Thoracic lymphadenopathies in diffuse systemic sclerosis: an observational study on 48 patients using computed tomography.

BACKGROUND: Thoracic multidetector computed tomography (MDCT) is essential for the detection of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). Thoracic MDCT assessment can reveal the presence of thoracic lymphadenopathies (LAP) whose signification remains uncertain. The purpose of the study was to describe the characteristics and to assess the significance of thoracic LAP in patients with diffuse SSc. METHODS: We conducted a monocentric observational study on adult patients with diffuse SSc, and collected general patient and first thoracic MDCT characteristics, PET-CT and outcome data. Comparisons were made between patients with and without thoracic LAP. RESULTS: Forty-eight patients were included. There were 30 patients (62.5%) with an ILD and 23 (48%) with at least one thoracic LAP on the first MDCT assessment. Median number per patient of thoracic LAP was 3 [1-8], with a mean size of 11.7 ± 1.7 mm, mainly located in right para-tracheal area (22.8% of the total number of LAP), right hilar area (20.3%), left hilar area (6.5%), and sub-carinal area (15.2%). PET-CT showed lymph node hypermetabolism in 11/15 patients (73.3%) with mean SUVmax at 4 ± 1.3. There were significantly more males (p = 0.002) and more patients exposed to silica (p = 0.001) in patients with thoracic LAP. ILD was significantly more extended according to Goh score (p = 0.03), and using semi-quantitative score for mixed ground-glass reticulation (p = 0.01) and global abnormalities (p = 0.03) in patients with thoracic LAP and ILD. Thirteen patients (27.1%) died during follow-up without significant difference according to the presence or not of thoracic LAP (p = 0.15). There was also no significant difference concerning immunosuppressive treatment initiation (p = 0.17). CONCLUSIONS: Thoracic LAP are common in diffuse SSc and are generally multiple, not bulky, moderately hypermetabolic, and located at the base of the mediastinum lymph node chains. Their presence correlates with the extent of ILD. In absence of ILD, thoracic LAP presence seems to be often explained by silica exposure. TRIAL REGISTRATION: NA.

Treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by skin and visceral fibrosis, vascular hyperreactivity and obliterative vasculopathy. Some of its complications such as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH) and heart involvement can be life-threatening and are associated with a high mortality and a poor prognosis. Many clinical trials were carried out in order to improve the survival and prognosis of SSc patients. The management of SSc is based on the frequent and regular assessment of the potential organ damage, and if present, the establishment of graduated pharmacological therapeutic strategies, associated with non-pharmacological procedures. Several randomized clinical trials have showed significant positive outcomes regarding some specific involvements. Many advances have been made, especially in the field of targeted therapies and personalized medicine, based on specific characteristics of the patient and the SSc.

Pathophysiology of systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vascular remodeling, fibroblast activation and extra-cellular matrix production in excess and autoimmunity. Environmental factors including mainly silica and solvents have been assumed to contribute to the development of SSc, together with genetic factors including gene variants implicated in innate immunity such as IRF5 and STAT4, and epigenetic factors including histone post-translational modifications, DNA hypomethylation, and microRNAs or long- non coding RNAs system were reported to participate in immune activation and fibrosis processes in patients with SSc. A number of animal models of SSc have been set up over the years, including genetic and induced SSc models. These models, together with data obtained from human SSc patients, contributed to better understand the mechanisms contributing to vasculopathy and fibrosis. Alongside the pathophysiological process of SSc, several cellular and molecular actors are involved, such as dysregulations in the innate and adaptive immune cells, of the fibroblast, the implication of pro-inflammatory and pro-fibrosing signaling pathways such as the Wnt, TGF-ß pathways or other cytokines, with a strong imprint of oxidative stress. The whole lead to the overactivity of the fibroblast with genetic dysregulation, apoptosis defect, hyperproduction of elements of extracellular matrix, and finally the phenomena of vasculopathy and fibrosis. These advances contribute to open new therapeutic areas through the design of biologics and small molecules.

Deleterious neurological impact of diagnostic delay in immune-mediated thrombotic thrombocytopenic purpura.

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare life-threatening thrombotic microangiopathy requiring urgent therapeutic plasma exchange (TPE). However, the exact impact of a slight delay in TPE initiation on the subsequent patients' outcome is still controversial. AIM: We aimed to study the frequency, short-term neurological consequences, and determinants of diagnostic delay in iTTP. METHODS: We conducted a retrospective monocentric study including patients with a first acute episode of iTTP (2005-2020) classified into 2 groups: delayed (>24h from first hospital visit, group 1) and immediate diagnosis (≤24h, group 2). RESULTS: Among 42 evaluated patients, 38 were included. Eighteen cases (47%) had a delayed diagnosis (median: 5 days). The main misdiagnosis was immune thrombocytopenia (67%). The mortality rate was 5% (1 death in each group). Neurological events (stroke/TIA, seizure, altered mental status) occurred in 67% vs 30% patients in group 1 and 2, respectively (p = 0.04). Two patients in group 1 exhibited neurological sequelae. The hospital length of stay was longer in group 1 (p = 0.02). At the first hospital evaluation, potential alternative causes of thrombocytopenia were more prevalent in group 1 (33% vs 5%, p = 0.04). Anemia was less frequent in group 1 (67% vs 95%, p = 0.04). All patients had undetectable haptoglobin levels. By contrast, 26% of schistocytes counts were <1%, mostly in group 1 (62% vs 11%, p = 0.01). CONCLUSION: Diagnostic delay is highly prevalent in iTTP, with a significant impact on short-term neurological outcome. In patients with profound thrombocytopenia, the thorough search for signs of incipient organ dysfunction, systematic hemolysis workup, and proper interpretation of schistocytes count are the key elements of early diagnosis of TTP.