Management of nonviral mixed cryoglobulinemia vasculitis refractory to rituximab: Data from a European collaborative study and review of the literature.

BACKGROUND: Glucocorticoids (GCs) plus rituximab (RTX) represent the first-line treatment of nonviral mixed cryoglobulinemia vasculitis (CryoVas). However, data on therapeutic management and outcome of patients refractory to RTX are lacking. METHODS: We conducted a European collaborative retrospective multicenter study of patients with nonviral mixed CryoVas refractory to RTX and performed a literature review. RESULTS: Twenty-six original cases and 7 additional patients from the literature were included. All patients but one had type 2 cryoglobulinemia, and causes were autoimmune disease (51%), malignant hemopathy (12%) or essential CryoVas (42%). CryoVas was primary refractory to RTX in 42%, while 58% had an initial response to RTX before immune escape. After RTX failure, patients received a median of 1 (IQR, 1-3) line of treatment, representing 65 treatment periods during follow-up. Main treatments used were GCs in 92%, alkylating agents in 43%, RTX in combination with other treatments in 46%, and belimumab in 17%. Combination of anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents provided the highest rates of clinical response in 100% 82% and 73%, respectively, but showed poor immunological response, in 50%, 30% and 38%, respectively. Rates of severe infection were 57%, 9% and 0% in patients receiving anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents, respectively. CONCLUSION: In patients with nonviral mixed CryoVas refractory to RTX, anti-CD20 plus belimumab, and alkylating agents associated or not with anti-CD20, provide the highest rates of clinical response. However, anti-CD20 plus belimumab was frequently associated with severe infections.

Spectrum and Prognosis of Antineutrophil Cytoplasmic Antibody-associated Vasculitis-related Bronchiectasis: Data from 61 Patients.

OBJECTIVE: To report on a large series of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and bronchiectasis, with a specific focus on the timeline of occurrence of both features. METHODS: Retrospective nationwide multicenter study of patients diagnosed with both AAV and bronchiectasis. RESULTS: Sixty-one patients were included, among whom 27 (44.25%) had microscopic polyangiitis (MPA), 27 (44.25%) had granulomatosis with polyangiitis (GPA), and 7 (11.5%) had eosinophilic GPA. Thirty-nine (64%) had myeloperoxidase (MPO)-ANCA and 13 (21%) had proteinase 3-ANCA. The diagnosis of bronchiectasis either preceded (n = 25; median time between both diagnoses: 16 yrs, IQR 4-54 yrs), was concomitant to (n = 12), or followed (n = 24; median time between both diagnoses: 1, IQR 0-6 yrs) that of AAV. Patients in whom bronchiectasis precedes the onset of AAV (B-AAV group) have more frequent mononeuritis multiplex, MPA, MPO-ANCA, and a 5-fold increase of death. The occurrence of an AAV relapse tended to be protective against bronchiectasis worsening (HR 0.6, 95% CI 0.4-0.99, P = 0.049), while a diagnosis of bronchiectasis before AAV (HR 5.8, 95% CI 1.2-28.7, P = 0.03) or MPA (HR 18.1, 95% CI 2.2-146.3, P = 0.01) were associated with shorter survival during AAV follow-up. CONCLUSION: The association of bronchiectasis with AAV is likely not accidental and is mostly associated with MPO-ANCA. Patients in whom bronchiectasis precedes the onset of AAV tend to have distinct clinical and biological features and could carry a worse prognosis.

The French Society of Internal Medicine's Top-5 List of Recommendations: a National Web-Based Survey.

BACKGROUND: The international project "Choosing Wisely" aims to target unnecessary and potentially harmful examinations and treatments. OBJECTIVE: To define the French Internal Medicine Top-5 list. DESIGN: Based on a review of existing Top-5 lists and personal experience, a working group of the French National Society of Internal Medicine selected 27 diagnostic and therapeutic procedures. They were submitted through a national web-based survey to French internists who rated from 1 to 5 the perceived frequency, uselessness, and risk of each procedure. A composite score was calculated as the unweighted addition of the three scores. PARTICIPANTS: Four hundred thirty internists answered the web-based survey (14% of all French internists including residents). All the French regions and status of the profession were represented. KEY RESULTS: For the 27 submitted procedures, the mean score (± SD) was 3.25 (± 0.48) for frequency, 3.10 (± 0.43) for uselessness, and 2.63 (± 0.84) for risk. The Top-5 list obtained with the composite score was as follows: 1. Do not prescribe long-term treatment with proton pump inhibitors without regular reevaluation of the indication 2. Do not administer preventive treatments (e.g., for dyslipidemia, hypertension…) in elderly people with dementia when potential risks outweigh the benefits 3. Do not administer hypnotic medications as first-line treatment for insomnia 4. Do not treat with an anticoagulant for more than 3 months a patient with a first venous thromboembolism occurring in the setting of a major transient risk factor 5. Do not screen for Lyme disease without an exposure history or related clinical examination findings We found that the composite score was strongly correlated to the risk score (rs = 0.88, p < 10-5) and not to the frequency (rs = 0.06, p = 0.75) or uselessness score (rs = 0.17, p = 0.38). CONCLUSIONS: This Top-5 list provides an opportunity to discuss appropriate use of health care practices in internal medicine.