[Scleroderma renal crisis].

Scleroderma renal crisis (SRC) occurs in patients with systemic sclerosis (SSc) and is defined by otherwise unexplained rapidly progressive renal insufficiency associated with oliguria or rapidly progressive arterial hypertension or both. SRC is a rare and severe complication of SSc, most often encountered during the first 4 years of disease, almost only in patients with diffuse SSc. Factors predicting SRC were identified, including high-dose corticosteroid administration.

[Interstitial lung disease in systemic sclerosis].

Interstitial lung diseases (ILD) associated with systemic sclerosis (SSc) are mainly encountered in patients with diffuse disease, although they may also be seen in patients with limited cutaneous SSc. ILD screening must be performed regularly, with high-resolution computed tomography and pulmonary function tests (TLCO). Up to 75% of patients with diffuse SSc develop a form of ILD.

[Systemic sclerosis: pathophysiology of a multifaceted disease].

Systemic sclerosis is a rare disease characterized by vascular hyperreactivity and collagen deposition. Endothelial cell, fibroblast and lymphocyte abnormalities have been reported in systemic sclerosis. Fibroblast dysfunction is characterized by uncontrolled activation of the transforming growth factor-beta (TGF-beta) pathway and excess synthesis of both connective tissue growth factor (CTGF) and free radicals.

Sjogren's syndrome is associated with and not secondary to systemic sclerosis.

Objectives: When Sjögren's syndrome (SS) is secondary to rheumatoid arthritis, the sicca syndrome is less serious and anti-SSA/SSB antibodies are found less frequently than in primary SS (pSS). When SS is associated with systemic lupus erythematosus, clinical and serological patterns are similar to those of pSS. We aimed to determine whether SS, accompanying systemic sclerosis (SSc), could be considered secondary to or associated with SSc and whether the coexistence of both modifies the severity and the outcome of each disease.

[Diagnosis of primary immunodeficiency in adult patients].

The molecular bases of approximately one hundred primary immune deficiencies (PID) have been identified over the last 15 years. In adults, the diagnosis of PID cannot be evoked before ruling out acquired immunodeficiencies, which are far more frequent. The search for specific PIDs may be oriented by the type of agent responsible for severe and/or recurrent infection.

[Diagnosis of lymphocytopenia].

Lymphopenia is defined as a peripheral lymphocyte count lower than 1500/mm3 in adults and 4500/mm3 in children younger than eight months of age. We propose a classification of lymphopenia according to the mechanism involved: lymphocyte production defects, including primary immune deficiencies and immune deficiencies secondary to malnutrition or zinc deprivation; excess catabolism, due to causes including radiotherapy, chemotherapy, immunosuppressive therapy, HIV infection, and systemic lupus erythematosus; abnormal lymphocyte trapping, including mainly splenomegaly, certain viral infections, septic shock, extended burns, systemic granulomatosis, and corticosteroids; other causes of lymphocytopenia, with mechanisms that remain poorly understood: ethnicity (Ethiopians), lymphoma, renal insufficiency, and idiopathic CD4 lymphocytopenia.

Marked efficacy of a therapeutic strategy associating prednisone and plasma exchange followed by rituximab in two patients with refractory myopathy associated with antibodies to the signal recognition particle (SRP).

We report two patients with myopathy associated with anti-signal recognition particle Ab, refractory to conventional therapy, who were treated with prednisone and plasma exchange, followed by rituximab. A marked response was observed in both patients, with partial to complete recovery of muscle strength, which was sustained.

[Indications for intravenous immunoglobulins].

Intravenous immunoglobulins (IgIV) are therapeutic preparations of polyclonal human IgG, obtained from a pool of plasma from more than 1000 healthy donors. This article discusses only some of the recognized indications (Group I) and some of those currently under evaluation (Group II) for the treatment of autoimmune and systemic inflammatory diseases. Perspectives for IgIV use are approached through three diseases, each providing a different model of immune system modulation: ocular cicatricial pemphigoid, where an autoimmune reaction is modulated; alloimmunization of chronic hemodialysis patients, where alloreactivity can be modulated; and streptococcal toxic shock, where anti-infectious immunity may be modulated.

[Mandibular resorption, an underdiagnosed manifestation of systemic scleroderma].

Introduction: Systemic sclerosis (SSc) is sometimes associated with bone resorption that can reach the mandible.

Cases: We report here the cases of two women (aged 47 and 57 years) with SSc diagnosed 13 and 26 years earlier, respectively. Both presented marked mandibular bone resorption.

[Bosentan for treatment of active digital ulcers in patients with systemic sclerosis].

Objectives: To describe the effect of bosentan and its dual inhibition of endothelin-1 ETA and ETB receptors on digital ulcers in patients with systemic sclerosis (SSc).

Methods: Patients receiving bosentan for SSc-related digital ulcers were identified in eight centers, and their characteristics and follow-up were recorded.

Results: Nine (six with diffuse and three with limited cutaneous forms of SSc) patients (median age: 54 years) had received bosentan for digital ulcers.

Anti-endothelial cell antibodies from patients with limited cutaneous systemic sclerosis bind to centromeric protein B (CENP-B).

By using a quantitative immunoblotting technique on protein extracts of human macrovascular and microvascular endothelial cells, we have analyzed the self-reactive repertoires of IgG from 20 patients with limited cutaneous SSc, 40 patients with diffuse SSc and 60 age- and sex-matched healthy controls. Serum IgG from 15/20 patients with limited cutaneous SSc and anti-centromere antibodies bound to at least one of the two 75- and 85-kDa protein bands in the different endothelial cell extracts, whereas IgG from healthy controls or patients with diffuse SSc did not. N-terminal sequencing of the 75- and 85-kDa bands identified CENP-B as the sole antigen in both bands.

Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study.

Objective: Screening allows for early management of pulmonary arterial hypertension (PAH), a severe complication of systemic sclerosis (SSc). Since no consensus has been reached on the method and criteria for optimal screening, we sought to develop an algorithm based on symptoms, Doppler echocardiography, and right heart catheterization (RHC) for application to a nationwide multicenter SSc population in France.

Methods: This prospective study was conducted from September 2002 to July 2003 by experts at 21 SSc centers.

A mimic of p21WAF1/CIP1 ameliorates murine lupus.

Systemic lupus erythematosus (SLE) is a progressive autoimmune disease characterized by the production of high levels of affinity-matured IgG autoantibodies to dsDNA and, possibly, visceral involvement. Pathogenic autoantibodies result from the activation and proliferation of autoreactive T and B lymphocytes stimulated by epitopes borne by nucleosomal histones. To inhibit the proliferation of autoreactive cells and abrogate the development of SLE, a novel tool, cell cycle inhibiting peptide therapy, was used.

Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome.

Background: Since testing for antineutrophil cytoplasmic antibodies (ANCA) became available for routine evaluation, no large homogeneous cohort of patients with the Churg-Strauss syndrome has been studied.

Objective: To define the clinical and biological characteristics of newly diagnosed Churg-Strauss syndrome, according to the presence or absence of ANCA.

Design: Cross-sectional analysis of manifestations of participants who were enrolled in treatment trials between December 1995 and December 2002.

Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients.

Although combining corticosteroids and cyclophosphamide has greatly improved the prognoses of severe necrotizing vasculitides, some patients continue to have fulminating disease and die within the first year of diagnosis. To evaluate the characteristics of these patients, we retrospectively studied the files of 60 patients who died within the first year (20 patients with hepatitis B virus-associated polyarteritis nodosa [HBV-PAN], 18 with non-HBV PAN, 13 with microscopic polyangiitis [MPA], and 9 with Churg-Strauss syndrome [CSS]) and 535 first-year survivors (89 patients with HBV-PAN, 182 with non-HBV PAN, 140 with MPA, and 124 with CSS), 85 of whom died during a mean follow-up of 6.4 years.

[Interstitial lung disease in connective tissue disorders].

Interstitial lung diseases (ILD) associated with connective tissue disorders differ from idiopathic ILD in several aspects, although most of them are comparable. In most patients, ILD occurs during the course, or at the time of diagnosis of connective tissue disease. Opportunistic pulmonary infections, together with adverse effects of treatment should always be discussed.

[Intravenous immunoglobulin therapy].

Intravenous immunoglobulins (IVIg) are therapeutic preparations of normal human IgG that are obtained from pools of healthy blood donors. They can be used at low dose in the substitutive therapy of patients with primary or secondary immune deficiencies, or at high dose as an immunomodulatory agent in a large number of autoimmune and/or systemic inflammatory diseases, particularly in hematologic or neurologic diseases. Tolerance to IVIg is excellent in most of the cases and the risk of transmission of an infectious agent is only theoretical.

Churg-strauss syndrome.

First described in 1951 as an allergic and granulomatous angiitis, Churg-Strauss syndrome (CSS) is a small-vessel vasculitis. Mean age at the time of diagnosis is approximately 50 years, with a sex ratio around 1. Asthma is the central feature of CSS and precedes the systemic manifestations in almost all cases, whereas 70% of the patients have maxillary sinusitis, allergic rhinitis, and/or sinus polyposis.

Intravenous immunoglobulins in autoimmune- or parvovirus B19-mediated pure red-cell aplasia.

Pure red-cell aplasia (PRCA) is defined as the absence of mature erythroid precursors in a bone marrow that otherwise exhibit normal cellularity. Acquired PRCA may occur in association with neoplasms (such as lymphoproliferative disorders), thymoma, autoimmune disorders, pregnancy, or as a consequence of chronic human parvovirus B19 (B19) infection in an immunologically incompetent host. PRCA may also develop after exposure to drugs (erythropoietin or tacrolimus).

Analysis of autoantibody repertoires in small- and medium-sized vessels vasculitides. Evidence for specific perturbations in polyarteritis nodosa, microscopic polyangiitis, Churg-Strauss syndrome and Wegener's granulomatosis.

In order to identify new antibody reactivities, we have used a quantitative immunoblotting technique on extracts of normal human tissues to analyze the repertoires of serum IgM, serum IgG and purified IgG autoantibodies of patients with systemic vasculitides. Patients fulfilled the American College of Rheumatology and Chapel Hill criteria for the diagnosis of polyarteritis nodosa (PAN) (n=8), PAN related to hepatitis B virus (HBV) infection (n=5), Wegener's granulomatosis (WG) (n=6), microscopic polyangiitis (MPA) (n=18) or Churg-Strauss syndrome (CSS) (n=8). Sera from patients with chronic HBV infection without PAN (n=5) and age- and gender-matched healthy individuals (n=45) were used as controls.

Anti-annexin V antibodies: are they prothrombotic?

Annexin V inhibits prothrombin activation and is able to prevent thrombus formation under normal venous and arterial blood flow conditions. Antibodies to annexin V have been identified in association with several pathological conditions, including systemic lupus erythematosus (SLE) with or without anti-phospholipid syndrome, recurrent spontaneous abortions and systemic sclerosis (SSc). These antibodies are suspected to exert a detrimental role and interfere with annexin V function.

[Immunomodulatory effects of intravenous immunoglobulins].

Intravenous immunoglobulins (IVIg) are therapeutic preparations of normal human IgG obtained from pools of more than 1000 healthy blood donors. They are currently used in the treatment of a wide range of auto-immune diseases, whether associated with auto-antibodies or auto-reactive T lymphocytes, as well as in the treatment of systemic inflammatory diseases. Several mechanisms of action have been identified during the last 20 years, including: (i) modulation of Fc receptors expression on leukocytes and endothelial cells; (ii) interaction with complement proteins; (iii) modulation of cytokines and chemokines synthesis and release; (iv) modulation of cell proliferation and apoptosis; (v) remyelinisation; (vi) neutralisation of circulating autoantibodies; (vii) selection of repertoires of B and T lymphocytes; (viii) interaction with other cell-surface molecules on lymphocytes and monocytes; (ix) corticosteroid sparing.

Intrasinusoidal cytotoxic CD8+ T cells in nodular regenerative hyperplasia of the liver.

Diffuse nodular regenerative hyperplasia (NRH) of the liver is an acquired architectural disturbance that can lead to portal hypertension. Although frequently associated with autoimmune or hematologic malignancies, its exact pathogenesis remains largely unknown. We observed CD8+ cytotoxic T cells in the liver sinusoids of 14 of 44 NRH patients and explored possible relationships between these lymphocytes and vascular damage.