[Neurological involvement of sarcoidosis: current diagnostic and therapeutic strategies]. / Atteinte neurologique de la Sarcoïdose : stratégies diagnostiques et thérapeutiques actuelles.

Neurosarcoidosis (NS) is a rare but severe form of sarcoidosis. NS is associated with significant morbidity and mortality. Mortality is about 10% at 10 years with more than 30% of patients who have a significant disability. The most frequent features are cranial neuropathy (the facial and optic nerve most commonly affected), cranial parenchymal lesions, meningitis, spinal corn abnormalities (20-30%) and more rarely peripheral neuropathy (approximately 10-15%). The challenge of diagnosis is to eliminate other diagnoses. Atypical presentations should make to discuss the need for cerebral biopsy in order to highlight the presence of granulomatous lesions while eliminating alternative diagnosis. Therapeutic management is based on corticosteroid therapy and immunomodulators. There are no comparative prospective study to allow us to define the first-line immunosuppressive treatment and the therapeutic strategy in refractory patients. Conventional immunosuppressants such as methotrexate, mycophenolate mofetil and cyclophosphamide are commonly used. Data on the efficacy of anti-TNFα (including infliximab) in refractory and/or severe forms are increasing during the last ten years. Additional data is necessary to assess their interest in first line in patients with severe involvement and a significant risk of relapse.

[Cardiac sarcoidosis: Diagnosis, prognosis and therapeutics]. / Sarcoïdose cardiaque : stratégies diagnostiques et thérapeutiques actuelles.

Sarcoidosis is a systemic granulomatous disease characterized by pulmonary involvement in most patients and more rarely by extrapulmonary involvement such as ocular, skin, salivary, lymph nodes and joints damages. Neurological and cardiac involvements are uncommon but are associated with increased morbidity and mortality. Cardiac sarcoidosis affects 5 to 20% of patients depending on the studies and autopsy studies even report cardiac involvement in 25% of sarcoidosis patients. This review aims to summarise main data on the diagnostic value of the different imaging techniques in cardiac sarcoidosis and to also detail the management of these patients who require a multidisciplinary approach.

The association of systemic lupus erythematosus and myasthenia gravis: a series of 17 cases, with a special focus on hydroxychloroquine use and a review of the literature.

The coexistence of systemic lupus erythematosus (SLE) and myasthenia gravis (MG) is rarely reported, and most of the published studies are case reports. Hydroxychloroquine, an antimalarial agent, is an essential treatment in patients with SLE but special caution is recommended when used in MG patients. We retrospectively analyzed the clinical features, laboratory findings, and outcome of 17 patients with both diseases with a special focus regarding hydroxychloroquine use and with a review of the literature. All patients were women. The mean age at MG onset and SLE diagnosis was 34.5 [14-64] and 37.8 [18-72] years, respectively. The presenting symptoms of MG were limb weakness (94%), ocular (88%) and bulbar involvement (53%). Autoantibodies against the acetylcholine receptor were positive in 94% of cases. The main manifestations of SLE included arthritis (88%), cytopenias (53%) and skin rash (41%). Treatment of SLE required hydroxychloroquine (94%), steroids (47%) and immunosuppressive drugs (18%). Among eight patients (47%) who developed MG after initiation of hydroxychloroquine, the question of induction of MG by hydroxychloroquine was raised in one patient. On the other hand, an exacerbation of myasthenic symptoms was only seen in one of the eight patients who received hydroxychloroquine after the diagnosis of MG. Including our cases, we reviewed a total of 70 patients with SLE and MG. Compared with a large series of 1,000 unselected SLE patients, those with associated MG were older, had lower incidence of cutaneous, renal, and neurological manifestations, and higher frequency of anticardiolipin antibodies and lupus anticoagulant. In conclusion, the clinical pattern of patients with SLE and MG seems to be characterized by a less severe course of SLE and higher frequency of antiphospholipid antibodies. Hydroxychloroquine treatment appears to be safe in this setting.

[Infliximab treatment for chronic sarcoidosis--a case series]. / Infliximab et sarcoïdose chronique. L'expérience française à propos de 31 cas.

The management of chronic forms of sarcoidosis can be a difficult therapeutic problem. The purpose of this observational study was to analyze the effectiveness and tolerance of infliximab in chronic sarcoidosis. This multicentre retrospective study involved 31 cases of chronic, systemic, and/or pulmonary sarcoidosis treated by infliximab. Disease had been present for 9 years and involved a mean of four organs. Patients had received several immunosuppressive drugs and 30/31 were treated with corticosteroids (19 ± 16 mg prednisone/day) with the addition in 17 cases, of one or more other immunosuppressive agents. The duration of infliximab therapy was 13 ± 12 months. A beneficial response to infliximab was observed in 62% of the cases across all organs involved: 65% for lung involvement, 67% for skin lesions and 50% for central nervous system lesions. For other organs, responses were disparate. The corticosteroid sparing effect was small (2.8 ± 9.7 mg/day). Effectiveness was more frequent in patients who were treated with additional immunosuppressive agents. Thirteen (41.9%) patients developed side effects; in seven out of 13, side effects were severe, sometimes requiring infliximab to be stopped. Our study supports the continuing interest in the use of infliximab for the treatment of chronic sarcoidosis, but also highlights the frequency and severity of side effects. Indications are difficult to specify, and currently, its use should be restricted to clinical trials.

Renal enlargement as presentation of isolated renal relapse in childhood leukemia.

Extramedullary relapses in children with acute lymphoblastic leukemia occur most frequently in the central nervous system and in the testis. In this report, the authors describe a 16-year-old girl with an isolated renal relapse of acute lymphoblastic leukemia after a disease-free interval of 2 years and 8 months. This clinically inconspicuous renal relapse was suggested by a routine follow-up renal sonography. No evidence of disease was found in bone marrow or peripheral blood. Renal biopsy was required to establish the diagnosis. Treatment consisted of intensive chemotherapy and autologous bone marrow transplantation. The patient has been in second complete continuous remission for 7 years. The authors recommend the use of an intensive multidrug salvage regimen.

[Intrabronchial inhaled seed migration. Value of ultrasonography in the diagnosis of pleural-cutaneous fistula]. / Epis de graminée intrabronchiques migrateures. Apport de l'échographie dans le diagnostic de fistule pleuro-cutanée.

We report two cases of inhalation of seeds in infants aged 11 months and two years. In the first the syndrome of inhalation had not been apreciated. The seed blocked the left bronchus, provoking an obstructive emphysema with superinfection. The outcome was statisfactory after removal by bronchoscopy. In the second case although the aspiration of the particle was appreciated the endoscopy was performed too late to prevent the migration of the seed. After having produced a pneumonia it crossed the pleura and gave a subcutaneous swelling. This migration could in part be followed by ultrasound which enabled the appropriate moment for surgical exploration to be defined. These two cases show the two possible evolutions when the inhalation of a seed occurs and the contribution that can be made by ultrasound.

Molecular phylogeny of the genus Frankia and related genera and emendation of the family Frankiaceae.

The members of the actinomycete genus Frankia are nitrogen-fixing symbionts of may species of woody dicotyledonous plants belonging to eight families. Several strains isolated from diverse actinorhizal plants growing in different geographical areas were used in this study. The phylogenetic relationships of these organisms and uncharacterized microsymbionts that are recalcitrant to isolation in pure culture were determined by comparing complete 16S ribosomal DNA sequences. The resulting phylogenetic tree revealed that there was greater diversity among the Alnus-infective strains than among the strains that infect other host plants. The four main subdivisions of the genus Frankia revealed by this phylogenetic analysis are (i) a very large group comprising Frankia alni and related organisms (including Alnus rugosa Sp+ microsymbionts that are seldom isolated in pure culture), to which Casuarina-infective strains, a Myrica nagi microsymbiont, and other effective Alnus-infective strains are related; (ii) unisolated microsymbionts of Dryas, Coriaria, and Datisca species; (iii) Elaeagnus-infective strains; and (iv) "atypical" strains (a group which includes an Alnus-infective, non-nitrogen-fixing strain). Taxa that are related to this well-defined, coherent Frankia cluster are the genera Geodermatophilus, "Blastococcus," Sporichthya, Acidothermus, and Actinoplanes. However, the two genera whose members have multilocular sporangia (the genera Frankia and Geodermatophilus) did not form a coherent group. For this reason, we propose that the family Frankiaceae should be emended so that the genera Geodermatophilus and "Blastococcus" are excluded and only the genus Frankia is retained.

Sclerosing hemangioma of the lung: radiological findings and pathological diagnosis.

We present a case of sclerosing hemangioma of the lung, revealed as a solitary round mass on routine chest radiography in a 14-year-old patient. CT and MRI findings were consistent with a solid neoplasm but no specific characteristics were identified. Analysis of the surgical biopsy material led to a cytological diagnosis of adenocarcinoma. Definitive diagnosis of sclerosing hemangioma of the lung was established on pathological examination of the whole surgical specimen.

Molecular characterization of Frankia microsymbionts from spore-positive and spore-negative nodules in a natural alder stand.

Among the Frankia strains capable of establishing a nitrogen-fixing symbiosis with actinorrhizal plants, in planta sporangial formation is not universal and has led to the distinction between spore-positive (Sp+) and spore-negative (Sp-) nodules. Numerous Frankia strains have been isolated in pure culture from Sp+ nodules of different host plants, but, although they were able to reinfect their respective host plant, none of them was able to differentiate endophytic sporangia under laboratory conditions. The first step of this study was to demonstrate, at the molecular level, the existence of specific Sp+ strain genotypes differing from Sp- strain genotypes in a single alder stand. In a second step, by way of PCR amplification and sequencing of the PCR products, we have characterized oligonucleotide primers specific for the genus Frankia and for each of the two types of Frankia microsymbionts able, or not, to differentiate sporangia inside natural green alder nodules. These primers applied in PCRs with DNA extracted from nodules confirmed the morphological identification and revealed the presence of nodules colonized by both types of actinomycetes. Finally, a preliminary PCR study was conducted with DNA extracted directly from soil samples which permitted checking the rhizosphere of Sp+ and Sp- nodules for the presence of the corresponding strains.

[Pancreatitis in systemic lupus erythematosus. Review of the literature apropos of 5 cases]. / Pancréatite au cours du lupus érythémateux disséminé. Revue de la littérature à propos de cinq observation.

We report five cases of pancreatitis in systemic lupus erythematosus. Three patients died. The cause of death was directly related to pancreatitis in two cases. Several causes of pancreatitis may be suspected: vasculitis, thrombosis when associated to antiphospholipid syndrome, biliary calculi, infection, metabolic abnormalities or adverse effects of therapy. About seventy cases of pancreatitis have been reported in systemic lupus erythematosus in the literature Pancreatitis was the inaugural sign of lupus in six cases. In 12 cases, besides lupus, no other cause of pancreatitis was found. However, pancreatic vasculitis or thrombosis was rarely demonstrated even in post-mortem examinations. The role of corticosteroids in pancreatitis in lupus is controversial since the evolution of pancreatitis in lupus is generally good with corticosteroids. We think that diagnosis of pancreatitis in lupus should not implicate discontinuation or decrease of corticosteroids dosage, unless their responsibility is absolutely demonstrated.

Morphological and molecular characterization of Frankia sp. isolates from nodules of Alnus nepalensis Don.

Nodules collected from Alnus nepalensis growing in mixed forest stands at three different sites around Shillong, were crushed in various culture media to obtain isolates of Frankia. The isolates were found to have typical Frankia morphology as revealed by the scanning electron microscope. Seedlings inoculated with isolates or crushed nodules formed nitrogen fixing nodules. Frankia specific DNA probes amplified the DNA of the tested isolate AnpUS4. Partial nucleotide sequence of the 16S rRNA gene indicated that AnpUS4 was phylogenetically distinct from all other Frankia strains characterized so far.

[Relapsing polychondritis and mesenteric panniculitis: apropos of 2 cases]. / Polychondrite atrophiante et panniculite mésentérique: à propos de 2 cas.

We report two cases of polychondritis associated with mesenteric panniculitis. Case 1. In February 1989, a woman born in 1949 presented with 40 degrees C fever accompanied by pain in the abdomen and pelvis. Eight days later, nodular skin lesions appeared on her lower limbs. The abdomen was swollen with gas and undepressible. An abdominal CT scan revealed partitioned peritoneal collections, and a guided needle aspiration produced a chylous fluid. Direct and indirect bacteriological examinations gave negative results. Histology showed intense inflammatory reaction with giant cells and lipophages, thereby confirming the presence of mesenteric panniculitis. Six months later, the development of chondritic lesions on the nose and the helix of the ear clinched the diagnosis of polychondritis. The patient was put on corticosteroid therapy for a few months, and in January this year (1993) she is durably asymptomatic. Case 2. In October 1977, a woman born in 1937 presented with polychondritis with prolonged fever, inflammatory syndrome and chondritic lesions of the nose, larynx and helix of the ear. In December 1978, she developed signs of abdominal obstruction. Laparotomy revealed infiltration by multiple nodular formations of the entire posterior line of attachment of the mesentery. Biopsies withdrew a puriform fluid. Histology showed a partly necrotic adipose tissue with giant cells and lipophages. High-dose corticosteroid therapy partially controlled the chondritic and abdominal manifestations. The occurrence of abdominal pain in patients with polychondritis may result from several disorders, such as iatrogenic complications, digestive tract vasculitis or ulcerative colitis, but also associated mesenteric panniculitis.

[Heart conduction disorders in long-term treatment with chloroquine. Two new cases]. / Troubles de la conduction cardiaque au cours d'un traitement prolongé par chloroquine. Deux nouvelles observations.

Cardiac complications are exceptional in long-term chloroquine therapy; congestive heart failure and restrictive cardiomyopathy may develop, but disorders of conduction are more frequent. The characteristics of these disorders emerge from 12 cases in the literature and from 2 personal cases. The usual disorder is fascicular block which may become a complete, syncopal, atrioventricular block, as in one of our 2 patients. The time elapsed between the beginning of treatment and the occurrence of these disorders (2 to 30 years) and the total dose of chloroquine received (100 to 2,500 g) are extremely variable. Retinopathy or neuromyopathy is present in 64 and 35 percent of the cases respectively. The diagnosis is confirmed by endomyocardial biopsy with electron microscopic study which shows vaculoar myopathy with numerous large secondary lysosomes containing a dense material of lamellar structure (myelinic figures, curvilinear bodies). Regression of heart conduction disorders after withdrawal of chloroquine seems to be inconstant and incomplete. The rare occurrence of this complication raises the question of genetic predisposition. We believe that chloroquine therapy should be contra-indicated in patients with a history of conduction disorders and that a 6-monthly electrocardiographic control of these patients would be justified.

[Chronic constrictive pericarditis. 27 cases]. / Péricardites chroniques constrictives. 27 observations.

Twenty-seven cases of chronic constrictive pericarditis seen between 1975 and 1990 in an internal medicine department were analyzed retrospectively. The chronic pericarditis was consecutive to one (n = 5) or several (n = 7) episodes of acute pericarditis. Echography demonstrated the presence of pericardial effusion in 74 percent of the cases, pericardial thickening in 41 percent and/or compression of right heart cavities in 55 percent. Computerized tomography of the chest, performed in 16 cases, showed pericardial effusion in 63 percent of the cases, pericardial thickening in 37 percent and lymph node enlargement in 19 percent. Magnetic resonance imaging of the chest was carried out in 2 patients but showed no abnormality. All 11 patients who underwent cardiac catheterization were found to be adiastolic. The cause of constrictive pericarditis, elicited in 13 patients was neoplasia in 4, sequelae of radiotherapy in 2, injuries in 2, mediastinal and retroperitoneal fibrosis in 2, myocardial infarction in 1, purulent pericarditis in 1 and bacteriologically proven tuberculosis in 1. Medical treatment with corticosteroids (n = 16) and/or antituberculous therapy (n = 15) was successful in 2 patients; 25 patients had to undergo surgery 7 +/- 11 months after constriction was diagnosed. Pericardial drainage (through a pericardiopleural window in 4 cases) proved to be sufficient in 10/15 patients but failed in 5. Pericardectomy was performed initially in 3 cases and after failure of medical treatment and/or drainage in 11 cases. The 4 patients with neoplastic constrictive pericarditis died 10 months on average after the diagnosis, but the remaining 23 patients were alive after à 9 to 48 months (mean: 19 +/- 15) follow-up. These results suggest that the data provided by echocardiography and computerized tomography of the chest usually point to the relevant therapeutic measures without a need for invasive haemodynamic exploration. Idiopathic constrictive pericarditis now accounts for 50 percent of the cases; tuberculosis has become exceptional, but the other, previously exceptional causes (neoplasia, heart surgery, radiotherapy, connective tissue diseases) are more frequent. Corticosteroids should be used in chronic constrictive pericarditis occurring after cardiac surgery or in the course of a connective tissue disease, but they are effective only in highly inflammatory forms of the disease. Modern treatment relies on early surgery, since functional results and patient's survival are closely related to the date of pericardectomy which must be carried out before very important myocardial repercussions develop.

[Vitamin deficiency-induced pancytopenia mimicking leukemia. Three cases]. / Pancytopénie carentielle mimant une leucémie. Trois observations.

Folate and vitamin B12 are indispensable to normal cell division. High turnover tissues, therefore, are the first to be affected when these vitamins are deficient. Such deficiencies, which are known to result in megaloblastic anaemia at a late stage, may also influence the granulocyte and platelet lines, but pancytopenia rarely occurs. We report 3 cases of pancytopenia associated with folate and/or vitamin B12 deficiency in elderly patients. In two of these patients bone marrow examination showed a misleading "pseudo-leukaemia" due to a significant proportion of strongly dystrophic young cells. Cure was obtained within 30 to 45 days of vitamin therapy, with complete normalization of the haemogram.

[Pulmonary hyalinizing granuloma. Apropos of 2 new cases]. / Les granulomes hyalinisants pulmonaires. A propos de 2 nouveaux cas.

Pulmonary hyalinising granuloma are nodular or localised fibrosing lesions of the pulmonary parenchyma and are single or multiple. We report two new cases of this disorder which is rare, as only 62 cases have been published in the literature. It is a pathology with few symptoms, sometimes revealed by general signs. Radiologically there are nodules which are most often round or oval, intra-parenchymal, well demarcated, single or multiple. The histological appearance is characteristic: the centre of the granuloma consists of a network of dense collagen fibres which are lamellar separated by clear spaces; the periphery is the seat of rich cellular infiltration of plasmocytes and lymphocytes in the peri-vascular region. Most often there is a spontaneous benign outcome. The frequent association of pulmonary hyalinising granuloma in fibrotic disorders and the similarity in the histological appearance leads to the hypothesis of a common pathogenesis in these disorders.