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Background: The systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a very rare condition characterized by recurrent life-threatening episodes of vascular hyperpermeability in the presence of a monoclonal gammopathy. Extended intravenous immunoglobulin (IVIG) treatment is associated with fewer recurrences and improved survival, but the optimal treatment dosage and duration remain unknown., Objective: We aim to evaluate the safety of IVIG tapering and withdrawal in patients with SCLS., Methods: We conducted a retrospective multicenter study including all adult patients with monoclonal gammopathy-associated SCLS from the EurêClark registry who received at least 1 course of IVIG. The primary end point was overall survival according to IVIG withdrawal., Results: Fifty-nine patients of mean ± SD age 51 ± 13 years were included. Overall cumulative probabilities of 2-, 5-, 10- and 15-year survival were 100%, 85%, 72%, 44%, respectively. The IVIG was withdrawn at least once in 18 patients (31%; W+ group) and never in 41 patients (69%; W- group). Cumulative probabilities of 10-year survival in W+ versus W- groups were 50% and 83% (log rank test, P = .02), respectively. Relapse rate and the median number of relapses in the W+ versus the W- groups were 72% versus 58% (P = 0.3) and 2.5 (0.3-4) versus 1 (0-2) (P = .03), respectively. The IVIG tapering was not statistically associated with increased person-year incidence of attacks using a mixed linear model., Conclusions: The IVIG withdrawal was associated with increased mortality and higher rate of recurrence in SCLS patients. The IVIG tapering might be cautiously considered in stable SCLS patients., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The Hereditary TTP Registry is an international cohort study for patients with a confirmed or suspected diagnosis of hereditary thrombotic thrombocytopenic purpura (hTTP) and their family members. Hereditary TTP is an ultra-rare blood disorder (prevalence of ∼1-2 cases per million), the result of autosomal-recessively inherited congenital ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency (ADAMTS13 activity <10% of the normal), and associated with yet many unanswered questions. Until December 2017, the Hereditary TTP Registry had enrolled 123 confirmed hTTP patients. Their median age at disease onset was 4.5 years (range: 0-70) and at clinical diagnosis 16.7 years (range: 0-69), a difference that highlights the existing awareness gap in recognizing hTTP. The systematic collection of clinical data of individual patients revealed their substantial baseline comorbidities, as a consequence of recurring TTP episodes in the past. Most notable was the high proportion of patients having suffered from premature arterial thrombotic events, mainly transient ischemic attacks, ischemic strokes, and to a lesser extent myocardial infarctions. At 40 to 50 years of age and above, more than 50% of patients had suffered from at least one such event, and many had experienced arterial thrombotic events despite regular plasma infusions every 2 to 3 weeks that supplements the missing plasma ADAMTS13. The article by van Dorland et al. (Haematologica 2019;104(10):2107-2115) and the ongoing Hereditary TTP Registry cohort study were recognized with the Günter Landbeck Excellence Award at the 50th Hemophilia Symposium in Hamburg in November 2019, the reason to present the Hereditary TTP Registry in more detail here., Competing Interests: J.A.K.H. is a member of advisory board of Shire, member of the Takeda group of companies and of Ablynx, now part of Sanofi. All honoraria are paid to her employer, Insel Gruppe AG, Bern, Switzerland. The other authors have nothing to declare., (Thieme. All rights reserved.)

Background: Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome., Methods: We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months., Results: Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality., Conclusions: We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The diagnosis of malignant hematologic diseases has become increasingly complex during the last decade. It is based on the interpretation of results from different laboratory analyses, which range from microscopy to gene expression profiling. Recently, a method for the analysis of RNA phenotypes has been developed, the nCounter technology (Nanostring® Technologies), which allows for simultaneous quantification of hundreds of RNA molecules in biological samples. We evaluated this technique in a Swiss multi-center study on eighty-six samples from acute leukemia patients., Methods: mRNA and protein profiles were established for normal peripheral blood and bone marrow samples. Signal intensities of the various tested antigens with surface expression were similar to those found in previously performed Affymetrix microarray analyses. Acute leukemia samples were analyzed for a set of twenty-two validated antigens and the Pearson Correlation Coefficient for nCounter and flow cytometry results was calculated., Results: Highly significant values between 0.40 and 0.97 were found for the twenty-two antigens tested. A second correlation analysis performed on a per sample basis resulted in concordant results between flow cytometry and nCounter in 44-100% of the antigens tested (mean = 76%), depending on the number of blasts present in a sample, the homogeneity of the blast population, and the type of leukemia (AML or ALL)., Conclusions: The nCounter technology allows for fast and easy depiction of a mRNA profile from hematologic samples. This technology has the potential to become a valuable tool for the diagnosis of acute leukemias, in addition to multi-color flow cytometry.

Objective: To evaluate the range of long term vascular manifestations of Coxiella burnetii infection., Design: Cohort study in Switzerland of people affected in 1983 by the largest reported outbreak of Q fever and who were followed up 12 years later. Follow up information about possible vascular disease and endocarditis was obtained through a mailed questionnaire and death certificates., Setting: Val de Bagnes, a rural Alpine valley in Switzerland., Participants: 2044 (87%) of 2355 people who had serum testing for Coxiella burnetii infection in 1983: 1247 were classed as not having been infected, 411 were classed as having been acutely infected, and 386 were classed as having been infected before 1983., Main Outcome Measures: Relative risk controlled for age and sex and 12 year risk of vascular diseases and endocarditis among infected participants as compared with those who had never been infected., Results: The 12 year risk of endocarditis or venous thromboembolic disease was not increased among those who had been acutely infected. The 12 year risk of arterial disease was significantly higher among those who had been acutely infected (7%) as compared with those who had never been infected (4%) (relative risk 2.2, 95% confidence interval 1.4 to 3.6). Specifically, there was an increased risk of developing a cerebrovascular accident (relative risk 3.7, 1.6 to 8.4) and cardiac ischaemia (relative risk 1.9, 1.04 to 3.4). 12 year mortality was significantly higher among the 411 people who had been acutely infected in 1983 (9.7%; age adjusted relative risk 1.8, 1.2 to 2.6) when compared with the 1247 participants who had remained serologically negative in 1983 (7.0%)., Conclusions: Coxiella burnetii infection may cause long term complications including vascular disease.