Peripheral nerve involvement in Fabry's disease: Which investigations? A case series and review of the literature.

BACKGROUND: Peripheral nerve system (PNS) involvement is common in Fabry's disease (FD), predominantly affecting the small nerve fibers that are difficult to investigate with conventional electrophysiological methods. PATIENTS AND METHODS: Eighteen patients followed for Fabry's disease underwent a prospective series of electroneurophysiological explorations, including a study of the cardiac parasympathetic autonomic nervous system (ANS) and electrochemical skin conductance (ESC) tests. Data were compared with those obtained in 18 matched healthy controls. RESULTS: All patients had at least one clinical sign suggestive of neuropathy: 16 reported an acrosyndrome and 12 had dyshidrosis. Cold hypoesthesia was found in 15 patients and heat hypoesthesia in 13. Electroneurophysiological investigations and study of the cardiac parasympathetic ANS were normal in all patients. The ESC was significantly lower in FD patients compared with controls. CONCLUSION: PNS involvement is common in FD and should be suspected in patients exhibiting an acrosyndrome, dyshidrosis and/or cold hypoesthesia. Conventional electrophysiological investigations are normal. New techniques, such as ESC, provide early diagnosis of small fiber involvement that currently requires more sophisticated tests difficult to apply in routine practice.

[Purtscher-like retinopathy associated with adult onset still disease: Case report and review of the literature]. / Pseudo-rétinopathie de Purtscher dans le cadre d'une maladie de Still de l'adulte : à propos d'un cas et revue de la littérature.

INTRODUCTION: Putscher-like retinopathy is a retinal disease that is similar to the syndrome initially described in 1910 by Purtscher, but occurring in a non-traumatic context. CASE REPORT: We describe a case of acute, Putscher-like retinopathy in a 48-year-old woman experiencing adult onset Still's disease. The diagnosis was based on fundus examination and fluorescein angiography. Based on a review of the literature, we discuss the current available data on the pathophysiology of this syndrome and its prognostic significance. The treatment remains controversial. CONCLUSION: When visual functional signs appear during adult Still's disease, it is necessary to evoke Putscher-like retinopathy, and to ask for an ophthalmological expertise.

Atteinte osseuse axiale de la sarcoïdose.

INTRODUCTION: Sarcoidosis is a multi-systemic disease characterized by non-caseating granulomas. Bone involvement initially considered as rare and described as a peripheral osteitis of the hands and feet, has recently been reported on the axial skeleton. CASE REPORTS: We report 4 clinical observations of sarcoidosis (3 women, 1 man) with axial bone involvement located to the spine (n = 4), pelvic bone (n = 2), scapular bone (n = 2), sternum (n = 1), mandible (n = 1). Sarcoidosis was already diagnosed in 3 cases. Bone pain was the main symptom, related in 3 cases. Magnetic resonance imaging appeared to be the best imaging test Histological bone analysis revealed typical granulomatous lesions (n = 2). Treatment included corticosteroids (n = 4), hydroxychloroquine (n = 2), and methotrexate (n = 2), with a good efficacy on bone pain in symptomatic patients. CONCLUSION: These 4 cases, as well as recent literature, illustrate bone involvement of sarcoidosis on the axial skeleton. It is symptomatic in around 50% of cases but may be a source of significant disability. Differential diagnosis with neoplasm may require bone histological analysis. This condition appears to be responsive to usual treatments for sarcoidosis.

Efficacy of intravenous iron therapy in non-anaemic iron-deficient patients with fatigue.

Iron deficiency, without anaemia, is common in the general population and induces various symptoms. Its management consists of oral and intravenous supplementation for cases of inefficacy of or intolerance to oral iron. We assessed the efficacy of intravenous iron therapy in non-anaemic iron-deficient patients with fatigue. We prospectively evaluated the level of fatigue, using the Fatigue Severity Scale (FSS), in patients suffering from iron deficiency without anaemia, treated by intravenous iron at the moment of the perfusion (W0), after 4 weeks (W4), and 12 weeks (W12). Of 25 patients, at W0, the mean FFS was 49.3+/-13.7. There was a significant improvement in FSS at W4 (44+/-15; p = 0.01) and a sustained response at W12 with an FFS of 35.8+/-17.1 (p < 0,0001). There was no correlation between FSS and serum ferritin level at W12 (p=0.54) or between serum ferritin at W12 and difference between FSS at W0 and W12 (p=0.58). There were six mild adverse events (24%): asthenia (8%), nausea (8%), headache (4%), local pain (4%); and no serious adverse events. Our results suggest the rapid efficacy of intravenous iron in improving fatigue in iron deficiency without anaemia with a good profile of tolerance.

[Gaucher Disease type 1 mimicking immune thrombocytopenia: Role of hyperferritinemia and hypergammaglobulinemia in the initial evaluation of an isolated thrombopenia]. / Maladie de Gaucher de type 1 simulant une thrombopénie immunologique : intérêt de l'hyperferritinémie et de l'hypergammaglobulinémie dans le bilan d'une thrombopénie isolée.

INTRODUCTION: Gaucher disease type 1 is a rare genetic disease. It can cause thrombocytopenia. Current guidelines do not support bone marrow examination in front of isolated thrombocytopenia if no evidence suggests malignant hemopathy. This strategy aiming at sparing unnecessary investigations makes such rare diseases more difficult to diagnose. CASE REPORT: A 31-year-old woman was diagnosed with immune thrombocytopenia according to current guidelines. She presented later with mild splenomegaly. Bone marrow aspirate smears showed Gaucher cells. Gaucher disease was then confirmed. Looking backward, initial biological clues (hyperferritinemia, hypergammaglobulinemia) should have enabled to consider the diagnosis. CONCLUSION: Gaucher disease type 1 can be responsible for apparently isolated thrombocytopenia. The disease must be looked for if the thrombocytopenia is associated with unexplained hypergammaglobulinemia or hyperferritinemia. Diagnosing immune thrombocytopenia without bone marrow sample requires to systematically pay attention to any clinical or biological abnormality, not to ignore rare differential diagnoses.

[Retinal vein occlusion in a young patient: Where does intraocular hypertension come from?] / Occlusion de la veine centrale de la rétine chez un sujet jeune : chercher d'où vient l'augmentation de pression intraoculaire.

INTRODUCTION: Retinal vein occlusion presents as an acute, painless and unilateral sight loss. We report two cases of retinal vein occlusion (CRVO) in which the etiology was unusual. CASE REPORTS: Case 1. A 54-year-old woman without any significant past medical history presented with an acute loss of vision. Medical history taking revealed the practice of yoga with headstand posture like "Sirsana". Case 2. A 35-year-old woman presented with an acute loss of vision related to a retinal vein occlusion. The investigation found prolonged and repeated vomiting the days before the retinal vein occlusion. CONCLUSION: Cardiovascular assessment is recommended in the investigation of CRVO. Furthermore, especially in young patients, a situation causing an increase of intraocular pressure as the practice of yoga with taking reverse "head down" body positions or even repeated vomiting efforts may be the cause of slower circulation of blood flow in the retinal veins.

[Chronic lymphoid leukemia and renal complication: Report on 10 cases from Marseille over 16 years]. / Néphropathies au cours de la leucémie lymphoïde chronique : à propos d'une étude monocentrique de 10 cas.

INTRODUCTION: Chronic lymphoid leukemia (CLL) is a hematological malignant disease, associated with a clonal B cell proliferation. The incidence is 4400 new cases per year in France. The prevalence increases with age with a median age at diagnostic of 65 years. Renal involvement is rare and estimated at 1.2% of patients with CLL. Renal pathological diagnoses associated with CLL are variable and are not always related to the hematological disease. We report here on cases of patients with CLL who underwent a renal biopsy over the past 16 years in Marseille. METHODS: All cases of renal biopsies performed in patients with CLL between2000 and 2016 in Marseille were included. Pathological analysis was performed by the same experimented pathologist. Data were collected at the time of biopsy and after treatment. RESULTS: Ten patients were included in this study. The reason for renal biopsy was acute kidney injury or the onset of nephrotic syndrome. We report on 4 cases of membranous nephropathy, 1 minimal change disease, 1 cryglobulinemia-related membrano-proliferative glomerulonephritis, 1 light chain amyloidosis, 1 fibrillary glomerulonephritis, 1 interstitial monoclonal infiltration and one case of non-specific tubular lesions. Only one patient was treated before the biopsy, 7 patients received a specific hematological treatment of CLL because of its renal involvement. Renal and hematological responses were variable. CONCLUSION: Renal involvement of CLL is rare and is not mentioned in the Binet classification. Yet, it can be severe, with acute kidney injury or nephrotic syndrome, and can lead to the initiation of a specific treatment. The most frequent presentation this series was secondary MN, which differs from previous series.

Acute transverse myelitis and primary urticarial vasculitis.

We report the case of a 56-year-old man with severe normocomplementaemic primary urticarial vasculitis for 16 years. Nine and 11 years after the onset of the symptoms, he developed two severe neurological complications, seizure and transverse myelitis, that must be attributed to the vasculitis. Transverse myelitis has been reported in other systemic diseases, particularly lupus erythematosus, but this is the first case of transverse myelitis complicating urticarial vasculitis.

Severe lower limbs lymphedema of late onset revealing polysplenia syndrome--a case report.

Polysplenia syndrome includes a group of congenital abnormalities involving the spleen, gastrointestinal tract, liver, and cardiovascular system. A case of severe lower limbs lymphedema occurring in a young woman with polysplenia, azygous continuation of the inferior vena cava, short pancreas, and preduodenal portal vein is reported. Lower limb lymphedema could represent a new clinical manifestation associated with polysplenia syndrome. Lymphedema could be the result of a primary anomaly of the lymphatic system or be induced by high pressure in the venous system or by compression of the lymphatic circulation by the hypertrophic azygous vessels in the posterior mediastinum.

Cannabis arteritis revisited--ten new case reports.

The purpose of this paper was to revisit the old concept of cannabis arteritis first described in the 1960s and report 10 new cases. Ten male patients, with a median age of 23.7 years developed subacute distal ischemia of lower or upper limbs, leading to necrosis in the toes and/or fingers and sometimes to distal limb gangrene. Two of the patients also presented with venous thrombosis and three patients were suffering from a recent Raynaud's phenomenon. Biological test results did not show evidence of the classical vascular risk factors for thrombosis. Arteriographic evaluation in all cases revealed distal abnormalities in the arteries of feet, legs, forearms, and hands resembling those of Buerger's disease. A collateral circulation sometimes with opacification of the vasa nervorum was noted. In some cases, arterial proximal atherosclerotic lesions and venous thrombosis were observed. All patients were moderate tobacco smokers and regular cannabis users. Despite treatment with ilomedine and heparin in all cases, five amputations were necessary in four patients. The vasoconstrictor effect of cannabis on the vascular system has been known for a long time. It has been shown that delta-8- and delta-9-tetrahydrocanabinols may induce peripheral vasoconstrictor activity. Cannabis arteritis resembles Buerger's disease, but patients were moderate tobacco smokers and regular cannabis users. These cases show that prolonged use of cannabis could be an additive risk factor for juvenile and young adult arteritis. Cannabis arteritis is a forgotten and severe occlusive vascular disease occurring in young adults. Search for cannabis use may be an important tool for a better knowledge of arteritis in young smokers.

[Isolated memory disorders disclosing antiphospholipid antibody syndrome]. / Troubles mnésiques isolés révélant un syndrome des anticorps anti-phospholipides.

Most of the neurological complications of the antiphospholipid syndrome are consequences of arterial or venous cerebral thromboses. We report the case of a 46-year-old woman presenting with the main signs of antiphospholipid syndrome: Raynaud's phenomenon, livedo, leg ulcers, repeated miscarriages, presence of a circulating anticoagulant and of antiphospholipid antibodies, who developed an isolated amnestic syndrome with a peculiar pattern; 1) almost complete sparing of the ability to learn new skills and of short-term recall; 2) deterioration, followed by disappearance of recent memories after a sufficient delay; 3) progressive alteration of increasingly old memories including knowledge memory suggested a gradual alteration of mnestic traces. The lack of neuroradiological signs of multiple infarcts suggests a direct intervention of antibodies in this patient's memorisation mechanisms.

[Heat shock proteins or "stress proteins"]. / Les heat shock proteins ou les "protéines de stress".

INTRODUCTION: Heat shock proteins (HSP) are molecular chaperones which facilitate the biosynthesis and maturation of proteins within cells (protein folding). They promote assembly and disassembly of polypeptides and play a major role in cellular function, not only during the stress response but also at basal state. CURRENT KNOWLEDGE AND KEY POINTS: As HSP are immunogenic molecules and can be expressed on cellular membranes, their role in auto-immune and inflammatory diseases, particularly in systemic lupus erythematosus, Behçet's disease and rheumatoid arthritis, has been studied. Cellular immune response of T cells and humoral response with antibodies production against HSP occurring in the course of those diseases have been observed. FUTURE PROSPECTS AND PROJECTS: Anti-HSP immune response might provide better understanding of the pathogenic mechanisms involved in those diseases. At present it is not known whether HSP can trigger them. Indeed, anti-HSP immunity could be induced by the immunological process or be part of a normal immunoregulatory response.

[Identifying hepatitis C virus by the gene amplification technique in the saliva of patients for whom the search is simultaneously negative in their serum: 9 cases]. / Découverte du virus d'hépatite C par technique d'amplification génomique dans la salive de patients pour qui la recherche est simultanément négative dans leur sérum: 9 cas.

RNA-PCR for Hepatitis C virus was positive in saliva sample of 9 patients, while it was negative in their serum. Clinical and biochemical results of these patients are presented. Saliva detection of HCV is useful for diagnostic of hepatitis, sicca syndrome.

[Heterozygous prothrombin gene mutation G20210A and associated diseases]. / Mutation G20210A du gène de la prothrombine à l'état hétérozygote et pathologies associées.

PURPOSE: Prothrombin gene mutation G20210A (factor II) is, in frequency, the second genetic polymorphism involved in venous thrombosis. We report a retrospective studies on 38 patients issued from our medical department, all heterozygous for the factor II mutation and a literature review. METHODS: We have studied 38 patients, all heterozygous for the factor II mutation, selected through a population of 516 tested patients issued from our medical department from 1997 to 2002. The research was performed face with history of thrombotic or obstetrical events, angiopathy or familial screening. RESULTS: Twenty out of thirty-eight patients have at least one episode of venous thrombosis: superficial thromboses, deep thromboses and/or pulmonary embolism. One case of cerebral thrombophlebitis is observed. Venous thrombotic risk factors are associated in 12 cases (60%). Four out of thirty-eight patients have one episode of arterial thrombosis: cardiovascular, peripheral or cerebral. Arterial thrombotic risk factors are associated in all cases. Median age of the first venous thrombosis is earlier than the one of arterial thrombosis (39.11 versus 49.25 years). CONCLUSION: Our studies confirms the interest to search the prothrombin gene mutation when faced with a venous thrombotic event (deep vein thrombosis and/or pulmonary embolism) with or without acquired risk factors. Its involvement in thrombotic arterial disease is still a matter of debate. Data concerning its involvement in systemic diseases and angiopathies (thromboangeitis obliterans, Raynaud's phenomenon and migraine) are still needed. Mechanisms of thromboses could be an increase of prothrombin plasma level with high thrombin synthesis.

[Pseudo-Glanzmann thrombasthenia in the course of autoimmune thrombocytopenic purpura]. / Pseudo-maladie de Glanzmann au décours d'un purpura thrombopénique auto-immun.

INTRODUCTION: Auto-immune thrombocytopenic purpura is associated with platelet anti-glycoprotein antibodies, particularly with anti-GPIIb/IIIa complex. Persistence of these antibodies sometimes leads to acquired auto-immune thrombopathy. EXEGESIS: We report the case of a woman treated by splenectomy for auto-immune thrombocytopenic purpura, who developed 5 years later an ecchymotic syndrome despite normal platelet count. High bleeding time and platelet aggregation defect in vitro were evidenced. Following the initial thrombocytopenia, anti-glycoproteins GPIIb/IIIa with lupus anticoagulant and benign monoclonal gammapathy were noticed. Platelet controls showed that hypoaggregant activity was secondary to the persistence of anti-GPIIb/IIa antibodies. CONCLUSION: This acquired auto-immune thrombopathy simulating Glanzmann's thrombasthenia was secondary to the persistence of platelet anti-glycoproteins GPIIb/IIIa.

[Kaposi disease, limited to the skin, in ulcerated hemorrhagic rectocolitis]. / Maladie de Kaposi strictement cutanée au cours d'une rectocolite ulcérohémorragique.

We report the first case of limited cutaneous Kaposi's sarcoma during ulcerative colitis, in a HIV-negative 68 year-old man without any risk factors for this tumor. In our case, the steroid-therapy necessitated by the colitis is the most important aetiological factor of the sarcoma and its withdrawal leads to a complete remission of the tumor. The link between steroid-therapy and Kaposi's sarcoma is well known. A link between ulcerative colitis and Kaposi's sarcoma can be discussed but not proven. The possible occurrence of this cutaneous tumor during ulcerative colitis is of interest.

[Is chronic or recurrent idiopathic pericarditis an autonomous inflammatory disease?]. / La péricardite idiopathique chronique ou récidivante est-elle une maladie inflammatoire autonome?

PURPOSE: Chronic pericarditis or recurrent pericarditis is mostly considered to be idiopathic even when up-to-date medical investigations are undertaken. The absence of aetiology and the associated inflammatory process are features of a common disease for internists. As there are only a few published reports on this disease, therapeutic options are not easily envisaged. CURRENT KNOWLEDGE AND KEY POINTS: Idiopathic pericarditis and its evolution, characterized by recurrence or chronicity, has long been diagnosed and studied. Faced with a case of acute pericarditis, no clinical or biological data can preclude evolution towards a chronic or a recurrent form. The two major complications are tamponade and constriction. Classical treatment is aspirin and nonsteroidal anti-inflammatories. Steroids have a spectacular effect but steroid dependence is frequently observed. Colchicine treatment seems to be efficacious and can be used to stop steroid therapy. There are only a few published reports on the importance of immunosuppressive drugs such as azathioprine and cyclophosphamide. FUTURE PROSPECTS AND PROJECTS: Through our own experience and literature review, we propose to consider chronic and/or recurrent pericarditis as an autonomous inflammatory disease of the pericardium. Thus, large-scale studies concerning the treatment should improve the outcome of patients.

[Acute transitory intrafamilial erythroblastopenia and hereditary spherocytosis: role of parvovirus B19]. / Erythroblastopénie aiguë transitoire intrafamiliale et sphérocytose héréditaire: responsabilité du parvovirus B19.

INTRODUCTION: Acute parvovirus B19 infection induces a transient inhibition of erythroid cell formation, which may induce an erythroblastopenia crisis in patients suffering from chronic hemolytic anemia. EXEGESIS: We report here an exceptional observation of acute erythroblastopenia crisis with good outcome, occurring at the same time in a mother and her son, both suffering from hereditary spherocytosis. Diagnosis of parvovirus infection is based on detection of serum parvovirus B19-specific immunoglobulin M antibodies in the mother and her son and by the positivity of parvovirus B19 DNA detected by PCR in serum in the mother. Outcome was good, with the end of the erythroblastopenia crisis obtained 7 to 10 days later, but requiring blood transfusion in the mother. CONCLUSION: Our observation is a reminder that the contagiosity of parvovirus B19 is high in household contacts and that protection of family members should rapidly be considered in hereditary spherocytosis.

[Retrospective study of 55 patients with circulating blood T gama/delta lymphocytosis]. / Etude rétrospective de 55 patients présentant une lymphocytose T gamma/delta dans le sang circulant.

PURPOSE: Gamma/delta T lymphocytes constitute a singular population due to their particular antigenic recognition and their localization inside the epithelium. Their functions are complementary to those of the alpha/beta T-cells and they are involved in the defense and regulation of the immune system. Their role in human diseases is not very well understood and the aim of our study was to analyze a population of patients with a peripheral gamma/delta T-cell lymphocytosis. METHODS: The study included 55 patients, recruited from 1997 to 2000, with a peripheral gamma/delta T lymphocytosis (defined by a proportion of gamma/delta T-cells of over 10% of total peripheral T lymphocytes). Analysis of the lymphocyte population was obtained by cytometry after peripheral blood sampling. RESULTS: Three main groups of diseases were observed: infectious diseases (viral infections and tuberculosis), inflammatory diseases (sarcoidosis and autoimmune diseases) and blood diseases (monoclonal gammopathies and hemopathies). Persistence of gamma/delta T lymphocytosis was dependent on the underlying disease (transitional when associated with an infectious disease and lasting when associated with sarcoidosis). The rest of the immunophenotyping analysis was usually normal. CONCLUSION: Our results confirm the data published in the literature concerning the role of the gamma/delta T lymphocytes in infectious, inflammatory and autoimmune diseases and neoplasias. These data are in agreement with the cytotoxic and regular functions of these lymphocytes.

[IGM hyperimmunoglobulinemia anti-phosphatidylethanolamine antibodies of the IgM isotype: clinical and biological study of 72 patients with immune disorders]. / Hyper-immunoglobulinémie M et anticorps antiphosphatidyléthanolamine d'isotype IgM: étude clinicobiologique de 72 patients porteurs d'immunopathie.

PURPOSE: Antiphosphatidylethanolamine antibodies (aPE) are zwitterionic antiphospholipid antibodies that have been recently described in antiphospholipid syndrome. IgM is the most frequently observed isotype. We assessed the potential relationship between serum IgM levels and their presence. METHODS: Seventy-two patients (66 females, 6 males) positive for aPE of the IgM isotype were followed up for 2 years. They suffered from either an autoimmune disease or had clinical signs suggesting the existence of antiphospholipid syndrome or other immune disorders. Seventy-two control patients (58 females, 14 males) of similar age, with other immune disorders were also included in the study. For each of them, the IgM level was obtained and hyper-immunoglobulinemia M (hyper-IgM) was defined as a value upper than 2.5 g/L. Search for aPE of the IgM isotype was made using an in-house Elisa test. RESULTS: Half of the aPE-positive patients had serum hyper-IgM, whereas none of the aPE-negative patients had hyper-IgM. All IgMs were polyclonal. There was a positive correlation (r = 0.57, P = 0.001) between the level of IgM and the optical densities obtained by Elisa. The presence of a hyper-IgM did not modify the clinical manifestations (arterial and venous thromboses, recurrent fetal losses), nor the positivity of lupus anticoagulant, anticardiolipin and anti-beta-2-glycoprotein 1 antibodies. CONCLUSION: The positive correlation between the IgM level and aPE level is of value, as it suggests a possible relationship between lymphocytic activation and auto-antibodies production, which does not concern only aPE. Further studies regarding the antigenic specificity of IgM will probably provide further insights on IgM and phospholipid interactions.