Nine patients received colchicine and/or hydroxychloroquine. First-line treatment consisted of excisional surgery in eight cases. At the date of last interview, 91% of the patients declared to be healed, 15 being free of treatment. However, 12/21 (57%) reported significant sequelae (unsightly scars: eight and/or lasting pain: six). Unsightly scars were not more prevalent in patients who had received steroids whereas they tended to be more frequent after breast excisional surgery. In addition, we found that excisional surgery did not prevent recurrences more successfully than a conservative approach. CONCLUSIONS: Despite its retrospective nature, this Caucasian series provides novel information regarding long-term outcomes in IGM and argues in favour of conservative approaches. The value of immunomodulatory drugs such as colchicine or hydroxychloroquine deserves further investigation.

[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.

[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.

[Disclosure of Behcet disease by concomitant dental infection]. / Poussée inaugurale de maladie de Behçet concomitante d'un foyer infectieux dentaire.

BACKGROUND: Behçet's disease can be aggravated by chronic infection. Our case illustrates how the disease can be disclosed during an acute activation of a chronic infectious focus. CASE REPORT: A 40-year-old man had Behçet's syndrome associating fever, bipolar aphtosis, cutaneous pseudo folliculitis, anterior uveitis, and meningitis following an acute episode of a dental infection, with periapical granuloma. Antibiotic therapy was ineffective in calming this first flare-up of Behçet's disease. Corticosteroid and colchicine therapy were effective. DISCUSSION: Clinical and experimental work would implicat buccal streptococcal flora in the pathogenesis of Behçet's disease. Antibiotics offer interesting perspectives but further studies are needed to define their role in the treatment of Behçet's disease.

Angiomagnetic resonance imaging of iliofemorocaval venous thrombosis.

Although magnetic resonance imaging has been proposed for the diagnosis of deep venous thrombosis (DVT), its role in diagnostic strategy remains to be defined. We compared prospectively magnetic resonance angiography (MRA) with two-dimensional time-of-flight with contrast venography (CV) and colour duplex sonography (CDS) in 25 patients with DVT of the pelvis confirmed by CV. All patients were examined by CV (gold standard) and MRA and 17 by CDS. These studies were compared for DVT diagnosis in the pelvis and inferior vena cava and analysis of thrombotic spread. MRA was positive in 25 patients whose DVT was diagnosed by CV (100% sensitivity). MRA sensitivity and negative predictive value were 100%, specificity 98.5% and positive predictive value 97.5% for the diagnosis of thrombosis at each anatomic level. There were discrepancies between MRA and CV (2 false-positive results for 2 venous segments) and between CDS and CV (2 false-positive and 3 false-negative results). CV was uninterpretable for 8.8% of segments and CDS was often technically limited to the pelvic level, whereas all venous segments explored were analysable in MRA. MRA gave excellent results for positive diagnosis and DVT spread. MRA is a potentially valuable technique for assessing iliofemorocaval venous thrombosis.

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.

[Diagnosis of venous thrombosis. Evaluation of immunoscintigraphy with 99M technetium labelled antifibrin]. / Diagnostic des thromboses veineuses. Evaluation de l'immunoscintigraphie antifibrine marquée au technétium 99m.

OBJECTIVES: We evaluated the interpretation, reliability and usefulness of 99m technetium labelled antifibrin immunoscintigraphy for the diagnosis of deep vein thrombosis in the lower limbs. METHODS: The diagnostic value of 99m technetium labelled antifibrin immunoscintigraphy was assessed in 44 patients with suspected venous thrombosis. The reference examination was bilateral ascending phlebography; 40 patients had doppler ultrasonography of the veins; 0.5 mg of antibody labelled by 17.5 mCi on average of 99m technetium were injected intravenously, and serial scintigraphic images were collected 1 min, 90 min and 18 hours after injection. RESULTS: The best results were obtained by comparison between the 90 min and the immediate post-injection images, with 86 percent sensitivity, 73 percent specificity and 81 percent accuracy. Heparin therapy and past history of phlebitis had no influence on the results. The doppler ultrasonography/immunoscintigraphy combination had a 100 percent specificity. 99m Technetium labelled antifibrin immunoscintigraphy had about the same diagnostic value as 111 indium labelled antifibrin immunoscintigraphy. CONCLUSION: The introduction of 99m technetium as isotopic marker will make immunoscintigraphy easier and available in numerous nuclear medicine centres. Antifibrin immunoscintigraphy can be an additional diagnostic tool for the difficult diagnosis of deep vein thrombosis.

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.

[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.

[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)).

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.

[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.

[Septic Campylobacter fetus thrombophlebitis: a new case]. / Thrombophlébite septique à Campylobacter fetus: un nouveau cas.

The diagnosis of septic thrombophlebitis is difficult and often delayed, but it must be borne in mind in all cases of venous thrombosis accompanied by signs of local and/or systemic infection, or deteriorating under heparin therapy. We report a case of septic thrombophlebitis caused by Campylobacter fetus subspecies fetus. The characteristic features, obtained from the literature, of septic thrombophlebitis caused by Campylobacter spp are presented.

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 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.

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.