[Interest of daratumumab in refractory AL amyloidosis in a 96-year-old patient]. / Intérêt du daratumumab dans l'amylose AL réfractaire chez une patiente de 96ans.

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+plasma cells, resulting in organ dysfunction. Cardiac involvement has a major prognostic value. Antiplasma cell chemotherapy reduces the synthesis of immunoglobulin light chains (precursors of amyloid deposits). We describe a case of AL amyloidosis in a 95-year-old patient. Our patient responded poorly to treatment with rituximab, cyclophosphamide-bortezomib-dexamethasone, and rituximab-bendamustine. Finally, the anti-CD38 antibody daratumumab was associated with the best hematologic responsiveness without significant adverse effects. In conclusion, our case suggests that daratumumab is an effective and well-tolerated alternative to chemotherapy in the treatment af AL amyloidosis in very elderly patients.

Descriptive study of pneumococcal vaccination in cases of inflammatory disease: Analysis of practices.

INTRODUCTION: Pneumococcal infections are frequent and potentially serious in patients with inflammatory diseases treated with immunosuppressants and/or biotherapies. This patient population considered to be at very high risk of infection is subject to national vaccination recommendations. The main objective of this study was to assess pneumococcal vaccine coverage in a day hospital (internal medicine and vascular disease) in patients treated with immunosuppressants. METHODS: An observational, descriptive, retrospective, and single-center study. We included 150 consecutive patients for 3 months (February to April 2018). We studied pneumococcal vaccination coverage and the time elapsed between the date of vaccination with the 13-valent polysaccharide conjugate vaccine (PCV13) and the start of immunosuppressive therapy. RESULTS: Among the 150 patients included in the study, vaccination coverage with PCV13 was 85% (127/150) and decreased to 46.7% (70/150) for the recommended vaccination schedule. Taking into account vaccine efficacy according to the date of initiation of the treatment, only 28.7% (43/150) of the patients in the study were able to benefit from an optimal complete vaccination schedule, i.e. 33.8% (43/127) among patients vaccinated with PCV13. CONCLUSION: Despite official recommendations, vaccination coverage against pneumococcus remains insufficient in patients under immunosuppressants and/or biotherapies. In addition to the continued training of doctors, optimizing computer prescription of vaccines in view of facilitating vaccination tracing and having vaccination carried out at the site of consultation are avenues for improvement to be considered.

[Gynecologic vasculitis revealing a giant cell arteritis: A case report and literature review]. / Vascularite des artères utérines révélant une artérite à cellules géantes : cas clinique et revue de la littérature.

INTRODUCTION: Genital vasculitis are uncommon. They may be localized or be a manifestation of a systemic vasculitis. We report a patient with a giant cell arteritis (GCA) involving uterine arteries and a literature review on genital vasculitis. CASE REPORT: A 65-year-old woman was referred to a gynecologist for a cervical intraepithelial neoplasia (CIN) associated with an ovarian mass. An unexpected diagnosis of GCA involving small to medium sized uterine arteries was made through the anatomopathological analysis while the patient was asymptomatic. Two weeks later, she presented typical cranial symptoms of giant cell arteritis (GCA). PET-scanner confirmed the diagnosis of GCA with an involvement of the ascending aorta, and the axillary and the subclavian arteries. CONCLUSION: Gynecologic vasculitis are rare and usually an asymptomatic manifestations of GCA.

Evolution of comorbidities in people living with HIV between 2004 and 2014: cross-sectional analyses from ANRS CO3 Aquitaine cohort.

BACKGROUND: The objective of the study was to describe the evolution of chronic non-AIDS related diseases and their risk factors, in patients living with HIV (PLHIV) in the French ANRS CO3 Aquitaine prospective cohort, observed both in 2004 and in 2014 in order to improve long-term healthcare management. METHODS: The ANRS CO3 Aquitaine cohort prospectively collects epidemiological, clinical, biological and therapeutic data on PLHIV in the French Aquitaine region. Two cross sectional analyses were performed in 2004 and 2014, to investigate the patient characteristics, HIV RNA, CD4 counts and prevalence of some common comorbidities and treatment. RESULTS: 2138 PLHIV (71% male, median age 52.2 years in 2014) were identified for inclusion in the study, including participants who were registered in the cohort with at least one hospital visit recorded in both 2004 and 2014. Significant increases in the prevalence of diagnosed chronic kidney disease (CKD), bone fractures, cardiovascular events (CVE), hypertension, diabetes and dyslipidaemia, as well as an increase in treatment or prevention for these conditions (statins, clopidogrel, aspirin) were observed. It was also reflected in the increase in the proportion of patients in the "high" or "very high" risk groups of the disease risk scores for CKD, CVE and bone fracture score. CONCLUSIONS: Between 2004 and 2014, the aging PLHIV population identified in the French ANRS CO3 Aquitaine prospective cohort experienced an overall higher prevalence of non-HIV related comorbidities, including CKD and CVD. Long-term healthcare management and long-term health outcomes could be improved for PLHIV by: careful HIV management according to current recommendations with optimal selection of antiretrovirals, and early management of comorbidities through recommended lifestyle improvements and preventative measures.

[Cough as the presenting feature of pulmonary AL amyloidosis: A case report]. / Amylose pulmonaire AL révélée par une toux : à propos d'une observation.

INTRODUCTION: Pulmonary lesions may be a presenting feature of AL amyloidosis. OBSERVATION: We report a 49-year-old male with AL amyloidosis secondary to a multiple myeloma with symptomatic interstitial pulmonary lesions and chronic cough as the presenting feature. CONCLUSION: Lung involvement is relatively frequent during AL amyloidosis but most of the time it remains asymptomatic. Interstitial pneumonia is the rarest condition of pulmonary amyloidosis. It is related to a large diffusion of the disease as demonstrated by the usual concurrent presence of cardiac lesions.

Hypereosinophilic syndrome - lymphocytic variant transforming into peripheral T-cell lymphoma with severe oral manifestations.

Hypereosinophilic syndrome (HES) is a rare disease defined by organ damage directly attributable to hypereosinophilia of any type. Here, we report for the first time the case of a patient with a lymphocytic type of HES (HES-L) who had liver, skin, spleen, lung, bone marrow, digestive track, and mouth involvement. Associated T-cells displayed an aberrant CD30+ phenotype and were monoclonal. Thymus activated and regulated chemokine serum level was positive. Despite steroids (Cortancyl 20 mg [Sanofi Aventis, France], imatinib mesylate [Glivec 400 mg; Novartis Europharm], interferon alpha 2A [Roferon-A 3 MUI/0.5 ml; Roche]) and other lines of therapy including imatinib mesylate treatment, an oral necrotic lesion developed, and finally progressed into a peripheral CD30+ T-cell lymphoma. CHOP chemotherapy (cyclophosphamide, hydroxydoxorubicin, oncovin, prednisone), interferon-α, and mepolizumab were ineffective. Although progression into peripheral T-cell lymphoma is documented as a rare complication of HES-L, severe oral extension of HES-L is described for the first time.

[Non-fortuitous dynamin II mutation-related association: neutropenia and Charcot-Marie-Tooth disease]. / Association non fortuite d'une neutropénie chronique et d'une maladie de Charcot-Marie-Tooth en rapport avec une mutation de la dynamine 2.

Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy is a genetically and clinically heterogeneous group of disorders of the peripheral nervous system. Mutations in multiple genes are currently known. We report an original case of CMT associated with chronic neutropenia in a patient with a K562del mutation in the dynamin 2 (DNM2) gene in a patient presenting with alterated cognitive function. Associated manifestations may guide molecular study.

[Lipoatrophia semicircularis: a case report]. / La lipoatrophie semi-circulaire des cuisses : à propos d'un cas.

We report a 54-year-old man who presented bilateral, symmetric depressions on the anterior aspect of his thighs corresponding to lipoatrophia semicircularis. The origin of this distinctive variant of lipoatrophy is unknown. Repeated external microtraumatisms were considered to be the most plausible explanation. Recently, as many recently affected subjects shared a status of administrative employee, the role of electromagnetic fields generated by computers and their wirings has been discussed. Prevention proposal includes adapting work environment related to the use of computerized devices.

[Antisynthetase syndrome: a retrospective study of 14 patients]. / Le syndrome des antisynthétases : étude rétrospective à propos d'une série de 14 patients.

PURPOSE: Antisynthetase syndrome is a rare entity characterized by myositis (dermatomyositis or polymyositis), interstitial lung disease, arthritis, Raynaud's phenomena and mechanic's hands skin manifestation, and the presence of autoantibodies against aminoacyl-transfer RNA synthetase. PATIENTS AND METHODS: Fourteen patients with antisynthetase syndrome followed-up between 1997 and 2009 were included. We studied retrospectively their clinical, radiological, and pathological findings. RESULTS: The sex ratio women/men was 2.5. Mean age at disease onset was 46 years. Arthritis (43%) and interstitial lung disease (38%) were the most frequent features at disease onset. Seven patients had myositis. Ten patients had anti-Jo1 autoantibodies, three had anti-PL7 and one anti-PL12. Corticosteroid therapy was given in all cases, immunosuppressive drugs in 12 cases, due to initial severity (n=8), disease relapse (n=3) or corticosteroid dependence (n=1). After a mean follow-up of 64 months, nine patients improved, four stabilized and one patient died after lung transplantation, required for pulmonary hypertension. CONCLUSION: The diffusion of immunologic assay will help us in the future to identify the specificity of this syndrome in order to improve care.

Rates of cardiovascular disease following smoking cessation in patients with HIV infection: results from the D:A:D study(*).

OBJECTIVES: The aim of the study was to estimate the rates of cardiovascular disease (CVD) events after stopping smoking in patients with HIV infection. METHODS: Patients who reported smoking status and no previous CVD prior to enrolment in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study were included in this study. Smoking status is collected at each visit as current smoker (yes/no) and ever smoker (yes/no). Time since stopping smoking was calculated for persons who had reported current smoking during follow-up and no current smoking subsequently. Endpoints were: myocardial infarction (MI); coronary heart disease (CHD: MI plus invasive coronary artery procedure or death from other CHD); CVD (CHD plus carotid artery endarterectomy or stroke); and all-cause mortality. Event rates were calculated for never, previous and current smokers, and smokers who stopped during follow-up. Incidence rate ratios (IRRs) were determined using Poisson regression adjusted for age, sex, cohort, calendar year, family history of CVD, diabetes, lipids, blood pressure and antiretroviral treatment. RESULTS: A total of 27 136 patients had smoking status reported, with totals of 432, 600, 746 and 1902 MI, CHD, CVD and mortality events, respectively. The adjusted IRR of CVD in patients who stopped smoking during follow-up decreased from 2.32 within the first year of stopping to 1.49 after >3 years compared with those who never smoked. Similar trends were observed for the MI and CHD endpoints. Reductions in risk were less pronounced for all-cause mortality. CONCLUSION: The risk of CVD events in HIV-positive patients decreased with increasing time since stopping smoking. Smoking cessation efforts should be a priority in the management of HIV-positive patients.

[Macroglobulinosis cutis revealing Waldenström macroglobulinemia]. / Une maladie de Waldenström révélée par une macroglobulinemia cutis.

Waldenström macroglobulinemia is defined by a bone marrow lymphoplasmacytic infiltration associated with serum IgM monoclonal gammopathy. Specific properties of the IgM gammopathy induce the main clinical manifestations revealing the disease: hyperviscosity syndrome, autoimmune peripheral neuropathy, cryoglobulinemia or hemolysis, and exceptional skin deposit such as macroglobulinosis cutis that we here report. Physicians should be aware of these clinical manifestations to avoid diagnostic delay.

[Wegener's granulomatosis with anti-MPO c-ANCA revealed by uveitis]. / Maladie de Wegener à c-ANCA de type anti-MPO révélée par une uvéite.

Wegener's granulomatosis (WG) is a rare systemic necrotizing granulomatous vasculitis affecting small- to medium-sized vessels, associated with antineutrophil cytoplasm antibodies (ANCA), mainly anti-proteinase 3. Rarely, ANCA may be directed against myeloperoxidase. We report a 58-year-old woman who developed an uveitis as the presenting manifestation of Wegener's granulomatosis who highlight the usefulness of internist and ophthalmologist collaboration.

Usefulness of combined nerve and muscle biopsy in the diagnosis of amyloid neuropathy--a study of 6 new cases.

OBJECTIVE: Most cases of familial amyloid polyneuropathy are identified by molecular genetic analysis of the transthyretin (TTR) gene. However, it is not uncommon to find unexpected amyloid deposits marked by the anti-TTR serum in the endoneurium of aged patients. Light chain amyloid deposits may also be found in the endoneurium. During these past 5 years, we studied the muscle and nerve biopsies from 6 patients which revealed amyloid deposits. There were 2 patients with an idiopathic polyneuropathy and 4 with monoclonal gammopathy (MG). METHODS: In each case, specimens from the superficial peroneal nerve and peroneus brevis muscle were taken by the same cutaneous incision. RESULTS: Amyloid deposits were visible in the endoneurium of 2 cases and only on muscle specimens in 3 other cases, 1 with a MG and 2 with an idiopathic polyneuropathy. Amyloid deposits were strongly stained with the anti-TTR serum in the muscle specimens of the 2 idiopathic cases, mainly located in vessel walls. In one patient with polyneuropathy and MG, a small endoneurial amyloid deposit surprisingly revealed to be immunostained by the anti-TTR serum. In another case, a small amyloid deposit in close relationship with a macrophage was only visible in the endoneurium by electron microscopy. COMMENTS: Amyloid deposits were only visible on muscle fragments in 3 cases and were strongly marked by the anti-TTR serum in 2 of them, indicating their familial origin. Combining muscle and nerve biopsy raises the number of cases with visible amyloid deposits.

Association of non-HDL cholesterol with subclinical atherosclerosis in HIV-positive patients.

OBJECTIVES: To assess the relationship between non-classical cardiovascular (CV) risk factors including non-HDL cholesterol (non-HDL-C), apolipoprotein B, triglycerides to HDL ratio, LDL size, inflammation or oxidative stress parameters and carotid intima-media thickness (CIMT), in order to better identify prevention or therapeutic targets. In addition, we studied the relationship between metabolic syndrome (MS) and CIMT. METHODS: Cross-sectional study including 232 HIV-positive (HIV+) adults (80% treated by combined antiretroviral therapy) extracted from the ANRS CO3 Aquitaine Cohort. RESULTS: There was a significant association of higher non-HDL-C (p<0.01), apolipoprotein B (p<0.01) levels or TG/HDL ratio (p<0.05) with higher CIMT when compared the first vs fourth quartile, while there is no association between CIMT and LDL-C (p=0.09) or LDL size (p=0.55). In multivariate analysis, only the TG/HDL molar ratio > 1.5 tend toward significance (p=0.08). MS was observed in only 7.3% of patients with the NCEP-ATP III definition and 11.2% with the IDF criteria. Whatever the used definition, there was a significant association between MS presence and increased CIMT (p<0.05) in univariate and multivariate model. CONCLUSIONS: Non-HDL-C, TG/HDL ratio and apolipoprotein B levels, which are closely linked to lipid disorders associated to the MS, appear as stronger predictive markers than LDL-C for screening subclinical atherosclerosis in HIV+ populations. Achieving non-HDL-C target defined by the NCEP-ATP III guidelines appears of great importance to reduce CV complications in HIV+ patients.

Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction.

BACKGROUND: Because of the known relationship between exposure to combination antiretroviral therapy and cardiovascular disease (CVD), it has become increasingly important to intervene against risk of CVD in human immunodeficiency virus (HIV)-infected patients. We evaluated changes in risk factors for CVD and the use of lipid-lowering therapy in HIV-infected individuals and assessed the impact of any changes on the incidence of myocardial infarction. METHODS: The Data Collection on Adverse Events of Anti-HIV Drugs Study is a collaboration of 11 cohorts of HIV-infected patients that included follow-up for 33,389 HIV-infected patients from December 1999 through February 2006. RESULTS: The proportion of patients at high risk of CVD increased from 35.3% during 1999-2000 to 41.3% during 2005-2006. Of 28,985 patients, 2801 (9.7%) initiated lipid-lowering therapy; initiation of lipid-lowering therapy was more common for those with abnormal lipid values and those with traditional risk factors for CVD (male sex, older age, higher body mass index [calculated as the weight in kilograms divided by the square of the height in meters], family and personal history of CVD, and diabetes mellitus). After controlling for these, use of lipid-lowering drugs became relatively less common over time. The incidence of myocardial infarction (0.32 cases per 100 person-years [PY]; 95% confidence interval [CI], 0.29-0.35 cases per 100 PY) appeared to remain stable. However, after controlling for changes in risk factors for CVD, the rate decreased over time (relative rate in 2003 [compared with 1999-2000], 0.73 cases per 100 PY [95% CI, 0.50-1.05 cases per 100 PY]; in 2004, 0.64 cases per 100 PY [95% CI, 0.44-0.94 cases per 100 PY]; in 2005-2006, 0.36 cases per 100 PY [95% CI, 0.24-0.56 cases per 100 PY]). Further adjustment for lipid levels attenuated the relative rates towards unity (relative rate in 2003 [compared with 1999-2000], 1.06 cases per 100 PY [95% CI, 0.63-1.77 cases per 100 PY]; in 2004, 1.02 cases per 100 PY [95% CI, 0.61-1.71 cases per 100 PY]; in 2005-2006, 0.63 cases per 100 PY [95% CI, 0.36-1.09 cases per 100 PY]). CONCLUSIONS: Although the CVD risk profile among patients in the Data Collection on Adverse Events of Anti-HIV Drugs Study has decreased since 1999, rates have remained relatively stable, possibly as a result of a more aggressive approach towards managing the risk of CVD.

[The fate of the abstracts presented to the biannual meetings of the French National Society of Internal Medicine]. / Devenir des travaux publiés sous forme de résumés dans les actes des congrès semestriels de la Société nationale française de médecine interne.

PURPOSE: Medical meetings give the opportunity to present oral communications or posters to the attending participants. However, the peer-reviewed publication of a full article allows to reach a wide readership. KEY POINTS: The survey that was performed on the oral communications and posters presented at the 43rd meeting of the French National Society of Internal Medicine, December 2000, showed that amongst the 303 selected podium presentations and posters, only 82 (27%) were published during the five following years. Podium presentations were more likely to be published than posters (36% versus 22%). CONCLUSION: Many oral communications and posters that are presented in medical meeting are not followed by the publication of a peer-reviewed full article despite the modern means of communication. However, this issue is of paramount importance as beyond the legitimate personal satisfaction of a publication, the scientific and academic recognition are the ground of medical career achievement for many physicians.

Extra-pulmonary paragonimiasis with unusual arthritis and cutaneous features among a tourist returning from Gabon.

Paragonimiasis is a helminthic disease that affect accidentally man after consumption of raw or poorly cooked crustacean dishes. The clinical feature is represented mainly by pulmonary signs. Extra-pulmonary manifestations including arthritic and skin attempt remain less frequent. The case is described of a young white French woman who become infected with Paragonimus while travelling to Gabon for a tourist trip. Clinical presentation accounted for extensive recurrent pruritic urticarian subcutaneous induration, permanent assymetrical pauciarthritis associated with joint swelling, and marked eosinophilia. Diagnosis was reached using serological testing showing seroconversion for specific antibodies. The patient was cured with a single oral dose of praziquantel. Even if the condition is rare among tourists to endemic zones, it must be considered when hypereosinophilia occurs in the returning traveller and migrant.

[Exophtalmia revealing a mantle cell lymphoma]. / Exophtalmie révélant un lymphome du manteau: à propos d'un cas.

INTRODUCTION: Mantle cell lymphoma reached rarely ophtalmic sphere and salivary glands. CAS REPORT: We reported a dry syndrome seen in a 67 year-old patient. The first patological analysis of accessory salivary glands evoked a primary Gougerot-Sjögren syndrome. Secondary, he presented a mantle cell lymphoma. DISCUSSION: The pathological lack of specifity and the discovery of atypical Gougerot-Sjögren syndrome must encourage complementary immunohistochemical study of salivary glands biopsy.

Carotid intima-media thickness is slightly increased over time in HIV-1-infected patients.

OBJECTIVES: HIV-infected patients are at risk of atherosclerosis and cardiovascular diseases. In a 12-month follow-up study, we aimed to investigate changes in carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis, and its determinants in HIV-1-infected patients. METHODS: Our multicentre prospective longitudinal cohort study included 346 HIV-infected patients, for each of whom two IMT measurements were taken by B-mode ultrasonography at baseline (M0) and 1 year later (M12). RESULTS: We observed a significant but moderate increase in the common carotid artery (CCA) median IMT, from 0.54 to 0.56 mm (P<10(-4)), i.e. an increase of 0.020 mm (95% confidence interval 0.012-0.029). There was a significant association between cross-sectional CCA IMT measures at M12 and conventional cardiovascular risk factors (higher CCA IMT with older age, P<10(-4); male gender, P=0.02; tobacco consumption, P=0.05), as well as higher CD4 cell count at M12 (>median 455 cells/microL, P=0.01). Only CD4 cell count at M0 was strongly and positively associated with the variation in IMT between M0 and M12 (P=4 x 10(-3)). IMT progression was +0.0020 mm for the lowest quartile of CD4 cell count distribution at M0, i.e. 3-253 cells/microL, +0.010 mm for 253-402 cells/microL, +0.043 mm for 402-590 cells/microL, and +0.028 mm for 590-2270 cells/microL. No association was found with type or duration of antiretroviral exposure. CONCLUSIONS: Conventional cardiovascular risk factors are major determinants of IMT evolution. The link between immunological status and carotid IMT requires further study.