Diagnostic and management of life-threatening Adult-Onset Still Disease: a French nationwide multicenter study and systematic literature review.

BACKGROUND: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disorder. A few patients develop organ complications that can be life-threatening. Our objectives were to describe the disease course and phenotype of life-threatening AOSD, including response to therapy and long-term outcome. METHODS: A multicenter case series of intensive care medicine (ICU) patients with life-threatening AOSD and a systematic literature review. RESULTS: Twenty patients were included. ICU admission mostly occurred at disease onset (90%). Disease manifestations included fever (100%), sore throat (65%), skin rash (65%), and arthromyalgia (55%). Serum ferritin was markedly high (median: 29,110 ng/mL). Acute respiratory failure, shock and multiple organ failure occurred in 15 (75%), 10 (50%), and 7 (35%) cases, respectively. Hemophagocytosis was demonstrated in eight cases. Two patients died. Treatment delay was significant. All patients received corticosteroids. Response rate was 50%. As second-line, intravenous immunoglobulins were ineffective. Anakinra was highly effective. After ICU discharge, most patients required additional treatment. Literature analysis included 79 cases of AOSD with organ manifestations, which mainly included reactive hemophagocytic syndrome (42%), acute respiratory failure (34%), and cardiac complications (23%). Response rate to corticosteroids was 68%. Response rates to IVIgs, cyclosporin, and anakinra were 50%, 80%, and 100%, respectively. CONCLUSIONS: AOSD should be recognized as a rare cause of sepsis mimic in patients with fever of unknown origin admitted to the ICU. The diagnosis relies on a few simple clinical clues. Early intensive treatment may be discussed. IVIgs should be abandoned. Long-term prognosis is favorable.

Autoimmunity in common variable immunodeficiency: correlation with lymphocyte phenotype in the French DEFI study.

Common variable immunodeficiency (CVID) is the most frequent clinically expressed primary immunodeficiency in adults and is characterized by primary defective immunoglobulin production. Besides recurrent infectious manifestations, up to 20% of CVID patients develop autoimmune complications. In this study, we took advantages of the French DEFI database to investigate possible correlations between peripheral lymphocyte subpopulations and autoimmune clinical expression in CVID adult patients. In order to analyse homogeneous populations of patients with precise clinical phenotypes, we first focused on patients with autoimmune cytopenia because they represent prototypic autoantibody mediated diseases. In a secondary analysis, we have tested our conclusions including all "autoimmune" CVID patients. We describe one of the largest European studies with 311 CVID patients, including 55 patients with autoimmune cytopenia and 61 patients with clinical or serologic autoimmune expression, excluding autoimmune cytopenia. We clarify previous reports and we confirm a very significant correlation between an increased proportion of CD21(low) B cells and CVID associated autoimmune cytopenia, but independently of the presence of other autoimmune disorders or of splenomegaly. Moreover, in CVID associated autoimmune cytopenia, T cells display an activated phenotype with an increase of HLA-DR and CD95 expression and a decrease in the naïve T cell numbers. Patients with other autoimmune manifestations do not harbour this "T and B cells phenotypic picture". In view of recent findings on CD21(low) B cells in CVID and RA, we suggest that both a restricted subset of B cells and a T cell help are required for a breakdown of B cell tolerance against membrane auto antigens in CVID.

Catastrophic adult-onset Still's disease as a distinct life-threatening clinical subset: case-control study with dimension reduction analysis.

OBJECTIVES: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosing AOSD can be challenging, as disease presentation and clinical course are highly heterogeneous. For unclear reasons, a few patients develop life-threatening complications. Our objective was to determine whether these cases resulted from therapeutic delay or could represent a peculiar AOSD subset. METHODS: We conducted a multicentre retrospective study of 20 AOSD patients with organ failure requiring intensive care unit admission and 41 control AOSD patients without organ failure. Clinico-biological data at hospital admission were explored using supervised analyses and unsupervised dimension reduction analysis (factor analysis of mixed data, FAMD). RESULTS: Disease duration before admission was shorter in patients with life-threatening AOSD (median, 10 vs 20 days, p = 0.007). Disease duration before AOSD therapy initiation also tended to be shorter (median, 24 vs 32 days, p = 0.068). Despite this shorter disease duration, FAMD, hierarchical clustering and univariate analyses showed that these patients exhibited distinctive characteristics at first presentation, including younger age; higher frequency of splenomegaly, liver, cardiac and/or lung involvement; less frequent arthralgia; and higher ferritin level. In multivariate analysis, 3 parameters predicted life-threatening complications: lack of arthralgia, younger age and shorter time between fever onset and hospitalisation. CONCLUSION: This study suggests that life-threatening complications of AOSD occur very early, in a peculiar subset, which we propose to name catastrophic adult-onset Still's disease (CAOSD). Its exact burden may be underestimated and remains to be clarified through large multicentre cohorts. Further studies are needed to identify red flags and define the optimal therapeutic strategy.

B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease.

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by recurrent infections and defective immunoglobulin production. METHODS: The DEFI French national prospective study investigated peripheral T-cell and B-cell compartments in 313 CVID patients grouped according to their clinical phenotype, using flow cytometry. RESULTS: In patients developing infection only (IO), the main B-cell or T-cell abnormalities were a defect in switched memory B cells and a decrease in naive CD4(+) T cells associated with an increase in CD4(+)CD95(+) cells. These abnormalities were more pronounced in patients developing lymphoproliferation (LP), autoimmune cytopenia (AC), or chronic enteropathy (CE). Moreover, LP and AC patients presented an increase in CD21(low) B cells and CD4(+)HLA-DR(+) T cells and a decrease in regulatory T cells. CONCLUSION: In these large series of CVID patients, the major abnormalities of the B-cell and T-cell compartments, although a hallmark of CVID, were only observed in half of the IO patients and were more frequent and severe in patients with additional lymphoproliferative, autoimmune, and digestive complications.

Acute pancreatitis following coronary artery angiography.

Coronary artery angiography has many well-documented complications. Acute pancreatitis is a rarely described complication with potentially life-threatening repercussions. This article reports the case of a woman with acute pancreatitis that occurred within a few minutes after coronary artery angiography. Contrast agent toxicity and cholesterol emboli are the two mechanisms involved in the occurrence of acute pancreatitis after coronary artery angiography.

Thoracic manifestations of primary humoral immunodeficiency: a comprehensive review.

Humoral immunodeficiencies, which are characterized by defective production of antibodies, are the most common types of primary immunodeficiency. Pulmonary changes are present in as many as 60% of patients with humoral immunodeficiency. Chronic changes and recurrent infections in the respiratory airways are the main causes of morbidity and mortality in those affected by a humoral immunodeficiency. Medical imaging, especially computed tomography (CT), plays a crucial role in the initial detection and characterization of changes and in monitoring the response to therapy. The spectrum of abnormalities seen at thoracic imaging includes noninfectious airway disorders, infections, chronic lung diseases, chronic inflammatory conditions (granulomatosis, interstitial pneumonias), and benign and malignant neoplasms. Recognition of characteristic CT and radiographic features, and correlation of those features with clinical and laboratory findings, are necessary to differentiate between the many possible causes of parenchymal and mediastinal disease seen in patients with primary humoral immunodeficiencies.

Chronic meningococcaemia and immunoglobulin A deficiency.

Chronic meningococcaemia is an unusual clinical presentation of Neisseria meningitidis infection. We describe the case of a patient, who presented with total IgA deficiency and partial IgM deficiency with a low switched memory B cells count, suggestive of a borderline form of common variable immunodeficiency (CVID). The role of IgA in the protection against Neisseria meningitidis, and the link between IgA deficiency and CVID are discussed.