[A fatal septic shock due to Capnocytophaga canimorsus and review of literature]. / Infection fulminante fatale à Capnocytophaga canimorsus : à propos d'un cas et revue de la littérature.

INTRODUCTION: Capnocytophaga canimorsus is a Gram-negative bacterium present in normal dogs and cats mouths. It can be responsible for septic shocks after dog or cat bite, especially in asplenic patients. CASE REPORT: We report here a case of C. canimorsus infection rapidly presenting as a multiple organ dysfonction syndrome in an immunocompetent 54 years old patient, who lives near a dog, without any sign of bite. The evolution was a rapidly fatal fulminant septic shock. CONCLUSION: Among patients with a septic shock of unknown etiology, fatal evolution due to C. canimorsus should be avoided by systematic use of early antibiotherapy with amoxicilline and clavulanic acid, especially in patients who live near a pet, even if they are immunocompetent.

[Diagnostic workup in front of an atypical non hemolytic anemia]. / Démarche diagnostique devant une anémie « non hémolytique ¼ sans étiologie apparente.

The most potential causes of "non hemolytic" anemias are iron, folate or vitamin B12 deficiencies, severe renal impairment, endocrine diseases, inflammation and medullary disorders. In a non-exceptionnal way no cause is found, sometimes because of a wrong interpretation of analysis results and sometimes because of a little known etiology. The goal of this review is to point out analytical difficulties and to remember some rarer etiologies.

[Two cases of myeloid sarcomas with review of literature]. / Sarcome granulocytaire : à propos de 2 cas et revue de la littérature.

INTRODUCTION: Myeloid sarcomas are uncommon proliferations of immature myeloid cells occurring in any extramedullary organ. We report here two cases of myeloid sarcomas in patients with, respectively, a polycythemia vera and a myelodysplastic syndrome. CASE REPORTS: The first is an 81-year-old woman who presented with osteolytic lesions. Diagnosis has been highlighted using anatomopathological study after bone marrow biopsy, but it was delayed because of a very localized basin lesion and few positive myeloid markers. The second patient is an 86-year-old man who presented with pancytopenia and several lymph nodes. Lymph node cytology failed because of the rarity of blast cells. Diagnosis was done after anatomopathological study on lymph node biopsy which revealed a localized form of myeloid sarcoma. CONCLUSION: The diagnosis of myeloid sarcoma must be considered when unusual tumors occur in patients with a chronic myeloid disease. In that case, therapeutic options are those of an acute myeloid leukemia.

The presence of cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA) in the course of subacute bacterial endocarditis with glomerular involvement, coincidence or association?

Antineutrophil cytoplasmic antibodies positivity with cytoplasmic pattern (C-ANCA) and proteinase-3 (PR-3) specificity was found in two patients with both subacute bacterial endocarditis (SBE) and glomerular involvement. Renal biopsy showed membranoproliferative glomerulonephritis in one case and focal segmental glomerulonephritis in the second case. Immunofluorescence study showed granular immune deposits in both cases evocating immune complex glomerulonephritis. Renal and biological manifestations disappeared with clinical improvement secondary to antibiotherapy. Physicians have to consider the possible occurrence of such C-PR-3 ANCA, claimed to be specific markers for Wegener's granulomatosis, in infectious diseases such as SBE. Hence we focus on the necessity of performing a renal biopsy with light microscopy and immunofluorescence studies in all patients with ANCA associated glomerular disease.

C-1-inhibitor binding monoclonal immunoglobins in three patients with acquired angioneurotic edema.

The syndrome of acquired angioneurotic edema (AAE) is characterized by the adult onset of angioedema, the lack of evidence for inheritance of the disorder, and the frequent association of the C1-inhibitor (C1-INH) deficiency with lymphoproliferative or other malignant diseases. Recently, a new type of AAE (type II AAE) has been described. The two major biologic differences of this new syndrome compared with all other previously reported AAE cases (type I AAE) are the presence in patients' sera of both anti-C1-INH autoantibodies, often monoclonal, and a circulating low molecular weight (95 kd) C1-INH protein. From the clinical point of view, the absence of underlying lymphoproliferative disease is the hallmark of type II AAE compared with type I AAE. However, the distinction between type I and type II AAE may not be so clear-cut. We report three patients with monoclonal gammopathies and AAE for whom the initial diagnosis was type I AAE. The demonstration by ELISA of the C1-INH binding ability of their monoclonal immunoglobulins in addition to the presence of 95 kd C1-INH protein enables us to change the diagnosis to type II AAE. From the therapeutic point of view, it is crucial to detect the anti-C1-INH antibody and to analyze the C1-INH size to distinguish type I and type II AAE, especially if patients have a monoclonal gammopathy, to give the appropriate treatment (attenuated androgens vs immunosuppressive regimen, respectively) to prevent a fatal outcome.

Non-coordinated biosynthesis of early complement components in a deficiency of complement proteins C1r and C1s.

We report on a 60-year-old woman with systemic lupus erythematosus and a total (95%) C1r and a partial (36%) C1s deficiency. The patient complained about cutaneous lesions on forearms and legs without other systemic involvement. Elevated anti-nuclear, anti-native DNA and anti-SSA antibodies were present. The finding of persistently depressed levels of haemolytic complement activity (CH50) on both serum and plasma, associated with normal levels of C3, C4 and C2 components, and normal alternative pathway haemolytic activity showed a deficiency of an early component of the classical pathway. Indeed C1r component was below the limits of detection whereas C1s component was lowered (36%). The depressed CH50 was only corrected by purified C1r. Biosynthesis of C1r and C1s by patient's monocytes was spontaneously normal but not up-regulated by interferon-gamma for C1r alone, whereas the biosynthesis of C1s, but also of interleukin-6, was increased, indicating a specific disregulation of C1r. The deficiency was associated with a lupus syndrome and a fatal assumed septic shock. This is in agreement with other reported cases.

[Detection of anti-neutrophil cytoplasmic antibodies with proteinase 3 specificity by immunoblotting]. / Détection des anticorps anti-cytoplasme des polynucléaires neutrophiles à spécificité anti-protéinase 3 par immunoempreintes.

Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies mainly directed against alpha granules' components (especially proteinase 3 (PR 3) and myeloperoxidase (MPO). They are usually detected by indirect immunofluorescence (IIF) giving essentially two staining patterns, cytoplasmic and perinuclear. Nevertheless the IIF method does not allow to precise the true specificity of ANCA. From now on a better classification of systemic vasculitis requires such a determination. This can be done only by solid phase tests that require to be reliable, highly purified antigen, and, from a practical point of view, only a MPO-ELISA is currently available. We report on our experience with Western blot analysis of 67 IIF-ANCA positive sera. Using Western blot analysis to characterize ANCA specificity is not so easy as in the case of antibodies directed against extractable nuclear antigens: only PR 3 ANCA detection could be done reproducibly. PR 3 ANCA are mainly detected in the c-ACPN positive sera of patients with Wegener's granylomatosis. Nevertheless using both MPO-ELISA and PR 3 blot seems to increase the frequency of serum containing the two types of ANCA (anti PR 3 and anti MPO).

[Autoantibodies against the Golgi apparatus]. / Les autoanticorps dirigés contre l'appareil de Golgi.

Anti-Golgi autoantibodies were first reported 10 years ago. They are routinely detected by standard immunofluorescence whereas other methods such as immunoblotting or immunoelectron microscopy have provided some informations relating to the autoantigens that they recognize. From a clinical point of view, a distinction is appropriate between antibodies occurring at low titer in patients with some viral infections as well as in normal subjects, and antibodies of high titers found in association with autoimmune diseases such as Sjögren's syndrome or systemic lupus erythematosus. An associated liver dysfunction is also often noticed. Anti-Golgi autoantibodies are polyclonal and often mainly of the IgG isotype. In each case studied by immunoelectron microscopy, the recognized molecules were exclusively located on membranes of several cisternae. Although the real nature remains unknown, molecular weights of some autoantigens begin to be ascertained: bands of 230, 150 and 79 kDa have been revealed by different sera when tested by immunoblotting. Beside eventual implications in the field of pathogenesis, the study of this new kind of autoantibodies, based on the description of more sera and patients, might help to characterize some particular subsets of patients.

Golgi autoantibodies and autoantigens.

Autoantibodies directed against cellular constituents rarely react with antigens localized in the Golgi apparatus and little information is available regarding these particular antibodies. Although thousands of samples have been examined for autoantibodies in our laboratory on a routine basis, only three human sera with anti-Golgi antibodies could be studied. Using pre-embedding immunoelectron microscopy we have demonstrated that these sera have antibodies reacting with antigens located in the Golgi apparatus. The reaction product was exclusively located on cisternal and vesicular Golgi membranes. No intraluminal staining was seen and some saccules were negative. No specificity for a peculiar tissue or cell line was noted, suggesting that the targets or these autoantibodies are evolutionarily conserved. The F(ab')2 fragments retained full binding capacity in indirect immunofluorescence experiments, confirming true antibody activity. When tested by immunoblotting, the three sera reacted with different antigens with relative molecular weights of respectively 230, 150 and 80 kDa. The antigens recognized by anti-Golgi antibodies in two of the three sera were insensitive to trypsin degradation. Together, these results suggest that a set of different autoantigens are recognized by sera from various patients.

Anti-myeloperoxidase antibodies and associated diseases.

Thirty five (41%) sera presented anti MPO specificity, 26 of them (74%) having a p-ANCA pattern. They were present in patients with vasculitis and isolated or predominant renal involvement, but also in 24% of Wegener patients.

[Role of the titration of anti-neutrophil cytoplasmic antibodies in therapeutic follow-up of patients with systemic vasculitis]. / Place du titrage des anticorps anticytoplasme des polynucléaires neutrophiles dans le suivi thérapeutique des patients atteints de vascularite systémique.

We studied clinical and biological data of 18 patients presenting ANCA associated diseases for 16 months at least. Five relapses were preceded by ANCA elevation, 1 relapse was not. Four transient elevations were noted without any clinical event. We think ANCA level elevation by itself is not enough for deciding therapy intensification, clinical data are necessary for doing so.