Objective
Because it has no unique clinical, biologic, or histologic features, reactive hemophagocytic syndrome may be difficult to distinguish from other diseases such as severe sepsis or ...hematologic malignancies. This study was undertaken to develop and validate a diagnostic score for reactive hemophagocytic syndrome.
Methods
A multicenter retrospective cohort of 312 patients who were judged by experts to have reactive hemophagocytic syndrome (n = 162), were judged by experts to not have reactive hemophagocytic syndrome (n = 104), or in whom the diagnosis of reactive hemophagocytic syndrome was undetermined (n = 46) was used to construct and validate the reactive hemophagocytic syndrome diagnostic score, called the HScore. Ten explanatory variables were evaluated for their association with the diagnosis of hemophagocytic syndrome, and logistic regression was used to calculate the weight of each criterion included in the score. Performance of the score was assessed using developmental and validation data sets.
Results
Nine variables (3 clinical i.e., known underlying immunosuppression, high temperature, organomegaly, 5 biologic i.e., triglyceride, ferritin, serum glutamic oxaloacetic transaminase, and fibrinogen levels, cytopenia, and 1 cytologic i.e., hemophagocytosis features on bone marrow aspirate) were retained in the HScore. The possible number of points assigned to each variable ranged from 0–18 for known underlying immunosuppression to 0–64 for triglyceride level. The median HScore was 230 (interquartile range IQR 203–257) for patients with a positive diagnosis of reactive hemophagocytic syndrome and 125 (IQR 91–150) for patients with a negative diagnosis. The probability of having hemophagocytic syndrome ranged from <1% with an HScore of ≤90 to >99% with an HScore of ≥250.
Conclusion
The HScore can be used to estimate an individual's risk of having reactive hemophagocytic syndrome. This scoring system is freely available online (http://saintantoine.aphp.fr/score/).
Kaposi sarcoma–associated herpesvirus/human herpesvirus 8 is associated with multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL). In MCD, infected B cells, although polyclonal, ...express a monotypic immunoglobulin Mλ phenotype, probably through editing toward λ light chain in mature B cells. They are considered to originate from pre–germinal center (GC) naive B cells. Both viral and human interleukin-6 contribute to the plasmacytic differentiation of these cells, and viral replication can be observed in some infected cells. PEL cells are clonal B cells considered as GC/post-GC B cells. One can also hypothesize that they originate from the same infected naive B cells and that additional factors could be responsible for their peculiar phenotype.
Abstract Objectives Current knowledge in reactive hemophagocytic syndrome mainly relies on single-center case series including a relatively small number of patients. We aimed to identify a ...multicenter large cohort of adult patients with reactive hemophagocytic syndrome and to describe relevant clinical and laboratory features, underlying conditions, and outcome. Methods We conducted a multicenter study in 3 tertiary care centers in France over a 6-year period. The medical files of 312 patients with suspected hemophagocytic syndrome were retrospectively reviewed. Patients were classified with a positive, negative, or undetermined diagnosis of hemophagocytic syndrome by experts' consensus. Results Among the 312 patients fulfilling our inclusion criteria, 162 were classified with positive hemophagocytic syndrome (male, 67%; median age, 48 35-62 years). Compared with patients without hemophagocytic syndrome, patients with hemophagocytic syndrome more frequently had an underlying immunodepression (45% vs 33%, P = .03) and exhibited higher temperature, ferritin, triglycerides, aspartate transaminase, bilirubin, lactate dehydrogenase, and C-reactive protein, and lower hemoglobin, leukocytes, platelets, and sodium levels. Only 70% of them had hemophagocytosis features on bone marrow aspiration. Hematologic malignancies, especially non-Hodgkin lymphomas, were the main trigger of hemophagocytic syndrome, accounting for 56% of cases. The early mortality rate (ie, within 1 month after diagnosis) was 20%. Patients with hematologic malignancies-associated hemophagocytic syndrome had a poorer early outcome than those with underlying infection. Conclusions In this large, multicenter study, hematologic malignancies are the main disease associated with hemophagocytic syndrome in adults. Early mortality is high, and outcome is influenced by the underlying disease.
Summary
The spectrum of Castleman disease (CD) has considerably extended since its first description in 1956. Recently, an international collaborative working group has reached consensus on the ...diagnostic criteria and classification of CD. We herein report 273 patients with lymph node histopathology consistent with CD and investigate the newly established diagnostic criteria. Twenty of these patients with Castleman‐like histopathology were removed from analyses, because they were diagnosed with an exclusionary disorder (18 with haematological malignancy). Among the 253 remaining patients, 57 were considered unicentric CD (UCD), 169 were multicentric CD associated with Human Herpesvirus 8 (HHV‐8+MCD), including 140 patients with human immunodeficiency virus (HIV) infection and 29 patients without HIV infection, and 27 were HHV‐8 negative/idiopathic multicentric CD (iMCD). 2‐(18F)fluoro‐2‐deoxy‐D‐glucose positron emission tomography/computed tomography was useful in 62 patients for staging/classification of the disease and for excluding associated lymphoma. UCD was mainly associated with hyaline‐vascular histopathological features, and most patients were asymptomatic. Of the 27 patients that we had originally diagnosed with iMCD, 26 met the newly established diagnostic criteria. Patients with iMCD and HHV‐8+ MCD demonstrated similar characteristics, including fever, splenomegaly, cytopenia and inflammatory symptoms. However, the disease was more aggressive in HHV‐8+ MCD, particularly in HIV‐infected patients.
Background Acquired hemophagocytic lymphohistiocytosis (HLH) is a life-threatening event that usually occurs as a complication of immunodeficiency. Lung involvement in HLH has received little ...attention. This article describes lung involvement in HLH and assesses whether it affects the prognosis. Methods We retrospectively studied 219 patients with HLH admitted to a national reference center over a 14-year period, including 118 (54%) with lung involvement. Results Dyspnea and cough were the most common onset symptoms. Radiographs revealed interstitial infiltrates with centrilobular nodules, ill-defined consolidation, or localized ground-glass opacities. Pleural effusions and mediastinal lymphadenopathies were found in approximately one-half of the patients. One or more causes of lung involvement were documented in 91 of 118 patients (77.1%) and included infection (n = 52), pulmonary edema (n = 34), and malignancies (n = 22 mostly lymphoma). HLH-specific treatment combined with treatment of the cause of lung involvement improved respiratory function in only 67 of the 188 patients (56.7%). Hospital mortality was higher in patients with lung involvement (52.5% vs 20%). Infection as the cause of lung involvement was the only determinant of death (56% vs 30%; P = .004). Conclusions Lung involvement is common and of poor prognosis in patients with HLH. Studies should assess whether specific diagnostic and therapeutic strategies are warranted in patients with HLH and lung involvement.
Preemptive rituximab infusions prevent relapses in immune thrombotic thrombocytopenic purpura (iTTP) by maintaining normal ADAMTS13 activity. However, the long-term outcome of these patients and the ...potential adverse events of this strategy need to be determined. We report the long-term outcome of 92 patients with iTTP in clinical remission who received preemptive rituximab after identification of severe ADAMTS13 deficiency (activity <10%) during the follow-up. Thirty-seven patients had >1 iTTP episode, and the median cumulative relapse incidence before preemptive rituximab was 0.33 episode per year (interquartile range IQR, 0.23-0.66). After preemptive rituximab, the median cumulative relapse incidence in the whole population decreased to 0 episodes per year (IQR, 0-1.32; P < .001). After preemptive rituximab, ADAMTS13 activity recovery was sustained in 34 patients (37%) during a follow-up of 31.5 months (IQR, 18-65), and severe ADAMTS13 deficiency recurred in 45 patients (49%) after the initial improvement. ADAMTS13 activity usually improved with additional courses of preemptive rituximab. In 13 patients (14%), ADAMTS13 activity remained undetectable after the first rituximab course, but retreatment was efficient in 6 of 10 cases. In total, 14 patients (15%) clinically relapsed, and 19 patients (20.7%) experienced benign adverse effects. Preemptive rituximab treatment was associated with a change in ADAMTS13 conformation in respondent patients. Finally, in the group of 23 historical patients with iTTP and persistently undetectable ADAMTS13 activity, 74% clinically relapsed after a 7-year follow-up (IQR, 5-11). In conclusion, persistently undetectable ADAMTS13 activity in iTTP during remission is associated with a higher relapse rate. Preemptive rituximab reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an advantageous risk-benefit balance.
•TTP patients who display persistent and severe ADAMTS13 deficiency after remission have a relapse rate of 74% during long-term follow-up.•Preemptive rituximab can decrease TTP relapses in 85% of patients with a favorable benefit-risk balance.
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Pregnancy may be complicated by a rare but life-threatening disease called thrombotic thrombocytopenic purpura (TTP). Most cases of TTP are due to an acquired autoimmune or hereditary ...(Upshaw-Schulman syndrome USS) severe deficiency of a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13). In the present study, we performed a cross-sectional analysis of the national registry of the French Reference Center for Thrombotic Microangiopathies from 2000-2010 to identify all women who were pregnant at their initial TTP presentation. Among 592 adulthood-onset TTP patients with a severe ADAMTS13 deficiency, 42 patients with a pregnancy-onset TTP were included. Surprisingly, the proportion of USS patients (n = 10 of 42 patients 24%; confidence interval, 13%-39%) with pregnancy-onset TTP was much higher than that in adulthood-onset TTP in general (less than 5%) and was mostly related to a cluster of ADAMTS13 variants. In the present study, subsequent pregnancies in USS patients not given prophylaxis were associated with very high TTP relapse and abortion rates, whereas prophylactic plasmatherapy was beneficial for both the mother and the baby. Pregnancy-onset TTP defines a specific subgroup of patients with a strong genetic background. This study was registered at www.clinicaltrials.gov as number NCT00426686 and at the Health Authority, French Ministry of Health, as number P051064.
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