Molecular B-cell clonality assay in minor salivary glands as a useful tool for the lymphoma risk assessment in Sjögren's syndrome.

OBJECTIVES: Non-Hodgkin's lymphoma (NHL) risk assessment is crucial in Sjögren's syndrome (SS). We studied the prevalence of clonal immunoglobulin gene rearrangements in minor salivary glands (MSG) and their correlations with lymphoma occurrence and with previously established NHL predictors. METHODS: Molecular B-cell expansion was studied in fresh-frozen MSG of 207 patients with either suspected SS or with suspected lymphoma during SS, using a standardised multiplex PCR assay combined with heteroduplex analysis by microcapillary electrophoresis. The assignation of clonal cases was based on EuroClonality consortium guidelines. RESULTS: Among 207 studied patients, 31 (15%) had MSG monoclonal B-cell infiltration. Monoclonality was significantly more frequent in patients with SS (28/123, 22.8%) compared with patients without SS (3/84, 3.6%, P<0.001). Monoclonal B-cell infiltration in MSG of SS patients correlated significantly with ongoing salivary gland NHL, salivary gland swelling, CD4+ T-cell lymphopenia, rheumatoid factor (RF) activity, low complement levels and type 2 mixed cryoglobulinemia. The accumulation of biological risk factors was associated with a higher rate of MSG B-cell monoclonality given that patients with only positive RF had no probability of MSG B-cell monoclonality, RF-positive patients with 1 or 2 other risk factors had a 25.0% and 85.7% probability of MSG B-cell monoclonality, respectively. CONCLUSION: The detection of MSG monoclonal B-cell expansion by this easy-to-perform molecular assay is useful, both at the time of diagnosis and during the course of SS. Monoclonal B-cell expansion is associated with a subset of SS patients presenting either ongoing lymphoma or other established lymphoma predictive factors.

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.

Impaired Granuloma Formation in Sepsis: Impact of Monocytopenia.

Granulomas are a collection of immune cells considered to be protective in infectious diseases. The in vitro generation of granulomas is an interesting substitution to invasive approaches of granuloma study. The monitoring of immune response through the determination of in vitro granuloma formation in patients with severe sepsis may be critical to individualize treatments. We compared the in vitro generation of granulomas by co-culturing circulating mononuclear cells from 19 patients with severe sepsis, 9 patients cured from Q fever and 12 healthy subjects as controls, and Sepharose beads coated either with BCG or Coxiella burnetii extracts to analyze both immune and innate granulomas, respectively. We showed that the great majority of patients with severe sepsis were unable to form granulomas in response to BCG and C. burnetii extracts whereas more than 80% of healthy controls and patients cured from Q fever formed granulomas. We also found that monocytopenia and defective production of tumor necrosis factor were associated with reduced formation of granulomas in patients with severe sepsis even if TNF did not seem to be involved in the defective granuloma formation. Taken together, these results suggest that the deficiency of granuloma formation may be a measurement of altered recruitment and activation of monocytes and lymphocytes in patients with severe sepsis.

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.

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.

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.