Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia: a case series.

BACKGROUND: Hyperhomocysteinemia has been suspected of favoring thrombosis. Several case-control studies and even a meta-analysis have confirmed a link between venous thrombosis and hyperhomocysteinemia. Homocysteine is due to genetic and acquired factors (poor diet in folate and vitamin B12, older age, renal impairment, thyroid diseases, and malignancies) induced by the intake and the concentrations of vitamin B9 or B12 in the majority of cases. CASES PRESENTATION: We report the cases of four Moroccan patients who presented with acute vein thrombosis of different sites: a 34-year-old man, a 60-year-old man, a 58-year-old man, and a 47-year-old woman. All patients had a low level of cobalamin with marked hyperhomocysteinemia with normal serum and red cell folic acid. Venous thrombosis revealed pernicious anemia in all patients. Their low levels of cobalamin, atrophic gastritis, and positive results for gastric parietal cell antibodies confirmed the diagnosis of pernicious anemia. There was no evidence of immobilization, recent surgery, malignancy, antiphospholipid antibody, myeloproliferative disorder, or hormone replacement therapy. No deficiencies in protein C and protein S were detected; they had normal antithrombin III function and factor V Leiden; no prothrombin gene mutations were detected. Treatment included orally administered anticoagulation therapy and cobalamin supplementation. The outcome was favorable in all cases. CONCLUSIONS: These reports demonstrate that pernicious anemia, on its own, can lead to hyperhomocysteinemia that is significant enough to lead to thrombosis. Understanding the molecular pathogenesis of the development of thrombosis in patients with hyperhomocysteinemia related to Biermer disease would help us to identify patients at risk and to treat them accordingly. The literature concerning the relationship between homocysteine and venous thrombosis is briefly reviewed.

[Mixed cryoglobulinemia with monoclonal IgA and biclonal IgM during hepatitis C virus infection]. / Cryoglobuline mixte à IgA monoclonale et IgM biclonale au cours d'une hépatite C.

Cryoglobulins are immunoglobulins that precipitate at low temperature and dissolve when warmed. According to Brouet, their classification relies upon the immunochemical study: type I comprises monoclonal immunoglobulins (IGG), when types II and III include both monoclonal and polyclonal components. During C hepatitis, the presence of a cryoglobulin, essentially made of mixed G-IGG and M-IGG, is a common feature with a prevalence of 40 to 80%. The authors report a case of a 63-year patient who presented with a vascular purpura and a peripheral polyneuropathy in a context of C hepatitis infection. The cryoglobulin found was composed of a monoclonal kappa A-IgG associated with a biclonal kappa and lambda M-IgG. No decrease of normal IgGs was found. This type of cryoglobulin does not belong to Brouet's classification, and argues for a new and more pertinent classification to be proposed.

[Acute Guillain-Barré-like polyradiculoneuritis revealing acute systemic lupus erythematosus: two case studies and review of the literature]. / Polyradiculonévrite aiguë de type Guillain-Barré révélant un lupus érythémateux aigu disséminé: étude de deux cas et revue de la littérature.

The involvement of the peripheral nervous system in systemic lupus erythematosus (SLE) is rare and is dominated by distal symmetric axonal polyneuropathy and multiple mononeuropathy. It usually occurs in late course of the disease. Acute polyradiculoneuropathy of Guillain-Barré syndrome type is very rare and can frequently constitute the first symptom of systemic lupus. We report two cases of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) complicated by respiratory failure due to systemic lupus. In the first case, the pure motor AIDP was the first manifestation of the SLE. The outcome under prednisone treatment was dramatically good with regression of clinical deficit and normalisation of nerve conduction within one month and 12 months of treatment respectively. In the second case the AIDP occurred only one week after diagnosis of SLE and corticotherapy. It was a demyelinating sensory-motor neuropathy. Clinical improvement was obtained after two cures of intravenous gammaglobulin (IVIg). The normalisation of nerve conduction was obtained within 8 months. AIDP is a very rare complication of SLE, but it should be searched as an aetiology of Guillain-Barré syndrome associated to systemic clinical symptoms or to blood inflammation. Corticotherapy could be sufficient, but in some cases the addition of IVIg or plasmapheresis might be necessary.

[Hyperhomocysteinemia and arterial or venous thrombosis. Retrospective study of 75 cases]. / Hyperhomocystéinémie et thromboses artérielles ou veineuses. Etude rétrospective de 75 observations.

OBJECTIVE: Previous studies suggest that hyperhomocysteinemia may be a risk factor for arterial and venous thrombosis. We retrospectively analyzed data from 75 patients with thrombosis. PATIENTS AND METHODS: Thirty-four patients had arterial thrombosis, 22 venous thrombosis and 19 venous and arterial thrombosis. Of the 75 patients (49 men and 26 women, mean age 49 +/- 15 years) about two-thirds had recurrent episodes of thrombosis. RESULTS: Hyperhomocysteinemia was defined as serum homocysteine level above 14.1 mumol/l (mean + 2.7 SD in healthy subjects) and was found in 67 patients (89%, CI95% = 80-95). Mean total homocysteine concentration was 21.6 +/- 13.6 mumol/l for the 75 patients. About half of the patients were smokers, 35% had hypertension and 25% high serum cholesterol. There was no significant relationship between serum homocysteine level and smoking status, hypertension or serum cholesterol level. Ten patients (13%, CI95% = 7-23) had low serum cobalamin (< 150 pmol/l). Serum folates were < or = 10 nmol in 41% of the patients in the arterial thrombosis group (CI95% = 25-59), in 27% in the venous thrombosis group (CI95% = 11-50), and in 31% in the arterial and venous thrombosis group (CI95% = 13-57). Thirteen patients received vitamin B supplementation. Hyperhomocysteinemia decreased in 12/13 patients (CI95% = 64-100) and returned to normal values in 9/13 patients (69%, CI95% = 38-91). CONCLUSION: Our data show that hyperhomocysteinemia is frequently found in arterial and venous thrombosis. Further studies are needed to determine the clinical impact of homocysteine lowering therapy.

[Angiosarcoma of the breast. Radiological aspects. About one case]. / Angiosarcome du sein. Aspects radiologiques. A apropos d'un cas.

Angiosarcoma of the breast in an uncommon entity. The authors report a well documented case of angiosarcoma. The patient, a 23 years old woman, had a voluminous mass of the left breast without inflammation. The evolution was rapidly fatal. Physical examination revealed a large painful breast mass with purplish discoloration cutaneous area in front of the lesion. The palpation revealed a thrill. The mammography had shown an area of increased density in the left breast. A complementary ultrasound examination detected a well circumscribed voluminous mass with hypoechogenic heterogenous echostructure. The Doppler examination detected a venous blood flow in the tumor. This finding was compatible with vascular tumor as angioma or angiosarcoma. The angioscanner showed a peripheral vascular enhancement and a centripetal diffusion of the contrast product. This vascular kinetic is seen commontly in the angioma. Magnetic resonance imaging in the T1 and T2 relaxation times detected an intermediate signal mass with bleeding areas. The patient had had a mastectomy and the histopathologic examination confirmed the diagnostic of angiosarcoma. The radiological aspacts of angiosarcoma of the breast are discussed depending on the literature data.

[Horton disease disclosed by a specific inflammatory arteriopathy of the lower limbs]. / Maladie de Horton démasquée par une artériopathie inflammatoire spécifique des membres inférieurs.

The authors report the case of a woman aged 67 years who presented an acute ischemia of the lower limbs. A surgical exploration showed no atherosclerosis or thrombus. A biopsy of the femoral artery found an extensive mononuclear cell infiltration of the media and a fragmentation of internal elastic lamina. The diagnosis of Horton disease was considered and confirmed by the presence of clinical signs of polymyalgia rheumatica and inflammatory syndrome (erythrocyte sedimentation rate: 75 mm). Corticosteroid therapy was started with success. A year after discharge there was no recurrence of ischemic manifestations and the erythrocyte sedimentation rate was normal. Involvement of lower limbs in Horton disease is rare and exceptionally proven. But postmortem studies indicate that it is more frequent than previously reported. The diagnosis should be considered in the differential diagnosis of any unexplained case of peripheral vascular disease occurring in the middle-aged or elderly.

[Spermatocytic seminoma. Apropos of a case and review of the literature]. / Le séminome spermatocytaire. A propos d'un cas et revue de la littérature.

We report a case of sperm cell seminoma caused by trauma. The data in the literature indicate the frequency is less than 5% of all seminomas. This case was exclusively located in the gonads and was a pure form. Orchidectomy with high ligature of the cord and adjuvant radiotherapy at the dose of 25 Gy centered on the para-aortic and subdiaphragmatic chains is adequate treatment. When inguinoscrotal surgery is performed, this zone must be irradiated with 25 Gy. Prognosis is satisfactory: 5-year survival is 100% with this protocol.

[Abdominal aortic aneurysms: contribution of genetics. From atheromatous theory to parietal theory]. / Anévrismes de l'aorte abdominale: apports de la génétique. De la théorie athéromateuse à la théorie pariétale.

Abdominal aortic aneurysms have usually been characterized as atheroslcerotic, but this view of their pathogenesis is a restricted one. As yet, no unified concept of pathogenesis has emerged, bat several factors appear to have an important role, including familial clustering, genetically determined and acquired biochemical alterations in the structural matrix of the aortic wall and bemodynamic mechanical factors. We review literature data concerning new pathogenic concepts of abdominal aortic aneurysms and particularly familial predisposition. Ultrasonographic screening is recommended in brothers (50 years) of patients with aneurysms of the abdominal aorta.

Sjögren's syndrome with acute renal failure caused by renal pseudolymphoma.

A 56-year-old man with Sjögren's syndrome was found to have acute renal failure. Immunopathologic analysis of renal biopsy specimens showed polyclonal lymphocytic interstitial infiltration. DNA analysis of the T-cell receptor and the heavy chain immunoglobulin genes showed a polyclonal pattern of gene rearrangements. Renal failure caused by this pseudolymphoma regressed dramatically with steroid therapy. This is the first reported case of proven renal pseudolymphoma that regressed with steroid therapy.

[Medical treatment of aortic abdominal aneurysms. Outstanding questions]. / Traitement médical des anévrysmes de l'aorte abdominale. Questions en suspens.

The low mortality of programmed surgical treatment of aortic abdominal aneurysms (2-4%) contrasts with a high mortality of surgical treatment in case of rupture (70-90%). These data underline the benefit of a "prophylactic" surgical treatment of aortic abdominal aneurysms, even those of small size or in older patients. Recently, experimental models and results of a few clinical studies suggest that medical treatment with beta-adrenergic blocking agents may reduce the expansion rate of aortic abdominal aneurysms and thus lower the risk of rupture. Several questions remains open. Should beta-blocking agents be reserved for aneurysms more than 5 cm in diameter in patients with a contraindication for surgery, or on the contrary proposed for aneurysms less than 4 cm in diameter in patients still free of contraindications? What is the mode and delay of action for beta-blockers, their effect on modulating blood pressure and their contribution to the use of endoluminal prostheses? Controlled prospective trials enrolling a large number of patients are required to answer these questions.

[Value of an extensive biological study in venous or arterial thromboses]. / Intérêt d'une exploration biologique approfondie au cours des thromboses veineuses ou artérielles.

OBJECTIVES: The aim of this work is to study the signification of an extensive biological evaluation in patients with "unexplained" thrombosis. We studied 78 patients with more than one arterial and/or venous thromboembolic event. METHODS: Fifty-four patients were admitted for unexplained deep venous thrombosis (group I, n = 19, 9 men and 10 women) and/or arterial thrombosis (group II, n = 35, 21 men and 14 women). A third group (group III) included 24 patients (13 men, 11 women) known to have a pathologic state which can lead to a thrombotic event. RESULTS: The patients in both groups I and II had, more often than normal subjects, a high level of homocysteinemia (26% vs 3%, p < 0.001), anti-beta 2 glycoprotein 1 (18.5% vs 3%, p < 0.001) and antiphospholipid antibodies (13% vs 3%, p < 0.02). We also found a significant association between an increase of erythrocytic aggregation and arterial thrombosis (group II). In the third group, for both arterial (n = 14) and venous (n = 10) thrombosis, we found a high level of anticardiolipin antibodies (25% vs 3%, p < 0.001), anti-beta 2 glycoprotein 1 antibodies (12.5% vs 3%, p < 0.05) and abnormal erythrocytic aggregation (16.5% vs 3%, p < 0.01). In these 3 groups the other studied parameters (Lp(a), platelet aggregation, cryoglobulin, cryofibrinogen, antinuclear antibodies, anticytoplasm antibodies, plasma and urine immunoelectrophoresis, protein C, protein S, antithrombin III, plasminogen) were not different from levels observed in normal subjects. CONCLUSION: An extensive biological analysis, including plasma homocystein level, anticardiolipin antibodies, anti-beta 2 glycoprotein 1 antibodies and a study of the erythrocytic aggregation would appear to be of value in patients presenting recurrent arterial or venous thromboembolic events. Specific therapy can be applied in case of abnormal results continued anticoagulant therapy for anticardiolipin and anti-beta 2 glycoprotein 1 antibodies, and a vitamin therapy for increased homocysteinemia.

[Autoimmune hepatitis and hepatitis C]. / Hépatites auto-immunes et infection par le virus de l'hépatite C.

From autoimmune hepatitis (AIH) classification which recognizes three types of AIH, we discuss the main relations between hepatitis C virus (HCV) infection and AIH. Type I AIH is associated with antinuclear and antismooth muscle antibodies, and with other autoimmune diseases. There is no relation between type I AIH and HCV. Type I anti-liver kidney microsome and anti-liver cytosol I antibodies represent the hallmark of type II AIH. Among type II AIH, two subgroups emerged: type IIa AIH (10-40%) are true AIH (sensitive to steroids but worsens with interferon alpha), whereas type IIb AIH (60-90%) appear as a particular form of HCV hepatitis. Type IIb AIH have a moderate activity, a low titer of autoantibodies, anti-GOR antibodies but never anti-liver cytosol I, no sensitivity to steroids but are sensitive to interferon alpha. The hallmark of type III AIH are anti-cytosol antibodies, but these AIH have the same characteristics as type I AIH. The classification between true AIH (I, IIa, III) or "pseudo-AIH" due to HCV infection has major therapeutic implications. Steroids or immunosuppressive treatments are effective in type I, IIa and III AIH but have no efficacy in type IIb AIH. Alpha interferon has an efficacy in type IIb AIH, but it has no efficacy and may even worsen hepatitis in type I, IIa and III AIH.

[Leg ulcers in systemic diseases]. / Les ulcères de jambe au cours des maladies systémiques.

The collagen vascular diseases and vasculitis, in particular, are occasionally associated with chronic, relapsing lower extremity ulcerations. Different mechanisms can induce such ulcerations, and an understanding of the type of ulcerations is important in the differential diagnosis of patients with leg ulcerations in general, and management of these patients in particular. In this review, the authors analyze the various mechanisms of the leg ulcerations in these patients and their treatments: vasculitis, thrombosis, traumatisms, calcinosis, panniculitis, pyoderma gangrenosum, infections, and induced by treatments.

[Drug-induced iatrogenic arterial diseases]. / Les artériopathies iatrogènes médicamenteuses.

Several drugs have been shown to cause vasomotor troubles such as Raynaud's phenomenon, erythromelalgia, vasculitis, livedo reticularis, or acrocyanosis. Vascular symptoms may develop a few weeks or more after drug initiation, particularly when other drugs are associated than can potentiate vascular side effects. In this review, the authors described the main characteristics of drug-induced vasculopathy, particularly those associated with ergotamine derivates, beta blocking agents or antineoplastic chemotherapy.

[Contribution of radiology to the diagnosis and treatment of nasopharyngeal fibroma. Apropos of 6 cases]. / Apport de la radiologie dans le diagnostic et le traitement du fibrome nasopharyngien. A propos de 6 cas.

The authors report about their experience with 6 cases of nasopharyngeal fibroma. They emphasize the interest of CT examinations in the diagnostic study, and above all in the assessment of regional extension. The angiographic study must be as complete as possible, and should include an embolization within 2 to 5 days prior to surgical excision as often as this is possible. Embolization is a simple procedure if performed strictly and carefully in order to avoid any complication.