[Autoimmune autonomic ganglionopathy: a case series of six patients and literature review]. / Ganglionopathie autonomique auto-immune : une série de six observations et revue de la littérature.

PURPOSE: Auto-immune autonomic ganglionopathy is a recently described clinical entity within the spectrum of autonomic neuropathies. Patients with auto-immune autonomic ganglionopathy typically present with rapid onset of severe autonomic failure. Acetylcholine receptor ganglionic antibodies, directed against ganglionic synapsis, disrupt synaptic transmission in autonomic ganglia and lead to autonomic failure. These antibodies are specific for auto-immune autonomic ganglionopathy and are present in 50% of patients. METHODS: Descriptive retrospective study. We report six French patients who presented with auto-immune autonomic ganglionopathy diagnosed between 1996 and 2002. RESULTS: Four patients were men and the median age at diagnosis was 45 years. All patients presented with a subacute autonomic failure with constant severe orthostatic hypotension. Serological testing of acetylcholine receptor ganglionic antibodies was performed in four out of the six patients and was found positive in three. All the patients received intravenous immunoglobulin and a clinical improvement was observed in four of them. CONCLUSION: Auto-immune autonomic ganglionopathy is an unusual and overlooked disorder. However, this autonomic neuropathy deserves to be better known as most of the patients respond to immunomodulatory therapy.

Spinal cord sarcoidosis: report of seven cases.

BACKGROUND: Spinal cord involvement in sarcoidosis is rare, occurring in <1% of patients with sarcoidosis. METHODS: We report seven cases of spinal cord sarcoidosis, seen in two French hospitals over a 13-year period. Presentation of disease, methods of diagnosis and response to treatment, with quantification according to the reduction of the modified Rankin scale (MRS), were noted. RESULTS: Six patients presented insidious paresthesias or weakness and one a sudden paraplegia. Average MRS at diagnosis was to 2. Spine MRI showed one or several intramedullary lesions in all cases. Diagnosis was confirmed by extra-neural tissue biopsies in all cases, including mediastinoscopy (two patients), coelioscopy (one patient), bronchoscopy (one patient), salivary gland biopsy (one patient) and skin biopsy (two patients). The average follow-up for the group was 49.4 months. All patients responded to corticosteroid therapy with a median reduction of MRS of one point. Five patients received immunosuppressive therapy: cyclophosphamide (two patients), methotrexate (two patients), azathioprine (one patient), mycophenolate mofetyl (one patient), with an inconstant benefit. Patients who received cyclophosphamide presented severe fungaemia. CONCLUSION: Based on our study and literature analysis, we propose an algorithm for treatment of spinal cord sarcoidosis.

[Hypocomplementemic urticarial vasculitis]. / Vascularite urticarienne hypocomplémentémique.

Hypocomplementemic urticarial vasculitis is a rare disorder characterized by the presence of C1q precipitins associated with a syndrome of urticarial vasculitis, arthralgias, ocular inflammation and obstructive-lung disease. We report the case of a 48-year-old woman with hypocomplementemic urticarial vasculitis. Because of dependance to corticosteroids, cyclophosphamide-pulse therapy was started and resulted in significant clinical improvement. Mycophenolate mofetil was effective as maintenance therapy and resulted in complete resolution of rash, arthralgias, arthritis and uveitis, but had no effect on the obstructive-lung disease.

[Tropheryma whipplei and Whipple disease: false positive PCR detections of Tropheryma whipplei in diagnostic samples are rare]. / Tropheryma whipplei et maladie de Whipple: résultats de la recherche par polymerase chain reaction (PCR) dans les échantillons à visée diagnostique.

BACKGROUND: PCR can be used to detect T. whipplei (Tw) in samples from variable tissue types and body fluids. We report clinical, evolutive characteristics and final diagnosis in patients with positive Tw PCR assay. METHODS: Retrospective study of Tw PCR realized since 10years in a microbiology laboratory. RESULTS: Twenty-five Tw PCR assays were positive among 200 realized. Diagnosis was not confirmed in six cases. One patient was missing for follow up. Eighteen patients presented with Whipple's disease. Among these 18 patients, 14 had a classic Whipple's disease, three patients presented an endocarditis and one patient isolated neurological manifestations. Ten patients presented fever, seven a weight loss and 12 joint involvement. Four patients presented cutaneous manifestations, only six had gastrointestinal symptoms. Neurological involvement was reported in five cases, pulmonary symptoms in four cases, cardiac involvement in six cases and ocular signs in two cases. Anemia was reported in four patients and elevated levels of acute-phase reactants in 14 cases. Positive predictive value of Tw PCR for Whipple's disease diagnosis was 75%. Thirteen patients had a good evolution with antibiotics. Three patients presented recurrence and two cases with cardiovascular involvement died. CONCLUSION: Whipple's disease is rare but often mentioned in internist experience. The diagnosis should be every time confirmed. Tw PCR assay is an important diagnostic tool but is not sufficient to establish the diagnosis and must be interpreted with histopathology and immunohistochemical testing results.

[Systemic sclerosis in men]. / Sclérodermie systémique chez l'homme.

PURPOSE: To study the initial clinical features and describe the outcome of systemic sclerosis in a cohort of French men. METHODS: Patients with systemic sclerosis based on Leroy's criteria were included. In this retrospective study we compared a cohort of men to a cohort of women, diagnosed between 1997 and 2005 in departments of internal medicine and rheumatology. RESULTS: One hundred and twenty-one patients were included amongst which thirty-six men. The mean follow-up duration was 6.5 years. The time to diagnosis was significantly shorter in men than in women. Diffuse cutaneous systemic sclerosis, cutaneous ulcers and interstitial syndrome on chest radiograph were more frequent at diagnosis in men than in women. An environmental factor (silica) was observed in only nine men. During the follow-up, incidence of restrictive lung disease was significantly higher in men than in women (37% versus 14% p=0.01) with higher rates of oxygen dependency (22% versus 5% p<0.01). Cumulated survival rates in men were 92% at 5 years, 72% at ten years and 43% at 15 years, respectively. The mean survival was 13 years in men (IC 95%: 10-16) versus 23 years in women (IC 95%: 10-36) with no statistical difference (p=0.27). CONCLUSION: If interstitial and restrictive lung disease, oxygen dependency and diffuse systemic sclerosis were more frequent in men than in women, this data did not provide any evidence of survival difference between men and women with systemic sclerosis.

[Non-tuberculous systemic granulomatosis mimicking sarcoidosis but related to a specific etiology. Study of 67 cases]. / Granulomatoses systémiques pseudosarcoïdosiques d'étiologie déterminée et non tuberculeuse. Etude de 67 observations.

PURPOSE: Systemic granulomatosis (SG) are frequently encountered in internal medicine. Despite a large list of aetiologies, the investigations remain often negative leading to the diagnosis of atypical sarcoidosis. The spectrum of the causes, as well as evolution of these SG is not clearly delineated in the literature. METHOD: We analyzed the case reports of all but tuberculous GS submitted at the National Meetings of the National French Society of Internal Medicine from 1990 to 2006. RESULTS: Sixty-seven cases were included in the study. The average age at the beginning of the symptoms was 47.8 years and 28.4% of the patients were female. The median diagnostic delay was one year. General symptoms were present in 73.1% of the cases. The involved organs were the liver (46.3%), lungs (25.4%), lymph nodes (22.4%), digestive tract (16.4%), skin (16.4%), spleen (14.9%). The granuloma were detected mainly in the liver (38.8%), lymph nodes (17.9%), bone marrow (16.4%) and lungs (11.9%). Elevated erythrocyte sedimentation rate or increased C reactive protein serum levels were noted in 65.6% of the patients. Before diagnosis, 19.4% of the patients received a corticotherapy. The most common diagnoses were infections (65.6%) followed by drugs (19.5%), "toxic substances" or various foreign bodies (5.9%), neoplasias (5.9%) and immune deficiencies (3%). The evolution was favourable in 80% of the cases but 8.3% of the patients died. The disease course of the patients having received a corticotherapy prior to the diagnosis was more unfavourable with a death rate of 45%. CONCLUSION: In atypical sarcoidosis (fever, advanced age, increased acute phase reactants...) a specific aetiology and especially an infectious disease should be ruled out before considering the diagnosis of sarcoidosis. Corticotherapy is a factor of poor prognosis.

[Toxic or drug-induced granulomatous reactions]. / Granulomatoses d'origine médicamenteuse ou toxique.

PURPOSE: To review the current concepts in toxic and drug-induced granulomatous reactions. CURRENT KNOWLEDGE AND KEY POINTS: Granulomatous reactions are induced by various chemical agents, treatments or foreign bodies. According to the breaking way into the organism, the lungs, the liver, the kidneys or the skin are mainly concerned, but systemic granulomatosis mimicking sarcoidosis is possible. Therefore systematic analysis of environmental, occupational and leisure exposures and quest for medical or illicit drugs is mandatory to identify the responsible agent. Over the recent period, chronic beryllium disease, interferon-alpha therapy, BCG immunotherapy and allopurinol have been more frequently involved. FUTURE PROSPECTS AND PROJECTS: Literature review uncovers a variety of potential toxic exposures and highlights the necessity of a clear sighted research to identify them.

[Sarcoidosis and sarcoid reactions in cancer]. / Place de la pathologie granulomateuse au cours des cancers.

PURPOSE: Relationships between granulomatosis and cancers have been suspected for a long time. Nevertheless, few evidence has been reported until recently. Here, we present a literature review about the association of granulomatosis and neoplasia. CURRENT KNOWLEDGE AND KEY POINTS: Aside from granulomatosis due to infectious disease, granulomas can be observed in cancer patients, mainly in two situations. Patients may rarely present with typical sarcoidosis occurring before, during or after the diagnosis of cancer. Recent studies have documented such a relationship particularly with lymphomas, testicular and lung cancers, melanomas and hepatocarcinomas. Secondly granulomas may be found as a sarcoid reaction in the vicinity of the tumour itself or more frequently in regional lymph nodes. Sarcoid reaction, reported in Hodgkin's disease and gastric adenocarcinomas, may be associated with a better prognosis. Granulomatous reaction could play an important role in the host's defences against metastatic extension. Immunotherapy such as interferon has been reported to induce systemic sarcoidosis probably by reproducing some physiopathological mechanisms involved in sarcoidosis. FUTURE PROSPECTS AND PROJECTS: Clinicians need novel non invasive diagnostic methods to differentiate neoplasia from benign sarcoid reactions. The 18-fluorodeoxyglucose (18-FDG) PET-scan has failed in this indication but the adjunction of a [3-(18)F]-alpha-methyltyrosine ((18)F-FMT) PET-scan could be useful. Biopsies is still necessary in most of cases.

[Chronic inflammatory demyelinating polyneuropathy and sarcoidosis: fortuitous association?]. / Polyradiculonévrite chronique et sarcoïdose: association fortuite.

We report the case of a 36-year-old-man who first presented two relapses of chronic inflammatory demyelinating polyneuropathy (CIDP) before a diagnosis of sarcoidosis was made. He subsequently presented two combined relapses of CIDP and sarcoidosis. Each time, the outcome was favorable after treatment with intravenous immunglobulins and steroids. The possible relationship between CIDP and sarcoidosis is discussed.

Treatment of isolated severe immune hemolytic anaemia associated with systemic lupus erythematosus: 26 cases.

The aim of this study was to evaluate the response to treatment and the long-term outcome in a cohort of patients in whom severe autoimmune hemolytic anaemia (AHA) was the leading manifestation of systemic lupus erythematosus (SLE). Twenty-six women with severe isolated AHA were included. Corticosteroids were used as the initial treatment for all patients in our study. An initial response was obtained in all but one patient (96%). The overall recurrence rate was three per 100 person-years, with an expected recurrence-free proportion of 73% with a 180 months median follow-up. Seven patients (27%) experienced a relapse of AHA. We found a higher proportion of pleuritis in relapsing patients. Only three patients experienced multiple relapses despite splenectomy and several immunosuppressants. Steroid-sparing effect of hydroxychloroquine and azathioprine could not be assessed because most of the patients received these treatments for other reasons than AHA. Intravenous immunoglobulins induced transient response in three cases. Splenectomy was efficient to definitively control AHA in one patient but two patients quickly experienced relapses while one patient did not benefit. Five patients received immunosuppressants that induced only transient responses. Rituximab was long-term efficient in one case. In conclusion, severe AHA is a serious complication of SLE that warrants appropriate management. On the basis of our experience, the ideal treatment of isolated AHA should be oral corticosteroids in first-line treatment. Our study does not support an important role for splenectomy. Patients refractory to conventional therapy should be treated either with few toxic immunosuppressive drugs, danazol or rituximab.

[Venous thromboembolism and cancer]. / Maladie veineuse thromboembolique et cancer.

OBJECTIVES: The risk of venous thrombosis during cancer is largely increased especially in case of chemotherapy, surgery, advanced stage disease, coagulation abnormalities. Survival of patients with cancer experiencing venous thrombosis seems to be worse. Although thrombosis may be a presenting feature of occult malignancy, there are insufficient data to support a more extensive screening than comprehensive medical history, physical examination, routine laboratory tests and chest radiography. CURRENT KNOWLEDGE AND KEY POINTS: Pathophysiology of venous thrombosis during cancer is unspecific: venous stasis, vessel wall damage, hypercoagulability). Other factors like platelet abnormalities or the direct responsibility of chemotherapy or hormonotherapy have recently been though to play a causative role. Treatment of cancer-associated thrombosis usually requires at least 6 months of low-molecular-weight heparin therapy rather than oral anticoagulant. Inferior vena cava filters are not indicated. Primary prophylaxis of thrombosis during cancer could safely been achieved with low-molecular-weight heparin. Central venous catheters can be associated with thrombotic complications. Many risks factors have been identified: catheter's type, modalities of catheter's implantation, type of perfusion, bulky mediastinal mass... Prophylactic anticoagulation is not routinely recommended. FUTURE PROSPECTS AND PROJECTS: Knew oral anticoagulants could facilitate the treatment of venous thrombosis occurring during cancer in the next years.

[Pentoxifylline: a cheap substitute for anti-TNFalpha agents?]. / Pentoxifylline: l'anti-TNF du pauvre?

PURPOSE: Pentoxifylline (PTX) is a phosphodiesterase inhibitor drug used to improve peripheral vascular disease. In vitro studies demonstrated that PTX has anti-TNFalpha properties. We did a selective review of clinical trials which used PTX in patients with inflammatory rheumatic and non-rheumatic diseases. CURRENT KNOWLEDGE AND KEY POINTS: Most of the identified clinical trials were uncontrolled and involved a low number of patients. Use of PTX in systemic lupus erythematous, Behçet's disease and sarcoidosis yielded significant preliminary results. Moreover, PTX markedly reduced proteinuria in several glomerulonephritis (lupus nephritis, membranous nephropathy, diabetic nephropathy). FUTURE PROSPECTS AND PROJECTS: Further randomized and controlled clinical trials are required to examine whether PTX can improve outcome in patients with inflammatory diseases. Meanwhile, PTX should not be used for the treatment of these diseases.

[Whipple's disease endocarditis: report of 5 cases and review of the literature]. / Endocardites de la maladie de Whipple: cinq observations et revue de la littérature.

PURPOSE: Endocarditic lesions (infectious endocarditis) associated with Whipple's disease are exceptional. We report five cases from the cardiovascular and pneumologic hospital Louis Pradel in Lyon. METHOD: We have collected all cases of Tropheryma whipplei endocarditis diagnosed between 1995 and 2004. RESULTS: Five men with a mean age of 53 years at time of diagnosis. The symptoms were essentially cardiovascular: murmur, embolism in 3 cases, and heart failure secondary to valvular insufficiency in 2 cases. The valvular involvement, double in 3 cases, was more often aortic. Vegetations were present in all patients and valvular destruction sometimes very important. A low grade fever was present in 4 cases, associated with weight loss in 2 cases. The only extra-cardiac symptoms were arthralgias or arthritis in all cases, considered in 3 patients as seronegative rheumatoid arthritis, B27+ spondylarthritis, and psoriasic arthritis. Their was no other clinical manifestations of Whipple's disease, particularly digestive, ocular, neurologic or adenopathy, and duodenal biopsies secondarily performed in 4 cases were non contributive. This differs from literature as an extra-cardiac location was identified in 11 out of 17 cases. The diagnosis was obtained by histology and PCR on the cardiac valves, as all the patients underwent surgery. The evolution was favourable with a prolonged antibiotic therapy. CONCLUSIONS: These report confirms the existence of endocarditic forms of the Whipple's disease, in which the single extra-cardiac manifestation is rheumatologic, and reminds us the usefulness of histology and PCR on the cardiac valves at the time of valvular surgery.

Diffusion-weighted magnetic resonance imaging in Marchiafava-Bignami disease: follow-up studies.

Marchiafava-Bignami disease (MBD), an acute toxic demyelination of the corpus callosum in alcoholics, is associated with poor evolution in the majority of patients. We report here the early and late diffusion magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) studies of two patients suffering from MBD with favourable outcome. Diffusion and anatomical MRI changes were parallel to the clinical evolution, suggesting that MRI studies can be helpful for diagnosis and follow-up. Unlike in stroke, restricted diffusion on ADC maps does not seem to be a sign of irreversibility.