Loïc Capron

Endothelial dysfunction in systemic lupus patients with low disease activity: evaluation by quantification and characterization of circulating endothelial microparticles, role of anti-endothelial cell antibodies

OBJECTIVE We attempted to evaluate endothelial dysfunction and the role of AECAs in systemic lupus (SL) with low disease activity. We quantified endothelial microparticles (EMps) and attempted to find the best flow cytometry method for that purpose. METHODS CD105, CD144 and CD146 were tested, individually or in combination, on EMp-enriched plasma. Twenty-three healthy blood donors and 27 SL patients were evaluated. SL patients with a SLEDAI <10 (median 2.6) were evaluated in our outpatient clinic. For each patient, EMps (CD105-CD146(+), CD45(-)) and AECAs were quantified and characterized. RESULTS The monochrome composite marker CD105-CD146 appeared to be the most efficient in detecting EMps. SL patients had more circulating EMps than healthy donors: respective median values were 2575 and 130 EMps/microl (P < 0.001). SL patients had more CD54(+) and CD54(-) EMps than healthy donors (496 vs 34 EMps CD54(+)/microl, P < 0.0001; 1875 vs 89 EMps CD54(-)/microl, P < 0.0001). The ratio CD54(+) EMps/total EMps was lower for lupus patients than for healthy individuals (20.3 vs 33.7%, P = 0.03). Twenty-four patients (89%) were positive for AECAs. EMp counts were not significantly higher for patients with AECAs. CONCLUSION Monochrome composite marker is efficient in detecting the whole population of EMps using flow cytometry. SL patients with low disease activity have a marked endothelial dysfunction. EMps released from the endothelium originate from activated and non-activated cells. AECAs do not seem to be the main cause of endothelial dysfunction in this population.

Agreement between Erythrocyte Sedimentation Rate and C-Reactive Protein in Hospital Practice

BACKGROUND Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are frequently prescribed jointly. The usefulness of this practice is uncertain. METHODS All patients with ESR and CRP measured at the same time in an academic tertiary hospital during a 1-year period were included. Concomitant measures of serum creatinine, hematocrit, and anti-Xa activity were recorded to study noninflammatory cause of increased ESR. Level of agreement between ESR and CRP was assessed with kappa coefficient, and their accuracy was determined in a medical chart review of 99 randomly selected patients with disagreement between both markers. RESULTS Among 5777 patients, 35% and 58% had an elevated CRP and ESR, respectively. ESR and CRP were in agreement in 67% of patients (both elevated in 30%, both normal in 37%). A disagreement was observed in 33% (elevated ESR/normal CRP in 28%, normal ESR/elevated CRP in 5%). The kappa coefficient showed poor agreement (k=0.38) between both markers. Review of medical chart showed that 25 patients with elevated CRP and normal ESR had an active inflammatory disease (false-negative ESR). Conversely, 74 patients had elevated ESR and normal CRP-32% had resolving inflammatory disorders, 28% disclosed a variable interfering with the ESR measure (false-positive ESR), 32% had unexplained discrepancies, and 8% had an active inflammatory disease (false-negative CRP). CONCLUSION In hospital practice, joint measurement of ESR and CRP is unwarranted. Because of slow variation and frequent confounding, ESR is frequently misleading in unselected patients. When an inflammatory disorder is suspected, priority should be given to CRP.

Visceral Leishmaniasis Mimicking Systemic Lupus Erythematosus

To the Editor: We read with interest the recent report by Kritikos et al on an atypical presentation of visceral leishmaniasis (VL) in a patient with rheumatoid arthritis previously treated with infliximab. We would like to emphasize another atypical presentation of this parasitic infection that may mimic systemic lupus erythematosus (SLE), and report on an erroneous diagnosis of lupusrelated hemophagocytic syndrome (HS) in a patient with VL. A 55-year-old woman originating from the south of France presented with a 2-month history of weight loss, fever, and pancytopenia. Her medical history was remarkable for a remote pulmonary tuberculosis, a Hashimoto thyroiditis, nonalcoholic steatohepatitis, and nonactive hepatitis B virus infection. Since September 2005, she was complaining of myalgia, wrist, and proximal interphalangeal arthralgia without synovitis, and Raynaud phenomenon. She denied sicca syndrome, photosensitivity, or skin rash. Physical examination was normal at that time. Laboratory findings were positive for antinuclear antibodies (ANA) (1/640, homogeneous pattern), with positive antidoublestranded DNA antibodies (antidsDNA, using Crithidia luciliae 1/10). C-reactive protein and blood count were normal except for a mild leukopenia. Rheumatoid factor was negative, but anticyclic citrullinated peptide testing was positive. Standard radiographs of both hands were unremarkable. A presumptive diagnosis of articular lupus erythematosus was considered. Nonsteroidal anti-inflammatory drugs were ineffective, and the patient was secondarily briefly treated with prednisone. She was admitted in January 2007 because of a 10 kg weight loss, spiking fever (up to 39°C), fatigue, and dry cough. Physical examination revealed moderate hepatomegaly and splenomegaly. Laboratory tests showed hemoglobin 11.2 g/dL, leukocytes 1,600/ L with neutrophils 980/ L and lymphocytes 410/ L, platelets 125,000/ L, Creactive protein 54 mg/L, ferritin 5,000 g/L, triglyceride serum level 3.7 g/L (N 1.8), elevated serum transaminase levels (4 N), estimated creatinine clearance of 53 mL/min, mild proteinuria (0.6 g/24 hours) without hematuria, and normal serum level of gammaglobulin. Blood and sputum bacterial and mycobacterial cultures were negative. Viral serologic tests including HIV and hepatitis B PCR testing were negative. ANA titer was 1/1000 (both speckled and homogenous pattern), antidsDNA title was 1/54 (by ELISA; negative by indirect immunofluorescence assay), and auto-antibodies against SSB and RNP were detected. Auto-antibodies against Sm, SSA, Scl-70, JO1, and neutrophil cytoplasm were absent. Isolated lupus anticoagulant was detected (anticardiolipin and anti2GPI antibodies were absent). Serum complement level was normal. Two bone marrow aspirations and biopsy did not show evidence of infectious agent, hemophagocytosis, or malignancy. Bone marrow culture for mycobacterium tuberculosis was negative. Serological test and culture for leishmaniasis were not performed at that time. Thoracic and abdominal CT scan confirmed hepatomegaly and splenomegaly, without lymph node enlargement. Fever persisted, pancytopenia, and hepatosplenomegaly became worse. A lupus-related HS was suspected but could not be demonstrated (negative bone marrow aspiration). Methylprednisolone pulse and then intravenous immunoglobulins (1 g/kg daily for 2 days) were ineffective. Intravenous etoposide (150 mg/ m) was then administered with a dramatic effect in 24 hours. Over the next 2 months, intravenous cyclophosphamide (0.6 g/m/ mo), hydroxychloroquine (400 mg daily), and prednisone (1 mg/kg daily) were added. Two suspected HS relapse with fever, pancytopenia, hyperferritinemia (up to 18,900 g/L), hypertriglyceridemia (up to 7.8 g/L), elevated liver enzymes, spleen and liver enlargement were treated with new etoposide pulses. In May 2007, at the time of the second suspected HS relapse, the general status was poor. ANA titer was 1/500 and antidsDNA was negative. Splenectomy and liver biopsy were performed. Histologic findings showed numerous intraand extracellular Leishmania amastigotes with signs of hemophagocytosis, both in the liver and spleen specimens (Figure 1). Testing for leishmaniasis infection was positive in blood, spleen, and liver using PCR, and culture revealed Leishmania infantum species. Retrospectively, serological testing for Leishmania antibodies and PCR test in the blood revealed that the patient had positive results since her initial admission, before intensification of immunosuppressive therapy. The patient was treated by intravenous liposomal amphotericin B (4 mg/kg/d, days 1–5 and 10 and then every week for 4 weeks). The fever disappeared within 24 hours, blood count and CRP normalized within 5 days, and detection of Leishmania by PCR was negative after 2 weeks. All immunosuppressive drugs were discontinued and prednisone rapidly tapered. Thirty months after amphotericin B therapy was completed, the patient was asymptomatic; ANA titer remained positive (1/500), without any specificity. L. infantum produces both cutaneous and VL, and is endemic in the South-East of France. The parasite invades and grows up in reticuloendothelial cells, which then rupture and release the organism into the bloodstream. The incubation period for VL varies from months to years, and during this time the parasite multiplies in the reticuloendothelial system, including the liver, the spleen, and the bone marrow. Underlying factors such as HIV coinfection, malnutrition, or treatment with corticosteroids or immunosuppressive drugs may lead to disease reactivation, which explains that VL may also occur in patients with SLE as an opportunistic infection and mimic a SLE flare as it has been previously reported in 11 patients. FIGURE 1. Spleen biopsy showing intraand extracellular Leishmania amastigotes within macrophages (RAL reagent 100).

Chronic lymphocytic leukaemia responsive to vitamin D administration

Chadi Al-Nawakil Sophie Park Nicolas Chapuis Francois Dreyfus Tali-Anne Szwebel Laure Gibault Thierry Molina Olivier Hermine Didier Bouscary Jerome Tamburini Université Paris Descartes, Service d’Hématologie Clinique, Groupe Hospitalier Cochin-Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris (AP-HP), Service d’Hématologie Biologique, Groupe Hospitalier CochinHôtel-Dieu, (AP-HP), Service de Médecine Interne, Groupe Hospitalier Cochin-Hôtel-Dieu, Site Hôtel-Dieu (AP-HP), Service d’anatomie pathologique, Groupe Hospitalier Cochin-Hôtel-Dieu, site Cochin, (AP-HP), Service d’anatomie pathologique, Groupe Hospitalier Cochin-Hôtel-Dieu, site Hôtel-Dieu, (AP-HP), and Service d’Hématologie Clinique, Groupe Hospitalier Necker-Enfants Malades (AP-HP), Paris, France. E-mail: jerome.tamburini@cch.aphp.fr

Endocardite marastique et adénocarcinome gastrique

We report a 74-year-old woman with acute heart failure and recurrent ischemic strokes as the presenting features of a nonbacterial thrombotic endocarditis complicating a gastric adenocarcinoma. The treatment only allowed a few months remission. Diagnosis of nonbacterial thrombotic endocarditis is rarely obtained while the patient is alive. Coagulation abnormalities due to the tumoral process are responsible of the valvular thrombotic process. Anticoagulation with heparin is recommended. Valvular surgery remains controversial.

Cas cliniqueEndocardite marastique et adénocarcinome gastriqueNonbacterial thrombotic endocarditis and gastric carcinoma

We report a 74-year-old woman with acute heart failure and recurrent ischemic strokes as the presenting features of a nonbacterial thrombotic endocarditis complicating a gastric adenocarcinoma. The treatment only allowed a few months remission. Diagnosis of nonbacterial thrombotic endocarditis is rarely obtained while the patient is alive. Coagulation abnormalities due to the tumoral process are responsible of the valvular thrombotic process. Anticoagulation with heparin is recommended. Valvular surgery remains controversial.

Recherche sur les pratiques : un enjeu pour la médecine interne

B. Goichot a,∗, P. Arlet b, J.-F. Bergmann c, L. Capron d, G. Grateau e, J. Pouchot d a Service de médecine interne et nutrition, hôpital de Hautepierre, hôpitaux universitaires de Strasbourg, avenue Molière, 67098 Strasbourg cedex, France b Service de médecine interne, hôpital La-Grave, hôpitaux de Toulouse, 31059 Toulouse cedex 9, France c Service de médecine interne A, hôpital Lariboisière, AP-HP, 75010 Paris, France d Service de médecine interne, hôpital européen Georges-Pompidou, AP-HP, 75908 Paris cedex 15, France e Service de médecine interne, CHU Tenon (AP–HP), 4, rue de la Chine, 75020 Paris, France