Sustained depression of B cell counts in lupus nephritis after treatment with rituximab and/or belimumab is associated with fewer disease flares.

OBJECTIVE: To study the risk of lupus nephritis flare (LNF) or severe lupus flare (SLF) as a function of B cell count kinetics in lupus nephritis (LN) patients after they achieve at least a partial renal response (PRR) with induction treatment that includes rituximab (RTX) and/or belimumab (BLM). METHODS: We performed a retrospective analysis of a cohort of 19 patients with severe LN that received a B cell agent (BCA), RTX and/or BLM, as part of an initial treatment regimen for an LN flare and had subsequent CD19+ B cell measurements in peripheral blood. We then characterized the follow-up periods, after B cell depressions occurred and PRR were achieved, by the corresponding trajectories of B cell counts (BCC). Time periods with sustained low BCC were type 1 (T1) episodes, while those with repletion of BCC>100 cells/µL were called type 2 (T2) episodes. Time periods with rapid BCC repletion, defined as >50 cells/µL in ≤6 months, were called T2b episodes. Corresponding C3, C4, and anti-dsDNA levels were recorded for each episode. The time from PRR until an event, either a LNF or SLF, or to censoring, either at the end of the study period or the end of available patient follow-up, was assessed for each episode type. Kaplan-Meier survival analysis was used to compare time to flare between T1 and T2 episodes. RESULTS: There were 26 episodes of B cell depression. Seventeen (65%) were T1 and 9 (35%) were T2. Compared to T1 episodes, T2 episodes were 9.0 times more likely to result in flare over the follow-up period (hazard ratio (HR) = 9.0, 95% CI for HR = 2.2-36.7); this risk was even larger for T2b vs T1 episodes. Median BCC was 14 cells/µL in T1 and 160 cells/µL in T2 episodes. Both C3 and C4 levels significantly increased over the duration of the episode in T1 episodes only. CONCLUSION: Sustained low BCC was associated with prolonged serologic and clinical response, whereas repletion, and particularly rapid repletion, of B cells after treatment with BCA was associated with subsequent disease flare.

Perioperative Management of Rheumatic Disease and Therapies.

Patients with rheumatic disease, including those with systemic lupus erythematous, rheumatoid arthritis, and spondyloarthritis, use total hip and knee arthroplasties at high rates. They represent a particularly vulnerable population in the perioperative setting because of their diseases and the immunosuppressant therapies used to treat them. Careful planning among internists, medical specialists, and the surgical team must therefore occur preoperatively to minimize risks in the postoperative period, particularly infection. Management of immunosuppressant medications, such as conventional synthetic disease-modifying antirheumatic drugs and targeted therapies including biologics, is one avenue by which this infectious risk can be mitigated.

Characteristics of Patients With Antiphospholipid Antibody Positivity in the APS ACTION International Clinical Database and Repository.

OBJECTIVE: To describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes. METHODS: The APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti-ß2 -glycoprotein I [anti-ß2 GPI]) antibodies by aPL profiles (LAC only, single, double, and triple aPL positivity). RESULTS: The 804 aPL-positive patients assessed in the present study had a mean age of 45 ± 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL-positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non-criteria manifestation. Among those with three aPLs tested (n = 660), 42% were triple aPL-positive. While single-, double-, and triple aPL-positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti-ß2 GPI only. CONCLUSION: Our study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification.

Perioperative Management of Rheumatic Disease and Therapies.

Patients with rheumatic disease, including those with systemic lupus erythematous, rheumatoid arthritis, and spondyloarthritis, use total hip and knee arthroplasties at high rates. They represent a particularly vulnerable population in the perioperative setting because of their diseases and the immunosuppressant therapies used to treat them. Careful planning among internists, medical specialists, and the surgical team must therefore occur preoperatively to minimize risks in the postoperative period, particularly infection. Management of immunosuppressant medications, such as conventional synthetic disease-modifying antirheumatic drugs and targeted therapies including biologics, is one avenue by which this infectious risk can be mitigated.

Use of Anakinra to Prevent Mechanical Ventilation in Severe COVID-19: A Case Series.

OBJECTIVE: To report the clinical experience with anakinra in preventing mechanical ventilation in patients with coronavirus disease 2019 (COVID-19), symptoms of cytokine storm syndrome, and acute hypoxemic respiratory failure. METHODS: To be included in this retrospective case series, patients must have had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), fever, ferritin levels >1,000 ng/ml with 1 additional laboratory marker of hyperinflammation, and acute hypoxemic respiratory failure. Acute hypoxemic respiratory failure was defined as requiring 15 liters of supplemental oxygen via a nonrebreather mask combined with 6-liter nasal cannula or use of ≥95% oxygen by high-flow nasal cannula. We excluded patients in whom there was suspicion of bacterial infection or who were receiving immunosuppressants. Subcutaneous anakinra was initiated at 100 mg every 6 hours and gradually tapered off completely. The primary outcome was the prevention of mechanical ventilation. RESULTS: Of the 14 patients who met the criteria, 11 patients received anakinra for a maximum of 19 days. Seven of the patients who started anakinra treatment ≤36 hours after onset of acute hypoxemic respiratory failure did not require mechanical ventilation, and all were discharged home. Four patients who started anakinra ≥4 days after onset of acute hypoxemic respiratory failure required mechanical ventilation. Of those, 3 patients were extubated (2 discharged home and 1 remained hospitalized), and 1 died. All 3 patients who met the criteria but did not receive anakinra required mechanical ventilation. Two patients were extubated (1 discharged home and 1 remained hospitalized), and 1 remained on mechanical ventilation. CONCLUSION: Our data suggest that anakinra could be beneficial in treating COVID-19 patients with evidence of cytokine storm syndrome when initiated early after onset of acute hypoxemic respiratory failure. Our patient selection and treatment approach should be considered for investigation in a clinical trial to determine the safety and efficacy of anakinra in treating patients with COVID-19 and symptoms of cytokine storm syndrome.

A Case of Lyme Carditis Presenting with Atrial Fibrillation.

We report a case of a 20-year-old man who presented to our institution with a new arrhythmia on a routine EKG. Serial EKG tracings revealed various abnormal rhythms such as episodes of atrial fibrillation, profound first degree AV block, and type I second degree AV block. He was found to have positive serologies for Borrelia burgdorferi. After initiation of antibiotic therapy, the atrial arrhythmias and AV block resolved. Here, we present a case of Lyme carditis presenting with atrial fibrillation, a highly unusual presentation of Lyme carditis.