Systemic mastocytosis and bone involvement in a cohort of 75 patients.

OBJECTIVES: To investigate bone involvement in a large cohort of systemic mastocytosis (SM) patients, and evaluate the efficacy of bisphosphonate therapy. PATIENTS AND METHODS: From 2000 to 2004, 75 patients with SM according to WHO criteria underwent skeletal x-rays and bone mineral density (BMD) assessment. Sequential BMD assessments were performed in nine patients treated with bisphosphonate (mean follow-up 65 months). RESULTS: 37 patients (49%) had bone involvement according to both x-rays and BMD evaluations: osteoporosis (23 patients, 31%, mean lumbar spine T score: -3 SD), with vertebral fracture (13 patients, 17%), axial skeleton osteosclerosis (six patients, 8%), mixed patterns (three patients), osteopenia with pre-existing fractures (four patients) and focal osteolytic lesion (one patient). Blood count abnormalities were associated with osteosclerosis (p=0.005). In nine patients with osteoporosis and bisphosphonate therapy, mean lumbar spine BMD increased from 0.83 to 0.92 g/cm(2) (+11.1%; ie, +2.05% per year) without recurrence of vertebral fracture. CONCLUSION: Half of adult patients with SM have bone involvement. Osteoporosis is the most prevalent bone manifestation in SM (31%). Bisphosphonate therapy seems efficient to improve lumbar spine BMD during SM-related osteoporosis. Spine x-ray and BMD should be performed in all SM patients to detect those who may benefit from anti-osteoporotic therapy.

[Osteoporosis induced either by unfractionated heparin or by low molecular weight heparin]. / Ostéoporose induite soit par l'héparine non fractionnée soit par l'héparine de bas poids moléculaire.

Since the first suggestion of heparin-induced osteoporosis in 1963, a large body of work has been published. The mechanism can be explained by the effect of heparin as a cofactor for physiological stimulators of osteoclasts. Low-molecular weight heparins are an interesting alternative to non-fractionate heparin as the risk is reduced with an equivalent anticoagulation activity. Prevention is based on screening for patients at risk, preferential use of low-molecular weight heparins, early switch to anti-vitamin K and vitamin and calcium supplementation in pregnant women an elderly subjects. Curative treatment combines vitamin-calcium supplementation with inhibitors of bone resorption.

[Aortic aneurysm with vena cava thrombosis occurring in Behcet's disease]. / Anévrisme aortique avec thrombose cave contiguë au cours d'une maladie de Behcet.

We report a case of Behcet's disease complicated by aortic aneurysm and contiguous vena cava thrombosis due to compression. Arterial aneurysms are uncommon in the course of Behcet's disease and are associated with a poor prognosis owing to the risk of rupture. Vena cava thrombosis is found in 10% of cases; pulmonary embolism is infrequent. Venous and arterial lesions usually evolve independently. In most cases they are consecutive to vasculitis. The case reported herein is uncommon because of simultaneous and contiguous venous and arterial lesions. Eighteen months after aorto bi-iliac graft and inferior vena cava ligature, there is no recurrence of thrombosis nor aneurysm with a treatment including heparin, colchicine and azathioprine.

[Popliteal venous aneurysm revealed by recurring pulmonary embolism. Echographic, phlebographic, x-ray computed tomographic and nuclear magnetic resonance aspects]. / Anévrisme veineux poplité révélé par des embolies pulmonaires récidivantes. Aspect échographique, phlébographique, tomodensitométrique et en résonance magnétique nucléaire.

We report a characteristic case of popliteal vein aneurysm which was demonstrated not only by Doppler ultrasonography and venographic examination, but also by CT scan and magnetic resonance imaging. A review of the literature underlines the rarity of these aneurysms, since less than 20 cases have been published. They are always true aneurysms, most often revealed after an episode of pulmonary embolism. Doppler ultrasonography and venography confirm the diagnosis. The place of CT scan and magnetic resonance imaging remains to be defined. Even if asymptomatic, the embolic risk necessitates surgical resection of the aneurysm and restoration of venous continuity.

[Fenofibrate induced polymyositis]. / Polymyosite induite par le fénofibrate.

In a 65-year old man complaining of myalgias and loss of muscular strength, the creatine phosphokinase level was found to be 35 times higher than normal values. The electromyogram was of the diffuse myogenic type. Muscle biopsy showed necrotic lesions of the muscle fibres associated with perivascular infiltrates of mononuclear cells, leading to the diagnosis of polymyositis. This patient had been treated for 10 years with fenofibrate for hyperlipidaemia; during the last 32 months he had taken this drug in doses of 600 mg per day. Eight days after fenofibrate was discontinued, all clinical and laboratory abnormalities had disappeared. A reintroduction test performed 6 weeks later raised the creatine phosphokinase level up to 43 times the normal value. Withdrawal of fenofibrate therapy resulted in rapid and lasting recovery. This case shows that fenofibrate should be added to the list of drugs that are responsible for iatrogenic polymyositis.

[An unknown cause of prolonged fever: apropos of 6 cases of chronic aortic dissection]. / Une cause méconnue de fièvre prolongée: à propos de six cas de dissection aortique chronique.

PURPOSE: Aortic arch dissection may be sometimes misdiagnosed due to the lack of mild to moderate chest pain. Definite diagnosis is often made while dissection has already occurred more than 15 days ago, being thereafter considered as chronic. Aortic dissection may then present as a prolonged febrile illness with fever and/or inflammation as main symptoms, with little or no pain. METHODS: We retrospectively reviewed cases of chronic aortic dissections seen in a department of internal medicine and a department of neurology between 1975 and 1992. RESULTS: We report six cases of patients presenting with aortic dissection and describe their outcome and treatments after the diagnosis was made based on either thoracic computerized tomography or trans-esophageal echocardiography evidence. Four patients had surgical aortic arch repair while one patient was treated with beta-blockers. CONCLUSION: Chronic aortic dissection has rarely been reported to cause fever or increased sedimentation rate. Treatment has to be discussed between medical and surgical teams involved in the therapeutical management of these unusual patients.

[Wegener's granulomatosis disclosed by clinical symptoms of Horton's disease]. / Granulomatose de Wegener révélée par un tableau évocateur de maladie de Horton.

In a series of 60 patients with Wegener's granulomatosis, 2 had initially presented with clinical signs suggestive of temporal arteritis. One of these two patients was a 69-year old woman suffering from inflammatory pain in the shoulders, wrists and knees, myalgias in the lower limbs and intermittent jaw claudication. The other patient was a 60-year old man with febrile polyarthritis predominantly affecting the knees and shoulders, and hyperaesthesia of the scalp. In both cases biopsy of the temporal artery gave negative results. Corticosteroids provided a dramatic improvement, but a relapse corrected the diagnosis. Three similar cases have been reported, but only one had a histological lesion of the temporal artery. Cases of temporal arteritis associated with pulmonary granulomatosis raise the problem of classification with localized Wegener's disease. An initial presentation suggestive of temporal arteritis may hide other systemic diseases, notably rheumatoid arthritis, periarteritis nodosa or Chug and Strauss angitis; Wegener's granulomatosis must be added to this list.

[Arterial manifestations of Behçet's disease. 12 cases]. / Manifestations artérielles de la maladie de Behçet. Douze observations.

Out of 196 patients with Behçet's disease, 12 (10 men and 2 women, mean age 34 +/- 7 years) had non-coronary arterial lesions. Behçet's disease was complete in 4 patients. The arterial lesions had appeared 8.6 +/- 8 years on average (20 years at most) after the first sign of the disease. Three patients showed evidence of stenosis or occlusion involving one or several arteries. Eight patients had both stenotic and aneurysmal lesions. One patient had an arteriovenous fistula. Another developed a false aneurysm at the site of introduction of a femoral catheter. Yet another patient developed an anastomotic aneurysm one year after implantation of an abdominal aortic graft. In 2 cases histology showed fragmentation of the media associated with vasculitis of the vasa vasorum. Two patients with pulmonary aneurysm died of massive haemoptysis. In 2 patients combined corticosteroid and cyclophosphamide therapy failed to prevent the development of aneurysmal lesions. Phlebitis was associated with arterial involvement in 7 patients. Comparison between patients with or without arterial lesions showed no significant difference in time of onset of Behçet's disease, sex, main clinical features and presence of HLA B5. Aneurysmal lesions respond poorly to medical treatment, and surgery is mandatory. Since recurrence at the site of anastomosis is possible, prolonged monitoring is required.

[Long-term results of the treatment of diffuse systemic scleroderma with interferon-gamma]. / Résultats à long terme du traitement des sclérodermies systémiques diffuses par l'interféron gamma.

There are very few drugs effective in the treatment of diffuse scleroderma and therefore we conducted an open study with gamma interferon. Among 20 diffuse scleroderma, evolving since less than 3 years, an improvement was observed in 8 patients. There was no serious side effect. Survival of these 20 patients was 85% at 5 years.

[Coccygodynia disclosing Tarlov's cysts]. / Coccygodynies révélant des kystes de Tarlov.

In a 63-year old male patient coccygodynia, initially isolated then complicated by incomplete cauda equina syndrome, could be attributed to large perineurel meningeal cysts on the sacral nerve roots. The diagnosis was suspected at computerized tomography and nuclear magnetic resonance and confirmed by sacculoradiculography. Intradural injections of corticosteroids provided lasting pain relief. Arachnoid cysts are often asymptomatic, by they may be responsible for coccygodynia and/or incomplete cauda equina syndrome. Their presence is suggested by the characteristics of the symptoms which are paroxysmal, exacerbated in standing position, relieved in dorsal position and revived by percussing the sacrum. Treatment is medical in most cases. The decision to operate depends on the persistence and intensity of pain and on whether signs of neurological defecit are present.

[Treatment of systemic mastocytosis]. / Traitement des mastocytoses systémiques.

BACKGROUND: Systemic mastocytosis is a rare disease, characterized by mast cells proliferation in various organs. Two types of clinical manifestations can be distinguished: those related to mast cells mediators release and those related to tumoral proliferation involving different organs, these later defining aggressive systemic mastocytosis. Until recently, treatment was mainly symptomatic, without anti tumoral effect. RECENT FACTS: These last years, advances have been made in the understanding of the disease with the discovery of the c-kit oncogene mutation and the approach of the disease as a myeloproliferative disorder. PERSPECTIVES: Based on experiences acquired in the treatment of this kind of disorders, evaluation of new therapeutics, such as cladribine or combination of interferon-alpha and cytarabine is in progress. At least, tyrosine kinase inhibitors, a new family of molecules, are able of inhibiting some types of the mutated c-kit protein and one of them, imatinib mesylate, has shown a great efficacy in the treatment of gastro intestinal stromal tumors (GIST) which also involves the c-kit mutation. By analogy, treatment of patients with c-kit susceptible mutation might be treated with this molecule.

[Pleuropulmonary manifestations of systemic vasculitis]. / Manifestations pleuropulmonaires des vascularites systémiques.

Pleuropulmonary manifestations of systemic vasculitis are common, polymorphic and of ambiguous significance: the same pulmonary lesion may reveal a specific manifestation of vasculitis as well as a therapy-induced complication, especially infection which may favor per se a flare-up. Two questions will be successively studied: what are the pleuropulmonary characteristics of Wegener's granulomatosis, Churg-Strauss syndrome, periarteritis nodosa, Behçet's disease, Takayasu's disease and temporal arteritis? What are the major adverse effects that may occur in the course of a treated systemic vasculitis?

[Sarcoidosis and pregnancy. A retrospective study of 11 cases]. / Sarcoïdose et grossess. Etude retrospective de 11 cas.

PURPOSE: To analyze the evolutive profile of sarcoidosis together with reciprocal interactions between pregnancy and sarcoidosis. METHODS: All events that occurred during pregnancy in 11 women presenting with sarcoidosis were analyzed. Histological confirmation was obtained for the 11 cases. For all pregnancies were analyzed the course of both sarcoidosis and pregnancy, and the influence of pregnancy on the disease evolution. RESULTS: Among 33 pregnancies, 23 led to the birth of healthy fetuses (five spontaneous abortions, four voluntary abortions, and one therapeutic abortion). The major event was fetal hypotrophy in six cases. Three of them occurred during pregnancy in prednisone-treated patients with active sarcoidosis. No relapse of cured sarcoidosis or further evolution of sarcoidosis that was inactivated as of the beginning of pregnancy were observed. The course of active sarcoidosis varied, as improvement (one case), worsening (two cases) and stabilization (two cases) were observed. During the first year of follow-up after delivery, four relapses and, in two cases, preliminary signs of the disease were observed. CONCLUSION: Apart from the hypothetical but not definite risk of hypotrophy, no negative interaction between sarcoidosis and pregnancy could be established. Pregnancy does not seem to interfere with the course of sarcoidosis. Considering the risk of relapse after delivery, pregnant women presenting with sarcoidosis should benefit from clinical and radiological follow-up.

[Loss of consciousness in a child due to loperamide]. / Perte de connaissance chez une jeune enfant secondaire à la prise de lopéramide.

Loperamide is an antidiarrheal peripheral opiate agonist, with rare neurological secondary effects. We report the case of a 26-month-old child who had impaired consciousness under treatment by loperamide, and was treated successfully with naloxone. Limitations of the use of loperamide in young children are underlined. Naloxone may be used in case of impaired consciousness, for a diagnostic as well as therapeutic purpose.

[Unusual good prognosis for X-linked myotubular myopathy]. / Forme inhabituelle de bon pronostic de la myopathie myotubulaire liée à l'X.

Recessive X-linked myotubular myopathy has recently been shown to be linked to the mutation of a gene located in the Xq28 region. Evolution is used to be considered as fatal but mild forms or forms with a better prognosis have been recorded since. We report a case in a patient, whose parents were warned of fatal outcome once the diagnosis was made during the neonatal period. The reaction of the parents was to avoid any relationship with medical care. Ten years later the patient was seen in relatively good health thus proving that the evolution was more favourable than anticipated.

[Organization of patient management in level II centers in the Paris area: a prospective survey]. / Organisation de la prise en charge dans les centres de niveau II en région parisienne: enquête prospective.

Perinatal asphyxia is a common emergency for both obstetricians and pediatricians. A prospective study was conducted in 14 maternity hospitals (type II centres) in the Paris suburbs in order to assess pediatric activity and neonatal morbidity associated with supposed perinatal asphyxia in term newborns. Pediatricians were called in at birth very frequently: 1/20 deliveries. Intubation and/or resuscitation procedures were needed in 20% of cases and 20% of infants were referred to a neonatal unit for birth asphyxia or associated pathology. Moderate encephalopathy was observed in 1.5% of all term newborns who needed medical intervention for supposed birth asphyxia.

[Wegener's granulomatosis in elderly subjects. 37 cases]. / Granulomatose de Wegener du sujet âgé. Trente-sept cas.

The clinical, biochemical and prognostic characteristics of 37 patients with Wegener's granulomatosis were studied in relation to age. Eleven patients were older than 60 years when the first sign of the disease appeared. Except for the fact that the renal lesions seemed to be more severe in these patients, there was no significant clinical or biochemical difference between them and patients under 60. Five patients over 60 years of age died during the first 2 years of Wegener's granulomatosis. Death was due to infection in 3 cases, to acute renal failure as complication of intra-alveolar haemorrhage in 1 case and to metastatic cancer in 1 case. Age-related comparisons of survival rates showed that the probability of surviving was lower in elderly subjects: 78 per cent at 1 year and 39 per cent at 3 and 5 years, as opposed to 96 per cent at 1 and 3 years and 84 per cent at 5 years in younger subjects (P less than 0.01). This poor prognosis is probably due to the renal lesions which constitute an important cause of death in the published series. Rapidly progressive glomerulonephritis being amenable to an early and intensive treatment, elderly patients should be treated as energetically as younger patients.

[Arterial embolism of the limbs in infectious endocarditis of the heart valves]. / Embolie artérielle des membres au cours des endocardites infectieuses sur valves natives.

Nine cases of infective endocarditis (IE) on native valves, complicated by arterial embolism of the limbs (AEL), were collected between June 1974 and October 1988 (prevalence 4.3 percent). Among the 11 AEL recorded, 9 involved the lower limbs and 2 the upper limbs. The diagnosis, suspected in patients with acute ischaemia (n = 6), transient (n = 1) or pseudophlebitic (n = 1) pain, or discovered by systematic pulse examination (n = 3), was confirmed by Doppler ultrasound (n = 3), angiography (n = 2) or oscillometry (n = 4). AEL occurred 2.8 weeks on average after the onset of treatment; it appeared 6 months after the end of treatment in 1 case and preceded the diagnosis of IE by 1 to 6 weeks in 3 cases. The causative organisms isolated in 7 cases were: non-haemolytic streptococci (n = 4), Staphylococcus aureus (n = 1), Haemophilus parainfluenzae (n = 1) and enterococcus (n = 1). Vegetations were found in 6 of the 7 patients explored by echocardiography. Two cases of embolism of the femoral artery required embolectomy. Effective heparin anticoagulation was obtained in only one patient. Six patients underwent valve replacement in the acute phase of endocarditis. After a mean follow-up period of 32 months (range 3 to 120 months), only one patient has symptoms (claudication of the left upper limb); 5 patients are asymptomatic with a reduced (n = 5) or abolished (n = 2) pulse. Three embolisms have left no sequelae. Altogether, AEL are not uncommon in infective endocarditis. They rarely influence the functional prognosis and are detected by systematic palpation of the pulses. Anticoagulation in effective doses is discussed. Attempts at removing the obstruction should be made only in cases with poorly tolerated proximal embolism. In patients with multiple or recurrent embolic accidents, valve replacement may be considered.

[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.

[Anti-Scl-70 antibodies in systemic scleroderma]. / Anticorps anti-Scl-70 dans la sclérodermie systémique.

We looked for anti-Scl-70 and anti-centromere antibodies in 109 patients (26 men and 83 women). Mean age was 43 +/- 15 years. Forty patients had systemic sclerosis according to ARA criteria. The extension of cutaneous involvement was defined by using Barnett and Coventry criteria: 12 patients were type I (sclerodactyly), 20 type II (acrosclerosis) and 8 type III (diffuse scleroderma). Among the 12 patients with type I, there were 8 cases of CREST syndrome defined as follows: presence of sclerodactyly, Raynaud's phenomenon and 2 of the 3 following criteria: oesophageal dysmotility, calcinosis, telangiectasia. Other organ involvement was recorded. Control patients had idiopathic Raynaud's phenomenon (n = 22), other connective tissue diseases (n = 20), and miscellaneous diseases (n = 28). Ninety-nine patients were prospectively included in this study. Patients' sera were stored at -20 degrees C. Ten previously stored sera obtained from patients with systemic sclerosis were also analyzed. Immunological tests were performed simultaneously and with no information on the diagnosis. When antinuclear antibodies were detected by indirect immunofluorescence, double immunodiffusion and immunoblotting were performed. Anti-Scl-70 antibodies were detected in systemic sclerosis only: 1 of 12 type I, 11 of 20 type II and 4 of 8 type III. One serum negative by immunodiffusion was positive using immunoblotting. We found that the specificity of anti-Scl-70 antibodies for systemic sclerosis was 100 p. 100 and their sensitivity 40 p. 100. There was a correlation between the presence of anti-Scl-70 antibodies and the presence of antinuclear antibodies (p less than 0.05) and the extent of cutaneous involvement (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)