Winters, Jeffrey L

AbstractBackgroundIdiopathic inflammatory myopathies (IIMs) encompass many rheumatologic diseases characterized by inflammatory muscle disease, typically unified by proximal muscle weakness. A subset of patients with IIM present with interstitial lung disease (ILD) with identifiable antibodies such as in anti‐synthetase syndrome (AS) with antibodies to aminoacyl‐tRNA synthetases, and clinically amyopathic dermatomyositis (CADM) with anti‐melanoma differentiation‐associated protein 5 (MDA5). Recent case reports demonstrate response to therapeutic plasma exchange (TPE) or column filtration plasmapheresis in IIM with ILD resistant to medical management. We present our experience with eight patients with IIM with ILD undergoing TPE at a large US‐based hospital system.Patient characteristicsEight patients with IIM with ILD were treated with TPE over the last 10 years. The therapy consisted of 5‐7 one plasma volume exchanges every other day to daily. Seven of eight patients had identifiable antibodies.ResultsFollowing completion of TPE, seven of eight demonstrated improvement in pulmonary function despite lack of improvement of pulmonary function with standard therapy.ConclusionIn antibody‐mediated, treatment refractory IIM with ILD, TPE may be a viable intervention. This is a disease for which the role of apheresis is evolving.Clinical trial registrationNot application.

AbstractEculizumab is effective for complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome. Although lifelong therapy had been suggested, discontinuation does not universally lead to relapse. Comprehensive data evaluating risk factors for recurrence following discontinuation are limited. Our aim was to systematically review available literature assessing the role of complement genetic variants in this setting. Reports on CM-TMA and eculizumab withdrawal published before 1 January 2021, were included. Key reasons for patient exclusion were no follow-up after drug withdrawal and patients lacking complement genetic testing. Two-hundred eighty patients from 40 publications were included. Median age was 28 years, and 25 patients had a known history of renal transplant. Complement genetic variants were identified in 60%, most commonly in CFH (n = 59) and MCP/CD46 (n = 38). Of patients with a complement gene variant, 51.3% had ≥1 likely pathogenic/pathogenic variant whereas the remaining had variants of uncertain significance (VUS). Overall relapse rate after therapy discontinuation was 29.6%. Relapse rate was highest among patients with CFH variants and MCP/CD46 variants in canonical splice regions. VUS (P < .001) and likely pathogenic/pathogenic variants (P < .001) were associated with increased relapse. Presence of a renal allograft (P = .009); decreasing age (P = .029); and detection of variants in CFH (P < .001), MCP/CD46 (P < .001), or C3 (P < .001) were all independently associated with relapse after eculizumab discontinuation. Eculizumab discontinuation is appropriate in specific patients with CM-TMA. Caution should be exerted when attempting such a strategy in patients with high risk of recurrence, including a subgroup of patients with MCP/CD46 variants.

Background: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED. Methods: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×10 5 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone. Results: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [−18.0 to 32.4] to 57.6 [16.3–98.3]%; P =0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P =0.00018), and sublingual nitroglycerin use/day (1 [0.4–3.5] to 0 [0–1], Wilcoxon signed-rank test, P =0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED. Conclusions: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03471611.

Cytapheresis (removal of cellular blood components) has been employed for treatment of infectious diseases since the 1960s. Techniques have included thrombocytapheresis (buffy coat apheresis) for loiasis, erythrocytapheresis for malaria and babesiosis, and leukocytapheresis for pertussis‐associated lymphocytosis. Published data on these applications is largely limited to case level data and small observational studies; as such, recommendations for or against the use of cytapheresis in the treatment of infections have been extrapolated from these limited (and at times flawed) data sets. Consequently, utilization of cytapheresis in many instances is not uniform between institutions, and typically occurs at the discretion of treating medical teams. This review revisits the existing literature on the use of cytapheresis in the treatment of four infections (loasis, malaria, babesiosis, and pertussis) and examines the rationale underlying current treatment recommendations concerning its use.

AbstractApheresis procedures have a role in treatment of disparate diseases involving many different organ systems. Often the disease processes where apheresis plays a role in treatment are considered “orphan diseases”—relatively rare disease processes that lack specific pharmaceutical agents or established treatment protocols. Many of these disease processes can affect the eye with devastating results for the eyesight of these patients. The unique ability of apheresis to affect disease by modifying blood plasma and modulating disease‐causing agents therein renders apheresis procedures valuable tools in the treatment of certain ophthalmologic diseases. This review comprehensively evaluates the role of apheresis in the treatment of ophthalmologic diseases of the eye and surrounding orbit including age‐related macular degeneration, bilateral diffuse uveal melanocytic proliferation, paraneoplastic retinopathy, atopic keratoconjunctivitis, sympathetic ophthalmia, and endocrine‐associated ophthalmopathy. Apheresis procedure parameters are provided for the apheresis practitioner based on review of the relevant literature.