P. Belenotti

Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey

Data on the clinical spectrum and therapeutic management of noninfectious mixed cryoglobulinemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. We analyzed data from 242 patients with noninfectious mixed CryoVas included in the French multicenter CryoVas survey. Baseline manifestations were purpura (75%), peripheral neuropathy (52%), arthralgia or arthritis (44%), glomerulonephritis (35%), cutaneous ulcers (16%), and cutaneous necrosis (14%). A connective tissue disease was diagnosed in 30% and B-cell non-Hodgkin lymphoma in 22%, whereas the CryoVas was considered to be essential in 48%. With the use of Cox-marginal structural models, rituximab plus corticosteroids showed the greater therapeutic efficacy compared with corticosteroids alone and alkylating agents plus corticosteroids to achieve complete clinical, renal, and immunologic responses and a prednisone dosage < 10 mg/d at 6 months. However, this regimen was also associated with severe infections, particularly when high doses of corticosteroids were used, whereas death rates did not differ between the therapeutic regimens. The role of each of these strategies remains to be defined in well-designed randomized controlled trials.

The Clinical Spectrum and Therapeutic Management of Hypocomplementemic Urticarial Vasculitis: Data From a French Nationwide Study of Fifty‐Seven Patients

Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV.

Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey

Background Data on the prognosis of non-infectious mixed cryoglobulinaemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. Methods The French multicentre and retrospective CryoVas survey included 242 patients with non-infectious mixed CryoVas. Causes of death and prognostic factors of survival were assessed and a prognostic score was determined to predict survival at 5 years. Results After a median follow-up of 35 months, 42 patients (17%) died. Causes of death were mainly serious infections (50%) and vasculitis flare (19%). One-, 2-, 5- and 10-year overall survival rates were 91%, 89%, 79% and 65%, respectively. A prognostic score, the CryoVas score (CVS), for the prediction of survival at 5 years was devised. Pulmonary and gastrointestinal involvement, glomerular filtration rate <60 ml/min and age >65 years were independently associated with death. At 5 years the death rates were 2.6%, 13.1%, 29.6% and 38.5% for a CVS of 0, 1, 2 and ≥3, respectively. At 1 year the death rates were 0%, 3.2%, 18.5% and 30.8% for a CVS of 0, 1, 2 and ≥3, respectively. The CVS was strongly correlated with the Five Factor Score (FFS) 2009, another prognostic score validated in primary necrotising vasculitis (r=0.82; p<0.0001). The area under the curve for the CVS was 0.74 compared with 0.67 for the FFS, indicating a better performance of the CVS (p=0.052). Conclusions In patients with non-infectious mixed CryoVas, the main prognostic factors are age >65 years, pulmonary and gastrointestinal involvement and renal failure. A score including these variables is significantly associated with the prognosis.

Non HCV-related infectious cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey and systematic review of the literature

In patients with infectious cryoglobulinemia vasculitis (CryoVas) in the absence of hepatitis C virus infection, data on presentation, therapeutic management and outcome are lacking. We conducted a nationwide survey that included patients with HCV-negative CryoVas. We describe here the presentation, therapeutic management and outcome of 18 patients with non-HCV infectious CryoVas and 27 additional patients identified form a systematic review of the literature. We included 18 patients, mean age 57.9±13.5 years. Infectious causes were viral infections in 8 patients [hepatitis B virus (HBV) in 4, and cytomegalovirus, Epstein Barr virus, parvovirus B19 and human immunodeficiency virus in one case each], pyogenic bacterial infection in 6 patients, parasitic infection in 2 patients, and leprosy and candidiasis in one case each. Baseline manifestations were purpura (78%), glomerulonephritis (28%), arthralgia (28%), peripheral neuropathy (22%), skin necrosis (22%), cutaneous ulcers (17%), and myalgia (11%). Cryoglobulinemia was type II in 2/3 of cases. Most cases received specific anti-infectious therapy as first-line therapy, sometimes associated with corticosteroids, achieving sustained remission in the majority of cases. Refractory or relapsing patients, frequently related to HBV infection, showed a complete remission after rituximab in addition to antiviral therapy. In contrast, corticosteroids and/or immunosuppressive agents used in the absence of anti-infectious agents were frequently associated with refractory CryoVas. Viral and pyogenic bacterial infections represent the main causes of non-HCV infectious CryoVas. Antimicrobial therapy is commonly associated with sustained remission. Immunosuppressive agents should be considered only as a second-line option in patients with refractory vasculitis.

Partially Reversible Cortical Metabolic Dysfunction in Familial Hemiplegic Migraine With Prolonged Aura

We report a SPECT and PET voxel‐based analysis of cerebral blood flow and metabolic rate for glucose in a 23‐year‐old woman with familial hemiplegic migraine (FHM) caused by ATP1A2 gene mutation. In comparison with healthy subjects, a PET scan showed brain glucose hypometabolism, controlaterally to the hemiplegia, in the perisylvian area early in the attack (Day 1), without any SPECT perfusion abnormalities. Decrease in metabolic rate was only partially reversible at Day 78, concordant at this time with a remaining hemisensory loss. These findings provide further evidence for a primary cortical metabolic dysfunction in FHM.

Predictors of early relapse in patients with non-infectious mixed cryoglobulinemia vasculitis: results from the French nationwide CryoVas survey.

OBJECTIVE Although in most patients induction therapy leads to complete or partial remission, relapses in patients with non-infectious mixed cryoglobulinemia vasculitis (CryoVas) remain a major problem. We aimed to identify predictors of early relapses occurring within the first 12months of treatment in such patients. METHODS Patients included in the French CryoVas survey exhibiting complete/partial clinical remission and followed-up for at least 12months after induction therapy (n=145) were analyzed for predictors of early relapses. RESULTS Forty out of 145 patients (28%) experienced early relapse. Relapses occurred after a median time of 9.5months after induction therapy (3-12) and involved skin (75%), joints and peripheral nerve (28% each), kidneys (25%) and gastrointestinal tract (5%). Baseline factors associated with an early relapse were purpura [HR 3.35 (1.02-10.97), P=0.046], cutaneous necrosis [HR 4.46 (1.58-12.57), P=0.005] and articular involvement [HR 2.20 (1.00-4.78), P=0.048]. The only factor negatively associated with an early relapse during follow-up was the achievement of complete immunological response [HR 0.07 (0.01-0.51), P=0.009]. The use of corticosteroids plus rituximab or cyclophosphamide tended to be associated negatively with early relapse [HR 0.43 (0.17-1.08), P=0.07]. CONCLUSION In patients with non-infectious CryoVas, main predictors of early relapses after initial remission are purpura, articular involvement, and cutaneous necrosis. The absence of complete immunological response during follow-up was associated with early relapse. These findings may help in adapting future treatment strategies.

Granulomatosis with polyangiitis: endoscopic management of tracheobronchial stenosis: results from a multicentre experience

OBJECTIVES Tracheobronchial stenosis (TBS) is noted in 12-23% of patients with granulomatosis with polyangiitis (GPA), and includes subglottic stenosis and bronchial stenosis. We aimed to analyse the endoscopic management of TBS in GPA and to identify factors associated with the efficacy of endoscopic interventions. METHODS We conducted a French nationwide retrospective study that included 47 patients with GPA-related TBS. RESULTS Compared with patients without TBS, those with TBS were younger, more frequently female and had less frequent kidney, ocular and gastrointestinal involvement and mononeuritis multiplex. Endoscopic procedures included 137 tracheal and 50 bronchial interventions, mainly endoscopic dilatation, local steroid injection and conservative laser surgery, and less frequently stenting. After the first endoscopic procedure, the cumulative incidence of endoscopic treatment failure was 49% at 1 year, 70% at 2 years and 80% at 5 years. Factors significantly associated with a higher cumulative incidence of treatment failure were a shorter time from GPA diagnosis to endoscopic procedure [hazard ratio (HR) 1.08 (95% CI 1.01, 1.14); P = 0.01] and a bronchial stenosis [HR 1.96 (95% CI 1.28, 3.00); P = 0.002]. A prednisone dose ≥30 mg/day at the time of the procedure was associated with a lower cumulative incidence of treatment failure [HR 0.53 (95% CI 0.31, 0.89); P = 0.02]. CONCLUSION TBS represents severe and refractory manifestations with a high rate of restenosis. High-dose systemic CSs at the time of the procedure and increased time from GPA diagnosis to bronchoscopic intervention are associated with a better event-free survival. In contrast, bronchial stenoses are associated with a higher rate of restenosis than subglottic stenosis.

Vena Cava Filter Migration: An Unappreciated Complication. About Four Cases and Review of the Literature

Inferior vena cava filter placement is performed to prevent pulmonary risk secondary to deep venous thrombosis. Indications for this treatment are limited to patients experiencing recurrences under well-managed anticoagulant treatment or presenting with contraindication to anticoagulant treatment. Nowadays, as these clinical situations are rare, this device is less and less used, all the more since, for several years now, thrombosis, fracture, or infectious complications as well as filter migration have been reported. Filter migrations are responsible for atypical and varied clinical presentations likely to defer diagnosis. To treat them, the filter is extracted, which is very risky in patients with a thromboembolic history. In our center, during a period of 14 years, we retrospectively collected and studied partial or complete vena cava filter migration cases that had been treated by extraction. We are reporting four very different clinical cases and, more specifically, the second published case of migration to a renal vein, which mimicked a systemic disease. Because of its very atypical clinical presentations, cava filter migration is an unappreciated and certainly underdiagnosed complication. However, this complication must not question cava filter placement when it is justified. In contrast, it prompts early filter extraction or long-term radiological surveillance.

Pulmonary embolism induced by methotrexate in a dermatomyositis patient

Joint Bone Spine - In Press.Proof corrected by the author Available online since mardi 20 septembre 2016

Primary cutaneous nocardiosis caused by Nocardia takedensis with pulmonary dissemination in an immunosuppressed patient.

We present a remarkable case of primary cutaneous nocardiosis with pulmonary dissemination due to Nocardia takedensis in a 76‐year‐old man suffering from marginal zone lymphoma and hypogammaglobulinaemia. We also discuss an alternative treatment to trimethoprim‐sulfamethoxazole, which could be contraindicated due to haematological and cutaneous toxicities. This case report is of interest due to the emergence of cutaneous nocardiosis in dermatology.