Objective
Earlier studies of eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA), with limited patient numbers and followup durations, demonstrated that clinical presentation at ...diagnosis, but not outcome, differed according to antineutrophil cytoplasmic antibody (ANCA) status. This study was undertaken to describe the main characteristics of a larger patient cohort and their long‐term outcomes.
Methods
A retrospective study of EGPA patients in the French Vasculitis Study Group cohort who satisfied the American College of Rheumatology criteria and/or Chapel Hill definitions was conducted. Patient characteristics and outcomes were compared according to ANCA status and year of diagnosis.
Results
We identified 383 patients diagnosed between 1957 and June 2009 (128 33.4% before 1997 or earlier) and followed up for a mean ± SD of 66.8 ± 62.5 months. At diagnosis, their mean ± SD age was 50.3 ± 15.7 years, and 91.1% had asthma (duration 9.3 ± 10.8 years). Main manifestations included peripheral neuropathy (51.4%); ear, nose, and throat (ENT) signs (48.0%); skin lesions (39.7%); lung infiltrates (38.6%); and cardiomyopathy (16.4%). Among the 348 patients tested at diagnosis for ANCA, the 108 ANCA‐positive patients (31.0%) had significantly more frequent ENT manifestations, peripheral neuropathy, and/or renal involvement, but less frequent cardiac manifestations, than the ANCA‐negative patients. Vasculitis relapses occurred in 35.2% of the ANCA‐positive versus 22.5% of the ANCA‐negative patients (P = 0.01), and 5.6% versus 12.5%, respectively, died (P < 0.05). The 5‐year relapse‐free survival rate was 58.1% (95% confidence interval 95% CI 45.6–68.6) for ANCA‐positive and 67.8% (95% CI 59.8–74.5) for ANCA‐negative patients (P = 0.35). Multivariable analysis identified cardiomyopathy, older age, and diagnosis during or prior to 1996 as independent risk factors for death and lower eosinophil count at diagnosis as predictive of relapse.
Conclusion
The characteristics and long‐term outcomes of EGPA patients differ according to their ANCA status. Although EGPA relapses remain frequent, mortality has declined, at least since 1996.
Objective
Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides (AAVs) are rarely revealed by TA ...manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA‐AAV) compared to controls with classic GCA.
Methods
In this retrospective case–control study, the characteristics of patients with TA‐AAV were compared to those of control subjects with classic GCA. Log‐rank test, with hazard ratios (HRs) and 95% confidence intervals (95% CIs), was used to assess the risk of treatment failure.
Results
Fifty patients with TA‐AAV (median age 70 years) were included. Thirty‐three patients (66%) presented with atypical symptoms of GCA (ear, nose, and throat involvement in 32% of patients, and renal, pulmonary, and neurologic involvement in 26%, 20%, and 16% of patients, respectively). Blood samples were screened for ANCAs at the time of disease onset in 33 patients, and results were positive in 88%, leading to a diagnosis of early TA‐AAV in 20 patients. The diagnosis of AAV was delayed a median interval of 15 months in 30 patients. Compared to controls with GCA, patients with TA‐AAV were younger (median age 70 years versus 74 years), were more frequently men (48% versus 30%), and had high frequencies of atypical manifestations and higher C‐reactive protein levels (median 10.8 mg/dl versus 7.0 mg/dl). In patients with TA‐AAV, temporal artery biopsy (TAB) showed fibrinoid necrosis and small branch vasculitis in 23% of patients each, whereas neither of these characteristics was evident in controls with GCA. Treatment failure–free survival was comparable between early TA‐AAV cases and GCA controls, whereas those with delayed TA‐AAV had a significantly higher risk of treatment failure compared to controls (HR 3.85, 95% CI 1.97–7.51; P < 0.0001).
Conclusion
TA‐AAV should be considered diagnostically in cases of atypical manifestations of GCA, refractoriness to glucocorticoid treatment, or early relapse. Analysis of TAB specimens for the detection of small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCAs should be performed in cases of suspected GCA with atypical clinical features and/or evidence of temporal artery abnormalities on TAB.
Summary
Azacitidine can be effective in myelodysplastic syndromes (MDS) associated with inflammatory/autoimmune diseases. Vacuoles, E1 Enzyme, X‐linked, Autoinflammatory, Somatic syndrome (VEXAS) is ...a new monogenic autoinflammatory syndrome caused by somatic ubiquitin‐like modifier‐activating enzyme 1 (UBA1) mutation, often associated with MDS, whose treatment is difficult and not yet codified. Based on a French nationwide registry of 116 patients with VEXAS, we report the efficacy and safety of azacitidine treatment in 11 patients with VEXAS with MDS. Clinical response of VEXAS to azacitidine was achieved in five patients (46%), during 6, 8+, 12, 21, 27+ months respectively, suggesting that azacitidine can be effective in selected patients with VEXAS and associated MDS.
•Borrelia garinii belongs to the B burgdorferi complex•Borrelia infections can be atypical in patients who are immunocompromised•Borrelia serology is often negative in patients treated with ...rituximab•Molecular biology is a valuable diagnostic tool in patients treated with rituximab•Borrelia infection may be associated with various type of lymphoma
We report an atypical Borrelia garinii infection in a patient who was immunocompromised. It was first suspected as a transformation of follicular lymphoma into high-grade lymphoma. Spirochetes were directly observed on a peripheral blood smear and the diagnosis was confirmed using molecular methods. The clinical presentation and the diagnosis are unique and contrast with the cases described in the literature in patients who are immunocompromised.
Sarcoidosis of the spinal cord is a rare disease. The aims of this study are to describe the features of spinal cord sarcoidosis (SCS) and identify prognostic markers. We analyzed 20 patients over a ...20-year period in 8 French hospitals. There were 12 men (60 %), mostly Caucasian (75 %). The median ages at diagnosis of sarcoidosis and myelitis were 34.5 and 37 years, respectively. SCS revealed sarcoidosis in 12 patients (60 %). Eleven patients presented with motor deficit (55 %) and 9 had sphincter dysfunction (45 %). The median initial Edmus Grading Scale (EGS) score was 2.5. The cerebrospinal fluid (CSF) showed elevated protein level (median: 1.00 g/L, interquartile range (IQR) 0.72–1.97), low glucose level (median 2.84 mmol/L, IQR 1.42–3.45), and elevated white cell count (median 22/mm
3
, IQR 6–45). The cervical and thoracic cords were most often affected (90 %). All patients received steroids and an immunosuppressive drug was added in 10 cases (50 %). After a mean follow-up of 52.1 months (range 8–43), 18 patients had partial response (90 %), 7 displayed functional impairment (35 %), and the median final EGS score was 1. Six patients experienced relapse (30 %). There was an association between the initial and the final EGS scores (
p
= 0.006). High CSF protein level showed a trend toward an association with relapse (
p
= 0.076). The spinal cord lesion was often the presenting feature of sarcoidosis. Most patients experienced clinical improvement with corticosteroids and/or immunosuppressive treatment. The long-term functional prognosis was correlated with the initial severity.
Type I cryoglobulinemia vasculitis (CryoVas) is considered a life-threatening condition; however, data on the characteristics and outcome are scarce. To analyze the presentation, prognosis, and ...efficacy and safety of treatments of type I CryoVas, we conducted a French nationwide survey that included 64 patients with type I CryoVas between January 1995 and July 2010: 28 patients with monoclonal gammopathy of unknown significance (MGUS) and 36 with hematologic malignancy.Type I monoclonal CryoVas was characterized by severe cutaneous involvement (necrosis and ulcers) in almost half the patients and high serum cryoglobulin levels, contrasting with a lower frequency of glomerulonephritis than expected. The 1-, 3-, 5-, and 10-year survival rates were 97%, 94%, 94%, and 87%, respectively. Compared to MGUS, type I CryoVas related to hematologic malignancy tended to be associated with a poorer prognosis. Therapeutic regimens based on alkylating agents, rituximab, thalidomide or lenalinomide, and bortezomib showed similar efficacy on vasculitis manifestations, with clinical response rates from 80% to 86%.Data from the CryoVas survey show that the prognosis of type I CryoVas does not seem to be as poor as previously suggested. Besides alkylating agents, the use of regimens based on rituximab, thalidomide or lenalinomide, and bortezomib are interesting alternative options, although the exact role of each strategy remains to be defined.
•DADA2 diagnosed in adulthood display specific clinical features distinguishing it from pediatric forms.•Adults with DADA2 vasculopathy experience more severe skin involvement but fewer ...strokes.•Hematological phenotypes are less common in adults and cluster with humoral immune deficiency.
Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease usually presenting before the age of 10 years. Non-specific clinical features or late–onset presentation may delay its diagnosis until adulthood.
To determine whether DADA2 diagnosed in adulthood is associated with specific characteristics compared to DADA2 diagnosed in childhood.
We pooled a cohort of 12 adult DADA2 patients followed in France with cases identified through a systematic literature review. For each patient, we determined the type of clinical presentation and assessed six key organ involvements.
A total of 306 cases were included. Among the 283 patients with available data regarding age at diagnosis, 140 were diagnosed during adulthood and 143 during childhood. The vascular presentation of DADA2 was more frequent in the adult diagnosis group (77.9% vs. 62.9%, p < 0.01), whereas the hematological presentation (bone marrow failure) prevailed in the pediatric diagnosis group (10.0% vs. 20.3% p = 0.02). In patients with vasculopathy, severe skin manifestations developed in 35% and 10% of the adult and pediatric diagnosis groups, respectively. Conversely, fewer strokes occurred in the adult group presenting with systemic vasculopathy (54% vs. 81%). Symptomatic humoral immune deficiency (HID) was rarely a clinical presentation in itself (5% and 2.8%) but accompanied other phenotypes of DADA2, especially the hematological phenotype in the adult group (33% vs. 4%).
DADA2 diagnosed in adulthood presents more often with a vascular phenotype and less often with bone marrow failure than DADA2 diagnosed in childhood. Adults diagnosed with DADA2 vasculopathy display more severe skin involvement but fewer strokes.
Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to splenectomy and the requirement for long-term treatment to reduce the risk of significant bleeding ...events. In this multicenter study, we included 37 patients with multirefractory ITP, defined as no response to splenectomy, rituximab, romiplostim, and eltrombopag. As compared with a historical cohort of 183 ITP patients, matched on the calendar year of ITP diagnosis with a 5:1 ratio, patients with multirefractory ITP were more likely to have secondary ITP (odds ratio OR, 4.84; 95% confidence interval CI, 1.31-17.86; P = .018) and monoclonal gammopathy of undetermined significance (OR, 5.94; 95% CI, 1.08-32.48; P = .04). The median duration of ITP before being recognized as multirefractory was 78 months (range, 6-450). The patients showed failure of a median of 10.5 prior treatment lines for ITP (range, 6-15). At the end of follow-up (median, 84 months; range, 12-455), only 1/14 patients achieved response with immunosuppressant therapy alone. By contrast, 7/10 patients achieved response with a combination of immunosuppressant therapy and thrombopoietin-receptor agonists that lasted for a median of 15 months (range, 6-32). Throughout the course of ITP, 5/37 patients died, 3 with ITP (bleeding, n = 2; sepsis n = 1); 15 (40%) had at least 1 bacterial infection and 9 (24%) at least 1 episode of thrombosis. In conclusion, multirefractory ITP was associated with high morbidity and mortality. Combining an immunosuppressant therapy with thrombopoietin-receptor agonists may be a good strategy for management for these patients with severe disease.
•The baseline characteristics of multirefractory ITP differed from “typical” ITP, outcome was severe, and was associated with high morbidity and mortality.•Combining immunosuppressant therapy with a thrombopoietin-receptor agonist may be a relevant option for these patients.
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