IgA vasculitis with underlying monoclonal IgA gammopathy: innovative therapeutic approach targeting plasma cells. A case series.

OBJECTIVE: There is currently no evidence of the possible benefit of plasma cell-targeting therapies (PCTT) in immunoglobulin A (IgA) monoclonal gammopathy (MG) associated with IgA vasculitis (IgAV). We report the outcome of different PCTT regimens in a cohort of MG-IgAV. METHODS: We used a French network to retrospectively describe the outcome of MG-IgAV patients treated with PCTT. RESULTS: Five patients were included (mean age 65 years). All patients had severe baseline presentation including extensive necrotic purpura (n = 5), gastrointestinal involvement (n = 2), peripheral neuropathies (n = 2), and glomerulonephritis (n = 1). Two patients had IgA indolent multiple myeloma and three had IgA "MG of undetermined significance." Monotypic IgA deposition in the skin vessels wall was highlighted using an immunofluorescence assay. Cases of vasculitis in three patients (n = 3) were refractory to multiple line therapies, including cyclophosphamide (n = 3) or rituximab. Finally, PCTT including bortezomib plus cyclophosphamide and dexamethasone, bortezomib plus melphalan and prednisone, or bortezomib plus lenalidomide and dexamethasone were proposed, allowing complete remission in 4/5 patients without major adverse drug events. CONCLUSION: This study suggests that the MG-IgAV phenotype might be distinctive of usual IgAV (severe and refractory to conventional immunosuppressive regimens) and supports the benefit of PCTT. This study sheds new light on the overall biology of IgAV, strengthening the pathogenic role of the monoclonal IgA component in IgAV.

Primary meningococcal arthritis in a COVID-19 18-year-old man: a case report and review of the literature.

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is associated with various complications. PMA (primary meningococcal arthritis) is a rare meningococcus-associated disease causing arthritis of the knee usually, without any signs of invasive meningococcal disease. No case of PMA in a COVID-19 (coronavirus disease, 2019) patient has yet been described. PMA mainly strikes young adults. PMA is not associated with any immunocompromising condition. It has a better outcome than usual septic arthritis CASE PRESENTATION: Herein, we report an 18-year-old man diagnosed with COVID-19, later admitted with persistent fever, right knee arthralgia and maculopapular rash. Due to family history, psoriasis and Henoch-Schönlein purpura were hypothesized and ruled out. Finally, synovial fluid culture confirmed Neisseria meningitidis serogroup B arthritis without any other symptoms of invasive meningococcal disease. Healing was achieved quickly with surgery and antibiotics. We concluded in a PMA. CONCLUSION: We describe here the first primary meningococcal arthritis in a COVID-19 patient and we hope to shine a light on this rare but serious complication.

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients.

OBJECTIVE: IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the baseline characteristics and/or outcome of vasculitis. We aimed to describe the presentation of IgAV in patients with cancer (IgAV ca+) compared to patients without cancer. METHODS: We conducted a nationwide retrospective study of adult patients in France who presented with both IgAV and cancer. Baseline characteristics were described and compared with those of the 260 patients included in a nationwide French IgAV study. RESULTS: Thirty patients were included. The mean age was 69 ± 12 years; 80% were men. Compared to patients without underlying cancer, IgAV ca+ patients were older (69 ± 12 vs. 50 ± 18 years; p < 0.0001) and they presented more frequently with necrotic purpura (53 vs. 26%; p < 0.002) and intra-alveolar hemorrhage (10 vs. 0.5%; p < 0.0001). IgAV ca+ patients frequently had elevated serum IgA levels (79 vs. 53%; p < 0.034); most (n = 22, 73%) had adenocarcinoma or urothelial carcinoma involving the large intestines (n = 6), bladder (n = 5), and lung (n = 5). Most IgAV ca+ patients had progressive cancer (n = 21); a minority had metastatic disease (n = 2) at IgAV diagnosis. After a median follow-up of 3 months, 8 deaths were observed but none was related to IgAV. CONCLUSION: Compared to their noncancer counterpart, patients with IgAV related to cancer were older and more frequently presented with necrotizing purpura, intra-alveolar hemorrhage, and elevated serum IgA levels. Adult patients with IgAV and these latter characteristics should be carefully screened for cancer. Key Points • Clinical and biological characteristics of patients presenting with IgAV are distinct depending on the underlying cause of vasculitis related to cancer. • Patients with IgAV related to cancer are older, and compared to their counterparts without IgAV, they present more frequently with necrotic purpura, alveolar hemorrhage, and elevated serum IgA levels. • All adult patients with IgAV should be screened for cancer, and there should be a focus on elderly male patients presenting with necrotic purpura and/or alveolar hemorrhage.

Clinical value of a [18F]-FDG PET-CT muscle-to-muscle SUV ratio for the diagnosis of active dermatomyositis.

OBJECTIVE: To study a muscle-to-muscle standardised uptake value (SUV) ratio with FDG-PET/CT (FDG-PET) as a marker for the detection of disease activity in dermatomyositis (DM). METHODS: Patients with DM (n = 24) who met the European Neuro-Muscular Centre diagnostic criteria were retrospectively identified over a 3-year period through a national survey. Muscle biopsy was performed in all patients. Maximum SUV was measured in proximal muscles (SUVPROX) that had the highest radiotracer uptake on visual grading as well as in the musculus longissimus thoracis (SUVMLT), whereas mean SUV was measured for the liver (SUVLIV). Muscle-to-liver SUV ratios for either muscle group were compared and a SUVPROX/SUVMLT ratio was calculated. SUVPROX/SUVMLT of DM patients were compared with age- and sex-matched control subjects (n = 24) with melanoma who had received FDG-PET scans. RESULTS: DM patients presented with proximal and symmetrical muscle uptake. Differences in SUVPROX/SUVLIV and SUVMLT/SUVLIV ratios in DM subjects were significant (p < 0.001). SUVPROX/SUVMLT ratios in DM and their controls also differed significantly (p = 0.0012). The SUVPROX/SUVMLT ratio threshold between DM subjects and controls was 1.73 with a sensitivity of 50% (CI95%, 29.1 to 70.9%) and specificity at 83.3% (CI95%, 62.6 to 95.3%). When amyopathic DM patients were removed from the analysis, specificity was increased to 95% (CI95%, 75.1 to 99.9%) with a likelihood ratio of 10 and an AUC of 83.4% (CI95%, 71.4 to 95.4%). CONCLUSION: A muscle-to-muscle SUVPROX/SUVMLT ratio with a cut-off value of 1.73 in FDG-PET imaging might serve as a non-invasive marker to determine disease activity in dermatomyositis. KEY POINTS: • [18F]-FDG PET-scanner standardised uptake value (SUV) could reflect disease activity in dermatomyositis (DM). • A ratio of SUV in proximal muscles (SUVPROX) to SUV in musculus longissimus thoracis (SUVMLT) could be used to determine active DM. • Active disease is suspected for SUV PROX /SUV MLT ratios greater than 1.73.

Tocilizumab in Giant Cell Arteritis: A Multicenter Retrospective Study of 34 Patients.

OBJECTIVE: To report the efficacy and safety of tocilizumab (TCZ) for giant cell arteritis (GCA). METHODS: A retrospective multicenter study that included 34 patients receiving TCZ for GCA. RESULTS: TCZ was effective in all but 6 patients, who still had mild symptoms. Mean glucocorticoid dose was tapered. One patient died and 3 patients had to stop TCZ therapy because of severe adverse events. Twenty-three patients stopped treatment; 8 of these experienced relapses after a mean of 3.5 ± 1.3 months. CONCLUSION: TCZ is effective in GCA. However, side effects occur. Whether this treatment has only a suspensive effect remains to be determined.

Asymptomatic myocardial ischemic disease in antiphospholipid syndrome: a controlled cardiac magnetic resonance imaging study.

OBJECTIVE: Antiphospholipid syndrome (APS) may cause coronary thrombosis. This study was undertaken to determine the prevalence of silent myocardial disease in patients with APS, using late gadolinium enhancement (LGE) of cardiac magnetic resonance imaging (CMRI). METHODS: Twenty-seven consecutive patients with APS and 81 control subjects without known cardiovascular disease underwent CMRI. The prevalence of occult myocardial ischemic disease, as revealed by LGE, was compared between patients with APS and controls, and factors associated with myocardial disease were identified in patients with APS. RESULTS: Myocardial ischemic disease, as characterized by LGE on CMRI, was present in 8 (29.6%) of 27 patients with APS, and imaging with LGE showed a typical pattern of myocardial infarction (MI) in 3 patients (11.1%). The myocardial scarring revealed on CMRI was not detected by electrocardiography or echocardiography. Although both patients with APS and control subjects shared a low risk of cardiovascular events, as calculated with the Framingham risk equation (mean +/- SD 5.1 +/- 8.2% and 6.5 +/- 7.6%, respectively, for the absolute risk within the next 10 years; P = 0.932), the prevalence of myocardial ischemia was more than 7 times higher in patients with APS (P = 0.0006 versus controls). No association was found between myocardial disease in patients with APS and classic coronary risk factors. The presence of myocardial scarring tended to be more closely associated with specific features of APS, such as duration of the disease, presence of livedo, and positivity for anti-beta(2)-glycoprotein I antibodies. CONCLUSION: The finding of a significant and unexpectedly high prevalence of occult myocardial scarring in patients with APS indicates the usefulness of CMRI with LGE for the identification of silent myocardial disease in such patients.

Treatment of relapsing polychondritis with rituximab: a retrospective study of nine patients.

OBJECTIVE: Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen expressed by B cells, is now considered an effective second-line therapy in various systemic diseases. We describe here the effects of rituximab in patients with relapsing polychondritis. METHODS: This was a retrospective study of 9 patients with relapsing polychondritis who received different regimens of rituximab in addition to their ongoing therapies. Clinical, laboratory, physiologic, and radiologic indicators were used to assess disease activity. We also examined their corticosteroid doses and any change in immunosuppressive agents. We then compared disease activity in the 6 months preceding rituximab administration and at 6 and 12 months after. RESULTS: At 6 months, 2 patients showed partial improvement, 4 were stable, and 3 had worsened disease; however, no patient had complete remission. At 12 months (after exclusion of the 3 patients whose disease had worsened at 6 months), 2 patients remained stable and 4 had worsened disease; however, there were no partial or complete remissions. B cells were counted in 8 patients during the first 6 months after treatment, and B cell depletion was observed in all of the patients. CONCLUSION: Although we cannot rule out the possibility that rituximab had a small effect, our patients' clinical courses did not improve significantly with this treatment.

Rituximab reversed cardiac involvement of Wegener's granulomatosis: magnetic resonance imaging assessment.

INTRODUCTION: Cardiac involvement is a rare manifestation of Wegener granulomatosis (WG). Because its prognosis can be poor, it must be diagnosed early to be treated adequately. We report the disease course of a patient who received rituximab to treat cardiac involvement documented by contrast-enhanced cardiac magnetic resonance imaging (ceCMR). CASE: This WG patient developed myocarditis with atrioventricular block. CeCMR proved useful in the diagnosis and follow-up of cardiac involvement. Several unsuccessful regimens preceded the prescription of rituximab. Two months later, regression of the myocarditis shown by ceCMR images was correlated with electrophysiological improvement. DISCUSSION: CeCMR assessment of a heart conduction defect in a patient with WG showed that this tool was useful for the diagnosis and follow-up of cardiac involvement in this vasculitis. Rituximab was an effective treatment in this patient.