Objective
Relapsing polychondritis (RP) is a rare condition characterized by recurrent inflammation of cartilaginous tissue and systemic manifestations. Data on this disease remain scarce. This study ...was undertaken to describe patient characteristics and disease evolution, identify prognostic factors, and define different clinical phenotypes of RP.
Methods
We performed a retrospective study of 142 patients with RP who were seen between 2000 and 2012 in a single center.
Results
Of the 142 patients, 86 (61%) were women. The mean ± SD age at first symptoms was 43.5 ± 15 years. Patients had the following chondritis types: auricular (89%; n = 127), nasal (63%; n = 89), laryngeal (43%; n = 61), tracheobronchial (22%; n = 32), and/orcostochondritis (40%; n = 57). The main other manifestations were articular (69%; n = 98), ophthalmologic (56%; n = 80), audiovestibular (34%; n = 48), cardiac (27%; n = 38), and cutaneous (28%; n = 40). At a mean ± SD followup of 13 ± 9 years, the 5‐ and 10‐year survival rates were 95 ± 2% and 91 ± 3%, respectively. Factors associated with death on multivariable analysis were male sex (P = 0.01), cardiac abnormalities (P = 0.03), and concomitant myelodysplastic syndrome (MDS) (P = 0.004) or another hematologic malignancy (P = 0.01). Cluster analysis revealed that separating patients into 3 groups was clinically relevant, thereby separating patients with associated MDS, those with tracheobronchial involvement, and those without the 2 features in terms of clinical characteristics, therapeutic management, and prognosis.
Conclusion
This large series of patients with definite RP revealed an improvement in survival as compared with previous studies. Factors associated with death were male sex, cardiac involvement, and concomitant hematologic malignancy. We identified 3 distinct phenotypes.
A subset of research in the history of economics is organizational history - i.e. the study of the organizations producing, circulating and applying economic ideas. This article maintains that some ...research questions in organizational history call for quantitative methods because they ask about magnitudes. More precisely, we claim that quantitative methods should complement rather than replace other research methods when the research question is at least partly about magnitudes. We walk the walk with a study of one type of organization, central banks, and of its changing relationship with economic science. Our results point unambiguously toward a growing dominance of central banks in the specialized field of monetary economics. Central banks have swelling research armies, they publish a growing share of the articles in specialized scholarly journals, and these articles tend to have more impact today than the articles produced outside central banks.
We describe myelodysplastic syndrome (MDS)-associated systemic inflammatory and autoimmune diseases (SIADs), their treatments and outcomes and the impact of SIADs on overall survival in a French ...multicentre retrospective study.
In this study, 123 patients with MDS and SIADs were analysed.
Mean age was 70 years (s.d. 13) and the male:female ratio was 2. The SIADs were systemic vasculitis in 39 (32%) cases, CTD in 31 (25%) cases, inflammatory arthritis in 28 (23%) cases, a neutrophilic disorder in 12 (10%) cases and unclassified in 13 cases (11%). The SIADs fulfilled the usual classification criteria in 75 (66%) cases, while complete criteria were not reached in 21 (19%) cases. A significant association was shown between chronic myelomonocytic leukaemia (CMML) and systemic vasculitis (P = 0.0024). One hundred and eighteen (96%) SIAD patients were treated (91% with steroids), with an 83% response to first-line treatment, including 80% for steroids alone. A second-line treatment for SIADs was required for steroid dependence or relapse in 48% of cases. The effect of MDS treatment on SIADs could be assessed in 11 patients treated with azacytidine and SIAD response was achieved in 9/11 (80%) and 6/11 (55%) patients at 3 and 6 months, respectively. Compared with 665 MDS/CMML patients without SIADs, MDS/CMML patients with SIADs were younger (P < 0.01), male (P = 0.03), less often had refractory anaemia with ring sideroblasts (P < 0.01), more often had a poor karyotype (16% vs 11%, P = 0.04) and less frequently belonged to low and intermediate-1 International Prognostic Scoring System categories, but no survival difference was seen between patients with MDS-associated SIADs and without SIADs (P = 0.5).
The spectrum of SIADs associated to MDS is heterogeneous, steroid sensitive, but often steroid dependent.
Immune checkpoint inhibitors (ICIs) are used in several advanced malignancies and may cause various immune-related adverse events (irAEs). Among them, hematological irAEs are less described. Acquired ...amegakaryocytic thrombocytopenia (AAT) is a rare immune hematologic disorder characterized by severe thrombocytopenia and complete absence of megakaryocytes in bone marrow.
Herein, we present the case of a patient in their 40s with metastatic melanoma who developed an AAT after 12 cycles of nivolumab (anti-PD1). His platelet count decreased by ≤5 × 10
/l without other cytopenia. Bone marrow biopsy showed normal cellularity with a complete absence of megakaryocyte and T-CD8+ lymphocyte infiltration. Given the failure of systemic steroids, eltrombopag was started, an oral thrombopoietin receptor agonist (TPO-RA), and his platelet count subsequently increased with complete response.
Four other cases are described on literature with the same features than non-ICI-related AAT. All cases occurred after anti-PD/PD-L1 treatment with a median onset of 5 weeks. The presentation of our case is quite different with delayed cytopenia. Both ciclosporin and TPO-RA seem to be efficient therapies.
TPO-RA could be preferred in oncologic patients, but safety data are still missing to define clear guidelines for immune-related AAT management.
Abstract
Objectives
To characterize lymphocytes dysregulation in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
Methods
Using flow cytometry, we analysed B- ...and T-cell subsets in peripheral blood from 37 untreated patients with active disease (29 GPA and 8 MPA) and 22 healthy controls (HCs).
Results
GPA patients had increased Th2 (1.8 vs 1.0%, P = 0.02), Th9 (1.1 vs 0.2%, P = 0.0007) and Th17 (1.4 vs 0.9%, P = 0.03) cells compared with HC. Patients with MPO-ANCAs had significantly more CD21– B cells than HC or PR3-ANCA patients (6.9 vs 3.3% and 4.4%, P = 0.01). CD69 expressing B cells were significantly higher in GPA and MPA (3.0 and 5.9 vs 1.4%, P = 0.02 and P = 0.03, respectively) compared with HC, whereas B-cell activating factor-receptor expression was decreased in GPA and MPA (median fluorescence intensity ratio 11.8 and 13.7 vs 45.1 in HC, P < 0.0001 and P = 0.003, respectively). Finally, IL-6-producing B cells were increased in GPA vs HC (25.8 vs 14.9%, P < 0.0001) and decreased in MPA vs HC (4.6 vs 14.9%, P = 0.005), whereas TNF-α-producing B cells were lower in both GPA and MPA patients compared with controls (15 and 8.4 vs 30%, P = 0.01 and P = 0.006, respectively).
Conclusion
Skewed T-cell polarization towards Th2, Th9 and Th17 responses characterizes GPA, whereas B-cell populations are dysregulated in both GPA and MPA with an activated phenotype and a decreased B-cell activating factor-receptor expression. Finally, inflammatory B cells producing IL-6 are dramatically increased in GPA, providing an additional mechanism by which rituximab could be effective.
The aim of this study was to describe the efficacy and safety of rituximab and MTX (RTX/MTX) combination therapy in ANCA-associated vasculitides (AAV).
A retrospective French nationwide study was ...conducted in patients with AAV who received RTX/MTX combination therapy for persistently active disease.
Seventeen patients were included. All patients had granulomatosis with polyangiitis (GPA), with positive ANCA in 76% of them, mainly with PR3-ANCA specificity. Sixteen patients (94%) had priorly failed to achieve remission with RTX and 11 (65%) with CYC. Patients had experienced a median of 3 (2-4) flares. Manifestations requiring RTX/MTX combination therapy were subglottic or bronchial stenosis in 6 patients (35%), orbital mass in 6 (35%), disabling ENT involvement in 2 (12%), and epiduritis and pachymeningitis in 1 case (6%) each. The median follow-up duration for the RTX/MTX combination therapy was 11 months (11-26 months). At 6 months, global response had been achieved in 15 patients (88%), including partial response in 11 (65%) and complete response in 4 (24%). At last evaluation, global response had been achieved in 16 patients (94%). Seven patients (41%) experienced severe adverse events (grade 3 or 4), including infections in 4 (24%) and hepatitis in 2 (12%). Combination therapy was withdrawn in 4 patients (24%), but never for safety concerns. In contrast, the MTX dose was decreased in 2 patients (12%) because of adverse events. One patient died of an unknown cause.
RTX/MTX combination therapy could be an effective salvage therapy to treat persistently active GPA with granulomatous manifestations, with an acceptable safety profile.
Sickle cell disease (SCD) is the most frequent inherited disorder in the world. It is caused by a single amino acid mutation on the beta-globin chain, which lead to red blood cell deformation, ...haemolysis, and chronic inflammation. Clinical consequences are vaso-occlusives crisis, acute chest syndrome, thrombosis, infection, and chronic endothelial injury.
Corticosteroids are an old therapeutic class, that are inexpensive and widely available, which can be administered in different forms. Their adverse effects are numerous and well-known. This class could appear to be useful in SCD treatment due to its anti-inflammatory effect. Moreover, corticosteroids remain an essential therapeutic class for many indications, besides SCD. Although specific adverse effects of corticosteroids have been suspected in SCD patients for decades, recent papers has reported strong evidence of specific and severe adverse effects in this population. Based on a literature review, we will discuss pathophysiological considerations, consequences, and practical use of corticosteroids in SCD.
High corticosteroid doses, for any indication , induce vaso-occlusive crises, acute chest syndrome, and re-hospitalization in patients with SCD. There is no evidence of any benefits of corticosteroid use in the SCD acute events. Prevention by hydroxyurea and/or red blood cell transfusion or exchange should be discussed when corticosteroid use is indispensable.
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